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Purpose: NCT01725165 was a phase II prospective trial in which patients with non-small cell lung cancer were randomized to local consolidative therapy (LCT) versus maintenance therapy or observation (MT/O)., Methods and Materials: Peripheral blood from patients enrolled on NCT01725165 were labeled as (1) baseline, (2) early follow-up (FU) if obtained in the first or second FU evaluation (6-18 weeks), and (3) late FU if obtained in the third to sixth FU evaluations (22-50 weeks). All patients who underwent LCT and were included in this analysis received radiation. Among 49 randomized patients, 21 patients underwent T cell CDR3 variable region sequencing using immunoSEQ, 31 patients underwent circulating tumor DNA (ctDNA) analysis using next-generation sequencing with a 1021 cancer gene panel, and cytokine concentration was assayed in 19 patients using enzyme-linked immunosorbent assay. All analyses were exploratory and not corrected for multiple testing., Results: No associations were identified between baseline T cell repertoire and ctDNA metrics with patient outcomes. Among baseline cytokines, interleukin 1α was the only cytokine associated with both overall survival (hazard ratio, 0.02; 95% confidence interval, 0.1-0.5; P = .0006) and progression-free survival (hazard ratio, 0.5; 95% confidence interval, 0.2-0.9; P = .03). At early FU, LCT was associated with decreased ctDNA burden, including lower number of detected mutations (median, 2 [interquartile range {IQR}, 1-6] vs 6 [IQR, 4-18]) and decreased average variable allele frequency (VAF; median, 0.006 [IQR, 0.003-0.010] vs 0.011 [IQR, 0.007-0.014]) compared with MT/O. Among 6 patients with serial ctDNA analysis, a rise in ctDNA detected mutation burden preceded clinical progression by 6.7 months. At early FU, LCT was associated with changes in T cell clonality that suggested oligoclonal expansion specifically increased T cell clonality (median, 0.15 [IQR, 0.12-0.24] vs 0.10 [IQR, 0.05-0.13]) and frequency of top 10 clones (median, 0.14 [IQR, 0.06-0.18] vs 0.21[IQR, 0.19-0.28])., Conclusion: LCT was associated with decreased ctDNA burden and oligoclonal expansion at early FU timepoints. Baseline interleukin 1α was associated with improved patient outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer., Methods and Materials: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure., Results: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord)., Conclusions: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation., (Copyright © 2012 Elsevier Inc. All rights reserved.)