Wolf Gregory T, Bellile Emily, Eisbruch Avraham, Urba Susan, Bradford Carol R, Peterson Lisa, Prince Mark E, Teknos Theodoros N, Chepeha Douglas B, Hogikyan Norman D, McLean Scott A, Moyer Jeffery, Taylor Jeremy M G, Worden Francis P
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor.
Department of Biostatistics, University of Michigan Health System, Ann Arbor.
JAMA Otolaryngol Head Neck Surg. 2017 Apr 1;143(4):355-366. doi: 10.1001/jamaoto.2016.3669.
Use of chemoradiotherapy for advanced laryngeal cancer led to a major shift in treatment as an alternative to laryngectomy. Despite widespread adoption of chemoradiotherapy, survival rates have not improved and the original premise of matching neoadjuvant chemotherapy tumor response to determine subsequent treatment has not been followed.
To determine whether improved survival could be achieved by incorporating a single cycle of neoadjuvant chemotherapy to select patients with advanced disease for either laryngectomy or concurrent chemoradiotherapy.
DESIGN, SETTING, AND PARTICIPANTS: An unselected cohort of 247 patients with laryngeal cancer in an academic institution between 2002 and 2012 was evaluated. Patients with limited disease (stages I and II) underwent endoscopic resection, radiotherapy, or chemoradiotherapy for deeply invasive T2 lesions. For patients with advanced disease (stages III and IV), neoadjuvant chemotherapy, concurrent chemoradiotherapy, or primary surgery was recommended. Overall survival (OS) and disease-specific survival (DSS) were analyzed. Median follow-up was 48 months. The study was conducted from January 1, 2002, to December 31, 2012; data analysis was completed December 1, 2015.
Endoscopic resection, radiotherapy, chemoradiotherapy, neoadjuvant chemotherapy, concurrent chemoradiotherapy, and primary surgery.
Overall survival and DSS.
Of the 247 patients, 191 (77.3%) were male; mean (SD) age was 59.6 (10.4) years. Of 94 patients with limited disease, 33 (35.1%) underwent endoscopic resection; 50 (53.2%), radiotherapy alone; and 11 (11.7%), chemoradiotherapy for deeply invasive T2 lesions. Of 153 patients with advanced disease, 71 (46.4%) received neoadjuvant chemotherapy; 50 (32.7%), concurrent chemoradiotherapy; and 32 (20.9%), surgery. Five-year OS and DSS was 75% (95% CI, 68%-81%) and 83% (95% CI, 77%-88%), respectively, for the entire cohort. The DSS was 92% (95% CI, 83%-97%) for patients with stage I or II and 78% (95% CI, 69%-84%) for patients with stage III or IV disease. For patients with advanced disease, 5-year OS and DSS ranged from 78% (95% CI, 55%-90%) and 91% (95% CI, 67%-98%), respectively, for surgery; to 76% (95% CI, 63%-85%) and 79% (95% CI, 67%-88%), respectively, for neoadjuvant bioselection; and to 61% (95% CI, 44%-75%) and 66% (95% CI, 48%-79%), respectively, for primary chemoradiotherapy. Propensity-adjusted, multivariable controlling for known prognostic factors DSS was significantly improved in the neoadjuvant group compared with the chemoradiotherapy group (hazard ratio [HR], 0.48; 95% CI, 0.29-0.80).
Superior survival rates were achieved with a bioselective treatment approach using a single cycle of neoadjuvant chemotherapy. Good survival rates were also achieved in patients selected for primary surgery, and both neoadjuvant chemotherapy and primary surgery were better than survival rates with concurrent chemoradiotherapy, suggesting that the optimal individualized treatment approach for patients with advanced laryngeal cancer has not yet been defined.
对于晚期喉癌，采用放化疗作为喉切除术的替代方案导致了治疗方式的重大转变。尽管放化疗已被广泛应用，但生存率并未提高，而且最初根据新辅助化疗肿瘤反应来确定后续治疗的前提并未得到遵循。
确定通过纳入单周期新辅助化疗来选择晚期疾病患者进行喉切除术或同步放化疗是否能提高生存率。
设计、地点和参与者：对2002年至2012年期间一所学术机构中247例未经过筛选的喉癌患者队列进行了评估。疾病局限（I期和II期）的患者对深度浸润性T2病变进行内镜切除、放疗或放化疗。对于晚期疾病（III期和IV期）的患者，推荐进行新辅助化疗、同步放化疗或一期手术。分析了总生存期（OS）和疾病特异性生存期（DSS）。中位随访时间为48个月。该研究于2002年1月1日至2012年12月31日进行；数据分析于2015年12月1日完成。
内镜切除、放疗、放化疗、新辅助化疗、同步放化疗和一期手术。
总生存期和疾病特异性生存期。
247例患者中，191例（77.3%）为男性；平均（标准差）年龄为59.6（10.4）岁。94例疾病局限的患者中，33例（35.1%）接受了内镜切除；50例（53.2%）仅接受了放疗；11例（11.7%）对深度浸润性T2病变进行了放化疗。153例晚期疾病患者中，71例（46.4%）接受了新辅助化疗；50例（32.7%）接受了同步放化疗；32例（20.9%）接受了手术。整个队列的5年总生存期和疾病特异性生存期分别为75%（95%CI，68%-81%）和83%（95%CI，77%-88%）。I期或II期患者的疾病特异性生存期为92%（95%CI，83%-97%），III期或IV期疾病患者为78%（95%CI，69%-84%）。对于晚期疾病患者，5年总生存期和疾病特异性生存期，手术患者分别为78%（95%CI，55%-90%）和91%（95%CI，67%-98%）；新辅助生物选择患者分别为76%（95%CI，63%-85%）和79%（95%CI，67%-88%）；一期放化疗患者分别为61%（95%CI，44%-75%）和66%（95%CI，48%-79%）。在对已知预后因素进行倾向调整的多变量控制后，新辅助组的疾病特异性生存期与放化疗组相比有显著改善（风险比[HR]，0.48；95%CI，0.29-0.80）。
采用单周期新辅助化疗的生物选择治疗方法可实现更高的生存率。选择一期手术的患者也有良好的生存率，新辅助化疗和一期手术的生存率均优于同步放化疗，这表明晚期喉癌患者的最佳个体化治疗方法尚未确定。
