Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma

Kahalley, Lisa S.; Peterson, Rachel K.; Ris, M. Douglas; Janzen, Laura; Okcu, M. Fatih; Grosshans, David R.; Ramaswamy, Vijay; Paulino, Arnold C.; Hodgson, David C.; Mahajan, Anita; Tsang, Derek S.; Laperrière, Normand; Whitehead, William E.; Dauser, Robert C.; Taylor, Michael D.; Conklin, Heather M.; Chintagumpala, Murali; Bouffet, Éric; Mabbott, Donald

doi:10.1200/jco.19.01706

Cited by 181 publications

(188 citation statements)

References 25 publications

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“…The uniform target dose can be achieved using the passive-scattering proton therapy (PSPT) technique or the more advanced intensity-modulated proton therapy (IMPT) technique employing scanned beams. Importantly, some clinical trials have indicated the advantages of proton therapy over traditional photon-based therapy [3][4][5][6] . However, there are still many challenging issues in modern proton therapy.…”

mentioning

confidence: 99%

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Ma¹,

Bronk²,

Kerr³

et al. 2020

Sci Rep

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in current treatment plans of intensity-modulated proton therapy, high-energy beams are usually assigned larger weights than low-energy beams. Using this form of beam delivery strategy cannot effectively use the biological advantages of low-energy and high-linear energy transfer (LET) protons present within the Bragg peak. However, the planning optimizer can be adjusted to alter the intensity of each beamlet, thus maintaining an identical target dose while increasing the weights of low-energy beams to elevate the Let therein. the objective of this study was to experimentally validate the enhanced biological effects using a novel beam delivery strategy with elevated LET. We used Monte Carlo and optimization algorithms to generate two different intensity-modulation patterns, namely to form a downslope and a flat dose field in the target. We spatially mapped the biological effects using high-content automated assays by employing an upgraded biophysical system with improved accuracy and precision of collected data. In vitro results in cancer cells show that using two opposed downslope fields results in a more biologically effective dose, which may have the clinical potential to increase the therapeutic index of proton therapy.Worldwide the number of proton therapy centers has increased dramatically in recent years 1 . The expansion of proton therapy centers can be attributed to multiple factors. The first and foremost advantage of protons is that a Bragg-peak dose profile appears at the end of the range of a proton beam. The use of different beam modulation and shaping techniques makes it possible to deliver a uniform high dose to the tumors while sparing the surrounding normal tissues 2 . The uniform target dose can be achieved using the passive-scattering proton therapy (PSPT) technique or the more advanced intensity-modulated proton therapy (IMPT) technique employing scanned beams. Importantly, some clinical trials have indicated the advantages of proton therapy over traditional photon-based therapy 3-6 . However, there are still many challenging issues in modern proton therapy. One of the them is that the radiobiological characteristics of proton therapy have yet to be completely understood. In current clinical practice, the relative biological effectiveness (RBE) of protons to reference photons, such as x-rays from a

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mentioning

confidence: 99%

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Ma¹,

Bronk²,

Kerr³

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

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“…74 Recently, a prospective, multi-centre, high-quality database-derived study was published which for the first time compared intellectual trajectories between paediatric patients treated with PBT versus those treated with photon RT and demonstrated a translation of theoretical dosimetric advantages into clinically measurable outcomes. 75 Randomised controlled trials are challenging to perform when testing new radiotherapy technologies. 1,73 This has been recognised by the Trans Tasman Radiation Oncology Group (TROG), and the Assessment of New Radiation Oncology Technologies and Treatment (ANROTAT) Project was developed to address these complexities.…”

Section: What Evidence Is Needed?mentioning

confidence: 99%

Particle therapy tumour outcomes: An updated systematic review

Hwang

Gorayski

et al. 2020

J Med Imag Rad Onc

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Particle therapy (PT) offers the potential for reduced normal tissue damage as well as escalation of target dose, thereby enhancing the therapeutic ratio in radiation therapy. Reflecting the building momentum of PT use worldwide, construction has recently commenced for The Australian Bragg Centre for Proton Therapy and Research in Adelaidethe first PT centre in Australia. This systematic review aims to update the clinical evidence base for PT, both proton beam and carbon ion therapy. The purpose is to inform clinical decision-making for referral of patients to PT centres in Australia as they become operational and overseas in the interim. Three major databases were searched by two independent researchers, and evidence quality was classified according to the National Health and Medical Research Council evidence hierarchy. One hundred and thirty-six studies were included, two-thirds related to proton beam therapy alone. PT at the very least provides equivalent tumour outcomes compared to photon controls with the possibility of improved control in the case of carbon ion therapy. There is suggestion of reduced morbidities in a range of tumour sites, supporting the predictions from dosimetric modelling and the wide international acceptance of PT for specific indications based on this. Though promising, this needs to be counterbalanced by the overall low quality of evidence found, with 90% of studies of level IV (case series) evidence. Prospective comparative clinical trials, supplemented by database-derived outcome information, preferably conducted within international and national networks, are strongly recommended as PT is introduced into Australasia.

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“…Meanwhile, 104 particle therapy facilities are in clinical operation worldwide 2 . For protons, reduced neurotoxic effect compared to photons was demonstrated by the studies of Kahalley et al [25,26]. Pediatric patients treated for brain tumors with protons showed less neuropsychological impairments in terms of intelligence, perceptual reasoning, processing speed, and working memory than those treated with X-rays [25,26].…”

Section: Neurotoxic Effects Of Ionizing Radiation On the Human Brainmentioning

confidence: 99%

Solving the Issue of Ionizing Radiation Induced Neurotoxicity by Using Novel Cell Models and State of the Art Accelerator Facilities

et al. 2020

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Cognitive dysfunction induced by ionizing radiation remains a major concern in radiation therapy as well as in space mission projects. Both fields require sophisticated approaches to improve protection of the brain and its neuronal circuits. Radiation therapy related research focusses on advanced techniques imposing maximal effect on the tumor while minimizing toxicity to the surrounding tissue. Research for example has led to the revival of spatially fractionated radiation therapy (SFRT) and the advent of FLASH radiotherapy. To investigate the influence of the space radiation environment on brain cells, low dose, high LET radiation in addition to simulated microgravity have to be studied. Both research areas, however, call for cutting-edge cellular systems that faithfully resemble the architecture of the human brain, its development and its regeneration to understand the mechanisms of radiation-induced neurotoxicity and their prevention. In this review, we discuss the proposed mechanisms of neurotoxicity such as the loss of complexity within the neuronal networks, vascular changes, or neuroinflammation. We compare the current in vivo and in vitro studies of neurotoxicity including animal models, animal and human neural stem cells, and neurosphere models. Particularly, we will address the new and promising technique of generating human brain organoids and their potential use in radiation biology.

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Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma

Cited by 181 publications

References 25 publications

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Exploring the advantages of intensity-modulated proton therapy: experimental validation of biological effects using two different beam intensity-modulation patterns

Particle therapy tumour outcomes: An updated systematic review

Solving the Issue of Ionizing Radiation Induced Neurotoxicity by Using Novel Cell Models and State of the Art Accelerator Facilities

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