Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer
Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer
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DOI：
10.1200/jco.1997.15.2.712
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发表时间：
1997-02-01
影响因子：
45.3
通讯作者：
Grillo, H
中科院分区：
文献类型：
--
作者：
Choi, NC;Carey, RW;Grillo, H
目的：本研究的主要目的是 (a) 确定 IIIA (N2) 期非小细胞肺癌 (NSCLC) 术前每日两次放射治疗和同步化疗、手术和术后治疗的可行性和毒性，以及 (b) 评估肿瘤反应、切除率、病理肿瘤降期和生存。方法：资格包括纵隔镜活检证实的 N2 病变（IIIA 期）、卡诺夫斯基评分大于或等于至70岁，诊断前3个月内体重减轻低于5%。治疗方案包括术前顺铂、长春碱、氟尿嘧啶（5-FU）两个疗程； 42 Gy 并发辐射，每次 1.5 Gy，每天两次；第 57 天进行手术；以及再进行一个疗程的术后化疗和每日两次 12 至 18 Gy 的同步放疗。结果：42 名 IIIA (N2) 期 NSCLC 患者（27 名男性和 15 名女性，年龄 38 至 77 岁）被纳入这项前瞻性研究。 42 名患者中的 40 名耐受了预定剂量 (42 Gy) 的术前放疗，39 名切除患者中的 37 名接受了规定的术后放疗。第一个、第二个和第三个疗程的化疗中，100%、70%和60%的患者接受了预定的化疗剂量。 14% 的患者（42 名患者中有 6 名）出现明显吞咽困难，需要静脉补液。在 113 个化疗疗程中，骨髓毒性包括 23% 的 3 级以上粒细胞减少症和 6% 的血小板减少症。在 113 个化疗疗程中，有 9% 出现需要住院的发热性中性粒细胞减少症。 93%的患者进行了手术切除。 7% 的患者出现与治疗相关的死亡。 Kaplan-Meier 法显示的 2 年、3 年和 5 年总生存率分别为 66%、37% 和 37%，中位随访时间为 48 个月。手术标本的病理检查显示，肿瘤范围从 IIIA 期 (N2) 向下转变为 II 期 (N1)，占 33%，向下转变为 I 期 (N0)，占 24%（42 例中的 10 例），向下转变为 0 期 (T0N0)，占 9.5%，总共 67%。肿瘤降期的程度也转化为生存获益：对于术后 0 期和 I、II 和 III 期肿瘤，从手术时算起的 5 年生存率分别为 79%、42% 和 18% (P = 0.04)。结论：使用每日两次放疗的同步放化疗是一种有效的诱导方案，可实现 67% 的肿瘤降期，以及令人鼓舞的 37% 5 年生存率。肿瘤降期的程度可能是 IIIA (N2) 期 NSCLC 生存获益的有用中间终点。 (C) 1997 年，美国临床肿瘤学会。
Purpose: The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival.Methods: Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score greater than or equal to 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation.Results: Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade greater than or equal to 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotheropy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2, 3, and 5 years, respectively, with a median follow-up time of 48 months. pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (N0) in 24% (10 of 42), and to stage 0 (T0N0) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04).Conclusion: Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC. (C) 1997 by American Society of Clinical Oncology.