LBA 02 - Primary Results for the Phase III Trial of Toxicity Reduction using Proton Beam Therapy for Oropharyngeal Cancer (TORPEdO; CRUK/18/010)
Presenter(s)
D. Thomson1, J. Price2, M. Tyler3, M. J. Beasley4, J. Lester5, C. M. Nutting6, N. Palaniappan7, R. J. Prestwich8, R. Shanmugasundaram9, A. Thompson10,11, H. Bulbeck12, J. A. Langendijk13, M. Lowe2, J. Tyler14,15, K. Chiu16, J. Christian17, C. Cruickshank3, D. Gardiner3, C. M. L. West18, and E. Hall3; 1The Christie NHS Foundation Trust and Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom, 2The Christie NHS Foundation Trust, Manchester, United Kingdom, 3The Institute of Cancer Research, London, United Kingdom, 4University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom, 5Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom, 6The Royal Marsden NHS Foundation Trust, London, United Kingdom, 7Velindre University NHS Trust, Cardiff, United Kingdom, 8Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 9University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, 10University College London Hospital, London, United Kingdom, 11Royal Free London NHS Foundation Trust, London, United Kingdom, 12Braintrust, Cowes, United Kingdom, 13University Medical Centre Groningen, Groningen, Netherlands, 14Royal Marsden Hospital, London, United Kingdom, 15National Radiotherapy Trials Quality Assurance Group, London, United Kingdom, 16East and North Hertfordshire NHS Trust, Middlesex, United Kingdom, 17Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, 18Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom
Purpose/Objective(s):
To investigate differences in clinical outcomes between intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) for patients with locally advanced oropharyngeal squamous cell carcinoma (OPSCC).Materials/Methods:
In this phase 3, randomised, controlled, multicentre trial participants with OPSCC requiring definitive bilateral chemoradiation were assigned in a 2:1 ratio to IMPT or IMRT (70 Gy (RBE) in 33 once daily fractions over 6.5 weeks), with two cycles of concurrent cisplatin chemotherapy (every 3 weeks, 100mg/m2). Co-primary endpoints at 12 months after radiation were: (i) clinician-reported gastrostomy dependence or CTCAE grade 3 weight loss (20% decrease from baseline) and (ii) patient-reported University of Washington quality of life (UW-QOL) physical composite score of saliva, taste, chewing, swallowing, speech and appearance; each tested at the 2.5% significance level. Analysis accounted for tumour (T) and nodal (N) stage, smoking status, chemotherapy received, baseline body mass index and baseline UW-QOL physical composite score. Secondary endpoints included MD Anderson Dysphagia Inventory (MDADI), freedom from loco-regional recurrence and overall survival.Results:
205 participants with locally advanced OPSCC (48% T3/4, 21% N2(c), 31% =10 pack year history) from 20 UK centres were allocated to IMPT (n=136) or IMRT (n=69) between March 2020 and June 2023. Treatment was delivered over a median of 44 days (IQR: 44, 44) for both IMPT and IMRT. A second cycle of chemotherapy was not given for 5 (3.8%) and 3 (4.5%) patients receiving IMPT and IMRT, respectively. 178/205 (119 IMPT; 59 IMRT) were evaluable for the clinical co-primary endpoint, with data recorded for gastrostomy dependence or weight loss. Both groups had low rates of gastrostomy dependence: IMPT 2/119 (1.7%) vs IMRT 1/59 (1.7%). A higher rate of grade 3 weight loss was seen for IMPT: 20/110 (18.2%) vs IMRT 3/53 (5.7%); taken together, the odds ratio for IMPT was 2.8 (97.5% CI: 0.8, 10.4, p=0.080). 155/205 participants (100 IMPT; 55 IMRT) were evaluable for the patient reported co-primary endpoint. There was no evidence of a difference in mean UW-QOL physical composite score for IMPT vs IMRT (78.3 vs 77.1, difference=1.3 (to 1 decimal place), 97.5% CI: -3.7, 6.2, p=0.563). MDADI mean composite scores at 12 months for IMPT vs IMRT were 79.4 vs 79.5. At a median follow-up of 27 months, 2-year freedom from loco-regional recurrence for IMPT and IMRT was 94.8% (99% CI: 85.8, 98.2) and 96.8% (81.6, 99.5) and for overall survival 94.4% (85.9, 97.9) and 94.9% (79.1, 98.8), respectively.Conclusion:
For locally advanced OPSCC, IMPT does not reduce long-term gastrostomy dependence or severe weight loss and does not improve long-term patient-reported physical quality of life or swallow function compared with IMRT. There is no requirement for IMPT as an alternative to high quality IMRT.