Current state of proton therapy for tumors of the central nervous system in Spain: physical bases, indications, controversies and perspectives.

The unique biophysical properties of proton therapy (PT), regarding the precise dose distribution, a remarkable better sparing of surrounding normal tissues, and the decreasing costs have promoted the spread of this technique worldwide. In Spain, eleven new PT centers, added to the currently two in function, are expected to be available in the near future. Indications for PT are currently evolving. The suitability of PT in central nervous system tumors of the adult population has been extrapolated from the favorable experience in children and adolescents. Given the lack of appropriate randomized trials, controversies remain regarding its use in lower grade tumors, re-irradiation, and other clinical scenarios in which an a priori dose distribution benefit is expected compared to photon-based radiotherapy. PT is a reasonable option in many brain and spinal tumors associating long life expectancy, in which cognitive decline, and the appearance of radiation-induced neoplasms can be minimized.Estado actual de la terapia con protones en los tumores del sistema nervioso central en España: bases físicas, indicaciones, controversias y perspectivas.

Riesgo de osteorradionecrosis de los maxilares según el tipo de radioterapia / Risk of Osteoradionecrosis of the Jaws according to Type of Radiotherapy

Introducción: El cáncer de cabeza y cuello es el séptimo más común a nivel mundial. Las opciones terapéuticas para su manejo incluyen la radioterapia, la cual debe procurar un equilibrio entre la eliminación del tumor y la preservación del tejido sano porque su aplicación implica el riesgo de desarrollar una osteorradionecrosis de los maxilares. Objetivo: Valorar si el riesgo de que se produzca osteorradionecrosis de los maxilares varía en función del tipo de radioterapia. Métodos: Diseño documental, retrospectivo basado en los principios de las revisiones sistemáticas exploratorias según lo establece la lista de chequeo PRISMA Extension for Scoping Reviews (PRISMA-ScR). Se realizaron búsquedas en inglés y español en PubMed, LILACS, ScienceDirect, Tripdatabase y Epistemonikos. Resultados: En total se incluyeron 12 estudios publicados entre 2016 y 2022 con diversos diseños de investigación; el estudio de cohorte retrospectivo fue el que tuvo mayor representación. Se analizaron distintas opciones de radioterapia y sus protocolos, entre ellos, la radioterapia de intensidad modulada, la terapia de protones de intensidad modulada, la radioterapia corporal estereotáctica y la radioterapia tridimensional. La literatura refiere que los protocolos que implican dosis totales más bajas representan un menor riesgo de osteorradionecrosis. Conclusiones: El riesgo de osteorradionecrosis de los maxilares debe atribuirse, en mayor medida, a la dosis total de radiación recibida por el paciente y a la dosis por fracción que al tipo de radioterapia(AU)

Introduction: Head and neck cancer is the seventh most common cancer worldwide. Therapeutic options for its management include radiotherapy, which should seek a balance between tumor elimination and preservation of healthy tissue because its application implies the risk of developing osteoradionecrosis of the jaws. Objective: To assess whether the risk of developing osteoradionecrosis of the jaws varies according to the type of radiotherapy. Methods : Documentary, retrospective design based on the principles of exploratory systematic reviews as established by the PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist. PubMed, LILACS, ScienceDirect, Tripdatabase and Epistemonikos were searched in English and Spanish. Results: In total, 12 studies published between 2016 and 2022 with various research designs were included; the retrospective cohort study had the highest representation. Different radiotherapy options and their protocols were analyzed, including intensity-modulated radiotherapy, intensity-modulated proton therapy, stereotactic body radiotherapy, and three-dimensional radiotherapy. The literature refers that protocols involving lower total doses represent a lower risk of osteoradionecrosis. Conclusions: The risk of osteoradionecrosis of the jaws should be attributed, to a greater extent, to the total radiation dose received by the patient and the dose per fraction than to the type of radiotherapy(AU)

Monte Carlo simulations of cell survival in proton SOBP.

Objective. The objective of this study is to develop a multi-scale modeling approach that accurately predicts radiation-induced DNA damage and survival fraction in specific cell lines.Approach. A Monte Carlo based simulation framework was employed to make the predictions. The FLUKA Monte Carlo code was utilized to estimate absorbed doses and fluence energy spectra, which were then used in the Monte Carlo Damage Simulation code to compute DNA damage yields in Chinese hamster V79 cell lines. The outputs were converted into cell survival fractions using a previously published theoretical model. To reduce the uncertainties of the predictions, new values for the parameters of the theoretical model were computed, expanding the database of experimental points considered in the previous estimation. Simulated results were validated against experimental data, confirming the applicability of the framework for proton beams up to 230 MeV. Additionally, the impact of secondary particles on cell survival was estimated.Main results. The simulated survival fraction versus depth in a glycerol phantom is reported for eighteen different configurations. Two proton spread out Bragg peaks at several doses were simulated and compared with experimental data. In all cases, the simulations follow the experimental trends, demonstrating the accuracy of the predictions up to 230 MeV.Significance. This study holds significant importance as it contributes to the advancement of models for predicting biological responses to radiation, ultimately contributing to more effective cancer treatment in proton therapy.

A systematic review of craniospinal irradiation for leptomeningeal disease: past, present, and future.

PURPOSE: Leptomeningeal disease (LMD) is a rare but deadly complication of cancer in which the disease spreads to the cerebrospinal fluid and seeds the meninges of the central nervous system (CNS). Craniospinal irradiation (CSI) involves treatment of the entire CNS subarachnoid space and is occasionally used as a last-resort palliative therapy for LMD. METHODS: This review examined literature describing the role of CSI for LMD from solid and hematologic malignancies in adults. A search for studies published until September 1, 2020 was conducted using PubMed database. RESULTS: A total of 262 unique articles were identified. Thirteen studies were included for analysis in which a total of 275 patients were treated with CSI for LMD. Median age at time of irradiation was 43 years, and most patients had KPS score of 70 and higher. The most common cancers resulting in LMD were acute lymphocytic leukemia, breast cancer, and acute myelogenous leukemia. Median CSI dose was 30 Gy and 18% of patients were treated with proton radiation. 52% of patients had stable-to-improved neurologic symptoms. Median overall survival for the entire cohort was 5.3 months. Patients treated with marrow-sparing proton radiation had median OS of 8 months. The most common treatment toxicities were hematologic and gastrointestinal events. CONCLUSIONS: Despite advances in systemic and radiation therapies, LMD remains a devastating end-stage complication of some malignancies. Treatment-related toxicities can be a significant barrier to CSI delivery. In select patients with LMD, marrow-sparing proton CSI may provide safer palliation of symptoms and prolong survival.

Adjuvant radiation therapy for bladder cancer: a dosimetric comparison of techniques.

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V35%), 65% (V65%), and 95% (V95%) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V35% rectum, V65% rectum, and V95% rectum; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V95% bowel, V65% bowel, or V35% bowel). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V65% bowel and V95% bowel for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.

The incidence of second brain tumors related to cranial irradiation.

Secondary brain tumor (SBT) is a devastating complication of cranial irradiation (CI). We reviewed the literature to determine the incidence of SBT as related to specific radiation therapy (RT) treatment modalities. The relative risk of radiation-associated SBT after conventional and conformal RT is well established and ranges from 5.65 to 10.9; latent time to develop second tumor ranges from 5.8 to 22.4 years, depending on radiation dose and primary disease. Theories and dosimetric models suggest that intensity-modulated radiation therapy may result in an increased risk of SBT, but clinical evidence is limited. The incidence of stereotactic radiosurgery-related SBT is low. Initial data suggest that no increased risk from proton therapy and dosimetric models predict a lower incidence of SBT compared with photons. In conclusion, the incidence of SBT related to CI is low. Longer follow-up is needed to clarify the impact of intensity-modulated radiation therapy, proton therapy and other developing technologies.

A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT).

With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as well as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients' average CT. All the plans delivered 50.4Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V18Gy), stomach (mean and V20Gy), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V18Gy), liver (mean dose), total bowel (V20Gy and mean dose), and small bowel (V15Gy absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose escalation and combining with radiosensitizing chemotherapy.

SU-E-T-602: Comparison of Treatment Techniques for Pelvic Node Irradiation: Intensity-Modulated Photons versus Protons.

PURPOSE: Radiotherapy planning for iliac pelvic nodes can be challenging due to the close proximity of sensitive healthy tissues such as the bowel and rectum. Modern treatment techniques like photon intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) offer improved healthy tissue sparing for similar target coverage. In this study we compare IMRT and IMPT plans for six post-cystectomy patients. METHODS: A dose of 50.4 Gy was prescribed to the planning target volume (PTV), which for IMRT is the clinical target volume (CTV) plus a 5 mm expansion for geometric uncertainties due to CTV and patient positioning errors, and for proton beams is the CTV plus the lateral 5 mm margin plus an additional longitudinal margin to allow for the proton range uncertainty. The optimization objectives are: 98% of the PTV receive at least 95% of the prescription, target maximum dose = 107% of prescription, rectum V[40Gy] < 30% and max = 105%, and bowel V[45Gy] < 125 cc and max = 107%. All IMRT and IMPT plans are made to achieve the target coverage objective. RESULTS: Using IMPT, the rectum would receive a mean dose of 9.0 Gy with an average (over the six patients) maximum dose of 38.1 Gy. Using IMRT, the rectum would receive a mean dose of 13.0 Gy and an average maximum dose of 37.6 Gy. The IMPT plans give a mean dose of 17.9 Gy and a maximum dose of 53.4 Gy for the bowel, whereas the IMRT plans give a mean dose of 23.8 Gy and a maximum dose of 53.2 Gy. Both the rectum and bowel show slightly lower mean doses for IMPT. CONCLUSIONS: Our results indicate that IMPT plans improve normal tissue sparing as compared to IMRT plans and provide adequate dose coverage of the target volume.

SU-E-T-266: Shielding Measurements for a Proton Therapy Facility.

PURPOSE: This paper is a follow up on the analytical calculations for the Roberts Proton Therapy Center with empirical data to determine the precision of the calculations from Avery, et al. METHODS: Neutrak dosimeters were placed in two sets around the facility while it was in operation at points of interest examined in Avery, et al. The doses to these dosimeters were recorded over one month for one set and two months for the other. Dosimeters that both recorded a dose and could be practically examined were compared to the doses predicted via the analytical method of Avery, et al. at their point of placement. RESULTS: Two points showed a less than 10% difference to the calculated doses. One point shielded by both concrete and pre-cast blocks and one point shielded by both concrete and the facility's cyclotron were not as precise. CONCLUSIONS: The analytical calculation method explored in Avery, et al. is fairly precise in describing the dose at various points in the facility shielded only by concrete. for materials other than concrete, such as the make-up of the cyclotron or varying wall material, it warrants follow up calculations using the same method.

TU-G-BRCD-01: Will the High Cost of Proton Therapy Facilities Limit the Availability of Proton Therapy Treatment?

The potential dose distribution advantages associated with proton therapy, and particularly with pencil beam scanning (PBS) techniques, have lead to considerable interest in this modality in recent years. However, the large capital expenditure necessary for such a project requires careful financial consideration and business planning. The complexity of the beam delivery systems impacts the capital expenditure and the PBS only systems presently being advocated can reduce these costs. Also several manufacturers are considering "one-room" facilities as less expensive alternatives to multi-room facilities. This presentation includes a brief introduction to beam delivery options (passive scattering, uniform and modulated scanning) and some of the new technologies proposed for providing less expensive proton therapy systems. Based on current experience, data on proton therapy center start-up costs, running costs and the financial challenges associated with making this highly conformal therapy more widely available will be discussed. Issues associated with proton therapy implementation that are key to project success include strong project management, vendor cooperation and collaboration, staff recruitment and training. Time management during facility start up is a major concern, particularly in multi-room systems, where time must be shared between continuing vendor system validation, verification and acceptance testing, and user commissioning and patient treatments. The challenges associated with facility operation during this period and beyond are discussed, focusing on how standardization of process, downtime and smart scheduling can influence operational efficiency. LEARNING OBJECTIVES: 1. To understand the available choices for proton therapy facilities, the different beam delivery systems and the financial implications associated with these choices. 2. To understand the key elements necessary for successfully implementing a proton therapy program. 3. To understand the challenges associated with on-going facility management to achieve an efficient fully operational system.

Simulação e análise dosimétrica de protonterapia e íons de carbono no tratamento do melanoma uveal / Simulation and dosimetric analysis of proton and carbon ion therapy in the treatment of uveal melanoma

OBJETIVO: Este artigo apresenta a avaliação dosimétrica da radioterapia por íons de carbono em comparação à protonterapia. MATERIAIS E MÉTODOS: As simulações computacionais foram elaboradas no código Geant4 (GEometry ANd Tracking). Um modelo de olho discretizado em voxels implementado no sistema Siscodes (sistema computacional para dosimetria em radioterapia) foi empregado, em que perfis de dose em profundidade e curvas de isodose foram gerados e superpostos. Nas simulações com feixe de íons de carbono, distintos valores de energia do feixe foram adotados, enquanto nas simulações com feixe de prótons os dispositivos da linha de irradiação foram incluídos e diferentes espessuras do material absorvedor foram aplicadas. RESULTADOS: As saídas das simulações foram processadas e integradas ao Siscodes para gerar as distribuições espaciais de dose no modelo ocular, considerando alterações do posicionamento de entrada do feixe. Os percentuais de dose foram normalizados em função da dose máxima para um feixe em posição de entrada específica, energia da partícula incidente e número de íons de carbono e de prótons incidentes. CONCLUSÃO: Os benefícios descritos e os resultados apresentados contribuem para o desenvolvimento das aplicações clínicas e das pesquisas em radioterapia ocular por íons de carbono e prótons.

OBJECTIVE: The present paper addresses the dosimetric evaluation of carbon ion radiotherapy as compared with proton therapy. MATERIALS AND METHODS: Computer simulations were undertaken with the Geant4 (GEometry ANd Tracking) code. An eye model discretized into voxels and implemented in the Siscodes system (computer system for dosimetry in radiation therapy) was utilized to generate and superimpose depth dose profiles and isodose curves. Different values for beam energy were adopted in the simulations of carbon ion beams, while in the simulation with proton beams irradiation line devices were included with different absorbing material thicknesses. RESULTS: The simulations outputs were processed and integrated into the Siscodes to generate the spatial dose distribution in the eye model, considering changes in the beam entrance position. The dose rates were normalized as a function of the maximum dose for a beam at a specific entrance position, incident particle energy and number of incident carbon ions and protons. CONCLUSION: The described benefits together with the presented results contribute to the development of clinical applications and researches on carbon ion and proton therapy.

Análise da distribuição espacial de dose absorvida em próton terapia ocular / Spatial distribution analysis of absorbed dose in ocular proton radiation therapy

OBJETIVO: Propõe-se avaliar os perfis de dose em profundidade e as distribuições espaciais de dose para protocolos de radioterapia ocular por prótons, a partir de simulações computacionais em código nuclear e modelo de olho discretizado em voxels. MATERIAIS E MÉTODOS: As ferramentas computacionais empregadas foram o código Geant4 (GEometry ANd Tracking) Toolkit e o SISCODES (Sistema Computacional para Dosimetria em Radioterapia). O Geant4 é um pacote de software livre, utilizado para simular a passagem de partículas nucleares com carga elétrica através da matéria, pelo método de Monte Carlo. Foram executadas simulações computacionais reprodutivas de radioterapia por próton baseada em instalações pré-existentes. RESULTADOS: Os dados das simulações foram integrados ao modelo de olho através do código SISCODES, para geração das distribuições espaciais de doses. Perfis de dose em profundidade reproduzindo o pico de Bragg puro e modulado são apresentados. Importantes aspectos do planejamento radioterápico com prótons são abordados, como material absorvedor, modulação, dimensões do colimador, energia incidente do próton e produção de isodoses. CONCLUSÃO: Conclui-se que a terapia por prótons, quando adequadamente modulada e direcionada, pode reproduzir condições ideais de deposição de dose em neoplasias oculares.

OBJECTIVE: The present study proposes the evaluation of the depth-dose profiles and the spatial distribution of radiation dose for ocular proton beam radiotherapy protocols, based on computer simulations in nuclear codes and an eye model discretized into voxels. MATERIALS AND METHODS: The employed computational tools were Geant4 (GEometry ANd Tracking) Toolkit and SISCODES (Sistema Computacional para Dosimetria em Radioterapia - Computer System for Dosimetry in Radiotherapy). Geant4 is a toolkit for simulating the passage of particles through the matter, based on Monte Carlo method. Computer simulations of proton therapy were performed based on preexisting facilities. RESULTS: Simulation data were integrated into SISCODES on the eye's model generating spatial dose distributions. Dose depth profiles reproducing the pure and modulated Bragg peaks are presented. Relevant aspects of proton beam radiotherapy planning are considered such as material absorber, modulation, collimator dimensions, incident proton energy and isodose generation. CONCLUSION: The conclusion is that proton therapy when properly modulated and directed can reproduce the ideal conditions for the dose deposition in the treatment of ocular tumors.