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C. Ho
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-011 - Comparison of EGFR and KRAS Mutations in Archival Tissue and Circulating Tumor DNA: The Impact of Tumor Heterogeneity (ID 4504)
14:30 - 14:30 | Author(s): C. Ho
- Abstract
Background:
In non-small cell lung cancer (NSCLC), circulating tumour DNA (ctDNA) has gained acceptance as a potential alternative to tissue biopsies to identify targetable mutations. Individual ctDNA platforms have varying abilities to detect specific mutations. A prospective, multicenter study was conducted to determine concordance, sensitivity, and specificity of ctDNA genotyping, with archival tissue DNA (atDNA) as the reference standard.
Methods:
Patients with incurable advanced NSCLC at the BC Cancer Agency were enrolled over 14 months. Next-Generation Sequencing (NGS) and high-throughput multiplex amplification of a 27-gene panel (Raindance) was used for atDNA analysis. Four mL of plasma was collected in Streck (Cell Free DNA BCT) tubes for ctDNA genotyping using the Boreal Genomic OnTarget. Analysis of concordance, sensitivity, and specificity was conducted with atDNA used as the standard.
Results:
Seventy-six patients were enrolled, median age 66, 33 (44%) male, 69 (91%) metastatic disease, 47 (62%) with primary disease in-situ. Twenty-six EGFR mutations in 22 atDNA samples, and 12 mutations in 11 ctDNA samples were detected, with a concordance of 78%, sensitivity of 39%, and specificity 98%. One EGFR T790M mutation was positive by ctDNA alone. Twenty-one KRAS mutations in 21 atDNA samples were detected. Within this subgroup, 10 ctDNA samples had KRAS mutations with a concordance of 76%, sensitivity of 50%, and specificity of 80%. Fourteen KRAS mutations were detected by ctDNA only. The interval between archival tissue and ctDNA collection, and time between treatment and ctDNA collection, did not significantly impact the rate of concordance (p> 0.05).
Conclusion:
Although the sensitivity is limited, the Boreal Genomic OnTarget ctDNA analysis is specific in identifying clinically relevant EGFR mutations and has acceptable concordance rates between ctDNA and atDNA testing. Targetable EGFR and KRAS mutations were detected in ctDNA but not atDNA, which may reflect site of biopsy, tumor heterogeneity, or technical limitations of assays used. Given the high specificity and non-invasive nature of this test, positive results in EGFR mutations can be used to direct therapeutic decisions, especially accounting for clonal evolution overtime in detection of resistance mutations.
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P1.05 - Poster Session with Presenters Present (ID 457)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Early Stage NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.05-060 - Adherence to Surveillance Guidelines in Resected NSCLC: Physician Compliance and Impact on Outcomes (ID 4624)
14:30 - 14:30 | Author(s): C. Ho
- Abstract
Background:
Guidelines on resected NSCLC have varying recommendations on appropriate post-operative surveillance. There is general consensus that patients require follow up q6m with clinic visits or CT scans for the first 2 y. This study evaluated compliance with surveillance guidelines and the impact on outcomes.
Methods:
The BC Cancer Agency provides comprehensive cancer control for a population of 4.5 million. Inclusion criteria included referred patients from 2005-2010, resected stage Ib/II NSCLC, minimum 2 y f/u at the BCCA, no prior lung cancer diagnosis. Retrospective chart review collected baseline parameters, follow up visits, CT imaging, recurrence and death.
Results:
479 were referred and 263 were eligible. Baseline characteristics median age 68, male 52%, current/former/never smoker 38/52/10%, stage Ib/II 51/49%, squamous/non 30%/70%, wedge/lobectomy/pneumonectomy 8/76/16%, adjuvant chemotherapy 46%. Adherence to 4 interventions in 2 y: clinic visits 62%, CT scans 18%, visit and/or CT 67%. Multivariate analysis (MVA) for predictors of guideline adherence demonstrated only stage was significant. Recurrence rate was 46% at 2 y with patterns of recurrence and treatment in table 1. Surveillance below vs per/above guidelines; PFS 26.6 m vs 22 m (p=0.54), OS 47 m vs 41.8 m (p=0.27).Follow up visits and/or CT scans below guidelines n=87 Follow up visits and/or CT scans per or above guidelines n=176 p value Recurrence within 2 years 32 (37%) 88 (50%) Method of detection 0.41 Surveillance 18 (56%) 41 (47%) Patient 14 (44%) 47 (53%) Distribution of recurrence 0.16 Second primary 1 (3%) 2 (2%) Locoregional recurrence only 10 (31%) 14 (16%) Metastatic 21 (66%) 73 (82%) Curative intent treatment at recurrence 5 (16%) 6 (7%) 0.16 Palliative chemotherapy 7/27 (26%) 32/82 (39%) 0.25
Conclusion:
Compliance with follow up recommendations for resected NSCLC was 67% in our study. Guideline conformity did not increase the rate of curative intent therapy at recurrence due to metastatic presentation nor did it increase the proportion of patients treated with palliative chemotherapy. Better adjuvant treatment and surveillance options need to be developed for resected NSCLC.
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P1.05-069 - Stage II NSCLC Treated with Non-Surgical Approaches: A Multi-Institution Report of Outcomes (ID 4552)
14:30 - 14:30 | Author(s): C. Ho
- Abstract
Background:
Standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. The optimal non-surgical management of stage II NSCLC is undefined, with a paucity of data to guide decision making in this setting. We examined outcomes of stage II NSCLC patients who were treated with curative, non-surgical approaches.
Methods:
We performed a multi-institution review of stage II NSCLC patients treated non-surgically with curative intent between January 2002 and December 2012, across three major Canadian academic cancer centres. Data on demographics, comorbidities, staging, treatment, and outcome were collected. The primary endpoint was overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for factors associated with choice of therapy and OS.
Results:
158 patients were included for analysis. Median age 74 years (range 50-91); 44% female; 94% current/former smokers; 67% performance status (PS) 0-1. Stage II groupings: T2b-T3 N0 in 55%; N1 in 45%. The commonest reasons for no surgery were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median 60 Gy [range 48-75]). 73% received RT alone; 24% and 3% of patients received concurrent and sequential chemoradiotherapy (CRT), respectively. Of those who received RT only, 39% received conventional (1.8-2 Gy/day), 51% received hypofractionated (2.5-4 Gy/day) and 10% received stereotactic body RT (≥7.5 Gy/day). In multivariate analyses, CRT was less likely in patients ≥70 years old (OR 0.28, 95% CI 0.11-0.70, p=0.006), as well as in those with higher (>5) Charlson comorbidity scores (OR 0.34, 95% CI 0.13-0.90, p=0.03) or low (<10x10[9]/L) white blood cell (WBC) counts (OR 0.26, 95% CI 0.09-0.73, p=0.01). At time of analysis, 74% have died. Median OS was 22.9 months (95% CI 17.1-26.6 months). Patients receiving CRT had significantly longer median OS than those receiving RT alone (39.1 vs 20.5 months, p=0.0019). RT fractionation schedule (p=0.16) and nodal status (p=0.14) did not influence survival. After adjusting for possible confounders, treatment with CRT was associated with improved survival (HR 0.38, 95% CI 0.21-0.69, p=0.001), while elevated WBC (HR 2.45, 95% CI 1.48-4.04, p=0.0005) and poor PS (ECOG 2-3) (HR 1.87, 95% CI 1.16-3.01, p=0.01) were poor prognostic factors.
Conclusion:
Non-surgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared to RT alone, and a randomized trial may be warranted in this population.
