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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7040 General Poster Session (Board #34G), Sat, 1:15 PM-5:15 PM
Matched-pair comparison of outcome of patients with clinical stage I
non-small cell lung cancer treated with resection or stereotactic radiosurgery.
Presenting Author: Julia Shelkey, Penn State Hershey Medical
Center, Hershey, PA
Background: Stereotactic body radiotherapy (SBRT) is an alternative to
surgery alone for certain patients with clinical stage I non-small cell lung
cancer (NSCLC), but comparing their effectiveness is difficult because of
differences in patient selection and staging. Methods: Two databases were
combined which contained 132 patients treated by lobectomy (LR) and 48
by sublobar resection (SLR) and 137 patients managed with SBRT after
negative staging between 1999-2009. We compared rates of overall
survival (OS), disease-free survival (DFS), and locoregional control (LRC)
between patients treated with surgery and SBRT to each other and in
relation to possible prognostic factors. We then performed a matched-pair
analysis comparing surgery and SBRT results. Median follow-up for the
entire study population was 25.8 months. Results: On univariate analysis,
OS was significantly correlated with histology, the Charlson Comorbidity
Index, tumor size, aspirin use, and use of SBRT; DFS was correlated only
with histology; and no variable was significantly correlated with LRC.
Multivariate analysis found improved OS in patients with adenocarcinoma
and those undergoing surgical resection. The NSCLC “not otherwise
specified” histology was associated with poorer DFS. Overall survival was
significantly poorer for SBRT patients in the matched-pair analysis than for
patients treated with surgery, but DFS and LRC were not significantly
different between these groups. Conclusions: Our retrospective study has
demonstrated similar LRC and DFS in patients treated with SBRT or
surgery, but worse OS in the former group, when patients were matched for
prognostic factors. Our investigation suggests that randomized trials are
needed to eliminate selection bias in treatment assignment in order to
accurately compare outcomes between these approaches.
7042 General Poster Session (Board #35A), Sat, 1:15 PM-5:15 PM
A phase II study of cisplatin (P), S-1 (S), and concurrent thoracic
radiotherapy (TRT) for locally advanced non-small cell lung cancer (LA-
NSCLC): Okayama Lung Cancer Study Group trial 0501. Presenting
Author: Daizo Kishino, National Hospital Organization Yamaguchi-Ube
Medical Center, Ube-shi, Yamaguchi, Japan
Background: We previously reported an efficacy and safety of fractionated
schedule ofP and docetaxel (D) (days 1, 8, 29, and 36, each) and
concurrent TRT (DP-TRT) for LA-NSCLC (JCO 2010). Although the median
survival time (MST: 26.3 months) was excellent, grade 3 or greater
pneumonitis (10%) and esophagitis (14%) were observed and treatmentrelated
death was 3%.Thus, further improvement in the safety as well as
efficacy is strongly warranted. S, an oral fluoropyrimidine, is a new active
agent possessing a radio-sensitizing effect. Additionally, combining S and
P offered an active and safe regimen for metastatic NSCLC. The objective
of this study was to assess the efficacy and safety of S � P with concurrent
TRT for LA-NSCLC. Methods: Patients with stage IIIA/IIIB, aged �75 years
and PS 0-1, and without any prior chemotherapy were eligible for this
study. Patients were treated with P (40 mg/m² on day 1, 8, 29 and 36) and
S (40 mg/m²/dose b.i.d. on days 1-14 and 29-42) and TRT (60 Gy/30 fr
over 6 weeks starting on day 1). Primary endpoint was response rate (RR),
and required sample size was 48 patients. Results: Between 2006 and
2009, 48 patients were enrolled (37 men; median age, 66 years; PS 0/1,
36/14; IIIA/IIIB, 23/25; sq/non-sq, 22/26). Partial response was observed
in 37 patients (77%; 95% confidence interval: 63-88%). The response
rate was higher in older patients (�65 yrs) than younger (�65 yrs) (89% vs.
64%, p�0.041). At a median follow-up of 40 months, median progressionfree
survival and MST were 9.3 months and 31.3 months, respectively. No
difference in efficacy (response and survivals) was observed stratified by
histology (sq vs. non-sq). Toxicities were generally mild, including G3/4
neutropenia (44%), G3/4 thrombocytopenia (13%), G3 febrile neutropenia
(8%) and G3 pneumonitis (4%). No one developed Gr3/4 esophagitis. No
toxic deaths occurred. Conclusions: This chemoradiotherapy regimen yielded
a favorable overall survival data. Also, it was well-tolerated in patients with
LA-NSCLC as compared with concurrent DP-TRT therapy especially in term
of TRT-related toxicities. A phase III trial of this regimen vs. DP-TRT is now
planned.
461s
7041 General Poster Session (Board #34H), Sat, 1:15 PM-5:15 PM
Amplification of fibroblast growth factor receptor type 1 gene (FGFR1) in
samples from 101 NSCLC patients (pts) with squamous cell carcinoma
(SCC) histology. Presenting Author: Alex Martinez Marti, Medical Oncology
Department, Vall d’Hebron University Hospital, Barcelona, Spain
Background: The FGFR1 gene is located in the chromosomal region 8p12
and encodes a transmembrane receptor tyrosine kinase. Amplification of
FGFR1 has been reported in lung cancer, predominantly in SCC (in up to ~
20%) and has been considered a potential target for treatment with
anti-FGFR1 agents. Different methods and cutoff levels to determine
FGFR1 amplification have been reported but as yet no consensus has been
reached on standard method. The aim of this study is to assess FGFR1
amplification determined by FISH analysis in a set of samples from
101SCC pts and to explore their clinical features. Methods: Tumor samples
from 101SCC pts diagnosed at our institution from August 2007 to August
2011 were screened for FGFR1 amplification by FISH using the ZytoLight
SPEC FGFR1/CEN8 probe. FGFR1 was considered FISH positive with a
ratio � 2.2 and FISH FGFR1 was polysomic with 3 or more signals in
�30% of tumor cells, any other result was considered as negative. For
exploratory analyses FGFR1 amplification was considered positive if a
median of 6 or more gene copies were identified and FISH were polysomic
with more than 2 gene copies but less than 6. Results: Pts characteristics:
median age 76 yrs (range 45-80), 91% male, 33% current smokers, 67%
former smokers, stage: 8% IA/ 15% IB/ 11% IIA/ 11% IIB/ 24% IIIA, 12%
IIIB/ 19% IV. With a median follow up of 48 months, the median overall
survival was 18 months. FISH FGFR1 was positive (ratio � 2.2) in 7 (6.9%)
pts: 6 were male, 4 former smokers. FISH FGFR1 was considered negative
but polysomic (3 or more signals in �30% of tumor cells) in 43/94 (45%)
pts. If we use for FISH positivity a cutoff of 6 or more copies only 3 patients
were considered as positive for FGFR1 amplification (2 were also FISH
positive by ratio�2.2). All those 5 patients considered FISH negative by
gen copy number (but positive by ratio) were polysomic. Conclusions: In our
experience FGFR1 amplification detected by FISH isrelatively uncommon
in SCC, although a relevant proportion of FGFR1 FISH negative tumors had
polysomy. Standarization of methods to determine FGFR1 amplification
and the potential clinical significance of the presence of FGFR1 polysomy
are needed.
7043 General Poster Session (Board #35B), Sat, 1:15 PM-5:15 PM
Predictors for locoregional recurrence for clinical stage III-N2 non-small
cell lung cancer with nodal downstaging after induction chemotherapy and
surgery. Presenting Author: Feiran Lou, Memorial Sloan-Kettering Cancer
Center, New York, NY
Background: Pathologic downstaging following induction chemotherapy in
patients with stage III-N2 NSCLC is a well-known positive prognostic
indicator. However, the predictive factors for locoregional recurrence (LRR)
in these patients are largely unknown. Methods: Between 1998-2008, 153
patients with clinically or pathologically-staged III-N2 NSCLC from two
cancer centers in the United States were treated with induction chemotherapy
and surgery. All patients had pathologic N0-1 disease, and no one
received postoperative radiotherapy. LRR were defined as disease recurrence
at the surgical site, lymph nodes (levels 1-14 including supraclavicular)
or both. Overall survival (OS) was calculated using the Kaplan and
Meier method and comparisons were made using the log-rank test.
Univariate and multivariate Cox proportional hazards model were used to
assess the association of LRR and risk factors. Results: The median follow
up time for survivors was 39.3 months. Baseline pretreatment N2 nodal
involvement was staged by either pathologic confirmation (18.2%) or
PET/CT (81.8%). Overall, the 5 year LRR rate was 30.8% (n�38), with
LRR being the first site of failure in 51% (22 of 43). The 5 year OS for
patients with LRR compared to those without was 21% versus 60.1%,
respectively (p�0.001). Using multivariate analysis, significant predictor
for LRR was pN1 versus pN0 disease at time of surgery (p�0.001, HR
3.43, 95% CI 1.80-6.56) and trended for squamous histology (p�0.072,
HR 1.93, 95% CI 0.94-3.98). The 5-year LRR rate for N1 versus N0
disease was 62% versus 20%, respectively. Neither single versus multistation
N2 disease (p�0.291) nor initial staging by mediastinoscopy versus
PET/CT (p�0.306) were predictors for LRR. We found that N1 status was
also predictive for higher distant recurrence rate (p�0.021, HR 1.91, 95%
CI 1.10-3.30) but only trended for poorer OS (p�0.123, HR 1.48, 95% CI
0.90-2.44). Conclusions: LRR remains high in resected stage III-N2
NSCLC patients after induction chemotherapy and nodal downstaging,
particularly in patients with persistent N1 disease. Postoperative radiotherapy
may be needed for these high-risk patients.
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