Barker Jerry L, Glisson Bonnie S, Garden Adam S, El-Naggar Adel K, Morrison William H, Ang K Kian, Chao K S Clifford, Clayman Gary, Rosenthal David I
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2003 Dec 1;98(11):2322-8. doi: 10.1002/cncr.11795.
Nonsinonasal neuroendocrine carcinomas (NSNEC) of the head and neck are rare and pose a diagnostic and management challenge. The authors undertook a retrospective study to gain insights into the spectrum of clinicopathologic characteristics, patterns of failure, and optimal management of patients with this disease.
The authors treated 23 adults with pathologically proven, nonmetastatic, primary NSNEC from 1984 to 2001. The majority (13 patients) had laryngeal origin with the following American Joint Committee on Cancer stage distribution: Stage I disease in 1 patient, Stage II disease in 2 patients, Stage III disease in 6 patients, and Stage IV disease in 14 patients. Nine patients underwent definitive surgery with or without postoperative radiation, and 14 patients received definitive radiotherapy. The median definitive radiation dose was 66 grays (Gy) (range, 44-72 Gy) using conventional fractionation. Fourteen patients received chemotherapy, with two to four cycles of induction platinum plus etoposide used most commonly.
The median follow-up time for surviving patients was 40 months (range, 15-89 months). The actuarial 2-year and 5-year overall survival (OS) rates were 53% and 33%, respectively; and the disease-free survival (DFS) rates were 41% and 25%, respectively. Both the 2-year OS rate (68% vs. 30%; P = 0.002) and the 2-year DFS rate (55% vs. 17%; P = 0.004) were improved with chemotherapy compared with local therapy alone. Seventy-five percent of patients with measurable disease had complete clinical responses to induction chemotherapy. There was 100% complete clinical response of tumor after radiotherapy. The actuarial 2-year local failure rate was 23%. Chemotherapy did not reduce local failure (P = 0.91). There was no regional failure. The 2-year and 5-year distant metastasis rates were 54% and 71%, respectively. The 2-year rates of metastases without and with chemotherapy were 79% and 39%, respectively (P = 0.006). The 2-year and 5-year rates of intracranial metastases were 25% and 44%, respectively, and the 2-year and 5-year rates of isolated brain metastases were 21% and 41%, respectively.
Based on these results, the authors' treatment strategy for patients with NSNEC is sequential chemotherapy and radiation. They recommend full-dose radiotherapy alone for patients with NSNEC who achieve a complete clinical response to induction chemotherapy. Newer chemotherapeutic regimens or additional adjuvant chemotherapy should be investigated for patients with NSNEC given the high rate of distant failure. Due to the very high rate of brain metastases among patients in the current study, the authors now consider incorporating prophylactic cranial irradiation into primary radiotherapy for individual patients who have complete clinical responses to induction chemotherapy.
头颈部非鼻窦神经内分泌癌（NSNEC）较为罕见，在诊断和治疗方面存在挑战。作者进行了一项回顾性研究，以深入了解该疾病患者的临床病理特征谱、失败模式及最佳治疗方法。
作者于1984年至2001年治疗了23例经病理证实的非转移性原发性NSNEC成年患者。大多数（13例）患者起源于喉部，美国癌症联合委员会分期分布如下：1例为I期疾病，2例为II期疾病，6例为III期疾病，14例为IV期疾病。9例患者接受了确定性手术，术后接受或未接受放疗，14例患者接受了确定性放疗。采用常规分割时，确定性放疗的中位剂量为66格雷（Gy）（范围44 - 72 Gy）。14例患者接受了化疗，最常用的是两到四个周期的诱导铂类加依托泊苷。
存活患者的中位随访时间为4个月（范围15 - 89个月）。2年和5年的精算总生存率（OS）分别为53%和33%；无病生存率（DFS）分别为41%和25%。与单纯局部治疗相比，化疗使2年OS率（68%对30%；P = 0.002）和2年DFS率（55%对17%；P = 0.004）均得到改善。75%可测量疾病的患者对诱导化疗有完全临床反应。放疗后肿瘤的完全临床反应率为100%。2年精算局部失败率为23%。化疗未降低局部失败率（P = 0.91）。无区域失败。2年和5年远处转移率分别为54%和71%。未化疗和化疗患者的2年转移率分别为79%和39%（P = 0.006）。2年和5年颅内转移率分别为25%和44%，孤立脑转移的2年和5年率分别为21%和41%。
基于这些结果，作者对NSNEC患者的治疗策略是序贯化疗和放疗。他们建议对诱导化疗有完全临床反应的NSNEC患者单独进行全剂量放疗。鉴于远处失败率高，应研究NSNEC患者的新型化疗方案或额外的辅助化疗。由于本研究中患者脑转移率非常高，作者现在考虑对诱导化疗有完全临床反应的个体患者在原发性放疗中加入预防性颅脑照射。
