{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:06:33Z","timestamp":1790035593246,"version":"4.0.1"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"Importance<\/jats:title>Intrathoracic progression remains the predominant pattern of failure in patients treated with concurrent chemoradiation followed by a consolidation immune checkpoint inhibitor for locally advanced, unresectable non\u2013small cell lung cancer (NSCLC).<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the maximum tolerated dose (MTD) and use of hypofractionated concurrent chemoradiation with an adaptive stereotactic ablative radiotherapy (SABR) boost.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This was an early-phase, single-institution, radiation dose-escalation nonrandomized controlled trial with concurrent chemotherapy among patients with clinical stage II (inoperable\/patient refusal of surgery) or III NSCLC (American Joint Committee on Cancer Staging Manual, seventh edition<\/jats:italic>). Patients were enrolled and treated from May 2011 to May 2018, with a median patient follow-up of 18.2 months. Patients advanced to a higher SABR boost dose if dose-limiting toxic effects (any grade 3 or higher pulmonary, gastrointestinal, or cardiac toxic effects, or any nonhematologic grade 4 or higher toxic effects) occurred in fewer than 33% of the boost cohort within 90 days of follow-up. The current analyses were conducted from January to September 2023.<\/jats:p><\/jats:sec>Intervention<\/jats:title>All patients first received 4 Gy\u2009\u00d7\u200910 fractions followed by an adaptive SABR boost to residual metabolically active disease, consisting of an additional 25 Gy (low, 5 Gy\u2009\u00d7\u20095 fractions), 30 Gy (intermediate, 6 Gy\u2009\u00d7\u20095 fractions), or 35 Gy (high, 7 Gy\u2009\u00d7\u20095 fractions) with concurrent weekly carboplatin\/paclitaxel.<\/jats:p><\/jats:sec>Main Outcome and Measure<\/jats:title>The primary outcome was to determine the MTD.<\/jats:p><\/jats:sec>Results<\/jats:title>Data from 28 patients (median [range] age, 70 [51-88] years; 16 [57%] male; 24 [86%] with stage III disease) enrolled across the low- (n\u2009=\u200910), intermediate- (n\u2009=\u20099), and high- (n\u2009=\u20099) dose cohorts were evaluated. The protocol-specified MTD was not exceeded. The incidences of nonhematologic acute and late (&amp;gt;90 days) grade 3 or higher toxic effects were 11% and 7%, respectively. No grade 3 toxic effects were observed in the intermediate-dose boost cohort. Two deaths occurred in the high-dose cohort. Two-year local control was 74.1%, 85.7%, and 100.0% for the low-, intermediate-, and high-dose cohorts, respectively. Two-year overall survival was 30.0%, 76.2%, and 55.6% for the low-, intermediate-, and high-dose cohorts, respectively.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This early-phase, dose-escalation nonrandomized controlled trial showed that concurrent chemoradiation with an adaptive SABR boost to 70 Gy in 15 fractions with concurrent chemotherapy is a safe and effective regimen for patients with locally advanced, unresectable NSCLC.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT01345851<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.6033","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T16:00:57Z","timestamp":1704988857000},"page":"352","source":"Crossref","is-referenced-by-count":21,"title":["Accelerated Hypofractionated Chemoradiation Followed by Stereotactic Ablative Radiotherapy Boost for Locally Advanced, Unresectable Non\u2013Small Cell Lung 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