Online first
Research paper
Published online: 2024-06-03

open access

Page views 44
Article views/downloads 23
Get Citation

Connect on Social Media

Connect on Social Media

Efficacy and safety of hypofractionated radiotherapy versus conventional fractionated radiotherapy in diffuse intrinsic pontine glioma: A systematic review and meta-analysis

Gustavo Viani12, Andre Guimaraes Gouveia32, Fabio Arcidiacono4, Gustavo Nader Marta526, Ana Carolina Hamamura1, Paola Anselmo4, Felipe S. Barbosa1, Fabio Y. Moraes72

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.

Article available in PDF format

View PDF Download PDF file

References

  1. Guillamo JS, Doz F, Delattre JY. Brain stem gliomas. Curr Opin Neurol. 2001; 14(6): 711–715.
  2. Wummer B, Woodworth D, Flores C. Brain stem gliomas and current landscape. J Neurooncol. 2021; 151(1): 21–28.
  3. Epstein F, Constantini S. Practical decisions in the treatment of pediatric brain stem tumors. Pediatr Neurosurg. 1996; 24(1): 24–34.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Brooke BS, Schwartz TA, Pawlik TM. MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. JAMA Surg. 2021; 156(8): 787–788.
  9. 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.
  10. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.4, 2023. https://training.cochrane.org/handbook/ (30 Oct 2023.).
  11. 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.
  12. 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.
  13. Hayashi A, Ito E, Omura M, et al. Hypofractionated radiotherapy in children with diffuse intrinsic pontine glioma. Pediatr Int. 2020; 62(1): 47–51.
  14. 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.
  15. 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.
  16. 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.
  17. Hargrave D, Bartels U, Bouffet E. Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol. 2006; 7(3): 241–248.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Atun R, Jaffray DA, Barton MB, et al. Expanding global access to radiotherapy. Lancet Oncol. 2015; 16(10): 1153–1186.
  26. Hanna SA, Gouveia AG, Moraes FY, et al. Lessons from the Brazilian radiotherapy expansion plan: A project database study. Lancet. 2022: 100333.
  27. 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.
  28. 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.
  29. 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).
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.



Reports of Practical Oncology and Radiotherapy