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J. Isbell
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.14 - Surgical Outcomes and Survival Analysis Following Second Pulmonary Resection for Non-Small Cell Lung Cancer (ID 9374)
15:45 - 17:30 | Author(s): J. Isbell
- Abstract
- Presentation
Background:
The early detection and improved survival of resected non-small cell lung cancer (NSCLC) may increase the number of patients who eventually undergo subsequent pulmonary resection. We investigated the surgical outcomes and survival of patients following second and third pulmonary resections for NSCLC.
Method:
Patients who underwent second or third pulmonary resections without induction therapy for synchronous or metachronous NSCLC (511 patients, 535 procedures, 2000-2014) were included in the analysis.
Result:
Among 535 operations, 361 (67%) were sublobar resection and 103 (19%) were performed by minimally invasive approach, with the proportion of minimally-invasive procedures increasing in recent years (Fig. 1). The majority of re-resections were performed within 4 years of the previous resection (Fig. 2). Risk regression analysis demonstrated that predicted postoperative (ppo) FEV1 (p<0.001) and same side operation (p=0.002) were independent risk factors for severe complications (CTCAE grade ≧ 3; N=45). Multivariable Cox regression analysis revealed that age at subsequent surgery, male sex, ppoDLCO, interval from prior surgery, and tumor stage were independently associated with overall survival.
Conclusion:
In this large cohort of pulmonary re-resections for NSCLC, predicted postoperative pulmonary function tests were indictive of major complications and overall survival. Figure 1 Figure 2
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OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Adrian G. Sacher, Pasi A Jänne
- Coordinates: 10/18/2017, 11:00 - 12:30, F201 + F202 (Annex Hall)
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OA 10.03 - Liquid Biopsy in the Lung Cancer Clinic: A Prospective Study of Plasma DNA next Generation Sequencing to Guide Matched Therapy (ID 8218)
11:00 - 12:30 | Author(s): J. Isbell
- Abstract
- Presentation
Background:
Liquid biopsy for plasma circulating tumor DNA (ctDNA) next generation sequencing (NGS) is now commercially available and increasingly adopted in clinical practice with a paucity of evidence based guidance. We set out to prospectively determine the utility of plasma ctDNA NGS in the lung cancer clinic.
Method:
Patients (pts) with advanced NSCLC who were driver unknown or resistance mechanism unknown were eligible. Pts were enrolled prospectively at Memorial Sloan Kettering (NY, USA) and Northern Cancer Institute (Sydney, Australia). Peripheral blood was collected in Streck tubes (10-20mL) and sent to Resolution Bioscience (Bellevue, WA) for targeted NGS of extracted DNA using a bias corrected hybrid capture 21 gene assay in a CLIA laboratory with unique reads at 3000x and sensitive detection at variant allele frequency above 0.1%. Clinical endpoints included detection of oncogenic drivers, turnaround time, comparison to tissue NGS when available, and ability to match pts to targeted therapy along with their treatment outcomes.
Result:
Seventy-six pts were prospectively accrued. Plasma NGS detected an oncogenic driver in 36% (27/76) of pts, of whom 14% (11/76) were matched to targeted therapy; including pts matched to clinical trials for HER2 exon 20 insYVMA, BRAF L597Q and MET exon14. Of the 10 evaluable pts, 10 partial responses were observed. Mean turnaround time for plasma was 6 days (3-12) vs 21 days (16-30) for tissue (P <0.0001). Plasma ctDNA was detected in 60% (46/76) of pts; detection rate was 46% (16/35) if blood was drawn on active therapy and 73% (30/41) if drawn off therapy, either at diagnosis or progression (Odds ratio 0.31, 95% CI 0.12 – 0.81; P=0.02). Of the 25 concurrent tissue NGS performed to date, there was a 96% plasma concordance with tissue and a 60% tissue concordance with plasma for driver mutations.
Conclusion:
In pts who were driver or resistance mechanism unknown, plasma NGS identified a variety of oncogenic drivers with significantly shorter turnaround time compared to tissue NGS, and matched patients onto targeted therapy with clinical benefit. Plasma ctDNA is best detected at diagnosis of metastatic disease or at progression. A positive finding of an oncogenic driver in plasma is highly specific and can immediately guide treatment, but a negative finding may still require tissue biopsy. Our findings provide evidence to support the incorporation of plasma NGS into practice guidelines.
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P3.15 - SCLC/Neuroendocrine Tumors (ID 731)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.15-011 - Contemporary Treatment and Prognosis of Non-Metastatic Atypical Bronchopulmonary Carcinoid Tumors (ID 10424)
09:30 - 16:00 | Author(s): J. Isbell
- Abstract
Background:
Despite rising incidence, there remains limited data guiding the prognostication and treatment of patients with bronchopulmonary carcinoid tumors, particularly atypical carcinoids. We report outcomes of a large, modern, single-institutional series of patients treated for localized or locally advanced atypical carcinoid of the lung.
Method:
We retrospectively analyzed the demographic, histologic and treatment histories of 69 patients (74% female) with median age of 65 at diagnosis (range 31-83) who were treated between 2004-2016. The Kaplan-Meier method was used for overall survival (OS) estimates and compared by log-rank. Cox proportional hazards models were used for univariate (UVA) and multivariate analyses (MVA).
Result:
Median follow-up time was 33.6 months. The majority (96%) of patients underwent surgical resection (86% R0, 9% R1, 3% R2) with common approaches being lobectomy (59%), wedge resection (13%) and pneumonectomy (9%). Three patients (4%) received definitive radiotherapy as their local treatment. Nearly half (49%) of patients had nodal involvement with a stage distribution of 39% stage I, 25% stage II and 36% stage III. Twenty-one patients received chemotherapy as part of their initial treatment, 81% of whom had stage III disease. Sixteen patients received radiotherapy (median 50.4 Gy, range 18-66 Gy) as part of their initial treatment, most of whom received postoperative radiation for N2 disease (63%). Five patients (31%) received postoperative radiotherapy due to concern of incompletely resected disease. Higher stage was significantly associated with poorer OS (p=0.04). 3-year OS for Stage I, II and III disease was 96%, 88% and 72%, respectively. Stage I disease also had a significantly lower risk of distant metastasis compared to Stage II/III disease (17% vs. 31% at 3 years p=0.04). On UVA, Stage III disease was significantly associated with poorer OS (HR 4.7, p=0.021) and risk of distant failure (HR 2.8, p=0.039). Multivariate modeling showed that older age (HR 1.05, p=0.03) and stage III status (HR 6.6, p=0.009) were predictive of poorer OS. For stage III patients treated surgically, receipt of adjuvant therapy (chemotherapy and/or radiotherapy) was not significantly associated with OS (p=0.36) or distant failure (p=0.69).
Conclusion:
This is one of the largest reported series of atypical pulmonary carcinoid patients treated with curative intent. We observed generally favorable prognosis in this cohort that was primarily treated with surgery. We did not observe a significant impact of adjuvant therapy on outcomes, but small patient numbers limit our ability to quantify their potential effect.
