Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study

Abstract

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.

Impact of proton therapy on the DNA damage induction and repair in hematopoietic stem and progenitor cells

“…Next to this, Liu et al 48 showed that proton cranio-spinal irradiation significantly decreased hematologic toxicity compared with those receiving photon therapy. Also, Ruggi et al 12 showed in pediatric patients treated for medulloblastoma that hematological toxicity was limited, even among high-risk patients who underwent hematopoietic stem-cell transplantation before proton therapy. For long-term risks, longer follow-up studies must be completed but current preliminary results on late effects and survival are certainly encouraging.…”

“…In these patients, approximately 20–30% of the active bone marrow is located in the cranium and cervical vertebrae 11 . Therefore, it is important to take red bone marrow into account during treatment of CNS tumors, as craniospinal irradiation is often standard of care in these patients 12 . This is further emphasized by the fact that bone marrow toxicity from radiation may limit subsequent local or systemic treatment regimens 13 .…”

Adolescents and Young Adults With Cancer: CNS Tumors

“…Proton beam radiation therapy is preferred to reduce the exposure of normal tissue to radiation delivered by photon beam RT. 44…”

“…Proton beam radiation therapy is preferred to reduce the exposure of normal tissue to radiation delivered by photon beam RT. 44 For patients with GTR/NTR and no metastatic disease (average-risk disease), the recommended dose of craniospinal irradiation (CSI) is 23.4 Gy with an additional RT boost to the tumor bed, delivering a total dose of 54 Gy. High-risk patients (those with residual disease ≥1.5 cm 2 and/or metastatic disease) are recommended 36 Gy CSI with a RT boost to the primary tumor bed delivering a total dose of 54 Gy.…”

Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study

“…This is especially relevant for children receiving radiotherapy [7] because the distance between the target and critical organs is often shorter than that of adults and the longer posttreatment lifespan of childhood cancer survivors presents more risk for the manifestation of late adverse effects. Developing pediatric tissues are also thought to be more sensitive to radiation than adult tissues, which may increase the likelihood of toxicities and secondary cancers [8][9][10][11][12].…”