Floyd Nathan S, Woo Shiao Y, Teh Bin S, Prado Charlotte, Mai Wei-Yuan, Trask Todd, Gildenberg Philip L, Holoye Paul, Augspurger Mark E, Carpenter L Steven, Lu Hsin H, Chiu J Kam, Grant Walter H, Butler E Brian
Department of Radiology, Section of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA.
Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):721-6. doi: 10.1016/S0360-3016(03)01623-7.
A pilot study was designed to evaluate the safety and efficacy of a novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the study was to combine the potential radiobiologic advantage of hypofractionation to GBM with a highly conformal radiotherapeutic technique. The study was designed to measure the acute and chronic morbidity of patients treated with this regimen, response of GBM to the treatment, overall survival, and time to disease progression after therapy completion.
Twenty eligible patients were accrued between February 1999 and May 2000 for the study. All patients had Karnofsky performance scores of >/=70. All patients were treated with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease, residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy daily fractions to surrounding edema. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity scores.
Of the 20 patients, 18 were evaluated for outcome. The median time to disease progression was 6 months after RT completion. The median overall survival was 7 months after treatment completion. All recurrences were within 2 cm of the operative bed. Neurotoxicity during therapy was minimal, with all patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity, manifesting as brain necrosis requiring surgical reexcision. The survival of the 3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases was the result of tumor recurrence, with no mortality resulting from brain necrosis.
This regimen of hypofractionated intensity-modulated RT did not improve the time to disease progression or overall survival compared with historical experience using conventional fractionation. However, the treatment duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit in certain subsets of patients. This treatment regimen demonstrated a greater incidence of brain necrosis requiring surgical intervention; however, the 3 patients experiencing this toxicity had longer survival times. Future investigation may be useful to determine which fraction size may be optimal for GBM when highly conformal RT is used in the adjuvant setting.
开展一项初步研究，以评估一种新型大分割调强放射治疗（RT）方案在多形性胶质母细胞瘤（GBM）辅助治疗中的安全性和有效性。该研究的基本原理是将大分割对GBM的潜在放射生物学优势与高度适形的放射治疗技术相结合。本研究旨在测量接受该方案治疗患者的急性和慢性发病率、GBM对治疗的反应、总生存期以及治疗结束后的疾病进展时间。
1999年2月至2000年5月期间招募了20名符合条件的患者参与本研究。所有患者的卡氏评分均≥70。所有患者均使用NOMOS Peacock系统接受调强放疗。给予增强的原发性疾病、残留肿瘤或手术腔50 Gy剂量，分5 Gy每日剂量，在2周内完成。同时，给予周围水肿30 Gy剂量，分3 Gy每日剂量。放疗结束后，通过系列神经系统检查和MRI或CT扫描测量疾病进展时间。使用放射治疗肿瘤学组神经毒性评分对急性和晚期毒性进行分级。
20名患者中，18名接受了结局评估。放疗结束后疾病进展的中位时间为6个月。治疗结束后的中位总生存期为7个月。所有复发均在手术床2 cm范围内。治疗期间神经毒性最小，所有患者均经历0级或1级毒性。晚期毒性包括10名0级患者、2名2级患者和3名4级患者，表现为需要手术再次切除的脑坏死。3名脑坏死患者的生存期分别为23、20和9个月。所有病例的死亡均由肿瘤复发导致，无因脑坏死导致的死亡。
与使用传统分割的历史经验相比，这种大分割调强放疗方案并未改善疾病进展时间或总生存期。然而，治疗时间从6周缩短至2周，这可能对某些患者亚组具有姑息益处。该治疗方案显示需要手术干预的脑坏死发生率更高；然而，3名出现这种毒性的患者生存期更长。未来的研究可能有助于确定在辅助治疗中使用高度适形放疗时，哪种分割剂量对GBM可能是最佳的。
