Risk-Grade Classification of Progress of Disease in Patients Undergoing Multimodality Treatments for Recurrent or Metastatic HNSCC

Abstract

Objective: Neither the factors that affect prognosis for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is not well investigated, nor are comparative efficacy of salvage treatments well assessed. To determine factors predicting the outcome after multimodality of treatments for R/M HNSCC, we classified the R/M HNSCC into three risk-grades based on progress-free survival time and investigated the tumor factors and treatments. Methods: A retrospective analysis was conducted at head and neck center of Sir Run Run Shaw hospital of clinical and follow-up data for 152 R/M HNSCC patients who underwent salvage surgery with or without microvascular flap reconstruction, salvage radiation, systemic treatments after prior unsuccessful cancer treatment using surgery, radiation, or chemotherapy. Results: According to the progress-free survival (PFS). 116 (76.3%) recurrence or metastasis HNSCC with progress of disease (PD) divided into 4 grades: 15 (12.9%) in every low-risk of PD, 19 (16.4%) in low-risk of PD, 38 (32.8%) in middle-risk of PD, 44 (37.9%) in high-risk of PD. The proportion of cigarettes in the high-risk of PD was significantly higher than other grades (60.00%, 73.68%, 60.53% and 86.36%, respectively, p=0.0431). The distribution of primary pathological differentiation, T stage, N stage was significantly different among four grades. The most predominant R/M or second malignance lesion of low-risk and every low-risk of PD was larynx (73.33%, 57.89%, 7.89%, and 9.09%, respectively, p<0.0001). Prior surgery followed with adjuvant chemoradiation in high-risk of PD were significantly higher than those in low-risk and every-low risk of PD (6.67%, 0.00%, 34.21% and 47.73%, respectively; P=0.0004). Notably, salvage surgeries without microvascular reconstruction apparently improved survival and were the main salvage treatments of low-risk and very low-risk patients (73.33%, 57.89%, 31.58%, and 13.64%, respectively; P=0.0138). Importantly, the short PFS did not significantly correspond to short DFS. Conclusions: The risk-grade classification may favor strategies for predict prognosis of R/M patients and identification likely to benefit from salvage treatments. Due to our risk classification, asymptomatic and local regional recurrence conferred decreased risk of PD for aggressive-recurrence patients. Radical surgical salvage remains the critical strategy for resectable disease, although proper patient selection for microvascular reconstruction is essential. For second R/M disease, patients with low-risk of PD would be possibility benefit from supportive care rather than aggressive re-salvage treatments. Funding: This work was supported by the National Natural Science Foundation of China (No. 62071415), Natural Science Foundation of Zhejiang Province (No. LY21H160031), Medical Health Science and Technology Project of Zhejiang Provincial Health Commission Grants (No. 2019336033 and No. 2020367813). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: According to the protocol approved by the Ethical Review Committee of the Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University.