The acute and late toxicity results of a randomized phase II dose-escalation trial in non-small cell lung cancer (PET-boost trial)

• Published in: Radiotherapy and oncology Vol. 131; pp. 166 - 173
• Main Authors: van Diessen, Judi, De Ruysscher, Dirk, Sonke, Jan-Jakob, Damen, Eugène, Sikorska, Karolina, Reymen, Bart, van Elmpt, Wouter, Westman, Gunnar, Fredberg Persson, Gitte, Dieleman, Edith, Bjorkestrand, Hedvig, Faivre-Finn, Corinne, Belderbos, José
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.02.2019
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Chemoradiotherapy; Dose Fractionation, Radiation; Dose painting; Dose-escalation; Dose-Response Relationship, Radiation; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Humans; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; Male; Medicin och hälsovetenskap; Middle Aged; Neoplasm Staging; Non-small cell lung cancer; PET-boost; Positron-Emission Tomography - methods; Radiopharmaceuticals - pharmacokinetics; Radiotherapy - adverse effects; Radiotherapy Planning, Computer-Assisted - methods; Toxicity; Dose-escalation; Toxicity; Dose painting; Non-small cell lung cancer; PET-boost
• ISSN: 0167-8140; 1879-0887; 1879-0887
• DOI: 10.1016/j.radonc.2018.09.019

•The acute and late toxicity rates of the randomized phase II trial investigating dose-escalation in inoperable stage II–III NSCLC are presented.•Toxicity rates of isotoxic integrated boost to either the entire primary tumour or redistributed to regions of high pre-treatment FDG-uptake within the primary tumour were investigated.•The toxicity rates did not exceed the predefined stopping rules. The PET-boost randomized phase II trial (NCT01024829) investigated dose-escalation to the entire primary tumour or redistributed to regions of high pre-treatment FDG-uptake in inoperable non-small cell lung cancer (NSCLC) patients. We present a toxicity analysis of the 107 patients randomized in the study. Patients with stage II–III NSCLC were treated with an isotoxic integrated boost of ≥72 Gy in 24 fractions, with/without chemotherapy and strict dose limits. Toxicity was scored until death according to the CTCAEv3.0. 77 (72%) patients were treated with concurrent chemoradiotherapy. Acute and late ≥G3 occurred in 41% and 25%. For concurrent (C) and sequential or radiotherapy alone (S), the most common acute ≥G3 toxicities were: dysphagia in 14.3% (C) and 3.3% (S), dyspnoea in 2.6% (C) and 6.7% (S), pneumonitis in 0% (C) and 6.7% (S), cardiac toxicity in 6.5% (C) and 3.3% (S). Seventeen patients died of which in 13 patients a possible relation to treatment could not be excluded. In 10 of these 13 patients progressive disease was scored. Fatal pulmonary haemorrhages and oesophageal fistulae were observed in 9 patients. Personalized dose-escalation in inoperable NSCLC patients results in higher acute and late toxicity compared to conventional chemoradiotherapy. The toxicity, however, was within the boundaries of the pre-defined stopping rules.