Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide
Abstract
:1. Introduction
2. Materials and Methods
3. Results
Prognostic Factors for OS and PFS
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number of Patients | 25 | ||
Sex | |||
Male | 18 | (72%) | |
Female | 7 | (28%) | |
Age | |||
Median (range) in years | 65 | (37–82) | |
<60 years | 5 | (20%) | |
60–65 years | 11 | (44%) | |
>65 years | 9 | (36%) | |
KPS Score | |||
Median (range), in % | 60 | (50–90) | |
<60% | 5 | (20%) | |
60–70% | 16 | (64%) | |
>70% | 4 | (16%) | |
RPA Class | |||
Median (range) | V | (IV–VI) | |
IV | 7 | (28%) | |
V | 10 | (40%) | |
VI | 8 | (32%) | |
CCI | |||
Median (range) | 8 | (5–14) | |
<7 | 6 | (24%) | |
7–9 | 18 | (72%) | |
>9 | 2 | (4%) | |
Mass Effect | |||
Yes | 15 | (60%) | |
No | 10 | (40%) | |
Surgery | |||
Complete | 3 | (12%) | |
Incomplete | 12 | (48%) | |
Unresectable (biopsy) | 10 | (40%) | |
Multifocal Tumor | |||
Yes | 7 | (28%) | |
No | 18 | (72%) | |
Poor Molecular Factors | |||
wild-type IDH | 25 | (100%) | |
Unmethylated MGMT | 19 | (76%) | |
Gross Tumor Volume | |||
Median (range), in cc | 50 | (31–135) | |
≤50 cc | 16 | (64%) | |
>50 cc | 9 | (36%) | |
Planning Target Volume | |||
Median (range), in cc | 220 | (117–358) | |
≤200 cc | 12 | (48%) | |
>200 cc | 13 | (52%) |
Variable | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95%CI | p | HR | 95%CI | p | |
Sex | 1.23 | 0.3–2.3 | 0.7 | - | - | - |
Age (≥65 years) | 1.622 | 0.48–5.38 | 0.04 | 2.88 | 0.72–11.43 | 0.1 |
KPS (≤60%) | 0.42 | 0.05–3.32 | 0.4 | - | - | - |
RPA (≥ V) | 1.78 | 0.37–8.38 | 0.04 | 0.19 | 0.01–2.78 | 0.2 |
CCI (≥8) | 1.201 | 0.34–4.17 | 0.7 | - | - | - |
Mass effect (yes) | 1.51 | 0.39–5.81 | 0.5 | - | - | - |
Multifocal tumor (yes) | 1.92 | 0.56–6.61 | 0.02 | 2.95 | 0.51–16.98 | 0.2 |
Surgery (yes) | 0.82 | 0.24–2.73 | 0.7 | - | - | - |
Resection (incomplete) | 2.29 | 0.04–6.43 | 0.01 | 0.96 | 0.16–5.78 | 0.9 |
MGMT methylation (absent) | 0.25 | 0.03–2.02 | 0.04 | 0.61 | 0.02–13.66 | 0.05 |
GTV (>50 cc) | 5.208 | 1.37–19.71 | 0.01 | 4.83 | 0.83–27.88 | 0.01 |
PTV (>200 cc) | 0.29 | 0.08–1.06 | 0.06 | 2.14 | 0.01–9.87 | 0.02 |
Variable | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
Sex | 0.81 | 0.27–2.39 | 0.7 | - | - | - |
Age (≥65 years) | 0.77 | 0.28–2.14 | 0.6 | - | - | - |
KPS (≤60%) | 0.89 | 0.25–3.17 | 0.8 | - | - | - |
RPA (≥ V) | 0.83 | 0.28–2.48 | 0.7 | - | - | - |
CCI (≥8) | 0.95 | 0.35–2.54 | 0.9 | - | - | - |
Mass effect (yes) | 1.47 | 0.05–4.23 | 0.04 | 1.32 | 0.29–5.97 | 0.7 |
Multifocal tumor (yes) | 1.38 | 0.04–6.72 | 0.04 | 1.76 | 0.31–8.12 | 0.05 |
Surgery (yes) | 1.76 | 0.02–3.04 | 0.05 | 1.32 | o.18–3.27 | 0.7 |
Resection (incomplete) | 2.96 | 0.3–22.42 | 0.02 | 2.91 | 0.31–27.07 | 0.01 |
MGMT methylation (absent) | 1.99 | 0.04–4.06 | 0.06 | 0.79 | 0.11–6.25 | 0.03 |
GTV (>50 cc) | 0.82 | 0.31–2.24 | 0.7 | - | - | - |
PTV (>200 cc) | 1.95 | 0.04–3.74 | 0.06 | 1.99 | 0.26–5.37 | 0.05 |
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. |
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Gregucci, F.; Surgo, A.; Bonaparte, I.; Laera, L.; Ciliberti, M.P.; Carbonara, R.; Gentile, M.A.; Giraldi, D.; Calbi, R.; Caliandro, M.; et al. Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide. J. Pers. Med. 2021, 11, 1145. https://doi.org/10.3390/jpm11111145
Gregucci F, Surgo A, Bonaparte I, Laera L, Ciliberti MP, Carbonara R, Gentile MA, Giraldi D, Calbi R, Caliandro M, et al. Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide. Journal of Personalized Medicine. 2021; 11(11):1145. https://doi.org/10.3390/jpm11111145
Chicago/Turabian StyleGregucci, Fabiana, Alessia Surgo, Ilaria Bonaparte, Letizia Laera, Maria Paola Ciliberti, Roberta Carbonara, Maria Annunziata Gentile, David Giraldi, Roberto Calbi, Morena Caliandro, and et al. 2021. "Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide" Journal of Personalized Medicine 11, no. 11: 1145. https://doi.org/10.3390/jpm11111145