Pneumonectomy After Chemoradiation Therapy
for Non-Small Cell Lung Cancer:
Does “Side” Really Matter?
Anthony W. Kim, MD, L. Penfield Faber, MD, William H. Warren, MD,
Sanjib Basu, PhD, Sean C. Wightman, BA, James A. Weber, BA, Philip Bonomi, MD,
and Michael J. Liptay, MD
Background. The long-term benefits and risks of pneumonectomy after neoadjuvant chemoradiation therapy
remain controversial. This study evaluated our experience with pneumonectomy for advanced non-small cell
lung cancer (NSCLC) after concurrent chemoradiation
therapy.
Methods. We reviewed medical records from patients
undergoing concurrent chemoradiation therapy, followed
by pneumonectomy (1983 to 2007). Clinical variables affecting Kaplan-Meier survival were analyzed.
Results. After chemoradiation therapy, 129 pneumonectomies (right, 65; left, 64) were performed. Postoperative pathologic stages were complete responders (CR),
21; I, 23; II, 19; III, 62; and IV, 4. The 90-day perioperative
mortality was 20% (13 of 65) after right-sided pneumonectomy vs 9% (6 of 64) after left-sided pneumonectomy
(p ⴝ 0.084). Complications occurred in 33% (43 of 129),
including bronchopleural fistula in 12% (16 of 129) and
acute respiratory distress syndrome in 2% (3 of 129).
Overall 5-year survival was 33%. Survival was 32% for
right-sided sections vs 34% for left-sided. CR patients
had a 5-year survival of 48%. Survival of patients with
postoperative N0, N1, and N2 nodes was 42%, 26%, and
28%, respectively. Multivariate analysis showed the development of major complications negatively affected
5-year survival for patients undergoing right-sided pneumonectomy (hazard ratio, 0.462; p ⴝ 0.0399).
Conclusions. Pneumonectomy after concurrent chemoradiation therapy achieved long-term survival. When
neoadjuvant therapy resulted in complete response or
nodal downstaging, survival was improved. The risk of
early perioperative death and complications was higher
for right-sided procedures, but long-term survival did
not differ between right- and left-sided pneumonectomy.
Major complications negatively affected 5-year survival
with right-sided pneumonectomies.
(Ann Thorac Surg 2009;88:937– 44)
© 2009 by The Society of Thoracic Surgeons
E
tion therapy remain controversial. The purpose of this
study was to evaluate the perioperative risks and longterm survival associated with pneumonectomy for advanced non-small cell lung cancer (NSCLC) after concurrent chemoradiation therapy.
xperience has proven that pneumonectomy is a safe
thoracic operation. However, it remains an operation that carries a higher morbidity and mortality than a
lobar or sublobar resection [1–3]. Certain investigators
have suggested that it is the scale of the operation—and
not the neoadjuvant therapy—that contributes to the
postoperative morbidity and mortality [3, 4]. The performance of a right-sided pneumonectomy has been thought
to be associated with a greater likelihood of morbidity and
mortality than a left-sided pneumonectomy [5]. The results
of the Intergroup 0139 trial have suggested that the benefits
of a right-sided pneumonectomy may not be worthwhile in
the setting of the added layer of complexity with neoadjuvant chemoradiation therapy [6]. This has led several
clinicians to believe that right pneumonectomy after
chemoradiation therapy should never be offered.
The long-term benefits and risks of pneumonectomy
(especially right-sided) after neoadjuvant chemoradia-
Accepted for publication April 22, 2009.
Presented at the Forty-fifth Annual Meeting of The Society of Thoracic
Surgeons, San Francisco, CA, Jan 26 –28, 2009.
Address correspondence to Dr Liptay, University Thoracic Surgeons, 1725 W
Harrison St, Ste 774, Chicago, IL 60612; e-mail: [email protected].
© 2009 by The Society of Thoracic Surgeons
Published by Elsevier Inc
Patients and Methods
From 1983 to 2007, the clinical records of all patients
undergoing chemoradiation therapy, followed by pneumonectomy, were reviewed. Inclusion criteria were:
1. the identification of locally advanced disease that
required neoadjuvant therapy to achieve complete
resection,
2. completion of chemotherapy and radiation therapy
in a concurrent fashion, and
3. nothing less than a pneumonectomy at the completion of the full course of neoadjuvant therapy.
Institutional Review Board approval was obtained to
perform this retrospective review. Individual patient consent was waived for this retrospective study.
The age, gender, chemoradiation therapy regimen,
histopathology, preoperative and postoperative T N M
0003-4975/09/$36.00
doi:10.1016/j.athoracsur.2009.04.102
GENERAL THORACIC
Division of Thoracic Surgery and Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois
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Ann Thorac Surg
2009;88:937– 44
Table 1. Complications Associated With Pneumonectomy
After Neoadjuvant Chemoradiation Therapya
Complication
GENERAL THORACIC
BPF
ARDS
Empyema without BPF
Secretions/pneumonia/aspiration
Cardiac arrhythmia
RLN injury
Esophageal perforation
Myocardial infarction
Intraoperative hemorrhage
Right-Sided,
N ⫽ 65
Left-Sided,
N ⫽ 64
11 (4)
3 (3)
1
2 (1)
4 (2)
1
0
0
0
5 (2)
0
1
2 (1)
6 (1)
1
1
1
1 (1)
a
Numbers in parenthesis are complications that were known to directly
contribute to the 90-day perioperative mortality rate.
ARDS ⫽ acute respiratory distress syndrome;
BPF ⫽ bronchopleural
fistula;
RLN ⫽ recurrent laryngeal nerve injury.
Right-sided and left-sided pneumonectomies were
performed in a standard fashion. No special distinction
was given to pneumonectomies requiring intrapericardial dissection. Carinal pneumonectomies were not included in this analysis. Pneumonectomies performed
for other malignancies such as mesothelioma, metastatic disease, and neuroendocrine malignancies were
excluded.
Lymphadenectomy, and not lymph node sampling,
was performed for all of the pneumonectomies. The
right-sided resections underwent dissection of the level
2, 4, 7, 8, 9, 10, and 11 lymph node stations. The left-sided
resections underwent dissection of the level 5, 6, 7, 8, 9,
10, and 11 lymph node stations.
For right-sided resection, routine stump coverage with
a pleural or pericardial fat pad buttress was performed.
Closure of the bronchus was routinely accomplished by
stapling.
Statistical Methods
stage, 90-day mortality, major complications, and survival were recorded. Major complication were defined as
bronchopleural fistula (BPF), cardiac arrhythmia, acute
respiratory distress syndrome (ARDS), respiratory secretions requiring bronchoscopic intervention, pneumonia,
myocardial infarction, pulmonary embolism, and recurrent laryngeal nerve injury.
Clinical Considerations
Locally advanced disease was defined as the presence of
central disease (T3 N0), or positive mediastinal lymph
nodes (N2 disease). Mediastinal lymphadenopathy was
confirmed by cervical mediastinoscopy or radiographic
evidence of disease, including (1) the presence of lymphadenopathy in the mediastinum greater than 2.0 cm on
short axis, or (2) the presence of the aforementioned
lymphadenopathy with positive findings on positron
emission tomography (PET), defined as more than maximum standard uptake value of 2.5. Radiographic staging
alone was relied on more frequently in the earlier time
period, whereas PET scan and mediastinoscopy were
used more systematically later in the study period. Patients with contralateral mediastinal lymph node involvement (N3 status 1) and limited stage IV disease
(isolated brain 4) were also included but the number was
very small.
The study excluded patients who were initially given
chemoradiation therapy in a neoadjuvant setting but in
whom progressive disease developed that precluded
surgical resection.
Chemotherapy was given concurrently with splitcourse radiotherapy in all of the regimens used. Chemotherapy consisted of platinum-based regimens. Before
1994, the regimen consisted of cisplatin and 5-fluorouracil. Etoposide was added later. After 1994, the regimen
changed to carboplatin, paclitaxel, and etoposide; eventually, etoposide was eliminated. There were some variations in these regimens. The mean split-course radiation
dose was 4299 cGy (range, 4000 to 4500 cGy), although
there were minor variations.
Kaplan-Meier 5-year survival curves were generated
based on the time from pneumonectomy. All univariate
comparisons of survival were made with log-rank tests
and represent virtually all of the p values in this article.
The exception to this was in the use of ␹2 analysis to
generate a p value in comparing the differences in the
90-day perioperative mortality between left-sided and
right-sided resections. A multivariate analysis using a
Cox proportional hazard regression model was performed to evaluate the effect of several covariates on the
side of resection. Additional clinical considerations and
values of p ⱕ 0.1 on univariate analysis were determined
the factors that would be used as the variables. Statistical
analysis was performed using SAS 9.1 software (SAS
Institute Inc, Cary, NC). Significance was defined as p ⬍
0.05.
Fig 1. The overall 5-year survival for the entire cohort was 33%.
The numbers in the parentheses represent the patients at risk.
Ann Thorac Surg
2009;88:937– 44
KIM ET AL
PNEUMONECTOMY AFTER CHEMORADIATION
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Table 2. Variables Compared in the Univariate Analysis of
5-Year Survival
Gender
Female
Male
Laterality of resectiona
Right
Left
Postoperative stagea
CR (0-T0 N0)
I
II
III
IV
Pathologic node statusa
N0
N1
N2
Nodal downstaginga
0 (No change)
1 (N2¡N1, N1¡N0)
2 (N2¡N0)
Major complicationsa
No
Yes
%
p Value
0.471
28
36
0.664
32
34
0.270b
48
43
26
27
25
GENERAL THORACIC
Variable
0.108b
42
26
28
0.320b
29
33
42
Fig 3. Survival stratified according to the pathologic stage of complete response (CR, solid line), stage I (small dashed line), stage II
(dotted line), stage III (dottted-dashed line), and stage IV (large
dashed line). The numbers representing patients at risk were not
included for clarity.
0.002
39
21
A total of 129 pneumonectomies, comprising 65 right and
64 left, were performed after concurrent chemoradiation
therapy. Patients were a mean age of 57 ⫾ 9 years (range,
30 to 72 years). The gender distribution was 50 women
and 79 men. Histologic subtypes were divided into squamous carcinoma in 77, adenocarcinoma in 44, large cell
carcinoma in 5, adenosquamous in 2, and carcinosarcoma
in 1. Pretreatment stages of the carcinomas were IB, 2;
IIB, 11; IIIA, 95; IIIB, 18; IV, in 3. Postoperative pathologic
stages were complete responders (CR), 21; IA, 11; IB, 12;
IIA, 10; IIB, 9; IIIA, 46; IIIB, 16, and IV, 4. Of the pathologic
Fig 2. Survival stratified according to right-sided (solid line) and
left-sided (dashed line) pneumonectomy demonstrated no statistically
significant difference at 5 years. The numbers in the parentheses
represent the patients at risk.
Fig 4. Survival stratified according to the pathologic lymph node
status of N0 (solid line), N1 (dashed line), and N2 (dotted line). The
numbers in the parentheses represent the patients at risk.
a
Variables included in multivariate analysis.
b
Pooled analysis.
CR ⫽ Complete response.
Results
940
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PNEUMONECTOMY AFTER CHEMORADIATION
Ann Thorac Surg
2009;88:937– 44
Table 3. Downstaged Grida
Variable
Pre-op
Post-op
...
2
11
113
3
21 (21)
23 (22)
19 (18)
62
4
...
2
28
80
19
22 (22)
31 (30)
42 (29)
17 (1)
17
14
28
86
1
52 (41)
23 (12)
54
0
GENERAL THORACIC
Stage
0 (CR)
I
II
III
IV
T
0
1
2
3
4
N
0
1
2
3
a
Numbers in parenthesis are patients who were truly downstaged to this
postoperative stage with neoadjuvant chemoradiation therapy.
stage IV disease, resection was used to treat 3 isolated
brain metastases and 1 adrenal metastasis.
Overall, complications occurred in 43 of the 129 patients (33%), including BPF in 16 (12%) and ARDS in 3
(2%; Table 1). Other complications were cardiac arrhythmias, empyema without BPF, respiratory secretions or
pneumonias requiring bronchoscopic intervention, recurrent laryngeal nerve injury, myocardial infarction,
esophageal injury, intraoperative hemorrhage.
Nineteen patients died within 90 days of pneumonectomy. Right pneumonectomy was associated with a
higher 90-day perioperative mortality of 20% (13 of 65)
compared with 9% (6 of 64) for left pneumonectomy (p ⫽
0.089). Of these 19 perioperative 90-day deaths, 14 were
secondary to the complications experienced after the
pneumonectomy. BPF accounted for 6 perioperative
deaths (right, 4; left, 2), and the 3 right-side patients with
Table 4. Distribution of 61 Patients Who Experienced
Downstaging With Neoadjuvant Chemoradiation Therapy
and Their Associated 5-Year Survival
Downstageda
By 1 stage
III ¡ II
II ¡ I
By 2 stages
III ¡ I
II ¡ CR
By 3 stages
III ¡ CR
Patients, No.
23
18
5
21
17
4
17
17
5-Year Survival, %
35
38
47
a
The sample size was too small to calculate those that were downstaged
from stage IV to pathologic complete response status.
CR ⫽ complete response.
Fig 5. The 5-year survival stratified according to nodal downstaging.
Node downstage 0 (solid line) was equivalent to no change in
pathologic node status from preoperative staging. Node downstage 1
(dashed line) was equivalent to N2 ¡ N1 or N1 ¡ N0 downstaging. Node downstage 2 (dotted line) was equivalent N2 ¡ N0
downstaging. The numbers in the parentheses represent the patients
at risk.
ARDS died. An additional 5 patients died of other causes,
including stroke, 1; massive aspiration, 1; pulmonary
embolism , 1; failure to thrive, 1; unknown, 1.
Overall 5-year survival was 33% (Fig 1). Univariate analysis of several factors on 5-year survival was performed
(Table 2). Survival of right-sided (32%) vs left-sided resections (34%) was not significantly different (Fig 2).
The 5-year survival according to the postoperative
stages was CR, 48%; I, 43%; II, 26%; III, 27%; 4, 25% (Fig
3). Differences between the individual stages were not
significant, although the observed survival for the CR
and stage I patients individually approached significance
compared with stage III patients (p ⬍ 0.1231 and p ⬍
0.1207, respectively).
The 5-year survival of patients according to pathologic
N status only was N0, 42%; N1, 26%; N2, 28%. Despite the
relatively small sample size, differences in survival between N0 and N1, and N0 and N2 approached significance (p ⬍ 0.0568 and p ⬍ 0.0988, respectively; Fig 4). Of
the 54 patients who had N2 disease, 34 were right-sided
and 20 were left-sided. The percentage of patients alive at
5 years after resection with positive N2 disease was 21%
(7 of 34) for right-sided pneumonectomy and 30% (6 of
20) for left-sided pneumonectomy.
Tumor downstaging occurred in 61 patients (Table 3).
The 5-year survivals improved according to degree of
downstaging that occurred (Table 4). When nodal downstaging was specifically evaluated, 5-year survivals according to nodal downstaging were downstaged from N2
to N0, 43%; downstaged from N1 to N0 or N2 to N1,
33%; no change in N2 or N1 status, 29% (Fig 5). Again,
Fig 6. Survival stratified according to the development of complications (dashed line) or no complications (solid line). The numbers in
the parentheses represent the patients at risk.
despite the obvious trend, significant differences were
not observed.
The 5-year survival was stratified according to the
development of complications. When patients did not
experience any complications, the 5-year survival was
39%. When any major complication occurred, the 5-year
survival was 21%. This difference was significant (p ⬍
0.002; Fig 6). When the major complications were limited
to BPF and ARDS, the 5-year survival of this cohort was
17%. This decreased survival was significantly different
compared with those who did not experience a complication (p ⬍ 0.0002). This was in contrast to those with
non-BPF or non-ARDS complications, whose 5-year survival was 28%. Unlike the BPF or ARDS complications,
this difference in survival was not significant (p ⬍ 0.2452).
The ARDS patients all died within 90 days.
Pathologic node status and major complications were
included into the multivariate analysis based on the
univariate statistical analysis. Age, postoperative stage,
and lymph node downstaging were additional covariates
that were included because of their perceived clinical
importance. Multivariate analysis showed that no variables negatively effected the 5-year survival for patients
undergoing left-sided pneumonectomy. Conversely,
multivariate analysis demonstrated that only the development of major complications negatively effected the
5-year survival for patients undergoing right-sided pneumonectomy (hazard ratio, 0.462; p ⫽ 0.0399).
Comment
Chemoradiation therapy in the neoadjuvant setting for
lung cancer is widely used. The Intergroup 0139 trial
suggested a mild benefit of neoadjuvant chemoradiation
therapy, followed by surgery. However, the subset
analysis demonstrated a higher perioperative mortality
KIM ET AL
PNEUMONECTOMY AFTER CHEMORADIATION
941
rate of 26% (14 of 54) was associated among patients
undergoing a pneumonectomy. More specifically, the
analysis demonstrated that a large percentage of the
deaths occurred in patients undergoing a right-sided
pneumonectomy.
The overall mortality associated with pneumonectomy
has been reported to be 6% to 12% [7–10]. Despite a few
reports citing 30-day and 90-day mortality rates within
ranges similar to when no neoadjuvant chemotherapy
has been used [11–14], the addition of neoadjuvant therapy to pneumonectomy has been thought to increase the
already elevated mortality [5, 15]. Right-sided pneumonectomy specifically has been associated with a mortality
of 12% to 37%, even in the absence of neoadjuvant
chemoradiation therapy [7, 10, 16, 17]. When distinguished by laterality, right-sided pneumonectomy has
been associated with increased mortality rates of 24% to
36% [5, 18, 19]. On the other hand, there has been
evidence to the contrary as other investigators have
found that after neoadjuvant chemotherapy, right-sided
pneumonectomy can have either a significantly lower
mortality or no increased mortality compared with pneumonectomies in general [1, 13, 20 –22].
The overall perioperative mortality in this study was
16%. The definition of perioperative mortality occurring
within a 90-day window from the date of the operation
rather than a 30-day window was because several of the
deaths within 90 days were considered related to the
pneumonectomy. Furthermore, the 90-day mortality rate
has been substantially greater than 30-day rate and is
believed to be a more accurate representation of the
sequelae associated with pneumonectomies [5, 13, 15].
Perioperative deaths appeared to be intimately associated with complications that developed during the postoperative stay or during the close postoperative follow-up period.
Although long-term survival did not differ, the difference in outcomes was fairly dramatic when the 90-day
perioperative mortality rate between left- and right-sided
pneumonectomies was evaluated. From our extensive
clinical experience, we believe that the higher 90-day
perioperative mortality rate for right-sided pneumonectomy simply does not represent an anecdotal finding that
only approaches significance; rather, we believe this is a
very real and meaningful concern that warrants more
attention than the statistical analysis supports. This series
represents one of the larger neoadjuvant chemoradiation
therapy followed by pneumonectomy-only experiences;
however, it still may have had insufficient power to drive
the observed difference to significance.
A review of the data (not shown) revealed that the date
of the operation did not affect the morbidity and mortality observed for the entire series. Although there was
some minor variability among the surgeons performing
the pneumonectomies, these resections were performed,
largely, in a similar manner using a stapled bronchial
closure for either left- or right-sided resection, with
routine pericardial fat pad or pleural flap coverage on the
right side.
GENERAL THORACIC
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GENERAL THORACIC
The 30% incidence of morbidity in this series was
similar to that associated with pneumonectomies after
neoadjuvant therapy [11]. The findings from the multivariate analysis underscored the negative effect of the
development of major perioperative complications demonstrated by the univariate analysis. This investigation
supports previous observations and provides additional
information with respect to the use of concurrent neoadjuvant chemoradiation therapy that suggests the development of BPFs negatively affect survival [15, 23]. This
complication is more prone to develop in right-sided
pneumonectomies even without neoadjuvant chemotherapy [17]. Reports showing an absence in an increased
incidence of BPFs between right and left-sided pneumonectomies [13] notwithstanding, most clinicians intuitively believe and others have, in fact, demonstrated a
higher BPF incidence in right-sided pneumonectomies
after neoadjuvant chemoradiation therapy [15]. The multivariate analysis performed by Gudbjartsson and colleagues [24] demonstrated an association between BPF
formation and right pneumonectomy after preoperative
chemoradiation therapy.
Observations such as these, as well as the results
reported in this article, support the role of any reasonable
measures to prevent bronchial stump disruption. Also,
the right-sided stumps in this series were routinely
buttressed with pleura or pericardial fat pad. Although it
could be argued that this technique did not result in a
significant decrease in the incidence of BPFs after pneumonectomy, it is possible that the incidence of BPFs
could have been higher without this added measure.
The 2% incidence of ARDS in this series was on the
lower end of spectrum of the 0.5% to 11% incidence that
has been reported after pneumonectomy, either with or
without induction therapy [3, 13, 17, 24 –27]. However, the
90-day mortality rate of 100% that we observed is consistent with the high perioperative mortality rate reported
in other studies [6, 25–27]. All of the ARDS cases occurred
after right-sided pneumonectomy, supporting the recommendations of judicious administration of intravenous
fluids, prevention of mediastinal shifting, and promotion
of aggressive pulmonary toilet [28].
The overall 5-year survival in this series was 33%. This
figure is consistent with that reported for pneumonectomies performed after neoadjuvant therapy [21]. Downstaging of disease suggested a survival benefit in this
series. This effect was greatest among patients who
achieved a complete response of the primary tumor and
lymph nodes (T0 N0) with neoadjuvant therapy. Even
without complete tumor sterilization, the results of this
study suggest that when the mediastinal lymph nodes
alone were downstaged, especially to an N0 status, there
was a survival benefit. This finding was consistent with
other investigations of nodal downstaging positively affecting long-term survival [29, 30].
As expected, the presence of pathologically positive N2
disease in this series was associated with a worse survival
compared with N0 disease. Nonetheless, survival after
resection of N2 disease was still acceptable given that
patients had locally advanced disease at the onset of
Ann Thorac Surg
2009;88:937– 44
treatment. Also, when patients with N2 disease were
evaluated by laterality of resection, 6 of 20 (30%) who
underwent left-sided and 7 of 34 (21%) who underwent
right-sided pneumonectomy were still alive 5 years after
their resections. Although not an ideal rate of survival,
this suggests that pneumonectomy in the presence of
pathologically positive N2 disease should not be considered as devastating as is often believed if discovered
either intraoperatively or postoperatively, even when
performing a right-sided pneumonectomy.
However, given the high perioperative mortality rate
and the lower 5-year survival, when right-sided pneumonectomy is being contemplated after neoadjuvant chemoradiation therapy, we recommend invasive mediastinal restaging to confirm the absence of persistent N2
lymph node disease. Having the benefit of this retrospective study, we believe that right-sided pneumonectomy
should not be offered in the subset of patients with
positive N2 involvement after therapy. Understood in
this recommendation is that extenuating circumstances
may justify a right-sided pneumonectomy. Despite the
possibility of a potentially fatal complication, if this
operation is to be considered, a lower—yet still acceptable—5-year survival can still be achieved. It is up to the
discretion of the clinician to select the optimal patient
to undergo a pneumonectomy under these specific
conditions.
This study has several limitations. First, as with all
retrospective studies, the data were collected post hoc.
Second, a tissue diagnosis for mediastinal lymph node
involvement was not secured in most patients. The argument against this was that we showed a survival with
positive N2 disease to be acceptable. These findings were
consistent with Mansour and colleagues’ [22] reported
5-year survivals for the patients who underwent induction chemotherapy. Clinical criteria of N2 disease using
imaging studies alone have been reported in investigations that have demonstrated the absence of any detrimental effect of neoadjuvant therapy [3, 14].
Third, an attempt was made to collect pulmonary
function studies of the patients undergoing surgical resection. However, these data were incomplete or not
collected in approximately one-third of the study population. Therefore, it was not possible to determine preoperative pulmonary condition of the patients.
Similarly, a fourth limitation was that it was difficult to
determine if other preoperative comorbidities that were
documented in patients preoperatively contributed to the
deaths observed in the postoperative period. Therefore,
our survival did not represent a disease-specific mortality. In reality, had the patients who died from their other
comorbidities been excluded, this would have only increased the observed survival.
Finally, the downstaged groups that were compared
represented a heterogeneous group of patients, and this
heterogeneity may have diluted the comparisons made
regarding downstaging.
In conclusion, this study demonstrated that with respect to pneumonectomy, side does matter under certain
circumstances. In general, long-term survival can be
achieved after concurrent chemoradiation therapy irrespective of side of pneumonectomy. The greatest survival
benefit derived from neoadjuvant therapy resulted when
there was a complete response or nodal downstaging.
The risk of early perioperative death, BPF, and ARDS
was higher for right-sided pneumonectomy, but overall,
5-year survival did not differ between right-sided and
left-sided resections. The development of any major
perioperative complication, however, negatively affected
long-term survival after right-sided pneumonectomies.
Even when positive mediastinal lymph nodes were removed, reasonable long-term survival was achieved.
However, we believe that when right-sided pneumonectomy is being contemplated after neoadjuvant therapy,
the presence of persistent positive N2 disease should
preclude resection due to the high perioperative morbidity and lower long-term survival. This reason alone,
above all others, is justification for performing invasive
mediastinal restaging before resection is considered.
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GENERAL THORACIC
Ann Thorac Surg
2009;88:937– 44
944
KIM ET AL
PNEUMONECTOMY AFTER CHEMORADIATION
Ann Thorac Surg
2009;88:937– 44
DISCUSSION
DR SCOTT J. SWANSON (Boston, MA): Great paper. Given the
length of time over which the cases were performed, has
anything changed in your management? Were there any timerelated factors in this analysis?
GENERAL THORACIC
DR KIM: The most consistent and constant change throughout
the experience was probably in the surgeons performing the
operations. If you look at the entire experience, we are talking
about four surgeons. I’m sure that how each individual surgeon
approached their pneumonectomy varied to some degree.
That being said, we stapled the bronchus in all of these cases.
For the right side, it was routine that we performed stump
coverage with either a pleural flap or pericardial fat pad. So
there were certain constancies in that respect.
From the chemotherapy standpoint, there were variations in
the management as the regimens evolved. Ultimately, there
were basically four iterations total, but they were all platinumbased regimens.
Lastly, the administration of the split course radiation therapy
was modified. Early in the series, our radiation oncologists
would use a shorter course of therapy with higher fractionated
dosages. Over time, the interval for the administration of radiation therapy increased with a concomitant lowering of the
dosage. The use of three preoperative cycles did not vary.
A review of our operative records indicated that, technically,
each pneumonectomy was performed in a similar manner with
the aforementioned stapled closures and buttressing with pericardial fat pad, pleura, or mediastinal tissue. Muscle flaps and
intercostal muscle were not used. Many of these cases were
advanced cancers and extensive dissection was required.
With respect to your second question regarding our 5-year
survival of 28% for resections with positive N2 lymph nodes, we
did not employ any special algorithm in patient selection. We
relied on restaging with the CT scan after the third cycle of
neoadjuvant therapy. In the early part of the series, clinically
positive N2 disease was defined by CT evidence of nodes larger
than 2 cm in largest dimension. Selected cases had mediastinoscopy. PET scan coupled with CT scan was a major factor in the
later portion of the series.
DR JEAN DES LAURIERS (Quebec, Canada): I would like to
know how reliable is a mediastinoscopy after you have done a
previous one and the patient has had radiotherapy over the
mediastinum. I ask this question because you recommend that
patients be restaged surgically which usually means by way of
mediastinoscopy. From my experience, it would be very difficult
to have accurate sampling and do a safe operation in such
patients.
DR SWANSON: And the tests didn’t cluster by time?
DR KIM: No, they did not and that is actually something we
reviewed. It appeared that there was an even distribution over
the entire time period.
DR PAUL DE LEYN (Leuven, Belgium): Thank you for this very
nice presentation. It clearly shows that you can indeed perform
right pneumonectomy in selected cases after chemoradiotherapy.
I have two questions. My first question is your incidence of
bronchopleural fistula after right pneumonectomy is 12%. This
is quite high despite buttressing the bronchus. Can you tell us
something about the technique, and do you use nowadays
another technique to buttress the bronchial stump?
And then the second question. In patients with persistent N2
disease, you had 5-year survival of 24%, which is very good. How
were these patients selected? How did you stage your patients?
Did you use PET? How did you restage your patients?
DR KIM: With respect to your first question, technically not
much has changed. We are still buttressing with pericardial fat,
pleura, and mediastinal tissue. When we looked at our numbers,
the incidence of BP fistulas on the right surprised us. We didn’t
expect it to be that high.
DR KIM: Based on our data, we now recommend that invasive
mediastinal staging be considered. Cervical mediastinoscopy
does not necessarily have to be the approach used. Bronchoscopic-guided needle biopsy or EUS for certain nodal stations is
certainly an acceptable alternative.
Repeat cervical mediastinoscopy following neoadjuvant therapy, like repeat cervical mediastinoscopy in any other setting,
warrants greater caution in avoiding the pitfalls. In the future,
EBUS may be the method to initially stage mediastinal nodes
with cervical mediastinoscopy reserved for restaging.
DR DES LAURIERS: Is Dr Faber your mediastinoscopist? I don’t
know if he is— he’s right here, yeah.
DR JOSHUA R. SONETT (New York, NY): I enjoyed your
presentation. I think it’s another third or fourth series that
bespeaks to the safety of pneumonectomy after chemo and
radiation since the Intergroup trial.
I would just say that the buttressing is not all equal, and most
of your complications and probably mortality were related to the
BPF on the right. And if you switch to muscle flaps, either
intercostal muscle or serratus, you may see that BPF rate go to an
amazingly low rate. That’s all, no other question.