Pragmatic patient choice-driven radical treatment approach (PRAGRAD) for very advanced Unresectable Oral Cavity Cancers

Balu Krishna Sasidharan; Sharief K Sidhique; Jino Victor Wilson; Manu Mathew; Amit Jiwan Tirkey; Ashish Singh; Jenifer Jeba Sundararaj; Hannah Mary Thomas T; Swathi B; Benny Rajendra Kuchipudi; Jerome Sunny; Anjana Joel; Annie Jacob; Konduru Vidya; Mansi Agarwal; Aparna Irodi; Jayashanth Riju; Natarajan R; Rajiv Michael; Rajesh Isiah; Anjana Chandran; Sharon Gikku George; Praveenraj C; Andre Dekker; Leonard Wee; Frank Hoebers; Simon P Pavamani

doi:10.1016/j.ijrobp.2025.05.088

Pragmatic patient choice-driven radical treatment approach (PRAGRAD) for very advanced Unresectable Oral Cavity Cancers

Int J Radiat Oncol Biol Phys. 2025 Jun 15:S0360-3016(25)03906-9. doi: 10.1016/j.ijrobp.2025.05.088. Online ahead of print.

Authors

Balu Krishna Sasidharan¹, Sharief K Sidhique², Jino Victor Wilson², Manu Mathew², Amit Jiwan Tirkey³, Ashish Singh⁴, Jenifer Jeba Sundararaj⁵, Hannah Mary Thomas T², Swathi B², Benny Rajendra Kuchipudi², Jerome Sunny², Anjana Joel⁴, Annie Jacob⁵, Konduru Vidya³, Mansi Agarwal³, Aparna Irodi⁶, Jayashanth Riju³, Natarajan R³, Rajiv Michael³, Rajesh Isiah², Anjana Chandran², Sharon Gikku George², Praveenraj C², Andre Dekker⁷, Leonard Wee⁷, Frank Hoebers⁷, Simon P Pavamani²

Affiliations

¹ Department of Radiation Oncology, Unit 2, Christian Medical College Vellore, India. Electronic address: balunair@cmcvellore.ac.in.
² Department of Radiation Oncology, Unit 2, Christian Medical College Vellore, India.
³ Department of Head and Neck Surgery, Unit 2, Christian Medical College Vellore, India.
⁴ Department of Medical Oncology, Christian Medical College Vellore, India.
⁵ Department of Palliative Medicine, Christian Medical College Vellore, India.
⁶ Department of Radiodiagnosis; Christian Medical College Vellore, India.
⁷ Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands.

PMID: 40527412
DOI: 10.1016/j.ijrobp.2025.05.088

Abstract

Background: The treatment of locally advanced unresectable oral cavity cancers (OCC) is challenging, with limited consensus on optimal management and poor outcomes. Our clinical practice identified a subset of unresectable OCC patients who respond favourably to aggressive alternate treatment with chemotherapy and radiotherapy. We propose a systematic design for optimal selection method that is patient choice-driven while attempting to managing unresectable OCC with radical therapy approach.

Methods: This observational pragmatic patient choice-driven cohort study enrolled patients deemed palliative by the multi-disciplinary team (MDT). Patients were offered a choice between upfront palliation (cohort UPA) or upfront radical treatment (cohort URAD). After induction chemotherapy, URAD patients were further stratified as responders(R) or non-responders(N) and offered a choice between radical chemoradiotherapy (RRAD, NRAD) or palliative treatment (RPA, NPA). We compared the overall survival (OS) and Quality-of-Life scores (UW QoL V4) between the cohorts.

Results: 103 patients were screened and 73 enrolled with buccal mucosa 37(49%) and oral tongue 26 (36%) being major sites; majority 57 (78%) chose URAD and UPA included 16 (22%) patients. After induction chemotherapy 35 (65%) were responders of which 27 (77%) opted to continue radical treatment (RRAD) and 8 (23%) chose palliation (RPA). Among the non-responders (n=19), 8 (42%) opted for radical treatment (NRAD) and 11 (58%) chose palliation (NPA). Overall QoL scores for URAD improved significantly from baseline to post intervention (30 to 60, p<0.05), compared to the UPA (17 to 25, p =0.75) with pain scores being the best in URAD (26 to 80, p<0.05). Following stratification, the RRAD cohort showed median OS of 37.9 (95% CI 18.4 - not reached) and RPA was 14.0 (5.0-15.0) months compared to UPA 6.0 (3.0-9.0) months.

Conclusion: The study assessed the feasibility or futility of managing unresectable oral cavity cancers with radical approach instead of palliation. The proposed patient choice-driven stratification protocol showed significantly better QoL in patients who were optimally selected to undergo aggressive treatment compared to palliative management, with a possible improved survival of at least 9 months.

Keywords: Palliation; Patient choice-driven; Quality-of-life; Unresectable Oral Cavity Cancer; radical treatment.