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Year : 2018  |  Volume : 14  |  Issue : 7  |  Page : 1482-1491

Treatment of high-grade gliomas using escalating doses of hypofractionated simultaneous integrated boost-intensity-modulated radiation therapy in combination with temozolomide: A modified Phase I clinical trial

1 Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
2 Department of Oncology, North China Petroleum Bureau General Hospital, Hebei Medical University, Renqiu, China
3 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China

Correspondence Address:
Xiaoying Xue
Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_51_18

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Background: Recent studies have shown that hypofractionated simultaneous integrated boost-intensity-modulated radiation therapy (SIB-IMRT) provided certain survival benefits over other fractionation methods for high-grade gliomas. However, the best hypofractionation mode and its efficacy have not been confirmed. The purpose of this study was to investigate the maximum tolerated dose (MTD) of hypofractionated SIB-IMRT with stepwise escalating doses combined with temozolomide (TMZ) for treating malignant gliomas. Methods: The patients received concurrent postoperative radiotherapy and chemotherapy. SIB-IMRT was adopted to increase the dose both in the surgical cavity and residual tumor (planning target volume 1). The dose at each fraction was gradually increased from 2.8 Gy/f (total of 20 times), with an escalating dose interval of 0.4 Gy. The planning target volume 2 involved the 2 cm region around surgical cavity, and residual tumor remained unchanged, with 2.5 Gy each time and a total of 50 Gy/20f. TMZ was administered with a dose of 75 mg/m2/day during radiotherapy. Adjuvant TMZ was given at 150–200 mg/m2/day for 5 days every 28 days. A total of 16 patients were enrolled. Results: Three patients exhibited dose-limiting toxicity (DLT), two cases reported Grade 3 headache in the 3.6 Gy/f and 4 Gy/f dose groups, and one patient developed persistent seizures attacks in the 4 Gy/f dose group. Therefore, 4 Gy/f was considered the DLT and the lower dose level of 3.6 Gy/f was regarded as the MTD in the study, with tolerable adverse reactions. The median overall survival (OS) and median progression-free survival (PFS) in this study were 19 and 16 months, respectively. The 1- and 2-year OS and PFS were 86.7%, 31.0% and 73.7%, 26.7%, respectively. Conclusions: It showed that the treatment of high-grade gliomas with hypofractionated SIB-IMRT combined with TMZ had an MTD of 3.6 Gy/f (72 Gy/20f). In addition, the results preliminarily showed improved survival.

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