Multimodality Treatment of Locally Advanced Oral Cancer: Can the Optimal Dose of Chemoradiation be Lowered? A Retrospective Cohort Study
Subbiah Shanmugam, Gerald Anandraja, R Pravenkumar Ramaswami
50 Gy chemoradiation in locally advanced oral cancer, 50 Gy chemoradiation, Definitive chemoradiation oral cancer, Locally advanced preoperative chemoradiation in locally advanced oral cancer, Oral cancer, Tobacco use
Citation Information :
Shanmugam S, Anandraja G, Ramaswami RP. Multimodality Treatment of Locally Advanced Oral Cancer: Can the Optimal Dose of Chemoradiation be Lowered? A Retrospective Cohort Study. Int J Head Neck Surg 2023; 14 (3):41-46.
Background: Locally advanced oral cancers are treated with a combination of surgery and chemoradiation. Definitive chemoradiation (Def CRT) or concurrent chemoradiation (CCRT) is employed only in rare instances when essential structures are at risk from unresectable tumors. The potential drawback of opting for radiation therapy upfront is the morbidity of surgery for residual tumors after Def CRT. Few centers have employed preoperative 50 Gy chemoradiation followed by surgery for resectable oral cancers. However, there is currently no well-established regimen for preoperative chemoradiation (50 Gy). We practice salvage surgery after Def CRT in our institution for some resectable locally advanced oral cancers due to patient, hospital, or logistical considerations. We found that there was considerable wound morbidity associated with these surgeries. With the knowledge that the preferred treatment approach for these patients would be surgery and adjuvant radiation, or Def CRT in a few patients, we decided to tread in-between the two standard treatment paradigms by treating such patients with preoperative chemoradiation (50 Gy) followed by surgery to reduce wound morbidity. We studied to compare the morbidity, functional (swallow) outcome, clinicopathological response pattern, locoregional recurrence, and disease-free survival between surgery following a definitive dose of chemoradiation (60–70 Gy) and 50 Gy chemoradiation.
Materials and methods: A total of 62 patients of moderately advanced (T4a) oral cancer who underwent surgery for residue following radiotherapy (RT) between 2015 and 2021 were studied. The 50 Gy group consisted of 32 patients, and the conventional radiation group had 30 patients. The patients were followed up for the following outcome measures—wound morbidity, swallowing efficiency, postoperative histopathology, disease progression, locoregional recurrence, distant recurrence, and disease-free survival and death.
Results: Wound morbidity was found to be lower in the 50 Gy preoperative radiation group compared to the conventional radiation group. We found no statistically significant difference in pathological response, swallowing outcomes, disease progression, recurrence, and disease-free survival.
Conclusion: Operating on patients who were treated with 50 Gy was associated with less morbidity in comparison with the conventional dose (60–70 Gy). Since a significant percentage of patients after Def CRT require salvage surgery, the option of multimodality treatment with 50 Gy preoperative chemoradiation may be worth considering. This requires a standard assessment after completing 50 Gy to identify patients not responding to radiation. Large prospective trials are needed to arrive at a definite conclusion.
Patil VM, Noronha V, Joshi A, et al. Induction chemotherapy in technically unresectable locally advanced oral cavity cancers: does it make a difference? Indian J Cancer 2013;50(1):1–8. DOI: 10.4103/0019-509X.112263
Soo KC, Tan EH, Wee J, et al. Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison. Br J Cancer 2005;93(3):279–286. DOI: 10.1038/sj.bjc.6602696
Iyer NG, Tan DS, Tan VK, et al. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer 2015;121(10):1599–1607. DOI: 10.1002/cncr.29251
Foster CC, Melotek JM, Brisson RJ, et al. Definitive chemoradiation for locally-advanced oral cavity cancer: a 20-year experience. Oral Oncol 2018;80:16–22. DOI: 10.1016/j.oraloncology.2018.03.008
Hosni A, Chiu K, Huang SH, et al. Non-operative management for oral cavity carcinoma: definitive radiation therapy as a potential alternative treatment approach. Radiother Oncol 2021;154:70–75. DOI: 10.1016/j.radonc.2020.08.013
Yi J, Huang X, Xu Z, et al. Phase III randomized trial of preoperative concurrent chemoradiotherapy versus preoperative radiotherapy for patients with locally advanced head and neck squamous cell carcinoma. Oncotarget 2017;8(27):44842–44850. DOI: 10.18632/oncotarget.15107
Lindholm P, Valavaara R, Aitasalo K, et al. Preoperative hyperfractionated accelerated radiotherapy and radical surgery in advanced head and neck cancer: a prospective phase II study. Radiother Oncol 2006;78(2):146–151. DOI: 10.1016/j.radonc.2005.11.002
Wennerberg J. Pre versus post-operative radiotherapy of resectable squamous cell carcinoma of the head and neck. Acta Otolaryngol 1995;115(4):465–474. DOI: 10.3109/00016489509139350
Schultze-Mosgau S, Grabenbauer GG, Radespiel-Tröger M, et al. Vascularization in the transition area between free grafted soft tissues and pre-irradiated graft bed tissues following preoperative radiotherapy in the head and neck region. Head Neck 2002;24(1):42–51. DOI: 10.1002/hed.10012
Schultze-Mosgau S, Grabenbauer GG, Wehrhan F, et al. [Histomorphological structural changes of head and neck blood vessels after pre- or postoperative radiotherapy]. Strahlenther Onkol 2002;178(6):299–306.
Kramer S, Gelber RD, Snow JB, et al. Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the Radiation Therapy Oncology Group. Head Neck Surg 1987;10(1):19–30. DOI: 10.1002/hed.2890100105
Tupchong L, Scott CB, Blitzer PH, et al. Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys 1991;20(1):21–28. DOI: 10.1016/0360-3016(91)90133-o
Murthy V, Gurram L, Kannan S, et al. Elective nodal dose of 60 Gy or 50 Gy in head and neck cancers: a matched pair analysis of outcomes and toxicity. Adv Radiat Oncol 2017;2(3):339–345. DOI: 10.1016/j.adro.2017.06.005
D'cruz A, Lin T, Anand AK, et al. Consensus recommendations for management of head and neck cancer in Asian countries: a review of international guidelines. Oral Oncol 2013;49(9):872–877. DOI: 10.1016/j.oraloncology.2013.05.010
Forner D, Noel CW, Wu V, et al. Nonsurgical management of resectable oral cavity cancer in the wake of COVID-19: a rapid review and meta-analysis. Oral Oncol 2020;109:104849. DOI: 10.1016/j.oraloncology.2020.104849
Klug C, Berzaczy D, Voracek M, et al. Preoperative radiochemotherapy in the treatment of advanced oral cancer: outcome of 276 patients. J Craniomaxillofac Surg 2009;37(6):344–347. DOI: 10.1016/j.jcms.2008.11.012
Hermann RM, Krech R, Hartlapp J, et al. [The value of qualitative regression grading as a prognostic factor for survival after preoperative radiochemotherapy in patients with advanced head and neck cancer]. Strahlenther Onkol 2001;177(6):277–282. DOI: 10.1007/pl00002408
Driemel O, Ettl T, Kölbl O, et al. Outcome and histopathologic regression in oral squamous cell carcinoma after preoperative radiochemotherapy. Strahlenther Onkol 2009;185(5):296–302. DOI: 10.1007/s00066-009-1914-y