ARTICLE IN PRESS
doi:10.1510/icvts.2010.259002
Editorial
www.icvts.org
Institutional report - Thoracic oncologic
Olivia Fanucchi, Marcello Carlo Ambrogi*, Paolo Dini, Marco Lucchi, Franca Melfi, Federico Davini,
Alfredo Mussi
Received 22 October 2010; received in revised form 31 December 2010; accepted 10 January 2011
Adult Comorbidity Evaluation 27 (ACE-27). Available at: http:yy
www.rtog.orgymembersyprotocolsy0815yACE-27.pdf. Accessibility verified
December 19, 2010.
1
*Corresponding author. Tel.: q39-050-995211; fax: q39-050-995352.
E-mail address: [email protected] (M.C. Ambrogi).
䊚 2011 Published by European Association for Cardio-Thoracic Surgery
Brief
Case Report
Communication
Statistical analysis was performed using Statistica software version 6.0 for the personal computer (PC) (Stat-Soft,
Historical
Pages
2.2. Statistical analysis
Nomenclature
From our surgical database (Ormawind 2000, Avelco SRL.,
Genova, Italy) we retrospectively selected all patients aged
80 years or more who underwent surgical resection for
NSCLC in the period 2001–2009.
Best Evidence
Topic
2.1. Study design and definitions
State-of-the-art
2. Materials and methods
The main aim of this study was to evaluate postoperative
surgical and oncological outcomes, investigating their relationship with data from the preoperative evaluation course,
surgical management and pathological findings.
All cases were re-staged according to the seventh edition
of the TNM classification w11x.
To identify the individual comorbid ailments and define
the severity of comorbid health, in such a limited number
of patients, we utilised a new 27-item validated comorbidity index for use in patients with cancer (ACE-27)1 w12x. For
the evaluation of preoperative and postoperative quality
of life, we utilised the Karnofsky Performance Status (KPS)
scale.
Treatment-related complications were defined as those
occurring within 30 days of treatment. Minor complications
were those resulting in no sequelae or in a short hospital
stay for observation (-10 days). Major complications were
those resulting in re-admission to the hospital for treatment, an unplanned increase in the level of care, extended
hospitalisation ()10 days), permanent adverse sequelae,
or death.
Follow-up
Paper
In recent decades health care has improved, and at the
same time the elderly population has increased w1x. Even
the definition of the ‘elderly’ population has changed, with
a cut-off rising from 65 years to 70 years or more w2, 3x,
and lung cancer incidence in older patients has increased
also w4x. Despite several studies regarding lung resection in
the older population having dismissed previous accounts of
prohibitively high mortality rates, and having suggested
that surgical resection is associated with a reasonable
perioperative risk, only a few of them deal with patients
over 80 years old w5–10x. To better understand the real
benefit of surgical treatment in octogenarians with nonsmall cell lung cancer (NSCLC), and to determine what
should be done or avoided during the selection course, we
retrospectively analysed our recent nine-year experience
and compared it with those of the literature.
Negative
Results
1. Introduction
Proposal for Bailout Procedure
Keywords: Lung cancer; Surgical resection; Geriatric; Octogenarian
ESCVS
Article
As the European population ages, surgeons are regularly faced with octogenarians with resectable early stage non-small cell lung cancer
(NSCLC). We compared our experience with those reported in the literature to comprehend the feasibility, outcomes and lessons learned
regarding surgical treatment. We reviewed octogenarians who underwent lung resection for NSCLC in the past nine years in our Department.
The purpose of this paper is to retrospectively analyse postoperative surgical and oncological outcomes of our series, trying to find possible
correlations between mortality, morbidity, survival and preoperative oncological and functional assessment, surgical approach and extent
of resection. Eighty-two patients (MyFs63y19), with a mean age 81.0 years (range 80–87 years) underwent lung resection for NSCLC: 63
lobectomies, one inferior bilobectomy, three segmentectomies, and 15 wedge resections. There were two perioperative deaths (2.4%). The
overall complication rate was 30.0%, with a major complication rate of 2.5%. Actuarial cancer-related survival rates at one, three and five
years were 90%, 44% and 36%, respectively, with a statistically-significant correlation with pathological stage. Octogenarians may benefit
from surgical treatment of NSCLC with an acceptable morbidity and mortality rate, if an accurate preoperative selection is pursued.
䊚 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
Institutional
Report
Abstract
Protocol
Division of Thoracic Surgery, Department of Cardiac Thoracic and Vascular Surgery, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
Work in
Progress Report
Surgical treatment of non-small cell lung cancer in octogenarians
New Ideas
Interactive CardioVascular and Thoracic Surgery 12 (2011) 749–753
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Inc, Tulsa, OK, USA). Analysis of continuous and categorical
variables was done by Student’s t-test and x2-test, respectively. Actuarial survival and disease-free survival were
estimated by Kaplan–Meier’s method, and the log-rank test
was used to assess statically significant differences. We
analysed possible correlations between morbidity, mortality, duration of hospitalisation, overallycancer specific survival rates and gender, preoperative forced expiratory
volume in 1 s (FEV1) () vs. -1.5 l), ACE-27 grade (grade
0–1 vs. grade 2–3), histology (squamous cell carcinoma vs.
other tumour cell types), pathologic stage (stage IyII vs.
stage III), extent of resection (lobectomyybilobectomy vs.
sub-lobar resection), and type of surgical approach (thoracotomy vs. VATS), both by univariate and multivariate
analysis (logit and Cox proportional regression models). A
P-value -0.05 was considered statistically significant.
3. Results
3.1. Demographics and clinical data
During the period, of the )3000 patients that underwent
pulmonary resection of NSCLC at our Institute, 82 were
older than 80 years of age. There were 63 males and 19
females with a mean age of 81.1 years (range 80–87 years).
Most of the patients were asympomatic and lung cancer
was revealed on an occasional chest X-ray. Preoperative
performance status, according to the Karnofsky scale, was
82% on average (range 70%–100%). The mean preoperative
FEV1 value was 1.74 l (range 1.1–2.4). In 28 cases (34.1%),
estimation of TLCO and quantitative perfusion scan were
performed in addition to routine lung function test. Most
patients (77.8%) exhibited comorbidities, and 25 patients
(30.5%) had two or more comorbid conditions (Table 1).
Based on the ACE-27 scoring system, 18 patients were
evaluated to be grade 0, 38 patients grade 1, 19 patients
grade 2, and seven patients grade 3.
Routine staging included chest radiograph, bronchoscopy,
blood tumour markers, CT of the chest and upper abdomen
in all cases. In nine cases, brain CT or bone scintigraphy
excluded disseminate disease. Mediastinoscopy (ns7) or
TBNA (ns10) were negative in 17 patients with enlarged
mediastinal nodes ()1 cm). Preoperative pathological
Table 1. Comorbidities and ACE-27 score
Comorbities
No. of
patients
Hypertension
COPD
Coronary artery disease
Diabetes mellitus
Chronic atrial fibrillation
Cerebrovascular events
Others
ACE-27 score
Grade 0
Grade 1
Grade 2
Grade 3
33
29
13
12
6
4
12
18
38
19
7
COPD, chronic obstructive pulmonary disease; coronary artery disease was
defined as a positive exercise testing or prior myocardial infarction or prior
coronary bypass.
diagnosis was obtained in 35 (42.6%) cases: seven adenocarcinomas, eight squamous cell carcimanomas and 20 less
well-established NSCLCs. Preoperative staging is summarised in Table 2. No patients underwent neo-adjuvant chemotherapy or radiation therapy.
3.2. Surgical data
Under general anaesthesia with double lumen intubation,
63 (76.8%) lobectomies, one (1.2%) inferior bilobectomy,
three (3.7%) segmentectomies and 15 (18.3%) wedge resections were performed. No pneumonectomy was recorded in
octogenarians. Two left upper lobectomies were en bloc
due to chest wall invasion. In one case a right upper extrapleural lobectomy was performed because of infiltration of
the parietal pleura. There were three bronchial sleeve
lobectomies (two right upper lobectomies and one left
upper lobectomy) and one arterial sleeve left upper lobectomy. Seven lobectomies and nine wedge resections were
performed by VATS.
3.3. Postoperative histology and staging
Pathologic evaluation revealed 33 adenocarcinomas, 36
squamous cell carcinomas, seven bronchiolar-alveolar carcinomas, and six large cell carcinomas. Pathologic TNM
stage confirmed the preoperative clinical staging in 50
(61.0%) cases (Table 2). Stage IIIA disease was due to
unexpected N2 disease in 14 cases, while in the other two
cases it was due to T3 N1 disease.
3.4. Mortality and morbidity analysis
Two deaths occurred in patients that underwent lobectomy, with an overall perioperative mortality rate of 2.4%. In
one case it was for acute myocardial infarction on the
second postoperative day, and in the second case for acute
respiratory failure on first postoperative day. The overall
morbidity rate was 30.4%. Major complications occurred in
two patients that underwent lobectomy. One case of brain
transient ischemic attack, and another case of cardiac
arrest promptly and successfully reanimated. In these two
cases hospital stay was prolonged until the 13th and the
15th postoperative day, respectively. No patients that
underwent sublobar resection had major complications.
One or more minor complications occurred in 22 patients
(Table 3). The median overall postoperative hospital stay
for the 80 surviving patients was 7.1 days (range 4–21
days).
Table 2. Clinical and pathological staging according to TNM seventh edition
Stages
IA
IB
II A
II B
III A
Clinical
Pathological
No. of
patients
%
No. of
patients
%
10
37
23
12
0
12.2
45.1
28.0
14.6
0
8
35
11
12
16
9.8
42.7
13.4
14.6
19.5
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Editorial
Table 3. Postoperative complications
Complications
Major complications
Transient ischaemic attack
Cardiac arrest
Minor complications
Prolonged air leaking
Supraventricular arrhythmia
Postoperative anaemia
Atelectasis
Urinary retention
New Ideas
No. of
patients
Work in
Progress Report
1
1
12
7
3
3
1
Protocol
3.5. Risk factor analysis
Postoperative
stay (days)
3%
0%
0.0356
28.1%
44.4%
0.187
6.3%
0%
0.2768
21.9%
44.4%
0.0562
7.3
6.8
0.49
Thoracotomy
VATS
P-value
3.3%
0%
0.0573
35.2%
9.1%
0.0832
5.6%
0%
0.4196
29.6%
9.1%
0.1536
7.6
6.0
0.11
ACE-27 grade 0–1
ACE-27 grade 2–3
P-value
0%
7.7%
0.0356
21.4%
53.8%
0.0033
1.8%
11.5%
0.0474
19.6%
42.3%
0.0311
6.6
8.8
0.00154
FEV1 )1.5 l
FEV1 -1.5 l
P-value
3.1%
0%
0.447
29.7%
38.9
0.458
6.3%
0%
0.277
23.4%
38.9%
0.191
7.4
6.7
0.388
Brief
Case Report
Communication
Minor
complication
Historical
Pages
(BI)lobectomy
Sublobar resection
P-value
Major
complication
Nomenclature
Overall
morbidity
Best Evidence
Topic
Mortality
State-of-the-art
Table 4. Analysis of possible correlations between mortality, overall morbidity, major and minor complications (x2 -test) and postoperative stay (Student’s
t-test) with extent of surgical resection, type of approach, ACE-27 grade, and FEV1 value
Follow-up
Paper
In European countries the population is ageing, so the
number of elderly patients with potentially resectable
NSCLC is concomitantly increasing w4x. In a recent paper
Janssen and Kunst found that by 2050 the average further
life expectancy of people reaching 80 years of age is
predicted to be 9.16 years for men and 12.65 for women
w1x. Based on these data, it is likely that the greatest
impact on an octogenarian’s survival will be their CR
mortality rather than their age alone. During the past few
years, some papers regarding lung resections in the octogenarian seem to dismiss the older accounts of prohibitively
high mortality and morbidity w5–8x. This seems to be
confirmed in our analysis, where we obtained an acceptable
mortality and morbidity rate of 2.4% and 30.4%, respective-
Negative
Results
4. Discussion
Proposal for Bailout Procedure
At the time of analysis, 34y80 (42.5%) patients were alive:
28 were disease-free, five had local disease recurrence,
one had local and distant recurrence. There were only
three cases with a deterioration in the quality of life,
corresponding to a KS of 60%, due to the progression of
Alzheimer’s disease. In the 46 patients who died during the
follow-up period, death was cancer-related (CR) in 28
(60.1%) of the cases. At a mean follow-up of 47 months
(range 11–94 months, median 48 months), the overall and
CR median survival were 30.9 and 34.5 months, respectively. Actuarial overall and CR survival at one, three and five
years were 87%, 37% and 27%, and 90%, 44% and 36%,
respectively (Fig. 1). There was no statistically-significant
association between survival and co-morbidity grade, FEV1
value, extent of resection, type of approach, histology (Fig.
2). On the contrary, long-term overall and CR survival were
closely associated with pathologic stage (Ps0.016 and
Ps0.00003, respectively) (Fig. 3).
ESCVS
Article
3.6. Follow-up and survival analysis
Fig. 1. Actuarial overall survival curve.
Institutional
Report
Table 4 summarises the risk factor analysis results. Male
gender was associated with a higher overall morbidity
(Ps0.0236), but not with higher mortality (Ps0.432). In
contrast, ACE-27 grade was strongly related with mortality
(Ps0.003), but also with major and minor (Ps0.03 and
Ps0.05, respectively). A borderline correlation was observed between mortality and type of approach (thoracotomy
vs. VATS) (Ps0.057). The extent of resection, instead,
significantly influenced mortality (Ps0.0356), and a trend
to correlation was observed with minor complications
(prevalently prolonged air leaking)(Ps0.056). A strong statistically-significant difference in postoperative hospital
stay was revealed comparing ACE-27 score (Ps0.0015).
Multivariate analysis confirmed ACE-27 score as an independent predictor of postoperative morbidity (Ps0.001),
mortality (ACE-27 grade 3, Ps0.00015) and hospital stay
(Ps0.008).
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Fig. 2. Comparison of survival between squamous cell carcinoma and other
cell type (P-values0.633).
Fig. 3. Comparison of survival between early stage (I and II) and other stages
(P-values0.00003).
ly, which are comparable with those reported by recent
studies, ranging between 0%–8.8% and 18–49%, respectively
w5–9x.
Not many studies analysed risk factors predicting morbidity and mortality. Dominguez-Ventura and co-workers, in a
large study, reported that a FEV1 value of 40% or less than
predicted was not associated with higher mortality, but it
increased the incidence of morbidity w10x. In contrast, Pagni
et al. reported no significant difference in perioperative
risk when patients were stratified by abnormal pulmonary
function test (FEV1-60% of predicted value) w9x. Moreover,
both Brock et al. and Port et al. observed no correlation
between morbidity and pulmonary function w5, 8x. Our
statistical analysis also revealed that a preoperative FEV1
value -1.5 l was not related with a higher incidence of
mortality and morbidity.
In our analysis, the most important risk factor that affected mortality and morbidity was the presence of serious
comorbidity conditions (ACE-27 grade 2–3). Port et al.
analysed postoperative complications in function of the
presence of single or multiple comorbidities, without
achieving statistical significance w5x. Other papers did not
provide a statistical analysis of risk factors, reporting solely
a lack of statistical significance for an unspecific comorbid
condition w8, 9x. Nevertheless, the methodical analysis of a
single comorbidity presented by Doninguez-Ventura et al.
emphasised that only the presence of congestive heart
failure and prior myocardial infarction were related with
higher mortality, while some comorbid conditions affected
morbidity w10x. Unfortunately, a comparison with our results
becomes difficult because of the different modalities of
comorbidities stratification.
The survival data in our study revealed a five-year overall
survival rate of 27%, which increased to 36% if we consider
CR survival. Such result, at the lower-level of those reported by authors in western countries, which ranged between
34% and 43% w5–8x, is probably affected by an unexpectedly
high incidence of stage III disease. This could be referred
to a lack of extensive use of brain CT or MR, PET-CT,
mediastinoscopy in our institute. Few studies investigated
the predictive factors regarding increased survival. Brock
et al. reported that a FEV1 -1.5 l and the ASA class
affected survival w8x. In the large study by DomingezVentura et al. w7x, as well as in the present paper, there
was no difference in survival according to FEV1 value. On
the contrary, our analysis confirmed the well-known correlation between pathologic stage and survival w5–8x,
achieving a five-year CR survival rate of 52% for stage IyII.
Our study has some limitations. The first one is that we
report a single centre experience. Another very significant
one is the retrospective nature of the study, which may
have resulted in a selection bias. Additionally, we did not
analyse single comorbidity in different organs, because the
small number of patients made the choice to evaluate the
general clinical status, attempting to quantify a global
operative risk, that was the result of each single disorder
occurring in different organs.
In conclusion, surgical resection of NSCLC in elderly
patients resulted as being safe, with acceptable long-term
survival. When surgeons have to take the controversial
decision of whether to offer resection to octogenarians,
they should base their choice first on the stage of the
disease, and then on an accurate assessment of the general
clinical conditions, rather than on pulmonary function
alone. In this sense, the ACE-27 scoring system seems to
be useful to track those patients with a high multi-factorial
operative risk.
References
w1x Janssen F, Kunst AJ. The choice among past trends as a basis for the
prediction of future trends in old-age mortality. Popul Stud (Camb)
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ESCVS
Article
Proposal for Bailout Procedure
Negative
Results
Follow-up
Paper
Authors: Dimitrios Paliouras, Department of Cardiothoracic Surgery,
Papageorgiou General Hospital, Thessaloniki, Greece; Michael Klimatsidas,
Georgios Samanidis, Stavros Daliakopoulos
doi:10.1510/icvts.2010.259002B
We read with great interest the article by Fanucchi et al. as we are
supporters of the trend suggesting that appropriately selected octogenarians
should not be excluded from surgical treatment w1x. However, since it is our
practice too, we are very much interested in further information regarding
patient characteristics. In particular, it would be very useful to our practice
to have insight into survival in relation to the histological type of carcinoma,
especially large cell carcinomas which seem to be a whole new entity with
poor prognosis w2, 3x.
Our concluding point is that there are hundreds of factors influencing
prognosis many of which are established as prognostic w4x. But since we are
referring to a new target age group and the operability guidelines, we have
to consider new, age-specific parameters for our practice, e.g excluding
patients with large cell carcinomas if survival proves to be low after surgical
treatment.
Institutional
Report
eComment: Octogenarians: do we have to consider new age specific
parameters in our practice?
Protocol
w1x Fanucchi O, Ambrogi MC, Dini P, Lucchi M, Melfi F, Davini F, Mussi A.
Surgical treatment of non-small cell lung cancer in octogenarians.
Interact CardioVasc Thorac Surg 2011;12:749–753.
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Work in
Progress Report
References
Best Evidence
Topic
w1x Fanucchi O, Ambrogi MC, Dini P, Lucchi M, Melfi F, Davini F, Mussi A.
Surgical treatment of non-small cell lung cancer in octogenarians.
Interact CardioVasc Thorac Surg 2011;12:749–753.
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State-of-the-art
Authors: Stefano Cafarotti, Department of Thoracic Surgery, Catholic
University, Rome, Italy; Giovanni Leuzzi, Filippo Lococo, Maria T. Congedo
doi:10.1510/icvts.2010.259002A
We read with great interest the article by Fanucchi et al. reporting on
surgical treatment of non-small cell lung cancer (NSCLC) in octogenarians
w1x. Western populations are generally fitter than in the past and the term
‘elderly’ should be redefined. In the past, the border between middle age
and old age was 65 years. Nowadays, some authors consider old age as 70
or 75 years. In developed countries median age of presentation of all cancer
patients is 69 years in males and 67 years in females. Sixty percent of all
cancers and two-thirds of cancer deaths occur over the age of 65 years w2x.
More than 50% of patients with lung cancer are over the age of 65 years
and over 30% are above the age of 70 years w3x. In this setting, the impact
of surgical treatment on this population needs to be further investigated.
To be applied, treatment options need to be modulated on the basis of the
individual fitness, beyond physiological aging effects, and taking into account
the risks of the procedures.
We retrospectively reviewed our data on 299 elderly patients surgically
treated for NSCLC at our institution from January 1996 to August 2006 and
relative follow-up. Mean age was 74.3 year with clinical stage III in only 12%
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New Ideas
eComment: Mortality, morbidity and late survival in lung resection
for non-small cell lung cancer in the elderly population
of cases. We performed 271 lobectomies (25 bilobectomies and seven sleeve
lobectomies), 15 pneumonectomies and 13 wedge resections. Morbidity was
6.6%, including hemorrhages, broncho-pleural fistulas, supra-ventricular
arrhythmias, respiratory failure and myocardial infarction. Recurrence rate
were 28.8%, and one-year, two-year and five-year survival were, respectively
90.9%, 83% and 65.7%. According to our results, we completely agree with
the authors that elderly may benefit from surgical treatment of NSCLC.
Editorial
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Nomenclature
Historical
Pages
Brief
Case Report
Communication