Trial Comparing Avg. Global Qual of Lifescore in Hypo Frac. RT vs Conv. Frac. in H&N Cancers

Radiotherapy forms an integral part of Head and Neck cancer treatment in both definitive as well as adjuvant setting. This study explores the use of hypofractionated radiotherapy, delivering 55Gy in 20 fractions over 4 weeks in comparison to the conventional approach which involves 70 Gy over 6 weeks. Hypofractionated radiotherapy would result in significant benefits in terms of shortening the overall treatment time, countering accelerated hypofraction effects that typically arise after the 4th week. The new approach is also anticipated to offer resource and financial advantages, involving less machine time per patient, and potentially leading to better patient compliance. Previous studies on hypofractionation in Head and Neck cancer have demonstrated good local control and acceptable toxicity levels compared to conventional methods. The primary objective of this study is to compare the average global quality of life following hypofractionated radiotherapy versus conventional fractionation, with secondary objectives including a comparison of locoregional control at 2 years and assessment of acute and late toxicities. The study will require 600 eligible patients randomly assigned to either the hypofractionated or conventional arm. For definitive chemoradiation, the control arm will receive 66Gy in 30 fractions over 6 weeks, while the experimental arm will receive 55Gy in 20 fractions over 4 weeks, along with Inj Cisplatin @ 100mg/m2 3 weekly for 2 cycles. In the adjuvant setting control arm will receive 60Gy in 30 fractions over 6 weeks and experimental arm will receive 52.5Gy in 20 fractions over 4 weeks along with Inj Cisplatin @ 100mg /m2 3 weekly for 2 cycles for both arms based on histopathological indications. Physician reported and patient reported acute toxicities like mucositis, dermatitis and dysphagia, weight loss, requirement and duration of feeding tubes as well as patients reported outcomes in the form of EORTC QLQ C30, HN43 and XeQoLS will be recorded both during and after treatment at regular intervals for 2 years. The study's duration is five years, aiming to determine whether the hypofractionated schedule is non-inferior to conventional radiotherapy in terms of safety and disease-related outcomes

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

1. Age ≥ 18 years
2. ECOG performance status 0 - 2.
3. Patients diagnosed with invasive squamous cell cancer of the head and neck region which includes lip, oral cavity, nasopharynx, oropharynx, hypopharynx, supraglottis, glottis and subglottis.
4. Patients who are being treated with curative intent treatment either with surgery followed by adjuvant radiotherapy with or without chemotherapy or definitive chemoradiation.
5. Patients must have a histopathological proof of malignancy, such as biopsy or post operative histopathology report. Biopsies or surgeries done outside must have been reviewed for pathological confirmation and specimen adequacy at the treating institute.
6. Patients with non metastatic cancer, optimally staged with the following:

   1. Contrast enhanced CT scan of the neck and thorax for cancer lip, oral cavity, oropharynx, hypopharynx, supraglottis, glottis and subglottis
   2. Magnetic Resonance Imaging of the neck and CT thorax for cancer of nasopharynx

Exclusion Criteria:

1. Concurrent illness like severe cardiac, renal or hepatic dysfunction and, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
2. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

• BACKGROUNDBaujat B, Bourhis J, Blanchard P, Overgaard J, Ang KK, Saunders M, Le Maitre A, Bernier J, Horiot JC, Maillard E, Pajak TF, Poulsen MG, Bourredjem A, O'Sullivan B, Dobrowsky W, Andrzej H, Skladowski K, Hay JH, Pinto LH, Fu KK, Fallai C, Sylvester R, Pignon JP; MARCH Collaborative Group. Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev. 2010 Dec 8;2010(12):CD002026. doi: 10.1002/14651858.CD002026.pub2. PMID 21154350
• BACKGROUNDBentzen SM, Gupta T, Jacinto AA, Rosenblatt E, Bhasker S, Napoles M, Binia S, Chansilpa Y, Aguiar S, Nagarajan M, Laskar SG, De Marchi P, Goloubeva O, Hopkins K, Zubizarreta E, Agarwal JP, Abdel-Wahab M. Hypofractionated Versus Normofractionated Accelerated Radiation Therapy With or Without Cisplatin for Locally Advanced Head and Neck Squamous Cell Carcinoma (HYPNO): A Randomized, Open-Label, Phase 3, Noninferiority Trial. Int J Radiat Oncol Biol Phys. 2026 Jun 1;125(2):387-398. doi: 10.1016/j.ijrobp.2025.12.056. Epub 2026 Feb 19. PMID 41711624
• BACKGROUNDFu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16. doi: 10.1016/s0360-3016(00)00663-5. PMID 10924966
• BACKGROUNDThomson DJ, Palma D, Guckenberger M, Balermpas P, Beitler JJ, Blanchard P, Brizel D, Budach W, Caudell J, Corry J, Corvo R, Evans M, Garden AS, Giralt J, Gregoire V, Harari PM, Harrington K, Hitchcock YJ, Johansen J, Kaanders J, Koyfman S, Langendijk JA, Le QT, Lee N, Margalit D, Mierzwa M, Porceddu S, Soong YL, Sun Y, Thariat J, Waldron J, Yom SS. Practice recommendations for risk-adapted head and neck cancer radiotherapy during the COVID-19 pandemic: An ASTRO-ESTRO consensus statement. Radiother Oncol. 2020 Oct;151:314-321. doi: 10.1016/j.radonc.2020.04.019. Epub 2020 Jul 27. PMID 32730830
• BACKGROUNDGupta T, Ghosh-Laskar S, Agarwal JP. Resource-sparing curative-intent hypofractionated-accelerated radiotherapy in head and neck cancer: More relevant than ever before in the COVID era. Oral Oncol. 2020 Dec;111:105045. doi: 10.1016/j.oraloncology.2020.105045. Epub 2020 Oct 20.