Accelerated hypofractionated radiotherapy with concurrent chemotherapy for NSCLC: a phase I/II study
PH-0279
Abstract
Accelerated hypofractionated radiotherapy with concurrent chemotherapy for NSCLC: a phase I/II study
Authors: Glinski|, Krzysztof(1);Socha|, Joanna(2);Wasilewska-Tesluk|, Ewa(1,3);Komosinska|, Katarzyna(2);Kepka|, Lucyna(2)*[lucynak@coi.waw.pl];
(1)Independent Public Health Care Facility of the Ministry of the Interior and Warmian& Mazurian Oncology Centre, Radiotherapy, Olsztyn, Poland;(2)Military Institute of Medicine, Radiotherapy, Warsaw, Poland;(3)Warmian and Mazurian Medical University, Radiotherapy, Olsztyn, Poland;
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Purpose or Objective
Prolongation of the overall radiation treatment time is deleterious for patients with locally advanced NSCLC and also contributes to the lack of benefit with dose escalation when conventionally fractionated radiotherapy (RT) is used concurrently with chemotherapy (CHT). Dose intensification via hypofractionation in concurrent approach deserves an investigation. We report the results of toxicity and survival in stage III NSCLC patients treated with accelerated hypofractionated concurrent RT–CHT within a prospective study.
Material and Methods
Stage III (PET-CT staged) NSCLC patients received 58.8 Gy /21 fractions (2.8 Gy/fraction, 5x/week, 6x in the third week) with 2 cycles of CHT (Cisplatin 80mg/m2 D1 and D22; and Vinorelbin 25mg/m2, D1, D8, D22 and D29) started with D1 of RT. RT was planned with 3D-CRT or IMRT technique. Elective nodal irradiation was not employed. The patients were evaluated for toxicity every week during treatment, then one month after treatment completion, and every three months thereafter. A follow-up chest CT was done at each visit. Non-hematological toxicity to esophagus, lung, skin and heart was evaluated using RTOG-EORTC criteria. Other kinds of toxicity possibly attributable to the high dose per fraction were also searched for.
Results
Ninety-two pts were included from 10.03.2014 to 05.02.2019: 2 did not receive the prescribed RT dose; 70 completed 2 cycles of CHT; 22 (24%) received only one CHT cycle. Median follow-up was 21.5 mths (range 1-65) for all pts and 32 mths (range 6-65) for living pts. There were 13 (14%) cases of grade III and higher acute esophageal toxicity. All but one grade III/IV esophageal toxicities were prolonged duration of >2 weeks. Additionally, there were: grade III acute pneumonitis (3), grade IV infectious complication (1), and grade III late pulmonary toxicity (2). Two toxic deaths occurred within 3 months after treatment completion: fatal hemoptysis (1) and complications of prolonged esophageal toxicity (1). Five other deaths that occurrred within one year after treatment were probably treatment-related: lung abscess (1), fatal hemoptysis - in patients with hemoptysis before RT and pulmonary arteries invasion (2), death from undetermined cause without progression in pts with prior pneumonitis (2). Median overall survival was 38 mths (95%CI:27-49) (fig.1.), median progression free survival was 25 mths (95%CI:12-38) (fig.2).
Conclusion
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Despite the encouraging survival rates, similar or even better than those observed in the modern series of conventionally fractionated RT-CHT, the observed rate of toxic and probably toxic deaths that occurred within one year after treatment challenges the safety of the routine use of accelerated hypofractionated RT with concomitant full dose CHT.