Proton versus photon radiotherapy for common pediatric brain tumors: Comparison of models of dose characteristics and their relationship to cognitive function

Merchant, Thomas E.; Hua, Chia‐Ho; Shukla, Hemant; Xiao-fei, Ying; Nill, Simeon; Oelfke, Uwe

doi:10.1002/pbc.21530

Cited by 315 publications

(217 citation statements)

References 19 publications

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“…13 Similar concepts are being used successfully with other localized CNS embryonal tumors in young children, such as ependymoma and medulloblastoma. 27,28 These associations among age, radiation delivery, and magnitude of the associated difference in survival for ATRT need to be confirmed in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis

Buscariollo

Park

Roberts

et al. 2011

Cancer

157

161

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BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is a rare central nervous system malignancy with a poor prognosis that affects mostly young children. Although radiotherapy (RT) historically has been delayed in patients aged <3 years, emerging evidence suggests a role for RT to achieve long-term survivorship. Clinical features and age-dependent trends of RT use were evaluated for patients with ATRT. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify 144 patients with ATRT from 1973 to 2008. The primary endpoint was median overall survival (OS). Clinical and treatment variables were assessed for an association with OS using Cox proportional hazards models. Landmark analysis was used to correct for immortal time bias of adjuvant RT. RESULTS: The median age at diagnosis was 1 year (range, 0-67 years). Gross total resection of the primary tumor was achieved in 39% of patients, and 33% of patients received RT. From 1992 to 2008, RT use increased 2.4-fold in patients aged 3 years. The median OS for was 10 months. In multivariate analyses, metastatic disease (hazard ratio, 2.83; 95% confidence interval, 1.53-5.23; P ¼ .001) and RT (hazard ratio, 0.10; 95% confidence interval, 0.01-0.73; P ¼ .02) were identified as independent predictors of survival. Landmark analysis confirmed a robust association between RT use and survival, which was attenuated in patients ages 4 to 17 years compared with younger patients. CONCLUSIONS: The current results indicated that RT may offer a significant survival benefit for patients with ATRT and that patients aged 3 years may derive more benefit from initial RT compared with older children. The authors concluded that prospective clinical trials are needed to examine the role of RT in the initial management of ATRT in patients aged <3 years. Cancer 2012;118:4212-9. V C 2011 American Cancer Society.KEYWORDS: atypical teratoid rhabdoid tumor, central nervous system, epidemiology, radiotherapy, children. INTRODUCTIONAtypical teratoid rhabdoid tumor (ATRT) of the central nervous system (CNS) is a highly malignant embryonal neoplasm (grade 4 according to the World Health Organization classification) that typically occurs in children aged <3 years. 1-5 ATRT is extremely rare in adults, and only 31 patients have been reported in the literature. 6 Originally described in the 1980s, ATRT has been widely recognized as a rare but important clinical entity only over the past decade. 2,4 The diagnosis of ATRT has been greatly facilitated by the rise in accessibility of immunohistochemical testing in the late 1990s, which takes advantage of the frequent loss of switch/sucrose nonfermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) (also known as SNF5 homolog [hSNF5] and INI1) tumor suppressor gene products in these tumors. 2,5,7 Although ATRT comprises <5% of CNS tumors in children aged <18 years, it reportedly represents up to 20% of CNS tumors in children aged <3 years...

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Section: Discussionmentioning

confidence: 99%

Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis

Buscariollo

Park

Roberts

et al. 2011

Cancer

157

161

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“…Currently, cranial radiation dose and method of delivery vary according to protocol, risk status, and treatment center. Additional methods of risk classification as well as new methods of treatment delivery are being developed, which may further reduce radiation dose exposure and related risk (Gajjar et al 2004;Merchant et al 2008). Additional risk variables have also been identified but their impact on cognitive outcome has not been as extensively substantiated.…”

Section: A Proposed Conceptual Modelmentioning

confidence: 99%

Neurodevelopmental impact on children treated for medulloblastoma: A review and proposed conceptual model

Palmer¹

2008

Dev Disabil Res Revs

116

131

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The population of survivors following diagnosis and treatment for medulloblastoma is thankfully on the rise. An increased focus on the quality of that survivorship has expanded the concept of cure to include efforts aimed at improving long-term cognitive outcome. It is well established in the literature that decline in overall intellect and academic performance is experienced by a majority of those undergoing treatment for pediatric medulloblastoma. This decline is believed to be secondary to decline in core cognitive abilities, which in turn are related to underlying damage to neuroanatomical substrates. A review of research on neurodevelopmental impacts following diagnosis and treatment for pediatric medulloblastoma is presented. Particular consideration is given to studies recently published that also reflect critical collaboration among those within the fields of neuropsychology and neuro-imaging. Results from the review are combined within a conceptual model upon which to guide future research and clinical efforts. Keywords medulloblastoma; cognitive deficits; brain tumor; model; processing speed; attention; working memory Callouts 1. Based on the knowledge derived from studies of long term outcomes, it is important to consider medulloblastoma, as well as other pediatric cancers, as a condition resulting in life long morbidities related to the treatment for, but separate from, the primary presenting disease. 2.Intellectual and academic outcomes are considered distal markers and secondary to changes in underlying core cognitive skills.3. While much of the research to date has focused on risk for deficits in cognitive function, attention should also be paid to resilience. 4.Consideration of the current literature on children diagnosed and treated for medulloblastoma reveals there is at least the start of a conceptual model illustrating the likely relationships between treatment, underlying

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“…Several reviews are available in the scientific literature on this subject [27] . Published reports on ependymoma, craniopharyngioma, retinoblastoma, and low-grade glioma suggest an improved acute and long-term toxicity profile [18,[28][29][30][31][32][33][34][35] .…”

Section: Pediatric Tumorsmentioning

confidence: 99%

The actual Interest in Radiotherapy for the Utilization of Proton Beam, Highlighting Physics Basis, Technology and Common Clinical Indications

Amichetti

2016

Journal of Tumor

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. Since that years, commercial entities began to build cyclotrons and synchrotrons for clinical purposes. Over the last 10 years, PBT has gathered more interest in the scientific community and more media and patient attention and is now flourishing in the US and abroad. As of December, 2015, 57 proton therapy centers are in operation worldwide, others are under construction and many more in a planning phase [3] . Most patients who have been treated with heavy-particle therapy were treated with protons: PTCOG (Particle Therapy Co-Operative Group) reports that between 1954 and 2014, 137 000 patients globally received part or all of their radiation therapy with particles, and in particular 86% of them with protons [4] . The generation of these particles and the building of dedicated centers, however, requires large investments and operational costs and big infrastructure. Only relatively few studies have demonstrated the effectiveness of proton therapy and the effects are surrounded with uncertainty [5] being the cost-effectiveness still the core of the controversy around the use of PBT. ABSTRACTManaging expensive technology is a debated issue in modern radiation oncology. Proton beam therapy (PBT) represents, considering its cost and its foreseen benefits, a typical case of discussion waiting for more robust results demonstrating the presumable clinical gains against the available radiation therapy (XRT) treatment alternatives based on the use of photons. The treatment with particles utilizes many different beams (neutrons, protons, pions, or helium, neon, argon, and carbon ions) that represent a distinct entity respect conventional XRT which uses photons. PBT is the most common form of heavy-particle radiation therapy used so far; it is not a new invention, being its clinical use proposed in a seminal article by R. Wilson in 1946 [1] and the first patients treated in 1954 at the Lawrence Berkeley National Laboratory in California [2] . Since cyclotron or synchrotron, used to accelerate protons to therapeutic energies, were used primarily for research in particle or nuclear physics, the initial clinical activity in proton therapy was carried out in research facilities and the use of protons in clinical practice has grown slowly for several years in non-clinical setting. More than fifty years later, after a long period of seminal work in a limited number of Institutions, PBT has gained public attention in recent years because of the rapidly increasing number of centers around the world, regardless of their high cost. Hospital-based proton beam facilities have been in operation since 1990 after the opening of the first dedicated clinical center at Loma Linda Medical

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Proton versus photon radiotherapy for common pediatric brain tumors: Comparison of models of dose characteristics and their relationship to cognitive function

Abstract: Differences in the overall dose distributions, as indicated by modeling changes in cognitive function, showed that a reduction in the lower-dose volumes or mean dose would have long-term, clinical advantages for children with MB, CR, and OPG.

Cited by 315 publications

References 19 publications

Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis

Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis

Neurodevelopmental impact on children treated for medulloblastoma: A review and proposed conceptual model

The actual Interest in Radiotherapy for the Utilization of Proton Beam, Highlighting Physics Basis, Technology and Common Clinical Indications

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