Annual Meeting Proceedings Part 1 - American Society of Clinical ...

468s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7068 General Poster Session (Board #38C), Sat, 1:15 PM-5:15 PM
Phase II trial: Concurrent chemotherapy and radiotherapy with nitroglycerin
in locally advanced non-small cell lung cancer patients. Presenting
Author: Dolores De la Mata, Instituto Nacional de Cancerología, Mexico
City, Mexico
Background: The treatment of choice for locally advanced non small cell
lung cancer (NSCLC) is concurrent chemoradiation (CRT). However, efforts
to improve treatment results include targeted therapy and the use of
radiosensitizers. Nitroglycerin (NTG), a nitric oxide (NO) donor agent,
reduces expression of Hypoxia-Induced Factor, which is associated to both
chemo and radio resistance. Methods: This is phase II trial in patients with
locally advanced NSCLC treated with chemotherapy (CT) based on cisplatin
and vinorelbin with NTG concurrent with radiation therapy. A 25 mg NTG
patch was administered to the patients during the first 5 days of each
induction treatment cycle and during chemo-radiotherapy. Blood samples
of VEGF were taken before any treatment and after two cycles of CT. The
protocol is registered with ClinicalTrials.gov, number NCT00886405.
Results: 35 patients were enrolled in this trial. Median Follow up was 16.6
months (SD �13.6). Mean age was of 59.9 years (�10.8), 68.6% of the
patients were smokers. ECOG status was 0 in 22.9%, 1 in 65.7% and 2 in
11.5%, respectively. Histopathology was adenocarcinoma in 68.6%,
epidermoid in 17.1% and undifferentiated in 14.3%. Stage distribution
was: IIIa, 57.6% and IIIb, 42.5%. All patients completed CRT treatment
and four underwent surgical treatment. Toxicity profile related to NTG was
grade 1 and 2 headache in 17.1%. Grade 3 and 4 toxicities were
esophagitis (17.1%), neutropenia (62.9%), and nausea (5.7%). Sixty-four
per cent of patients achieved partial response after CT and 75.8% after
CRT. PFS was 11.8 months (95%, IC 7.8-15.6) and OS was 42.9 months
(95%IC 31.3-52.1). After two cycles of CT, plasma VEGF levels were
significantly lower (Median 132�79 vs. 53�78 pg/ml, p�0.001). No
differences on PFS and OS were found between patients with a reduction �
93 pg/ml (median of differences between VEGFR before and after chemotherapy).
Conclusions: The addition of NTG to induction CT, and concurrent
CRT on locally advanced NSCLC patients seems to increase the response
rate, PFS and OS with an acceptable toxicity profile. A prospective trial is
warranted to confirm these findings.
7070 General Poster Session (Board #38E), Sat, 1:15 PM-5:15 PM
Multicenter phase II study of concurrent high-dose (72Gy) threedimensional
conformal radiotherapy (3D-CRT) without elective nodal
irradiation with chemotherapy using cisplatin and vinorelbine for unresectable
stage III non-small cell lung cancer (NSCLC). Presenting Author:
Hidehito Horinouchi, Division of Internal Medicine and Thoracic Oncology,
National Cancer Center Hospital, Tokyo, Japan
Background: The optimal dose of radiotherapy remains unclear in concurrent
chemoradiotherapy for unresectable stage III NSCLC. We previously
concluded that the recommended dose for further trial was 72Gy in a phase
I study (Sekine et al., Int J Radiat Oncol Biol Phys. 953-959, 2012).
Methods: Eligible patients (unresectable stage III NSCLC, age between 20
and 74, PS 0-1, V20 � 30%) received cisplatin (80 mg/m2 day 1) and
vinorelbine (20 mg/m2 days 1 and 8) repeated every 4 weeks for 3-4 cycles.
The 3D-CRT started at the first day of chemotherapy at a total dose of 72 Gy
in 36 fractions. The primary endpoint was a 2-year survival rate and the
planned sample size was 60 to reject the rate of 45% under the expectation
of 65% with a power of 90% and an alpha error of 5%. Results: Thirty-one
patients from 4 institutions were enrolled between May 2009 and March
2010. This trial was terminated early due to slow accrual and grade 5
pulmonary toxicities in 2 patients. There were 25 men and 6 women with a
median (range) age of 59 (32-72) years. Of these, 23 had adenocarcinoma
and 21 had stage IIIA disease. The median (range) V20 value was 20
(9-30). The full planned dose of radiotherapy could be administered in 30
(97%) patients, and 26 (84%) of the patients received 3-4 cycles of
chemotherapy. During the chemoradiotherapy, grade 3-4 febrile neutropenia,
infection and esophagitis were noted in 5, 4 and 1 of the 31 patients,
respectively. After completion of the planned chemoradiotherapy, 5 patients
had grade 3 or higher radiation pneumonitis, and 2 (6%) of these
patients died at 6.6 and 7.3 months after the treatment started. The overall
response rate was 97% (95% confidence interval: 83.3-99.9). Twenty-four
patients are alive and thirteen patients experienced recurrence (2 had
loco-regional recurrences, 7 had distant recurrence and 4 had mixed
recurrence pattern) at a median follow up of 16.4 months. Conclusions:
Concurrent high-dose (72Gy) 3D-CRT with chemotherapy using cisplatin
and vinorelbine may have a too excessive incidence of pulmonary toxicities
to warrant any further evaluation.
7069 General Poster Session (Board #38D), Sat, 1:15 PM-5:15 PM
Mediastinal lymph node examination and survival in resected early-stage
non-small cell lung cancer in the Surveillance, Epidemiology, and End
Results (SEER) database. Presenting Author: Raymond U. Osarogiagbon,
Boston Baskin Cancer Foundation, Germantown, TN
Background: Pathologic nodal stage is a key prognostic factor in resectable
non-small cell lung cancer (NSCLC). Mediastinal lymph node (MLN)
metastasis connotes a poor prognosis. Yet, some NSCLC resections in the
US do not include MLN examination. Methods: We analyzed SEER data
from 1998 to 2002 to quantify the long-term survival impact of failure to
examine MLN in resected NSCLC. We used Kaplan-Meier methods to
compare the unadjusted survival difference between patients with, and
without, MLN examination. We used Cox proportional hazards and competing
risk models to serially adjust for the impact of risk factors on survival
differences. Results: Sixty-two percent of patients with pathologic N0 or N1
NSCLC had no MLN examined. Men, African-Americans, patients with
more advanced stage, and those who had less than pneumonectomy were
less likely to have MLN examination. Five-year all-cause mortality (46.9% v
51.7%, p�.001), and lung cancer-specific mortality (31.5% v 36%,
p�.001), rates were higher in those without MLN examination. After
adjustment for potential confounders, MLN examination was associated
with a 6% reduction in all-cause mortality (HR, 0.94; CI, 0.89-0.99;
p�.014), and 10% reduction in lung cancer-specific mortality (HR, 0.90;
95% CI, 0.84-0.96; p�.002) rates. The excess risk in 1 year’s cohort of
U.S. lung resections was 2,700 lives over 5 years. Conclusions: Failure to
examine MLN was a common practice in �MLN-negative� NSCLC resections,
which significantly impaired long-term survival. Efforts to understand
the etiology of this quality gap, and measures to eliminate it, are warranted.
7071 General Poster Session (Board #38F), Sat, 1:15 PM-5:15 PM
Anatomic segmentectomy versus lobectomy for clinical stage I non-small
cell lung cancer: A propensity-matched analysis. Presenting Author:
Matthew J. Schuchert, Department of Cardiothoracic Surgery, University of
Pittsburgh Medical Center, Pittsburgh, PA
Background: Although anatomic segmentectomy is considered a “compromised”
procedure by many surgeons, new information from several retrospective,
single-institution series has countered negative premises regarding
tumor recurrence and patient survival. The primary objective of this study
was to utilize propensity score matching to compare outcomes following
these anatomic resection approaches for stage I NSCLC. Methods: Patients
undergoing lobectomy (n�392) vs. segmentectomy (n�793) for clinical
stage I NSCLC were matched 1:1 using a propensity score that accounted
for the potential confounding effects of pre-operative patient variables.
Matching based on propensity scores produced 312 patients in each group.
Primary outcome variables included recurrence-free and overall survival.
Factors affecting survival were assessed by proportional hazards (Cox)
regression and Kaplan-Meier survival function estimates. Results: Perioperative
mortality was 1.2% in the segmentectomy group and 2.5% in the
lobectomy group (p�0.38). Ninety-day mortality was 2.6% and 4.8%
(p�0.20), respectively. At a mean follow-up of 5.4 years, no differences
were noted in locoregional (5.5% vs. 5.1%, p�1.00), distant (14.8% vs.
11.6%, p�0.29) or overall recurrence rates (20.2% vs. 16.7%, p�0.30)
when comparing segmentectomy with lobectomy. Furthermore, no significant
differences were noted in time to recurrence (p�0.415) or overall
survival (p�0.258) when comparing the matched groups. Five year
freedom from recurrence (95% CI) was: Segment 0.70 [95% CI: (0.63,
0.78) vs. Lobe 0.71 [95% CI: 0.64, 0.78]. Overall survival (95% CI) was:
Segment 0.54 [95% CI: (0.47, 0.51) vs. Lobe 0.60 [95% CI: 0.54, 0.67].
Segmentectomy was not found to be an independent predictor of recurrence
(HR: 1.11, 95% CI: 0.87, 1.40) or overall survival (HR � 1.17, 95%
CI: 0.89.1.52). Conclusions: In this large propensity-matched comparison,
anatomic segmentectomy is associated with similar time to recurrence and
overall survival rates when compared to lobectomy for clinical stage I
NSCLC. These results will need further validation by prospective, randomized
trials (CALGB 140503).
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