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S. Laurie



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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-006 - Outcomes of Elderly Patients with Locally-Advanced Non-Small Cell Lung Cancer (LA-NSCLC) Treated with Radiation +/- Chemotherapy at the Ottawa Hospital Cancer Centre (ID 1331)

      09:30 - 09:30  |  Author(s): S. Laurie

      • Abstract

      Background
      Concurrent chemoradiation (C-CRT) is standard therapy for fit patients with unresectable, LA-NSCLC. We evaluated outcomes of patients treated with curative intent at our centre for quality assurance, and to compare outcomes between elderly (≥75) and younger patients.

      Methods
      Patients with stages IIIA/ IIIB NSCLC from 2002 to 2008 were identified, and those planned for curative-intent radiation (minimum 50Gy) included, irrespective if therapy was actually completed. Charts were reviewed for patient demographics, baseline prognostic factors, treatments planned and administered, hospitalizations and outcomes. Multivariable analyses were performed to determine factors associated with survival.

      Results
      329 patients were included: median age 66 (range 40-89), 60% male, 15% ECOG 2+, 60% IIIB, 35% weight loss >5%. 20% (66/329) were ≥75. C-CRT, sequential CRT and radiation alone were delivered in 85%, 5%, and 10% of cases, respectively; the elderly were less likely to receive C-CRT (61% vs. 91%). Median survival (all patients) was 18.4 months; for < and ≥75 cohorts, MS were 20.8 and 16.4 months (p=0.0533). 3 and 5 year OS (all patients) were 29% and 17%; for the < and ≥75 cohorts values were 31/21% and 19/8%. Elderly patients had lower treatment-related hospitalization (6% vs. 20%) and death (2% vs. 5%). Radiation compliance was equivalent however chemotherapy completion was higher in younger patients (78% vs. 45%). In multivariate analysis, age ≥75 (HR=1.68, 95% CI 1.03-2.75, p=0.038), female gender (HR=0.60, 95% CI 0.41-0.87, p=0.008), and completion of radiation therapy (HR=0.39, 95% CI 0.25-0.62, p<0.0001) were independent predictors of outcome. Figure 1

      Conclusion
      Outcomes of patients with LA-NSCLC offered curative therapy at the Ottawa Hospital Cancer Centre are comparable to those obtained in clinical trials of C-CRT, despite a more unselected population with a higher proportion of poor prognostic features. Those ≥75 were less likely to be offered C-CRT and were less likely to complete planned chemotherapy. However fit patients ≥75 offered radical therapy still have reasonable MS and 3-year OS.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-044 - Clinical impact of EGFR mutation fraction and tumour cellularity in EGFR mutation positive NSCLC (ID 2982)

      09:30 - 09:30  |  Author(s): S. Laurie

      • Abstract

      Background
      We investigated the impact of mutation fraction, tumour sample cellularity, and diagnostic specimen type on EGFR TKI response, time to treatment failure (TTF) and overall survival (OS), as well as patterns of treatment in a population-based cohort of advanced EGFR mutation positive NSCLC patients.

      Methods
      From March 2010 to May 2012, EGFR testing in the province of Ontario (Canada) was conducted at a single centre, using fragment analysis for exon 19 deletion and Sau961 restriction enzyme digest for exon 21 mutations. Patients with EGFR mutation positive samples were identified and tumour sample cellularity, mutation fraction (percent of tumour cells mutated), demographic, treatment and outcome data were collected. Regression analysis was undertaken to assess the association between demographic variables, mutation fraction, tumour sample cellularity and sample type on clinical outcomes.

      Results
      Among 293 patients identified with EGFR mutation positive NSCLC, 253 received EGFR TKIs and are included in this analysis. Most are female (72%), never smokers (59%), have exon 19 deletions (53%; 47% exon21 L858R), and median age 65 years (range 26 to 96). Tumour specimens tested include resection (32%), cytology (30%), and core biopsies (38%). Median EGFR mutation fraction is 30% (range 0.4% to 96%); 24% had a low (≤10%) mutation fraction, and 13% had a mutation fraction ≤5%. Responses (any tumour reduction) were seen in 62%, mixed response or stable disease in 25%, and progression as the best response in 13%. Median TTF from the start of EGFR TKI therapy is 13.2 months (range 0-43.7 months). Median OS from TKI start is 22.3 months (95% CI: 19.5-28.2 months), with 1-, 2- and 3-year survival rates of 72%, 49% and 37%. In multivariable analysis, factors associated with TTF included female sex (HR 0.69, p=0.03) and sample type (resection HR 0.56, cytology HR 0.82, core biopsy as reference, p=0.01). Age at metastatic diagnosis (p=0.01), sample cellularity (p=0.01) and sample type were significantly associated with OS, (resection HR 0.51, cytology HR 0.70, core biopsy as reference, p=0.04). Proportional odds logistic regression identified that mutation frequency and age at metastatic diagnosis were significantly associated with the odds of response, (p=0.047, p=0.04 respectively). Responses were seen even in those with lower EGFR mutation fraction, 48% (24/50) at a mutation frequency of ≤10% and 33% (9/27) at a mutation frequency of ≤5%. The average cellularity in the high (>10%) mutation fraction group was 53% (95%CI 50– 56%), and 36% (95%CI 29 – 43%) in those with a low mutation fraction (p<.0001).

      Conclusion
      Pathologic features may be relevant to clinical outcomes in EGFR mutation positive NSCLC, including mutation fraction, sample cellularity, and specimen tested. The clinical relevance of sample tumour cellularity and sample type tested remains unclear. In particular, initial stage and prognosis may be confounders in the association between resected specimens and favourable outcomes. Given that those with mutation fractions ≤5% may have significant response from EGFR TKI therapy, treatment should not be withheld on the basis of mutation frequency alone.