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T4期口咽鳞状细胞癌的治疗结果

Treatment Outcomes for T4 Oropharyngeal Squamous Cell Carcinoma.

作者信息

Zenga Joseph, Wilson Michael, Adkins Douglas R, Gay Hiram A, Haughey Bruce H, Kallogjeri Dorina, Michel Loren S, Paniello Randal C, Rich Jason T, Thorstad Wade L, Nussenbaum Brian

机构信息

Department of Otolaryngology-Head and Neck Surgery, Washington University, St Louis, Missouri.

medical student at Washington University, School of Medicine, St Louis, Missouri.

出版信息

JAMA Otolaryngol Head Neck Surg. 2015 Dec;141(12):1118-27. doi: 10.1001/jamaoto.2015.0764.

Abstract

IMPORTANCE

Little is known about treatment outcomes for T4 oropharyngeal squamous cell carcinoma (OPSCC), particularly in the era of human papillomavirus (HPV)-related disease.

OBJECTIVE

To evaluate oncologic outcomes for T4 OPSCC treated with primary surgical and nonsurgical therapies.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 131 patients from a single academic hospital, who were treated for T4a or T4b OPSCC (with any N stage and without distant metastatic disease at presentation) between 1998 and 2012 and had a minimum 2-year follow-up (the median follow-up time was 34.6 months). This study was conducted between January 1, 1998, and November 1, 2012.

INTERVENTIONS

Sixty-nine patients underwent nonsurgical therapy, 47 (68%) of whom had p16-positive tumors. Nonsurgical treatment paradigms included induction chemotherapy followed by chemoradiotherapy (n = 36 [54%]), concurrent chemoradiotherapy (n = 29 [43%]), and induction chemotherapy followed by radiation therapy alone (n = 2 [3%]). Sixty-two patients underwent surgical treatment, 50 (81%) of whom had p16-positive tumors. Fifty-seven surgical patients (92%) received adjuvant therapy.

MAIN OUTCOMES AND MEASURES

Overall survival (OS) was the primary outcome measure. Secondary outcome measures included disease-specific survival (DSS), disease-free survival (DFS), 2-year gastrostomy and tracheostomy tube rates, and major complication rates.

RESULTS

Significant baseline differences between the surgical vs nonsurgical groups included age (mean 59.8 vs 55.4 years [P = .005]), sex (male, 95% vs 84% [P = .04]), body mass index (<18.5 [calculated as weight in kilograms divided by height in meters squared], 3% vs 16% [P = .02]), and smoking history of 10 or more pack-years (48% vs 77% [P = .003]). For p16-positive patients, Kaplan-Meier estimates of OS, DSS, and DFS were significantly higher for surgically treated patients than for the nonsurgical group (χ(2)(1) = 7.335 for log-rank P = .007, χ(2)(1) = 8.607 for log-rank P = .003, and χ(2)(1) = 7.763 for log-rank P = .005, respectively). For p16-negative patients, Kaplan-Meier estimates of OS and DSS were higher for the surgical group but did not reach statistical significance (χ(2)(1) = 2.649 for log-rank P = .10 and χ(2)(1) = 2.077 for log-rank P = .15, respectively), while estimates of DFS were significantly higher for patients treated with primary surgery (χ(2)(1)= 3.869 for log-rank P = .049. In a multivariable Cox survival analysis, p16-positive immunohistochemical status had a significant positive association with OS (hazard ratio [HR], 0.55; 95% CI, 0.32-0.95 [P = .03]), DSS (HR, 0.45; 95% CI, 0.22-0.92 [P = .03]), and DFS (HR, 0.55; 95% CI, 0.32-0.95 [P = .03]), and nonsurgical treatment had a significant negative association with OS (HR, 2.79; 95% CI, 1.51-5.16 [P = .001]), DSS (HR, 3.38; 95% CI, 1.59-7.16 [P = .002]), and DFS (HR, 2.59; 95% CI, 1.51-4.45 [P = .001]).

CONCLUSIONS AND RELEVANCE

Primary surgical treatment may be associated with improved outcomes in patients with T4 OPSCC. p16 Immunohistochemical status remains a strong prognostic indicator even in patients with locally advanced disease.

摘要

重要性

关于T4期口咽鳞状细胞癌(OPSCC)的治疗结果,人们了解甚少,尤其是在人乳头瘤病毒(HPV)相关疾病的时代。

目的

评估采用原发性手术和非手术疗法治疗T4期OPSCC的肿瘤学结果。

设计、设置和参与者:对一家学术医院的131例患者进行回顾性队列研究,这些患者在1998年至2012年间接受了T4a或T4b期OPSCC治疗(任何N分期,就诊时无远处转移疾病),且至少有2年的随访期(中位随访时间为34.6个月)。本研究于1998年1月1日至2012年11月1日进行。

干预措施

69例患者接受了非手术治疗,其中47例(68%)为p16阳性肿瘤。非手术治疗模式包括诱导化疗后行放化疗(n = 36 [54%])、同步放化疗(n = 29 [43%])以及诱导化疗后单纯放疗(n = 2 [3%])。62例患者接受了手术治疗,其中50例(81%)为p16阳性肿瘤。57例手术患者(92%)接受了辅助治疗。

主要结局和测量指标

总生存期(OS)是主要结局指标。次要结局指标包括疾病特异性生存期(DSS)、无病生存期(DFS)、2年胃造口术和气管造口术插管率以及主要并发症发生率。

结果

手术组与非手术组之间存在显著的基线差异,包括年龄(平均59.8岁对55.4岁[P = 0.005])、性别(男性,95%对84%[P = 0.04])、体重指数(<18.5[计算方法为体重(千克)除以身高(米)的平方],3%对16%[P = 0.02])以及吸烟史达10包年或以上(48%对77%[P = 0.003])。对于p16阳性患者,手术治疗患者的OS、DSS和DFS的Kaplan-Meier估计值显著高于非手术组(对数秩检验χ(2)(1) = 7.335,P = 0.007;χ(2)(1) = 8.607,P = 0.003;χ(2)(1) = 7.763,P = 0.005)。对于p16阴性患者,手术组的OS和DSS的Kaplan-Meier估计值较高,但未达到统计学显著性(对数秩检验χ(2)(1) = 2.649,P = 0.10;χ(2)(1) = 2.077,P = 0.15),而原发性手术治疗患者的DFS估计值显著较高(对数秩检验χ(2)(1)= 3.869,P = 0.049)。在多变量Cox生存分析中,p16阳性免疫组化状态与OS(风险比[HR],0.55;95%置信区间,0.32 - 0.95[P = 0.03])、DSS(HR,0.45;95%置信区间,0.22 - 0.92[P = 0.03])和DFS(HR,0.55;95%置信区间,0.32 - 0.95[P = 0.03])有显著正相关,非手术治疗与OS(HR,2.79;95%置信区间,1.51 - 5.16[P = 0.001])、DSS(HR,3.38;95%置信区间,1.59 - 7.16[P = 0.002])和DFS(HR,2.59;95%置信区间,1.51 - 4.45[P = 0.001])有显著负相关。

结论及相关性

原发性手术治疗可能与T4期OPSCC患者的预后改善相关。即使在局部晚期疾病患者中,p16免疫组化状态仍然是一个强有力的预后指标。

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