Dose Escalation in 5-Fraction Palliative Thoracic Radiotherapy: A Feasibility and Safety Planning Study

Abstract

Short course palliative radiotherapy is an effective and convenient treatment in patients with incurable advanced lung cancer to manage symptoms. Standard 5-fraction regimens often deliver a lower overall dose, limiting durable local control. We performed a planning study to evaluate the feasibility and safety of 5-fraction dose escalation. In this research ethics board approved study, 10 patients with advanced lung cancer who received palliative thoracic radiotherapy between 2015-2016 were identified from our institutional database. Four 5-fraction plans were generated for each patient: 20 Gy using a parallel opposed pair (POP) beam arrangement, as compared with 25 Gy, 30Gy and 35 Gy using volumetric modulated arc therapy (VMAT). The gross target volume (GTV) was expanded volumetrically by 1 cm to obtain the planning target volume (PTV). The fields for POP plans were defined by extending 8mm from the PTV. VMAT plans were optimized by prioritizing organs at risk (OARs) allowing compromise of PTV coverage (PTV-eval =PTV - overlapping OARs, with an aim for D95≥95%). Conservative dose constraints were selected from literature, with OARs including spinal cord, esophagus, trachea, proximal bronchial tree and brachial plexus. For Lung-eval (lung-GTV), a V20 of ≤10% was targeted, with ≤15% accepted if required. Published radiobiological models were employed to evaluate the likelihood for toxicity to OARs, with a specific focus on esophageal toxicity. The median PTV was 316cc (range 165 -551cc). In the reference 20Gy POP plans, the median lung-eval V20 were 6% (range 1%-22%) and D95≥95% coverage was achieved in 30% cases. For 25Gy VMAT plans, the pre-specified OARs tolerance were met in all cases. For 30-35 Gy VMAT plans, the pre-specified OARs tolerance were met in all except 1 case, which had a lung-eval V20 of 15.5% and 19.5% with the 30 Gy and 35Gy plans respectively. The D95≥95% coverage was achieved in 90 % cases for 25Gy, 20% for 30Gy, and 0% for 35Gy. The coverage evaluated by D90 were as following: 25Gy median 97% (range 97%-100%), 30Gy median 96% (92%-98%), and 35Gy median 88% (range 83-96%). The predicted probability of ≥grade 2 esophagitis for 20Gy, 25Gy, 30Gy and 35 Gy plans were 1.7%, 3.3%, 5.0% and 5.0% respectively, based on the Belderbos normal tissue complication probability model. In this planning study of 5-fraction palliative thoracic radiotherapy, dose escalation from 25 to 35 Gy in 5 fractions appeared feasible using VMAT techniques without significant predicted toxicity. While dose escalation to 25Gy without PTV compromise was feasible in most cases, significant compromise of PTV was required for 30- and 35Gy to minimize predicted toxicity. Based on these data, a dose-escalation clinical trial is planned under the auspices of the Canadian Pulmonary Radiotherapy Investigators (CAPRI) Group.