PMID- 24495592 OWN - NLM STAT- MEDLINE DCOM- 20140424 LR - 20181202 IS - 1879-355X (Electronic) IS - 0360-3016 (Linking) VI - 88 IP - 4 DP - 2014 Mar 15 TI - Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma. PG - 793-800 LID - S0360-3016(13)03667-5 [pii] LID - 10.1016/j.ijrobp.2013.12.011 [doi] AB - PURPOSE/OBJECTIVES: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m(2)/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m(2)/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. RESULTS: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. CONCLUSIONS: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Iuchi, Toshihiko AU - Iuchi T AD - Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan. Electronic address: tiuchi@chiba-c.jp. FAU - Hatano, Kazuo AU - Hatano K AD - Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan. FAU - Kodama, Takashi AU - Kodama T AD - Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan. FAU - Sakaida, Tsukasa AU - Sakaida T AD - Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan. FAU - Yokoi, Sana AU - Yokoi S AD - Division of Gene Diagnosis, Chiba Cancer Center, Chiba, Japan. FAU - Kawasaki, Koichiro AU - Kawasaki K AD - Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan. FAU - Hasegawa, Yuzo AU - Hasegawa Y AD - Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan. FAU - Hara, Ryusuke AU - Hara R AD - Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140201 PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (Antineoplastic Agents, Alkylating) RN - 7GR28W0FJI (Dacarbazine) RN - YF1K15M17Y (Temozolomide) SB - IM MH - Antineoplastic Agents, Alkylating/*administration & dosage/adverse effects MH - Brain/pathology/radiation effects MH - Brain Neoplasms/drug therapy/mortality/*radiotherapy/surgery MH - Cause of Death MH - Chemotherapy, Adjuvant MH - Dacarbazine/administration & dosage/adverse effects/*analogs & derivatives MH - Disease-Free Survival MH - Dose Fractionation, Radiation MH - Drug Administration Schedule MH - Female MH - Glioblastoma/drug therapy/mortality/*radiotherapy/surgery MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Necrosis/mortality/pathology MH - Neoplasm, Residual MH - Prospective Studies MH - Radiation Injuries/mortality/pathology MH - Radiotherapy, Intensity-Modulated/adverse effects/*methods/mortality MH - Temozolomide EDAT- 2014/02/06 06:00 MHDA- 2014/04/25 06:00 CRDT- 2014/02/06 06:00 PHST- 2013/09/14 00:00 [received] PHST- 2013/12/05 00:00 [revised] PHST- 2013/12/10 00:00 [accepted] PHST- 2014/02/06 06:00 [entrez] PHST- 2014/02/06 06:00 [pubmed] PHST- 2014/04/25 06:00 [medline] AID - S0360-3016(13)03667-5 [pii] AID - 10.1016/j.ijrobp.2013.12.011 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):793-800. doi: 10.1016/j.ijrobp.2013.12.011. Epub 2014 Feb 1.