Analysis of efficacy and prognosis of neoadjuvant chemotherapy and (or) surgery plus radiotherapy for hypopharyngeal squamous cell carcinoma
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摘要: 目的 分析影响下咽鳞状细胞癌(hypopharyngeal squamous cell carcinoma，HPSCC)患者预后的危险因素；比较手术+术后根治性放疗(SR)治疗、尼妥珠单抗/西妥昔单抗联合铂类+氟尿嘧啶新辅助化疗+SR治疗对患者的总生存期(overall surviva，OS)、术后进食情况、气管套管拔除率以及2种新辅助化疗的肿瘤缓解情况。方法 回顾性分析2012至2019年上海交通大学医学院附属第一人民医院就诊且既往尚未接受治疗，入院后行SR或新辅助化疗+SR治疗的HPSCC患者资料。分析预后影响因素，进行2种新辅助化疗方案对行SR患者的生存分析。结果 纳入108例患者，单因素分析结果显示性别(P=0.850)对接受SR的HPSCC患者的生存率无明显相关性，而年龄、吸烟史、饮酒史、血小板与淋巴细胞计数比(platelet to lymphocyte ratio，PLR)、中性粒细胞与淋巴细胞计数比(neutrophil to lymphocyte ratio，NLR)、T分期、N分期、尼妥珠单抗/西妥昔单抗+铂类+氟尿嘧啶新辅助化疗、病理分级与预后相关(P < 0.05)。多因素分析显示其中吸烟史、病理分级、尼妥珠单抗/西妥昔单抗+铂类+氟尿嘧啶新辅助化疗是影响HPSCC预后的独立危险因素(P < 0.05)。经过新辅助化疗的患者OS长于仅SR治疗的患者(P < 0.001)。2种新辅助化疗肿瘤缓解情况和OS比较, 差异无统计学意义(P>0.05)，且3种治疗方案的患者经口进食情况和气管套管拔管情况比较差异无统计学意义(P>0.05)。结论 单因素分析显示肿瘤发病年龄、吸烟史、饮酒史、NLR、PLR、T分期、N分期、是否接受新辅助化疗和病理分级等与SR治疗的HPSCC患者预后相关；且多因素分析显示吸烟史、病理分级及新辅助化疗是影响预后的独立危险因素，联合尼妥珠单抗/西妥昔单抗的新辅助化疗可延长患者OS，为HPSCC的治疗提供了一定的依据和参考。Abstract: Objective To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma(HPSCC) and to compare the efficacy of surgical resection followed by adjuvant radiotherapy(SR) with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival(OS) of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies.Methods A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed.Results A total of 108 patients were included in the study. The results of the univariate analysis showed that gender(P=0.850) had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio(PLR), neutrophil-to-lymphocyte ratio(NLR), T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis(P < 0.05). The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC(P < 0.05). Patients who received neoadjuvant therapy had longer OS than those who underwent SR only(P < 0.001). There was no significant difference in tumor response to the two neoadjuvant therapies and in OS(P>0.05), and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups(P>0.05).Conclusion Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.
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表 1 与HPSCC预后相关的单因素Cox回归分析(n=108)
指标 P HR 95%CI 性别 0.850 1.145 0.279~4.698 发病年龄 0.007 0.450 0.252~0.805 吸烟史 < 0.001 5.778 2.957~11.293 饮酒史 < 0.001 3.776 2.017~7.070 NLR 0.002 1.332 1.107~1.604 PLR 0.002 1.007 1.003~1.011 T分期 0.023 1.832 1.088~3.085 N分期 0.006 2.120 1.246~3.605 是否接受新辅助化疗 < 0.001 是否接受尼妥珠单抗+铂类+氟尿嘧啶新辅助化疗 0.003 0.388 0.208~0.722 是否接受西妥昔单抗+铂类+氟尿嘧啶新辅助化疗 < 0.001 0.288 0.151~0.552 病理分级 0.008 0.434 0.235~0.801 
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表 2 与HPSCC预后相关多因素Cox回归分析
指标 回归系数 标准误 HR 95%CI P 是否接受新辅助化疗 0.002 是否接受尼妥珠单抗+铂类+氟尿嘧啶新辅助化疗 -0.896 0.342 0.408 0.209~0.798 0.009 是否接受西妥昔单抗+铂类+氟尿嘧啶新辅助化疗 -1.083 0.344 0.339 0.173~0.664 0.002 发病年龄 -0.581 0.315 0.559 0.301~1.037 0.065 吸烟史 1.141 0.484 3.129 1.211~8.082 0.018 饮酒史 0.766 0.466 2.150 0.862~5.362 0.101 NLR 0.236 0.140 1.266 0.963~1.664 0.091 PLR 0.002 0.003 1.002 0.996~1.008 0.475 T分期 0.432 0.321 1.540 0.821~2.891 0.179 N分期 0.354 0.284 1.425 0.816~2.486 0.213 病理分级 -0.703 0.334 0.495 0.257~0.952 0.035
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表 3 接受新辅助化疗组与未接受新辅助化疗组基线情况比较
例(%) 变量 接受新辅助化疗组
(n=74)未接受新辅助化疗组
(n=34)P 年龄 ≤60岁 41(55.4) 24(70.6) 0.134 >60岁 33(44.6) 10(29.4) 性别 男 71(95.9) 33(97.1) 1.000 女 3(4.1) 1(2.9) T分期 T1+T2期 45(60.8) 17(50.0) 0.291 T3+T4期 29(39.2) 17(50.0) N分期 N0+N1期 39(52.7) 16(47.1) 0.586 N2+N3期 35(47.3) 18(52.9) 病理分级 低分化 11(14.9) 7(20.6) 0.643 中分化+高分化 63(85.1) 27(79.4) 吸烟史 无 36(48.6) 12(35.3) 0.195 有 38(51.4) 22(64.7) 饮酒史 无 32(43.2) 16(47.1) 0.711 有 42(56.8) 18(52.9)
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表 4 2种新辅助化疗方案的肿瘤缓解情况比较
例 肿瘤缓解情况 接受尼妥珠单抗+铂类+氟尿嘧啶新辅助化疗2个周期(n=31) 接受西妥昔单抗+铂类+氟尿嘧啶新辅助化疗2个周期(n=43) PR 16 26 SD 15 17
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