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I.I. Wistuba



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    O02 - NSCLC - Combined Modality Therapy I (ID 111)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Combined Modality
    • Presentations: 1
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      O02.03 - Value of Adding Erlotinib to Thoracic Radiation Therapy with Chemotherapy for Stage III Non-Small Cell Lung Cancer: A Prospective Phase II Study (ID 2436)

      10:30 - 12:00  |  Author(s): I.I. Wistuba

      • Abstract
      • Presentation
      • Slides

      Background
      The molecular basis for radiation resistance seems to involve an enhanced survival response with increased capacity for DNA repair and suppressed apoptosis. Both properties are controlled in part by upstream signal transduction pathways triggered by activation of the epidermal growth factor receptor (EGFR). Hypothesizing that the response of non-small cell lung cancer (NSCLC) to current standard chemoradiotherapy can be improved through the addition of therapy targeted to the epidermal growth factor receptor (EGFR), we undertook a single-institution phase II trial to test whether adding the EGFR tyrosine kinase inhibitor (TKI) erlotinib to concurrent chemoradiation therapy for previously untreated, locally advanced, inoperable NSCLC would improve survival and response rates without increasing toxicity.

      Methods
      Forty-eight patients with previously untreated NSCLC received radiation (63 Gy/35 fractions) on Monday‒Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin AUC=2) given every Monday and erlotinib (150 mg orally 1/d) Tuesday–Sunday for 7 weeks, followed by two cycles of consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were toxicity; response, overall survival (OS), and disease control rates; and whether any endpoint differed by EGFR mutation status.

      Results
      Of 46 patients (96%) evaluable for response, 40 were former or never smokers; 23 had adenocarcinoma; and 41 were evaluable for EGFR mutations (37 wild-type [wt] and 4 mutations [all adenocarcinomas]). Median time to progression was 14.5 months and did not differ according to EGFR status. Toxicity was acceptable (no grade 5, one grade 4, and eleven grade 3). Fourteen patients (31%) had complete responses (3 mutations and 11 wt), 24 (52%) partial (20 wt and 4 unknown EGFR mutation status), and 8 (18%) had stable or progressive disease (6 wt, 1 mutation and 1 unknown EGFR mutation status); 3 patients with mutations (75%) had complete response vs. 11 wt (30%) (p=0.07 for EGFR mutation vs wt groups). For alive patients, the median follow-up was 44.7 months’ follow-up (range, 29.3–54.6 months). OS rates were 82.6% at 1 year, 67.4% at 2 years, 48.5% at 3 years, and 32.2% at 4 years and did not differ by mutation status (wt vs mutation, p=0.17). For all patients the median follow-up was 30.6 months’ follow-up (range, 3.4–54.6 months). 14 patients were free from progression and 32 had local failure, distant failure, or both. Eleven of the 27 distant failures were in the brain (7 wt, 3 mutation, 1 unknown; P=0.04); the local control rate was 75% among the 4 patients with EGFR mutations. Median time to progression was 13.6 months (95% confidence interval 10.2-20) and did not differ by EGFR status (wt vs mutation p=0.39).

      Conclusion
      Overall survival was promising, but time to progression was disappointing. Toxicity was acceptable. The prevalence of distant failures underscores the need for more effective systemic therapy, perhaps including maintenance EGFR-TKI for patients with mutated EGFR.

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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-017 - The prevalence of micrometastasis (MM) in discarded intrapulmonary lymph nodes (LN) in resected non-small cell lung cancer (NSCLC). (ID 3000)

      09:30 - 16:30  |  Author(s): I.I. Wistuba

      • Abstract

      Background
      44% of pN0 NSCLC resection patients die within 5 years. We recently showed 12% of pN0 NSCLC resection specimens have discarded LN with metastasis on H&E microscopy. ACOSOG Z0040 demonstrated the prognostic impact of immunohistochemistry positive (IHC+) LN MM. In this report, we investigated the prevalence of IHC+ LN MM in patients with and without H&E + LN metastasis in discarded lung resection specimens.

      Methods
      Using a fastidious redissection special pathology examination (SPE) protocol, we retrieved LN from discarded NSCLC resection specimens after the routine pathology examination (RPE). All retrieved LN were examined for metastasis by H&E light microscopy. We matched 26 patients with 1 or more H&E+ LN (irrespective of whether detected on RPE or SPE) with 28 patients without detectable nodal metastasis. Fresh sections were cut from all retrieved LN tissue blocks of these 54 patients and stained with AE1/AE3 immunostain (Dako) at an independent institution. All slides were examined independently by pathologists at two different institutions, and discordant reports resolved at a consensus review session. The prevalence of IHC positivity was determined from the final consensus of pathologists.

      Results
      Figure 1

      Conclusion
      Micrometastatic disease is evident in a significant proportion of the LN retrieved from discarded NSCLC resection specimens, further extending the potential clinical implications of incomplete LN examination. IHC+ nodes were not found in LN from patients with H&E negative disease after fastidious examination by SPE. The survival implications of these findings will be investigated in future clinical trials.