Table 1.
The basic information of included studies for systematic review and meta-analysis.
| Study | Year | Study Design | Cases | HFR dose | Systemic therapy with HFR | Median followed-up (M) | Median OS | Median PFS | Toxicity, QOL, and neurocognitive function |
|---|---|---|---|---|---|---|---|---|---|
| Navarria et al. (15) | 2018 | Phase II | 30 | 3.5 Gy ×15 | CAAT | 8 M | 8 M | 5 M | The neurologic status remained stable, Grade 2–3 fatigue was observed in 3 patients. |
| Shenouda et al. (22) | 2016 | Phase II | 3 Gy ×20 | Neo-adjuvant TMZ and CAAT | 44 M | 22.3 M | 13.7 M | Grade 5 pancytopenia occurred in one patient, Grade 4 hepatic toxicity was observed in one patient,Grade 3 toxicities consisted of fatigue in 4, nausea and vomiting in 3, and electrolytes imbalances in 3 patients. | |
| Mallick et al. (23) | 2018 | Phase II RCT | 89 | 3 Gy ×20 vs. 2 Gy ×30 | CAAT | 11.4 M | 25.18 vs. 18.07 M | The entire cohort was 13.5 M | Only two patients required hospital admission for features of raised intracranial tension. One patient in the HFR arm required treatment interruption. |
| Malmstrom et al. (24) | 2012 | Phase III,RCT | 342 | 3.4 Gy ×10 vs. 2 Gy ×30 vs. TMZ | - | 6 M | 7.5 M vs. 6.0 M vs. 8.3 M | - | Nausea and vomiting and hematological toxic effects were more frequently seen in patients treated with TMZ than in those treated with radiotherapy. Grade 3–5 infections were similar among patients in each group. |
| Phillips et al. (25) | 2003 | Phase II RCT | 68 | 3.5 Gy ×10 vs. 2 Gy ×30 | - | 2-monthly | OS:8.7 M vs. 10.3 M | Similar to OS | No late toxicity. No formal QOL comparison was possible as only 30% of patients completed a form. |
| Roa et al. (26) | 2004 | RCT, Phase III | 95 | 2.67 Gy ×15 vs. 2 Gy ×30 | - | - | 5.6 vs. 5.1 M | - | Karnofsky performance status were similar. The rate of Functional Assessment of Cancer Therapy-Brain were too low to performed a meaning comparison. |
| Floyd et al. (27) | 2004 | Phase II | 18 | 5 Gy ×10 | - | Every 3 M | 7 M | 6 M | Three patients with brain necrosis (16.7%). |
| Reddy et al. (28, 29) | 2012 | Phase II | 24 | 6 Gy ×10 | CAAT | 14.8 M | 16.6 M | - | Significant improvement in insomnia, future uncertainty, motor dysfunction, and drowsiness. Significant worsening was observed in cognitive functioning, social functioning, appetite loss and communication deficit. |
| Hulshof et al. (30) | 2000 | Phase II | 155 | 5 ×8 vs. 2 Gy ×33 7 Gy ×4 |
- | - | 5.6 M vs. 7 M vs. 6.6 M | - | No toxicity were observed. |
| Omuro et al. (31) | 2014 | Phase II | 40 | 6 Gy ×6 | CAAT | 42 M | 19 M | 10 M | The QOL and neuropsychological test scores were stable. |
| Roa et al. (32) | 2015 | RCT, Phase III | 98 | 5 Gy ×5 vs. 2.67 Gy ×15 | - | 6.3 M | 7.9 vs. 6.4 M | 4.2 vs. 4.2 M | the QOL between both arms at 4 weeks after treatment and 8 weeks after treatment was similar. |
| Perry et al. (33) | 2017 | RCT, Phase III | 562 | 2.67 Gy ×15 alone/plus CAAT | CAAT | 17 M | 7.6 vs. 9.3 M | 3.9 M vs. 5.3 M | QOL was similar in the two groups |
| Minniti et al. (34) | 2012 | Phase II | 71 | 2.67 Gy ×15 | CAAT | - | 12.4 M | 6 M | Four patients was worsening of their neurologic status. Grade 3 fatigue in 4 patients and cognitive disability in 1 patient. |
| Ney et al. (35) | 2015 | Phase II | 30 | 6 Gy ×10 | Combined with TMZ and BEV | 15.9 M | 16.3 M | 14.3 M | cranial wound dehiscence/infection in two patients, sepsis in one patient and sudden death from a presumed seizure in one patient. |
| Iuchi et al. (36) | 2014 | Phase II | 37 | 8.5 Gy ×8 | CAAT | 16.3 M | 20 M | - | Radiation necrosis was diagnosed in 20 patients (54.1%). |
| Scoccianti et al. (37) | 2017 | Phase II | 24 | 4.5 Gy ×15 | CAAT | Every 3 M | 15.1 M | 8.6 M | Three patients (12.5%) had Grade 3 myelotoxicity, One patient had radionecrosis (4.2%). |
BEV, bevacizumab; CAAT, concurrent and adjuvant temozolomide. HFR, Hypofractionated radiotherapy; M, months; OS, overall survival; PFS, progression free survival; QOL, quality of life; RCT, randomized controlled trial; TMZ, temozolomide.