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M.J. Mann



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    OA19 - Translational Research in Early Stage NSCLC (ID 402)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Early Stage NSCLC
    • Presentations: 1
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      OA19.06 - Adjuvant Chemotherapy Decisions Based on Molecular Risk Status Improves Outcomes in Early Stage, Non-Small Cell Lung Cancer (ID 5321)

      11:55 - 12:05  |  Author(s): M.J. Mann

      • Abstract
      • Presentation
      • Slides

      Background:
      A clinically certified, 14-gene quantitative PCR expression assay has been found to assess mortality risk more accurately than clinicopathologic criteria in early-stage, non-squamous, non-small cell lung cancer (NSCLC). Clinically validated molecular stratification may provide a more informative approach to identify early stage NSCLC patients who are most likely to benefit from chemotherapy than current National Comprehensive Cancer Network (NCCN) high-risk clinicopathologic features.

      Methods:
      Prospective molecular risk-stratification by the 14-gene quantitative PCR expression assay was performed on 91 consecutive patients with stage I-IIA non-squamous NSCLC after complete surgical resection at a single institution. Information from molecular risk profiling was used in conjunction with pathologic stage and NCCN criteria to make adjuvant chemotherapy recommendations. Fisher’s exact test was used to compare recurrence rates, and Kaplan-Meier analysis and log-rank tests were used to evaluate differences in disease free survival.

      Results:
      Median age was 69 years, 57% were female and median follow up was 23±2 months. Among all patients, 33 (36%) met NCCN high-risk criteria for adjuvant chemotherapy and 27 (30%) were molecular high risk. Recommendations for adjuvant chemotherapy were discordant in 18 (55%) of NCCN high-risk patients and in 12 (44%) who were molecular high-risk. Twelve (44%) of molecular high-risk patients agreed to receive adjuvant chemotherapy. Whereas recurrence was observed in 33% of molecular high-risk patients who did not receive adjuvant chemotherapy, none of the molecular high-risk patients who underwent chemotherapy recurred (log-rank p=0.001).

      Conclusion:
      This prospective single-institution study demonstrates the clinical utility of molecular testing of early-stage NSCLC to supplement pathologic stage and NCCN guidelines in making adjuvant chemotherapy recommendations. Molecular risk scores better differentiated prospective recurrence rates than did NCCN risk criteria. This study provides preliminary evidence that molecular testing followed by adjuvant chemotherapy in molecularly high-risk patients may prevent a significant number of recurrences and improve outcomes.

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    P1.03 - Poster Session with Presenters Present (ID 455)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.03-066 - Incorporation of a Molecular Prognostic Classifier Improves Conventional Non-Small Cell Lung Cancer TNM Staging (ID 5831)

      14:30 - 14:30  |  Author(s): M.J. Mann

      • Abstract

      Background:
      Tumor size, nodal spread, and distant metastases form the basis of current non-small cell lung cancer staging. Despite undergoing a major revision in 2009, the poor outcomes of early-stage lung cancer patients relative to other solid tumors such as breast and colorectal cancer suggests that further improvement to our ability to stage non-small cell lung cancers is needed. In this study, we demonstrate the benefit of integrating a clinically validated molecular prognostic signature into conventional TNM staging.

      Methods:
      A new staging system integrating a 14-gene molecular prognostic classifier with TNM descriptors was developed using 332 patients with stage I-IIIB non-squamous, non-small cell lung cancer resected at the University of California, San Francisco. This staging system was subsequently validated on a separate multi-institutional international cohort of 1379 patients with stage I-IIIB disease. Reclassification measures were used to assess for improvements in calibration and discrimination beyond conventional TNM staging.

      Results:
      In the validation cohort, 78.2% of patients were reclassified using the new staging system. 73% of these patients were reclassified more accurately. The new staging system demonstrated improved measures of model fit including the modified Nagelkerke’s R[2] statistic as well as the c-index. In addition, incorporation of the molecular classifier resulted in a Net Reclassification Improvement of 16.6% (95%CI 7.9-25.2%) and a relative Integrated Discrimination Improvement of 27.9% (95%CI 6.4-49.4%). Kaplan-Meier analysis of overall survival after surgical resection demonstrated superior survival curve separation with the addition of the molecular classifier. Figure 1. Kaplan-Meier analysis of overall survival from time of surgical resection (A: TNM staging, B: TNMB staging). Figure 1



      Conclusion:
      Incorporation of a molecular classifier of tumor biology offers substantial improvements to conventional TNM staging and encourages application of molecular prognostic classifiers into the refinement of TNM staging systems for other solid tumors.