PATHOS: A phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for human papillomavirus (HPV)-positive oropharyngeal cancer.

Abstract

TPS6097 Background: Incidence of Oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing as a result of Human Papillomavirus (HPV), genotype 16 infection. Existing treatments for HPV+ OPSCC have high survival rates but often result in significant long-term toxicities, particularly affecting swallowing function, impacting on quality of life (QoL). PATHOS is a UK phase II-III randomized, multi-centre study. Patients undergo Transoral Surgery (Transoral Laser Microsurgery or Transoral Robotic Surgery) prior to post-operative stratification, according to pathological risk factors. Aim: To determine whether reducing intensity of adjuvant treatment; by lowering radiotherapy (RT) dose or, in patients with positive margins and/or Extracapsular Spread (ECS), omitting concurrent chemotherapy, will result in better long-term swallowing function whilst maintaining high Overall Survival rates. Methods: Patients are eligible if requiring primary resection and neck dissection, fit for surgery/treatment, histologically confirmed OPSCC (TNM T1-T3, N0-N2b), and ≥ 18 years. Following informed consent, patients are confirmed as HPV+. Baseline swallowing panel (including QoL) is carried out prior to surgery and during follow-up. Post-op group allocation: Clinical trial information: NCT02215265. PATHOS has recruited 152 patients across 18 UK sites to date, clearly demonstrating feasibility of recruitment. PATHOS will proceed to an international Phase III in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) subject to funding being awarded. Funded by Cancer Research UK (A17161). Coordinated by the Centre for Trials Research, Cardiff University.A no pathological risk factors No adjuvant treatment B close (1-5mm) primary tumour margins (-ve marginal biopsies), T3 tumours, N2, perineural invasion, vascular invasion Post op: Randomised 1:1 B1: RT 60Gy in 30# over 6 wks (Control) B2: RT 50Gy in 25# over 5 wks (Test) C positive ( < 1mm) margins (-ve marginal biopsies), ECS Post-op: Randomised 1:1 C1: RT 60Gy in 30# over 6 wks with concurrent Cisplatin chemotherapy (CT) (Control) C2: RT 60Gy in 30# over 6 wks without CT (Test)