Table 4.
Literature review of studies regarding elderly/frail patients with high-grade gliomas and treated with hypofractionated RT.
| Author/Publication Year | Study Years | Study Type | Patient Selection | Comparison | No. of Patients | RT Schedule | Median PFS | Median OS | Toxicities |
|---|---|---|---|---|---|---|---|---|---|
| Phillips et al. 2003 [9] |
1990–1996 | Randomized Phase III |
Age > 45 y ECOG 0–3 |
Hypo-RT Standard RT |
32 36 |
35 Gy/10 fx (WB) 60 Gy/30 fx |
NS | 8.7 months 10.3 months |
None |
| Roa et al. 2004 [11] |
1996–2001 | Randomized Phase III |
Age ≥ 60 y KPS ≥ 50 |
Hypo-RT Standard RT |
48 47 |
40 Gy/15 fx 60 Gy/30 fx |
NS | 5.6 months 5.1 months |
NS |
| Malmström et al. 2012 [12] |
2000–2009 | Randomized Phase III |
Age ≥ 60 y ECOG 0–2 | TMZ Hypo-RT Standard RT |
93 98 100 |
NA 34 Gy/10 fx 60 Gy/30 fx |
NS | 8.3 months 7.5 months 6 months |
No G > 3 acute toxicity |
| Roa et al. 2015 [18] |
2010–2013 | Randomized Phase III |
Age ≥ 65 y KPS 50–70 |
Hypo-RT Hypo-RT |
48 50 |
25 Gy/5 fx 40 Gy/15 fx |
4.2 months 4.2 months |
7.9 months 6.4 months |
No G > 3 acute toxicity |
| Guedes de Castro et al. 2017 [19] |
NS | Randomized Phase III |
Age ≥ 65 y KPS 50–70 |
Hypo-RT Hypo-RT |
26 35 |
25 Gy/5 fx 40 Gy/15 fx |
4.3 months 3.2 months |
6.8 months 6.2 months |
No G > 3 acute toxicity |
| Perry et al. 2017 [16] |
2007–2013 | Randomized Phase III |
Age ≥ 65 y ECOG 0–2 | Hypo-RT + TMZ Hypo-RT |
281 281 |
40 Gy/15 fx | 5.3 months 3.9 months |
9.3 months 7.6 months |
No G > 3 acute toxicity |
| Pedretti et al. 2019 [24] |
2010–2015 | Randomized Phase II |
RPA Class 5 or 6 | Hypo-RT alone TMZ alone |
14 17 |
30 Gy/6 fx over 2 weeks | 3.8 months | 6.3 months | No G > 3 acute toxicity |
| Bauman et al. 1994 [27] |
1990–1992 | Prospective | Age ≥ 65 y KPS ≤ 50 |
Hypo-RT | 29 | 30 Gy/10 fx (WB) | NS | 6 months | NS |
| Thomas et al. 1994 [29] |
1991–1993 | Prospective | KPS ≤ 50 or Age 55–70 y KPS 50–70 or Age ≥ 70 y |
Hypo-RT | 38 | 30 Gy/6 fx over 2 weeks | NS | 6 months | None |
| Hulshof et al. 2000 [19] |
1988–1998 | Prospective | Age ≥ 65 y MRC ≥ 2 | Hypo-RT Hypo-RT Standard RT |
48 41 66 |
28 Gy/4 fx 40 Gy/8 fx 66 Gy/33 fx |
NS | 6.6 months 5.6 months 7 months |
Mild; No difference between groups |
| Minniti et al. 2009 [21] |
2002–2006 | Prospective | Age ≥ 70 y KPS ≥ 60 |
Hypo-RT + adj TMZ |
43 | 30 Gy/6 fx over 2 weeks | 6.3 months | 9.3 months | 8 patients presented neurological deterioration (Grade 2/3 confusion and/or somnolence). 12 patients had Grade 3/4 hematological toxic effects |
| Omuro et al. 2014 [26] |
NS | Prospective | Age ≥ 18 years (median 55 y) KPS ≥ 70 (median 90) Partial resection or biopsy (75%) |
Hypo-RT + TMZ + BEV | 40 | 30 Gy/6 fx over 2 weeks | 10 months | 19 months | None |
| Navarria et al. 2019 [17] |
2013–2016 | Prospective | Age ≥ 70 y KPS ≤ 60 |
Hypo-RT | 30 | 52.5 Gy/15 fx | 5 months | 8 months | No severe acute or late neurologic toxicity was recorded |
| McAleese et al. 2003 [8] |
1991–1999 | Retrospective | KPS ≤ 50 or Age 50–70 y KPS 50–90 or Age ≥ 70 y |
Hypo-RT | 92 | 30 Gy/6 fx over 2 weeks | NS | 5 months | NS |
| Chang et al. 2003 [10] |
1988–2001 | Retrospective | RPA Class ≥ 4 | Hypo-RT | 59 | 50 Gy/20 fx | 3.9 months | 7 months | 3 patients showed radio-necrosis |
| Minniti el al. 2015 [23] |
2004–2013 | Retrospective | Age ≥ 65 y KPS ≥ 60 |
Hypo-RT + TMZ Standard RT + TMZ |
116 127 |
40 Gy/15 fx 59.4–60 Gy/30–33 fx |
6.7 months 5.6 months |
12.5 months 12 months |
28 patients receiving standard RT and 11 subjected to short-course RT had acute worsening of neurologic status. 20 patients receiving standard RT and 3 patients receiving short-course RT had late neurologic deterioration (G2–3 cognitive disability) G3–4 thrombocytopenia and lymphocytopenia were seen in 24 patients and 51 patients. G3 neutropenia developed in 14 patients, and 10 patients displayed G3 anemia |
| Jablonska et al. 2019 [15] |
2010–2017 | Retrospective | RPA Class ≥ 4 | Hypo-RT with SIB + TMZ | 17 | 50–45–40 Gy/15 fx | 7 months | 7 months | No acute G3–5 toxicities were observed. Radio-necrosis occurred in 1 patient. |
| Present study | 2019–2021 | Retrospective | Poor prognosis RPA Class ≥ 4 |
Hypo-RT with SIB + TMZ | 25 | 52.5–40 Gy/15 fx | 8.4 months | 13 months | No acute or late neurological side effects of grade ≥ 2 were reported. No cases of radio-necrosis. Grade 3–4 hematologic toxicity occurred in 3 cases. |
KPS, Karnofsky performance status; ECOG, Eastern Cooperative Oncology Group; MRC, Medical Research Council scale; RPA, recursive partitioning analysis; y, years; fx, fractions; TMZ, temozolomide; BEV, bevacizumab; WB, whole brain; SIB, simultaneous integrated boost; NA, not applicable; NS, not specified.