Acute Toxicity Patterns in Adaptive High Precision Radiotherapy for Head and Neck Cancer - a Randomised Controlled Trial

Abstract

Adaptive Radiation therapy (ART) aims to take into account the changes in target volume and organs at risk during the course of fractionated radiation therapy & this has possible advantage in terms of improved local control, reduced toxicities and improved the QOL. This study aims to assess the clinical impact of ART in terms of toxicities in primary SCC of HNC undergoing radical/adjuvant concurrent chemo-radiotherapy treatment. The study enrolled 100 patients of histopathologically proven primary head-and-neck cancer and were randomized into ART and non-ART arms. Target/OAR delineation was done after CT simulation following rigid immobilization. All patients were started treatment with VMAT & image guidance. After treatment start, the patients were re-simulated using CT imaging again at 3rd, 5th and 7th week. Predefined adaptive re-contouring workflow using deformable image registration was applied to generate adaptive plan. For patients in ART Arm, the new plan was executed for the remaining fractions. In Non ART Arm treatment was continued as per the original plan. All the patients were observed for total volume of Parotid glands at week 1, 3, 5 and 7. RTOG Criteria was used for documenting acute reactions in form of acute xerostomia, mucositis and dysphagia in both arms at week 3, 5 and 7. Median follow-up was 6mo. The percentage volume change in parotid glands was observed to be 6.25%, 16.37% and 28.39% in adaptive arm and 11.53%, 23.54% and 32.56% at 3, 5 and 7 weeks (P-value 0.009 and 0.0123rd and 5th wk respectively). On clinical examination Grade 2 Xerostomia at 3, 5 and 7 wk was seen in 10%, 36% and 70% patients in adaptive arm whereas in 16%, 46% and 88% in non-adaptive arm (P-value 0.006 at 7th wk). The significant difference in mucosal reactions between both arms was observed throughout the course of study in favour of adaptive arm. None of the patients in adaptive arm had Grade 3 mucosal reactions as compared to 26% in non adaptive arm. The difference in mucosal reaction was most significant at 7th week of treatment (p value 0.004). At week 3 and 5, patients having grade 2 or higher reactions were 14% and 46% in adaptive arm as compared to 26% and 70% in non-adaptive arm. (p values 0.029, 0.023). Dryness of mouth has a significant impact on swallowing. In our study we observed grade 2 or higher dysphagia to be 6%, 38% and 80% in adaptive arm whereas 2%, 48% and 84% in non-adaptive arm at 3, 5 and 7 weeks. Though absolute number of patients having adverse dysphagia reaction was lower in adaptive arm, this difference was not statistically significant (p value 0.15, 0.59, 0.09). Volume changes in parotid glands and gross tumour is observed throughout the course of radiation treatment and ART can aid in better sparing of parotid glands with an advantage over non-ART in terms of reduced acute toxicity reactions. Present study is first RCT reported in literature where an attempt is made to correlate dosimetric and toxicity criteria.