Response-Adapted Strategy Based on Early Response to Radiotherapy Achieves Favorable Survival With Functional Larynx in Resectable, Locally Advanced Hypopharyngeal Cancer: An Analysis of 423 Real-World Cases

Purpose/Objective(s) The survival and larynx preservation were both important in hypopharyngeal cancer. For primary surgery, most patients need total laryngectomy. For primary radical concurrent chemoradiotherapy (CCRT), the non-responders to CCRT had worse outcome compared with surgery. Thus, our cancer center explored a new response-adapted strategy based on early response to radiotherapy. Materials/Methods A total of 423 patients with resectable, III/IVA hypopharyngeal cancer were reviewed between May 2009 and October 2019. There were three main treatment strategies for locally advanced hypopharyngeal carcinoma in our institution, surgery followed by radiotherapy (S+RT group), response-adapted group and radical CCRT/RT (CRT group). The response-adapted strategy was determined by primary tumor regression evaluated at DT 50 Gy, only primary lesions reaching large PR were recommended for radical CCRT, otherwise planned surgery. We defined the survival with functional larynx as total laryngectomy or death from local disease. Results With a medial follow-up of 66.5 months, the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), distance metastasis free survival (DMFS) and survival with functional larynx were 49.5%, 45.7%, 47.0% and 52.5% for whole cohort. For different groups, the 5-year OS, LRRFS, DMFS and survival with functional larynx were 54.4%, 52.5%, 52.3% and 47.4% for S+RT group (n = 144); 52.7%, 47.0%, 49.5% and 58.6% for response-adapted group (n = 212); 27.7%, 28.6%, 26.3% and 41.3% for CRT group (n = 67). The response-adapted strategy achieved similar survival and better survival with functional larynx compared with S+RT group, but the baseline between them were unbalanced. We use PSM to balance the two arms, the adjusted 5-year OS, LRRFS and DMFS were 54.8%, 48.7%, 53.5% for response-adapted group vs 52.2% 50.8%, 50.8% for S+RT group, without significant difference. But the adjusted 5-year larynx preservation rate and survival with functional larynx in response-adapted group were 75.1% and 53.8%, better compared with 56.1% and 50.1% in S+RT group (P 0.05) for two groups had no difference. In subgroup analysis, 87.7% (186/212) required total laryngectomy when evaluated before treatment in the response-adapted group, but the 5-year survival with functional larynx were still 57.4%. In multivariable analysis, treatment strategies, ECOG, T and N stage were independently significant for OS, LRRFS, DMFS and survival with functional larynx. Conclusion The response-adapted strategy achieved favorable survival with functional larynx and equally oncologist outcome compared with S+RT strategy. Besides, the response-adapted strategy did not result in additional operative complications and was well tolerated. Therefore, the response-adapted strategy might be an innovative, desirable for locally advanced hypopharyngeal cancer, especially for those with organ preservation intention.