Chougule P B, Suk S, Chu Q D, Leone L, Nigri P T, McRae R, Lekas M, Barone A, Bhat D, Bellino J
Department of Radiation Oncology, Rhode Island Hospital, Providence 02903.
Cancer. 1994 Oct 1;74(7):1927-32. doi: 10.1002/1097-0142(19941001)74:7<1927::aid-cncr2820740717>3.0.co;2-p.
Surgery and radiotherapy mainstays in the management of advanced head and neck cancer, although historically, only 20-30% of patients survive. Therefore, in an attempt to improve locoregional control and survival, a multimodal protocol using cisplatin as a radiosensitizer was implemented.
Between 1984 and 1990, 68 patients with advanced head and neck cancer (Stages III and IV) were treated with a regimen consisting of an induction phase of 4500 cGy and two cycles of cisplatin followed by an eradicative phase of either radical surgery (Group A, 27 patients) or radical radiotherapy (Group B, 41 patients). The maintenance phase chemotherapy consisted of adjuvant 5-fluorouracil (5-FU) and cisplatin after completion of locoregional treatment. Of the 68 patients, 19 had Stage III disease, and 49 had Stage IV; 21 had no regional lymph node metastases (N0), and 47 had regional lymph node metastases (N+).
The induction phase yielded a 26% (18 patients) complete response (CR) rate and a 57% (39 patients) partial response (PR) rate (response > 50%), yielding an overall response rate of 83%. Eleven patients (16%) had stable disease (ST) (i.e., < 50% response). The 2-year survival rates by initial treatment response for patients who had a CR, a PR, and stable disease were 53%, 56%, and 36%, respectively; for Groups A and B, 63% and 45%, respectively; for Stages III and IV, 68% and 43%, respectively; and for N0 and N+, 69% and 43%, respectively. In Group A, 14 of 27 patients (52%) had no viable tumor in the surgical specimen (i.e. had pathologic complete tumor clearance [CTC]); this subgroup had a 5-year survival rate of 58%. Ten patients (37%) who had gross total resection of tumor with negative margins but had tumor present in the specimen had a 5-year survival of 22%. In Group B, the 5-year survival rate was 43% for 27 patients who achieved CR after completion of radical radiotherapy (total tumor dose, 6480-7020 cGy). The 5-year survival rate of the 14 patients who had a PR and stable disease after radical radiotherapy and 3 patients whose resection was incomplete was 0%. The overall 2- and 5-year survival rates for all patients were 53% and 32%, respectively. Of 21 patients in whom treatment failed, most (90%) had a locoregional recurrence: 13 local recurrences (62%), 5 regional (24%), and 1 locoregional (5%). Two patients (10%) experienced failure at distant sites (the lung). Major treatment-related morbidity developed in two patients.
Although induction chemotherapy-radiotherapy produces a high clinical response rate, this does not translate into improved survival compared with historical controls. A subgroup that showed complete tumor clearance (CTC or pathologic complete response) at surgery had an apparent improved survival and merits further study. Patient selection did not appear to be a factor for the CTC group, because the majority of patients in this group had partial responses to induction therapy, nodal disease and advanced tumor stage, and tumor presence in unfavorable sites.
手术和放疗是晚期头颈癌治疗的主要手段，尽管从历史数据来看，仅有20%-30%的患者能够存活。因此，为了提高局部区域控制率和生存率，实施了一项以顺铂作为放射增敏剂的多模式治疗方案。
在1984年至1990年间，68例晚期头颈癌（Ⅲ期和Ⅳ期）患者接受了一种治疗方案，该方案包括一个4500 cGy的诱导期和两个周期的顺铂治疗，随后是根治性手术（A组，27例患者）或根治性放疗（B组，41例患者）的根治期。维持期化疗包括在局部区域治疗完成后使用辅助性5-氟尿嘧啶（5-FU）和顺铂。68例患者中，19例为Ⅲ期疾病，49例为Ⅳ期；21例无区域淋巴结转移（N0），47例有区域淋巴结转移（N+）。
诱导期的完全缓解（CR）率为26%（18例患者），部分缓解（PR）率为57%（39例患者）（缓解率>50%），总缓解率为83%。11例患者（16%）疾病稳定（ST）（即缓解率<50%）。CR、PR和疾病稳定患者的初始治疗缓解后的2年生存率分别为53%、56%和36%；A组和B组分别为63%和45%；Ⅲ期和Ⅳ期分别为68%和43%；N0和N+分别为69%和43%。在A组中，27例患者中有14例（52%）手术标本中无存活肿瘤（即病理完全肿瘤清除[CTC]）；该亚组的5年生存率为58%。10例肿瘤切缘阴性但标本中有肿瘤的患者（37%）5年生存率为22%。在B组中，27例根治性放疗后达到CR的患者（总肿瘤剂量为6480-7020 cGy）5年生存率为43%。14例根治性放疗后PR和疾病稳定的患者以及3例手术切除不完全的患者5年生存率为0%。所有患者的总体2年和5年生存率分别为53%和32%。在21例治疗失败的患者中，大多数（90%）出现局部区域复发：13例局部复发（62%），5例区域复发（24%），1例局部区域复发（5%）。2例患者（10%）出现远处转移（肺部）。两名患者出现了与治疗相关的严重并发症。
尽管诱导化疗-放疗产生了较高的临床缓解率，但与历史对照相比，这并没有转化为生存率的提高。手术时显示完全肿瘤清除（CTC或病理完全缓解）的亚组患者生存率明显提高，值得进一步研究。患者选择似乎不是CTC组的一个因素，因为该组中的大多数患者对诱导治疗有部分缓解、有淋巴结疾病和晚期肿瘤分期，且肿瘤位于不利部位。
