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

454s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7008 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Accuracy of FDG-PET to diagnose lung cancer in the ACOSOG Z4031 trial.
Presenting Author: Eric L Grogan, Vanderbilt University Medical Center,
Nashville, TN
Background: Fluoro-deoxyglucose positron emission tomography (FDG-PET)
is recommended for diagnosis and staging of known or suspected NSCLC.
Meta-analyses examining the accuracy of FDG-PET to diagnose lung cancer
demonstrated high sensitivity 94% and specificity 83% but were performed
in select centers. The purpose of this study is to evaluate the
accuracy of FDG-PET to diagnose NSCLC and examine enrolling site
differences in the national prospective ACOSOG Z4031 trial. Methods:
1,074 patients with clinical stage I (cT1-2N0M0) known or suspected
NSCLC were enrolled between 2004 and 2006 in the Z4031 study and
underwent surgical resection. The final diagnosis was determined by
pathological examination. FDG-PET results were abstracted from radiology
interpretations included in the case report forms. FDG-PET avidity was
categorized based on either radiologist description or reported maximum
standard uptake value (SUV). The four categories were: not avid and not
cancerous (SUV�0), low avidity and likely not cancerous (SUV�0 and
�2.5), avid and probably cancerous (SUV�2.5 and �5) and highly avid
and likely cancerous (SUV�5). Sensitivity analysis of FDG-PET diagnostic
accuracy was performed for varying levels of avidity and by preoperative
lesion size. Differences in accuracy by enrolling site were examined.
Results: There were 51 enrolling sites in 39 cities with 969 eligible
participants. Preoperative FDG-PET results were available for 682 participants.
Lung cancer prevalence was 83%. FDG-PET sensitivity was 82%
(95% CI: 79-85), and specificity was 31% (95% CI: 23-40). Positive and
negative predictive values were 85% and 26%, respectively and accuracy
improved with lesion size. There were 80 false positive scans and 69% were
granulomas. False negative scans occurred in 101 patients (11were
�10mm) with adenocarcinoma, squamous, bronchoalveolar cell and neuroendocrine
tumors responsible for 64%, 12%, 10% and 8% of false
negative results, respectively. Specificity did not differ between the 8 sites
with �25 patients (p�0.74). Conclusions: In a national surgical population
with clinical stage I NSCLC, FDG-PET to diagnose lung cancer performed
poorly compared to published studies. Reasons for poor test performance
should be explored.
7010 Poster Discussion Session (Board #2), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
The SELECT study: A multicenter phase II trial of adjuvant erlotinib in
resected epidermal growth factor receptor (EGFR) mutation-positive nonsmall
cell lung cancer (NSCLC). Presenting Author: Joel W. Neal, Stanford
University, Palo Alto, CA
Background: Cancers with activating EGFR mutations are exquisitely
sensitive to EGFR tyrosine kinase inhibitors (TKIs) and retrospective data
suggests adjuvant TKIs may improve outcomes in EGFR mutants. This
prospective trial investigates the safety and efficacy of adjuvant erlotinib in
EGFR mutation-positive NSCLC. Methods: Patients (pts) with surgically
resected stage IA-IIIA NSCLC harboring activating EGFR mutations were
treated with 150 mg/day of erlotinib for 2 years (y) after completion of any
standard adjuvant chemotherapy and/or radiotherapy. The trial was designed
to enroll 36 patients, and powered to demonstrate a primary
endpoint of 2 y disease free survival (DFS) exceeding 85%, which would
suggest improvement over the historically expected 70% 2 y DFS in early
stage EGFR-mutant NSCLC (J Thorac Oncol 6:569). Results: Thirty-six pts
were enrolled at five sites between 1/08 and 11/09; 53% stage I; 19%
stage II; 28% stage IIIA. Toxicities were typical of erlotinib; no grade 4 or 5
events or pneumonitis occurred. 8 pts (22%) required one dose reduction
to 100 mg/day and 5 (14%) two reductions to 50 mg/day for grade 3 or
persistent grade 2 toxicities. 11 pts discontinued before 2 full years (�1
month (mo) [4], 1-12 mo [2] and 12-23 mo [5]) for toxicities [6], patient
preference [3], prostate cancer [1] and recurrence [1]. After a median
follow-up of 2.5 y, the 2 y DFS from enrollment is 94% (95% CI 80%,
99%). 10 patients have recurred, 1 during erlotinib treatment and the
others after stopping erlotinib (interval before recurrence 2 mo [1], 6-12
mo [4], �12 mo [4]). Genotyping on repeat biopsies from seven of the
recurrent cases is underway, as is assessment of response to subsequent
erlotinib therapy. Two pts have died of recurrence: one at 1.5 y who stopped
erlotinib after 1 mo for toxicity, and one at 2 y who progressed while on
erlotinib. Conclusions: This is the first prospective study to report the
efficacy of adjuvant erlotinib in NSCLC pts with EGFR mutations. This
approach is feasible and yields excellent 2y DFS compared to historical
genotype-matched controls. This trial was subsequently expanded to 100
pts to permit subgroup analysis by stage.
7009 Poster Discussion Session (Board #1), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Stages I-II non-small cell lung cancer treated using either lobectomy by
video-assisted thoracoscopic surgery (VATS) or stereotactic ablative radiotherapy
(SABR): Outcomes of a propensity score-matched analysis. Presenting
Author: Suresh Senan, Department of Radiation Oncology, VU University
Medical Center, Amsterdam, Netherlands
Background: VATS procedures are increasingly used in early-stage NSCLC.
As high local control rates are also seen with stereotactic ablative
radiotherapy (SABR), we performed a propensity score-matched analysistocompare
loco-regional control (LRC) after both treatments. Methods:
Patients with stage I-II NSCLC treated at 6 hospitals (1 university and 5
regional hospitals) with VATS lobectomy were eligible. Details of SABR
patients were obtained from a single-institutional database. All VATSlobectomies
were performed in accordance with ESTS guidelines. Patients
were matched using propensity scores based on cTNM, age, gender,
Charlson comorbidity score, lung function and performance score. Matching
was performed blinded to all outcomes. Excluded were: synchronous
lung tumors, COPD GOLD class 4 or history of prior lung cancer. A total of
86 VATS- and 527 SABR patients were eligible for matching (1:1 ratio,
caliper distance of 0.025 without replacement). Loco-regional failure was
defined as recurrence in/adjacent to the radiation planning target volume or
surgical margins, the ipsilateral hilum or mediastinum. Recurrences were
either biopsy-confirmed or PET-positive and reviewed by a tumor board.
Patients upstaged during VATS and those developing recurrence were
treated in accordance with national guidelines. Results: The matched
cohort consisted of 128 patients with cT1-3N0 NSCLC following SABR
(n�64) or VATS-lobectomy (n�64). Median follow-up was 30 and 16
months, respectively. The groups were well matched on baseline variables.
SABR patients had better LRC rates at 1- and 3-years (96.8% and 93.3%
vs. 86.9% and 82.6%, respectively, p� .03). Three-year progression-free
survival (PFS) did not significantly differ after SABR (79.3% versus
63.2%, p � .09). Distant recurrence rates and overall survival (OS) did not
significantly differ. Conclusions: Although loco-regional control was superior
after SABR compared to VATS-lobectomy, PFS and OS did not differ at
this time-point. Our findings support the current randomized controlled
trial evaluating both treatments (ACOSOG Z4099).
7011 Poster Discussion Session (Board #3), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Pilot SCAT trial: Spanish customized adjuvant chemotherapy (CT) based on
BRCA1 mRNA expression levels (l) in resected stage II-IIIA non-small cell
lung cancer (NSCLC) patients (p). Presenting Author: Jose Miguel Sanchez,
Hospital M. D. Anderson Internacional, Madrid, Spain
Background: Surgical resection is the standard treatment in early stages of
NSCLC. Nonetheless, long-term survival rate even after surgical resection
is disappointing. Several randomized trials and meta-analyses confirmed
the survival benefit of adjuvant cisplatin-based CT for stage II and IIIA.
BRCA1 is a component of multiple DNA repair pathways, functions as a
molecular determinant of response to cytotoxic chemotherapeutics agents,
and is an independent prognostic variable in resected p. Since BRCA1
mRNA expression has been linked to differential sensitivity to cisplatin and
antimicrotubule drugs, BRCA1 expression may provide additional information
for customizing adjuvant CT. Methods: Completely resected p with
pathological lymph node involvement (N1, N2) received 4 cycles of
customized adjuvant CT according BRCA1 l. Low l: gemcitabine-cisplatin,
intermediate l: docetaxel-cisplatin, high l: docetaxel. Overall survival (OS)
was the primary endpoint. Multivariate analysis for time to relapse (TTR)
and survival was performed. Results: Eighty-three p were elegible. Most of
the patients were male (83%). Type of surgery: 23% pneumonectomy, and
77% lobectomy or bilobectomy. Fifty-three per cent had low BRCA1 l,
33,7% intermediate l, and 13,3% expressed high l. Most of the tumors
with adenocarcinoma histology had low l (71%). With a median follow-up of
41.6 months (m), median TTP for the whole group was 22.9 m (13.4-
32.5): 20.3 m for low l, 56.5 m for intermediate l, and 51.9 m for high l
(P�0.31). Median OS for the whole group was 63.6 m (33.3-93.9): 55 m
for low l, and not reached for intermediate and high l (P�0.58). Forty-three
p (51.8%) are still alive. Conclusions: Selection of customized CT based on
BRCA1 expression l is feasible and could increase time to relapse and
survival in resected N1-N2 p. No statistical differences for survival: 55
months for gemcitabine-cisplatin, and not reached for docetaxel-cisplatin
and for docetaxel as single agent. Randomized phase III SCAT trial with the
addition of a non-pharmacogenomic control arm is ongoing (372 patients
included).
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