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Systematic Review and Meta-Analysis of Adjuvant Radiation Dose for Pediatric Patients (≤22y) with Non-Metastatic Intracranial Ependymomas.

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Title: Systematic Review and Meta-Analysis of Adjuvant Radiation Dose for Pediatric Patients (≤22y) with Non-Metastatic Intracranial Ependymomas.
Authors: Rose, M.L.1,2 (AUTHOR), Sachdeva, R.1 (AUTHOR), Mezgueldi, Y.1 (AUTHOR), Yen, R.1,3 (AUTHOR), Serraj, L.1 (AUTHOR), Corbett, K.1,4 (AUTHOR), Yock, T.I.5 (AUTHOR)
Source: International Journal of Radiation Oncology, Biology, Physics. 2024 Supplement, Vol. 120 Issue 2, pe712-e713. 2p.
Subjects: Child patients, Tumors in children, Radiation doses, Brain tumors, Overall survival, Ependymoma, Central nervous system cancer
Abstract: Ependymomas are the third most common brain tumors in children. The current standard of care for curative intent treatment is maximal safe resection followed by adjuvant radiotherapy. Controversy in the literature still exists over optimal radiotherapy dose. The most important prognostic factor for these tumors is the extent of resection followed by the addition of adjuvant radiotherapy. We completed a systematic review and meta-analysis of the available literature to determine the optimal radiotherapy dose regarding outcomes, including local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients (≤22y). We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science from inception to January 2024. We included cohort studies that compared adjuvant radiotherapy doses of ≤54Gy to >54Gy in pediatric patients (≤22y) with non-metastatic intracranial ependymomas treated with curative intent therapy. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We quantitatively pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and statistical heterogeneity via I2. When HRs were unavailable, we transformed 3-year risks using established methods. We narratively summarized qualitative outcomes. Seven cohort studies met our inclusion criteria, covering a combined 1321 pediatric patients. Studies included a range of doses from 45-66.6Gy. Compared with patients receiving adjuvant radiotherapy dose of >54Gy, we found no difference in LC for those receiving ≤54Gy (HR = 0.83, 95% CI = 0.56-1.24, I2 = 49.1%), in EFS (HR = 1.02, 95% CI = 0.95-1.09, I2 = 0.00%), and OS (HR = 0.99, 95% CI = 0.82-1.20, I2 = 37.5%). Three studies methodically placed younger children in the lower dose cohorts due to concerns of late-effects of therapy. Two studies reported on the extent of resection by radiotherapy dose, with neither study reporting a statistical difference in LC, EFS, or OS, though the number of patients included in each study analysis was small (n≤30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequently reported toxicities. Toxicities were not reported in relation to the specific doses of radiotherapy received. Overall study quality was high, though lower scores were consistently seen in the comparability of cohorts. We found no difference in LC, EFS, or OS for those treated with ≤54Gy compared to >54Gy. Many of the children who were in the lower dose cohorts were younger in age, a group with historically worse outcomes, which may artificially increase rates of relapse, events, and mortality. There was insufficient data to complete a subgroup meta-analysis on radiotherapy dosing based on the extent of resection or molecular subgroups, an important question for future research. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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  Data: Systematic Review and Meta-Analysis of Adjuvant Radiation Dose for Pediatric Patients (≤22y) with Non-Metastatic Intracranial Ependymomas.
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  Data: <searchLink fieldCode="AR" term="%22Rose%2C+M%2EL%2E%22">Rose, M.L.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sachdeva%2C+R%2E%22">Sachdeva, R.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mezgueldi%2C+Y%2E%22">Mezgueldi, Y.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yen%2C+R%2E%22">Yen, R.</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Serraj%2C+L%2E%22">Serraj, L.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Corbett%2C+K%2E%22">Corbett, K.</searchLink><relatesTo>1,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yock%2C+T%2EI%2E%22">Yock, T.I.</searchLink><relatesTo>5</relatesTo> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Radiation+Oncology%2C+Biology%2C+Physics%22">International Journal of Radiation Oncology, Biology, Physics</searchLink>. 2024 Supplement, Vol. 120 Issue 2, pe712-e713. 2p.
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  Data: <searchLink fieldCode="DE" term="%22Child+patients%22">Child patients</searchLink><br /><searchLink fieldCode="DE" term="%22Tumors+in+children%22">Tumors in children</searchLink><br /><searchLink fieldCode="DE" term="%22Radiation+doses%22">Radiation doses</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+tumors%22">Brain tumors</searchLink><br /><searchLink fieldCode="DE" term="%22Overall+survival%22">Overall survival</searchLink><br /><searchLink fieldCode="DE" term="%22Ependymoma%22">Ependymoma</searchLink><br /><searchLink fieldCode="DE" term="%22Central+nervous+system+cancer%22">Central nervous system cancer</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Ependymomas are the third most common brain tumors in children. The current standard of care for curative intent treatment is maximal safe resection followed by adjuvant radiotherapy. Controversy in the literature still exists over optimal radiotherapy dose. The most important prognostic factor for these tumors is the extent of resection followed by the addition of adjuvant radiotherapy. We completed a systematic review and meta-analysis of the available literature to determine the optimal radiotherapy dose regarding outcomes, including local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients (≤22y). We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science from inception to January 2024. We included cohort studies that compared adjuvant radiotherapy doses of ≤54Gy to >54Gy in pediatric patients (≤22y) with non-metastatic intracranial ependymomas treated with curative intent therapy. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We quantitatively pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and statistical heterogeneity via I2. When HRs were unavailable, we transformed 3-year risks using established methods. We narratively summarized qualitative outcomes. Seven cohort studies met our inclusion criteria, covering a combined 1321 pediatric patients. Studies included a range of doses from 45-66.6Gy. Compared with patients receiving adjuvant radiotherapy dose of >54Gy, we found no difference in LC for those receiving ≤54Gy (HR = 0.83, 95% CI = 0.56-1.24, I2 = 49.1%), in EFS (HR = 1.02, 95% CI = 0.95-1.09, I2 = 0.00%), and OS (HR = 0.99, 95% CI = 0.82-1.20, I2 = 37.5%). Three studies methodically placed younger children in the lower dose cohorts due to concerns of late-effects of therapy. Two studies reported on the extent of resection by radiotherapy dose, with neither study reporting a statistical difference in LC, EFS, or OS, though the number of patients included in each study analysis was small (n≤30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequently reported toxicities. Toxicities were not reported in relation to the specific doses of radiotherapy received. Overall study quality was high, though lower scores were consistently seen in the comparability of cohorts. We found no difference in LC, EFS, or OS for those treated with ≤54Gy compared to >54Gy. Many of the children who were in the lower dose cohorts were younger in age, a group with historically worse outcomes, which may artificially increase rates of relapse, events, and mortality. There was insufficient data to complete a subgroup meta-analysis on radiotherapy dosing based on the extent of resection or molecular subgroups, an important question for future research. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Group: Ab
  Data: <i>Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.ijrobp.2024.07.1565
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        Text: English
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        StartPage: e712
    Subjects:
      – SubjectFull: Child patients
        Type: general
      – SubjectFull: Tumors in children
        Type: general
      – SubjectFull: Radiation doses
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      – SubjectFull: Brain tumors
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      – SubjectFull: Overall survival
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      – SubjectFull: Ependymoma
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      – SubjectFull: Central nervous system cancer
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      – TitleFull: Systematic Review and Meta-Analysis of Adjuvant Radiation Dose for Pediatric Patients (≤22y) with Non-Metastatic Intracranial Ependymomas.
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