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CLINICAL TRIALS AND OBSERVATIONS
Positron emission tomography has a high negative predictive value for
progression or early relapse for patients with residual disease after first-line
chemotherapy in advanced-stage Hodgkin lymphoma
Carsten Kobe,1 Markus Dietlein,1 Jeremy Franklin,2 Jana Markova,3 Andreas Lohri,4 Holger Amthauer,5 Susanne Klutmann,6
Wolfram H. Knapp,7 Josee M. Zijlstra,8 Andreas Bockisch,9 Matthias Weckesser,10 Reinhard Lorenz,11
Mathias Schreckenberger,12 Roland Bares,13 Hans T. Eich,14 Rolf-Peter Mueller,14 Michael Fuchs,2,15 Peter Borchmann,2,15
Harald Schicha,1 Volker Diehl,2 and Andreas Engert2,15
1Department
of Nuclear Medicine, University of Cologne, Cologne, Germany; 2German Hodgkin Study Group, University of Cologne, Cologne, Germany;
of Clinical Hematology, Third Faculty of Medicine, Charles University, Prague, Czech Republic; 4Schweizer Arbeitsgruppe für Klinische
Krebsforschung, Bern, Switzerland; 5Klinik für Strahlenheilkunde, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; 6Department
of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 7Department of Nuclear Medicine, Hanover University Medical
School, Hanover, Germany; 8Department of Hematology, VU University Medical Centre, Amsterdam, The Netherlands; 9Department of Nuclear Medicine,
University of Duisburg-Essen, Essen, Germany; 10Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany; 11Department of Nuclear
Medicine, University of Wuerzburg, Wuerzburg, Germany; 12Department of Nuclear Medicine, Gutenberg University Hospital, Mainz, Germany; 13Department of
Nuclear Medicine, University of Tuebingen, Tuebingen, Germany; 14Department of Radiation Oncology, University of Cologne, Cologne, Germany; and
15Department I of Internal Medicine, University of Cologne, Cologne, Germany
3Department
In the HD15 trial of the German Hodgkin
Study Group, the negative predictive value
(NPV) of positron emission tomography
(PET) using [18F]-fluorodeoxyglucose in
advanced-stage Hodgkin lymphoma (HL)
was evaluated. A total of 817 patients
were enrolled and randomly assigned to
receive BEACOPP-based chemotherapy.
After completion of chemotherapy, residual disease measuring more than or
equal to 2.5 cm in diameter was assessed
by PET in 311 patients. The NPV of PET
was defined as the proportion of PETⴚ
patients without progression, relapse, or
irradiation within 12 months after PET
review panel. The progression-free survival was 96% for PETⴚ patients (95%
confidence interval [CI], 94%-99%) and
86% for PETⴙ patients (95% CI, 78%-95%,
P ⴝ .011). The NPV for PET in this analysis was 94% (95% CI, 91%-97%). Thus,
consolidation radiotherapy can be omitted in PETⴚ patients with residual disease
without increasing the risk for progres-
sion or early relapse compared with patients in complete remission. The impact
of this finding on the overall survival at
5 years must be awaited. Until then, response adapted therapy guided by PET
for HL patients seems to be a promising
approach that should be further evaluated in clinical trials. This trial is registered at http://isrctn.org study as #ISRCTN32443041.
(Blood.
2008;112:
3989-3994)
Introduction
Hodgkin lymphoma (HL) is one of the best curable malignancies in
adult oncology, with reported disease-free survival in excess of
80% at 5 years.1,2 Because of the risk of secondary malignancies
and other sequelae, the reduction of toxicity has become one of the
major goals in the treatment of HL patients, including those in
advanced stages.3,4 After establishing 8 cycles of BEACOPP
(cyclophosphamide, adriamycin, etoposide, procarbazine, prednisone, vincristine and bleomycin) escalated as new treatment of
choice in this group of patients,5 the German Hodgkin Study Group
(GHSG) follow-up studies HD12 and HD15 aimed at reducing
toxicity while maintaining the improved disease control with an
overall survival of 92% and freedom from treatment failure of 88%
at 5 years.
One possible approach to reduce toxicity is to omit or substantially reduce the number of patients receiving additional radiotherapy.6-8 More recently, smaller studies suggested that positron
emission tomography (PET) using [18F]-fluorodeoxyglucose (FDG)
might discriminate between active and inactive tissue in HL,
suggesting a high negative predictive value (NPV) for FDG-PET in
this malignancy.9-11 Thus, the GHSG HD15 study for advancedstage HL included a PET question (HD15-PET) evaluating the
NPV of PET in patients after BEACOPP. Radiotherapy after
chemotherapy was restricted to those patients in partial remission
(PR) who had PET-positive (PET⫹) residual tissue. PET-negative
(PET⫺) patients received no additional radiotherapy.
Here we present the results of HD15-PET demonstrating a NPV
of 94% after 6 to 8 cycles of BEACOPP for PET⫺ patients.
Submitted June 2, 2008; accepted August 9, 2008. Prepublished online
as Blood First Edition paper, August 29, 2008; DOI 10.1182/blood-200806-155820.
payment. Therefore, and solely to indicate this fact, this article is hereby
marked ‘‘advertisement’’ in accordance with 18 USC section 1734.
The publication costs of this article were defrayed in part by page charge
© 2008 by The American Society of Hematology
BLOOD, 15 NOVEMBER 2008 䡠 VOLUME 112, NUMBER 10
Methods
Patients
All patients of the HD15-PET study were recruited into the prospectively
randomized HD15 multicenter trial of the GHSG. Inclusion criteria were
newly diagnosed, histology-proven HL in clinical stages IIB with extranodal disease and/or large mediastinal mass (ⱖ one-third of the maximum
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BLOOD, 15 NOVEMBER 2008 䡠 VOLUME 112, NUMBER 10
KOBE et al
Table 1. Flowchart
Patients, n
Randomized in HD15 before May 29, 2007
Analysis set
1788
Randomized not later than July 1, 2005
995
Qualified for HD15
962
Evaluable for outcome
817
PET performed and assessed by the panel
355
HD15 analysis set (AS1)
Qualified for PET
311
PET analysis set (AS2)
12-month follow-up after panel or event
275
NPV analysis set (AS3)
thoracic diameter), III, and IV. Patients had to be 18 to 60 years and free of
other concurrent disease precluding protocol treatment. Patients with HL as
part of a composite lymphoma, previous malignancy, chemotherapy or
radiotherapy, pregnancy, or lactation were not eligible. Entry criterion for
the PET question in this trial was a PR after chemotherapy (6-8 cycles of
BEACOPP) and at least one involved nodal site of more than or equal to
2.5 cm in the transversal or longitudinal diameter as measured by computed
tomography (CT). Exclusion criteria included diabetes mellitus, elevated
fasting blood sugar level more than 130 mg/dL, and skeletal involvement
with risk of instability.
Written informed consent was obtained from all patients in accordance
with the Declaration of Helsinki. The trial coordinators obtained a vote of
approval from the responsible ethical committee of the medical faculty of
the University of Köln and have registered the trial with the responsible
authorities (state president of Northrhine-Westphalia and BfArM) according to the German drug regulations (AMG V. 1.1.2002). For PET
diagnostics, the trial coordinators obtained the approval of the German
Authority for Radiation Safety (Bundesamt für Strahlenschutz).
Study design
Patients were contributed by approximately 400 study centers in Germany,
Switzerland, Austria, The Netherlands, and the Czech Republic. After
clinical staging, patients were randomly assigned to 3 arms: patients in the
standard arm A had 8 cycles, patients in arm B had 6 cycles of BEACOPP
escalated, and patients in arm C 8 cycles of time-condensed BEACOPP14.
After 4 cycles of chemotherapy, an interim staging was performed,
including CT of all initially involved regions. PET was performed at a
median of 21 days after the last administration of chemotherapy in qualified
PET centers using the [18F]-fluorodeoxyglucose technique. Local radiotherapy (30 Gy) was restricted to patients who were PET⫹ after chemotherapy and had PR with residual disease measuring more than or equal to
2.5 cm, as described in “Central PET review panel.”
Chemotherapy
BEACOPP in standard and baseline doses (BEACOPP14) was administered as previously described.5,12
cutoff date for randomization was chosen so that the target population had
time to complete treatment, PET, and 12 months’ follow-up before the
analysis. The planned analysis set (AS2) for the HD15-PET question
comprised all AS1 patients deemed qualified for PET in whom PET had
been performed and reviewed by the PET panel. For the analysis of
progression or relapse, AS2 was restricted to patients with at least
12 months of follow-up or with an event within 12 months (AS3). The NPV
in PET⫺ patients was calculated as the proportion of AS3 patients with
progression, relapse, or radiotherapy within 12 months of the panel
decision. A 95% confidence interval (CI) for the NPV was calculated using
the normal approximation to the binomial distribution: ␯ ⫾ 1.96.SQRT
(␯(1 ⫺ ␯)/n) with ␯ ⫽ NPV and n ⫽ total number of cases (SQRT indicates
square root). For progression-free survival (PFS), progression, relapse, and
death from any cause were defined as failures. For comparison between
PET⫹ and PET⫺ groups, PFS was measured from the date of the PET panel;
for comparison of these groups with patients who achieved complete
remission (CR), PFS was measured from the date of randomization.
Kaplan-Meier analysis and the log-rank test were used to compare PFS of
PET⫺ and PET⫹ patients in PR (with residual mass ⱖ 2.5 cm) with those in CR.
Results
Patients
Between January 2003 and May 2007, 1788 patients in HD15 were
randomly assigned to treatment arms, 995 of whom before the
deadline of July 1, 2005 (Table 1). A total of 33 patients were not
qualified for this study and excluded from additional analysis.
Reasons for exclusion were review pathology diagnosis not HL
(n ⫽ 20), wrong stage (n ⫽ 9), concurrent disease (n ⫽ 1), patient’s age more than 60 years (n ⫽ 1), and treatment before
randomization (n ⫽ 2). Documentation was completed for 817 of
these 962 patients (85%). Thus, 817 patients were included in the
analysis set 1 (AS1). PET was performed and assessed by the PET
panel in 355 patients of AS1 (43%). A total of 44 patients were not
qualified for the PET question and were excluded from additional
analysis. Reasons for exclusion were residual tissue less than
2.5 cm (n ⫽ 39), diabetes (n ⫽ 1), elevated blood sugar levels
(n ⫽ 1), or skeletal involvement with risk of instability (n ⫽ 3).
Consequently, 311 patients (38% of AS1) were included in the
analysis set 2 (AS2). Patients in AS2 had been randomly assigned
as follows: 95 to 8 cycles of BEACOPP escalated, 117 to 6 cycles
of BEACOPP escalated, and 99 to 8 cycles of BEACOPP14.
Patient characteristics were well balanced between treatment
arms (Table 2).
PET activity in residual mass after 6 to 8 cycles of BEACOPP
Central PET review panel
A multidisciplinary panel consisting of a medical oncologist, a radiologist, a
radiation oncologist, and a nuclear medicine physician, accompanied by a
statistician, reviewed PET and CT scans as well as available conventional
X-rays blinded to the treatment arm. Inclusion and exclusion criteria were
also assessed. A PET⫹ was defined according to the standard criteria as
focal or diffuse uptake above background incompatible with normal
anatomy or physiology, without a specific standardized uptake value cutoff.
Exceptions were mild and diffusely increased FDG uptake at the site of
moderate-sized or large residual masses with intensity lower than or equal
to that of mediastinal blood pool structures.13,14 The further treatment
recommendation was based on the central interpretation of PET and CT
scans.
Statistics
The planned analysis set for the present analysis (AS1) comprised all
patients randomized in HD15 not later than July 1, 2005 (Table 1). The
Of 311 patients who had residual tissue measuring more than or
equal to 2.5 cm by CT after 6 to 8 cycles of BEACCOPP, PET was
positive in 66 patients (21% of AS2) and negative in 245 (79% of
AS2; Table 3). A total of 244 of 245 PET⫺ cases received no further
treatment as defined in the protocol. One patient with a very large
initial and residual mediastinal mass had radiation as recommended
by the review panel. A total of 66 patients had PET⫹ residues, with
radiotherapy recommended in 63: in 2 cases, the panel assessment
came too late and in one patient, the PET⫹ residue was confined to
the liver.
As defined in the protocol, patients were irradiated or not
according to the panel decision. The adherence to protocol was
good with 242 of 246 AS2 cases in whom “no radiation” was
recommended actually received no radiotherapy. Four patients
were radiated against the panel decision, 3 of whom had radiotherapy to skeletal lesions that were PET⫺. All 63 patients for
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BLOOD, 15 NOVEMBER 2008 䡠 VOLUME 112, NUMBER 10
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Table 2. Patient characteristics
Characteristic
HD15 analysis set AS1, no. (%)
(n ⴝ 817)
PET analysis set AS2, no. (%)
(n ⴝ 311)
NPV analysis set AS3, no. (%)
(n ⴝ 275)
Age group, y
18-20
59
(7.2)
28
(9)
27
(9.8)
20-30
267
(32.7)
120
(38.6)
99
(36.0)
30-40
229
(28.0)
102
(32.8)
92
(33.5)
40-50
154
(18.9)
47
(15.1)
44
(16.0)
50-60
102
(12.5)
14
(4.5)
13
(4.7)
Female
318
(38.9)
129
(41.5)
112
(40.7)
Male
499
(61.1)
182
(58.5)
163
(59.3)
Sex
Stage
IIB
136
(16.7)
94
(30.2)
80
(29.1)
IIIA
192
(23.5)
54
(17.4)
48
(17.5)
IIIB
210
(25.7)
63
(20.3)
57
(20.7)
IVA
77
(9.4)
33
(10.6)
32
(11.6)
IVB
202
(24.7)
67
(21.5)
58
(21.1)
(15.3)
Reference histology
Missing
113
(13.8)
52
(16.7)
42
LP
26
(3.2)
2
(0.6)
2
(0.7)
cHL
65
(8.0)
28
(9.0)
25
(9.1)
NS cHL
418
(51.2)
173
(55.6)
154
(56.0)
LR cHL
16
(2.0)
3
(1.0)
2
(0.7)
MC cHL
174
(21.3)
50
(16.1)
47
(17.1)
LD cHL
5
(0.6)
3
(1.0)
3
(1.1)
LP indicates lymphocyte predominant HL; cHL, classic Hodgkin’s lymphoma; NS, nodular sclerosis; LR, lymphocyte rich classic HL; MC, mixed cellularity; and LD,
lymphocyte depletion.
whom irradiation of residual tissues was recommended actually
received radiotherapy (Table 3).
Freedom from progression and relapse after PET
Those patients with at least 12 months of follow-up after PET and
those with progressive disease or relapse within 12 months after
PET were included in this analysis (n ⫽ 275; AS3 ⫽ 88% of AS2).
Table 4 displays events within 12 months of PET. Nine of 216 (4%)
patients with PET⫺ residues and 9 of 59 (15%) patients with PET⫹
residues had an event (ie, progression or relapse). Event rates were
significantly different between those patients with PET⫺ residual
tissue or those having PET⫹ residual tissue (P ⫽ .005). Of
18 events, 7 were confined to residual tissue sites, whereas
11 occurred outside these sites (Table 4).
PFS of PET⫺ and PET⫹ patients starting from the date of the
PET panel is shown in Figure 1. At 12 months, PFS for PET⫺
patients was 96% (CI, 94%-99%) and 85% (CI, 78%-95%) for
those who were PET⫹ (P ⫽ .011). The median observation time for
patients included was 18 months. Thus, a positive PET after
effective chemotherapy was predictive of subsequent treatment
failure, even though the PET⫹ patients had additional radiotherapy.
PFS of PET⫺ and PET⫹ patients starting from the date of
randomization was compared with that of patients in CR (with or
without CR-compatible residues) at restaging after completing
chemotherapy (Figure 2). It is apparent that PET⫺ patients in PR
with more than or equal to 2.5 cm residual disease at the end of
chemotherapy had a prognosis very similar to those in CR.
NPV of PET after chemotherapy
All patients in analysis set AS3 with PET⫺ residual mass (n ⫽ 216)
were included for calculating the NPV. There were 9 patients with
progression or relapse within 12 months and 5 patients with
radiotherapy after PET, although being PET⫺, of whom 4 were
otherwise failure-free. Thus, the NPV was calculated as follows:
NPV ⫽ (216 ⫺ 13)/216 ⫽ 94% with a 95% CI ranging from
91% to 97%.
Discussion
The HD15-PET trial evaluated the NPV of PET in advanced-stage
HL patients with residual disease after 6 to 8 cycles of BEACOPP.
Depending on the PET results, those patients who were PET⫺ were
followed up without additional radiotherapy, whereas those with
PET⫹ tumors more than or equal to 2.5 cm received radiotherapy
(30 Gy) to residual masses. The following findings emerge from
Table 3. PET panel results, panel recommendation, and radiotherapy
Residual tissues
PET panel results, n (%)
Radiotherapy
recommended/performed, n
No radiotherapy
recommended/performed, n
244/240
Negative
245 (79)
1*/5†
Positive
66 (21)
63/64
3‡/2§
311 (100)
64/69
247/242
Total
Analysis set: all patients qualified for HD15 and for the PET question. PET performed and seen by the PET panel (AS2, number of patients ⫽ 311). Reason for divergent
recommendation/performance:
*Negative residues but radiotherapy recommended due to very large initial and residual mediastinal mass.
†Negative residues but radiotherapy against recommendation in 4 cases: PET regarded as positive by local physician (n ⫽ 2), unknown reason (n ⫽ 2).
‡Positive residues but no radiotherapy recommended in 3 cases: positive residue in the liver (n ⫽ 1), panel too late to recommend radiotherapy (n ⫽ 2).
§In one case, radiotherapy was performed where no radiotherapy was recommended.
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KOBE et al
Table 4. Progression and relapse and PET results: analysis set 3 (number of patients ⴝ 275)
Progression/relapse within 12 months
Negative residues, n (%)
Positive residues, n (%)
Total, n (%)
No (total)
207 (96)
50 (85)
257 (93)
Yes (total)
9 (4)
9 (15)
Total
216
this planned analysis, including 311 patients qualified for and
receiving PET, of whom 275 had sufficient follow-up: (1) 79%
evaluable patients were PET⫺ and 21% were PET⫹ after 6 to 8
cycles of BEACOPP and received additional radiotherapy; (2) PFS
at 18 months after randomization was 96% for PET⫺ patients and
85% for PET⫹ patients (P ⫽ .011) (the corresponding PFS for
patients in CR after chemotherapy was 95%); and (3) the NPV for
PET in this analysis was 94%.
This is the first randomized trial that has proven a high NPV
(94%) of PET in HL. The NPV was defined as the proportion of
PET⫺ patients without progression, relapse, or radiotherapy within
12 months of follow-up after central PET review panel recommendation, which is equivalent to 18 months of follow-up after
randomization. Because PET⫺ patients who had radiotherapy were
counted as failures as predefined in the protocol, the analysis
presented here is very conservative.
The follow-up period of 12 months after central PET review
panel was chosen for different reasons. First, PET certainly is a
sensitive method to detect viable tumor masses in HL as it could be
shown in numerous nonrandomized studies. Accordingly, in case of
a true-positive PET, indicating a malignant process and residual
masses more than or equal to 2.5 cm as defined in our study,
relapses are expected to occur within some months. This hypothesis is confirmed in our study, where 8 of 9 relapses were
documented within the first 6 months for PET⫹ patients. In
addition, 8 of 9 relapses occurred within the PET⫹ residual tissue.
Thus, PET obviously is able to detect emerging relapses some
months before they can be displayed by CT scan, but, for technical
reasons, the resolution of PET is presumably not good enough to
detect minimal residual disease, which can cause late relapses
(⬎ 12 months) in HL.15 Thus, a negative PET should predict PFS
for at least 12 months in most cases.
Second, in the preceding HD9 trial for advanced stages HL,
59% of all events during the 5-year follow-up period occurred
59
18 (7)
275
within the first 12 months after randomization.5 These events are
defined as primary progressive disease or early relapse. Therefore, the NPV of PET at the predefined follow-up period of
12 months after PET in our study covered the majority of events
expected and was considered a clinically relevant milestone.
This hypothesis is supported by the recent data published by
Gallamini et al,16 who had a PFS of only 12.8% at 2 years in case
of an early positive PET after 2 cycles of chemotherapy. In this
study, almost all relapses occurred within the time frame of our
observation period reported here.
Third, this study was accompanied by major safety concerns.
Patients with large residual tumor masses (eg, 8 cm in one patient)
received no radiotherapy in case of a negative PET. To ensure the
safety of this concept, an early analysis was regarded to be
mandatory.
On the basis of these prerequisites, the 12-month follow-up
after PET review panel was chosen for the determination of the
NPV. Taking into account the identical PFS of PET⫺ PR patients
compared with CR patients in our study, major differences in the
final outcome seem to be improbable at least. Nonetheless, the
impact on established outcome parameters as PFS or overall
survival at 5 years remains to be awaited. The results from our
study indicate that PET-guided response adapted therapy is a
promising approach in HL patients.17
In contrast to the NPV, the impact of a positive PET after
chemotherapy is much weaker.18 Several trials reported positive
predictive values (PPVs) ranging between 40% and 50% after
doxorubicin, bleomycin, vinblastine, and dacarbazine-based chemotherapy.9-11 To investigate the PPV of a PET⫹ residual disease after
chemotherapy in our study, interventions such as radiotherapy
would have been impossible. Because radiotherapy still is the
standard of care for patients with residual disease, omission of this
intervention was regarded too risky and unethical. Thus, the PPV
was not an end point in our study.
Figure 1. Progression-free survival for patients with
PETⴙ and PETⴚ residual tissues starting from the
date of the PET panel.
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Figure 2. Progression-free survival for patients in
complete remission (CR) at restaging after completion of chemotherapy starting from the date of randomization.
PET⫹ patients after treatment with BEACOPP had a significantly higher risk of progression or relapse (15%) compared with
PET⫺ patients (4%) at 12 months. However, this rate was lower
than expected. Several factors may have contributed:
One reason might be the PET interpretation. To ensure consistency, a central multidisciplinary review panel was arranged. In
accordance with the criteria of the imaging subcommittee of the
international harmonization project in lymphoma, PET was also
judged positive in cases with residual masses and an uptake slightly
higher than the mediastinal blood pool.13,14 This contrasts with
recent observations,16 in which such findings were classified as
minimal residual uptake and thus PET might result in a higher
number of false-positive PET scans in our study.
Many groups have investigated the value of PET showing a
poor outcome for PET⫹ patients compared with PET⫺ patients.16,19-21 One area of uncertainty is the best timing of PET.
Although a minimum of 3 weeks between PET and the last
chemotherapy had been advocated earlier,13 a minimum of 10 days
after chemotherapy seems sufficient in more recent recommendations.22 To allow radiotherapy on time in our study, PET was
performed after a median of 3 weeks after the last administration of
chemotherapy. Thus, the interval used could result in more
false-positive cases because of the obligatory use of prednisone and
growth factors in the BEACOPP regimen.23,24
Finally, radiotherapy might be a very effective therapy turning
truly positive PET lesions into remission. Because, for the reasons
discussed, a treatment arm without radiotherapy was not foreseen,
this question cannot be answered by our study.
Notably, 85% of PET⫹ patients had neither progression nor
early relapse, but the rate of progression and relapse was significantly increased despite additional radiotherapy compared with the
PET⫺ patients. Taking biopsies from PET⫹ lesions would be the
only way to determine the rate of truly positive PET results.
Because relapses occurred not only infrequently, but also both
inside PET⫹ residual masses (8 of 9) and outside (4 of 9), taking
biopsies for a histologic proof of residual disease for all PET⫹
patients is not justified by our results. In addition, the most
common site of residual disease in HL is the mediastinum, and a
biopsy would require invasive procedures associated with the risk
of morbidity in most cases.
So far, our data do not support additional aggressive consolidation regimens such as high-dose chemotherapy with autologous
stem cell transplantation for PET⫹ patients because the majority of
patients would be overtreated. These approaches should be evaluated earlier during the treatment course, to further improve the
outcome of high-risk patients. In summary, based on the high NPV
of PET in this large study, radiotherapy can be omitted in patients
with PET⫺ residual tumor without increasing the risk of primary
progressive disease or early relapses compared with patients in CR
after BEACOPP chemotherapy. The 5-year follow-up period must
be completed for a definite conclusion on PFS and overall survival.
Until then, response adapted therapy guided by PET for HL
patients seems to be a promising approach that should be further
evaluated in clinical trials.16,19-24
Acknowledgments
The authors thank the PET Centers in Switzerland (Zurich, Bern, and
Basel), Austria (Linz, Innsbruck), Germany (Augsburg, Leipzig, Frankfurt, Heidelberg, Regensburg, Homburg, Munich TU, Munich LMU,
Freiburg, Goettingen, Kiel, Ulm, Nuernberg, Stuttgart,Aachen, Koblenz,
Juelich, Bad Berka, Dresden, Erlangen, Fulda, Karlsruhe, and Bonn),
and Czech Republic (Prague, Brno); as well as A. Gossmann (Radiology); H. Stein and M. Hansmann (Pathology); K. Hansemann and R.
Skripnitchenko (Radiotherapy); H. Bredenfeld, A. Josting, L. Nogova,
and B. Klimm (GHSG Physicians); B. Pfistner, A. Pluetschow, H.
Haverkamp, and C. Brillant (GHSG Statisticians); and B. Koch and H.
Nisters-Backes (GHSG Documentation).
Authorship
Contribution: C.K., M.D., P.B., and A.E. wrote the paper; R.-P.M.,
H.T.E., M.D., M.F., P.B., V.D., and A.E. designed and conceptualized the study; J.F. performed statistical analysis; J.M., A.L., and
J.M.Z. enrolled patients and assembled and documented clinical
data; and H.A., S.K., W.H.K., A.B., M.W., R.L., M.S., R.B., and
H.S. performed and analyzed the PET scans.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Andreas Engert, Department I of Internal
Medicine, University of Cologne, Kerpener Strasse 62, 50924
Cologne, Germany; e-mail: [email protected].
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From www.bloodjournal.org by guest on June 14, 2017. For personal use only.
2008 112: 3989-3994
doi:10.1182/blood-2008-06-155820 originally published
online August 29, 2008
Positron emission tomography has a high negative predictive value for
progression or early relapse for patients with residual disease after
first-line chemotherapy in advanced-stage Hodgkin lymphoma
Carsten Kobe, Markus Dietlein, Jeremy Franklin, Jana Markova, Andreas Lohri, Holger Amthauer,
Susanne Klutmann, Wolfram H. Knapp, Josee M. Zijlstra, Andreas Bockisch, Matthias Weckesser,
Reinhard Lorenz, Mathias Schreckenberger, Roland Bares, Hans T. Eich, Rolf-Peter Mueller, Michael
Fuchs, Peter Borchmann, Harald Schicha, Volker Diehl and Andreas Engert
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