P value of <0.05 (Wilcoxon paired test) was considered statistically significant. Result: The median time between primary LC diagnosis and BM occurrence was 13 months range, 0 to 91 months), and synchronous BM were diagnosed in 12% of patients. Overall survival in the entire group was 22.5 months. The number of CNA was significantly higher in BM than in primary tumor, regardless of clinical/demographic data or type of aneuploidy (gains/losses). Primary tumors harbored significantly more gains and almost no losses. In both tumor sites, the most frequent gains affected 1q, 5p, 7p, 8q and 20q, whereas gains of 17q and 19q, and losses of 4p, 4q, 5q, 8p, 9p, 16q, 17p, 18q, 22q were identified only in BM. The fraction of the genome affected by mutational events in BM correlated positively with time to BM development. Three the top altered genes (IL7R, MLT11, SETDB1) were identical in both primary lesions and BM. Conclusion: Our results indicate that while primary LC lesions harbor frequent amplifications, the CNA landscape of BM is dominated by deletion events. Higher number of CNA harbored by late compared to synchronous BM suggests high levels of genomic instability.
expected total cumulative dose received. Objective response rate (CR+PR) in the entire cohort was 66%. Median progression-free survival (PFS) from start of alternate schedule is 17.1 months (95% CI 5.2not reached). 6-month PFS is 65% (95% CI 46%-79%) starting from when alternate schedule of Nivo was begun. We will present updated toxicity and treatment outcomes in the meeting. Conclusion: Nivolumab 240mg administered at q 4 weeks or longer is feasible. Further investigation is needed to optimize patient selection for alternate dosing schedule.
Background: SBRT is an effective treatment for ES-NSCLC. Five fraction approaches have been advocated to limit treatment induced toxicity. In this report, we evaluate 3-year patterns of failure for an institutional 5 fraction protocol. Method: Medically inoperable patients were treated with frameless robotic SBRT. PET/CT was completed for staging and at 6 month follow up intervals. A tumor was considered central if it was located within 2 cm of the proximal bronchial tree (PBT). Result: From December 2010 to December 2015, 50 patients with biopsy proven ES-NSCLC (stage I-31; stage II e 19) with median age of 75 were treated to 50 Gy in 5 fractions. Thirty-nine tumors were peripheral and 11 were centrally located. The majority of peripheral tumors were adenocarcinoma (73%) and the majority of central tumors were squamous cell carcinoma (73%). At median follow up of 36 months, local control, regional control, distant metastasis free survival (DMFS) and overall survival (OS) were 88%, 92%, 83% and 52% for all patients. Local control for peripheral tumors was significantly better than central tumors (94% vs. 60% p-value¼0.018). Squamous tumors constituted 60% of local failures despite making up 40% of the entire cohort. Conversely, 12% of peripheral adenocarcinoma failed regionally comprising the only regional failures in this series. DMFS (88% vs. 81% p-value¼0.445) and OS (46% vs. 54% P¼0.421) were not different for central and peripheral tumors. Conclusion: Acceptable outcomes are achievable for central and peripheral inoperable ES-NSCLC patients treated with 5-fraction SBRT alone. However, future trials should consider the addition of systemic therapy to reduce the risk of locoregional and distant failures.
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