Journal Article

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up

Ghigi, Giulia, Gavelli, Giampaolo, Monti, Manuela, Tesei, Anna, Sarnelli, Anna, Parisi, Elisabetta, Arpa, Donatella, Polico, Rolando, Genestreti, Giovenzio, Burgio, Marco Angelo, Scarpi, Emanuela, Romeo, Antonino, Rossi, Alice

2019

Overview

Background Concurrent chemotherapy and radiation using conventional fractionation is the standard treatment for inoperable, locally advanced non-small-cell lung cancer (NSCLC). We tested accelerated hypofractionated radiotherapy (AHR) and chemotherapy for the treatment of locally advanced NSCLC. Methods Eligible patients with locally advanced NSCLC were treated with induction chemotherapy (cisplatin and docetaxel), followed by AHR using tomotherapy and consolidation chemotherapy. The prescribed doses were 30 Gy/5 daily fractions at the reference isodose (60–70%) to the tumor, and 25 Gy/5 daily fractions to the clinically involved lymph nodes. The primary end-point was response rate (RR); the secondary end-points were acute and late side-effects, local progression-free survival (PFS), metastasis-free survival (MFS) and overall survival (OS). This trial closed before the first planned interim analysis due to poor accrual. Results From January 2009 to January 2012, 17 of the 23 enrolled patients were evaluable. Treatment yielded an overall RR of 82%. Median follow-up was 87 months (range: 6–87), local PFS was 19.8 months (95% CI 9.7 - not reached), MFS was 9.7 months (95% CI 5.8–46.0) and OS was 23 months (95% CI 8.4–48.4). 70% of patients experienced acute G4 neutropenia, 24% G4 leukopenia, 24% G3 paresthesia, 4% G3 cardiac arrythmia, 4% underwent death after chemotherapy. Late toxicity was represented by 24% dyspnea G3. Conclusions AHR combined with chemotherapy is feasible with no severe side-effects, and it appears highly acceptable by patients. Trial registration This study is registered with the EudractCT registration 2008-006525-14 . Registered on 9 December 2008.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Accelerated hypofractionation / Accelerated tests / Adenocarcinoma - pathology / Adenocarcinoma - therapy / Adult / Aged / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Background radiation / Biomedical and Life Sciences / Biomedicine / Biopsy / Cancer metastasis / Cancer Research / Cancer therapies / Carboplatin / Carcinoma, Non-Small-Cell Lung - pathology / Carcinoma, Non-Small-Cell Lung - therapy / Carcinoma, Squamous Cell - pathology / Carcinoma, Squamous Cell - therapy / Care and treatment / Chemoradiotherapy - mortality / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Clinical Radiation Oncology / Docetaxel - administration & dosage / Dyspnea / Esophagus / Female / Fractionation / Humans / Imaging / Inoperable locally advanced non-small-cell lung cancer / Intensity modulated arc therapy (IMAT) / Leukopenia / Lung cancer / Lung Neoplasms - pathology / Lung Neoplasms - therapy / Lymph nodes / Lymphatic system / Male / Medical imaging / Metastases / Metastasis / Middle Aged / Neutropenia / Non-small cell lung cancer / Non-small cell lung carcinoma / Oncology / Paresthesia / Patients / Prognosis / Prospective Studies / Radiation / Radiation (Physics) / Radiation Dose Hypofractionation / Radiation therapy / Radiology / Radiotherapy / Radiotherapy and chemotherapy / Respiration / Side effects / Simulation / Survival / Survival Rate / Tomography / Toxicity / Tumors