ESTRO
4 - 8 April 2014
Vienna, Austria
WWW.ESTRO.ORG
CONGRESS REPORT
CONTENTS
INTRODUCTION
INTRODUCTION
p3
CLINICAL
p4
BRACHYTHERAPY
INTRODUCTION
p 27
1_ Using MRI and integrated ultrasound to guide
brachytherapy for cervix cancer
p 28
1_BREAST Lymph node RT improves survival in breast
cancer: 10 years results of the EORTC ROG and
BCG phase III trial 22922/10925
p6
2_ Report on real-time electromagnetic seed
drop position validation for low dose rate
brachytherapy
p 30
2_BREAST Improved survival with internal mammary
node irradiation: a prospective study on 3,072 breast
cancer patients
p7
3_ Preservation of erectile function after prostate permanent
implantation for localised prostate cancer
p 32
INTRODUCTION
p5
3_RECTAL First results of the PETACC-6 randomised
phase III trial in locally advanced rectal cancer
p8
4_RECTAL The value of postoperative chemotherapy for
rectal cancer patients after preoperative (chemo)radiotherapy and TME surgery
p 10
5_HEAD & NECK DAHANCA19: A randomized
phase III study of primary (chemo-) radiotherapy and
zalutumumab in head and neck carcinomas
p 11
6_ PROSTATE 3D-CRT/IMRT with/without short term
androgen deprivation in localised T1b-cT2aN0M0
prostatic carcinoma (EORTC 22991)
p 12
7_ SECONDARY RISK Risk of second primary lung cancer
in women after radiotherapy for breast cancer; a
DBCG based dose-response study
p 13
8_ HEALTH ECONOMICS IN RADIATION ONCOLOGY
(HERO) Risk of second primary lung cancer in women
after radiotherapy for breast cancer; a DBCG based
dose-response study
p 14
PHYSICS
INTRODUCTION
p 16
p 17
1_ Online 3D dose verification for VMAT
treatments
p 18
2_ Application of dose warping for MR-Linac dose
calculations
p 19
3_ Can particle beam therapy be improved using helium
ions? – A treatment planning study focusing on
paediatric patients
p 21
4_ Patient-specific motion and treatment margins in
pancreatic Stereotactic Body Radiation Therapy
p 23
5_ Validation of a hypoxia TCP model and dose
painting in HNC: Planned interim analysis of a phase II
trial
p 24
4_ Salvage reirradiation for recurrent prostate cancer
patients: three fractions of high-dose-rate
brachytherapy
p 34
RTT
INTRODUCTION
p 37
With almost 5000 participants, ESTRO 33 was a successful meeting. It was the perfect place for all professionals in the radiation oncology area, to gather together to exchange comments on the latest outcomes, in the inspiring atmosphere of Vienna.
On behalf of the scientific committee, we would like to thank you all for contributing to the success of this event.
In this report you can find a selection of some of the papers that were presented on site. We chose to include them according
to their scientific relevance, in each track: clinical, physics, brachytherapy, radiation therapy (RTT) and radiobiology. The
awarded studies are also presented in the last part of the report. Finally, ESTRO 33 was largely commented on Twitter with the
hashtag #ESTRO33. Two ESTRO members, active on the social media, report at the end of this report on how the #ESTRO33
tweets were spread out during the congress.
We hope that you enjoyed the scientific relevance of the sessions. It seems that once again, the interdisciplinary track proved
necessary to bridge between the various disciplines of our area and no doubt next year the 3rd ESTRO Forum, 24-28 April
2015 will go even further in this direction.
2_ Library of plans for VMAT irradiation of cervical
cancer: first clinical experience
p 40
With warm regards,
3_ Multi-Criteria optimisation individualises treatment
plan selection in stage III lung cancer patients
p 42
Vincenzo Valentini
Past-president of ESTRO and Chair of the congress
RADIOBIOLOGY
INTRODUCTION
p 44
p 45
1_ Analysis of 5434 patients shows a link between the ATM
codon 1853 SNP and the risk of radiation-induced
toxicity
p 46
Daniel Zips
Chair of the Scientific Programme Committee
Claudio Fiorino
Chair of the Scientific Programme Committee
2_ Complementarity of genomic instability & hypoxia
indices for predicting prostate cancer recurrence
p 48
3_ 18F-FAZA PET as a predictive marker to guide hypoxiadriven interventions (carbogen breathing or dose
escalation) in radiotherapy
p 49
AWARDS
p 52
LIST OF AWARDS
p 52
Donal Hollywood Award
p 53
ESTRO-Jack Fowler University of Wisconsin Award
p 55
ESTRO-Accuray Award
p 57
ESTRO-Varian Award
p 59
ESTRO-Nucletron Brachytherapy Award
p 60
GEC-ESTRO Best Junior Presentation
Sponsored by Nucletron
p 61
A personal view from two delegates and tweeters
CONTENTS | 2ND ESTRO FORUM - REPORT
p 36
1_ Coronary dosimetry based on heart CT angiographies
for Hodgkin lymphoma radiation therapy
p 38
TWITTER AT ESTRO
2
p 26
p 62
ESTRO
ESTRO
CONGRESS REPORT | INTRODUCTION
3
CLINICAL
INTRODUCTION
INTRODUCTION
During ESTRO 33 a large number of excellent clinical papers were presented – many of them for the first
time at a meeting – which reflect the development of our discipline towards better treatment and which
also contributed to the success of the Vienna meeting. Of note is that large national consortia such as the
Danish DAHANCA and DBCG as well as the European collaborative trial group EORTC have decided to
present their results from large clinical trials at the ESTRO meeting.
p5
1. BREAST
Lymph node RT improves survival in breast cancer: 10 years results of the EORTC ROG and BCG
phase III trial 22922/10925
p6
2. BREAST
Improved survival with internal mammary node irradiation: a prospective study on 3,072 breast
cancer patients
3. RECTAL
First results of the PETACC-6 randomised phase III trial in locally advanced rectal cancer
p7
p8
4. RECTAL
The value of postoperative chemotherapy for rectal cancer patients after preoperative
(chemo)radiotherapy and TME surgery.
p 10
5. HEAD & NECK
DAHANCA19: A randomised phase III study of primary (chemo-) radiotherapy and zalutumumab
in head and neck carcinomas
p 11
6. PROSTATE
3D-CRT/IMRT with/without short term androgen deprivation in localized T1b-cT2aN0M0
prostatic carcinoma (EORTC 22991)
Results from two very important randomised trials in multimodal therapy of rectal cancer (abstract 3, Haustermans K et
al.; abstract 4, Breugrom AJ et al.) were presented. Both trials contribute important evidence to the ongoing discussion over
optimal systemic treatment, i.e. more intense chemotherapy concurrent to radiation, and the benefit from standard adjuvant
5-FU/leucovorin or capecitabine. Evaluation of the primary endpoint and meta-analyses will show whether our current practice might change.
In head and neck cancer a number of very important studies and analyses were presented. For example, the DAHANCA19
trial presented by Jesper Eriksen (abstract 5). This study is the second large randomised trial that has failed to show a benefit
for EGFR inhibition with radiochemotherapy. Apparently, EGFR inhibition to sensitise tumours for radiation therapy is back
from the clinic to the bench.
On behalf of the EORTC, Michel Bolla presented for the first time the results from the EORTC 22991. As emphasised by the
discussant Dr Rob Bristow from PMH Toronto, this landmark trial addressed the key issue of androgen deprivation therapy
to improve outcome in intermediate risk prostate cancer patients treated with contemporary radiation doses. Although longer
follow-up and evaluation of overall survival will be necessary, the size of the effect of six-month ADT on clinical progression
free survival at five years is substantial and should be considered when treatment options are discussed with patients, while, of
course, including the risk of side-effects and impaired quality of life.
In order to provide the advantages of modern state-of-the-art radiation therapy to all cancer patients in Europe appropriate
resources including personnel and equipment are essential. At ESTRO 33 for the first time results from the ESTRO HERO
(Health Economics in Radiation Oncology) project were presented by C. Grau. The inventory of European radiotherapy
indicates enormous heterogeneity and in a number of European countries an alarming shortage of modern radiation therapy
equipment.
p 12
Daniel Zips
Chair of the Scientific Advisory Group for Clinical Radiotherapy and Chair of the Scientific Programme Committee
7. SECONDARY RISK
Risk of second primary lung cancer in women after radiotherapy for breast cancer; a DBCG based
dose-response study
Two trials performed by EORTC/BCG (abstract 1, P. Poortmans et al.) and the Danish Breast Cancer
Group (abstract 2, Thorsen LBJ et al.) provide high-level evidence for irradiation of regional lymph
nodes in breast cancer. The discussant, the current president of ASTRO Dr Bruce Haffty, pointed out that these data, in
addition to other recently published trials, will change practice towards a more personalised approach for regional radiation
therapy. Another highlight of the congress in breast cancer research was presented by Trine Grantzau (abstract 7). She and her
colleagues interrogated the registry data from the Danish Breast Cancer Group, including more than 20,000 patients, to assess
the dose-effect-relationship for developing lung cancer after radiotherapy for breast cancer. The linear dose-effect-relationship
is an important scientific basis with immediate clinical relevance: lowering the dose to the lung by 1 Gy decreases the risk for
lung cancer by 8.5%. A great case for high-precision radiation therapy.
p 13
8. HEALTH ECONOMICS IN RADIATION ONCOLOGY (HERO)
Radiotherapy equipment and departments in the European countries: Final results
from the ESTRO-HERO survey
4
CLINICAL | CONGRESS REPORT
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ESTRO
ESTRO
CONGRESS REPORT | CLINICAL
5
1. BREAST
2. BREAST
LYMPH NODE RT IMPROVES SURVIVAL IN BREAST CANCER: 10 YEARS RESULTS
OF THE EORTC ROG AND BCG PHASE III TRIAL 22922/10925.
IMPROVED SURVIVAL WITH INTERNAL MAMMARY NODE IRRADIATION:
A PROSPECTIVE STUDY ON 3,072 BREAST CANCER PATIENTS
Philip Poortmans, Henk Struikmans, Sandra Collette, Carine Kirkove, Volker Budach, Philippe
Maingon, Maria Carla Valli, Alain Fourquet, Walter Van den Bogaert, Harry Bartelink
L.B.J. Thorsen1, M. Berg2, H.J. Brodersen3, H. Danø4, I. Jensen5, J. Overgaard1, M. Overgaard6, A.N.
Pedersen7, S.J. Zimmermann8, B.V. Offersen6
For the EORTC (European Organisation for Research and Treatment of Cancer) Radiation Oncology and Breast Cancer Groups
Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark | 2Vejle Hospital, Department
of Medical Physics, Vejle, Denmark | 3Malteser Krankenhaus St. Franziskus-Hospital, Klinik für Strahlentherapie, Flensburg,
Germany | 4Herlev Hospital, Department of Oncology, Herlev, Denmark | 5Aalborg University Hospital, Department of Medical
Physics, Aalborg, Denmark | 6Aarhus University Hospital, Department of Clinical Oncology, Aarhus, Denmark | 7Rigshospitalet,
Department of Oncology, Copenhagen, Denmark | 8Odense University Hospital, Department of Oncology, Odense, Denmark
BACKGROUND
Locoregional radiation therapy improves overall survival
in all patients with involved lymph nodes and in patients
without involved lymph nodes when treated with breast
conserving surgery. EORTC trial 22922-10925 investigates
the role of the internal mammary and medial supraclavicular
lymph node component of postoperative radiation therapy.
OVERVIEW OF ABSTRACT
Eligible patients had axillary lymph node involvement and/
or a centrally or medially located tumour. The main aim of
the trial was to detect and statistically validate an increase of
4% in 10-year overall survival from 75 to 79% with internal mammary and medial supraclavicular lymph radiation
therapy. Secondary endpoints were disease-free survival,
distant metastasis-free survival and cause of death. Between
1996 and 2004, 4004 patients from 43 centres participated,
of which 55.6% had involved axillary lymph nodes. The majority (76.1%) were treated with breast conserving therapy.
Nearly all node-positive (99.0%) and 66.3% of node-negative
patients received adjuvant systemic treatment.
cancer without an increase in non-breast cancer related
mortality. Since the greatest effect is seen in lower risk
patients and those who receive effective adjuvant systemic
therapy, rather than the high risk group (as expected by
many), the context of the complex interaction between patient-, tumour- and treatment- (systemic and locoregional)
related factors should be revisited. In the meantime, we advise clinicians to strongly consider giving radiation therapy
to the internal mammary and medial supraclavicular lymph
nodes for patients with involved axillary lymph nodes and/
or a medially located primary tumour.
1
BACKGROUND
The internal mammary lymph nodes (IMNs) are known to
be metastatically involved in some cases of breast cancer.
Even so, there is conflicting evidence as to whether treating
the IMNs with adjuvant radiotherapy has any beneficial
effect on survival. As the IMNs on the left side are situated
in close proximity to the heart, IMN treatment in left-sided
breast cancer is particularly challenging.
OVERVIEW OF ABSTRACT
The DBCG-IMN study investigates whether adjuvant
radiotherapy to the IMNs improves overall survival in more
than 3000 patients with lymph node positive breast cancer.
Patients with cancer in the right breast were treated with
standard radiotherapy plus IMN radiotherapy, while patients
with cancer in the left breast did not receive IMN radiotherapy, as this could cause radiotherapy-induced damage to the
heart. Patients in the two groups were comparable with respect to independent risk factors for breast cancer death, e.g.
pN-stage, T-stage etc. All patients were allocated to adjuvant
systemic treatment.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
1. Overall survival at 10 years was 82.3% with and 80.7%
without radiation therapy to the internal mammary and
medial supraclavicular lymph nodes (HR=0.87 (95%CI:
0.76, 1.00), Logrank p=0.056). The causes of death were
similar except for breast cancer (259 vs. 310).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The results are potentially practice changing, as they support
IMN radiotherapy in patients with lymph node positive
breast cancer.
Follow up will continue, as both breast cancer recurrence
and late side-effects due to radiotherapy can develop many
years after initial treatment.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
This research supports the findings of the EORTC trial
22922/10925, and the NCIC-CTG MA.20, both documenting the benefit of regional radiotherapy in patients with
generally lower pN-stage than those in the DBCG-IMN.
As earlier DBCG studies in the postmastectomy setting
have shown, the beneficial effect of regional radiotherapy
is substantial for all node positive disease, and although
the IMNs are rarely the site of isolated regional metastasis,
their treatment can nevertheless be of crucial importance in
patients with node positive breast cancer.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
1. After a median follow up of seven years, overall survival was 78% versus 75% in favour of IMN radiotherapy,
HR=0.86 (95% CI (0.75; 0.99), p=0.04).
2. DFS (Disease Free Survival) and DMFS (Distant Metastases Free Survival) were also greater after lymph node
irradiation: 72.1 vs. 69.1% (HR=0.89 (95%CI: 0.80, 1.00),
Logrank p=0.044) and 78.0 vs. 75.0% (HR=0.86 (95%CI:
0.76, 0.98), Logrank p=0.020), respectively.
2. Disease free survival (HR=0.94) and metastasis free survival (HR=0.94) displayed a similar trend.
3. The number of deaths from cardiac disease was comparable in the two groups, with 9 deaths in the no IMN
radiotherapy group and 8 deaths in the IMN radiotherapy
group. Death from breast cancer was more frequent in
the no IMN radiotherapy group (n=366) than in the IMN
radiotherapy group (n=309).
3. Only the rate of lung and skin toxicity was slightly higher
in the regionally irradiated group. No increase in cardiac
events or lethal complications was observed.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
With a median follow-up of 10 years, postoperative radiation
therapy to the internal mammary and medial supraclavicular lymph nodes improves overall, disease free and distant
metastasis-free survival in patients with stage I-III breast
6
CLINICAL | CONGRESS REPORT
ESTRO
ESTRO
CONGRESS REPORT | CLINICAL
7
3. RECTAL
FIRST RESULTS OF THE PETACC-6 RANDOMIZED PHASE III TRIAL IN LOCALLY
ADVANCED RECTAL CANCER
K. Haustermans1, H.J. Schmoll2, T. Price3, B. Nordlinger4, R.D. Hofheinz5, J.F. Daisne6, J. Janssens7, P.
Schmidt8, H. Reinel9, E. Van Cutsem10.
University Hospital Gasthuisberg, Radiation Oncology, Leuven, Belgium | Martin Luther Universitaet, Department of Internal
Medicine IV Hematology & Oncology, Halle, Germany | 2 Queen Elizabeth Hospital, Haematology-Oncology Department,
Woodville, Australia | 3 CHU Ambroise Paré Assistance Publique Hôpitaux de Paris, Department of Surgery and Oncology,
Boulogne-Billancourt, France | 4 Universitaetsmedizin Mannheim, Interdisciplinary Tumour Centre, Mannheim, Germany |
5
Clinique et Maternité Sainte Elisabeth, Department of Radiation Oncology, Namur, Belgium | 6 AZ Turnhout, Department of
Gastroenterology, Turnhout, Belgium | 7 Staedt. Klinikum Neunkirchen, Department of Hematology and Oncology, Neunkirchen,
Germany | 8 Leopoldina-Krannkenhaus der Stadt Schweinfurt GGMBH, Department of Hematology and Oncology, Schweinfurt,
Germany | 9 University Hospitals Gasthuisberg, Digestive Oncology Unit, Leuven, Belgium
1
BACKGROUND
PETACC-6 studies the role of adding oxaliplatin to
capecitabine in the pre- and postoperative treatment
of patients with locally advanced rectal cancer. The
primary endpoint of this trial is disease-free survival.
The preliminary results of the primary endpoint will be
presented at ASCO. At the ESTRO meeting in Vienna the
secondary endpoints were presented.
OVERVIEW OF ABSTRACT
Between 11/2008 and 09/2011, patients with rectal cancer
within 12 cm of the anal verge, T3/4 and/or node-positive,
with no evidence of metastatic disease and considered
either resectable at the time of entry or expected to become
resectable, were randomly assigned to receive 5 weeks of
preoperative CRT (45 Gy in 25 fractions with an optional
boost to a total dose of 50.4 Gy) with capecitabine (825 mg/
m² twice daily), followed by 6 cycles of adjuvant CT with
capecitabine (1000 mg/m2 twice daily/days 1-15 every three
weeks) (arm 1) or to receive the same regimen with the addition of oxaliplatin before (50 mg/m²/days 1, 8, 15, 22, 29)
and after surgery (130mg/m²/day 1, every three weeks) (arm
2). Pathological down-staging (ypT0-2N0) rate, complete
remission (ypT0N0) rate, sphincter preservation and R0 resection rate were secondary endpoints. Patients not operated
upon or not resected were scored as failures (intent-to-treat
analysis).
s
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
1094 patients were randomized (547 in each arm). 98% and
92% of patients received at least 45 Gy of preoperative RT
in arms 1 and 2 respectively. More than 90% of full dose
concurrent CT was delivered in 91% and 63% of patients
in arms 1 and 2.The compliance to RT was similar in arm
1 (97.4%) and arm 2 (93.8%). RT was delivered as 3D
conformal RT (82.6% vs. 80.8%), IMRT (13.4% vs. 13.9%)
or 2D RT(3.7% vs. 5.1%) in arms 1 and 2 respectively. RT
was administered in the prone position (arm 1: 70.8%; arm
2: 64.6%) or supine position (arm1: 27.2%; arm 2:32%). The
median volume covered by the 95% isodose was 1619 cc
(50.0 cc -5384.0 cc) in arm 1 and 1559.0 cc (95.0 cc - 3741.0
cc) in arm 2. The median D95 was 44.3 Gy in arm 1 and
44.4 Gy in arm 2. The median boost volume to 50.4 Gy was
smaller (813 cc and 636 cc in arm 1 and 2 respectively). R0
resection rate was 92.0% in arm 1 and 86.3% in arm 2. The
ypT0N0 rate was equal in both arms with 11.3% in arm 1
and 13.3% in arm 2 (p=0.31). There was no difference in
pathological down-staging (43.5% in arm 1 vs. 41.5% in
arm 2). The anal sphincter was preserved in 70% vs. 65%
(p=0.09) in arms 1 and 2. Preoperative grade 3/4 toxicity
occurred in 15.1% of patients in arm 1 vs. 36.7% in arm 2.
Radiation associated dermatitis was recorded in 27.8% of
the patients in arm 1 (1.5% grade 3-4) and in 21.8% of the
patients in arm 2 (1.7% grade 3-4). The occurrence of diarrhoea was higher in arm 2 (70.2%, 18.4% grade 3-4) than in
arm 1 (57.9%; 5.7% grade 3-4). Postoperative complications
were not different between arms (38% vs. 41%).
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
The main problem today in locally advanced rectal cancer is
distant metastasis. Intensification of the systemic treatment
by adding cytotoxic drugs to the standard treatment is one
approach to overcome this problem. Another approach is to
increase the dose of these drugs by combining them with a
short course of radiotherapy and administer the full dose of
drugs in the interval prior to surgery(see RAPIDO trial). As
well as increasing dose intensity, the drugs are also administered earlier during treatment. In this way we hope that
fewer metastatic tumour cells would need to be killed and
response rates could be higher.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The addition of oxaliplatin to preoperative fluoropyrimidine-based CRT led to decreased treatment compliance and
increased toxicity but did not improve pathological downstaging, complete remission, R0 resection rate or sphincter
preservation. We have to wait for the results on the primary
endpoint before we can come to a definitive conclusion on
the role of oxaliplatin in the treatment of locally advanced
rectal cancer.
8
CLINICAL | CONGRESS REPORT
ESTRO
ESTRO
CONGRESS REPORT | CLINICAL
9
4. RECTAL
5. HEAD & NECK
THE VALUE OF POSTOPERATIVE CHEMOTHERAPY FOR RECTAL CANCER
PATIENTS AFTER PREOPERATIVE (CHEMO)RADIOTHERAPY AND TME
SURGERY.
DAHANCA19: A RANDOMIZED PHASE III STUDY OF PRIMARY (CHEMO-)
RADIOTHERAPY AND ZALUTUMUMAB IN HEAD AND NECK CARCINOMAS
A.J. Breugom1, C.B.M. van den Broek1, W. van Gijn1 H. Putter1, E. Meershoek – Klein Kranenbarg1, B.
Glimelius2, L. Påhlman2, H.J.T. Rutten3, C.A.M. Marijnen1, C.J.H. van de Velde (PI)1, and cooperative
investigators of the Dutch Colorectal Cancer Group.
Leiden University Medical Center, Leiden, The Netherlands | 2 Akademiska Sjukhuset, Uppsala, Sweden | 3 Catharina Hospital,
Eindhoven, The Netherlands
1
OVERVIEW OF ABSTRACT
The role of adjuvant chemotherapy after preoperative
(chemo)radiation and total mesorectal excision (TME)
surgery is still under discussion. The aim of the PROCTOR-SCRIPT study is to investigate the additional value of
postoperative chemotherapy with respect to overall survival,
disease-free survival, and local and distant tumour control.
Patients with stage II or III rectal adenocarcinoma were
randomly assigned (1:1) to postoperative chemotherapy
or observation after preoperative (chemo)radiation and
TME-surgery. Postoperative chemotherapy consisted of
5-FU/Leucovorin according to the Mayo or Nordic regimen
(PROCTOR) or eight courses of 1250 mg/m2 oral capecitabine (SCRIPT) twice daily, given on days 1-14, every 21
days.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
There is currently no evidence to support administration of
adjuvant chemotherapy for patients with rectal cancer after
preoperative (chemo)radiation and TME surgery. Overtreatment could be reduced if adjuvant chemotherapy were not
offered as standard treatment to stage II and III rectal cancer
patients.
However, the question remains whether there are subgroups
of patients that might benefit from adjuvant chemotherapy.
A meta-analysis of all trials on adjuvant chemotherapy after
preoperative (chemo)radiation and TME surgery would be
of great value to investigate this. This could contribute to a
more individualized approach for rectal cancer patients.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
Between March 1st 2000 and January 1st 2013, 470 patients
were included. This study was finally closed due to poor patient accrual. Of the 440 eligible patients, 222 patients were
randomized to observation and 218 patients to adjuvant
chemotherapy.
BACKGROUND
Head and Neck Squamous Cell Carcinomas (HNSCC)
tend to overexpress the Epidermal Growth Factor
Receptor, EGFR. Preclinically, EGFR has been related
to radioresistance and possibly increased repopulation.
Antibodies against EGFR have been suggested to increase
tumour control and survival of patients with HNSCC when
combined with radiotherapy. The Danish Head and Neck
Cancer group, DAHANCA, has obtained encouraging
results with zalutumumab, a fully human equivalent to
cetuximab, in a phase I/II trial.
PURPOSE OF THE STUDY
In a randomised, non-blinded setting we evaluated if concurrent treatment with the EGFR-inhibitor zalutumumab
during (chemo-) radiotherapy was better than (chemo-)
radiotherapy alone in terms of loco-regional tumour control,
disease specific and overall survival. Furthermore we evaluated changes in the pattern of toxicity when zalutumumab
was added to standard treatment.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
In an unselected population of HNSCC patients, there were
no benefits of adding zalutumumab to standard (chemo-)
radiotherapy. The conclusions seemed to be unaffected by
whether the patient received cisplatin or not.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
The results of this study are very much in line with data
from the RTOG 0552 phase III trial of chemo-radiotherapy
+/- cetuximab to locally advanced HNSCC or the CONCERT-1 phase II trial with chemo-radiotherapy +/- panitumumab, showing no benefit of adding an EGFR-inhibitor
to chemoradiation with cisplatin. The reason might be that
EGFR-antibodies and cisplatin share similar mechanisms of
action, predominantly inhibition of DNA repair and proliferation. Further studies of EGFR-inhibition should therefore
be performed in selected patient groups. Several trials are
underway to elucidate the possible place of EGFR-inhibition
in curative radiotherapy of HNSCC patients.
The trial recruited more than 600 patients that were randomized to standard treatment (mainly moderately accelerated radio-therapy 66-68Gy in 33-34 fractions plus the
hypoxic radiosensitizer, nimorazole, with weekly low-dose
cisplatin 40 mg/m² during radiotherapy offered to patients
with locally advanced disease) or the experimental arm
(standard treatment plus zalutumumab 8mg/kg, initiated
the week before start of radiotherapy and continuing weekly
during radiation). After a median observation time of 42
months it was concluded that:
Addition of zalutumumab to accelerated (chemo-) radiotherapy for HNSCC did not increase loco-regional control
(3-year loco-regional control rate 77% in the standard-arm versus 76% in the zalutumumab-arm).
Response to zalutumumab was not related to tumour
HPV/p16 status.
Addition of zalutumumab increased acute but not late
morbidity.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The results of this underpowered trial, as well as the results
of three other trials on this subject, suggest that there is no
role for standard administration of adjuvant chemotherapy
after preoperative (chemo)radiation and TME surgery. This
could possibly result in a change in treatment strategy for
countries that currently offer adjuvant chemotherapy as
standard treatment for patients with rectal cancer.
CLINICAL | CONGRESS REPORT
Dept. of Oncology, Odense University Hospital, Denmark | 2 Dept. of Oncology, Herlev Hospital, Denmark | 3 Dept. of Oncology,
Aarhus University Hospital, Denmark | 4 The Norwegian Radium Hospital, Oslo University Hospital, Norway | 5 Dept. of Oncology,
Copenhagen University Hospital, Denmark | 6 Dept. of Oncology, Aalborg University Hospital, Denmark | 7 Dept. of Experimental
Clinical Oncology, Aarhus University Hospital, Denmark.
1
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
At a median follow-up of 5.0 years, five-year overall survival
was 79.2% in the observation group and 80.4% in the
adjuvant chemotherapy group (HR 0.90, 95% CI 0.60-1.36;
p=0.62). No differences in disease-free survival (HR 0.80,
95% CI 0.60-1.09; p=0.15 or recurrence rates (HR 0.91,
95% CI 0.66-1.25; p=0.56) were observed between the two
treatment arms.
10
Jesper Grau Eriksen1, Christian Maare2, Jørgen Johansen1, Hanne Primdahl3, Jan Evensen4, Claus
Andrup Kristensen5, Lisbeth Juhler Andersen6 and Jens Overgaard7 on behalf of DAHANCA.
ESTRO
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CONGRESS REPORT | CLINICAL
11
6. PROSTATE
7. SECONDARY RISK
3D-CRT/IMRT WITH/WITHOUT SHORT TERM ANDROGEN DEPRIVATION IN
LOCALIZED T1B-CT2AN0M0 PROSTATIC CARCINOMA (EORTC 22991)
RISK OF SECOND PRIMARY LUNG CANCER IN WOMEN AFTER RADIOTHERAPY
FOR BREAST CANCER; A DBCG BASED DOSE-RESPONSE STUDY
Trine Grantzau¹, Mette Skovhus Thomsen2, Jens Overgaard¹
M. Bolla1, P. Maingon2, A.C.M. van den Bergh3, C. Carrie4, S. Villa5, P. Kitsios6, P. Poortmans7, S.
Sundar8, E.M. van der Steen-Banasik9, L. Collette10.
Grenoble University Hospital - Hospital A. Michallon, Radiotherapy, Grenoble Cedex 9, France | 2 Georges-Francois-Leclerc
Center, Radiotherapy, Dijon, France | 3 University Medical Center Groningen, Radiotherapy, Groningen, The Netherlands | 4 Leon
Berard Center, Radiotherapy, Lyon, France | 5 Catalan Institute of Oncology Badalona, Oncology & Radiotherapy, Badalona,
Spain | 6 Bank Of Cyprus Oncology Centre, Radiotherapy, Nicosia, Cyprus | 7 Dr. Bernard Verbeeten Institute, Radiotherapy,
Tilburg, The Netherlands | 8 Nottingham University Hospitals NHS Trust - City Hospital, Oncology & Radiotherapy, Nottingham,
United Kingdom | 9 Arnhem Radiotherapy Institute, Radiotherapy, Arnhem, The Netherlands | 10 European Organisation for
Research and Treatment of Cancer, Statistics, Brussels, Belgium.
1
BACKGROUND
This phase III trial is devoted to intermediate and high risk
localized prostate cancer (PCa) patients according to the
d’Amico classification; this classification is based on clinical
stage, histological differentiation according to Gleason
and baseline prostate specific antigen (PSA). Patients who
have chosen to be treated by external beam radiotherapy
-i.e. three dimensional conformal radiotherapy (3D-CRT)
+/-intensity modulated RT- were invited to participate. The
aim was to determine whether 6-months of concomitant and
adjuvant androgen deprivation therapy (ADT) with a Luteotrophine Hormone Releasing Hormone agonist (LHRHa)
could improve 5-year biochemical progression free survival
and clinical progression-free survival. LHRHa inhibits
the secretion of testosterone from the testis and achieves a
chemical castration which potentiates local irradiation and
may sterilize sub-clinical disease outside the pelvis.
OVERVIEW OF ABSTRACT
Up to 30% patients with intermediate or high risk localized
PCa treated by 3D-CRT +/-intensity modulated RT relapse
biochemically within 5 years of primary irradiation. For
locally advanced PCa treated by 3D-CRT the combination
with long-term ADT significantly improved overall survival.
This study investigates the impact of a shorter ADT (6
months) combined with irradiation; at the time the trial
was launched (2001) there was no consensus regarding the
dose level to be prescribed, which explains why centres were
offered 3 dose levels: 70 Gy delivered in 35 fractions over 7
weeks (5 fractions per week), 74Gy/37 fractions or 78 Gy/39
fractions.
Clinical progression-free survival was also significantly
improved, by 7.9% at 5 years (P=0.001).
Late genito-urinary toxicity was reported by 5.9% vs
3.6% of patients receiving RT+HT and RT respectively
(P=0.14), whereas 27.0% vs 19.4% reported severe impairment of sexual function (P=0.010).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
From a public health point of view, the results of this trial
enable the radiation oncology community to propose to
patients with intermediate or high risk localized PCa treated
by radiotherapy, an optimized modality of external beam
radiotherapy with dose escalation combined with a 6-month
ADT with LHRHa, provided that the benefits and potential side-effects of ADT are explained. Regarding clinical
research, new modalities of ADT must be considered in
combination with irradiation.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
This research may be considered as having a significant
impact on daily practice since clinical progression free
survival, i.e. the likelihood of being alive at 5 years without
clinical relapse or death by any cause, is improved from 80.8
% to 88.7%. It is too early to evaluate the impact on overall
survival.
1
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark | ² Department of Medical Physics,
Aarhus University Hospital, Denmark
BACKGROUND
Advances in breast cancer treatment with improved survival
rates have lead to an increased awareness of treatmentinduced second cancers. It has been shown in several
epidemiological studies that irradiated breast cancer patients
have an increased risk of second lung cancer. However,
uncertainty still exists about the dose-response relationship
in the context of high dose radiation therapy. The purpose of
this study was to assess the effects of the delivered radiation
dose to the lung and the risk of second primary lung cancer.
OVERVIEW OF ABSTRACT
Within a population based cohort of 23,627 early breast
cancer patients treated with post-operative radiotherapy
between 1982 and 2007, a nested case–control study was
conducted. The cohort included 151 cases diagnosed with
second primary lung cancer and 443 matched controls.
Individual dose-reconstructions were performed and the
delivered dose to the center of the second lung tumour and
the comparable location for the controls were estimated. All
dose-estimations were based on the individual patient-specific radiotherapy charts. The dose-response relationship of
second primary lung cancer after breast cancer irradiation
was assessed according to delivered radiation dose to the
lung.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The results indicate that second lung cancer after radiotherapy to early breast cancer patients is linearly associated with
the delivered dose to the lung and that any reduction of the
dose to the lung would result in a reduction of the risk. With
the growing number of long-term survivors after breast
cancer this is a clinical challenge that highlights the need for
advances in normal tissue sparing radiation techniques.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
This research reflects a growing awareness of the long-term
adverse side-effects of radiotherapy. Darby et al. recently estimated the risk of radiation induced ischemic heart disease.
The risk increased linearly with the mean dose to the heart
by 7.4% per Gray. This is of a similar magnitude to the excess
risk of developing a radiation-induced second lung cancer
shown in this study. With the growing number of long-term
survivors after breast cancer treatment the adverse effects
of radiation to normal tissue are becoming more apparent
and treatment techniques that spare the lung need to be
considered in daily clinical practice. A trend towards more
advanced techniques, such as gating, that spare normal
tissues are slowly entering clinical practice.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
The median time from breast cancer treatment to second
lung cancer diagnosis was 12 years (range 1 to 26 years).
69% of the lung cancers were diagnosed five or more years
after radiation therapy. The mean radiation dose to the lung
tumour site was 8.7 G (range 0.04 to 52.2) and the mean
dose to the comparable anatomical site for controls was 5.6
G (range 0.01 to 52.3), p=0.01.
For patients diagnosed with a second primary lung cancer
five or more years after breast cancer treatment the rate of
lung cancer increased linearly by 8.5% per delivered G (95%
confidence interval 3.1 to 23.3; p< 0.001).
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
After a median follow-up of 7.2 years, biochemical
progression-free survival appeared to be significantly
improved with RT+HT at all radiation doses with an
increase at 5 years from 69.3% to 82.5% (P<0.001)
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8. HEALTH ECONOMICS IN RADIATION
ONCOLOGY (HERO)
RADIOTHERAPY EQUIPMENT AND DEPARTMENTS IN THE EUROPEAN
COUNTRIES: FINAL RESULTS FROM THE ESTRO-HERO SURVEY
C Grau1, N Defourny2, J Malicki3, P Dunscombe4, JM Borras5, M Coffey6, B Slotman7,
M Bogusz8, C Gasparotto9, Y Lievens10, on behalf of the HERO consortium
Aarhus University Hospital, Aarhus, Denmark | 2 European Society for Radiotherapy and Oncology, Brussels, Belgium | 3 Greater
Poland Cancer Center, Poznan, Poland | 4 Tom Baker Cancer Centre, Calgary AB, Canada | 5 University of Barcelona, Barcelona,
Spain | 6 Trinity College Dublin, Dublin, Ireland | 7 VU University Medical Center, Amsterdam, The Netherlands | 8 Cancer
Diagnosis and Treatment Center, Katowice, Poland | 9 European Society for Radiotherapy and Oncology, Brussels, Belgium | 10
Ghent University Hospital, Ghent, Belgium
1
BACKGROUND
New evidence-based regimens and novel high precision
technology have reinforced the important role of radiotherapy (RT) in contemporary multimodality management of
cancer. Current data estimate that about 50% of all cancer
patients would benefit from radiotherapy during the course
of their disease, with many of them requiring several courses
of treatment. Due to significant technical improvements, it
is now possible to cure more patients with fewer side effects.
This requires, however, access to modern equipment, including intensity modulated RT (IMRT), image-guided radiotherapy (IGRT), stereotactic RT and, most recently, particle
therapy. The European situation is highly diverse with large
differences in demographics, cancer incidence and economic
resources between countries. The ESTRO initiated HERO-project (Health Economics in Radiation Oncology) has
the overall aim of developing a knowledge base and model
for health economic evaluation of radiation treatments at the
level of individual European countries. To accomplish these
objectives, the HERO project addresses availability, needs,
cost and cost-effectiveness of radiotherapy.
OVERVIEW OF ABSTRACT
This first part of the HERO programme is based on a
detailed survey providing an inventory of European radiotherapy in terms of resource availability (departments,
equipment, and personnel), guidelines and reimbursement.
The current study focused on the distribution of radiotherapy equipment in European countries, and will be the first
of three papers analysing contemporary and comprehensive
data from a large questionnaire on the infrastructure of
European radiotherapy.
An 84-item questionnaire was sent out to European
countries, principally through their national societies. The
current report includes a detailed analysis of radiotherapy
departments and equipment, analysed in relation to the
annual number of treatment courses and the socioeconomic
status of the countries.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
A large variation between countries was found for most
parameters studied. There were 2,190 linear accelerators, 96
stereotactic SRS units, and 77 cobalt machines reported in
the 26 countries. A total of 12 countries (46%) had at least
one cobalt machine in use. The number of MV machines
(cobalt, linear accelerators and dedicated stereotactic
machines) per million inhabitants ranged from 1.3 to 9.6
(median 5.3) and the average number of MV machines
per department from 0.9 to 8.0 (median 2.6). The average
number of treatment courses per year per MV machine varied from 262 to 1,098 (median 422). Only 56% of the total
number of MV units was capable of IMRT and only 39%
were equipped for image guidance (IGRT). There was a clear
relation between socio-economic status, as measured by
GNI per capita, and availability of radiotherapy equipment
in the countries. In many low income countries in Southern
and Central-Eastern Europe there was very limited access to
radiotherapy and especially to equipment for IMRT or IGRT.
equipment in general and machines capable of delivering
high precision conformal treatments (IMRT, IGRT) in
particular.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
The next step in the HERO framework is to benchmark the
data to the equipment needs in the individual countries,
based on cancer incidence and stage mix. This will be performed in collaboration with the Collaboration for Cancer
Outcomes, Research and Evaluation (CCORE) in Australia.
The data will also be used in developing the HERO costing
model for European countries, in order to provide budgetary
estimates of the radiotherapy optimisation process in various
jurisdictions.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The results of this study document significant heterogeneity
in access to modern radiotherapy equipment in Europe.
Although the average number of MV machines per million
inhabitants and per department is now more in line with
QUARTS (QUAntification of RadioTherapy infrastructure
and Staffing needs) recommendations from 2005, there
is still significant heterogeneity in access to radiotherapy
equipment in Europe. While high income countries especially in Northern-Western Europe are well-served, other
countries are facing important shortages of radiotherapy
Diagramme showing the relationship between economic status (GNI per capita) and the average number of
radiotherapy treatment machines (MV units) per million inhabitants in 26 European countries.
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PHYSICS
INTRODUCTION
Overview of the best-scoring Physics Abstracts, Vienna
1.
Online 3D dose verification for VMAT treatments
2.
Application of dose warping for MR-Linac dose calculations INTRODUCTION
Each of the selected works represents the abstract with the highest score obtained during the blind
reviewing process, from five general categories (dosimetry, dose calculation, planning/optimisation/
modeling, inter and intra-fraction motion management, imaging). All submitted abstracts were assigned
to one of these 5 groups and each contained relatively equal numbers of abstracts.
p 17
p 18
4.
Patient-specific motion and treatment margins in pancreatic Stereotactic Body Radiation Therapy 5.
Validation of a hypoxia TCP model and dose painting in HNC: Planned interim analysis of a phase II trial
In the dose calculation topic group, an elegant solution to the complex problem of dose calculation in magnetic fields during
MRI-guided radiotherapy was proposed and tested by Pfaffenberger et al., by applying dose warping methods. One of the
major aims was to overcome the limitations of MC-based calculation with the objective of development towards on-line adaptation of the dose distribution to anatomical changes, being better visible with MRI.
p 19
In the planning/optimization/modeling group, the selected abstract by Fuchs et al reported interesting results of a planning
comparison between protons and helium ions for paediatric treatments. The relatively small differences between the two modalities have to be considered in the context of the significant efforts in reducing the risk of secondary cancer.
p 21
In the intra/inter fraction motion management group of abstracts, a study about the possibility of individualising margins for
pancreatic cancer patients treated with SBRT, taking intra-fraction motion into account, was selected. This study, performed
by Miften et al, represents a nice example of the large improvements in terms of reduction of the treated volumes when individual information can be considered and safely modeled to predict individual motion of the tumour. This work may also be
considered part of the topical field of developing methods and approaches to overcome the population-based approach in the
definition of margins.
3.
Can particle beam therapy be improved using helium ions? – A treatment planning study
focusing on paediatric patients The dosimetry best-scoring paper (Spreeuw et al.) demonstrated how in-vivo dosimetry using EPID may
become the future paradigm for automatic verification of advanced treatment modalities. The authors
incorporated safety procedures aimed at guaranteeing the accurate delivery of all fractions, including the
implementation of a trigger system capable of stopping the treatment once a defined threshold of deviation between expected
and actual doses was exceeded.
p 23
p 24
Finally, in the wide imaging group of abstracts, that by Thorwarth et al. was selected. This work is a high-level example of multi-disciplinary integration of imaging skills, clinical intuition and radiobiology modeling aiming to explore in a rational way
the potential of functional imaging in personalising radiotherapy treatments.
Although only a small selection of the large volume of high-quality abstracts submitted and presented in the meeting, these
five well represent the vitality of current radiotherapy physics research and its contribution to developments in clinical practice
and in the utilisation of the most advanced technical innovations.
Claudio Fiorino
Chair of the Scientific Advisory Group for Radiation Physics and Chair of the Scientific Programme Committee
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1.
2.
ONLINE 3D DOSE VERIFICATION FOR VMAT TREATMENTS
APPLICATION OF DOSE WARPING FOR MR-LINAC DOSE CALCULATIONS
Hanno Spreeuw, Roel Rozendaal, Igor Olaciregui-Ruiz, Anton Mans, Ben Mijnheer and Marcel van
Herk
Asja Pfaffenberger1, Uwe Oelfke1,2
Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
German Cancer Research Center, Heidelberg, Germany | 2 The Institute of Cancer Research / The Royal Marsden, London,
United Kingdom
BACKGROUND
BACKGROUND
At our institute, EPID images are acquired in vivo, i.e.
while the patient is being irradiated, but EPID dosimetry is
performed offline, i.e. the EPID-based dose reconstruction
is compared with the planned 3D dose distribution after a
fraction has been delivered. For most VMAT treatments
the dose differences are then evaluated after the delivery of
the first three fractions to confirm that they are within the
acceptance criteria.
OVERVIEW OF ABSTRACT
For optimum patient safety, all fractions should in principle
be verified online, i.e. while the dose is being delivered. The
verification should also be done in real time, such that the
dose reconstruction and the comparison between the cumulative planned and reconstructed dose keeps pace with the
EPID frame acquisition rate (3 frames per second). In this
way, in case of serious delivery errors, a trigger is generated
to halt the linac automatically before any serious harm can
be done to the patient. For monitoring the total dose delivered, it is required that the EPID-based dose reconstruction
is done in 3D.
1
tion such a tool would then be a major step forward towards
optimal safety in radiation oncology practice, without
increasing the clinical workload.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Improvements in speed have been the subject of research
in radiation oncology for over a decade, but many involve
the application of a graphics processing unit (GPU). This
software package is a profound example of parallel processing using multithreading on a multi-core CPU after the
implementation of efficient algorithms. Furthermore, new
technology has increased the complexity of external beam
radiotherapy and the therapy team must ensure the safety
and quality of these new approaches. This new tool would fit
into a comprehensive error prevention programme as developed and implemented by many radiation oncology centres.
OVERVIEW OF ABSTRACT
Existing methods for radiation dose calculation in a magnetic field, namely Monte Carlo (MC) simulations, still need at
least minutes to determine the dose distribution for a given
patient anatomy and set of radiation beams [Bol et al. 2012].
A faster calculation method would allow ful exploitation of
the potential of linac-MRI integration by adapting the dose
distribution directly to the observed position and shape of
the tumour as well as to surrounding organs present at the
time of treatment.. Our approach aims to derive the dose
within the magnetic field by deforming a dose distribution
calculated without any magnetic field.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
We built a software package that computes all necessary
input fields upfront, except, of course, for the portal image.
We optimised the dose reconstruction algorithm thus
reducing the CPU time to about 100 ms on a dual quad-core
CPU. Also, we optimised I/O performance. As a result, the
delivered 3D dose distribution is verified in sub-real time,
in less than 200 ms per portal image, which includes the
comparison between the reconstructed and planned dose
distribution. We were able to generate a trigger that halted
the linac after a large delivery error was introduced. In one
of our experiments this trigger was generated after the root
mean square (RMS) of the difference between the cumulative planned and reconstructed dose values surpassed a 10
cGy threshold (see Fig.1).
Fig. 1. RMS of difference of cumulative planned and reconstructed 3D dose
distributions as a function of gantry angle for correct and incorrect treatment.
After establishing robust criteria for triggers, our software
can be used routinely in all radiotherapy clinics having
EPIDs on their linacs. In combination with setup verifica-
PHYSICS | CONGRESS REPORT
WHAT IMPACT COULD YOUR RESEARCH HAVE?
Fast adaptation of the radiation dose distribution to the actual patient anatomy during the time of treatment carries the
potential to tailor the high dose region much more closely
to the tumour and further reduce safety margins involving
surrounding healthy tissues. In this manner, toxicity of the
treatment may be reduced. Research in the coming years
will establish the benefits and limitations of online image
guidance.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Modern radiation therapy devices include on-board imaging
devices, since patient anatomy changes between the initial
imaging for treatment planning and subsequent treatment
sessions stretching over a period of days or weeks. Reasons
for this include the variable contents of hollow organs,
weight loss or gain, breathing motion and others. Currently,
therapy-integrated imaging is based on x-ray absorption,
yielding a high contrast between bone and soft tissues but
little contrast between different types of soft tissues. In this
respect, MRI is known to be superior, and that is why several
groups worldwide have chosen to work on MRI integration
with radiation therapy devices. Another advantage of MRI
is the absence of imaging doses caused by ionising radiation, such that no constraints exist with respect to imaging
time or frequency. More frequent and more precise imaging
opens up new possibilities to adapt the dose prescription and
beam settings to temporal changes or individual response.
Investigation of adaption strategies is a current subject of
research, aiming to further improve treatment outcome.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
WHAT IMPACT COULD YOUR RESEARCH HAVE?
18
In recent years, radiation therapy has focussed on image-guided treatments where it is expected that, by closely
monitoring anatomical and functional changes in the patient
over multiple irradiation sessions, the treatment can be
adapted even more specifically, aiming to increase tumour
control and reduce side effects of the therapy. Currently several groups worldwide are working on integrating magnetic
resonance imaging (MRI) with linear accelerators (linacs)
employed for radiation treatment. MRIs provide excellent
soft tissue contrast, and can be used to characterise function
and physiology of tissues. One challenge in using these
devices is that the magnetic field of the MRI alters the radiation dose deposition [Raaijmakers et al. 2005, 2008, Kirkby
et al. 2008], such that conventional dose calculation algorithms cannot be applied. This work presents an approach
for fast photon dose calculation in a magnetic field.
ESTRO
Our work presents the first non-MC dose calculation method in a magnetic field. Validation by means of MC phantom
simulation studies reveals that within homogeneous tissues,
dose warping results agree with the MC dose profiles in
shape and height (cf. Fig.1). This is where the highest benefit
of MRI guidance is expected. In more heterogeneous tissue,
deviations are significant, with up to 25 % observed at soft
tissue – lung interfaces. Dose warping was further used in a
simulation study of patient treatments, showing its applicability in the treatment planning process (cf. Fig.2). Thorough
validation of the method with MC results in patient geometries still remains to be done.
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3.
CAN PARTICLE BEAM THERAPY BE IMPROVED USING HELIUM IONS? –
A TREATMENT PLANNING STUDY FOCUSING ON PAEDIATRIC PATIENTS
Fuchs H, Knäusl B, Dieckmann K, Georg D
Department of Radiation Oncology & Christian Doppler Laboratory for Medical Radiation research for Radiation Oncology,
Medical University of Vienna/AKH Vienna, Austria
BACKGROUND
simple biological model for 4He. After validation of the
physical dose model with Monte Carlo methods it was integrated in the development version of a treatment planning
system. The first systematic plan comparison based on beam
scanning between protons and helium ions is presented to
quantify the potential benefits of Helium in a more realistic
clinical scenario.
Light-particles such as protons or helium ions (4He) show
superior physical dose characteristics compared to high
energy photon beams. Healthy tissues and sensitive organs so called organs at risk – which surround the treatment site,
can be spared more efficiently with these particles. Consequently treatment-related side effects can be minimised and
quality of life can be improved.
OVERVIEW OF ABSTRACT
In Europe four synchrotron-based cancer treatment and
research centres are in operation or under construction,
which offer both proton and carbon ion treatments. All of
them use pencil beam scanning for beam delivery. These
ion beam centers offer a wide range of research opportunities, including the exploration of novel ion species besides
protons and carbon ions.
Particles current use in clinical applications are protons and
carbon ions. Clinical experience has thus been gathered
with both types of particles especially during the last decade.
However, the first particle therapy treatments taking place
in Berkeley in the 80s explored several different particle
species. Since then particles other than protons and carbon
ions have been less studied, but further improvement of
radiation oncology by selecting the optimal particle is an
open research issue.
He has some theoretical advantages over protons that could
potentially improve dose distributions. Due to their higher
mass compared to protons, beam spreading and range
uncertainties are reduced by a factor of two. For example,
the beam penumbra of protons at greater depths is no longer
superior to photon beam therapy. But the penumbra of 4He
is superior to that of protons which enables the delivery of
steep dose gradients in the direction of OAR also at rather
large depth. Furthermore, 4He still resides in the low LET
area, which reduces uncertainties in biological models that
are encountered when using heavier ions such as carbon
ions.
The potential of scanned helium ion beam therapy compared
to proton beam therapy was explored for paediatric patients.
Especially in children, 4He is a promising new beam quality,
due to the superior biological and physical characteristics.
Helium ions could potentially reduce low dose areas that are
known to be related to an increased induction of secondary
cancer.
More specifically, the treatment planning study was conducted for five paediatric neuroblastoma and five Hodgkin
lymphoma patients.
For this purpose a newly in-house developed dose calculation engine and a simple biological model for 4He was
utilized, which we integrated into the research version of the
Hyperion treatment planning system.
4
Up to now, these theoretical benefits of 4He could not be
quantified in treatment planning studies, because no treatment planning system was available which supports dose
calculations with scanned Helium ion beams.
We developed a new dose calculation engine and a first
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WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
Systematically steeper PTV dose-volume-histogram curves
were obtained for helium ions, with increased V95% values.
Improved organ at risk sparing was observed for helium
ions for those OAR located in close vicinity to the target. On
average helium ions delivered 26% less dose to the kidneys
in neuroblastoma patients compared to protons. The liver
was spared equally well for helium ions and protons with
D50% < 1 Gy(RBE).
Dose weighted difference maps showed reduced entrance
doses for 4He for both indications, as illustrated in fig. 1
for one representative neuroblastoma patient. Regarding
the proton plan for this patient, 4% of the voxels received
a higher dose than in the corresponding helium ion plan
(difference > 1 Gy(RBE)).
For Hodgkin lymphoma patients helium ion and proton
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21
4.
beam therapy performed comparably, which can be explained by the rather large PTV sizes in relation to organ at
risk volumes.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
PATIENT-SPECIFIC MOTION AND TREATMENT MARGINS IN PANCREATIC
STEREOTACTIC BODY RADIATION THERAPY
Our study offers the first step towards exploring the potential of helium ions for paediatric patients. In a further study
we would like to assess more indications and treatments
with higher doses, such as brain tumour patients.
The theoretical results obtained so far stimulated a more
in-depth look at the clinical potential of 4He. In order to
facilitate this we would appreciate the experimental verification of the biological and physical models at new particle
beam therapy centres having access to helium ion beams. A
long term goal would be the future consideration of helium
ions in clinical studies.
Moyed Miften, Bernard Jones, Norio Fukami, and Tracey Schefter
University of Colorado School of Medicine, USA
BACKGROUND
Using very high doses of radiation to ablate tumours is an
emerging treatment option for pancreatic cancer. However,
there is little room for error when delivering these high
doses, as the pancreas sits very close to the radiationsensitive small bowel. Additionally, the pancreas undergoes
significant respiratory-induced motion, which makes
avoiding nearby critical structures even more difficult.
4-Dimensional CT is often used to measure and account
for respiratory motion; however, pancreatic motion is much
more unstable than lung or liver motion.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Particle beam therapy has already had a distinct impact on
radiation oncology in providing novel treatment options
with excellent outcomes. The potential of helium ions has
been already known for a long time and could further
improve particle beam therapy. The installation of helium
ion sources, tuning of synchrotrons and thus the availability of helium ions for experimental non-clinical research
based facilities is envisaged in some centres. Other groups
explored more sophisticated radiobiological models, i.e. the
MKM model, for helium ions. These activities demonstrate
an increased interest of the scientific community in 4He.
Moreover some initial studies investigating the potential of
helium ions for particle CT have been started recently.
OVERVIEW OF ABSTRACT
The goal of this work was to develop patient-specific methods to account for motion during pancreatic radiotherapy.
Our hypothesis is that it may be possible to escalate dose
in patients with very consistent motion. Likewise, it may
be necessary to expand treatment margins in patients with
inconsistent motion. We developed an algorithm to calculate
the motion trajectory of pancreatic tumours using existing
pre-treatment images. From these trajectories, we calculated
the dosimetric impact of several motion-management strategies. We used this to analyse the motion of 15 patients who
underwent ablative pancreas radiotherapy.
Seeing the potential of proton and carbon ion therapy all
over the world encourages us to investigate new particle
species for radiation oncology more generally.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
As we learn more about cancer, we find less utility in
one-size-fits-all cancer treatments. Radiation oncology is
improving outcomes through the use of ablative radiotherapy, with extremely precise deliveries of high doses to specific
locations within each patient’s body. Our work takes this a
step further, and examines the specific ways each patient’s
tumour moves. Our methods will allow clinicians to target
pancreatic tumours more precisely, sparing dose in those
with consistent breathing and expanding treatment when
uncertainty is higher. This type of analysis will allow for
the creation of treatment plans that are tailor-made to each
patient’s anatomy and motion.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
We found significant variation in motion between patients
(from ±0.7 mm to ±10.8 mm uncertainty in position). However, on an individual level, the motion observed was remarkably stable; in other words, patients can be divided into
stable/unstable motion groups. We found that patient-specific treatment margins needed to encompass this motion were
an average of 6 mm smaller than a population-based margin
achieving the same level of coverage.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
This work demonstrates the possibility of using individualized treatment margins for pancreatic radiotherapy which
account for individual variations in the consistency of
motion. By shrinking margins in patients with consistent
motion, it may be possible to escalate dose with the goal of
improving local control. In future work, these methods will
be used to analyse the effectiveness of other motion-compensation strategies, such as breath-hold or gated treatment.
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ESTRO
Fig. Respiratory-induced tumour motion for 15 patients in the left-right (LR),
anterior-posterior (AP), and superior-inferior (SI) directions. Motion was
predominantly in the SI direction, although some patients display significant LR/
AP deviations. There were large differences between patients, but the breathing
of each individual patient was self-consistent and stable.
CONGRESS REPORT | PHYSICS
23
5.
VALIDATION OF A HYPOXIA TCP MODEL AND DOSE PAINTING IN HNC:
PLANNED INTERIM ANALYSIS OF A PHASE II TRIAL
Daniela Thorwarth, Linda Wack, Christina Pfannenberg, Markus Alber, Daniel Zips, Stefan Welz
Section for Biomedical Physics, University Hospital for Radiation Oncology Tübingen, Germany
BACKGROUND
Tumour hypoxia, i.e. the lack of oxygen in tumours, has
for long been known to increase radiation resistance. Our
study investigates whether the escalation of radiation dose
focussed to hypoxic areas of the tumour is clinically feasible
and leads to a better outcome after radiotherapy (RT).
OVERVIEW OF ABSTRACT
The purpose of this phase II study was to assess the clinical
feasibility of hypoxia dose painting (HDP) in head-and-neck
cancer (HNC) based on dynamic positron emission (PET)
using the hypoxia tracer FMISO. A further aim of the study
was to validate a mathematical model relating hypoxia as
measured by dynamic FMISO PET with an individual tumour control probability (TCP). All patients were examined
with dynamic FMISO PET before the start of treatment. If
patients presented with hypoxic tumours, they were stratified into two treatment arms: 1) standard IMRT with 70 Gy
or 2) HDP with 77 Gy to the hypoxic volume (HV). The data
presented in the context of this planned interim analysis are
from the first n=20 patients enrolled into the study.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The results of this randomised phase II trial showed that
hypoxia PET imaging is able to stratify HNC patients into
different risk groups. As a consequence, we will be able to
identify patients who need treatment intensification. This
group of patients may profit in the future from HDP in
terms of higher control rates.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
One of the major trends in oncology at the moment is the
idea of personalising cancer treatment according to the individual needs of the patient. In this study, we intend to measure individual functional parameters which are prognostic
for therapy success by using hypoxia PET and apply an
individual radio-oncologic intervention by means of HDP.
Thus, HDP based on functional PET imaging is potentially
one possible approach to personalised medicine.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
1. HDP based on dynamic FMISO PET is clinically feasible.
All patients completed imaging and therapy as planned.
N=5 patients did not present with any tumour hypoxia,
whereas among the remaining patients, n=7 were randomised into the experimental treatment arm.
2. HVs were very small, the mean HV size was 8.6 mL ranging from 0.2 to 49.7 mL. As a consequence, the prescribed
HDP dose level could only be realised in HVs larger than
approx. 5 mL.
3. The previously derived hypoxia TCP model was validated by the FMISO PET data acquired within this study
(p=0.54) and permitted stratification into two patient
groups (hypoxic/non-hypoxic) presenting with significantly different local control rates after RT (p=0.023).
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BRACHYTHERAPY
INTRODUCTION
1.
Using MRI and integrated ultrasound to guide brachytherapy for cervix cancer
2.
Report on real-time electromagnetic seed drop position validation for low dose rate brachytherapy
3.
Preservation of erectile function after prostate permanent implantation for localised prostate cancer INTRODUCTION
We have had, as always, a large selection of abstracts submitted from which we have selected an
exciting programme of high-quality proffered papers for the brachytherapy track of ESTRO 33. These
reflect many aspects of modern image-guided brachytherapy covering some of the major sites; gynaecology and prostate, as well as a major physics contribution and less common clinical indications
such as choroidal melanoma. We have ‘donated’ our best papers to the ‘highlights’ sessions to ensure
that brachytherapy is seen by a wide audience as a major important modality in radiation oncology.
In addition I have selected five of those chosen for presentation in the brachytherapy track which are
shown here demonstrating the breadth and depth of the brachytherapy programme.
p 27
p 28
p 30
p 32
4.
Salvage reirradiation for recurrent prostate cancer patients: three fractions of high-dose-rate brachytherapy p 34
Image guided brachytherapy for cervical cancer is now generally accepted as the gold standard however many radiotherapy centres, particularly in less well developed health care environments struggle to apply the GEC-ESTRO guidelines
which are based on MR imaging. The paper from Melbourne evaluating ultrasound as a means of imaging to define the
target volume is therefore of great importance in developing the image-guided concept beyond MR. No clinically significant differences in measurement using MR or ultrasound in 141 patients was seen providing considerable reassurance
for those who are able to access ultrasound but not MR or CT that this offers a viable and potentially equivalent approach
which can be used to integrate the advantages of image-guided cervical brachytherapy into practice.
LDR brachytherapy is now well established as an effective treatment for early prostate cancer having a highly favourable
toxicity profile. Considerable advances have been made in the technique based on real time implant dosimetry. These
however depend upon accurate tracking of seed deposition at the time of implantation. The paper from Quebec is therefore of considerable interest in describing a novel approach using RF/electromagnetic technology to accurately validate the
seed drop position during a seed implant. Evaluation in a phantom using this EM hollow needle prototype has achieved
a detection rate of 100% with a mean position error of only 1.5mm. Successful integration of this novel technology into
brachytherapy systems for LDR prostate implantation will have a further impact on improving implant quality as we strive
to optimise our techniques.
One of the major advantages of LDR brachytherapy over radical surgery is the different toxicity profile and in particular
the chance for many men to retain potency. The series from Vienna featured here is therefore important in providing
mature data on this effect after seed brachytherapy with either palladium or iodine. The strength of this study lies in the
prospective evaluation of erectile function with patient-based questionnaires using the internationally recognised IIEF
scale. Overall potency was maintained in 46% at two years and 51% over five years in a large cohort of 285 patients with
no major effect seen in age up to 70 years, previous use of androgen deprivation therapy or external beam therapy. This
series confirms therefore the very high potency rates to be expected after seed brachytherapy and gives us robust data with
which to counsel patients considering this approach.
Local relapse of prostate cancer presents a difficult management problem with no clear preferred option; until recently re-irradiation has not been widely considered but the ability to deliver localised high doses to the prostate using
brachytherapy is now being exploited by several groups in this setting. The contribution from the group in Gliwice
describing their experience using high dose rate brachytherapy for recurrent prostate cancer in 61 men is therefore of
great interest. Toxicity after reirradiation is always of concern and it is encouraging to note only one grade 3 acute urinary
toxicity event and late toxicity limited to grade 2 or less in 55 patients. Three year disease-free survival was 69% with
eight patients developing metastatic disease and an overall survival at three years of 98% falling to 83% at five years. Their
conclusion that HDR brachytherapy is a good option in carefully selected patients is borne out by their data and should
encourage other groups to explore this approach in well-designed prospective studies.
In addition don’t miss out on reading the two abstracts which have received awards. The paper by V. Rudzianskas from
Lithuania has been selected for the GEC-ESTRO Best Junior Presentation Award. This addresses the important area of
reirradiation in head and neck cancer and reports on 64 cases treated in a prospective randomised study using salvage
external beam or HDR brachytherapy. Superior local control rates were achieved with brachytherapy. The authors are to be
congratulated for completing a prospective randomised study in this difficult area providing us with important data supporting HDR brachytherapy as the preferred salvage modality. The ESTRO-Nucletron brachytherapy award is presented to
H. Westerveld for her paper on a novel dose reporting method for vaginal dose in gynaecological brachytherapy demonstrating the utility of the new reporting parameters in comparing vaginal dosimetry across seven centres in the EMBRACE
study (European and international study on MRI-guided brachytherapy in locally advanced cervical cancer).
Peter Hoskin
Chair of the Scientific Advisory Group for Brachytherapy
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1.
USING MRI AND INTEGRATED ULTRASOUND TO GUIDE BRACHYTHERAPY FOR
CERVIX CANCER
Sylvia van Dyk, Srinivas Kondalsamy-Chennakesavan, Michal Schneider, Kailash Narayan
Peter MacCallum Cancer Centre, Australia
BACKGROUND
Incorporating MRI imaging into multi-fractionated
gynaecological brachytherapy programmes is difficult.
Alternative imaging modalities have to be sought which
enable imaging to be used at all fractions and all stages of
the procedure. Ultrasound is an accessible imaging modality
that can be used to guide applicators into treatment position,
identify the target volume and surrounding tissues, assess
dosimetry, and verify treatment (Fig.1).
OVERVIEW OF ABSTRACT
The purpose of this research was twofold:
1. To compare measurements of the cervix and uterus made
with MRI and ultrasound to determine the level of agreement between the imaging modalities.
greater precision of dose delivery. This has the potential to
enable individualised conformal treatment to be planned
and delivered. The impact of this is better targeted radiation
with scope for dose escalation and reduced toxicity.
Fig. 1. Uses for ultrasound at each insertion and step of the brachytherapy
procedure.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
This research is indicative of trends in oncology that seek to
offer individualised treatment to patients. Use of imaging to
verify beam placement and target coverage prior to treating
with external beam is becoming standard of care. This
research highlights how this is possible in gynaecological
brachytherapy.
2. To evaluate changes in brachytherapy volume over the
course of treatment with ultrasound.
Fig. 2. Ultrasound used to guide applicator insertion, verify the brachytherapy volume, and assess dosimetry over
the course of brachytherapy.
A. Transabdominal ultrasound – longitudinal view of uterus with applicator in-situ at fx 1 showing ultrasound
based isodose coverage
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
B. Transabdominal ultrasound – longitudinal view of uterus with applicator in-situ at fx 2 showing same isodose
distribution as fx 1, there was no change to treatment volume or isodose coverage
1. There was good agreement of measurements of the cervix
and uterus on MRI and ultrasound. This means ultrasound can be used in conjunction with or as an alternative
to MRI in limited resource settings.
C. Transabdominal ultrasound – longitudinal view of uterus with applicator in-situ at fx 3 showing same isodose
distribution as fx 1, there was no change to treatment volume or isodose coverage
D. Transabdominal ultrasound – longitudinal view of uterus with applicator in-situ at fx4 showing same isodose
distribution as fx 1, there was no change to treatment volume or isodose coverage
2. Agreement was strongest at the posterior surface of the
cervix and uterus. This is important as accurate identification of the posterior uterine wall ensures radiation can
be conformed to the uterus and so avoid the surrounding
rectum and bowel.
E. T2 sagittal MRI - view of uterus with applicator (taken at fx 1). Isodose coverage was devised on ultrasound
and back projected onto MRI after treatment had been delivered
F. T2 coronal MRI - view of uterus with applicator (taken at fx 1). Isodose coverage was devised on ultrasound
and back projected onto MRI after treatment had been delivered.
3. Changes in measurements to the posterior uterine wall
over the course of brachytherapy were not statistically significant. This means a conformal plan devised at fraction
one can be used over the course of treatment reducing the
rate of replanning (Fig.2).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The implications of these findings are that it is possible to
integrate an accessible imaging modality (ultrasound) into
gynaecological brachytherapy programmes. Use of imaging
at each insertion and at each stage of the procedure ensures
greater technical accuracy of applicator placement and
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2.
REPORT ON REAL-TIME ELECTROMAGNETIC SEED DROP POSITION
VALIDATION FOR LOW DOSE RATE BRACHYTHERAPY
Emmanuel Racine1, Dirk Binnekamp2, Gilion Hautvast3 and Luc Beaulieu1
Département de Radio-Oncologie et Centre de Recherche du CHU de Québec, Canada | 2 Philips Healthcare Imaging Systems,
Best, The Netherlands | 3 Philips Group Innovation - Biomedical Systems, Eindhoven, The Netherlands
1
BACKGROUND
Low dose rate (LDR) brachytherapy involves precise
implantation of radioactive seeds in a targeted region of the
body to locally treat cancer. The context of this study relates
to the evaluation of electromagnetic (EM) tracking devices
in terms of accuracy, stability and compatibility for their
potential integration in clinical treatment protocols. EM
devices can provide real-time precise 3D tracking of needles
or other surgical tools with no line-of-sight requirement,
and can therefore be of great benefit for treatment assistance
and/or delivery.
OVERVIEW OF ABSTRACT
The purpose of this research is to assess the performance
of an EM LDR brachytherapy needle prototype (cf. Fig. 1)
which, in addition to standard 3D tracking capabilities, possesses the ability to detect the passing of seeds in its embedded RF coils and generate corresponding seed drop position
estimates. Our study characterises the accuracy of the seed
drop detection mechanism of the needle by comparing true
positions of seeds dropped in a phantom with those estimated by the EM detection mechanism.
interesting real-time alternative to more time consuming
intra-operative x-ray based imaging methods as a means of
asserting seed positions in a region of interest. Research on
automatic EM/RF seed passing detection is likely to develop
further with the optimisation of hardware components and
associated detection algorithms or the adaptation of the
technology to other medical uses.
Fig. 1. EM LDR brachytherapy needle prototype
Fig. 3. Drop position error analysis: History of error distribution
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
RECORDED AMONG ALL TRIALS [MM]
Research, development and interest in 3D EM tracking
systems for medical uses have been particularly prominent
over the past decade. This work alongside the construction
of a first EM LDR needle prototype has been mainly driven
by the potential benefits and improvements they can offer
toward increased accuracy and real-time tracking needed for
LDR seeds procedures. This work also assesses a significant
trend toward tool integration by virtue of new technologies
as a means of improving overall treatment efficiency for
needle or catheter-based medical procedures.
MIN. VALUE
MAX. VALUE
AVG. VALUE
MEAN ERROR
1.1
2.0
1.5
ERROR STD
0.7
1.0
0.9
MAXIMUM
ERROR
2.9
4.0
3.4
Table 1. Drop position error analysis: Summary of important statistical results
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
A total of 200 seeds were dropped in a specially designed
phantom from 10 separate executions. The EM-tracked
needle achieved a detection rate of 100% without any false
detection. A detailed analysis showed that mean drop
position errors averaged 1.5 mm (over all trials), and that
maximum drop position errors averaged 3.4 mm (cf. Fig 2,
3 and Table 1). Measurement errors also include undesirable
and uncontrollable effects such as seed motion upon deposition. The average positional error of 1.5 mm is below the
commonly accepted 2 mm accuracy threshold in the field,
which demonstrates the potential clinical suitability of the
technology for its use in LDR brachytherapy protocols.
Fig. 2. Seed drop position validation (one trial)
WHAT IMPACT COULD YOUR RESEARCH HAVE?
EM detection of seed passages in embedded RF coils of 3D
tracking devices is a completely new technology. The incorporation of such tools in clinical protocols could greatly
speed up treatment validation procedures by providing an
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3.
PRESERVATION OF ERECTILE FUNCTION AFTER PROSTATE PERMANENT
IMPLANTATION FOR LOCALISED PROSTATE CANCER
VARIOUS DEGREES OF ED (SCORE 1-21)
%
≤ 60
NR
70
31
44,29
> 60
246
186
75,61
R. Oismueller, K. Poljanc, C. Somay, S. Schuch, M. Rauchenwald, St. Madersbacher , R. Hawliczek
NR
SMZ-Ost Donauspital , Vienna
SEVERE (1-7)
%
≤ 60
70
11
15,71
> 60
246
103
41,87
MODERATE (8-11)
%
NR
OVERVIEW OF ABSTRACT
The IIEF 15 is a validated questionnaire, which helps to
define erectile function (EF) by patient’s self-assessment (not
influenced by someone else). It includes questions related to
sexual activity, erection, as well as sexual desire and sexual
satisfaction.
In our study we only used 5 questions related to achieve
and maintain an erection and sexual satisfaction. Definition of erectile dysfunction (ED) in urological as well as
radio-oncological studies varies tremendously. Therefore
comparisons of data have to be interpreted carefully and it is
important to use validated questionnaires to obtain reliable
and comparable results.
EF is a crucial issue in men with prostate cancer, especially
in younger men. Therefore it is very important to be able to
offer reliable data with regard to EF after definitive therapy
for prostate cancer.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
1. ED is very common before definitive therapy. 46.75% of
men < 60 ys and 75.51% men > 60 ys had ED to varying
degrees (“none”, “mild”,”mild-moderate”, “severe” ED)
(Table 1).
2. Approximately fifty percent of primarily potent men
maintain potency after two and five years after permanent implantation of the prostate. Preservation of erectile
function was significantly influenced by patient’s age at
treatment time.
Tumour localisation can often be precisely identified
on multi-parametric MRI.
In selected patients, MRI images fused with transrectal ultrasound in real-time, enable focal therapy (implants in well-defined areas of tumour). Thus toxicity
in general and erectile dysfunction in particular is
expected to decrease.
≤ 60
70
2
2,86
> 60
246
14
5,69
MILD - MODERATE (12-16)
%
NR
≤ 60
70
5
7,14
> 60
246
26
10,57
MILD (17-21)
%
NR
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
1. Cancer therapies in general are becoming more sophisticated. Therapy for prostate cancer is no exception.
Increased use of new diagnostic instruments like multiparametric imaging (MRI, Choline-PET) offer better
information regarding clinical tumour stage and subsequently allow more individualised treatment decisions,
taking into account clinical and functional status and
individual patient preferences. In caring for prostate
cancer patients, it is crucial that specialists provide them
with information regarding all treatment modalities and
their associated side effects. This is especially true in the
delicate area of sexual activity.
≤ 60
70
13
18,57
> 60
246
43
17,48
Table 1. Pretreatment ED
Fig. 1. 55,6% of patients < 60 years with “no” ED remain in that category after
60 months
2. Research on focal therapy, as mentioned above, will make
a difference in toxicity and also in preservation of EF
when interstitial brachytherapy is used in the future.
3. Short term androgen deprivation therapy before permanent brachytherapy showed no significant influence on
potency preservation after two and five years respectively
(Fig. 1 & 2).
Fig. 2. 35,3% of patients > 60 years with “no” ED remain in that category after
60 months
In our analysis only patient’s pre-treatment age was significant for predicting erectile preservation after brachytherapy.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
It is important to identify more pre-treatment parameters
which predict preservation of EF after therapy.
Further investigations for optimisation of treatment techniques could also add to preservation of erectile function
e.g.: “Focal therapy”:
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4.
SALVAGE REIRRADIATION FOR RECURRENT PROSTATE CANCER PATIENTS:
THREE FRACTIONS OF HIGH-DOSE-RATE BRACHYTHERAPY
Piotr Wojcieszek, Sylwia Kellas-Sleczka, Brygida Bialas, Marek Fijalkowski
MSC Memorial Cancer Centre and Insitute of Oncology, Gliwice Branch, Poland
BACKGROUND
There are a lot of modalities available in the primary
management of prostate cancer patients. Management
of recurrence is difficult, particularly after irradiation.
Local relapse of prostate cancer after radiotherapy is
still a problem. It may cause decrease in quality of life,
dissemination and death. Due to patient’s performance
status or lack of his consent salvage surgery is often
not possible. External beam (EBRT) reirradiation may
be dangerous, because of retreated volumes and high
probability of early and late toxicity. Salvage brachytherapy
seems to be a very useful tool in prostate recurrence
management.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Hopefully IGRT and ultrahypofractionation will reduce the
number of prostate cancer relapses. HDR brachytherapy
has a strong impact on local control and overall survival in
prostate cancer patients. Although the future is promising,
we are now following patients treated with suboptimal total
doses (≤72 Gy) or without daily IGRT. There are still many
centres worldwide without state-of-art IGRT LINACs. That
is why HDR brachytherapy remains a useful tool for recurrent prostate cancer patients.
OVERVIEW OF ABSTRACT
We wanted to evaluate efficacy and toxicity of salvage highdose-rate brachytherapy (HDR BT). Our schedule is based
on HDR BT alone, however we decided to decrease the
total dose. We started to use 30 Gy in 3 fractions every 14
days, instead of 33 Gy in 3 fractions. Main inclusion criteria
were: localised prostate cancer relapse after EBRT (alone
or combined with BT), no prior radical prostatectomy and
histopathological confirmation of recurrence. Patients had to
be anatomically suitable for temporary implantation under
transrectal ultrasound guidance with epidural anaesthesia.
Acute and late toxicity were evaluated using the EORTC/
RTOG scale.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
Salvage HDR brachytherapy has acceptable toxicity (acute
GU grade 3 – 1 pt; late GU grade 4 – 4 pts, late GI grade 1
toxicity – 4 pts). There is good overall survival (3-year OS =
98%; 5-year OS=83%). There were 13 biochemical recurrences, but no local relapses. This means that most of these
patients had distant failures (8 pts).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The most important is to change thinking on HDR
brachytherapy as a radical salvage treatment of prostate recurrences. Additionally, we need to find the lowest possible,
but still effective HDR BT dose schedule. Patient selection
should be done extremely careful, due to the risk of distant
failures.
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RTT (Radiation TherapisT)
INTRODUCTION
At ESTRO 33, RTTs had the opportunity to learn about recent innovations in
the field of radiation therapy and particularly in the areas of contouring, ART
and treatment planning.
We have selected three abstracts that best illustrate these innovations for your
interest.
INTRODUCTION
1.
Coronary dosimetry based on heart CT angiographies for Hodgkin lymphoma radiation therapy
2.
Library of plans for VMAT irradiation of cervical cancer: first clinical experience
3.
Multi-Criteria optimisation individualises treatment plan selection in stage III lung cancer patients
p 37
p 38
p 40
p 42
Moignier et al from the Institute of Radiation Protection and Nuclear Safety,
Fontenay aux Roses, France studied the data of 50 patients from a cohort of 250 who had been previously treated with
radiotherapy for Hodgkin’s Lymphoma and diagnosed with stenosis of the coronary arteries. For 10 of these patients, their
full medical history was obtained. On each CT, the whole heart, aorta, left main coronary, left anterior descending coronary, circumflex coronary artery and right coronary artery were delineated. Dose reconstructions using the recorded beam
set up and dosimetric data were performed.
This group found that doses associated with the stensoses ranged from 29 Gy to 48 Gy, a dose that was consistently higher
than 95% of the tumour dose prescription. It was concluded that dose may be a determining factor in the manifestation of
such stenoses in this patient population.
Kager et al from the NKI, The Netherlands, reported on the development of a ‘library of plans’ method to improve motion
management caused by variations in bladder filling in the treatment of six cervical patients using VMAT. The library of
plans consisted of four plans including full and empty bladder, as well as two equally spaced intermediate bladder volumes. The authors found that a cone beam CT prior to treatment yielded appropriate image quality for RTTs to select the
most appropriate plan.
Finally, Loeters et al. from RISO and the NKI in the Netherlands presented their multi-criteria optimisation strategy for
individual plan selection in advanced stage lung cancer patients. Three plans were constructed for each patient. The first
used conventional IMRT, while the next was optimised with multi-criteria optimisation using a standard protocol. Both
of these plans were constructed by RTTs. The third plan was constructed by the Radiation Oncologist using multi-criteria optimisation, taking specific clinical factors as well as patient characteristics into consideration. The plans were then
ranked by a Radiation Oncologist following plan evaluation. In the majority of cases, the plan created by the radiation
oncologist, that also considered clinical and patient-specific factors, was the most frequently selected; leading the authors
to conclude that multi-criteria optimisation, including the radiation oncologist’s clinical and patient-specific knowledge
yields personalised treatment for each patient.
We hope you enjoy the following interviews with the authors of these studies and learning about their work in more detail.
Michelle Leech & Martijn Kamphuis
Co-chairs of the Scientific Advisory Group for Radiation Technology
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1.
CORONARY DOSIMETRY BASED ON HEART CT ANGIOGRAPHIES FOR
HODGKIN LYMPHOMA RADIATION THERAPY
A. Moignier1, S. Derreumaux2, D. Broggio1, A. Beaudré3, T. Girinsky4, J.F. Paul5, B. Aubert2, D.
Lefkopoulos3, E. Deutsch4, J. Bourhis4.
Institute of Radiation Protection and Nuclear Safety, PRP-HOM/SDI/LEDI, Fontenay aux Roses, France | 2 Institute of Radiation
Protection and Nuclear Safety, PRP-HOM/SER/UEM, Fontenay aux Roses, France | 3 Institut Gustave Roussy, Medical physics
department, Villejuif, France | 4 Institut Gustave Roussy, Radiation therapy service, Villejuif, France | 5 Marie Lannelongue Surgery
Center, Radiology Department, Le Plessis-Robinson, France
1
Fig 1: Examples of 3D coronary dose mapping with location of the coronary lesions.
BACKGROUND
Cardiovascular diseases are a major concern following
radiation therapy (RT). At the Gustave Roussy institute,
a prospective coronary heart disease screening in
asymptomatic Hodgkin lymphoma patients was performed
using coronary CT angiography (CCTA). Coronary stenoses
were diagnosed in approximately 25% of the patients (46 out
of 179 patients). The risk factor analysis demonstrated that
age at treatment, hypertension, hypercholesterolemia as well
as the radiation dose to the coronary artery origins (CAO)
were prognostic factors.
OVERVIEW OF ABSTRACT
Our study aimed to benefit from the coronary tree visualisation on the patient’s CCTA to retrospectively assess the
coronary dose distribution. Where available, anatomical data
from the RT treatment planning CT scan and the CCTA
were fused in a sole anatomical representation of the patient.
The beams from the treatment planning were setup and
the monitor units attributed. Calculations were performed
using a treatment planning system and heterogeneities were
taken into account (lungs, sternum and backbone). The dose
reconstructions were performed for 12 cases (patients with
coronary lesions) and 21 matched controls (patients without
coronary lesions).
coronary diseases increased linearly with the median dose
to the coronary segment by 3.8% per Gray (95% confidence
interval, 2.4 to 5.3; p<0.000001). Considering a conditional
logistic regression with damaged segments of the cases and
normal segments of the cases and controls, this increase was
assessed as 4.9% per gray (95% confidence interval, 0.4 to
9.5; p-value<0.05).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
Such detailed coronary dosimetry seems quite unique. It is
of major interest for the normal tissue complication probability evaluation and for improving treatment techniques
in order to better spare cardiac function. Similar research is
required to confirm the findings larger cohort.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Our increased coronary disease rate per additional gray to
the coronary segment median dose after Hodgkin lymphoma radiotherapy can be considered in parallel with the
increased major coronary event rate with the mean dose to
the heart after breast radiotherapy by 7.4% per Gray [Darby
et al, N Engl J Med, 2013].
Fig 2: Comparison of the median doses (Dmed) to the coronary segments between cases and controls by describing the mean and the standard deviation (SD).
Data from the cases are in purple; data from the controls are in green.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
To the best of our our knowledge, this is the first time that
retrospective coronary dose reconstructions have been
performed with such precision regarding cardiovascular
anatomy and were directly matched to clinical reports on
coronary disease location (Fig. 1).
Our dosimetric approach, based on the median dose to the
9 coronary segments yielded the results shown in Fig. 2. Segments with lesions received doses significantly higher than
segments without lesions (p<0.001).
A conditional logistic regression between damaged and
normal segments of the cases indicated that the rate of
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2.
LIBRARY OF PLANS FOR VMAT IRRADIATION OF CERVICAL CANCER: FIRST
CLINICAL EXPERIENCE
P.M. Kager, F. Koetsveld, M. Bloemers, P. Remeijer
Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
BACKGROUND
Variation in bladder volume during the course of
radiotherapy affects cervix-uterus position and shape. In
our clinic, cervical cancer patients follow a full bladder
drinking protocol to obtain favourable anatomy and OAR
sparing. Setup and geometry are verified prior to treatment
with Cone Beam CT (CBCT). Despite the full bladder
drinking protocol, variations in cervix-uterus geometry are
present. Therefore, a relatively large CTV to PTV margin is
necessary. To improve motion management, we developed a
library of plans (LoP) methodology for cervical cancer.
OVERVIEW OF ABSTRACT
A LoP was made consisting of four VMAT plans corresponding to full bladder volume (LP1), empty bladder
volume (LP4) and two equally spaced intermediate bladder
volumes (LP2 and LP3). An anisotropic CTV to PTV
margin of 1 cm left-right and 2 cm in other directions was
used. Prior to each fraction a CBCT scan was acquired for
online setup correction and for plan selection by two trained
RTTs. In this study the first clinical experience with this new
method was evaluated.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
LoP for VMAT irradiation of cervical cancer improves
management of cervix-uterus motion caused by changing
bladder volume. In the first week of treatment, LP1 was
chosen most often and in the final week of treatment LP4
was chosen most often (Fig. 1).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
With LoP a large part of cervix-uterus motion is taken into
account that originally is covered by the relatively large CTV
to PTV margin. Due to improved management of cervix-uterus motion, the current CTV to PTV margin can be
reduced. Consequently, this will improve OAR sparing and
allow better opportunity for dose escalation with, for example, brachytherapy. Margin reduction with improved OAR
sparing also will reduce long term side effects and therefore
improve QOL.
Currently, a retrospective study is ongoing in our institute
to investigate by how much the CTV to PTV margin can be
reduced. The endpoint is better OAR sparing with the same
remaining coverage of the target volume.
Fig 1: Selection frequency of the 4 different VMAT plans (LP1 to LP4) for the total of 6 patients.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Except for cervical cancer, a LoP methodology is also applicable for other treatment sites, e.g. bladder cancer, where the
bulk of variation is dominated by a single factor, e.g. bladder
volume. Currently, several institutes have already developed
a LoP methodology for irradiation of cervical and / or bladder cancer. Other target areas that are subject to predictable
motion or volume change might also benefit from a LoP
methodology. Ultimately, the LoP methodology allows for
reducing CTV to PTV margins and therefore increasing
OAR sparing and hence quality of life.
A CBCT scan prior to treatment provides sufficient image
quality for trained RTTs to consistently select the most
appropriate plan (Fig. 2). Retrospectively, specialised RTTs
would have chosen a different plan for only 1 out of 138
pre-treatment CBCT scans.
For 6 out of 50 post-treatment CBCT scans a different plan
was chosen compared to pre-treatment. Therefore, intra
fraction motion due to increasing bladder volume should
be monitored and taken into account when selecting a
pre-treatment plan.
Fig 2: Sagittal view of cervix-uterus on the planning CT (pCT) and pre-treatment CBCT scans of fraction 5, 7 and 23. The CTVs corresponding to LP1 to LP4 are
projected on the pCT. The CTVs corresponding to the selected VMAT plans are projected on the pre-treatment CBCTs.
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3.
MULTI-CRITERIA OPTIMISATION INDIVIDUALISES TREATMENT PLAN
SELECTION IN STAGE III LUNG CANCER PATIENTS
E. Loeters1, J. Politiek1, T. Eiland1, H. Westendorp1, R. Kattevilder1, Z. van Kesteren2, A. Minken1
RISO, Radiation Oncology Department, Deventer, The Netherlands | 2 Academic Medical Centre (AMC), Radiation Oncology
Department, Amsterdam, The Netherlands
1
BACKGROUND
patient. MCO leads to an individualised high quality plan in
a time-efficient way. The MCO-approach, involves the RTO
in the treatment planning process and enhances the interaction between radiation oncologist and RTT. Pareto optimisation gives a quicker notion of contradictory objectives and
leads to clinically acceptable treatment plans more quickly.
In inverse planning, patient specific tradeoffs between
tumour coverage and healthy tissue sparing are resolved by
defining a set of planning objectives. The inverse planning
problem is solved by manually modifying optimisation
weights and values. The Radiation TherapisT (RTT) creates
a clinically acceptable plan by iteratively re-optimising
the treatment plan. The inverse planning approach can be
time consuming, resulting in an inefficient generation of
multiple plans per patient and eventually gives the radiation
oncologist only a binary choice of approving the proposed
plan. The question remains if this is an optimal solution for
the patient.
Multi-Criteria Optimisation (MCO) is a new intuitive
technique of approaching intensity-modulated radiotherapy planning. The workflow in this method of planning is
a problem formulation without giving importance weights
to the planning objectives. A set of relevant Pareto optimal
plans is generated based on a user-specified set of objectives
and constraints. Plans are Pareto optimal when there is
no objective that can be improved without compromising
another objective (Fig. 1).
With MCO the user can balance tradeoffs in real time by
navigating the Pareto surface. By actively involving the
radiation oncologist (RTO) in navigation, MCO leads to an
optimal plan, taking into account clinical guidelines and patient specific characteristics. The navigated dose distribution
is fluence-based. To obtain a deliverable plan, the navigation
step is followed by segmentation of the plan.
OVERVIEW OF ABSTRACT
The purpose of the research is to assess the benefit of Multi-Criteria Optimisation in clinical practice for stage III lung
cancer patients in comparison to inverse planning. Clinical
individualisation, treatment plan quality and time-efficiency
were considered in this study.
For 20 lung cancer patients, three plans (prescribed dose
66 Gy) were generated. An RTT made one conventional
IMRT-plan and one optimised with MCO (RayStation 4.0,
RaySearch Labs, Stockholm, SE), based on dose prescription
for the PTV and Quantec goals for the OAR. To review the
influence of MCO to clinical decision-making, a radiation
oncologist navigated and generated a third plan, taking
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Based on these clinical results, this MCO-concept for lung
cancer patients may also be implemented for other target
areas. MCO could lead to a new approach in treatment
planning.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Individualisation of radiotherapy is of high priority to
further improve treatment outcome. Through automation,
treatment planning becomes more efficient. Therefore the
emphasis will be increasingly to have a patient-individualised
plan. Patients have also become more outspoken and expect
to be considered as a full partner in decision making. Each
patient has unique clinical properties and wishes that could
be taken into account. By individualising and involving the
radiation oncologist in treatment planning using MCO, we
could give the patient an optimal treatment and also meet
with the broader developments in oncology.
Fig 1: A Pareto-front considering two objectives: PTV coverage vs. OAR sparing.
Both objectives could not be met perfectly. Each point represents a treatment
plan. There should be a minimal PTV coverage and a maximum OAR sparing
therefore all red points are not acceptable. All blue points are clinically acceptable
but not necessarily optimal plans. The green points represent plans that are feasible and where no objective can be improved without compromising the other,
these are Pareto-optimal plans.
into account clinical guidelines and patient specific characteristics. At a later stage the three created plans (presented
as random and single-blind) were ranked by the radiation
oncologist according to patient specific needs and general
guidelines.
Fig 2: According to the Quantec guidelines, all three plans were clinically acceptable. The radiation oncologist preferred the MCO_RTO1 plan despite a higher MLD
because of hotspots in the esophagus in the IMRT_RTT and MCO_RTT plan.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
Individualised treatment planning based on clinical guidelines and taking into account patient specific characteristics
has become more important nowadays. By actively involving
the radiation oncologist, MCO leads to a more patient-specific plan choice by the radiation oncologist, showing that
constraints can be weighed individually (Fig. 2 and Fig. 3). In
most cases the MCO approach leads to better dose distributions according to Quantec guidelines and proved to be
more time-efficient (Table 1).
Fig 3: According to the achieved clinical goals (equally weigthed) the MCO_RTO1 was the worst case. Despite that the radiation oncologist has chosen the MCO_RTO1
plan as the most optimal plan. The IMRT_RTT and MCO_RTT plans have hotspots in and nearby the heart. This patient suffers from heart failure therefore these two
plans are not feasible in this particular case.
radiation oncologist
1
WHAT IMPACT COULD YOUR RESEARCH HAVE?
MCO is a protocolised, individualised and intuitive approach of IMRT in which all parameters, clinical and patient
specific factors, can be taken into account for the individual
ESTRO
Table 1: Quantitative results
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RADIOBIOLOGY
INTRODUCTION
INTRODUCTION
p 45
1.
Analysis of 5434 patients shows a link between the ATM codon 1853 SNP and the risk
of radiation-induced toxicity
2.
Complementarity of genomic instability & hypoxia indices for predicting prostate cancer recurrence
p 46
p 48
3.
18
F-FAZA PET as a predictive marker to guide hypoxia-driven interventions
(carbogen breathing or dose escalation) in radiotherapy p 49
ESTRO 33 included a diverse and interesting radiobiology programme that caters to both biologists
in our discipline as well as to the larger ESTRO membership. The programme this year has been
designed with cross-disciplinary science as a theme. A large number of radiobiology sessions are integrated together with the clinical and physics programmes to ensure as much interaction as possible
between members of the society. As a result, the radiobiology featured sessions took place primarily
in the morning sessions and included a number of important emerging areas. The afternoon sessions
are multi-disciplinary sessions containing important biological components that are highly relevant
to other members of our discipline. The goal is to share knowledge and to stimulate further translational studies to capitalise on the new knowledge.
This year there were a large number of highly rated abstracts, and three of these have been selected that reflect important
milestones in research and emerging trends. All 3 of these abstracts move our field towards increased personalisation of
treatment based on biological features of either the patient or the tumour.
The first abstract by Andreassen and colleagues reports results on an association between a genetic variant in the ATM
gene and the risk of radiation-induced toxicity. In the past 5-10 years, there has been immense interest in the possibility of
identifying patients at higher risk of radiation toxicity based on differences in their underlying genetic makeup. ATM is a
key player in the response to DNA damage, and thus variants in this gene have been hypothesised to influence normal tissue response to radiation. The current study reports results on 5434 patients from a large international genomics consortium. This is the largest study of its kind and demonstrated a small but significant effect. The study shows that genetic differences between patients can indeed influence risk and suggest that there are likely more genetic variants left to discover.
The second abstract by Bristow and colleagues also presents data from an investigation of the importance of genetics for
radiation response, but focuses on the prostate cancer. In addition, they considered genetic changes in the tumour together
with hypoxia, which has been shown previously to influence outcome in this disease. Interestingly, they show that both of
these factors influence response, and can be used to identify patients with high risk of treatment failure. This study paves
the way for introduction of personalised medicine in these patients.
Finally, the abstract by Gallez and colleagues presents a very nice study investigating the ability of the hypoxia imaging
agent FAZA to report on tumour hypoxia and predict tumour response. FAZA allows 3D imaging by PET and is currently
being evaluated in the clinic. The investigators were able to show that FAZA accurately reports oxygenation status through
validation studies using definitive measurements of oxygenation with EPR oximetry. Furthermore, they identified critical
levels of FAZA signals that were associated with radioresistance. These sorts of tools will be needed as personalised treatments for hypoxia enter the clinic.
Brad Wouters
Chair of the Scientific Advisory Group for Radiobiology
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1.
ANALYSIS OF 5,434 PATIENTS SHOWS A LINK BETWEEN THE ATM CODON 1853
SNP AND THE RISK OF RADIATION-INDUCED TOXICITY
C.N. Andreassen1, G.C. Barnett2, S.L. Kerns3, A. Vega4, C.J. Talbot5, K. De Ruyck6, M. Parliament7, C.A.
Koch8, S. Gutiérrez-Enríquez9, J. Alsner10
Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus C, Denmark | 2 Addenbrooke’s Hospital,
Department of Oncology, Cambridge, United Kingdom | 3 Mount Sinai Hospital, Icahn School of Medicine, New York, USA |
4
University Hospital of Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela,
Spain | 5 University of Leicester, Department of Genetics, Leicester, United Kingdom | 6 Gent University, Department of Basic
Medical Sciences, Gent, Belgium | 7 University of Alberta, Department of Radiation Oncology, Edmonton, Canada | 8 Princess
Margaret Cancer Centre, Department of Radiation Oncology, Toronto, Canada | 9 University Hospital of Vall d’Hebron, Institute
of Oncology-VHIO, Barcelona, Spain | 10 Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus,
Denmark
1
BACKGROUND
The ability to predict an individual patient’s risk of
developing side effects to radiotherapy has been a long
sought goal in radiobiology. For the last decade, increasing
interest has been taken in the hypothesis that normal tissue
radiosensitivity is influenced by genetic factors and that the
risk of adverse effects can be predicted by genetic profiling.
OVERVIEW OF ABSTRACT
ATM plays a crucial role in the biological response to
ionising radiation. A number of smaller clinical studies have
indicated that the ATM codon 1853 Asp/Asn SNP may affect
normal tissue toxicity risk. Nevertheless, the results have
been difficult to interpret. The present study was conducted
to test this SNP in the setting of a well-powered multicentre
meta-analysis. Within the framework of the International
Radiogenomics Consortium, individual patient data were
collected from 17 different study cohorts. The dataset
comprised more than 190,000 individual toxicity recordings
from 2,779 patients with prostate cancer and 2,655 patients
with breast cancer.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
Using a t-test comparing the Asp/Asn and Asn/Asn genotypes with the Asp/Asp genotype, a small but significant
increase in normal tissue radio-responsiveness was found for
patients having one or two Asn alleles with regard to acute
toxicity (p=0.001), late toxicity (p=0.029) and overall toxicity
(p=0.003) as well as for acute skin toxicity (p=0.001) and
telangiectasia (p=0.003). We also calculated odds for having
a toxicity score in the upper quartile for patients with Asp/
Asn or Asn/Asn vs. Asp/Asp genotype (fig. 1). This indicates
an odds ratio of around 1.2 for late toxicity and around 1.5
for acute toxicity.
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RADIOBIOLOGY | CONGRESS REPORT
WHAT IMPACT COULD YOUR RESEARCH HAVE?
This study, by far the largest of its kind, demonstrated a
small but significant impact of the ATM codon 1853 Asn allele upon normal tissue radiosensitivity. The influence seems
to be stronger for acute than for late toxicity. The effect size
is in the same order of magnitude as those reported for SNPs
affecting various other phenotypes. So far, compelling associations have only been reported for very few SNP in normal
tissue radiobiology. Thus, the present finding represents an
important proof of principle that normal tissue radiosensitivity is affected by genetic factors.
Fig 1: Impact of the ATM codon 1853 SNP upon risk various types of normal tissue toxicity.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Quite recently, large international cooperative research
groups like the Radiogenomics Consortium (RGC) has been
established to foster large scale research assessing gene-radiation effect relationships. Furthermore, microarray based
genome wide SNP genotyping has become increasingly accessible. This provides unprecedented opportunities to pursue a comprehensive understanding of the genetic variation
probably underlying differences in normal tissue complication risk. The ultimate aim of this research is to establish a
gene based predictive test for radiosensitivity and to unravel
mechanisms and pathways that could serve as targets for
pharmacological intervention against radiation induced
normal tissue damage. Thus, the research may represent an
important step towards individualised cancer therapy.
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2.
3.
COMPLEMENTARITY OF GENOMIC INSTABILITY & HYPOXIA INDICES FOR
PREDICTING PROSTATE CANCER RECURRENCE
F-FAZA PET AS A PREDICTIVE MARKER TO GUIDE HYPOXIA-DRIVEN
INTERVENTIONS (CARBOGEN BREATHING OR DOSE ESCALATION) IN
RADIOTHERAPY
18
R.G. Bristow, E. Lalonde, M. Milosevic, J. Sykes, T. van der Kwast, M. Fraser, A. Fotouhi-Ghiam, P.
Boutros
Princess Margaret Cancer Centre and University of Toronto, Toronto, Canada
Ly-Binh-An Tran, Anne Bol, Daniel Labar, Oussama Karroum, Vanesa Bol, Bénédicte Jordan,
Vincent Grégoire and Bernard Gallez
Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group - Université catholique de Louvain, Brussels,
Belgium
BACKGROUND
At the time of surgery or radiotherapy, patients are not
categorised well enough by clinical prognostic factors alone
(e.g. TNM staging, Gleason score, pre-treatment PSA) to
accurately determine which patients will respond to therapy
and which patients will not respond. We therefore require
additional information (such as genetic factors) to provide
personalised medicine to prostate cancer patients based on
their individual tumour characteristics.
OVERVIEW OF ABSTRACT
Clinical prognostic groupings for localised prostate cancers
(CaP) are imperfect for guiding curative precision medicine.
In fact, despite the use of clinical prognostic factors (PSA,
TNM stage and Gleason score), 30-50% of patients recur
after image-guided radiotherapy or radical prostatectomy.
We tested whether combined genomic and hypoxia indices
could help differentiate patients at high risk for local therapy
failure as a means to direct treatment intensification to improve prostate cancer therapy outcome. We developed a test
that will work in either surgery or radiotherapy patients that
will predict treatment failure with 80% accuracy. We believe
this is a signature for occult metastases and such patients
should receive intensified therapies.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
It would personalise treatment in prostate cancer patients
It would lead to novel Phase II trials with intensify
treatments in order to improve prostate-cancer specific
survival.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
This research is an example of how whole genome sequencing in clinically-appropriate samples can be added value to
current clinical factors. The synthesis of this information can
then be used to optimise treatment with high precision to an
individual case.
BACKGROUND
Translated into a clinical context, 18F-FAZA PET may be
used to identify the hypoxic status of individual tumours
and their response to carbogen. Based on the T/B ratio,
18
F-FAZA PET may help to define the best hypoxia-driven
intervention to potentiate the response to irradiation. For
patients with hypoxic tumours found to be responsive to
carbogen, carbogen breathing would be a more favorable
choice than using escalated doses that may induce toxic
effects.
OVERVIEW OF ABSTRACT
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
One strategy to overcome the hypoxia-induced resistance
to radiotherapy is to deliver associated co-treatments to
alleviate tumour hypoxia or to deliver escalated doses in
tumour regions of increased radioresistance. To do that,
linking the oxygen status in each individual tumour to the
treatment outcome is mandatory. Here, we evaluated the
value of hypoxia imaging using 18F-FAZA (a PET tracer that
is accumulated selectively in viable hypoxic cells) to predict
the outcome and to guide hypoxia-driven interventions
(namely by modulation of the oxygen content in tumours or
by escalating the dose delivered to the tumours).
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
100-fold heterogeneity exists amongst intermediate risk
prostate cancers suggesting that some patients should
receive differential therapy
The uptake of 18F-FAZA was consistent with the real pO2
measured by EPR oximetry.
Genetic instability was a predictor of outcome following
image-guided radiotherapy
WHAT IMPACT COULD YOUR RESEARCH HAVE?
Tumour hypoxia is acknowledged as a major factor of
resistance of solid tumours to radiotherapy. Given its critical
role in therapeutic efficiency, tumour hypoxia should be
considered as a potential target that needs to be exploited in
therapy. For this purpose, qualifying imaging of biomarkers
of hypoxia is mandatory, not only in terms of the intrinsic
value of the method to measure oxygenation, but also for
the ultimate relevance in terms of guidance for radiation
planning and the actual tumour response.
Tremendous innovations have occurred over the past decade
in radiation oncology, including: (1) Intensity Modulated
Radiation Therapy that enables the delivery of radiation dose
at a millimetre level as a function to overcome local radioresistance (dose painting), (2) new capabilities to alleviate
tumour hypoxia, (3) non-invasive predictive tools to predict
the tumour outcome after cytotoxic therapy. Combined with
these developments, hypoxia imaging modalities would offer
the opportunity to integrate the tumour hypoxia parameters in the definition of radiation protocols and radiation
dose. Hypoxia-induced radioresistance, optimal treatment
planning and tumour response should lead to the individualization of radiation protocols for a better response of the
cancer patients.
F-FAZA PET could predict outcome following radiotherapy. It appeared that a T/B ratio of 1.7 is the critical point
to discriminate the radiosensitive tumours from those that
are more radioresistant.
18
The combination of hypoxia and genetic instability measurements was the best prognostic index for these patients
F-FAZA PET could identify the response of tumours
to carbogen breathing. For 9L-gliomas that were highly
responsive to carbogen breathing, there was a clear benefit
from respiratory challenge. In contrast, for rhabdomysarcomas that did not respond well to gas challenge, dose
escalation could lead to a significant increase in tumour
growth delay.
18
We were able to develop a new DNA-based signature for
radiotherapy failure using the genetics of the patient’s own
tumours.
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Fig 1: 18F-FAZA accumulation in tumours. (a) 18F-FAZA T/B ratio measured by PET imaging for Rhabdomyosarcomas (filled symbol) and 9L-gliomas (open symbol)
(Mean values ± SEM). (b) Representative PET image of Rhabdomyosarcoma in basal condition. (c) Representative PET image of Rhabdomyosarcoma in a rat breathing
carbogen. (d) Representative PET image of 9L-glioma in basal condition. (e) Representative PET image of 9L-glioma in a rat breathing carbogen. Note the higher
responsiveness of 9L-gliomas to carbogen breathing compared to Rhabdomyosarcomas
Fig 5: Effect of dose escalation (20 Gy vs 15 Gy) on the response to irradiation for
the Rhabdomyosarcomas breathing air or breathing carbogen. Dose escalation
led to a significant increase in survival.
Fig 2: Mean values ± SEM of pO2 obtained by EPR oximetry for Rhabdomysarcoma (n = 13 under basal condition, n = 12 under carbogen breathing) and
9L-glioma (n = 4 under basal condition, n = 4 under carbogen breathing). Both
tumour models were responsive to carbogen. Note that the pO2 remained under
10 mmHg for the Rhabdomyosarcomas contrarily to 9L-gliomas.
Fig 4: Effect of carbogen breathing on the response to irradiation (15 Gy, Top or
20 Gy, Bottom) for the Rhabdomyosarcomas. Breathing carbogen did not lead to a
significant increase in survival.
Fig 6: Relationship between individual 18F-FAZA tumour accumulation (T/B ratio) and tumour growth delay. Each point was representative for one individual
tumour subjected either to room air (filled symbol) or to carbogen (open symbol). Top: 9L-gliomas with linear relationship (left) or best fitted curve (right). Bottom:
Rhabdomyosarcomas irradiated with 15 Gy (left) or 20 Gy (right). The dotted line separates the tumours based on the threshold of T/B ratio = 1.7
Fig 3: Effect of carbogen breathing on the response to irradiation for the 9L-gliomas. Breathing carbogen led to a significant increase in survival.
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AWARDS
ESTRO AWARD LECTURE
LIFETIME ACHIEVEMENT AWARD
NO PROGNOSTIC IMPACT OF HPV ON RT-OUTCOME IN ADVANCED NONOROPHARYNX CANCER - ANALYSIS OF 1,606 DAHANCA PATIENTS
DONAL HOLLYWOOD AWARD
Fiona Stewart (The Netherlands)
Jean-Claude Horiot (Switzerland)
Jean-François Bosset (France)
Michael Goitein (Switzerland)
Dieter Kogelnik (Austria)
P. Lassen1,2, H. Primdahl2, J. Johansen3, CA. Kristensen4, E. Andersen5, LJ. Andersen6, JF. Evensen7,
J. Eriksen3 and J. Overgaard1. On behalf of DAHANCA.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark | 2 Department of Oncology, Aarhus
University Hospital, Denmark | 3 Department of Oncology, Odense University Hospital, Denmark | 4 Department of Oncology,
Rigshospitalet, University of Copenhagen, Denmark | 5 Department of Oncology, Herlev Hospital, University of Copenhagen,
Denmark | 6 Department of Oncology, Aalborg Hospital, University of Aarhus, Denmark | 7 Department of Oncology,
Rikshospitalet, University of Oslo, Norway
1
ESTRO AWARD LECTURES
Emmanuel van der Schueren Award
“Back to the future: synergies between physics and medicine from history to horizon” David Thwaites (Australia)
Donal Hollywood Award
“No prognostic impact of HPV on RT-outcome in advanced non-oropharynx cancer – analysis of 1,606 DAHANCA patients”
Pernille Lassen (Denmark)
GEC-ESTRO Iridium 192 Award
“From milligram-hour over absorbed dose to equieffective dose and EQD2” André Wambersie (Belgium)
Klaas Breur Award
“Image guided adaptive radiotherapy – the paradigm of cervix cancer brachytherapy” Richard Pötter (Austria)
HONORARY MEMBER AWARD LECTURES
“Innovation of radiation therapy from 3DRT to 4DRT” Masahiro Hiraoka (Japan)
“Cobalt-60, carbon ions, nanotechnology and beyond” Bhadrasain Vikram (USA)
BACKGROUND
Human Papillomavirus (HPV) has been detected in head
and neck cancer (HNSCC) from all anatomical sub-sites
but the prevalence of the virus is reported to be significantly
higher in oropharyngeal carcinoma (OPC) compared
to tumours arising outside oropharynx (non-OPC).
Numerous clinical studies have demonstrated a highly
significant impact of tumour HPV-status on radiotherapy
(RT) outcome in loco-regionally advanced OPC, but the
prognostic impact of HPV in RT of non-OPC has been
much less widely investigated, and could potentially have
clinical implications for this group of patients also.
OVERVIEW OF ABSTRACT
Approximately 1600 patients with stage III-IV larynx and
pharynx carcinoma were identified in the DAHANCA
database. All patients were treated with curative intent using
primary RT according to DAHANCA guidelines from 19922012. Tumour specimens were analysed for HPV-associated
p16-expression and the purpose of the study was to evaluate
UNIVERSITY AWARD
ESTRO-Jack Fowler University of Wisconsin Award
“Real-time dose reconstruction during volumetric modulated arc therapy with dynamic MLC tracking”
Thomas Ravkilde (Denmark)
whether the potent prognostic impact of HPV also extends
to tumours of non-oropharyngeal origin.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
The prevalence of HPV was found to be significantly higher
in OPC (569/1001, 57%) than in non-OPC (77/605, 13%),
p<0.0001, supportive of the current understanding that
HPV-association seems to be strongest in OPC.
In OPC, p16-positivity was significantly correlated with
improved loco-regional tumour control (5-year actuarial
values 81% vs 55%, adjusted HR [95% CI]: 0.44 [0.34-0.59]),
disease-specific survival (89% vs 54%, HR 0.29 [0.21-0.40]),
and overall survival (82% vs 38%, HR: 0.32 [0.25-0.42]),
respectively, compared with p16-negativity.
However, in non-OPC no prognostic impact of p16-status
was found for either endpoint: loco-regional tumour control
(57% vs 51%, adjusted HR: 0.97 [0.69-1.36]), disease-specific
COMPANY AWARDS
ESTRO-Accuray Award
“Real time prostrate gland motion and deformation during cyberknife stereotactic body radiotherapy”
Deepak Gupta (India)
ESTRO-Varian Award
“PET imaging for characterisation of head and neck tumours” Bianca Hoeben (The Netherlands)
ESTRO-Nucletron Brachytherapy Award
“Evaluation and comparison of a novel vaginal dose reporting method in 153 cervical cancer patients”
Henrike Westerveld (The
Netherlands)
GEC-ESTRO Best Junior Presentation – sponsored by Nucletron
“Investigation of radiation therapy effectiveness and safety of recurrent head and neck squamous cell carcinoma”
Viktoras
Rudzianskas (Lithuania)
On the following pages you can find summaries of the abstracts which were selected for some of the awards sessions at
ESTRO 33 together with short interviews with the authors.
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53
survival (58% vs 54%, HR: 0.88 [0.60-1.30]), and overall
survival (44% vs 37%, HR: 0.75 [0.53-1.05]) (Fig. 1).
WHAT IMPACT COULD YOUR RESEARCH HAVE?
These findings confirm the highly significant independent
influence of HPV-associated p16-expression on tumour control and survival in loco-regionally advanced OPC treated
with primary RT. Given this very potent prognostic impact
of HPV in OPC, it is interesting that HPV-status appears to
have no impact on prognosis for tumours arising outside
oropharynx when treated with RT.
We know from preclinical data, that tumour cell-lines positive for HPV/p16 are much more sensitive to RT than HPV/
p16-negative cell lines, so one would expect the responsiveness of the HPV-positive tumours to RT to be comparable
whether located inside or outside the oropharynx. Apparently, based on the results from the present study, this seems
not to be the case and the reasons for this are not known at
present but must probably be ascribed to biological/genetic
differences between the tumours other than the HPV-status.
Of particular interest in this regard are genetic changes
caused by tobacco smoking and we already know that
smoking also negatively affects prognosis in HPV-positive
tumours. Therefore, tumours with mixed aetiology (HPV/
tobacco) represent a challenge in daily clinical practice and
investigation into the exact biological differences within this
apparently heterogeneous group of tumours would be the
next natural step forward.
We have already started analysing all the tumour samples
with a complementary HPV-detection method (PCR), in
order to investigate the correlation between p16-status and
HPV-DNA in non-OPC, since not many data are available
in this regard. This may also shed some light on the natural
history of HPV-induced carcinogenesis in HNSCC.
UNIVERSITY AWARD
ESTRO-JACK FOWLER UNIVERSITY
OF WISCONSIN AWARD
REAL-TIME DOSE RECONSTRUCTION DURING VOLUMETRIC MODULATED
ARC THERAPY WITH DYNAMIC MLC TRACKING
T. Ravkilde1, R. O’Brien2, P.J. Keall.2, C. Grau1, M. Høyer1, P.R. Poulsen1
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark and Institute of Clinical Medicine, Aarhus University,
Denmark | 2 Sydney Medical School, University of Sydney, Sydney, Australia
1
BACKGROUND
Using current radiotherapy methods to treat moving
tumours (e.g. lung tumours) large volumes of healthy tissue
are irradiated in order to adequately treat the tumour,
leading to additional toxicity in the pursuit of cure. Dynamic
multileaf collimator (DMLC) tracking is a technique that
allows real-time tumour motion adaptation on standard
linear accelerators, and therefore has the potential for
widespread use. It is a very promising treatment technique
for moving tumours, increasing the likelihood of accurately
hitting the tumour and reducing toxicity to the surrounding
healthy tissues, without prolonging treatment time or
increasing treatment costs. However, DMLC tracking is a
challenge for conventional plan specific quality assurance
(QA) since the actual in-treatment motions of the linear
accelerator parts are unknown prior to treatment. It is thus
clear that new QA methods are warranted.
OVERVIEW OF ABSTRACT
We have developed a rapid simple dose algorithm that
enables dose reconstruction in real-time. The underlying
concept was that even a very basic dose calculation, one
reminiscent of the calculations done by hand by medical physicists for many years, could be used to quantify
motion-induced dosimetric errors in delivered dose by comparison with the planned dose. A preliminary version of the
algorithm was recently implemented into prototype DMLC
tracking software. For this abstract, the reconstructions were
done in real-time, but used offline during rerun simulations
of previously undertaken experiments.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
Doses were reconstructed in real-time with acceptable
accuracy to detect gross dose errors (mean absolute dose difference of 3.9%, 15% γ failure rate with 3%/3 mm criteria).
The simple algorithm was seen to provide better accuracy for
dose reconstruction of moving tumours than standard dose
algorithms where no motion is assumed: ignoring target
motion led to mean absolute dose differences in the actually
54
AWARDS | CONGRESS REPORT
ESTRO
ESTRO
measured accumulated dose of more than 10%, corresponding to γ failure rates >60%, from the planned dose in some
cases. Just prior to the ESTRO 33 conference, the algorithm
was used and validated experimentally for online real-time
dose reconstruction during VMAT with and without DMLC
tracking.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
The dose algorithm may be used for the early detection of
treatment errors such that any erroneous delivery errors can
be quickly detected and terminated. While this important
dose validation tool was developed for DMLC tracking, it is
also applicable for standard treatments. This algorithm furthermore opens up new possibilities for research by allowing
large scale simulations of the impact of tumour motion
on dose that were not previously attainable. Finally, better
knowledge of actually delivered dose distributions for moving tumours will eventually lead to a better understanding of
clinical results and improvements in radiotherapy delivery.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
As technology and knowledge of organ motion during
treatment has improved, motion management in general has
become a hot topic, in which tumour tracking represents
the more complex and detailed end of the spectrum. While
other, more specialised, types of tumour tracking have been
clinically available for some time, the first patient treatment with DMLC tracking on a standard therapeutic linear
accelerator was performed recently in Sydney, Australia.
The emergence of new treatment modalities often requires
adjustments in QA. Therefore, although the trend for dose
algorithms is in general towards increasing sophistication,
we have instead opted to prioritise the inclusion of tumour
motion.
CONGRESS REPORT | AWARDS
55
Mean abs DD
transient (%)
Mean abs DD
cumulative (%)
20
Typical
10
0
0
High frequency breathing Predominantly left−right
20
20
20
10
50
10
0
0
0
0
50
15
15
15
15
10
10
10
10
5
5
5
5
0
0
0
0
0
0
50
Time (s)
50
Time (s)
Measured
Reconstructed
10
0
0
50
0
0
50
Time (s)
COMPANY AWARD
Baseline shifted
50
Measured
Reconstructed
50
Time (s)
Transient
4
3
2
1
Latitudinal profiles
Measured
Reconstructed
4
3
2
1
Dose rate (cGy/s)
Longitudunal profiles
Dose rate (cGy/s)
Reconstruction
0
0
Comparison of measured and reconstructed transient doses for high modulation VMAT of a lung tumor travelling along the Baseline shifts motion trajectory without
DMLC tracking. Left: 2D measured and reconstructed transient dose distributions in a detector plane for a time interval of 0.5 seconds at gantry angle 140° with
overlay showing the MLC aperture.. Right: dose profiles for the measured (thick lines) and reconstructed (thin lines) doses along the white lines marked on the 2D dose
distributions.
AWARDS | CONGRESS REPORT
Medanta -The Medicity, Division of Radiation Oncology, Gurgaon, India.
BACKGROUND
RESULTS
OVERVIEW OF ABSTRACT
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
The radiobiology of prostate cancer makes
hypofractionation an attractive option for increasing
tumour control. Hypofractionation studies in localised
prostate cancer have shown improvement in biochemical
failure-free survival. It is well known that the prostate moves
and deforms during treatment. A planning target volume
[PTV] margin is added to compensate for this motion, but
this also increases the probability of complications due to
inclusion of larger volumes of surrounding normal tissues.
Hypofractionation studies thus require reduced treatment
margins. Tracking of implanted fiducials is an effective way
of monitoring intrafraction movement of the prostate during
cyberknife-based stereotactic hypofractionated radiotherapy.
Translational movements have been documented in earlier
studies but intrafraction rotation and deformation have not
been studied in depth. Thus uncertainty exists about the
margins required to encompass these variations.
The aim of the study is to analyse real time intrafraction
rotational and translational motion as well as deformation
of the prostate during cyberknife-based stereotactic body
radiotherapy (CK-SBRT). Also, to evaluate the impact of
rotational errors and deformation on PTV margins required
to ensure adequate target coverage during CK-SBRT.
Measured (thick lines) and reconstructed (thin lines) doses to the diode in the center of the phantom for high modulation VMAT of a lung tumor travelling along the
Baseline shifts motion trajectory without DMLC tracking. Transient doses are shown in the left column and the resulting cumulative doses in the right column.
56
REAL TIME PROSTATE GLAND MOTION AND DEFORMATION DURING
CYBERKNIFE STEREOTACTIC BODY RADIOTHERAPY
Deepak Gupta, Tejinder Kataria, Ashu Abhishek, Shyam S Bisht, Karrthick KP, Vikraman
Subramani, Anurita Srivastava, Shikha Goyal.
Comparison of measured (thick lines) and reconstructed (thin lines) 3%/3 mm γ failure rates during the deliveries of high modulation VMAT to a lung tumor travelling
along four clinically measured lung tumor motion trajectories without tracking. Top rows: γ-test failure rate of transient doses. Bottom row: γ-test failure rate of cumulative doses. Note the different y-scales between rows.
Measurement
ESTRO-ACCURAY AWARD
ESTRO
MATERIALS AND METHODS
We analysed 1,360 alignment shifts in target positions during seventeen treatment sessions in five consecutive prostate
cancers treated with CK-SBRT. The shifts were obtained by
tracking 3-4 intraprostatic gold seeds via a pair of in-room
kV X-ray imagers. Images were acquired every 15 seconds
for the first twenty minutes of treatment. For each sequential pair of images, the correction to the target position was
calculated in six-degrees of motion (3 rotations and 3 translations). Rigid body error (RBE) was also analysed for each
patient to assess the prostate deformation during the course
of treatment. The thresholds for translational, rotational and
RBE were 10 mm for translational movements, 2° for roll, 5°
for pitch, 3° for yaw; and 1.5 mm for rigid body errors.
ESTRO
The mean rotational and translational errors for the intrafraction prostate motion were 0.95° ± 1.43, 0.64° ± 3.92 and
-0.27° ±0.72 in roll, pitch and yaw and 0.29mm± 0.56,0.58mm± 0.75 and 0.70mm ± 0.67 in the left-right (LR),
anterior-posterior (AP), superior-inferior (SI) directions
respectively. Intrafraction prostate motion of less than 3°
was observed in 85.6%, 76.2%, and 93.2%, while greater than
5° was observed in 5.8%, 14.7% and 0.5% in roll, pitch, and
yaw, respectively. Intrafraction prostate motion of less than 2
mm was observed in 92.8%, 92.7%, and 96.9%, and less than
3 mm was observed in 94.3%, 94.2%, and 98.9%, in LR, AP,
and SI directions, respectively. Intrafraction prostate motion
greater than 5 mm was observed in 2%, 2% and 0.7%, in
LR, AP, and SI directions, respectively. Mean and standard
deviation of rigid body errors between 3 fiducials were
0.62+/-0.52, 0.66+/-0.44, 0.93+/-0.54. Prostate deformation
of >1.5mm was observed in 9% of images.
Intra-fraction prostate motion was highest in the SI and
AP directions and the least in the LR direction.
A margin of 3 mm in all directions would be sufficient to
ensure that more than 94% of the patients receive at least
95% of the prescribed dose.
Rotational errors and deformation are not negligible
during intrafraction motion but a PTV margin of 3 mm
would adequately encompass these errors.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
PTV margin reductions can give the confidence to escalate the dose further without increasing rectal and bladder
toxicity .
Currently the PTV margins practiced at most centres
are: 5 mm all around except 3 mm posteriorly. For 1 mm
reduction in PTV margin, 10% dose reduction to critical
structure can be achieved. Keeping the NTCP constant, 10%
CONGRESS REPORT | AWARDS
57
dose escalation can be achieved which might help increase
tumour control.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
The guiding principle for disease control with radiotherapy in malignant tumours is maximising tumour control
probability while keeping the normal tissue complications at
a minimum. In prostate cancers, treatment has evolved with
the advent of principles of hypofractionation and sophisticated delivery techniques such as intensity modulation,
image guidance and real time tracking of tumour motion,
enabling dose escalation and better tumour control while
keeping rectal and bladder toxicities at a minimum. The current study aims to quantify the tumour motion during treatment, guiding the margins for errors and reducing target
volumes. This in turn would translate into the possibility of
further improving disease control rates with a lower toxicity
profile and thus improved quality of life in these patients.
COMPANY AWARD
ESTRO-VARIAN AWARD
PET IMAGING FOR CHARACTERISATION OF HEAD AND NECK TUMOURS
Bianca A.W. Hoeben
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
BACKGROUND
In the past decades, radiotherapy has become a preferred
treatment modality for advanced head and neck cancer
(HNC). To improve treatment outcomes, radiotherapy is
given in accelerated schedules, escalated to higher tumour
doses and combined with chemotherapy and/or biologically
targeted therapies. There is a need for more individualised
therapy regimens, tailored to target specific tumour characteristics, in order to increase HNC control and survival. A
simultaneous aim is to decrease treatment toxicity as much
as possible and to select patients who will not benefit from
treatment intensification. For patients with tumours that
are likely to respond well to radiotherapy, dose / treatment
de-escalation might be an option. HNC require more
extensive characterisation than is currently undertaken, in
order to enhance prognosis, to give direction to tailored
therapy, and to enable early therapy response prediction
when treatment modifications are feasible. Molecular and biological tumour characteristics such as proliferation rate and
extent of hypoxia, which are known radiotherapy resistance
mechanisms, can be analysed using immunohistochemistry
and, on a macroscopic level, with PET, in parallel with the
histopathological and anatomical tumour features that are
commonly used to determine treatment currently.
Fig 1: Translational error
Fig 1: Rotational error
OVERVIEW OF ABSTRACT
We analysed the potential of PET imaging to reflect consequential HNC characteristics. In HNC xenograft models,
we performed autoradiography, PET and SPECT imaging
studies with the metabolism tracer 18F-FDG, CAIX hypoxia
tracer 89Zr-cG250-F(ab’)2 [F(ab’)2 fragments have better
penetration and a shorter T1/2 than entire antibodies], and
EGFR tracers 111In-cetuximab and 111In-cetuximab-F(ab’)2.
Imaging features were compared with immunohistochemical features.
HNC patients treated with (chemo)radiotherapy underwent
2 or 3 18F-FLT PET-CT scans before therapy and in the 2nd
and 4th week of treatment. Automatic PET segmentation
methods were used to delineate consecutive tumour proliferative volumes. SUV- and volume-based PET parameters
were correlated with clinical outcome.
58
AWARDS | CONGRESS REPORT
ESTRO
ESTRO
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
A limited set of immunohistochemistry markers enables
phenotypically uniform head and neck tumours to be
classified into groups. 18F-FDG does not adequately provide this distinction.
The use of labeled F(ab’)2 fragments of monoclonal antibodies enables early specific PET/SPECT visualisation
of tumour CAIX and EGFR expression, 4-24 hours after
injection.
F-FLT tumour uptake in patients treated with (chemo)
radiotherapy decreased significantly early during
therapy. Pre-treatment 18F-FLT tumour SUVmax and the
visually-delineated PET tumour volume, as well as their
decrease early during treatment, were predictive for 3-year
disease-free survival and loco-regional control. The fuzzy
locally-adaptive Bayesian method (FLAB) could robustly
segment proliferative tumour volumes during therapy.
18
WHAT IMPACT COULD YOUR RESEARCH HAVE?
Stratification of phenotypically similar tumours using combined molecular markers, rapid PET imaging of molecular
target traits with radiolabeled F(ab’)2 fragments of monoclonal antibodies, and quantification of tumour proliferation rate (changes) may allow individualised selection of
radiation-based therapy and early treatment adaptation to
improve outcomes in head and neck cancer patients.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Over the broad spectrum of oncology treatments, efforts are
made to target individualised therapy according to specific
tumour traits, in order to improve treatment outcomes and
prognosis. A simultaneous aim is to decrease treatment
toxicity as much as possible, especially considering the longterm detriment for patients when better survival outcomes
are achieved. The techniques and treatment options to attain
these goals are increasing, in line with the need to apply them
selectively. Proper imaging and quantification of relevant
tumour characteristics, both microscopically with immunohistochemistry but also macroscopically with PET, can direct
treatment decisions and enable early evaluation of therapy
effects in order to adjust treatment regimens where needed.
CONGRESS REPORT | AWARDS
59
COMPANY AWARD
COMPANY AWARD
EVALUATION AND COMPARISON OF A NOVEL VAGINAL DOSE REPORTING
METHOD IN 153 CERVICAL CANCER PATIENTS
INVESTIGATION OF RADIATION THERAPY EFFECTIVENESS AND SAFETY IN
RECURRENT HEAD AND NECK SQUAMOUS CELL CARCINOMA
Henrike Westerveld, Astrid de Leeuw, Kathrin Kirchheiner, Pittaya Dankulchai, Kari Tanderup,
Christian Kirisits, Richard Pötter
V. Rudzianskas, E. Juozaityte, A. Inciura, M. Rudzianskiene, S. Vaitkus, E. Padervinskis
ESTRO-NUCLETRON
BRACHYTHERAPY AWARD
GEC-ESTRO BEST JUNIOR
PRESENTATION Sponsored by Nucletron
Lithuanian University of Health Sciences, Oncology Institute
Department of Radiotherapy, Academic Medical Centre, Amsterdam, The Netherlands
BACKGROUND
Many cervical cancer patients suffer from sexual dysfunction
after treatment with definitive (chemo)radiotherapy. It is
thought that the radiotherapy dose to the vagina plays an
important role. Until now, little has been known about the
dose-effect relationships for vaginal morbidity. Recently, we
published a paper proposing a novel dose reporting method
for the vagina, in a selected, single-centre cervical cancer
patient group (n=65). All patients were treated with a tandem-ring applicator and high dose rate (HDR) brachytherapy. This reporting method permits reporting not only of the
high doses at the top of the vagina adjacent to the cervix, but
also of the doses to the lower parts of the vagina (defined
by an anatomical landmark, namely the Posterior-Inferior
Border of Symphysis (PIBS))(Fig. 1).
OVERVIEW OF ABSTRACT
The purpose of this study was to test whether the newly
introduced vaginal dose reporting method is more widely
applicable, and useful for different applicators (tandem-ring
and -ovoids) and dose rates (HDR, PDR) within various
institutional protocols. In addition, we wished to evaluate and
compare the effects of the different applicators, dose rates and
institutional protocols on the dose to the vagina both from
external beam radiotherapy (EBRT) and brachytherapy (BT).
This novel method not only gives us the opportunity to compare dose given to the vagina between individual patients
and different centres, but could also lead to increased awareness regarding the (distal part of the) vagina as an organ at
risk. Consequently, efforts could be taken to better spare
the vagina and set dose constraints for this organ, which
hopefully would lead to a decrease in vaginal morbidity.
Finally, this method allows the investigation of dose-effect
relationships between dose to the vagina, vaginal morbidity
and sexual dysfunction.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
3D image-guided radiotherapy and more sophisticated
planning techniques, such as Intensity Modulated Radiation
Therapy (IMRT), enable dose-escalation to the target, but also
dose-de-escalation to organs at risk. Reducing side effects of
oncologic therapies is becoming more and more important
as more patients survive. Until now, no clear dose-effect
relationship between dose to the vagina and morbidity has
been found. Hopefully, systematic evaluation of the vaginal
dose and morbidity will lead to a better understanding of the
development of vaginal side effects and sexual dysfunction
after definitive radiotherapy for gynaecological cancers. This
newly introduced vaginal reporting method provides a tool to
evaluate dose applied throughout the vagina.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
60
AWARDS | CONGRESS REPORT
The aim of this study was to evaluate and compare the efficacy
and toxicity of three-dimensional conformal radiotherapy
(3D-CRT) and high-dose-rate brachytherapy (HDR-BRT) in
the treatment of recurrent head and neck cancer.
Sixty-four patients with recurrent head and neck cancer were
randomly assigned in a 1:1 ratio to receive either 3D-CRT (50
Gy/25 fractions) in the control group or HDR-BRT (30 Gy/12
fractions) in the experimental group. In our study we found
that HDR-BRT was a more effective treatment approach in
terms of overall survival and local control for head and neck
cancer recurrences than 3D-CRT. At ESTRO we present our
two-year follow–up results.
effectiveness and safety of treatment are not yet forthcoming. Following the positive outcome of this study, HDR-BRT
should be considered an essential component in the management of recurrence of head and neck cancer in previously
irradiated patients. To further evaluate the advantages of
HDR-BRT, studies comparing effectiveness and toxicity of
HDR-BRT and intensity-modulated radiotherapy or stereotactic radiotherapy are required.
WHAT WERE THE THREE MAIN FINDINGS OF YOUR
RESEARCH?
The 2-year overall survival rate for the HDR-BRT group
was 67% versus 32% in the 3D-CRT group (p = 0.002) (Fig.
1). Local control at 2-years in patients who received the
HDR-BRT was 63%, compared to 25% in patients who received 3D-CRT (p < 0.001) (Fig. 2). Severe late toxicity was
observed in 11 (35.5%) patients in the 3D-CRT group, but in
only one (3.1%) patient in the HDR-BRT group (p = 0.001).
There was no grade 5 toxicity. From our results, we conclude
that HDR-BRT is a more effective and safer treatment approach for head and neck cancer recurrences than 3D-CRT.
Fig 1: Overall survival of the experimental (HDR-BRT) and control (3D-CRT)
groups from re-irradiation.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
This reporting method allows comparison of dose to the vagina between centres, independently of applicator used and
protocol. Due to steep dose gradients and limitations of the
EQD2 model, the dose assessment at the vaginal surface may
be prone to considerable uncertainties. The 5mm depth dose
may therefore give a better and more robust representation
of the vaginal dose to the top of the vagina than the vaginal
surface dose. The dose at the level of PIBS±2cm represents
the dose throughout the vagina and is mainly dependent on
the vaginal reference length (VRL) and the location of the
EBRT field border.
WHAT IMPACT COULD YOUR RESEARCH HAVE?
OVERVIEW OF ABSTRACT
The overall survival and local control rates with HDR-BRT
were better than those with 3D-CRT. Using HDR-BRT for
re-irradiation, we hope to improve patients’ quality of life by
reducing severe late toxicity (xerostomia, dysphagia, and osteoradionecrosis) and also to prolong their overall survival.
IS THIS RESEARCH INDICATIVE OF A BIGGER TREND
IN ONCOLOGY?
Although the number of publications presenting the results of
3D-CRT retreatment or HDR-BRT in head and neck cancer
recurrence has increased recently, research comparing their
Fig 1: Vaginal dose points
ESTRO
ESTRO
Fig2: Local control of the experimental (HDR-BRT) and control (3D-CRT)
groups from reirradiation
CONGRESS REPORT | AWARDS
TWITTER AT ESTRO
A PERSONAL VIEW FROM TWO DELEGATES AND TWEETERS.
Dr Richard Simcock, Consultant Oncologist, Brighton UK (@BreastDocUK)
Teresa Munoz Migueláñez , Radiation Oncologist, Alicante, Spain (@MsConcu)
It is now impossible to ignore social media; many of us use
it in our lives away from the clinic or laboratory but now it
is becoming an important tool in medicine. Many of you
already ‘like’ ESTRO on its Facebook page but Twitter, where
communications are reduced to 140 characters, is becoming
very visible in medical and research conversations. Twitter
has been used to establish research partnerships, recruit
patients to trials, break new data and this year saw delegates
at ESTRO 33 tweet more than ever before.
Using the hashtag (#) ESTRO 33 Twitter users at the congress were able to share their insights from the conference
immediately – as well as using the messaging tool to debate
with each other and arrange to meet. Messages sent to a
user’s followers were often then retweeted to be delivered to
the timelines of further followers. 66% of users were sending
tweets from their mobiles with 30% using a desktop based
application (1).
#ESTRO33 tweets started to be sent in the week before the
conference but peaked during the days of the meeting with
maximum use occurring during David Thwaites’ excellent
award lecture covering the History of Radiotherapy; during
the session 31 tweets related to the talk were delivered to
26,135 separate timelines! One slide from Dr Petersen’s
comprehensive overview of cardiac risks from breast radio-
62
TWITTER AT ESTRO | CONGRESS REPORT
therapy on Monday morning was retweeted 6 times to 5600
timelines in 4 continents within one hour. Overall during
the conference 475 tweets were sent and delivered to 359,675
separate timelines – a massive and immediate spreading of
information from the conference.
Some have expressed concern about this unregulated spread
of data which occurs without peer review. It is clear that
information spread from Twitter comes with a ‘Health
Warning’ but it is also clear that users will continue to grow
and that congress insights will be shared widely and quickly.
Other medical congresses now have appointed ‘Twitter
Ambassadors’ to spread relevant data from the meeting to
their followers.
ESTRO 33 also saw the launch of the @ESTRO_RT Twitter
account which has already proved to be useful in getting
information about the congress and future meetings. We are
certain that we will see Twitter grow at future meetings so
we look forward to tweeting and meeting you all.
The figures come from www.hashtracking.com. The missing 4% came from
Bots (internet software designed to automatically tweet messages)
(1)
ESTRO
ESTRO
CONGRESS REPORT | TWITTER AT ESTRO
63
24 - 28 April 2015
Barcelona, Spain
ESTRO 35
29 April – 3 May 2016
Turin, Italy
CLINICAL
PHYSICS
BRACHYTHERAPY
RADIOBIOLOGY
RTT
THANK YOU TO...
ESTRO would like to thank the authors of the abstracts for
taking the time to answer our questions about their work,
the chairpersons of the congress for having selected the
most outstanding abstracts and introducing each section,
and also to Anne Kiltie, David Thwaites, Anthony Chalmers, who together with the Chairs reviewed the content of
this report.
A special thank you goes out to the National Organising
Committee chairs, Richard Pötter and Dietmar Georg, for
having gracefully accepted to host ESTRO 33.
CONTACT
ESTRO
Rue Martin V, 40
1200 Brussels - Belgium
Tel.: +32 2 775 93 40
[email protected]
www.estro.org