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Johannes R. Kratz



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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.16-12 - Expanded Data Confirm Molecular Testing Identifies Lung Adenocarcinoma Patients, Including Stage IA, Who Benefit from Adjuvant Chemotherapy (ID 14532)

      16:45 - 18:00  |  Author(s): Johannes R. Kratz

      • Abstract
      • Slides

      Background

      A clinically certified, 14-gene quantitative PCR expression assay has been validated to assess mortality risk in early-stage lung adenocarcinoma. Molecular stratification may identify those stage I-IIA patients who are in most need of potentially life-saving intervention after resection, including stage IA patients for whom chemotherapy is never recommended.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Prospective molecular risk-stratification by the 14-gene assay was performed on 200 consecutive patients with stage I-IIA lung adenocarcinoma after complete surgical resection at a single institution. Adjuvant chemotherapy was recommended for molecular high-risk patients. Kaplan-Meier analysis and log-rank tests were used to evaluate differences in disease free survival.

      4c3880bb027f159e801041b1021e88e8 Result

      Average age of patients was 68 +/- 10 years, 62% were female and mean follow up was 24 months. The recurrence rate among all patients was 9%. However, 87 patients (44%) were found to be molecular high-risk and had a recurrence rate of 17%, whereas the 113 patients (56%) who were molecular low-risk had a recurrence rate of only 3% (p<0.0001). Even among the stage IA patients, 41 (33%) were found to be molecular high-risk. The recurrence rate in molecular low-risk stage IA patients was only 1%, compared to 15% in stage IA patients who were identified as molecular high-risk (log-rank p=0.003). Of the 41 stage IA patients found to be molecular high-risk, 24% agreed to undergo adjuvant chemotherapy; there have been no recurrences among these treated high-risk patients. In contrast, the KM estimate of 5-year disease free survival among stage IA high-risk patients who did not receive adjuvant chemotherapy was 51% (log-rank p=0.005). pervenio stage ia figure.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      This prospective, single-institution study further demonstrates the clinical utility of the 14-gene molecular prognostic assay in the management of early stage lung adenocarcinoma. Adjuvant chemotherapy guided by molecular prognosis in the earliest stages of disease, including stage IA, may prevent a significant number of recurrences and deaths.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-24 - Incorporation of a Molecular Prognostic Classifier Improves Conventional Non-Small Cell Lung Cancer Staging (ID 14531)

      12:00 - 13:30  |  Author(s): Johannes R. Kratz

      • Abstract
      • Slides

      Background
      Despite significant advancements in the understanding of the molecular genetics of tumor biology, the 8th Edition of Non-Small Cell Lung Cancer (NSCLC) staging adopted in 2018 remains dependent upon tumor size, nodal spread, and metastasis. The survival of patients with early stage NSCLC remains poor and further improvement in staging is needed to better inform adjuvant therapy. In this study, we explored the integration of a clinically validated, molecular prognostic classifier into conventional staging.
      a9ded1e5ce5d75814730bb4caaf49419 Method
      A novel staging system, TNMB (“B” indicating Biology), that integrates a 14-gene molecular prognostic classifier with the 8th Edition, was developed using 332 patients with non-squamous NSCLC resected at the University of California, San Francisco (UCSF). TNMB was subsequently validated on a separate multi-institutional international cohort of 1,373 patients. Reclassification metrics were evaluated from adoption of TNMB and the 8th Edition. 4c3880bb027f159e801041b1021e88e8 Result
      Adoption of TNMB improved prognostication of overall survival significantly more than adoption of the 8th Edition. TNMB resulted in Net Reclassification Improvement of 0.33 (95% CI 0.24-0.41), relative Integrated Discrimination Improvement of 22.1% (95% CI 8.8-35.3%), and Reclassification Calibration Statistic from 36 to 18 (P-Value 0.03 to 0.73). In contrast, the 8th Edition resulted in no change in Net Reclassification Improvement 0.03 (95% CI -0.00-0.06) or relative Integrated Discrimination Improvement -2.5% (95% CI -17.6-12.4%) and resulted in Reclassification Calibration Statistic from 134 to 22 (P-Value <0.01 to 0.27). 8eea62084ca7e541d918e823422bd82e Conclusion
      Incorporation of a molecular prognostic classifier offers substantial improvement to conventional staging of NSCLC and may lead to a significant impact on clinical decision-making in early stage disease where identification of high risk patients is needed to guide adjuvant therapy. Our findings may encourage application of molecular prognostic classifiers into the refinement of conventional staging for other solid tumors.

      Overall Survival of Non-Small Cell Lung Cancer Patients Following Surgical Resection by 7th Edition, 8th Edition, and TNMB Staging. TNMB had distinct separation of survival by stage and larger range of survival between early and late stages compared to conventional staging.

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      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.