del Charco J O, Bolek T W, McCollough W M, Maria B L, Kedar A, Braylan R C, Mickle J P, Buatti J M, Mendenhall N P, Marcus R B
Department of Radiation Oncology, University of Florida College of Medicine, Gainesville 32610-0385, USA.
Int J Radiat Oncol Biol Phys. 1998 Aug 1;42(1):147-54. doi: 10.1016/s0360-3016(98)00197-7.
Time-dose relationships have proven important in many cancer sites. This study evaluates the time factors involved in the successful postoperative radiotherapy of medulloblastoma, based on a 30-year experience in a single institution.
Fifty-three patients with medulloblastoma received postoperative craniospinal radiotherapy with curative intent between 1963 and 1993. Seven patients (13%) underwent biopsy alone, 28 patients (53%) had subtotal excision, and 18 patients (34%) had gross total excision. Eleven patients received adjuvant chemotherapy. The mean posterior fossa dose was 53.1 Gy; most patients received 54.0 Gy (range, 34.3 to 69.6 Gy). For 41 patients receiving once-a-day therapy, the mean dose was 50.6 Gy (range, 34.3 to 56.0 Gy). For 12 patients receiving twice-a-day therapy, the mean dose was 61.8 Gy (range, 52.6 to 69.6 Gy). Minimum follow-up was 2 years, and median follow-up was 10.7 years. Survival, freedom from relapse, and disease control in the posterior fossa were calculated using the Kaplan-Meier method, and multivariate analysis was performed for prognostic factors. Variables related to radiotherapy were examined, including dose to the craniospinal axis, dose to the posterior fossa, fractionation (once-a-day vs. twice-a-day), use of adjuvant chemotherapy, risk group [high (> or =T3b or > or =M1) or low (< or =T3a and M0-MX)], interval between surgery and radiotherapy (excluding patients receiving chemotherapy before radiotherapy), and duration of radiotherapy.
At 5 and 10 years, overall survival rates were 68 and 64%, respectively, and freedom-from-relapse rates were 61 and 52%, respectively. Rates of disease control in the posterior fossa at 5 and 10 years were 79 and 68%, respectively. At 5 years, absolute survival rates after biopsy alone, subtotal excision, and gross total excision were 43, 67, and 78%, respectively (p=0.04), and posterior fossa control rates were 27, 89, and 83%, respectively (p=0.004). Duration of the treatment course was the only radiotherapy-related variable with a significant impact on freedom from relapse and posterior fossa control. For patients whose radiation treatment duration was < or =45 days, posterior fossa control was 89% at 5 years, compared with 68% for those treated for >45 days (p=0.01). Duration of treatment also affected freedom from relapse at 5 years: < or =45 days (76%) compared with >45 days (43%), p=0.004.
Our study demonstrates that if adequate doses are used, then radiotherapy treatment duration will significantly affect the outcome in terms of control of disease in the posterior fossa and freedom from relapse. Fractions of at least 1.75 Gy given once a day, or a twice-a-day regimen should yield optimal local control results.
时间 - 剂量关系在许多癌症部位已被证明很重要。本研究基于单一机构30年的经验，评估髓母细胞瘤术后放疗成功所涉及的时间因素。
1963年至1993年间，53例髓母细胞瘤患者接受了旨在治愈的术后颅脊髓放疗。7例患者（13%）仅接受活检，28例患者（53%）行次全切除，18例患者（34%）行全切除。11例患者接受辅助化疗。后颅窝平均剂量为53.1 Gy；大多数患者接受54.0 Gy（范围34.3至69.6 Gy）。对于41例接受每日一次治疗的患者，平均剂量为50.6 Gy（范围34.3至56.0 Gy）。对于12例接受每日两次治疗的患者，平均剂量为61.8 Gy（范围52.6至69.6 Gy）。最短随访时间为2年，中位随访时间为10.7年。采用Kaplan - Meier方法计算生存率、无复发生存率以及后颅窝疾病控制率，并对预后因素进行多因素分析。检查了与放疗相关的变量，包括颅脊髓轴剂量、后颅窝剂量、分割方式（每日一次与每日两次）、辅助化疗的使用、风险组[高（≥T3b或≥M1）或低（≤T3a且M0 - MX）]、手术与放疗之间的间隔（不包括放疗前接受化疗的患者）以及放疗持续时间。
5年和10年时，总生存率分别为68%和%，无复发生存率分别为61%和52%。后颅窝疾病控制率在5年和10年时分别为79%和68%。5年时，仅接受活检、次全切除和全切除后的绝对生存率分别为43%、67%和78%（p = 0.04），后颅窝控制率分别为27%、89%和83%（p = 0.004）。治疗疗程持续时间是唯一对无复发生存率和后颅窝控制有显著影响的放疗相关变量。对于放疗持续时间≤45天的患者，5年后颅窝控制率为89%，而治疗时间>45天的患者为68%（p = 0.01）。治疗持续时间也影响5年时的无复发生存率：≤45天（76%）对比>45天（43%），p = 0.004。
我们的研究表明，如果使用足够的剂量，放疗治疗持续时间将在后颅窝疾病控制和无复发生存方面显著影响治疗结果。每日一次给予至少1.75 Gy的分次剂量，或每日两次的方案应能产生最佳的局部控制效果。
