Schultz C, Scott C, Sherman W, Donahue B, Fields J, Murray K, Fisher B, Abrams R, Meis-Kindblom J
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Clin Oncol. 1996 Feb;14(2):556-64. doi: 10.1200/JCO.1996.14.2.556.
This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL).
Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy.
As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients.
Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.
本研究是由放射治疗肿瘤学组（RTOG）开展的一项前瞻性I/II期试验，旨在测试对于原发性中枢神经系统淋巴瘤（PCNSL）患者，放疗前使用环磷酰胺、阿霉素、长春新碱及地塞米松（CHOD）进行化疗，随后进行大体积、高剂量脑部放射治疗（RT）的耐受性及疗效。
54例（52例可评估）人类免疫缺陷病毒（HIV）阴性的PCNSL患者入组本研究，接受了两个周期（n = 20）或三个周期（n = 32）的CHOD化疗（6例脑脊液细胞学检查呈阳性的患者除接受CHOD化疗外，还接受了鞘内注射甲氨蝶呤）。化疗后进行全脑放疗，剂量为41.4 Gy，肿瘤区域加量至18 Gy（总剂量59.4 Gy）。
截至1994年7月，最小潜在随访时间为20个月，52例可评估患者中有12例仍存活且无疾病进展迹象。整个组的中位生存时间为16.1个月，2年生存率为42%。单因素分析发现，患者年龄是生存的一个显著预后因素（P = .005），年龄小于60岁者生存更有利。卡氏功能状态评分（KPS）具有临界显著性（P = .057）。将RTOG 88 - 06研究中治疗的患者生存率与RTOG 83 - 15研究中单纯接受放疗的患者生存率进行比较，未发现总生存率有差异（P = .53）。51例患者在化疗期间有29例出现4级中性粒细胞减少。化疗期间有2例死亡：1例死于败血症，1例死于肺栓塞。52例患者中有50例在放疗期间的最严重毒性为≤2级。
对于PCNSL患者，放疗前CHOD化疗相较于单纯放疗并不能显著提高生存率。年龄仍然是一个独立于治疗的有力预后因素，在测试替代联合治疗方案时必须予以考虑。
