Brain and brain stem necrosis after reirradiation for recurrent childhood primary central nervous system tumors: A PENTEC comprehensive review Review
| Authors: | Ajithkumar, T.; Avanzo, M.; Yorke, E.; Tsang, D. S.; Milano, M. T.; Olch, A. J.; Merchant, T. E.; Dieckmann, K.; Mahajan, A.; Fuji, H.; Paulino, A. C.; Timmermann, B.; Marks, L. B.; Bentzen, S. M.; Jackson, A.; Constine, L. S. |
| Review Title: | Brain and brain stem necrosis after reirradiation for recurrent childhood primary central nervous system tumors: A PENTEC comprehensive review |
| Abstract: | Purpose: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation. Methods and Materials: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies. Results: Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD22; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P =.46). Conclusions: Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation. © 2024 Elsevier Inc. |
| Keywords: | adolescent; child; preschool child; child, preschool; primary tumor; young adult; cancer radiotherapy; nuclear magnetic resonance imaging; follow up; glioma; cell death; neoplasm recurrence, local; incidence; pathology; radiation injury; necrosis; risk factor; central nervous system tumor; childhood cancer; radiation response; central nervous system neoplasms; brain; tumors; systematic review; tumor recurrence; medulloblastoma; radiation injuries; recurrent disease; ependymoma; central nervous systems; tumor growth; patient treatment; regression analysis; germ cell tumor; normal tissue; brain necrosis; brain stem; radiation necrosis; qualitative analysis; neurophysiology; cumulative incidence; latent period; reirradiation; young adults; re-irradiation; task force; dose volume histogram; pontine glioma; methods and materials; humans; human; article; x-ray computed tomography; preferred reporting items for systematic reviews and meta-analyses; literature search; children and adolescents; brain stem necrosis |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 119 |
| Issue: | 2 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-06-01 |
| Start Page: | 655 |
| End Page: | 668 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2023.12.043 |
| PUBMED: | 38300187 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work