GENERAL THORACIC
ORIGINAL ARTICLES: GENERAL THORACIC
GENERAL THORACIC SURGERY:
The Annals of Thoracic Surgery CME Program is located online at http://www.annalsthoracicsurgery.org/cme/
home. To take the CME activity related to this article, you must have either an STS member or an
individual non-member subscription to the journal.
Salvage Lung Resections After Definitive
Chemoradiotherapy: A Safe and Effective
Oncologic Option
Adam J. Bograd, MD, Catherine Mann, MD, Jed A. Gorden, MD,
Christopher R. Gilbert, DO, Alex S. Farivar, MD, Ralph W. Aye, MD, Brian E. Louie, MD,
and Eric Valli
eres, MD
Division of Thoracic Surgery, Swedish Cancer Institute, Seattle, Washington
Background. Patients with locally advanced, non-small
cell lung cancer treated with definitive chemo-
radiotherapy alone often demonstrate persistent or
recurrent disease. In the absence of systemic progression,
salvage lung resection after definitive chemoradiotherapy
has been used as a treatment option. Given the paucity of
data, we sought to evaluate the safety and efficacy of
salvage pulmonary resections occurring greater than 90
days after definitive chemoradiotherapy.
Methods. Retrospective institutional database review
identified patients undergoing salvage lung resection at
least 90 days after the completion of definitive chemo-
radiotherapy. Primary outcomes evaluated were overall
survival and recurrence-free survival.
Results. Thirty patients met inclusion criteria between
January 1, 2004 and December 31, 2015. Median time to
surgery after definitive radiotherapy was 279 days
(interquartile range, 168-474 days). Extended resections
were performed in 11 patients (37%). Ottawa Thoracic
Morbidity and Mortality Classification System grade IIIA
T he optimal treatment for locally advanced non-small
cell lung cancer (NSCLC) is an often debated and
controversial topic. Options include definitive chemo-
radiotherapy (dCRT) without intent for surgery, dCRT
followed by immunotherapy, induction chemotherapy
alone or induction concurrent chemoradiotherapy fol-
lowed by resection, and resection followed by chemo-
therapy and sequential radiation therapy. Patients
deemed inoperable or not favorable for surgery at diag-
nosis are offered curative intent dCRT with high-dose
Accepted for publication Apr 6, 2020.
Presented at the Canadian Association of Thoracic Surgery Annual
Meeting, Toronto, Ontario, Canada, Sep 8-10, 2016.
Address correspondence to Dr Bograd, Division of Thoracic Surgery,
Swedish Cancer Institute, 1101 Madison St, Ste 900, Seattle, WA 98104;
email: adam.bograd@swedish.org.
Ó 2020 by The Society of Thoracic Surgeons
Published by Elsevier Inc.
or greater complications occurred in 12 patients (40%).
Thirty-day mortality was 6.7% (2 patients). Median
overall survival after salvage resection was 24 months.
Median overall survival for an R1 resection was 5.3
months vs 108 months for an R0 resection (P [ .001).
Persistent pN1-positive salvage resections also did
less well compared with pN0 (8.9 vs 28.2 months;
P [ .06). For patients who underwent nonextended
salvage resection (simple lobectomy or simple pneumo-
nectomy), median overall survival was 108.4 months, vs
8.9 months for extended salvage resections
(P [ .02).
Conclusions. With proper patient selection, salvage
lung resections can be performed with acceptable
morbidity, mortality, and oncologic outcomes, particu-
larly when a ypN0R0 resection can be achieved by non-
extended surgical means.
(Ann Thorac Surg 2020;110:1123-30)
Ó 2020 by The Society of Thoracic Surgeons
radiation (greater than 59 Gy), with increasing incorpo-
ration of immunotherapy. Although the goal of treatment
for these patients is cure and long-term survival, patients
historically treated with dCRT alone have notable rates of
local failure and poor overall survival (OS).1 After dCRT,
the presence of persistent or recurrent local disease in the
absence of systemic progression has given rise to the
concept that lung resection after dCRT may represent a
chance for long-term survival. These pulmonary re-
sections after dCRT have been aptly termed salvage
resections.
True salvage lung resections refer to surgeries per-
formed in patients who were treated with curative-intent,
high-dose chemoradiotherapy with no initial plan for
surgical resection. By definition, salvage resections thus
occur outside the usual 6- to 8-week window when
standard postinduction pulmonary resections are
attempted. This delay leads to technically more difficult
0003-4975/$36.00
https://doi.org/10.1016/j.athoracsur.2020.04.035
 1124 BOGRAD ET AL Ann Thorac Surg
GENERAL THORACIC

SALVAGE LUNG RESECTION AFTER DCRT 2020;110:1123-30

operations, most often as a consequence of operating in a calculated from time of pulmonary resection to imaging-
field of radiation fibrosis and unclear tissue planes.2 As a or biopsy-proven recurrence. Similarly, patients still alive
result of such delays, tissue ischemia inherent in the ef- without recurrence were censored at the date of last
fect of radiating lung tissue and airways may compromise follow-up.
wound healing and increase the risk for postresection All statistical analyses were performed using GraphPad
bronchopleural fistulas (BPF). Prism software (version 8.0.0, GraphPad Software, San
Although several previous studies attempted to eval- Diego, CA).
uate the utility of salvage resections, there are several
shortcomings in the available literature.3-6 More specif-
ically, these studies included a large number of patients Results
resected less than 90 days after the completion of A total of 30 patients who met inclusion criteria under-
radiotherapy, patients who received lower doses of ra- went salvage pulmonary resections after dCRT during the
diation (ie, 40 Gy), and those who had lung resections study period (median age, 65.5 years; interquartile range
contralateral to the field of radiation. [IQR], 57.6-69.9 years). Most patients were ever-smokers
Given these limitations and the lack of clear guidelines, (Table 1).
we sought to report our experience with salvage pulmo- Decisions to treat initially with dCRT were most often
nary resections in individuals who had previously made at an outside institution; surgical input was rarely
completed dCRT (with no initial plans for resection) at a documented at these institutions (n ¼ 22; 73%). Of the 8
minimum of 90 days before surgery. The goal of this patients with clear documentation of the decision to treat
study was to examine a group of true salvage resection with dCRT, 5 were evaluated by thoracic surgeons at
patients to assess the safety, feasibility, and oncologic outside institutions before treatment began. Most patients
outcomes of the procedure. (n ¼ 28; 93%) received platinum-based chemotherapy
concurrently with radiotherapy; 2 (7%) received sequen-
Patients and Methods tial radiotherapy after platinum-based chemotherapy.
The chemotherapy regimen was not standardized. All
We performed a retrospective review of all lung cancer patients received curative-intent radiotherapy to the pri-
patients at our institution who received dCRT followed mary lung mass ranging from 45 to 70 Gy (median dose,
by surgical resection between January 1, 2004 and 60 Gy); 83% (n ¼ 25) were treated with a radiation dose of
December 31, 2015; this was to ensure adequate post- greater than 59 Gy.
operative follow-up interval. Inclusion criteria were (1) Clinical stage distributions before dCRT varied
age greater than 18 years, (2) treatment with curative- widely (Table 2). Rationales for the decision to treat
intent chemoradiotherapy with no initial plan for sur- with dCRT was also heterogeneous (Table 3). Clear
gery in the patient’s treatment algorithm, (3) interval documentation of the rationale for treatment with dCRT
between completion of radiotherapy and elective sur- was not identified in 6 patients (20%). Several patients
gery greater than 90 days, (4) resection extent of at least a were clinically thought (by imaging alone) have stage
lobectomy, and (5) site of resection ipsilateral to the site IV disease upon presentation and were treated
of lung radiation. We excluded patients who presented
with complications of dCRT (hemoptysis, abscess, or
BPF) that led to nonelective surgery. This study was
Table 1. Clinical Characteristics of Study Cohort
approved by the Swedish Medical Center Institutional
Review Board, with a waiver of individual patient Characteristics Values
consent.
Age, y
The salvage pulmonary resections in this study
Median 65.5
included resections for either recurrent tumor after an
Q1, Q3 (IQR) 57.6, 69.9 (12.3)
initial response to dCRT or documented persistent dis-
ease or suspicion for it despite dCRT. Initial clinical Sex, n (%)
characteristics and operative and postoperative variables Men 18 (57)
were identified through retrospective chart review. Post- Women 12 (43)
operative complications were graded by the Ottawa Smoking history, n (%)
Thoracic Morbidity and Mortality Classification system.7 Never 2 (7)
Oncological outcomes examined were OS and Former 22 (73)
recurrence-free survival (RFS). Current 6 (20)
All patients were restaged according to the Eighth Radiotherapy dose, Gy, n (%)
edition of the American Joint Committee on Cancer tu- 59 25 (83)
mor necrosis marker staging system. <59 5 (17)
Overall survival and RFS analyses were calculated us- Follow-up, mo
ing the Kaplan-Meier method. Overall survival analysis Median 19.4
included all deaths from any cause during the patient’s Q1, Q3 (IQR) 5.9, 76.9 (70.9)
follow-up. Patients alive at the date of last follow-up were
censored at that time point. Recurrence-free survival was IQR, interquartile range; Q, quartile.
Ann Thorac Surg BOGRAD ET AL 1125

GENERAL THORACIC
2020;110:1123-30 SALVAGE LUNG RESECTION AFTER DCRT

Table 2. Pre- and Postsalvage Resection Staging Table 4. Surgical Characteristics of Salvage Resection Cohort
Staging and Histology Values Characteristics Values

Preoperative clinical stage, n (%) Time from radiotherapy to surgery, d

IA2 1 (3.3) Median 279
IIA 1 (3.3) Q1, Q3 (IQR) 168, 474 (306)
IIB 4 (13.3) Preoperative mediastinal staging, n (%)
IIIA 16 (53.3) Yes 25 (83)
IIIB 4 (13.3) No 5 (17)
IV 4 (13.3) Resection extent, n (%)
Postsalvage resection pathologic stage, n (%) Lobectomy 16 (53)
pCR 4 (13.3) Extended lobectomy 6 (20)
IA1 1 (3.3) Bilobectomy 1 (3)
IA2 1 (3.3) Pneumonectomy 2 (7)
IB 2 (6.7) Extended pneumonectomy 5 (17)
IIA 5 (16.7) Bronchial stump coverage, n (%)
IIB 9 (30) Intercostal muscle 21 (70)
IIIA 8 (26.7) Pericardial fat 2 (7)
Postoperative histology, n (%) Pleura 1 (3)
Squamous cell 15 (50) Omentum 2 (7)
Adenocarcinoma 7 (23.3) None 4 (13)
pCR 4 (133) Completeness of resection, n (%)
LCNE 2 (6.7) R0 24 (80)
Sarcomatoid 1 (3.3) R1 6 (20)
Mucoepidermoid 1 (3.3) R2 0
Surgical estimated operative blood loss, mL
LCNE, large cell neuroendocrine; pCR, pathologic complete response.
Median 150
Q1, Q3 (IQR) 100, 475 (375)
nonsurgically. Upon workup at our center, these pa- Operating room time, min
tients were found not to have stage IV disease. In Median 293
addition, several patients with stage I to II disease had Q1, Q3 (IQR) 241, 341 (100)
been treated with dCRT because of medical comorbid- Length of stay, d
ities or concern for unresectability; despite being Median 7
deemed unresectable, many of these patients had no Q1, Q3 (IQR) 4, 15.2 (11.2)
documentation from a thoracic surgeon. 30-d mortality, n (%)
Patients were referred for salvage resection for either Yes 2 (7)
recurrent (n ¼ 6) or persistent (n ¼ 16) disease. The No 28 (93)
rationale for referral was unclear in 8 patients, all from 90-d mortality, n (%)
the earlier part of the group. All patients were presented Yes 3 (10)
for evaluation for salvage resection at a multidisciplinary
No 27 (90)
tumor board composed of thoracic surgeons,
Adjuvant treatment, n (%)
Chemotherapy 7 (24)
Radiotherapy 1 (3)
Table 3. Rationale for Initial Treatment With Definitive None 22 (73)
Chemoradiotherapy
IQR, interquartile range; Q, quartile.
Reason Values

Unresectable owing to disease extent, n (%)

interventional pulmonologists, medical oncologists, radi-
Stage IIIB 4 (13)
ation oncologists, interventional radiologists, diagnostic
Stage IV 4 (13)
radiologists, and a pathologist. All underwent restaging
T4 (spine invasion) 3 (10)
positron emission tomography or computed tomography
IIIA-N2 (multistation) 2 (7) and brain magnetic resonance imaging. Invasive medi-
IIIA-N2 (single station) 2 (7) astinal staging was performed in 25 patients (83%); no
T4 (recurrent laryngeal nerve invasion) 1 (3) patients with persistent N2-positive mediastinal lymph
Small cell carcinoma (questionably identified on initial 5 (17) nodes identified at invasive mediastinal staging pro-
biopsy), n (%)
ceeded to salvage resection. Presalvage resection tissue
Medically inoperable (well-documented), n (%) 3 (10)
confirmation of persistent or recurrent malignancy was
Inoperable for unclear reasons, n (%) 6 (20) obtained in 16 patients (53%).
 1126 BOGRAD ET AL
GENERAL THORACIC
SALVAGE LUNG RESECTION AFTER DCRT
Figure 1. (A) Overall survival
(OS) for entire salvage resection
cohort. (B) Recurrence-free sur-
vival (RFS) excluding R1
resections.
Median interval from the conclusion of radiotherapy to
salvage resection was 279 days (IQR, 168-474 days) (Ta-
ble 4). Sixteen patients underwent a lobectomy (53%), 1
underwent a bilobectomy (3%), and 2 underwent a
pneumonectomy (7%). Extended resections involving
intrapericardial resection or en bloc resection of the chest
wall, great vessel, superior vena cava (SVC), or vertebral
body were performed in 11 patients: 6 by extended lo-
bectomy (20%) and 5 by extended pneumonectomy (17%).
All surgeries were performed by posterolateral thoracot-
omy. Table 4 lists surgical characteristics of the cohort.
Several intraoperative complications were encoun-
tered. Four patients (13%) experienced major vascular
injuries during surgery: 1 aortic injury (3%), 1 pulmonary
artery injury requiring primary repair (3%), 1 SVC injury
requiring patch reconstruction (3%), and 1 pulmonary
artery injury requiring conversion from lobectomy to
pneumonectomy (3%). One additional patient underwent
intentional SVC resection with graft reconstruction and
developed acute graft thrombosis that required immedi-
ate revision (3%).
Median hospital length of stay was 7 days (IQR, 4-15
days). Two patients died within 30 days (7%); there was 1
additional death at 30 to 90 days.
An R0 resection was accomplished in 24 patients (80%).
Microscopically positive (R1) margins were seen in 6
patients (20%). Pathologic complete response was seen in
4 patients (13%), whereas a viable tumor was identified in
26 patients (87%). The predominant histology identified at
salvage resection was squamous cell carcinoma (n ¼ 15;
50%). Postsalvage resection pathology is shown in
Table 2. Most patients were pN0 (n ¼ 23, 77%). Persistent
pN1 disease was identified in 7 patients (23%). No
patients demonstrated persistent pN2 disease.
Figure 2. Effect on overall sur-
vival (OS) of (A) completeness of
resection and (B) persistent nodal
disease identified at salvage
resection.
Ann Thorac Surg
2020;110:1123-30
Postoperative complications occurred in 17 patients
(57%). Ten patients experienced more than 1 complica-
tion after surgery (33%). Major complications (Ottawa
grade greater than IIIA) occurred in 12 patients (40%).
These complications consisted of 3 tracheostomy or
percutaneous endoscopic gastrostomy placements, 2
vocal cord injections for vocal cord paresis, 1 stroke, 1
Claggett window for postpneumonectomy empyema, 1
postlobectomy empyema with persistent space requiring
muscle flap obliteration, and 3 deaths (1 resulted from
multisystem organ failure, 1 from aortoesophageal fistula
[from salvage resection requiring esophageal myotomy
and aortic graft reconstruction], and 1 from recurrent SVC
graft thrombosis and renal failure). One postlobectomy
BPF was documented during patient follow-up; this was
treated conservatively with a pigtail catheter requiring an
11-day hospital admission. Median follow-up was 19.4
months (IQR, 70.9 months). Median OS for the entire
cohort was 24 months (Figure 1A). Excluding patients
with R1 resections, 5-year RFS was 65% (Figure 1B). In
patients with R0 resections, there were 8 postoperative
recurrences (range, 5.4-17.7 months). After R0 resection,
the dominant site of recurrence was distant in 6 (75%),
half of which were in the brain; it was regional in 1 and
local in 1. All R1 resections recurred locally as the first site
of recurrence (1-4.8 months after surgery). Overall sur-
vival was significantly stratified by completeness of
resection (Figure 2A). Median OS for R1 salvage re-
sections was 5.3 months vs 108 months for an R0 salvage
resection (p ¼ .001); no patients with an R1 resection
survived past 11 months.
Although not statistically significant, patients with
persistent pathologic N1 lymph nodal involvement after
salvage resection had decreased median OS compared
Ann Thorac Surg
2020;110:1123-30
with pN0 resections: 8.9 vs 28.2 months (P ¼ .06),
respectively (Figure 2B). However, among the 7 patients
who were found on final pathology to have N1 lymph
node involvement, 2 were long-term survivors, with 127-
and 130-month survival after a nonextended left upper
lobectomy and left pneumonectomy, respectively.
Figures 3A and 3B demonstrate OS as described by
resection extent. For patients who underwent non-
extended salvage resection (simple lobectomy or simple
pneumonectomy), median OS was 108.4 months,
compared a median OS of 8.9 months for extended
salvage resections (P ¼ .02).
A subgroup analysis of patients with preoperative
clinical stage IIIA disease demonstrated similar findings
(Figures 4, 5). More specifically, median OS was 26.1
months with a 5-year RFS of 68%. Similarly, clinical IIIA
patients who were able to undergo an R0 resection
and nonextended salvage resection demonstrated
improved OS.
Comment
In this study, we report on the largest group of patients
undergoing salvage resection at a minimum of 90 days
after curative-intent dCRT.
In appropriately selected patients, at specialized
thoracic surgical centers, we demonstrate that salvage
resection after dCRT is technically feasible and may be
accomplished with reasonable morbidity and mortality.
Median interval from conclusion of radiotherapy to
salvage resection was 279 days, with the earliest resec-
tion occurring at 118 days. Median OS of the cohort was
24 months, with many long-term survivors (>5 years).
Patients who were resectable with a simple
BOGRAD ET AL 1127
GENERAL THORACIC
SALVAGE LUNG RESECTION AFTER DCRT
Figure 3. Overall survival (OS)
stratified by (A) extent of resection
and (B) simple vs extended
resection.
(nonextended) lobectomy or pneumonectomy demon-
strated excellent long-term OS (108.4 months) and
acceptable perioperative morbidity. The outcomes and
complication rates identified in this study are similar
those previously reported for salvage resections. Only 4
patients within the current cohort were found to have a
pathologic complete response to dCRT, which suggests
that the survival demonstrated in this study was not
driven by this, as it may have been in previous
studies.4,6,8
Patients with R1 resections did poorly, with a median
OS of 5.3 months and none surviving past 11 months after
surgery. Early studies from Memorial Sloan-Kettering
Cancer Center detailing postinduction pulmonary
resections for regionally advanced lung cancer demon-
strated a marked difference in OS for R0 resection vs R1/2
resection, with median OS of 27 vs 12 months, respec-
tively.9 Subsequent studies examining the surgical treat-
ment of locally advanced NSCLC echoed this finding.10-13
Although the current cohort was small, our data support
that performing an incomplete (R1) resection is not of
much benefit in the salvage setting and should be avoi-
ded when possible. Looking in greater detail at the pa-
tients who had R1 resections, this subgroup of patients
was composed solely of those with extended resections
(Table 5); according to operative reports, a greater extent
of resection was not possible or feasible. Furthermore, a
greater parenchymal resection, namely a pneumonec-
tomy, would not have helped the margin status in these
patients. As illustrated by these cases, in salvage re-
sections it is often exceedingly difficult to determine the R
status until fairly late in the procedure, when one may
already have committed to the resection (ie, vertebral
resections).
Figure 4. Preoperative stage IIIA
(A) overall survival (OS) and (B)
recurrence-free survival (RFS).
 1128 BOGRAD ET AL
GENERAL THORACIC
SALVAGE LUNG RESECTION AFTER DCRT
Figure 5. Preoperative stage IIIA overall survival (OS) stratified by
(A) completeness of resection, (B) pN status, and (C) simple vs
extended resection.
Patients with residual N1 lymph nodal disease also
did less well, with a median OS of 8.9 months, compared
to 28.2 months for node-negative patients. However, 2
(of 7) resected ypN1 patients were 10-year survivors,
both of whom had nonextended resections (1 lobectomy
and 1 pneumonectomy). These data are consistent
with prior investigations detailing worse OS for
patients with persistent nodal disease after induction
chemoradiotherapy regimens for locally advanced
Ann Thorac Surg
2020;110:1123-30
NSCLC.12,14,15 In this context, one must be thoughtful
about offering salvage resections for patients with
persistent N1 nodal disease. In the setting of salvage
attempts, in which the optimal selection of the patients
who could potentially benefit from resection appears to
be critical, we strongly recommend aggressive pre-
resection mediastinal and hilar nodal evaluation
with video mediastinoscopy and endobronchial ultra-
sound. Although persistent N2 disease after chemo-
radiotherapy was previously documented to be
associated with worse outcomes in this population, our
data lend support to persistent N1 disease also being an
adverse prognostic factor for OS after salvage resection.
One should be careful in offering salvage surgery to
ycN1 patients.
No patients with residual N2 lymph node disease were
identified in this study, which reflects in part our phi-
losophy of aggressive mediastinal staging before offering
salvage resections. Multiple previous studies examining
induction regimens for locally advanced NSCLC
demonstrated improved OS within the subgroup of pa-
tients with mediastinal lymph node sterilization.12,15,16
Most recently in the Intergroup-0139 trial, patients with
pathologic N0 status after resection demonstrated mark-
edly improved OS compared with those with residual
mediastinal nodal disease. The accuracy of invasive
mediastinal staging in this pretreated population was
reported to be somewhat less, particularly when
attempting to repeat the mediastinoscopy after interval
induction therapy.17-20 We previously reported on our
experience with such complex mediastinoscopies, and
although the accuracy is diminished compared with naïve
mediastinoscopies, positive returns are informative when
evaluating for possible salvage resection.21 Accurate
identification of persistent cancer within lymph nodes in
the presence of significant treatment effect may be diffi-
cult, however.
The extent of resection had a major impact on OS.
Patients who were resectable with a nonextended or
simple anatomic resection (lobectomy or pneumonec-
tomy) had markedly improved median OS compared
with patients who required more extensive, extended
resections. Two of the 3 early postoperative deaths
occurred in the extended pneumonectomy subgroup.
Furthermore, only 1 5-year survivor within the
extended resection group had undergone an extended
right upper lobectomy. Prior studies22 detailing the
postpneumonectomy outcomes of patients with NSCLC
demonstrated that extended resections are associated
with adverse outcomes and poor OS. Our data support
this observation in the salvage setting as well. The role
of extended resections, especially extended pneumo-
nectomy, may have a limited role in the treatment of
these patients. Given the poor outcomes observed
within this subgroup in the salvage setting, one needs
to be exceedingly cautious about to whom this type of
resection is offered, if at all. Unfortunately, the need for
an extended resection is sometimes determined during
surgery, after hilar structures have already been
divided.
Ann Thorac Surg BOGRAD ET AL 1129

GENERAL THORACIC
2020;110:1123-30 SALVAGE LUNG RESECTION AFTER DCRT

Table 5. Surgical and Pathologic Characteristics of R1 Resection Subgroup

Where Was Margin Would Pneumonectomy Viable Overall
Resection Positive? Have Helped? Tumor? Survival, mo

Left pneumonectomy, esophageal myotomy/muscle Esophageal N/A Yes 1.3

resection, aortic arch reconstruction
Anterior left trapdoor, partial sternotomy, resection of ribs Subclavian artery, No Yes 5.1
1-3 en bloc with left upper lobectomy,subclavian artery vertebral body
and vein resection, bypass from left carotid to left axillary
artery, bypass from left carotid artery to left vertebral
artery; partial resection and stabilization of 2 vertebral
bodies
Intrapericardial left pneumonectomy, esophageal Esophagus N/A Yes 5.0
myotomy/muscle resection
Left upper lobectomy, en bloc hemivertebrectomy and ribs Vertebral body No Yes 5.3
2-4
Extrapleural right upper lobectomy, with en bloc superior Parietal pleural near No Yes 8.9
segmentectomy, middle lobectomy spine
Extrapleural left upper lobectomy Parietal pleura, aortic No Yes 11.5
adventitia

N/A, not available.

While this study was not focused on the intraoperative
management of salvage resections, we adhere to several
key tenets during the conduct of these procedures. Dur-
ing surgery, it is crucial to maintain close communication
with the anesthesia team. Our practice is to keep these
patients euvolemic to slightly dry, because we have found
that the irradiated mediastinum and lung parenchyma
has difficulty handling excess fluid during and after sur-
gery. Bronchial stump coverage, most commonly with an
intercostal muscle flap, was routinely performed in an
attempt to prevent BPF. The low incidence of BPF for-
mation in this study was possibly a consequence of
consistent bronchial stump coverage. Obtaining proximal
pulmonary artery control is helpful to prevent major
bleeding that can be encountered during dissection of
fibrosed hilar structures; this was done selectively in the
current cohort. For left-sided resections, the ante-
roposterior window nodal dissection may put the left
recurrent laryngeal nerve at risk for injury; when suspi-
cious of injury, early vocal cord medialization is critical.
This study had several limitations. First, it had a
retrospective design, which carries with it all of the usual
concerns of a retrospective study. Furthermore, this was a
small, highly selected cohort from a single institution,
which may have affected the study’s generalizability to a
wider population. Second, there was no control group
with which to compare the salvage resection outcomes.
Third, there was an absence of quality-of-life outcome
data. Finally, our protocol was not standardized; patients
presenting for salvage resection were at varying time
points after the completion of dCRT.
Our experience highlights that in properly selected
patients, salvage pulmonary resection may be performed
with acceptable morbidity, mortality, and oncologic out-
comes, particularly when a ypN0R0 resection can be
achieved by nonextended surgical means. Considering
the enhanced risks for resection in the salvage setting,
when possible, we advocate documenting the presence of
active malignancy in patients, to minimize the possibil-
ities of submitting complete responders to surgery. Our
data suggest that only patients with complete resections
(R0) benefit from salvage surgery and that there are no
benefits from R1 resections. According to our limited
data, it also appears that persistent ypN1 disease may be
a harbinger of poor survival.
References
1. Auperin A, Le P echoux C, Rolland E, et al. Meta-analysis of
concomitant versus sequential radiochemotherapy in locally
advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:
2181-2190.
2. Novakova-Jiresova A, van Luijk P, van Goor H, et al.
Changes in expression of injury after irradiation of
increasing volumes in rat lung. Int J Radiat Oncol Biol Phys.
2007;67:1510-1518.
3. Kuzmik GA, Detterbeck FC, Decker RH, et al. Pulmonary
resections following prior definitive chemoradiation therapy
are associated with acceptable survival. Eur J Cardiothoracic
Surg. 2013;44(1):e66-e70.
4. Yang CFJ, Meyerhoff RR, Stephens SJ, et al. Long-term
outcomes of lobectomy for non-small cell lung cancer after
definitive radiation treatment. Ann Thorac Surg. 2015;99:1914-
1920.
5. Casiraghi M, Maisonneuve P, Piperno G, et al. Salvage sur-
gery after definitive chemoradiotherapy for non–small cell
lung cancer. Semin Thorac Cardiovasc Surg. 2017;29:233-241.
6. Bauman JE, Mulligan MS, Martins RG, et al. Salvage lung
resection after definitive radiation (>59 Gy) for non-small
cell lung cancer: surgical and oncologic outcomes. Ann
Thorac Surg. 2008;86:1632-1639.
7. Seely AJE, Ivanovic J, Threader J, et al. Systematic classifi-
cation of morbidity and mortality after thoracic surgery. Ann
Thorac Surg. 2010;90:936-942.
8. Shimada Y, Suzuki K, Okada M, et al. Feasibility and efficacy
of salvage lung resection after definitive chemoradiation
therapy for Stage III non-small-cell lung cancer. Interact
Cardiovasc Thorac Surg. 2016;23:895-901.
9. Martini N, Kris MG, Flehinger BJ, et al. Preoperative
chemotherapy for stage IIIa (N2) lung cancer: the Sloan-
 1130 BOGRAD ET AL
GENERAL THORACIC
SALVAGE LUNG RESECTION AFTER DCRT
Kettering experience with 136 patients. Ann Thorac Surg.
1993;55:1365-1374.
10. Decaluw e H, De Leyn P, Vansteenkiste J, et al. Surgical
multimodality treatment for baseline resectable stage IIIA-
N2 non-small cell lung cancer. Degree of mediastinal
lymph node involvement and impact on survival. Eur J
Cardiothoracic Surg. 2009;36:433-439.
11. Martin J, Ginsberg RJ, Venkatraman ES, et al. Long-term
results of combined-modality therapy in resectable non-
small-cell lung cancer. J Clin Oncol. 2002;20:1989-1995.
12. Spicer JD, Shewale JB, Nelson DB, et al. Multimodality
therapy for N2 non-small cell lung cancer: an evolving
paradigm. Ann Thorac Surg. 2019;107:277-284.
13. van Meerbeeck JP, Kramer GWPM, Van Schil PEY, et al.
Randomized controlled trial of resection versus radiotherapy
after induction chemotherapy in stage IIIA-N2 non-small-
cell lung cancer. J Natl Cancer Inst. 2007;99:442-450.
14. Suntharalingam M, Paulus R, Edelman MJ, et al. RTOG 0229:
A phase II trial of neoadjuvant therapy with concurrent
chemotherapy and high-dose radiotherapy (XRT) followed
by resection and consolidative therapy for LA-NSCLC. J Clin
Oncol. 2010;28(15 suppl):7024.
15. Albain KS, Swann RS, Rusch VR, et al. Radiotherapy plus
chemotherapy with or without surgical resection for stage III
non-small cell lung cancer: a phase III randomised controlled
trial. Lancet. 2009;374:379-386.
Ann Thorac Surg
2020;110:1123-30
16. Suntharalingam M, Paulus R, Edelman MJ, et al. Radia-
tion Therapy Oncology Group Protocol 02-29: a phase II
trial of neoadjuvant therapy with concurrent chemo-
therapy and full-dose radiation therapy followed by sur-
gical resection and consolidative therapy for locally
advanced non-small cell carcinoma. Int J Radiat Oncol Biol
Phys. 2012;84:456-463.
17. Marra A, Hillejan L, Fechner S, Stamatis G. Remediastino-
scopy in restaging of lung cancer after induction therapy.
J Thorac Cardiovasc Surg. 2008;135:843-849.
18. De Waele M, Serra-Mitjans M, Hendriks J, et al. Accuracy
and survival of repeat mediastinoscopy after induction
therapy for non-small cell lung cancer in a combined series
of 104 patients. Eur J Cardiothoracic Surg. 2008;33:824-828.
19. Call S, Rami-Porta R, Obiols C, et al. Repeat mediastinoscopy
in all its indications: experience with 96 patients and 101
procedures. Eur J Cardiothoracic Surg. 2011;39:1022-1027.
20. Stamatis G, Fechner S, Hillejan L, et al. Repeat
mediastinoscopy as a restaging procedure. Pneumologie.
2005;59:862-866.
21. Louie BE, Kapur S, Farivar AS, et al. Safety and utility of
mediastinoscopy in non-small cell lung cancer in a complex
mediastinum. Ann Thorac Surg. 2011;92:278-283.
22. Riquet M, Mordant P, Pricopi C, et al. A review of 250 ten-
year survivors after pneumonectomy for non-small-cell
lung cancer. Eur J Cardiothoracic Surg. 2014;45:876-881.