Judi van Diessen1, Dirk De Ruysscher2, Jan-Jakob Sonke1, Eugène Damen1, Karolina Sikorska3, Bart Reymen2, Wouter van Elmpt2, Gunnar Westman4, Gitte Fredberg Persson4, Edith Dieleman5, Hedvig Bjorkestrand6, Corinne Faivre-Finn7, José Belderbos8. 1. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 2. Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 3. Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Oncology, Rigshospitalet Copenhagen University Hospital, Denmark. 5. Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands. 6. Department of Radiation Oncology, Karolinska Institute, Stockholm, Sweden. 7. The University of Manchester, Division of Cancer Sciences, The Christie NHS Foundation Trust, United Kingdom. 8. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: j.belderbos@nki.nl.
Abstract
BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: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. RESULTS: 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. CONCLUSION: 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.
RCT Entities:
BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: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. RESULTS: 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. CONCLUSION: Personalized dose-escalation in inoperable NSCLCpatients results in higher acute and late toxicity compared to conventional chemoradiotherapy. The toxicity, however, was within the boundaries of the pre-defined stopping rules.
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