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Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

ABSTRACT: Local failure rates after radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined.Seventy-nine patients with NSCLC were enrolled on a prospective single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy. Escalation of dose per fraction was performed according to patients' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy. The MTD was defined as the maximum dose with ? 20% risk of severe toxicity.No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual. However, with a longer follow-up period, grade 4 to 5 toxicity occurred in six patients and was correlated with total dose (P = .004). An MTD was identified at 63.25 Gy in 25 fractions. Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree.Although this dose-escalation model limited the rates of clinically significant pneumonitis, dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures. The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocols, especially when using hypofractionation.

SUBMITTER: Cannon DM

PROVIDER: S-EPMC3837093 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

Cannon Donald M DM Mehta Minesh P MP Adkison Jarrod B JB Khuntia Deepak D Traynor Anne M AM Tomé Wolfgang A WA Chappell Richard J RJ Tolakanahalli Ranjini R Mohindra Pranshu P Bentzen Søren M SM Cannon George M GM

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20131021 34

<h4>Purpose</h4>Local failure rates after radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined.<h4>Patients and methods</h4>Seventy-nine patients with NSCLC were enrolled on a prosp ...[more]

PMID: 24145340

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Project description:BackgroundThis study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART).MethodsTwenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test.ResultsPatients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1%, range?-?2.9-44.0%). The V51 of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p?=?0.452). Only 11.1% of patients had above 5% relative decrease in V51 of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase <?5%) was observed in doses of total lung (mean dose, V20 and V30), esophagus (mean dose, maximum dose) and heart (mean dose, V30 and V40) in accumulated plans. Less than 30% of patients had above 5% relative increase of lung or heart doses. Patients with quick tumor regression or baseline obstructive pneumonitis showed more notable increase in doses to normal structures. Patients with baseline obstructive atelectasis showed notable decrease (10.3%) in dose coverage of PTV-GTV.ConclusionsLANSCLC patients treated with HRT had sufficient tumor dose coverage and acceptable normal tissue dose deviation. ART should be applied in patients with quick tumor regression and baseline obstructive pneumonitis/atelectasis to spare more normal structures.

Dataset Information

Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

Publications

Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

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