Efficacy and safety of hypofractionated radiotherapy versus conventional fractionated radiotherapy in diffuse intrinsic pontine glioma: A systematic review and meta-analysis
Abstract
Background: Diffuse intrinsic pontine glioma (DIPG) stands as the predominant type of brainstem glioma. It is characterized by a notably brief median survival period, with the majority of patients experiencing disease progression within six months following radiation therapy. This systematic review and meta-analysis aims to assess the efficacy and safety of hypofractionated radiotherapy (HFRT) compared to conventionally fractionated radiotherapy (CFRT) in DIPG treatment.
Materials and methods: A systematic literature search was conducted in four databases, and relevant studies comparing HFRT and CFRT in DIPG were included. Data were extracted and analyzed for overall survival (OS), progression-free survival (PFS), and treatment-related toxicities. Statistical analysis was performed using random-effects models with heterogeneity assessment.
Results: Five studies met the inclusion criteria, comprising 518 patients. No significant difference in one-year OS was observed between HFRT and CFRT (29% vs. 22%, p = 0.94). The median OS was similar in both treatment groups (9.7 vs. 9.3 months, p = 0.324). Similarly, no significant difference in one-year PFS was found between HFRT and CFRT (19.8% vs. 16.6%, p = 0.82), with comparable median PFS (9.3 vs. 9.4 months, p = 0.20). In meta-regression analysis, there was no association of chemotherapy (p > 0.05) or radiation biologically effective dose (BED) (p > 0.05) regarding OS or PFS outcomes. There were no significant differences in treatment-related toxicities.
Conclusions: HFRT yields one-year OS and PFS rates similar to CFRT in DIPG, with no significant differences in treatment-related toxicities. Chemotherapy and BED did not affect OS or PFS.
Keywords: diffuse intrinsic pontine gliomahypofractionated radiotherapyoverall survivalprogression-free survivaltreatment-related toxicities
References
- Guillamo JS, Doz F, Delattre JY. Brain stem gliomas. Curr Opin Neurol. 2001; 14(6): 711–715.
- Wummer B, Woodworth D, Flores C. Brain stem gliomas and current landscape. J Neurooncol. 2021; 151(1): 21–28.
- Epstein F, Constantini S. Practical decisions in the treatment of pediatric brain stem tumors. Pediatr Neurosurg. 1996; 24(1): 24–34.
- Massimino M, Spreafico F, Biassoni V, et al. Diffuse pontine gliomas in children: changing strategies, changing results? A mono-institutional 20-year experience. J Neurooncol. 2008; 87(3): 355–361.
- Korones DN, Fisher PG, Kretschmar C, et al. Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer. 2008; 50(2): 227–230.
- Janssens GO, Gidding CEM, Van Lindert EJ, et al. The role of hypofractionation radiotherapy for diffuse intrinsic brainstem glioma in children: a pilot study. Int J Radiat Oncol Biol Phys. 2009; 73(3): 722–726.
- Page MJ, McKenzie JE, Bossuyt PM, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol. 2021; 134(3): 103–112.
- Brooke BS, Schwartz TA, Pawlik TM. MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. JAMA Surg. 2021; 156(8): 787–788.
- Higgins JPT, Altman DG, Gøtzsche PC, et al. Cochrane Bias Methods Group, Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928.
- Cochrane Handbook for Systematic Reviews of Interventions. Version 6.4, 2023. https://training.cochrane.org/handbook/ (30 Oct 2023.).
- Janssens GO, Jansen MH, Lauwers SJ, et al. Hypofractionation vs conventional radiation therapy for newly diagnosed diffuse intrinsic pontine glioma: a matched-cohort analysis. Int J Radiat Oncol Biol Phys. 2013; 85(2): 315–320.
- Zaghloul MS, Eldebawy E, Ahmed S, et al. Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): a randomized controlled trial. Radiother Oncol. 2014; 111(1): 35–40.
- Hayashi A, Ito E, Omura M, et al. Hypofractionated radiotherapy in children with diffuse intrinsic pontine glioma. Pediatr Int. 2020; 62(1): 47–51.
- Izzuddeen Y, Gupta S, Haresh KP, et al. Hypofractionated radiotherapy with temozolomide in diffuse intrinsic pontine gliomas: a randomized controlled trial. J Neurooncol. 2020; 146(1): 91–95.
- Zaghloul MS, Nasr A, Tolba M, et al. Hypofractionated Radiation Therapy For Diffuse Intrinsic Pontine Glioma: A Noninferiority Randomized Study Including 253 Children. Int J Radiat Oncol Biol Phys. 2022; 113(2): 360–368.
- Park J, Yea JiW, Park JW. Hypofractionated radiotherapy versus conventional radiotherapy for diffuse intrinsic pontine glioma: A systematic review and meta-analysis. Medicine (Baltimore). 2020; 99(42): e22721.
- Hargrave D, Bartels U, Bouffet E. Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol. 2006; 7(3): 241–248.
- Korones DN, Fisher PG, Kretschmar C, et al. Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer. 2008; 50(2): 227–230.
- Massimino M, Spreafico F, Biassoni V, et al. Diffuse pontine gliomas in children: changing strategies, changing results? A mono-institutional 20-year experience. J Neurooncol. 2008; 87(3): 355–361.
- Cohen KJ, Heideman RL, Zhou T, et al. Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group. Neuro Oncol. 2011; 13(4): 410–416.
- Bailey S, Howman A, Wheatley K, et al. Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy--results of a United Kingdom phase II trial (CNS 2007 04). Eur J Cancer. 2013; 49(18): 3856–3862.
- Sirachainan N, Pakakasama S, Visudithbhan A, et al. Concurrent radiotherapy with temozolomide followed by adjuvant temozolomide and cis-retinoic acid in children with diffuse intrinsic pontine glioma. Neuro Oncol. 2008; 10(4): 577–582.
- Cury FL, Viani GA, Gouveia AG, et al. Sequential or concomitant chemotherapy with hypofractionated radiotherapy for locally advanced non-small cell lung cancer: a meta-analysis of randomized trials. J Thorac Dis. 2021; 13(11): 6272–6282.
- Zubizarreta EH, Fidarova E, Healy B, et al. Need for radiotherapy in low and middle income countries – the silent crisis continues. Clin Oncol (R Coll Radiol). 2015; 27(2): 107–114.
- Atun R, Jaffray DA, Barton MB, et al. Expanding global access to radiotherapy. Lancet Oncol. 2015; 16(10): 1153–1186.
- Hanna SA, Gouveia AG, Moraes FY, et al. Lessons from the Brazilian radiotherapy expansion plan: A project database study. Lancet. 2022: 100333.
- Viani GA, Gouveia AG, Bratti VF, et al. Prioritising locations for radiotherapy equipment in Brazil: a cross-sectional, population-based study and development of a LINAC shortage index. Lancet Oncol. 2022; 23(4): 531–539.
- Mendez LC, Moraes FY, Fernandes GD, et al. Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System. Clin Oncol (R Coll Radiol). 2018; 30(1): e29–e36.
- Starling MT, Thibodeau S, de Sousa CF, et al. Optimizing Clinical Implementation of Hypofractionation: Comprehensive Evidence Synthesis and Practical Guidelines for Low- and Middle-Income Settings. Cancers (Basel). 2024; 16(3).
- Mendez LC, Raziee H, Davidson M, et al. Should we embrace hypofractionated radiotherapy for cervical cancer? A technical note on management during the COVID-19 pandemic. Radiother Oncol. 2020; 148: 270–273.
- Yan M, Gouveia AG, Cury FL, et al. Practical considerations for prostate hypofractionation in the developing world. Nat Rev Urol. 2021; 18(11): 669–685.
- Viani GA, Gouveia AG, Moraes FY. Sequential or concomitant chemotherapy with hypofractionated radiotherapy for locally advanced non-small cell lung cancer: a meta-analysis of randomized trials. J Thorac Dis. 2021; 13(11): 6272–6282.
- Viani GA, Gouveia AG, Jacinto AA, et al. Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis. Am J Clin Oncol. 2021; 44(11): 553–558.
- Viani GA, Gouveia AG, Moraes FY, et al. Once daily (OD) versus twice-daily (BID) chemoradiation for limited stage small cell lung cancer (LS-SCLC): A meta-analysis of randomized clinical trials. Radiother Oncol. 2022; 173: 41–48.
- Viani GA, Gouveia AG, Leite ET, et al. Moderate hypofractionation for salvage radiotherapy (HYPO-SRT) in patients with biochemical recurrence after prostatectomy: A cohort study with meta-analysis. Radiother Oncol. 2022; 171: 7–13.
- Viani GA, Gouveia AG, Moraes FY, et al. Meta-analysis of Elective Pelvic Nodal Irradiation Using Moderate Hypofractionation for High-Risk Prostate Cancer. Int J Radiat Oncol Biol Phys. 2022; 113(5): 1044–1053.