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William G Richards
OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
OA13.01 - SPECS2 Lung Cancer Consortium Prospective Multicenter Validation of Prognostic Signature for Early Stage Squamous Lung Cancer (Now Available) (ID 2723)
11:30 - 13:00 | Author(s): William G Richards
Squamous Lung Cancer (SC) which constitutes 30% of all non-small cell lung cancers (NSCLC) has few targeted therapy options for advanced disease. Surgery for early SC is the best treatment strategy; however, even patients who undergo surgery for stage IA or IB disease are still at a substantial risk for recurrence and death. Adjuvant therapy is not currently indicated for stage I SC smaller than 4 cm. Prior reports suggest gene expression-based signatures that may predict recurrence in patients with stage I SC, but none has been validated or is in clinical use. The SPECS2 Lung Cancer Consortium was assembled to compare and attempt to validate previously published prognostic signature(s) according to the guidelines proposed by Subramanian and Simon (J Natl Cancer Inst 2010; 7:327).Method
The multi-institutional team assembled 249 frozen SC samples representing six participating institutions (cohort 1). These samples were fully annotated in a redcap database hosted by the independent statistical core. Cohort 2 was assembled utilizing 234 frozen SC samples from a prospective multi-institutional NCTN lung biobanking protocol (NCT00899782). RNA was extracted and profiled with U133A microarrays (Affymetrix) in independent core facilities. The data was transferred directly to the SPECS2 Lung statistical core in collaboration with the Alliance Statistical core and the performance of 6 most promising candidate signatures was evaluated relative to a base model that included only age, gender and AJCC stage (editions 6, 7, 8).Result
Analysis of Cohort 1 demonstrated that only one signature (Raponi et al, Cancer Res 2006; 66:7466) significantly enhanced prognosis relative to the base model, independent of AJCC edition. This was also observed in Cohort 2, where Uno’s C index associated with AJCC 8th edition stage, sex and age (0.561; 0.468-0.654) was significantly (p <0.05) increased when the prognostic signature was added to the model (0.683; 0.611-0.755).Conclusion
The SPECS2 Lung Cancer Consortium was successful in validating a previously published prognostic molecular signature for early stage SC using rigorous experimental design. To our knowledge, this is the first unbiased validation of a lung cancer prognostic signature using multi-institutional prospective specimens. These results support a clinical trial designed to evaluate the potential role of adjuvant therapy in completely resected early stage SC.
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