Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)

Raj Singh; Andrew Koempel; Beck French; Casey Crawford; Haley K. Perlow; Sophie Rauh; Tugce Kutuk; Sasha Beyer; John Grecula; Dukagjin Blakaj; Simeng Zhu; Raju R. Raval; Rupesh Kotecha; William C. Chen; David R. Raleigh; Kelsey M. Frechette; Eric J. Lehrer; Rushmin Khazanchi; Rahul K. Chaliparambil; Nishanth S. Sadagopan; Alexander Ho; Mark W. Youngblood; Sean Sachdev; Stephen T. Magill; Laura Burgess; Maximilian Y. Deng; Juergen Debus; Laila König; Arjun Sahgal; Joshua D. Palmer

doi:10.1016/j.ijrobp.2026.03.036

Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)

Raj Singh
, Andrew Koempel
, Beck French
, Casey Crawford
, Haley K. Perlow
, Sophie Rauh
, Tugce Kutuk
, Sasha Beyer
, John Grecula
, Dukagjin Blakaj
, Simeng Zhu
, Raju R. Raval
, Rupesh Kotecha
, William C. Chen
, David R. Raleigh
, Kelsey M. Frechette
, Eric J. Lehrer
, Rushmin Khazanchi
, Rahul K. Chaliparambil
, Nishanth S. Sadagopan

Alexander Ho, Mark W. Youngblood, Sean Sachdev, Stephen T. Magill, Laura Burgess, Maximilian Y. Deng, Juergen Debus, Laila König, Arjun Sahgal, Joshua D. Palmer

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose: We performed an individual patient–level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT). Methods and Materials: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT. Results: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%). Conclusions: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.

Original language	English
Journal	International Journal of Radiation Oncology Biology Physics
DOIs	https://doi.org/10.1016/j.ijrobp.2026.03.036
State	Accepted/In press - 2026
Externally published	Yes

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Singh, R., Koempel, A., French, B., Crawford, C., Perlow, H. K., Rauh, S., Kutuk, T., Beyer, S., Grecula, J., Blakaj, D., Zhu, S., Raval, R. R., Kotecha, R., Chen, W. C., Raleigh, D. R., Frechette, K. M., Lehrer, E. J., Khazanchi, R., Chaliparambil, R. K., ... Palmer, J. D. (Accepted/In press). Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM). International Journal of Radiation Oncology Biology Physics. https://doi.org/10.1016/j.ijrobp.2026.03.036

@article{cf7cbbcb90a74d51a0fdc84872098f2f,

title = "Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)",

abstract = "Purpose: We performed an individual patient–level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT). Methods and Materials: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT. Results: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8\%) were World Health Organization grade 2, and 103 cases (41.5\%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2\%). Three- and 5-year PFS rates were 62.8\% (95\% CI, 55.8\%-69.0\%) and 45.0\% (95\% CI, 37.3\%-52.3\%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4\% vs 55.6\%) and 5-year (65.8\% vs 38.8\%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95\% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95\% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9\%) versus SD-RT (25 of 189; 13.2\%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1\% vs SD-RT 3.2\%). Conclusions: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.",

author = "Raj Singh and Andrew Koempel and Beck French and Casey Crawford and Perlow, \{Haley K.\} and Sophie Rauh and Tugce Kutuk and Sasha Beyer and John Grecula and Dukagjin Blakaj and Simeng Zhu and Raval, \{Raju R.\} and Rupesh Kotecha and Chen, \{William C.\} and Raleigh, \{David R.\} and Frechette, \{Kelsey M.\} and Lehrer, \{Eric J.\} and Rushmin Khazanchi and Chaliparambil, \{Rahul K.\} and Sadagopan, \{Nishanth S.\} and Alexander Ho and Youngblood, \{Mark W.\} and Sean Sachdev and Magill, \{Stephen T.\} and Laura Burgess and Deng, \{Maximilian Y.\} and Juergen Debus and Laila K{\"o}nig and Arjun Sahgal and Palmer, \{Joshua D.\}",

note = "Publisher Copyright: {\textcopyright} 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.",

year = "2026",

doi = "10.1016/j.ijrobp.2026.03.036",

language = "English",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier Inc.",

}

Singh, R, Koempel, A, French, B, Crawford, C, Perlow, HK, Rauh, S, Kutuk, T, Beyer, S, Grecula, J, Blakaj, D, Zhu, S, Raval, RR, Kotecha, R, Chen, WC, Raleigh, DR, Frechette, KM, Lehrer, EJ, Khazanchi, R, Chaliparambil, RK, Sadagopan, NS, Ho, A, Youngblood, MW, Sachdev, S, Magill, ST, Burgess, L, Deng, MY, Debus, J, König, L, Sahgal, A & Palmer, JD 2026, 'Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)', International Journal of Radiation Oncology Biology Physics. https://doi.org/10.1016/j.ijrobp.2026.03.036

Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM). / Singh, Raj; Koempel, Andrew; French, Beck et al.
In: International Journal of Radiation Oncology Biology Physics, 2026.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas

T2 - An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)

AU - Singh, Raj

AU - Koempel, Andrew

AU - French, Beck

AU - Crawford, Casey

AU - Perlow, Haley K.

AU - Rauh, Sophie

AU - Kutuk, Tugce

AU - Beyer, Sasha

AU - Grecula, John

AU - Blakaj, Dukagjin

AU - Zhu, Simeng

AU - Raval, Raju R.

AU - Kotecha, Rupesh

AU - Chen, William C.

AU - Raleigh, David R.

AU - Frechette, Kelsey M.

AU - Lehrer, Eric J.

AU - Khazanchi, Rushmin

AU - Chaliparambil, Rahul K.

AU - Sadagopan, Nishanth S.

AU - Ho, Alexander

AU - Youngblood, Mark W.

AU - Sachdev, Sean

AU - Magill, Stephen T.

AU - Burgess, Laura

AU - Deng, Maximilian Y.

AU - Debus, Juergen

AU - König, Laila

AU - Sahgal, Arjun

AU - Palmer, Joshua D.

PY - 2026

Y1 - 2026

N2 - Purpose: We performed an individual patient–level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT). Methods and Materials: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT. Results: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%). Conclusions: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.

AB - Purpose: We performed an individual patient–level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT). Methods and Materials: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT. Results: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%). Conclusions: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.

UR - https://www.scopus.com/pages/publications/105036421960

U2 - 10.1016/j.ijrobp.2026.03.036

DO - 10.1016/j.ijrobp.2026.03.036

M3 - Article

C2 - 41956162

AN - SCOPUS:105036421960

SN - 0360-3016

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

ER -

Singh R, Koempel A, French B, Crawford C, Perlow HK, Rauh S et al. Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM). International Journal of Radiation Oncology Biology Physics. 2026. doi: 10.1016/j.ijrobp.2026.03.036