Outcomes Following Radiation Therapy for Embryonal Tumor with Multilayered Rosettes (ETMR): Results from the Pediatric Proton/Photon Consortium Registry (PPCR)

Outcomes Following Radiation Therapy for Embryonal Tumor with Multilayered Rosettes (ETMR): Results from the Pediatric Proton/Photon Consortium Registry (PPCR) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Outcomes Following Radiation Therapy for Embryonal Tumor with Multilayered Rosettes (ETMR): Results from the Pediatric Proton/Photon Consortium Registry (PPCR) Jacquelyn M. Krisch, Ralph P. Ermoian, Daniel J. Indelicato, Jae Y. Lee, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6273163/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 May, 2025 Read the published version in Journal of Neuro-Oncology → Version 1 posted 15 You are reading this latest preprint version Abstract Purpose : Embryonal tumor with multilayered rosettes (ETMR) is a rare pediatric CNS embryonal tumor with poor survival. The Pediatric Proton/Photon Consortium Registry (PPCR) was queried for outcomes data from prospectively consenting pediatric patients with ETMR treated with proton radiation therapy (RT). Methods : 20 patients (2013-2021) at 9 institutions had ETMR; 2 with prior RT were excluded from statistical analyses (PPCR ETMR, N=18). Overall Survival (OS) and Event Free Survival (EFS) analyses were performed using the Kaplan-Meier method and log-rank values. Median follow-up was calculated using the reverse Kaplan-Meier method. Results : Median age at RT was 3.0 years (1.7-12.2); median follow-up was 55.5 months (2.6-119.4). 8 patients (44%) expired and 6 patients (33%) are surviving ≥55 months. 11 (61%) patients received systemic therapy with stem cell support. The majority (89%) had focal RT, while 2 patients received craniospinal irradiation (CSI). 4-year OS and EFS were 59.6% and 54.2%, respectively. Local control (LC) at 4 years was 81%. No differences in OS or EFS were observed for receipt of systemic therapy with stem cell support (p=0.361, p=0.57), progression prior to RT (p=0.127, p=0.18), or surgery to RT ≥200 days (p=0.35, p=0.254). Symptomatic radionecrosis was not reported. Conclusion : Focal proton RT provided effective local control as part of multimodality therapy for ETMR, with encouraging survival for this rare and often infant age tumor. Outcomes for CSI were limited to 2 patients treated upfront, and 1 patient receiving salvage CSI for disseminated relapse after focal RT who is surviving >1 year. Trial: DFCI protocol 12-103, clinicaltrials.gov NCT01696721, date of registration 9/27/2012 Pediatric Proton Radiation ETMR Cancer Figures Figure 1 Figure 2 Figure 3 Introduction Embryonal tumor with multilayered rosettes (ETMR) is a rare and aggressive central nervous system (CNS) tumor affecting young children. First described by Eberhart in 2000 as embryonal tumors with abundant neuropil and true rosettes (ETANR), ETANTR, ependymoblastoma (EBL), and medulloepithelioma (MEPL) have since been shown to represent three variants of rosette-forming neuroepithelial CNS tumors within the single classification of ETMR [ 1 – 3 ]. Molecular characteristics include amplification of the oncogenic miRNA C19MC , positive immunoreactivity for the tumorigenic protein LIN28A, and DICER1 mutation [ 4 – 10 ]. The 2016 WHO Classification of Tumors of the CNS first recognized ETMR as a new diagnostic category, with subsequent update in 2021 to include the DICER1 alteration was updated in 2021 to include ETMR with the DICER1 mutation [ 8 – 10 ]. There exist limited epidemiological and survival data for ETMR, given both the rarity of disease and relatively recent diagnostic WHO classification [ 11 ]. A recent large cohort study of 159 patients with molecular-confirmed ETMR diagnosis from the Rare Brain Tumor clinical registry showed an overall survival (OS) of just 29% at 2 years. Multiple reports have supported the use of RT for improved outcomes [ 12 – 14 ] however only a handful of patients (often 5 or less) receive RT. As ETMR is an aggressive disease with poor prognosis and lacking definitive treatment guidelines, further information is needed to estimate outcomes according to treatment received. In this series, we investigated clinical outcomes following RT on patients prospectively enrolled on the Proton Photon Consortium Registry (PPCR). Materials and Methods Patient Selection From 2012–2021, all 20 ETMR patients enrolled on PPCR were included from 9 centers that included Massachusetts General Hospital, Washington University, University of Florida, University of Washington, ProCure Proton Therapy Center NJ, Mayo Clinic, Oklahoma Protons, Cincinnati Children’s Hospital Medical Center, and California Protons. Data analysis and outcome reporting were limited to patients who did not have prior radiation at the time of enrollment (N = 18). The mission of the PPCR, as well as the methodology for data collection, have been previously reported [ 15 ]. Patient, disease, and treatment characteristics were submitted prospectively and informed consent was obtained for all patients prior to registration. This series queried the PPCR regarding extent of surgery, disease stage (M0 or M+), chemotherapy given, RT dose, RT volume including focal, CSI, or boost, and disease progression. Statistical Analyses Study data were collected and managed using REDCap electronic data capture tools hosted at Massachusetts General Hospital. All follow-up disease control endpoints are measured from the start date of radiotherapy. The follow-up data cutoff date was August 13, 2024. An event was defined as a local recurrence, distant recurrence, second malignancy, or death from any cause. Median follow up time was estimated using the reverse Kaplan-Meier method. We estimated EFS and OS using the Kaplan-Meier method. Hazard ratios between groups were estimated using univariate Cox proportional hazard ratio model and p values were calibrated by Wald method. All analysis were performed using R Statistical Software (v4.1.2) at a statistical significance level of alpha = 0.05[ 16 ]. Given the sample size available for analysis, no multivariate Cox models were performed to remove potential confounding associated with observed significance. Results Patient characteristics A total of 18 patients comprised the ETMR PPCR cohort with patient characteristics summarized in Table 1 . Two patients were excluded due to prior radiation. The median follow-up is 55.5 months (range 2.6-119.4). Median age at the time of radiation was 3.0 years (1.7–12.2). A gross total resection was achieved upfront in 12 (67%) patients, near total resection in 4 (22%) patients, and subtotal resection in 2 (11%) patients. All patients had M0 disease. 10 (56%) patients were treated with chemotherapy, with chemotherapy sequencing prior to RT in 14 (78%) patients; prior and during in 2 (11%) patients; during and after in 2 (11%) patients; or prior, during, and after in 2 (11%) patients. Table 1 Patient Characteristics. a n(%). GTR: Gross Total Resection, NTR: Near Total Resection, STR: Subtotal Resection, RT: Radiotherapy, CSI: Craniospinal Irradiation Characteristic N = 18 a Follow-up (months) Median (min-max) 55.5 (2.6-119.4) Gender Male 8 (44%) Female 10 (56%) Tumor Location Supratentorial 15 (83%) Infratentorial 3 (17%) Extent of Surgery GTR 12 (67%) NTR 4 (22%) STR 2 (11%) M Stage M0 18 (100%) Radiation Target Focal RT 16 (89%) CSI 2 (11%) Chemotherapy with Stem Cell Rescue Yes 11 No 7 Age at RT (years) Median (min-max) 3.0 (1.7–12.2) Primary RT dose (Gy) Median (min-max) 54 (53-57.6) CSI dose (Gy) 30.6 (1 patient) or 36 (1 patient) Long term survival > 55 months 6 (33%) RT details RT details according to field and dose are summarized in Table 2 . Focal RT was provided for 16 (89%) patients, with the remaining 2 (11%) patients receiving CSI plus boost. The most common primary RT dose was 54 Gy (89%). In the two patients receiving CSI, the doses were 30.6 Gy or 36Gy with 54Gy primary boost. Table 2 Individual Patient, Tumor, and Treatment Details Patient Sex Location Surgery Protocol Age at RT, yrs Time to RT, mos PD Prior (Y/N) CSI dose (Gy*) Primary Tumor dose (Gy*) Failure (N/Y, Location, Time in mos Last status OS from RT, mos 1 F S STR ACNS 0332 9.7 119.4 N 55.8 N A 119.4 2 F S NTR DFCI 02-294⁺ 3.6 81.8 N 54 N A 81.9 3 M S GTR DFCI 02-294⁺ 2.3 38.1 Y 57.6 Y, Distant 10.6 E 38.1 4 F S GTR ETMR One⁺ 2.9 9.1 N 54 Y, Distant 2.8 E 9.1 5 M S GTR ACNS 0334 3.4 2.6 N 30.6 23.4 Y, Local & Distant 2.1 E 2.6 6 M S GTR Other 2.7 26.9 N 54 Y, Local 6.0 E 26.9 7 M I GTR ACNS 0333 1.7 101.7 N 54 N A 101.7 8 M S GTR Other 12.2 25.9 N 36 18 N A 25.9 9 M S STR Other 3.3 65.7 N 54 N A 65.7 10 F S NTR ACNS 0334 2.5 71.8 Y 54 N^ E 73.7 11 F S NTR Other 5.6 34.3 N 54 Y, Distant 18.3 A 34.3 12 F I GTR Head Start IV 1.9 2.6 Y 54 N E 2.6 13 F S GTR ACNS 0333* 4.1 45.2 N 54 N A 45.2 14 M I NTR Head Start IV 2.4 7.0 N 54 Y, Local & Distant 6.1 E 7.0 15 F S GTR ACNS 0334 3.1 5.8 Y 54 N E 5.8 16 F S GTR DFCI 02-294⁺ 2.4 55.5 N 54 N A 55.4 17 M S GTR Head Start IV 5.9 45.0 Y 53 N A 45.0 18 F S GTR Head Start IV 2.7 49.1 N 54 N A 49.1 S: supratentorial, I: infratentorial, GTR: gross total resection, NTR: near total resection, STR: subtotal resection, A: alive, E: expired, mos: months, yrs: years, ACNS0332: Children’s Oncology Group ACNS0332[ 17 ], DFCI 02-294: Dana Farber Cancer Institute 02-294[ 18 ], ETMR One: ClinicalTrials.gov ID NCT04794686, ACNS0334: Children’s Oncology Group ACNS0334 ClinicalTrials.gov ID NCT00336024, ACNS0333: Children’s Oncology Group ACNS0333[ 19 ], Head Start IV: ClinicalTrials.gov ID NCT02875314 IMPT: intensity modulated proton therapy; 3DCRT: three dimensional conformal radiation therapy * Indicates GyRBE ⁺ Indicates intrathecal chemotherapy ^: Second malignancy, high grade glioma, occurred at 71 months Outcomes Median follow-up for all patients was 55.5 months (range 2.6-119.4). Of all 18 patients, 8 expired (44%). No patients were considered lost to follow-up as the maximum time from last follow-up to the data cut off was 20 months for surviving patients. Recurrence occurred in 6 (33%) patients; 1 was local only, 3 distant only, and 2 patients had combined local and distant failure. All but one relapse occurred within 2 years of RT. When comparing relapses to RT field, 16 patients had focal RT and 5 relapsed (1 local only, 3 distant only, 1 combined local and distant). 2 patients had CSI with 1 experiencing combined local and distant failure. One patient developed a second malignancy of high grade glioma at 71 months following RT and ultimately expired at 73.7 months. The 2- and 4-year overall survival (OS) were 72.2% and 59.6%, respectively (Fig. 1 ). Outcomes of EFS and OS are summarized in Table 3 . Local control (LC) at 4 years was 81% (Fig. 2 a). Distant control at 4 years was 68.1% (Fig. 2 b). The 4-year OS for focal RT was 61.9% and for CSI was 50% (p = 0.307). GTR was not associated with improved OS (4-year OS GTR 75%, NTR/STR 55.6%, p = 0.910) or EFS (4-year EFS GTR 75%, NTR/STR 83.6%, p = 0.811, Fig. 3 a). One patient received salvage CSI (36Gy plus metastatic boost to 54Gy) for a disseminated relapse that occurred 18.7 months after focal RT. This patient is surviving at last follow-up (16 months after salvage CSI). Table 3 Local Control (LC), Event Free Survival (EFS), and Overall Survival (OS) at 2- and 4- Years According to Patient and Treatment Characteristics Characteristic N 2-year / 4-year EFS p-value 2-year / 4-year OS p-value Entire cohort 18 72.2% / 54.2% 72.2% / 59.6% Local Control 18 81% / 81% Distant Control 18 68.1% / 68.1% RT volume 0.621 0.307 Focal RT 16 56.2% /5 6.2% 75% / 61.9% CSI 2 50% / 50% 50% / 50% Surgical Extent 0.811 0.91 GTR 12 75% / 75% 75% / 75% NTR&STR 6 83.6% / 83.6% 71.4% / 55.6% HDCT 0.621 0.307 Yes 10 50% / 50% 50% / 50% No 8 56.2% / 56.2% 75% / 61.9% Stem cell rescue Yes 11 63.6% / 63.6% 0.570 72.7% / 72.7% 0.361 No 7 42.9% / 42.9% 71.4% / 35.7% Surgery to RT 0.254 0.350 ≤ 200 days 10 70% / 70% 90% / 67.5% >200 days 9 37.5% / 37.5% 50% / 50% Progression prior to RT 0.180 0.127 Yes 5 40.0% / 40.0% 60.0% / 40% No 13 61.5% / 61.5% 76.9% / 68.4% Of six patients (32%) with gross disease pre-RT, all had 54Gy focal RT and 4 are alive at follow up. The median time from surgery to RT start was 186 days. The 4-year EFS for surgery to RT time > 200 days was 37.5%, and 4-year OS was 50%; the 4-year EFS for surgery to RT time ≤ 200 days was 70%, and 2-year OS was 67.5% (Fig. 3 b). All 8 patients with a surgery to RT time > 200 days received chemotherapy exclusively prior to RT. There was no difference in OS comparing patients who received chemotherapy with stem cell rescue (SCR) as compared to those who did not (Fig. 3 c). The 4-year OS (p = 0.361) and EFS (p = 0.57) for chemotherapy with SCR was 72.7% and 63.6%, respectively compared to 35.7% and 42.9%, respectively. Patients who experienced progression prior to RT had a 4-year OS of 40% compared to 68.4% in those without progression (p = 0.127, Fig. 3 d). There were 6 patients who received focal RT without high dose chemotherapy: 2 expired (1 received multiple repeat RT courses) and 3 are alive without relapse, including 1 of which is surviving 15.2 months after salvage CSI (36Gy plus metastatic site boost) for disseminated only relapse. Proton beam radiation for ETMR was safe and well-tolerated. There were no PPCR ETMR patients with reported radionecrosis and radiation brainstem injury, which was confirmed directly with the treating physicians. Neurologic symptoms (n = 12) that were reported during the course of therapy (including pre-treatment) included seizure, cerebellar symptoms (gait, coordination), speech impairment, cranial nerve deficits, and weakness. Further details include: 5 patients with symptoms have subsequently died of disease progression including 2 with cranial nerve involvement, 5 patients were known to have neurologic symptoms prior to RT and are alive without recurrence, and 2 additional patients developed neurologic symptoms in an unknown time frame and are alive without recurrence. Two patients were excluded from data analysis due to prior RT. Both patients had focal reirradiation (re-RT) after enrollment on PPCR. Patient 1 (prior RT and surgical details unknown) received 54Gy focal IMPT re-RT for an infratentorial primary and expired 4.6 months after re-RT. This patient received salvage chemotherapy with etoposide, temozolomide, and topotecan. Patient 2 (initial surgical extent GTR with prior RT of 45Gy focal RT) received 36Gy focal re-RT for a supratentorial primary and expired 9.2 months following re-RT. This patient received high dose chemotherapy with stem cell support before RT, along with chemotherapy during and after RT following COG ACNS0334. Discussion ETMR is a rare and aggressive brain tumor occurring typically in young children under 3 years old, with treatment consisting of surgery, systemic chemotherapy, and variable inclusion of RT [ 9 , 11 ]. There is limited available clinical outcome data and no standard treatment for ETMR, thus guidance is lacking for how to include RT into treatment regimens. We report RT for ETMR on the PPCR was consisted of focal RT in 89% of patients and was associated with favorable primary site disease control (4-year LC of 81%). The 4-year EFS (59.6%) and OS (54.2%) are similar or higher to reported database studies however, these did not uniformly employ RT. This series (PPCR ETMR) builds on prior literature detailing ETMR treatment with further details analyzed specific to RT [ 12 , 13 ]. Survival outcomes for ETMR are limited by very small patient numbers due to extreme tumor rarity, and the impact of RT has been inconsistent across different investigations [ 11 – 14 , 20 – 26 ]. There is a certainly a concern for neurocognitive impact due to very young patient age [ 11 , 20 , 25 , 27 , 28 ]. In the present series that largely favored focal RT (89%), proton beam RT was given for all patients to optimally spare developing brain tissue from low or medium dose RT exposure. Our data support continued incorporation and investigation of focal RT in treatment protocols for ETMR. With long-term follow-up (median 55.5 months) on PPCR ETMR, 8 of 18 patients expired. There was 1 local-only failure and 3 distant-only failures seen among 16 patients receiving focal RT, suggesting efficacy for RT with primary site disease control in ETMR. It remains unknown from PPCR ETMR whether the 3 distant-only failures following focal RT would be improved with CSI, and 2 of these patients were under 3 (2.3 and 2.9 years old) at the time of RT. Long term survival of greater than or equal to 55 months occurred in 6 patients. Of these, 2 had GTR, 2 had NTR, and 2 had STR. All patients received focal RT, and 5 patients received intensive chemotherapy that included stem cell rescue. Long-term survival in ETMR seems to be more common when RT is employed [ 12 , 13 ]. Jaramillo reported results of a literature search of ETMR identifying 208 cases reported and only 18 long-term survivors alive ≥ 36 months. Of 18 long term survivors, 14 had CSI, 1 received focal RT, 2 had RT details unknown, and only 1 did not receive RT. In contrast, a Rare Brain Tumor Registry study reported long-term survival (defined ≥ 24 months) in 21 patients with molecular-confirmed diagnosis of ETMR and 9 (43%) had received focal RT. CSI use was not reported in the long-term survival cohort, and use of RT overall was associated with improved OS on multivariate analysis. In a recent multi-institutional retrospective review of 49 ETMR patients who received adjuvant therapy, only 14 received upfront RT [ 14 ]. Notably, relapse or progression occurred in 34 of 35 (97%) RT-naïve patients, 5 of 10 patients who received CSI (50%), and in 1 of 4 patients (25%) who received focal RT. A multi-institutional review of clinical trials SJYC07 and SJMB03 from St. Jude’s Children’s Research Hospital report of 28 ETMR patients reported only 5 (18%) long term survivors. There was variable use of focal RT (13 patients, 46%), CSI (5 patients, 18%), RT avoidance (8 patients, 29%), or palliative treatment (2 patients, 7.1%). Four of 5 survivors received RT without specification of RT field [ 21 ]. The German-led P-HIT trial experience adds further support for inclusion of RT with ETMR, in a combined patient analysis of the P-HIT trial, the HIT2000-interim-registry, and previously enrolled patients. Long term survival of at least 3.0 years was reported in 9/35 patients: RT was either CSI (4 patients), focal RT (2 patients), or not given (3 patients). All 4 patients who received adjuvant RT after completion of carboplatin and etoposide induction followed by high dose chemotherapy exhibited long-term survival. Notably, RT was not found to be as an independent prognostic factor for OS. Herein, we report the largest cohort published to our knowledge of ETMR where all patients received RT and outcomes according to RT variable were analyzed. Focal RT (88%) predominated, and 2 patients received CSI. We did not find progression prior to RT, RT timing from surgery to RT start, extent of surgery, and choice of chemotherapy to be statistically significant for OS or EFS. The sample size while including 18 patients with upfront RT and a median follow-up of 55 months, is a study limitation for statistical analyses. While patients were enrolled prospectively on the PPCR protocol, the delivery of RT (dose, technique, target) was at the discretion of the treating physician and therefore not uniform. As expected for ETMR which is known to have a predilection for local recurrence as well as primarily affecting very young patients, only 2 patients had CSI. This prohibits any investigation into the efficacy of craniospinal radiation for lowering the risk of distant recurrence. Of 3 patients who received focal RT but developed distant only failure, only one patient was age > 3 where CSI can typically be considered. The PPCR registry includes a heterogenous patient population with regard to chemotherapy protocols followed (Supplementary Table 1). This is particularly apparent with ETMR, where due to very rare nature of this disease there is no current consensus for optimal chemotherapy protocol [ 29 ]. Any potential differences in patient outcomes according to systemic therapy regimen were not able to be studied due to several common regimens used within the 18 patient study cohort. Neurocognitive injury and necrosis following brain RT in pediatric patients poses a therapeutic challenge. The use of proton versus photon therapy has been studied extensively in the pediatric population, with the advantage of proton radiation in potentially reducing both dose volumes and mean dose henceforth lessening long term cognitive and endocrine effects [ 30 – 32 ]. Furthermore, proton therapy spares adjacent normal tissue while maintaining therapeutic dose to target volumes [ 33 , 34 ]. Focal RT offers a large advantage for mean brain dose and volume, of which both are associated with neurocognitive effects including a below-average intelligence quotient [ 31 ]. This is particularly true for the youngest age patient population of infant brain tumors. In the PPCR ETMR cohort, no cases of brainstem injury or radionecrosis were reported and proton beam RT was well-tolerated. Data was unavailable for detailing the neurocognitive impact of proton beam RT in the PPCR ETMR cohort. One patient unfortunately experienced a radiation induced high grade glioma 71 months following RT and expired at 73 months. While incredibly rare, RT induced high grade gliomas typically occur after a long latency period averaging 14 ± 8 years and are associated with very poor outcomes [ 35 ]. Exciting future directions include the awaited results from the currently enrolling ETMR One protocol, which also includes an accompanying multi-institutional database (clinicaltrials.gov ID NCT04794686). Patients are treated on a uniform chemotherapy regimen that includes intrathecal chemotherapy, concurrent temozolamide during RT, and high-dose chemotherapy with autologous stem cell rescue. Patients receive 54Gy focal RT, however for patients age > 3 years old or with M + disease CSI can be considered at the discretion of the treating physician. Data analysis is anticipated after further patient accrual is completed, which will provide the much-needed opportunity to evaluate ETMR outcomes for patients treated under a unified treatment protocol. In this study, we have PPCR outcomes for ETMR patients treated with proton RT. With a median follow-up period of 55 months, the 4-year LC of 81%, 4-year OS of 59.6% ,and 4-year EFS of 54.2% suggest the continued incorporation of focal RT within ETMR treatment protocols is warranted. Utilization of proton RT offers advantages in reducing long term sequelae from RT on the brain and tissues adjacent to the treatment field. Prospective uniform inclusion of RT on ETMR studies, notably ETMR one, is anticipated to provide further evidence of the positive impact of RT for this very rare, aggressive tumor. Declarations Funding : Data for this project was obtained from the multi-center Pediatric Proton and Photon Consortium Registry (PPCR) sponsored by the National Institutes of Health/Massachusetts General Hospital. The PPCR is supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. Competing Interests: Authors 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13 declare they have no competing interests to disclose. Author 12 has received grant funding from Mim Software, received consulting fees from Mevion Medical Advisory Board, and serves on the Proton Collaborative Group Data Safety Monitoring Committee. Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jacquelyn Krisch and Paul Aridgides. Statistical analysis was performed by Dongliang Wang. The first draft of the manuscript was written by Jacquelyn Krisch and Paul Aridgides, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability: The data will be made available upon reasonable request Ethics Approval: Patient, disease, and treatment characteristics were submitted prospectively with Institutional Board Approval (DFCI protocol 12-103, clinicaltrials.gov NCT01696721) Informed Consent : Informed consent was obtained for all patients prior to registration References Korshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DT, Remke M, Northcott P, Perry A, Picard D, Rosenblum M, Antonelli M, Aronica E, Schuller U, Hasselblatt M, Woehrer A, Zheludkova O, Kumirova E, Puget S, Taylor MD, Giangaspero F, Peter Collins V, von Deimling A, Lichter P, Huang A, Pietsch T, Pfister SM, Kool M (2014) Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. 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Neuro Oncol 23: 1597-1611 doi:10.1093/neuonc/noab136 Hess CB, Indelicato DJ, Paulino AC, Hartsell WF, Hill-Kayser CE, Perkins SM, Mahajan A, Laack NN, Ermoian RP, Chang AL, Wolden SL, Mangona VS, Kwok Y, Breneman JC, Perentesis JP, Gallotto SL, Weyman EA, Bajaj BVM, Lawell MP, Yeap BY, Yock TI (2018) An Update From the Pediatric Proton Consortium Registry. Front Oncol 8: 165 doi:10.3389/fonc.2018.00165 Team RC (2021)). R: A language and environment for statistical computing. R Foundation for Statistical Computing. https://www.r-project.org/. Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM (2021) Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol 7: 1313-1321 doi:10.1001/jamaoncol.2021.2224 Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, Rorke-Adams LB, Fisher MJ, Janss A, Mazewski C, Goldman S, Manley PE, Bowers DC, Bendel A, Rubin J, Turner CD, Marcus KJ, Goumnerova L, Ullrich NJ, Kieran MW (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27: 385-389 doi:10.1200/JCO.2008.18.7724 Reddy AT, Strother DR, Judkins AR, Burger PC, Pollack IF, Krailo MD, Buxton AB, Williams-Hughes C, Fouladi M, Mahajan A, Merchant TE, Ho B, Mazewski CM, Lewis VA, Gajjar A, Vezina LG, Booth TN, Parsons KW, Poss VL, Zhou T, Biegel JA, Huang A (2020) Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333. J Clin Oncol 38: 1175-1185 doi:10.1200/JCO.19.01776 Horwitz M, Dufour C, Leblond P, Bourdeaut F, Faure-Conter C, Bertozzi AI, Delisle MB, Palenzuela G, Jouvet A, Scavarda D, Vinchon M, Padovani L, Gaudart J, Branger DF, Andre N (2016) Embryonal tumors with multilayered rosettes in children: the SFCE experience. Childs Nerv Syst 32: 299-305 doi:10.1007/s00381-015-2920-2 Liu APY, Dhanda SK, Lin T, Sioson E, Vasilyeva A, Gudenas B, Tatevossian RG, Jia S, Neale G, Bowers DC, Hassall T, Partap S, Crawford JR, Chintagumpala M, Bouffet E, McCowage G, Broniscer A, Qaddoumi I, Armstrong G, Wright KD, Upadhyaya SA, Vinitsky A, Tinkle CL, Lucas J, Chiang J, Indelicato DJ, Sanders R, Klimo P, Jr., Boop FA, Merchant TE, Ellison DW, Northcott PA, Orr BA, Zhou X, Onar-Thomas A, Gajjar A, Robinson GW (2022) Molecular classification and outcome of children with rare CNS embryonal tumors: results from St. Jude Children's Research Hospital including the multi-center SJYC07 and SJMB03 clinical trials. Acta Neuropathol 144: 733-746 doi:10.1007/s00401-022-02484-7 Gessi M, Giangaspero F, Lauriola L, Gardiman M, Scheithauer BW, Halliday W, Hawkins C, Rosenblum MK, Burger PC, Eberhart CG (2009) Embryonal tumors with abundant neuropil and true rosettes: a distinctive CNS primitive neuroectodermal tumor. Am J Surg Pathol 33: 211-217 doi:10.1097/PAS.0b013e318186235b Alexiou GA, Stefanaki K, Vartholomatos G, Sfakianos G, Prodromou N, Moschovi M (2013) Embryonal tumor with abundant neuropil and true rosettes: a systematic literature review and report of 2 new cases. J Child Neurol 28: 1709-1715 doi:10.1177/0883073812471434 Manjila S, Ray A, Hu Y, Cai DX, Cohen ML, Cohen AR (2011) Embryonal tumors with abundant neuropil and true rosettes: 2 illustrative cases and a review of the literature. Neurosurg Focus 30: E2 doi:10.3171/2010.10.FOCUS10226 Chadda KR, Solano-Paez P, Khan S, Llempen-Lopez M, Phyu P, Horan G, Trotman J, Tarpey P, Erker C, Lindsay H, Addy D, Jacques TS, Allinson K, Pizer B, Huang A, Murray MJ (2023) Embryonal tumor with multilayered rosettes: Overview of diagnosis and therapy. Neurooncol Adv 5: vdad052 doi:10.1093/noajnl/vdad052 Mayr L, Gojo J, Peyrl A, Azizi AA, Stepien NM, Pletschko T, Czech T, Dorfer C, Lambo S, Dieckmann K, Haberler C, Kool M, Slavc I (2020) Potential Importance of Early Focal Radiotherapy Following Gross Total Resection for Long-Term Survival in Children With Embryonal Tumors With Multilayered Rosettes. Front Oncol 10: 584681 doi:10.3389/fonc.2020.584681 Ferri Niguez B, Martinez-Lage JF, Almagro MJ, Fuster JL, Serrano C, Torroba MA, Sola J (2010) Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. Childs Nerv Syst 26: 1003-1008 doi:10.1007/s00381-010-1179-x Antonelli M, Korshunov A, Mastronuzzi A, Diomedi Camassei F, Carai A, Colafati GS, Pfister SM, Kool M, Giangaspero F (2015) Long-term survival in a case of ETANTR with histological features of neuronal maturation after therapy. Virchows Arch 466: 603-607 doi:10.1007/s00428-015-1736-5 Juhnke BO, Gessi M, Gerber NU, Friedrich C, Mynarek M, von Bueren AO, Haberler C, Schuller U, Kortmann RD, Timmermann B, Bison B, Warmuth-Metz M, Kwiecien R, Pfister SM, Spix C, Pietsch T, Kool M, Rutkowski S, von Hoff K (2022) Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial. Neuro Oncol 24: 127-137 doi:10.1093/neuonc/noab100 Merchant TE, Hua CH, Shukla H, Ying X, Nill S, Oelfke U (2008) Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function. Pediatr Blood Cancer 51: 110-117 doi:10.1002/pbc.21530 Mahajan A, Stavinoha PL, Rongthong W, Brodin NP, McGovern SL, El Naqa I, Palmer JD, Vennarini S, Indelicato DJ, Aridgides P, Bowers DC, Kremer L, Ronckers C, Constine L, Avanzo M (2024) Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review. Int J Radiat Oncol Biol Phys 119: 401-416 doi:10.1016/j.ijrobp.2020.11.073 Baliga S, Gandola L, Timmermann B, Gail H, Padovani L, Janssens GO, Yock TI (2021) Brain tumors: Medulloblastoma, ATRT, ependymoma. Pediatr Blood Cancer 68 Suppl 2: e28395 doi:10.1002/pbc.28395 McGovern SL, Okcu MF, Munsell MF, Kumbalasseriyil N, Grosshans DR, McAleer MF, Chintagumpala M, Khatua S, Mahajan A (2014) Outcomes and acute toxicities of proton therapy for pediatric atypical teratoid/rhabdoid tumor of the central nervous system. Int J Radiat Oncol Biol Phys 90: 1143-1152 doi:10.1016/j.ijrobp.2014.08.354 Boehling NS, Grosshans DR, Bluett JB, Palmer MT, Song X, Amos RA, Sahoo N, Meyer JJ, Mahajan A, Woo SY (2012) Dosimetric comparison of three-dimensional conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated radiotherapy for treatment of pediatric craniopharyngiomas. Int J Radiat Oncol Biol Phys 82: 643-652 doi:10.1016/j.ijrobp.2010.11.027 Woo PYM, Lee JWY, Lam SW, Pu JKS, Chan DTM, Mak CHK, Ho JMK, Wong ST, Po YC, Lee MWY, Chan KY, Poon WS (2024) Radiotherapy-induced glioblastoma: distinct differences in overall survival, tumor location, pMGMT methylation and primary tumor epidemiology in Hong Kong chinese patients. Br J Neurosurg 38: 385-392 doi:10.1080/02688697.2021.1881445 Additional Declarations Competing interest reported. Authors J.K., R.E., D.I., J.L., J.P., S.P., N.L., J.C., I.M., S.W., D.W., and P.A. declare they have no competing interests to disclose. Author T.Y. has received grant funding from Mim Software, received consulting fees from Mevion Medical Advisory Board, and serves on the Proton Collaborative Group Data Safety Monitoring Committee. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6273163","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432826187,"identity":"e335f572-832e-4330-b50b-f6471940b2f4","order_by":0,"name":"Jacquelyn M. Krisch","email":"","orcid":"","institution":"SUNY Upstate Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jacquelyn","middleName":"M.","lastName":"Krisch","suffix":""},{"id":432826188,"identity":"e47c16dd-f66f-499a-a7b4-762005ec11c9","order_by":1,"name":"Ralph P. Ermoian","email":"","orcid":"","institution":"University of Washington/ Fred Hutchinson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Ralph","middleName":"P.","lastName":"Ermoian","suffix":""},{"id":432826189,"identity":"1a350187-9206-4969-897b-1217af8e81c2","order_by":2,"name":"Daniel J. Indelicato","email":"","orcid":"","institution":"University of Florida College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"J.","lastName":"Indelicato","suffix":""},{"id":432826190,"identity":"69621f10-33b8-484e-82ca-95f228be075a","order_by":3,"name":"Jae Y. Lee","email":"","orcid":"","institution":"ProCure (United States)","correspondingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Y.","lastName":"Lee","suffix":""},{"id":432826191,"identity":"8ce598e6-1066-42ef-b21c-84ca4e71ea35","order_by":4,"name":"John P. 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Aridgides","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYFACxgYJBgNmBn4kIQPitEg2ANkHIKoJaWFgkGBgYGYwOECsFv7ZhxtvfimwzjO+kXv484eaP3IM7M3bJPDacC6x2VrGIL3Y7EZemsSBYwbGDDzHyvBqYTjD2CYtYXA4cduNHDOGA2wGiQ0SOWZ4tcjDtGyekWP84cA/g/oG+Tf4tRgAtUh+AGrZIJFjIHGwzSCBQYIHvxbDM4zN1gxAv0iceZcmcbbP2LCNJ63YAp8WuTPsD2/++GOdx9+ee/hDxTc5eX72wxtv4NMCAsw8DAwJDAw8EB4bIeUgwPgDWcsoGAWjYBSMAnQAAG51SeSG5tMVAAAAAElFTkSuQmCC","orcid":"","institution":"SUNY Upstate Medical University","correspondingAuthor":true,"prefix":"","firstName":"Paul","middleName":"D.","lastName":"Aridgides","suffix":""}],"badges":[],"createdAt":"2025-03-21 01:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6273163/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6273163/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11060-025-05065-2","type":"published","date":"2025-05-13T15:57:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79175373,"identity":"371b48a0-f80e-4013-95d5-9bbbf549553f","added_by":"auto","created_at":"2025-03-25 09:54:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":227006,"visible":true,"origin":"","legend":"\u003cp\u003ea) Overall Survival and b) Event Free Survival of the entire Proton/Photon Consortium Registry (PPCR) embryonal tumor with multilayered rosettes (ETMR) cohort (N=18) from start of Radiation Therapy\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6273163/v1/604cdafb45aef519986eaab0.png"},{"id":79175387,"identity":"5f9f9507-0747-4717-adde-edef9ab1867b","added_by":"auto","created_at":"2025-03-25 09:54:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":240855,"visible":true,"origin":"","legend":"\u003cp\u003ea) Local Control and b) Distant Control of the entire Proton/Photon Consortium Registry (PPCR) embryonal tumor with multilayered rosettes (ETMR) cohort (N=18) from the start of Radiation Therapy\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6273163/v1/3c6d74d72487a0db489fb867.png"},{"id":79175337,"identity":"8d97a658-46ee-4899-b7ed-60077191c729","added_by":"auto","created_at":"2025-03-25 09:54:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":385358,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival by a) Surgical Extent, b) Surgery to RT Time, gt: greater than, lt: less than c) Stem Cell Rescue, and d) Progression Prior to RT of the entire Proton/Photon Consortium Registry (PPCR) embryonal tumor with multilayered rosettes (ETMR) cohort (N=18) from the start of Radiation Therapy\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6273163/v1/d6cd3fa22cc9d569bc3da095.png"},{"id":83067950,"identity":"eb7f3d04-dc6b-4e93-9ef1-b1827b7ebd45","added_by":"auto","created_at":"2025-05-19 16:08:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1799539,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6273163/v1/116fbb3c-9beb-496f-afca-662e9068f0d9.pdf"},{"id":79175372,"identity":"7e18451a-a94a-47d6-bbda-7e9f8bb5056a","added_by":"auto","created_at":"2025-03-25 09:54:15","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17408,"visible":true,"origin":"","legend":"","description":"","filename":"JNOSupplementalTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-6273163/v1/90a441937f0e843956fab525.docx"}],"financialInterests":"Competing interest reported. Authors J.K., R.E., D.I., J.L., J.P., S.P., N.L., J.C., I.M., S.W., D.W., and P.A. declare they have no competing interests to disclose. Author T.Y. has received grant funding from Mim Software, received consulting fees from Mevion Medical Advisory Board, and serves on the Proton Collaborative Group Data Safety Monitoring Committee.","formattedTitle":"Outcomes Following Radiation Therapy for Embryonal Tumor with Multilayered Rosettes (ETMR): Results from the Pediatric Proton/Photon Consortium Registry (PPCR)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEmbryonal tumor with multilayered rosettes (ETMR) is a rare and aggressive central nervous system (CNS) tumor affecting young children. First described by Eberhart in 2000 as embryonal tumors with abundant neuropil and true rosettes (ETANR), ETANTR, ependymoblastoma (EBL), and medulloepithelioma (MEPL) have since been shown to represent three variants of rosette-forming neuroepithelial CNS tumors within the single classification of ETMR [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Molecular characteristics include amplification of the oncogenic miRNA \u003cem\u003eC19MC\u003c/em\u003e, positive immunoreactivity for the tumorigenic protein LIN28A, and \u003cem\u003eDICER1\u003c/em\u003e mutation [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The 2016 WHO Classification of Tumors of the CNS first recognized ETMR as a new diagnostic category, with subsequent update in 2021 to include the \u003cem\u003eDICER1\u003c/em\u003e alteration was updated in 2021 to include ETMR with the \u003cem\u003eDICER1\u003c/em\u003e mutation [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere exist limited epidemiological and survival data for ETMR, given both the rarity of disease and relatively recent diagnostic WHO classification [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A recent large cohort study of 159 patients with molecular-confirmed ETMR diagnosis from the Rare Brain Tumor clinical registry showed an overall survival (OS) of just 29% at 2 years. Multiple reports have supported the use of RT for improved outcomes [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] however only a handful of patients (often 5 or less) receive RT. As ETMR is an aggressive disease with poor prognosis and lacking definitive treatment guidelines, further information is needed to estimate outcomes according to treatment received. In this series, we investigated clinical outcomes following RT on patients prospectively enrolled on the Proton Photon Consortium Registry (PPCR).\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Selection\u003c/h2\u003e \u003cp\u003eFrom 2012\u0026ndash;2021, all 20 ETMR patients enrolled on PPCR were included from 9 centers that included Massachusetts General Hospital, Washington University, University of Florida, University of Washington, ProCure Proton Therapy Center NJ, Mayo Clinic, Oklahoma Protons, Cincinnati Children\u0026rsquo;s Hospital Medical Center, and California Protons. Data analysis and outcome reporting were limited to patients who did not have prior radiation at the time of enrollment (N\u0026thinsp;=\u0026thinsp;18). The mission of the PPCR, as well as the methodology for data collection, have been previously reported [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Patient, disease, and treatment characteristics were submitted prospectively and informed consent was obtained for all patients prior to registration. This series queried the PPCR regarding extent of surgery, disease stage (M0 or M+), chemotherapy given, RT dose, RT volume including focal, CSI, or boost, and disease progression.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eStudy data were collected and managed using REDCap electronic data capture tools hosted at Massachusetts General Hospital. All follow-up disease control endpoints are measured from the start date of radiotherapy. The follow-up data cutoff date was August 13, 2024. An event was defined as a local recurrence, distant recurrence, second malignancy, or death from any cause. Median follow up time was estimated using the reverse Kaplan-Meier method. We estimated EFS and OS using the Kaplan-Meier method. Hazard ratios between groups were estimated using univariate Cox proportional hazard ratio model and p values were calibrated by Wald method. All analysis were performed using R Statistical Software (v4.1.2) at a statistical significance level of alpha\u0026thinsp;=\u0026thinsp;0.05[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Given the sample size available for analysis, no multivariate Cox models were performed to remove potential confounding associated with observed significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 18 patients comprised the ETMR PPCR cohort with patient characteristics summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Two patients were excluded due to prior radiation. The median follow-up is 55.5 months (range 2.6-119.4). Median age at the time of radiation was 3.0 years (1.7\u0026ndash;12.2). A gross total resection was achieved upfront in 12 (67%) patients, near total resection in 4 (22%) patients, and subtotal resection in 2 (11%) patients. All patients had M0 disease. 10 (56%) patients were treated with chemotherapy, with chemotherapy sequencing prior to RT in 14 (78%) patients; prior and during in 2 (11%) patients; during and after in 2 (11%) patients; or prior, during, and after in 2 (11%) patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Characteristics. \u003csup\u003ea\u003c/sup\u003en(%). GTR: Gross Total Resection, NTR: Near Total Resection, STR: Subtotal Resection, RT: Radiotherapy, CSI: Craniospinal Irradiation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;18\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (min-max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.5 (2.6-119.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (44%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (56%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor Location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupratentorial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (83%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfratentorial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtent of Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (67%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiation Target\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (89%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy with Stem Cell Rescue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at RT (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (min-max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0 (1.7\u0026ndash;12.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary RT dose (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (min-max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (53-57.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSI dose (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.6 (1 patient) or 36 (1 patient)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLong term survival\u0026thinsp;\u0026gt;\u0026thinsp;55 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRT details\u003c/h3\u003e\n\u003cp\u003eRT details according to field and dose are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Focal RT was provided for 16 (89%) patients, with the remaining 2 (11%) patients receiving CSI plus boost. The most common primary RT dose was 54 Gy (89%). In the two patients receiving CSI, the doses were 30.6 Gy or 36Gy with 54Gy primary boost.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIndividual Patient, Tumor, and Treatment Details\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProtocol\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAge at RT, yrs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTime to RT,\u003c/p\u003e \u003cp\u003emos\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePD Prior (Y/N)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCSI dose\u003c/p\u003e \u003cp\u003e(Gy*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePrimary Tumor dose\u003c/p\u003e \u003cp\u003e(Gy*)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eFailure (N/Y, Location, Time in mos\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eLast status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOS from RT,\u003c/p\u003e \u003cp\u003emos\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eACNS 0332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e119.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e55.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e119.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDFCI 02-294⁺\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e81.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e81.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDFCI 02-294⁺\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e38.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e57.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eY, Distant\u003c/p\u003e \u003cp\u003e10.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e38.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eETMR One⁺\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eY, Distant\u003c/p\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eACNS 0334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e23.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eY,\u003c/p\u003e \u003cp\u003eLocal \u0026amp; Distant\u003c/p\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e26.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eY,\u003c/p\u003e \u003cp\u003eLocal\u003c/p\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e26.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eACNS 0333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e101.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e101.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e65.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e65.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eACNS 0334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e71.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN^\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e73.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e34.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eY, Distant\u003c/p\u003e \u003cp\u003e18.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e34.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHead\u003c/p\u003e \u003cp\u003eStart IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eACNS 0333*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e45.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e45.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHead\u003c/p\u003e \u003cp\u003eStart IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eY,\u003c/p\u003e \u003cp\u003eLocal \u0026amp; Distant\u003c/p\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e7.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eACNS 0334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDFCI 02-294⁺\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e55.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e55.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHead Start IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e45.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e45.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHead Start IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e49.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e49.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eS: supratentorial, I: infratentorial, GTR: gross total resection, NTR: near total resection, STR: subtotal resection, A: alive, E: expired, mos: months, yrs: years, ACNS0332: Children\u0026rsquo;s Oncology Group ACNS0332[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], DFCI 02-294: Dana Farber Cancer Institute 02-294[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], ETMR One: ClinicalTrials.gov ID NCT04794686, ACNS0334: Children\u0026rsquo;s Oncology Group ACNS0334 ClinicalTrials.gov ID NCT00336024, ACNS0333: Children\u0026rsquo;s Oncology Group ACNS0333[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], Head Start IV: ClinicalTrials.gov ID NCT02875314\u003c/p\u003e \u003cp\u003eIMPT: intensity modulated proton therapy; 3DCRT: three dimensional conformal radiation therapy\u003c/p\u003e \u003cp\u003e* Indicates GyRBE\u003c/p\u003e \u003cp\u003e⁺ Indicates intrathecal chemotherapy\u003c/p\u003e \u003cp\u003e^: Second malignancy, high grade glioma, occurred at 71 months\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eMedian follow-up for all patients was 55.5 months (range 2.6-119.4). Of all 18 patients, 8 expired (44%). No patients were considered lost to follow-up as the maximum time from last follow-up to the data cut off was 20 months for surviving patients. Recurrence occurred in 6 (33%) patients; 1 was local only, 3 distant only, and 2 patients had combined local and distant failure. All but one relapse occurred within 2 years of RT. When comparing relapses to RT field, 16 patients had focal RT and 5 relapsed (1 local only, 3 distant only, 1 combined local and distant). 2 patients had CSI with 1 experiencing combined local and distant failure. One patient developed a second malignancy of high grade glioma at 71 months following RT and ultimately expired at 73.7 months.\u003c/p\u003e \u003cp\u003eThe 2- and 4-year overall survival (OS) were 72.2% and 59.6%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Outcomes of EFS and OS are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Local control (LC) at 4 years was 81% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Distant control at 4 years was 68.1% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). The 4-year OS for focal RT was 61.9% and for CSI was 50% (p\u0026thinsp;=\u0026thinsp;0.307). GTR was not associated with improved OS (4-year OS GTR 75%, NTR/STR 55.6%, p\u0026thinsp;=\u0026thinsp;0.910) or EFS (4-year EFS GTR 75%, NTR/STR 83.6%, p\u0026thinsp;=\u0026thinsp;0.811, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). One patient received salvage CSI (36Gy plus metastatic boost to 54Gy) for a disseminated relapse that occurred 18.7 months after focal RT. This patient is surviving at last follow-up (16 months after salvage CSI).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLocal Control (LC), Event Free Survival (EFS), and Overall Survival (OS) at 2- and 4- Years According to Patient and Treatment Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2-year / 4-year EFS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2-year / 4-year\u003c/p\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEntire cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.2% / 54.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.2% / 59.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81% / 81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.1% / 68.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRT volume\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.2% /5 6.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75% / 61.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50% / 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50% / 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical Extent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75% / 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75% / 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNTR\u0026amp;STR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.6% / 83.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.4% / 55.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50% / 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50% / 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.2% / 56.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75% / 61.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStem cell rescue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.6% / 63.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.570\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.7% / 72.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.9% / 42.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.4% / 35.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery to RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.350\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le; 200 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70% / 70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90% / 67.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;200 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5% / 37.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50% / 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression prior to RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.0% / 40.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.0% / 40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.5% / 61.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.9% / 68.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOf six patients (32%) with gross disease pre-RT, all had 54Gy focal RT and 4 are alive at follow up. The median time from surgery to RT start was 186 days. The 4-year EFS for surgery to RT time\u0026thinsp;\u0026gt;\u0026thinsp;200 days was 37.5%, and 4-year OS was 50%; the 4-year EFS for surgery to RT time\u0026thinsp;\u0026le;\u0026thinsp;200 days was 70%, and 2-year OS was 67.5% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). All 8 patients with a surgery to RT time\u0026thinsp;\u0026gt;\u0026thinsp;200 days received chemotherapy exclusively prior to RT. There was no difference in OS comparing patients who received chemotherapy with stem cell rescue (SCR) as compared to those who did not (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). The 4-year OS (p\u0026thinsp;=\u0026thinsp;0.361) and EFS (p\u0026thinsp;=\u0026thinsp;0.57) for chemotherapy with SCR was 72.7% and 63.6%, respectively compared to 35.7% and 42.9%, respectively. Patients who experienced progression prior to RT had a 4-year OS of 40% compared to 68.4% in those without progression (p\u0026thinsp;=\u0026thinsp;0.127, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed). There were 6 patients who received focal RT without high dose chemotherapy: 2 expired (1 received multiple repeat RT courses) and 3 are alive without relapse, including 1 of which is surviving 15.2 months after salvage CSI (36Gy plus metastatic site boost) for disseminated only relapse.\u003c/p\u003e \u003cp\u003eProton beam radiation for ETMR was safe and well-tolerated. There were no PPCR ETMR patients with reported radionecrosis and radiation brainstem injury, which was confirmed directly with the treating physicians. Neurologic symptoms (n\u0026thinsp;=\u0026thinsp;12) that were reported during the course of therapy (including pre-treatment) included seizure, cerebellar symptoms (gait, coordination), speech impairment, cranial nerve deficits, and weakness. Further details include: 5 patients with symptoms have subsequently died of disease progression including 2 with cranial nerve involvement, 5 patients were known to have neurologic symptoms prior to RT and are alive without recurrence, and 2 additional patients developed neurologic symptoms in an unknown time frame and are alive without recurrence.\u003c/p\u003e \u003cp\u003eTwo patients were excluded from data analysis due to prior RT. Both patients had focal reirradiation (re-RT) after enrollment on PPCR. Patient 1 (prior RT and surgical details unknown) received 54Gy focal IMPT re-RT for an infratentorial primary and expired 4.6 months after re-RT. This patient received salvage chemotherapy with etoposide, temozolomide, and topotecan. Patient 2 (initial surgical extent GTR with prior RT of 45Gy focal RT) received 36Gy focal re-RT for a supratentorial primary and expired 9.2 months following re-RT. This patient received high dose chemotherapy with stem cell support before RT, along with chemotherapy during and after RT following COG ACNS0334.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eETMR is a rare and aggressive brain tumor occurring typically in young children under 3 years old, with treatment consisting of surgery, systemic chemotherapy, and variable inclusion of RT [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. There is limited available clinical outcome data and no standard treatment for ETMR, thus guidance is lacking for how to include RT into treatment regimens. We report RT for ETMR on the PPCR was consisted of focal RT in 89% of patients and was associated with favorable primary site disease control (4-year LC of 81%). The 4-year EFS (59.6%) and OS (54.2%) are similar or higher to reported database studies however, these did not uniformly employ RT. This series (PPCR ETMR) builds on prior literature detailing ETMR treatment with further details analyzed specific to RT [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSurvival outcomes for ETMR are limited by very small patient numbers due to extreme tumor rarity, and the impact of RT has been inconsistent across different investigations [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. There is a certainly a concern for neurocognitive impact due to very young patient age [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In the present series that largely favored focal RT (89%), proton beam RT was given for all patients to optimally spare developing brain tissue from low or medium dose RT exposure. Our data support continued incorporation and investigation of focal RT in treatment protocols for ETMR. With long-term follow-up (median 55.5 months) on PPCR ETMR, 8 of 18 patients expired. There was 1 local-only failure and 3 distant-only failures seen among 16 patients receiving focal RT, suggesting efficacy for RT with primary site disease control in ETMR. It remains unknown from PPCR ETMR whether the 3 distant-only failures following focal RT would be improved with CSI, and 2 of these patients were under 3 (2.3 and 2.9 years old) at the time of RT. Long term survival of greater than or equal to 55 months occurred in 6 patients. Of these, 2 had GTR, 2 had NTR, and 2 had STR. All patients received focal RT, and 5 patients received intensive chemotherapy that included stem cell rescue.\u003c/p\u003e \u003cp\u003eLong-term survival in ETMR seems to be more common when RT is employed [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Jaramillo reported results of a literature search of ETMR identifying 208 cases reported and only 18 long-term survivors alive \u0026ge; 36 months. Of 18 long term survivors, 14 had CSI, 1 received focal RT, 2 had RT details unknown, and only 1 did not receive RT. In contrast, a Rare Brain Tumor Registry study reported long-term survival (defined \u0026ge; 24 months) in 21 patients with molecular-confirmed diagnosis of ETMR and 9 (43%) had received focal RT. CSI use was not reported in the long-term survival cohort, and use of RT overall was associated with improved OS on multivariate analysis.\u003c/p\u003e \u003cp\u003eIn a recent multi-institutional retrospective review of 49 ETMR patients who received adjuvant therapy, only 14 received upfront RT [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Notably, relapse or progression occurred in 34 of 35 (97%) RT-na\u0026iuml;ve patients, 5 of 10 patients who received CSI (50%), and in 1 of 4 patients (25%) who received focal RT. A multi-institutional review of clinical trials SJYC07 and SJMB03 from St. Jude\u0026rsquo;s Children\u0026rsquo;s Research Hospital report of 28 ETMR patients reported only 5 (18%) long term survivors. There was variable use of focal RT (13 patients, 46%), CSI (5 patients, 18%), RT avoidance (8 patients, 29%), or palliative treatment (2 patients, 7.1%). Four of 5 survivors received RT without specification of RT field [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The German-led P-HIT trial experience adds further support for inclusion of RT with ETMR, in a combined patient analysis of the P-HIT trial, the HIT2000-interim-registry, and previously enrolled patients. Long term survival of at least 3.0 years was reported in 9/35 patients: RT was either CSI (4 patients), focal RT (2 patients), or not given (3 patients). All 4 patients who received adjuvant RT after completion of carboplatin and etoposide induction followed by high dose chemotherapy exhibited long-term survival. Notably, RT was not found to be as an independent prognostic factor for OS.\u003c/p\u003e \u003cp\u003eHerein, we report the largest cohort published to our knowledge of ETMR where all patients received RT and outcomes according to RT variable were analyzed. Focal RT (88%) predominated, and 2 patients received CSI. We did not find progression prior to RT, RT timing from surgery to RT start, extent of surgery, and choice of chemotherapy to be statistically significant for OS or EFS. The sample size while including 18 patients with upfront RT and a median follow-up of 55 months, is a study limitation for statistical analyses. While patients were enrolled prospectively on the PPCR protocol, the delivery of RT (dose, technique, target) was at the discretion of the treating physician and therefore not uniform. As expected for ETMR which is known to have a predilection for local recurrence as well as primarily affecting very young patients, only 2 patients had CSI. This prohibits any investigation into the efficacy of craniospinal radiation for lowering the risk of distant recurrence. Of 3 patients who received focal RT but developed distant only failure, only one patient was age\u0026thinsp;\u0026gt;\u0026thinsp;3 where CSI can typically be considered. The PPCR registry includes a heterogenous patient population with regard to chemotherapy protocols followed (Supplementary Table\u0026nbsp;1). This is particularly apparent with ETMR, where due to very rare nature of this disease there is no current consensus for optimal chemotherapy protocol [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Any potential differences in patient outcomes according to systemic therapy regimen were not able to be studied due to several common regimens used within the 18 patient study cohort.\u003c/p\u003e \u003cp\u003eNeurocognitive injury and necrosis following brain RT in pediatric patients poses a therapeutic challenge. The use of proton versus photon therapy has been studied extensively in the pediatric population, with the advantage of proton radiation in potentially reducing both dose volumes and mean dose henceforth lessening long term cognitive and endocrine effects [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Furthermore, proton therapy spares adjacent normal tissue while maintaining therapeutic dose to target volumes [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Focal RT offers a large advantage for mean brain dose and volume, of which both are associated with neurocognitive effects including a below-average intelligence quotient [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. This is particularly true for the youngest age patient population of infant brain tumors. In the PPCR ETMR cohort, no cases of brainstem injury or radionecrosis were reported and proton beam RT was well-tolerated. Data was unavailable for detailing the neurocognitive impact of proton beam RT in the PPCR ETMR cohort. One patient unfortunately experienced a radiation induced high grade glioma 71 months following RT and expired at 73 months. While incredibly rare, RT induced high grade gliomas typically occur after a long latency period averaging 14\u0026thinsp;\u0026plusmn;\u0026thinsp;8 years and are associated with very poor outcomes [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExciting future directions include the awaited results from the currently enrolling ETMR One protocol, which also includes an accompanying multi-institutional database (clinicaltrials.gov ID NCT04794686). Patients are treated on a uniform chemotherapy regimen that includes intrathecal chemotherapy, concurrent temozolamide during RT, and high-dose chemotherapy with autologous stem cell rescue. Patients receive 54Gy focal RT, however for patients age\u0026thinsp;\u0026gt;\u0026thinsp;3 years old or with M\u0026thinsp;+\u0026thinsp;disease CSI can be considered at the discretion of the treating physician. Data analysis is anticipated after further patient accrual is completed, which will provide the much-needed opportunity to evaluate ETMR outcomes for patients treated under a unified treatment protocol.\u003c/p\u003e \u003cp\u003eIn this study, we have PPCR outcomes for ETMR patients treated with proton RT. With a median follow-up period of 55 months, the 4-year LC of 81%, 4-year OS of 59.6% ,and 4-year EFS of 54.2% suggest the continued incorporation of focal RT within ETMR treatment protocols is warranted. Utilization of proton RT offers advantages in reducing long term sequelae from RT on the brain and tissues adjacent to the treatment field. Prospective uniform inclusion of RT on ETMR studies, notably ETMR one, is anticipated to provide further evidence of the positive impact of RT for this very rare, aggressive tumor.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: Data for this project was obtained from the multi-center Pediatric Proton and Photon Consortium Registry (PPCR) sponsored by the National Institutes of Health/Massachusetts General Hospital. The PPCR is supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13 declare they have no competing interests to disclose. Author 12 has received grant funding from Mim Software, received consulting fees from Mevion Medical Advisory Board, and serves on the Proton Collaborative Group Data Safety Monitoring Committee.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jacquelyn Krisch and Paul Aridgides. Statistical analysis was performed by Dongliang Wang. The first draft of the manuscript was written by Jacquelyn Krisch and Paul Aridgides, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data will be made available upon reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e Patient, disease, and treatment characteristics were submitted prospectively with Institutional Board Approval (DFCI protocol 12-103, clinicaltrials.gov NCT01696721)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eInformed Consent\u003c/strong\u003e: Informed consent was obtained for all patients prior to registration\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKorshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DT, Remke M, Northcott P, Perry A, Picard D, Rosenblum M, Antonelli M, Aronica E, Schuller U, Hasselblatt M, Woehrer A, Zheludkova O, Kumirova E, Puget S, Taylor MD, Giangaspero F, Peter Collins V, von Deimling A, Lichter P, Huang A, Pietsch T, Pfister SM, Kool M (2014) Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. 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Int J Radiat Oncol Biol Phys 90: 1143-1152 doi:10.1016/j.ijrobp.2014.08.354\u003c/li\u003e\n\u003cli\u003eBoehling NS, Grosshans DR, Bluett JB, Palmer MT, Song X, Amos RA, Sahoo N, Meyer JJ, Mahajan A, Woo SY (2012) Dosimetric comparison of three-dimensional conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated radiotherapy for treatment of pediatric craniopharyngiomas. Int J Radiat Oncol Biol Phys 82: 643-652 doi:10.1016/j.ijrobp.2010.11.027\u003c/li\u003e\n\u003cli\u003eWoo PYM, Lee JWY, Lam SW, Pu JKS, Chan DTM, Mak CHK, Ho JMK, Wong ST, Po YC, Lee MWY, Chan KY, Poon WS (2024) Radiotherapy-induced glioblastoma: distinct differences in overall survival, tumor location, pMGMT methylation and primary tumor epidemiology in Hong Kong chinese patients. Br J Neurosurg 38: 385-392 doi:10.1080/02688697.2021.1881445\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pediatric, Proton, Radiation, ETMR, Cancer","lastPublishedDoi":"10.21203/rs.3.rs-6273163/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6273163/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: Embryonal tumor with multilayered rosettes (ETMR) is a rare pediatric CNS embryonal tumor with poor survival. The Pediatric Proton/Photon Consortium Registry (PPCR) was queried for outcomes data from prospectively consenting pediatric patients with ETMR treated with proton radiation therapy (RT).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: 20 patients (2013-2021) at 9 institutions had ETMR; 2 with prior RT were excluded from statistical analyses (PPCR ETMR, N=18). Overall Survival (OS) and Event Free Survival (EFS) analyses were performed using the Kaplan-Meier method and log-rank values. Median follow-up was calculated using the reverse Kaplan-Meier method.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Median age at RT was 3.0 years (1.7-12.2); median follow-up was 55.5 months (2.6-119.4). 8 patients (44%) expired and 6 patients (33%) are surviving ≥55 months. 11 (61%) patients received systemic therapy with stem cell support. The majority (89%) had focal RT, while 2 patients received craniospinal irradiation (CSI). 4-year OS and EFS were 59.6% and 54.2%, respectively. Local control (LC) at 4 years was 81%. No differences in OS or EFS were observed for receipt of systemic therapy with stem cell support (p=0.361, p=0.57), progression prior to RT (p=0.127, p=0.18), or surgery to RT ≥200 days (p=0.35, p=0.254). Symptomatic radionecrosis was not reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Focal proton RT provided effective local control as part of multimodality therapy for ETMR, with encouraging survival for this rare and often infant age tumor. Outcomes for CSI were limited to 2 patients treated upfront, and 1 patient receiving salvage CSI for disseminated relapse after focal RT who is surviving \u0026gt;1 year.\u003c/p\u003e\n\u003cp\u003eTrial: DFCI protocol 12-103, clinicaltrials.gov NCT01696721, date of registration 9/27/2012\u003c/p\u003e","manuscriptTitle":"Outcomes Following Radiation Therapy for Embryonal Tumor with Multilayered Rosettes (ETMR): Results from the Pediatric Proton/Photon Consortium Registry (PPCR)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-25 09:54:04","doi":"10.21203/rs.3.rs-6273163/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-14T02:23:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-13T17:28:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-11T15:26:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-08T02:28:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-02T16:29:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66165694484156589010036442076893171866","date":"2025-04-02T13:43:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"200696644126421995913193170605863468829","date":"2025-04-01T04:42:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"170662709712097792903411028983047938243","date":"2025-03-31T11:57:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184469418787809118468955195951511088088","date":"2025-03-30T13:04:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144750576610712820825774679844446817689","date":"2025-03-21T14:56:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"102447043854679648109623197713234879292","date":"2025-03-21T11:00:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-21T10:52:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-21T08:15:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-21T08:12:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neuro-Oncology","date":"2025-03-21T01:48:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuro-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neon","sideBox":"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)","snPcode":"11060","submissionUrl":"https://submission.nature.com/new-submission/11060/3","title":"Journal of Neuro-Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b6e47145-fee3-4c9d-8bef-2d544fc27127","owner":[],"postedDate":"March 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-19T16:04:46+00:00","versionOfRecord":{"articleIdentity":"rs-6273163","link":"https://doi.org/10.1007/s11060-025-05065-2","journal":{"identity":"journal-of-neuro-oncology","isVorOnly":false,"title":"Journal of Neuro-Oncology"},"publishedOn":"2025-05-13 15:57:48","publishedOnDateReadable":"May 13th, 2025"},"versionCreatedAt":"2025-03-25 09:54:04","video":"","vorDoi":"10.1007/s11060-025-05065-2","vorDoiUrl":"https://doi.org/10.1007/s11060-025-05065-2","workflowStages":[]},"version":"v1","identity":"rs-6273163","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6273163","identity":"rs-6273163","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}