A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma

Ho, Evangeline S Q; Barrett, Sarah; Mullaney, L.

doi:10.1080/0284186x.2017.1324207

Cited by 36 publications

(24 citation statements)

References 54 publications

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“…Translation into quality of life (QoL) has been studied in a prospective trial 111. QoL scores were found to improve over time after proton CSI, and after 5 years, children-reported scores were statistically similar to those of healthy children, but the parent-reported scores remained statistically lower than those reported by the parents of healthy children 112. To evaluate the superiority of proton therapy in medulloblastoma treatment with an evidence-based approach, a review recently compared the outcomes of pediatric medulloblastoma patients between proton- and photon-mediated CSI,113 and revealed the advantage of proton therapy in organs at risk sparing, normal organ dysfunction, and secondary malignancy risks compared to various (mostly 3D-CRT) photon techniques.…”

Section: Optimizing Care From Molecular Classificationmentioning

confidence: 99%

“…The only way to determine with any certainty whether proton therapy should be developed as a standard of care for CSI would be through a prospective randomized controlled trial comparing both treatment modalities. Such a trial should include cost-effectiveness analysis since proton therapy is undoubtedly associated with higher initial infrastructural costs than those for photon therapy 112. At the present time, proton therapy remains a limited resource, and socioeconomic factors impact access to this treatment 113…”

Section: Optimizing Care From Molecular Classificationmentioning

confidence: 99%

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<p>Medulloblastoma: optimizing care with a multidisciplinary approach</p>

Thomas

Noël

2019

JMDH

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Medulloblastoma is a malignant tumor of the cerebellum and the most frequent malignant brain tumor in children. The standard of care consists of maximal resection surgery, followed by craniospinal irradiation and chemotherapy. Such treatment allows long-term survival rates of nearly 70%; however, there are wide disparities among patient outcomes, and in any case, major long-term morbidity is observed with conventional treatment. In the last two decades, the molecular understanding of medulloblastoma has improved drastically, allowing us to revolutionize our understanding of medulloblastoma pathophysiological mechanisms. These advances led to an international consensus in 2010 that defined four prognostic molecular subgroups named after their affected signaling pathways, that is, WNT, SHH, Group 3 and Group 4. The molecular understanding of medulloblastoma is starting to translate through to clinical settings due to the development of targeted therapies. Moreover, recent improvements in radiotherapy modalities and the reconsideration of craniospinal irradiation according to the molecular status hold promise for survival preservation and the reduction of radiation-induced morbidity. This review is an overview of the current knowledge of medulloblastoma through a molecular approach, and therapeutic prospects currently being developed in surgery, radiotherapy and targeted therapies to optimize the treatment of medulloblastoma with a multidisciplinary approach will also be discussed.

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Section: Optimizing Care From Molecular Classificationmentioning

confidence: 99%

Section: Optimizing Care From Molecular Classificationmentioning

confidence: 99%

<p>Medulloblastoma: optimizing care with a multidisciplinary approach</p>

Thomas

Noël

2019

JMDH

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“…Besides continuous advances in image-guided (IG) intensity-modulated (IM) photon radiotherapy, particle therapy with protons is establishing itself as a high-conformal RT modality which is able to improve normal tissues dose sparing while maintaining excellent target coverage [5]. Indeed, thanks to the physical characteristics of protons—such as the typical dose distribution within the “Bragg peak” [6], Proton Beam Therapy (PBT) could represent a safe alternative to photon RT for pediatric tumors or other neoplasms arising next to critical OARs [1]. Nevertheless, radiobiological uncertainties about the interaction of these charged particles with normal and neoplastic cells still persist [6].…”

Section: Introductionmentioning

confidence: 99%

Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

Carbonara

Rito

Monti

et al. 2019

Journal of Oncology

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Background Radiotherapy (RT) plays a fundamental role in the treatment of pediatric central nervous system (CNS) malignancies, but its late sequelae are still a challenging question. Despite developments in modern high-conformal photon techniques and proton beam therapy (PBT) are improving the normal tissues dose-sparing while maintaining satisfactory target coverage, clinical advantages supporting the optimal treatment strategy have to be better evaluated in long-term clinical studies and assessed in further radiobiological analyses. Our analysis aimed to systematically review current knowledge on the dosimetric advantages of PBT in the considered setting, which should be the basis for future specific studies. Materials and Methods A PubMed and Google Scholar search was conducted in June 2019 to select dosimetric studies comparing photon versus proton RT for pediatric patients affected by CNS tumors. Then, a systematic review and meta-analysis according to the PRISMA statement was performed. Average and standard deviation values of Conformity Index, Homogeneity Index, and mean and maximum doses to intracranial and extracranial organs at risk (OARs) were specifically evaluated for secondary dosimetric comparisons. The standardized mean differences (SMDs) for target parameters and the mean differences (MDs) for OARs were summarized in forest plots (P < 0.05 was considered statistically significant). Publication bias was also assessed by the funnel plot and Egger's regression test. Results Among the 88 identified papers, a total of twelve studies were included in the meta-analysis. PBT showed dosimetric advantages in target homogeneity (significant especially in the subgroup comparing PBT and 3D conformal RT), as well as in the dose sparing of almost all analyzed OARs (significantly superior results for brainstem, normal brain, and hippocampal dose constraints and for extracranial OARs parameters, excluding the kidneys). Publication bias was observed for Conformity Index. Conclusion Our analysis supports the evidence of dosimetric advantages of PBT over photon RT, especially in the dose sparing of normal growing tissues. Confirmations from wider well-designed studies are required.

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“…More recently, proton therapy has emerged as a major RT modality for the treatment of medulloblastoma. Multiple dosimetric studies of RT for medulloblastoma have demonstrated the superior dose distribution of protons as compared to photons [65], and emerging clinical evidence suggests that proton-based CSI/boost therapy for pediatric patients with medulloblastoma reduces acute and late effects without reducing tumor control [66][67][68][69][70].…”

Section: Advances In Radiotherapy Techniquesmentioning

confidence: 99%

Preclinical Models of Craniospinal Irradiation for Medulloblastoma

Stripay

Merchant

Roussel

et al. 2020

Cancers

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Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the realization that medulloblastoma is a heterogeneous disease comprising four distinct molecular subgroups (wingless [WNT], sonic hedgehog [SHH], Group 3 [G3], and Group 4 [G4]) with distinct clinical characteristics and prognoses has refocused efforts to better define the optimal role of CSI within and across disease subgroups. The ability to deliver clinically relevant CSI to preclinical models of medulloblastoma offers the potential to study radiation dose and volume effects on tumor control and toxicity in these subgroups and to identify subgroup-specific combination adjuvant therapies. Recent efforts have employed commercial image-guided small animal irradiation systems as well as custom approaches to deliver accurate and reproducible fractionated CSI in various preclinical models of medulloblastoma. Here, we provide an overview of the current clinical indications for, and technical aspects of, irradiation of pediatric medulloblastoma. We then review the current literature on preclinical modeling of and treatment interventions for medulloblastoma and conclude with a summary of challenges in the field of preclinical modeling of CSI for the treatment of leptomeningeal seeding tumors.Cancers 2020, 12, 133 2 of 16 for, medulloblastoma. The review concludes with a summary of outstanding questions in the field of preclinical modeling of RT for pediatric brain tumors and a consideration of future directions for treating leptomeningeal seeding tumors with these approaches. Clinical Management of Medulloblastoma: The Evolving Role of Radiation Therapy BackgroundLike many embryonal tumors, medulloblastoma shows a predilection for distant metastatic spread and leptomeningeal seeding, with subarachnoid dissemination present in approximately 20% to 35% of cases at diagnosis and in most cases at relapse [7,8]. CSI targeting the entire neuraxis has been a standard-of-care therapy for most patients. As cure became a reality, however, long-term survivors were noted to suffer from significant radiation-associated late effects, including neurocognitive and neuroendocrine deficits, bone and soft tissue hypoplasia, vascular insults, and subsequent malignant neoplasms. Thus, efforts have been directed toward maintaining or improving overall survival rates while minimizing treatment-related toxicity. These efforts have primarily focused on modifications to RT approaches that can be broadly grouped as follows: investigations of the effects of adding concurrent and/or adjuvant chemotherapy regimens [9,10]; investigations of the effects of delaying or omitting RT for very young children [11][12][13][14]; investigations of the effects of reductions in the RT dose and field size [15,16]; and, over the past...

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A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma

Abstract: Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Cited by 36 publications

References 54 publications

<p>Medulloblastoma: optimizing care with a multidisciplinary approach</p>

<p>Medulloblastoma: optimizing care with a multidisciplinary approach</p>

Proton versus Photon Radiotherapy for Pediatric Central Nervous System Malignancies: A Systematic Review and Meta-Analysis of Dosimetric Comparison Studies

Preclinical Models of Craniospinal Irradiation for Medulloblastoma

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