OA13.01 SPECS2 Lung Cancer Consortium Prospective Multicenter Validation of Prognostic Signature for Early Stage Squamous Lung Cancer

AbstractPurposeLung cancer is the leading cause of cancer deaths worldwide, with substantially better prognosis in early stage as opposed to late stage disease. Identifying genetic factors for lung squamous carcinoma (SqCC) risk will enable their use in risk stratification, and personalized intensive surveillance, early detection, and prevention strategies for high-risk individuals.Study Design and ParticipantsWe analyzed whole-exome sequencing datasets of 318 cases and 814 controls (discovery cohort) and then validated our findings in an independent cohort of 444 patients and 3,479 controls (validation cohort), all of European descent, totaling a combined cohort of 765 cases and 4,344 controls. We focused on rare pathogenic variants found in the ClinVar database and used penalized logistic regression to identify genes in which such variants are enriched in cases. All statistical tests were two-sided.ResultsWe observed an overall enrichment of rare, deleterious germline variants in Fanconi Anemia genes in cases with SqCC (joint analysis OR=3.08, p=1.4e-09, 95% confidence interval [CI]=2.2–4.3). Consistent with previous studies, BRCA2 in particular exhibited an increased overall burden of rare, deleterious variants (joint OR=3.2, p=8.7e-08, 95% CI=2.1–4.7). More importantly, rare deleterious germline variants were enriched in Fanconi Anemia genes even without the BRCA2 rs11571833 variant that is strongly enriched in lung SqCC cases (joint OR=2.76, p=7.0e-04, 95% CI=1.6–4.7).ConclusionsThese findings can be used towards the development of a genetic diagnostic test in the clinic to identify SqCC high-risk individuals, who can benefit from personalized programs, improving prognosis.

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A Robust 8-Gene Prognostic Signature for Early-Stage Non-small Cell Lung Cancer

Frontiers in Oncology ◽

10.3389/fonc.2019.00693 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 9

Author(s):

Ru He ◽

Shuguang Zuo

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Prognostic Signature ◽

Small Cell Lung

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Development and Validation of an Individualized Immune Prognostic Signature in Early-Stage Nonsquamous Non–Small Cell Lung Cancer

JAMA Oncology ◽

10.1001/jamaoncol.2017.1609 ◽

2017 ◽

Vol 3 (11) ◽

pp. 1529 ◽

Cited By ~ 112

Author(s):

Bailiang Li ◽

Yi Cui ◽

Maximilian Diehn ◽

Ruijiang Li

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Prognostic Signature ◽

Small Cell Lung ◽

Development And Validation

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Single agent bevacizumab and bevacizumab in combination with docetaxel and cisplatin as induction therapy for resectable IB-IIIA non-small cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18045 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18045-18045 ◽

Cited By ~ 7

Author(s):

N. A. Rizvi ◽

V. Rusch ◽

B. Zhao ◽

E. Senturk ◽

L. Schwartz ◽

...

Keyword(s):

Lung Cancer ◽

Induction Therapy ◽

Early Stage ◽

Clinical Stage ◽

Single Agent ◽

Induction Treatment ◽

R0 Resection ◽

Stage Ib ◽

Early Stage Nsclc ◽

Squamous Lung Cancer

18045 Background: Bevacizumab (Bev) improves response and survival in patients with advanced non-squamous lung cancer with chemotherapy however there are limited data as single agent therapy and in early stage NSCLC. Methods: Patients with resectable stage IB-IIIA NSCLC were eligible. Patients with adenocarcinoma (Cohort 1) received preoperative Bev and docetaxel and cisplatin (DC). Patients with squamous histology, central location or recent hemoptysis received DC induction therapy without Bev (Cohort 2). Cohort 1 received Bev (15 mg/kg) followed by CT 2 weeks later to assess single agent Bev response. Subsequently D (75 mg/m2) and C (75 mg/m2) were given q 3 weeks; an additional 2 cycles of Bev was administered with C2 and C3 of DC (total of 3 preoperative doses of Bev). Cohort 2 received DC alone followed by resection. Both cohorts received adjuvant Bev x 1 year. Study endpoints included response to single agent Bev, downstaging, safety and survival. Results: 19 patients of planned 70 were enrolled (11 Cohort 1 and 8 Cohort 2). On Cohort 1, there were 2 clinical stage IIB and 9 IIIA patients. After single agent Bev (by bimensional measurement), > 10% reduction in tumor size was observed after 2 weeks in 6/11 patients (- 20%, 15%, 16%, 15%, 13% and 20%). After Bev + DC, there were 6/10 (60%) PRs and DC delivery was 96%. 6/10 patient underwent R0 resection; 1 R2 and 2 were unresectable. 1 patient developed hemoptysis preoperatively and 1 patient developed an upper GI bleed post-operatively. There were otherwise no Bev related operative complications observed. 5/9 patients were downstaged by induction treatment. 3 patients received adjuvant bevacizumab to date (median 5.7 cycles). 8 patients were treated on Cohort 2 (3 with stage IB, 1 with IIB and 4 with IIIA). All 8 patients underwent R0 resection. DC delivery was 94% and there were 6/8 PRs. Downstaging was observed in 5/8 patients and 6/8 are receiving adjuvant Bev (median # cycles to date = 6.7). Conclusions: Bev as a single agent demonstrates regression of tumors after 2 weeks. To date, Bev has been safely administered in the neoadjuvant and adjuvant setting. Preoperative chemotherapy is well tolerated with more than 90% full dose drug delivery. The study is ongoing. Supported by Genentech, Inc. [Table: see text]

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