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Background and Purpose: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing., Materials and Methods: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared., Results: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2)., Conclusion: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective studies have reported higher rates of brainstem injury after PBT than after photon therapy (XRT). We report a national multicenter study of the incidence of brainstem injury after XRT versus PBT, and their correlations with dosimetric data., Material and Methods: We included all patients aged < 25 years who were treated with PBT or XRT for intracranial ependymoma at five French pediatric oncology reference centers between 2007 and 2020. We reviewed pre-irradiation MRI, follow-up MRIs over the 12 months post-treatment and clinical data., Results: Of the 83 patients, 42 were treated with PBT, 37 with XRT, and 4 with both (median dose: 59.4 Gy, range: 53‑60). No new or progressive symptomatic brainstem injury was found. Four patients presented asymptomatic radiographic changes (punctiform brainstem enhancement and FLAIR hypersignal), with median onset at 3.5 months (range: 3.0‑9.4) after radiation therapy, and median offset at 7.6 months (range: 3.7‑7.9). Two had been treated with PBT, one with XRT, and one with mixed XRT-PBT. Prescribed doses were 59.4, 55.8, 59.4 and 54 Gy., Conclusion: Asymptomatic radiographic changes occurred in 4.8% of patients with ependymoma in a large national series. There was no correlation with dose or technique. No symptomatic brainstem injury was identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Irradiation of the vertebrae in prepubertal patients, if non-homogenous, can result in future growth deformities including kyphoscoliosis. Vertebral delineation and dosimetry were assessed for 101 paediatric cases reviewed within QUARTET-affiliated trials. Despite the availability of published consensus guidelines, a high variability in vertebral delineation was observed, with impact on dosimetry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to evaluate retrospectively the clinical results of re-irradiation for children with a locally recurrent brain ependymoma., Methods: 33 full-dose re-irradiations were delivered to 31 children with a recurrent brain ependymoma after a standard treatment. Each child was followed up with clinical and MRI examinations. We evaluated overall survival, local recurrence free-survival and short term toxicity according to CTCAE 4.0 scale., Results: With a median follow-up of 37 months (range, 0 to 107), median local recurrence free-survival was 31 months (range, 2 to 63) and median overall survival was 34 months (range, 3 to 63). It was significantly higher in patients who underwent surgery first, compared with re-irradiation only. Cumulated dosimetric data were available for 22 patients. On average, maximal BED to brain stem was 106,2 Gy α/β3 (±35,4) for infratentorial re-irradiation. No acute toxicity grade >2 was reported and 1 case of brain radionecrosis treated successfully with steroids was reported after radiosurgery., Conclusion: Local recurrence of brain ependymoma can be treated with full-dose re-irradiation, which can be hypofractionated with an acceptable short term toxicity in spite of high total doses delivered to OARs, especially brain stem., (Copyright © 2018. Published by Elsevier B.V.)

Background and Purpose: Skull-base chondrosarcoma (ChSa) is a rare bone tumor and the outcome of patients with this malignancy has been documented only in a limited number of series with a restricted number of patients., Objective: This study was conducted to assess the outcome and prognostic factors of a large cohort of ChSa patients treated with radiotherapy in two proton therapy centers., Materials and Methods: From 1996 to 2015, 251 (male, 43.4%) patients (mean age, 42.0 ± 16.2 years) were treated with protons with (n = 135; 53.8%) or without photons (n = 116; 46.2%). Median delivered dose was 70.2 Gy RBE . Failure-free survival (FFS), overall survival (OS) and CTCAE grade ≥3 toxicity free survival (TFS) were calculated using the Kaplan-Meier method., Results: After a median follow-up of 88.0 months for surviving patients, local and distant failures were observed in 12 (4.8%) and 4 (1.6%) patients, respectively. Late failures >6 years were observed in 4 (33.3%) patients. The estimated 7-year FFS was 93.1%. Twenty-five (10%) patients died. The estimated 7-year OS was 93.6%. Tumor volume (p = 0.006) and optic pathway compression (p = 0.027) were significantly associated with the risk of treatment failure on univariate analysis. Treatment failure was significantly associated with a higher risk of death (hazard ratio = 126). The estimated 7-year TFS was 84.2%., Conclusions: The outcome of skull-base ChSa patients treated with high-dose protons with or without photons is excellent, particularly for patients with small tumors with no optic pathway compression. Treatment failure was however associated with a significantly increased risk of death., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: To evaluate clinical results and safety of a dose adaptive protocol based on tumor volume coverage and critical structure constraints, for the treatment of skull base chordomas., Material and Methods: Between May 2006 and October 2012, 106 patients with skull base chordoma were treated by combined photon and proton irradiation. Prescribed dose levels were 68.4, 70.2, 72 and 73.8 Gy(RBE) in once daily fractionation of 1.8 Gy(RBE). Dose level and dosimetric constraints to organs at risk depended on postoperative residual Gross Tumor Volume (GTV) coverage. Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method., Results: With a median follow-up of 61 months, the 2-year, 4-year, and 5-year LC rates were 88.6%, 78.3%, and 75.1%, respectively. GTV > 25 mL (p = 0.034, HR = 2.22; 95%CI 1.06-4.62) was an independent unfavorable prognostic factor of LC. The 2-year, 4-year, and 5-year OS rates were 99%, 90.2%, and 88.3%, respectively. Grade 3-5 late toxicity was observed in 7 patients, resulting in 93% 5-year freedom from high-grade toxicity., Conclusions: This study suggests that the probability of LC of skull base chordomas depends on postoperative GTV. The dose adaptive protocol achieves acceptable local control. Future studies should investigate whether further dose escalation to doses in excess of 74 Gy(RBE) would achieve better results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: Ependymoma is the third most common brain tumor in children. Radiation therapy (RT) is systematically administered after maximum surgical resection, utilizing recent advances in radiation delivery. Imaging can make a significant contribution to improving treatment outcome. This prompted us to look for significant preoperative and postoperative imaging markers for survival., Material and Methods: We undertook a national retrospective review of 121 patients who had undergone resection followed by RT. Preoperative tumor volumes on T1 and FLAIR images were delineated, together with postoperative hyperintense volumes on FLAIR images. Overall survival (OS) and disease-free survival (DFS) analyses included clinical data and volumes extracted from images., Results: After a median follow-up of 38.5 months, 80.2% of patients were alive, but 39.7% had experienced at least one event. Statistically significant differences between patients with and without postoperative FLAIR abnormalities were found for both DFS (71.9% vs. 40.3%; p = 0.006) and OS (93.7% vs. 72.4%; p = 0.023) in the univariate analyses, and for OS (p = 0.049) in the multivariate analyses., Conclusions: Postoperative FLAIR hyperintensities are a negative prognostic factor for intracranial ependymoma and may be a surrogate for residual disease. They could therefore prove helpful in patients' surgical and radiotherapeutic management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To investigate the patterns of failure after radiotherapy for pediatric intracranial ependymoma and their correlation with dose parameters., Methods: Between 2000 and 2013, 206 patients were treated in France. MRI scans at relapse were registered to the original planning CTs for topographic analysis of failure patterns. To compare relapse patients (RP) with non relapse patients (NRP), several dose parameters were derived from dose volume histograms., Results: Over a median follow-up of 53.8months, 84 patients presented with relapse. Topographic analysis showed 50 patients with local relapse in the radiation field, 6 in the edge of field, 6 locoregional outside the field, 10 in the spine, 5 supratentorial and 7 local and distant. The median coverage, target coverage and homogeneity indices did not differ significantly between RP and NRP. The median volume of in-field relapse was 1.25cc [0.11, 27], with a median dose of 57.83Gy [50.04, 61.69]., Conclusions: Local relapse in the tumor bed and the higher dose regions was the predominant pattern of failure. Improving coverage of the target volume and increasing the dose to the high radioresistant regions, taking into consideration other clinical and biological pronostic factors, may be an effective way of reducing local failures., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)