King S C, Acker J C, Kussin P S, Marks L B, Weeks K J, Leopold K A
Department of Radiation Oncology, Duke University Medical Center, Durham, NC USA.
Int J Radiat Oncol Biol Phys. 1996 Oct 1;36(3):593-9. doi: 10.1016/s0360-3016(96)00353-7.
The treatment of nonsmall cell lung cancer (NSCLC) with conventional radiotherapy (RT) results in inadequate local tumor control and survival. We report results of a Phase II trial designed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated, accelerated treatment schedule with a concurrent boost technique.
A total of 49 patients with unresectable Stage IIIA/IIIB (38 patients) or medically inoperable Stage I/II (11 patients) NSCLC were prospectively enrolled in this protocol. Radiation therapy was administered twice daily, 5 days/week with > 6 h between each treatment. The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each. Using a concurrent boost technique, electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy.
Median survival for the entire group of 49 patients is 15.3 months. Actuarial survival at 2 years is 46%: 60% for 11 Stage I/II patients, 55% for 21 Stage IIIA patients, and 26% for 17 Stage IIIB patients. The actuarial rate of freedom from local progression at 2 years is 64% for the entire group of 49 patients: 62% for Stage I/II patients, 70% for Stage IIIA patients, and 55% for Stage IIIB patients. Patients who underwent serial bronchoscopic reevaluation (4 Stage I/II, 8 Stage IIIA, and 6 Stage IIIB) have an actuarial rate of local control of 71% at 2 years. The median total treatment time was 32 days. Nine of 49 patients (18%) experienced Grade III acute esophageal toxicity. The 2-year actuarial risk of Grade III or greater late toxicity is 30%. The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20% and 15%, respectively.
This treatment regimen administers a substantially higher biologically effective dose compared with conventional and pure hyperfractionation treatment schedules. The overall rate of acute and late toxicity was acceptable. Preliminary rates of overall survival and local control and freedom from local progression compare favorably to results reported with pure hyperfractionated radiotherapy and chemoradiotherapy.
采用传统放疗（RT）治疗非小细胞肺癌（NSCLC），局部肿瘤控制和生存率均不理想。我们报告了一项II期试验的结果，该试验旨在使用超分割加速治疗方案并结合同步推量技术，在缩短的总治疗时间内给予患者显著增加的总剂量。
共有49例不可切除的IIIA/IIIB期（38例）或因医学原因无法手术的I/II期（11例）NSCLC患者前瞻性纳入本方案。放疗每天进行两次，每周5天，每次治疗间隔>6小时。原发肿瘤和相邻肿大淋巴结接受总量73.6 Gy的照射，分46次，每次1.6 Gy。使用同步推量技术，在最初的36次分割中，选择性照射的淋巴结区域同时接受每次1.25 Gy的剂量照射，总量达45 Gy。
49例患者的中位生存期为15.3个月。2年精算生存率为46%：11例I/II期患者为60%，21例IIIA期患者为55%，17例IIIB期患者为26%。49例患者的2年局部无进展精算率为64%：I/II期患者为62%，IIIA期患者为70%，IIIB期患者为55%。接受系列支气管镜重新评估的患者（4例I/II期、8例IIIA期和6例IIIB期）2年局部控制精算率为71%。中位总治疗时间为32天。49例患者中有9例（18%）出现3级急性食管毒性。3级或更高级别晚期毒性的2年精算风险为30%。严重晚期肺部和皮肤皮下毒性的2年精算率分别为20%和15%。
与传统和单纯超分割治疗方案相比，该治疗方案给予了显著更高的生物有效剂量。急性和晚期毒性的总体发生率是可接受的。总体生存率、局部控制率和局部无进展率的初步结果与单纯超分割放疗和放化疗报告的结果相比更优。
