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This roadmap reviews the new, highly interdisciplinary research field studying the behavior of condensed matter systems exposed to radiation. The Review highlights several recent advances in the field and provides a roadmap for the development of the field over the next decade. Condensed matter systems exposed to radiation can be inorganic, organic, or biological, finite or infinite, composed of different molecular species or materials, exist in different phases, and operate under different thermodynamic conditions. Many of the key phenomena related to the behavior of irradiated systems are very similar and can be understood based on the same fundamental theoretical principles and computational approaches. The multiscale nature of such phenomena requires the quantitative description of the radiation-induced effects occurring at different spatial and temporal scales, ranging from the atomic to the macroscopic, and the interlinks between such descriptions. The multiscale nature of the effects and the similarity of their manifestation in systems of different origins necessarily bring together different disciplines, such as physics, chemistry, biology, materials science, nanoscience, and biomedical research, demonstrating the numerous interlinks and commonalities between them. This research field is highly relevant to many novel and emerging technologies and medical applications.
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Ultra-high dose-rate 'FLASH' radiotherapy may be a pivotal step forward for cancer treatment, widening the therapeutic window between radiation tumour killing and damage to neighbouring normal tissues. The extent of normal tissue sparing reported in pre-clinical FLASH studies typically corresponds to an increase in isotoxic dose-levels of 5-20%, though gains are larger at higher doses. Conditions currently thought necessary for FLASH normal tissue sparing are a dose-rate ≥40 Gy s-1, dose-per-fraction ≥5-10 Gy and irradiation duration ≤0.2-0.5 s. Cyclotron proton accelerators are the first clinical systems to be adapted to irradiate deep-seated tumours at FLASH dose-rates, but even using these machines it is challenging to meet the FLASH conditions. In this review we describe the challenges for delivering FLASH proton beam therapy, the compromises that ensue if these challenges are not addressed, and resulting dosimetric losses. Some of these losses are on the same scale as the gains from FLASH found pre-clinically. We therefore conclude that for FLASH to succeed clinically the challenges must be systematically overcome rather than accommodated, and we survey physical and pre-clinical routes for achieving this.
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Purpose: Inhibiting HMG-CoA reductase with simvastatin prevents breast cancer metastases in preclinical models and radiosensitizes monolayer and stem-like IBC cell lines in vitro . Given the extensive use of simvastatin worldwide and its expected penetration into the brain, we examined whether regulating cholesterol with simvastatin affected IBC3 HER2+ brain metastases. Methods and Materials: Breast cancer cell lines KPL4 and MDA-IBC3 were examined in vitro for DNA repair after radiation with or without statin treatment. Brain metastasis endpoints were examined in the MDA-IBC3 brain metastasis model after ex vivo exposure to lipoproteins and after tail vein injections with and without whole-brain radiotherapy (WBR) and oral statin exposure. Results: Ex vivo preculture of MDA-IBC3 cells with very low-density lipoprotein (vLDL) enhanced the growth of colonized lesions in the brain in vivo compared with control or high-density lipoprotein (HDL), and concurrent oral simvastatin/ WBR reduced the incidence of micrometastatic lesions evaluated 10 days after WBR. However, statin, with or without WBR, did not reduce the incidence, burden, or number of macrometastatic brain lesions evaluated 5 weeks after WBR. Conclusions: Although a role for cholesterol biosynthesis is demonstrated in DNA repair and response to whole brain radiation in this model, durable in vivo efficacy of concurrent whole brain irradiation and oral statin was not demonstrated.
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Purpose: Radiotherapy delivery in the definitive management of lower gastrointestinal (LGI) tract malignancies is associated with substantial risk of acute and late gastrointestinal (GI), genitourinary, dermatologic, and hematologic toxicities. Advanced radiation therapy techniques such as proton beam therapy (PBT) offer optimal dosimetric sparing of critical organs at risk, achieving a more favorable therapeutic ratio compared with photon therapy. Materials and Methods: The international Particle Therapy Cooperative Group GI Subcommittee conducted a systematic literature review, from which consensus recommendations were developed on the application of PBT for LGI malignancies. Results: Eleven recommendations on clinical indications for which PBT should be considered are presented with supporting literature, and each recommendation was assessed for level of evidence and strength of recommendation. Detailed technical guidelines pertaining to simulation, treatment planning and delivery, and image guidance are also provided. Conclusion: PBT may be of significant value in select patients with LGI malignancies. Additional clinical data are needed to further elucidate the potential benefits of PBT for patients with anal cancer and rectal cancer.
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Although Medical Physics educators have historically contributed to the education of the non-physics healthcare professions, their role was not studied in a systematic manner. In 2009, EFOMP set up a group to research the issue. In their first paper, the group carried out an extensive literature review regarding physics teaching for the non-physics healthcare professions. Their second paper reported the results of a pan-European survey of physics curricula delivered to the healthcare professions and a Strengths-Weaknesses-Opportunities-Threats (SWOT) audit of the role. The group's third paper presented a strategic development model for the role, based on the SWOT data. A comprehensive curriculum development model was subsequently published, whilst plans were laid to develop the present policy statement. This policy statement presents mission and vision statements for Medical Physicists teaching non-physics users of medical devices and physical agents, best practices for teaching non-physics healthcare professionals, a stepwise process for curriculum development (content, method of delivery and assessment), and summary recommendations based on the aforementioned research studies.
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Educação Médica , Física Médica , Humanos , Física Médica/educação , Currículo , Políticas , Atenção à SaúdeRESUMO
A paradigm shift is occurring in clinical oncology exploiting the recent discovery that short pulses of ultra-high dose rate (UHDR) radiation-FLASH radiotherapy-can significantly spare healthy tissues whilst still being at least as effective in curing cancer as radiotherapy at conventional dose rates. These properties promise reduced post-treatment complications, whilst improving patient access to proton beam radiotherapy and reducing costs. However, accurate dosimetry at UHDR is extremely complicated. This work presents measurements performed with a primary-standard proton calorimeter and derivation of the required correction factors needed to determine absolute dose for FLASH proton beam radiotherapy with an uncertainty of 0.9% (1[Formula: see text]), in line with that of conventional treatments. The establishment of a primary standard for FLASH proton radiotherapy improves accuracy and consistency of the dose delivered and is crucial for the safe implementation of clinical trials, and beyond, for this new treatment modality.
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Neoplasias , Terapia com Prótons , Humanos , Prótons , Dosagem Radioterapêutica , Radiometria , Neoplasias/radioterapiaRESUMO
PURPOSE: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. METHODS: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeV energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D(0)) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D(0). The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD(RBPC). The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD(full). The calculated values of PISD(RBPC) obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD(full)∕PISD(RBPC) at different depths for PPBSs of different energies. RESULTS: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD(RBPC) values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD(full) values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. CONCLUSIONS: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.
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Algoritmos , Prótons , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Alta Energia/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To demonstrate predictive anatomical modelling for improving the clinical workflow of adaptive intensity-modulated proton therapy (IMPT) for head and neck cancer. METHODS: 10 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT, weekly verification CTs during radiotherapy and predicted weekly CTs from our anatomical model. Predicted CTs were used to create predicted adaptive plans in advance with the aim of maintaining clinically acceptable dosimetry. Adaption was triggered when the increase in mean dose (Dmean) to the parotid glands exceeded 3 Gy(RBE). We compared the accumulated dose of two adaptive IMPT strategies: 1) Predicted plan adaption: One adaptive plan per patient was optimised on a predicted CT triggered by replan criteria. 2) Standard replan: One adaptive plan was created reactively in response to the triggering weekly CT. RESULTS: Statistical analysis demonstrates that the accumulated dose differences between two adaptive strategies are not significant (p > 0.05) for CTVs and OARs. We observed no meaningful differences in D95 between the accumulated dose and the planned dose for the CTVs, with mean differences to the high-risk CTV of -1.20 %, -1.23 % and -1.25 % for no adaption, standard and predicted plan adaption, respectively. The accumulated parotid Dmean using predicted plan adaption is within 3 Gy(RBE) of the planned dose and 0.31 Gy(RBE) lower than the standard replan approach on average. CONCLUSION: Prediction-based replanning could potentially enable adaptive therapy to be delivered without treatment gaps or sub-optimal fractions, as can occur during a standard replanning strategy, though the benefit of using predicted plan adaption over the standard replan was not shown to be statistically significant with respect to accumulated dose in this study. Nonetheless, a predictive replan approach can offer advantages in improving clinical workflow efficiency.
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Neoplasias Nasofaríngeas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Fluxo de TrabalhoRESUMO
PURPOSE: To incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatment plans. METHODS: A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3-field to 5-field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weekly CT. RESULTS: Among four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D mean $_{\text{mean}}$ ) of parotid 11.87 Gy, increase in max dose (D max $_{\text{max}}$ ) of brainstem 20.82 Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D mean $_{\text{mean}}$ by 4.88 Gy, increase in brainstem D max $_{\text{max}}$ by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low-risk CTV. CONCLUSION: This study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocenter shift.
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Neoplasias de Cabeça e Pescoço , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Estudos Retrospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em RiscoRESUMO
PURPOSE: To provide ultrahigh dose rate (UHDR) pencil beam scanning (PBS) proton dosimetry comparison of clinically used plane-parallel ion chambers, PTW (Physikalisch-Technische Werkstaetten) Advanced Markus and IBA (Ion Beam Application) PPC05, with a proton graphite calorimeter in a support of first in-human proton FLASH clinical trial. METHODS: Absolute dose measurement intercomparison of the plane-parallel plate ion chambers and the proton graphite calorimeter was performed at 5-cm water-equivalent depth using rectangular 250-MeV single-layer treatment plans designed for the first in-human FLASH clinical trial. The dose rate for each field was designed to remain above 60 Gy/s. The ion recombination effects of the plane-parallel plate ion chambers at various bias voltages were also investigated in the range of dose rates between 5 and 60 Gy/s. Two independent model-based extrapolation methods were used to calculate the ion recombination correction factors ks to compare with the two-voltage technique from most widely used clinical protocols. RESULTS: The mean measured dose to water with the proton graphite calorimeter across all the predefined fields is 7.702 ± 0.037 Gy. The average ratio over the predefined fields of the PTW Advanced Markus chamber dose to the calorimeter reference dose is 1.002 ± 0.007, whereas the IBA PPC05 chamber shows â¼3% higher reading of 1.033 ± 0.007. The relative differences in the ks values determined from between the linear and quadratic extrapolation methods and the two-voltage technique for the PTW Advanced Markus chamber are not statistically significant, and the trends of dose rate dependence are similar. The IBA PPC05 shows a flat response in terms of ion recombination effects based on the ks values calculated using the two-voltage technique. Differences in ks values for the PPC05 between the two-voltage technique and other model-based extrapolation methods are not statistically significant at FLASH dose rates. Some of the ks values for the PPC05 that were extrapolated from the three-voltage linear method and the semiempirical model were reported less than unity possibly due to the charge multiplication effect, which was negligible compared to the volume recombination effect in FLASH dose rates. CONCLUSIONS: The absolute dose measurements of both PTW Advanced Markus and IBA PPC05 chambers are in a good agreement with the National Physical Laboratory graphite calorimeter reference dose considering overall uncertainties. Both ion chambers also demonstrate good reproducibility as well as stability as reference dosimeters in UHDR PBS proton radiotherapy. The dose rate dependency of the ion recombination effects of both ion chambers in cyclotron generated PBS proton beams is acceptable and therefore, both chambers are suitable to use in clinical practice for the range of dose rates between 5 and 60 Gy/s.
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Grafite , Prótons , Protocolos Clínicos , Humanos , Radiometria/métodos , Reprodutibilidade dos Testes , ÁguaRESUMO
PURPOSE: To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. RESULTS: Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). CONCLUSIONS: Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.
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Neoplasias da Mama/radioterapia , Terapia com Prótons , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Resultado do TratamentoRESUMO
Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.
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Neoplasias da Mama/radioterapia , Terapia com Prótons/métodos , Mama/efeitos da radiação , Consenso , Análise Custo-Benefício , Feminino , Humanos , Transferência Linear de Energia , Recidiva Local de Neoplasia , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica RelativaRESUMO
PURPOSE: In pencil beam scanning proton therapy, target coverage is achieved by scanning the pencil beam laterally in the x- and y-directions and delivering spots of dose to positions at a given radiological depth (layer). Dose is delivered to the spots on different layers by pencil beams of different energy until the entire volume has been irradiated. The aim of this study is to investigate the implementation of proton planning parameters (spot spacing, layer spacing and margins) in four commercial proton treatment planning systems (TPSs): Eclipse, Pinnacle3 , RayStation and XiO. MATERIALS AND METHODS: Using identical beam data in each TPS, plans were created on uniform material synthetic phantoms with cubic targets. The following parameters were systematically varied in each TPS to observe their different implementations: spot spacing, layer spacing and margin. Additionally, plans were created in Eclipse to investigate the impact of these parameters on plan delivery and optimal values are suggested. RESULTS: It was found that all systems except Eclipse use a variable layer spacing per beam, based on the Bragg peak width of each energy layer. It is recommended that if this cannot be used, then a constant value of 5 mm will ensure good dose homogeneity. Only RayStation varies the spot spacing according to the variable spot size with depth. If a constant spot spacing is to be used, a value of 5 mm is recommended as a good compromise between dose homogeneity, plan robustness and planning time. It was found that both Pinnacle3 and RayStation position spots outside of the defined volume (target plus margin). CONCLUSIONS: All four systems are capable of delivering uniform dose distributions to simple targets, but their implementation of the various planning parameters is different. In this paper comparisons are made between the four systems and recommendations are made as to the values that will provide the best compromise in dose homogeneity and planning time.
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Tomografia Computadorizada Quadridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/radioterapia , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Humanos , Movimento , Imagens de Fantasmas , Dosagem RadioterapêuticaRESUMO
BACKGROUND: To quantify the geometrical changes of each neck nodal level (NNL) and estimate the geometric planning target volume (PTV) margin during image-guided radiotherapy (IGRT) for nasopharyngeal cancer (NPC). METHODS: Twenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) and 6 weekly repeat CT (CTrep) scans during chemoradiotherapy. Each CTrep was rigidly registered to the CTplan. All the NNLs were manually delineated in each transverse CT section. When comparing the NNL in CTrep with CTplan, their volumes, displacement of the center of the mass, and the shortest perpendicular distance (SPD) were automatically calculated. This was followed by calculation of the systematic and random errors, overlapping index (OI), and dice similarity coefficient (DSC). With PTVs isotropically expanded from NNL by 1, 2, 3, 4, and 5 mm, they were compared with NNL itself; OI >0.95 was defined as the acceptable geometrical coverage. The Mann-Whitney test was used for statistical analysis. RESULTS: All volumes, OI, and DSC of the NNLs (not including level IA) showed a linear decrease over time throughout the treatment course. The volume of NNLs decreased by 1-6% in the first week and 10-21% in the sixth week. The mean SPD was 1.3-1.7 and 1.9-3.5 mm in the first and sixth week respectively. The DSCs for nodal level IB, II, III, and IV were >0.7 and that of level V was <0.7 throughout the treatment course. For level IA and VI, DSC was <0.7 after the 2nd week. To maintain the OI >0.95, 2-5 mm was needed to expand the different NNLs. CONCLUSIONS: The geometrical changes of each NNL are substantial and the necessary margin of 2-5 mm depended on individual NNL is needed to maintain geometrical coverage throughout the course of IGRT for NPC.
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The National Cancer Institute's (NCI) Radiation Research Program (RRP) is endeavoring to increase the relevance of preclinical research to improve outcomes of radiation therapy for cancer patients. These efforts include conducting symposia, workshops and educational sessions at annual meetings of professional societies, including the American Association of Physicists in Medicine, American Society of Radiation Oncology, Radiation Research Society (RRS), Radiosurgery Society, Society of Nuclear Medicine and Molecular Imaging, Society for Immunotherapy of Cancer and the American Association of Immunology. A symposium entitled "Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities" was conducted by the NCI's RRP during the 63rd Annual Meeting of the RRS on October 16, 2017 in Cancun, Mexico. In this symposium, discussions were held to address the challenges in developing radiation-drug combinations, optimal approaches with scientific evidence to replace standard-of-care, approaches to reduce normal tissue toxicities and enhance post-treatment quality-of-life and recent advances in antibody-drug conjugates. The symposium included two broad overview talks followed by two talks illustrating examples of radiation-drug combinations under development. The overview talks identified the essential preclinical infrastructure necessary to accelerate progress in the development of evidence and important challenges in the translation of drug combinations to the clinic from the laboratory. Also addressed, in the example talks (in light of the suggested guidelines and identified challenges), were the development and translation of novel antibody drug conjugates as well as repurposing of drugs to improve efficacy and reduce normal tissue toxicities. Participation among a cross section of clinicians, scientists and scholars-in-training alike who work in this focused area highlighted the importance of continued discussions to identify and address complex challenges in this emerging area in radiation oncology.
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Quimiorradioterapia , Efeitos Adversos de Longa Duração/prevenção & controle , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Quimiorradioterapia/efeitos adversos , Reposicionamento de Medicamentos , Humanos , Imunoconjugados/uso terapêutico , México , Radiossensibilizantes/uso terapêutico , Sociedades Médicas , Padrão de Cuidado , Pesquisa Translacional Biomédica , Resultado do TratamentoRESUMO
Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials ((18)O, Cu, and (68)Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm(-3)) and beef (~1.0 g cm(-3)) were embedded with Cu or (68)Zn foils of several volumes (10-50 mm(3)). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils' PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.
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Marcadores Fiduciais , Tomografia por Emissão de Pósitrons , Terapia com Prótons , Radioterapia Guiada por Imagem/normas , Humanos , Metais , Imagens de Fantasmas , Próteses e ImplantesRESUMO
PURPOSE: Proton-accelerated partial breast irradiation (APBI) is early in its developmental phase without standardized treatment parameters. We report an approach to multibeam proton APBI using a universally available supine setup and deliberate beam arrangement strategy to limit the total area of skin receiving a full dose while being robust for interfraction variation. METHODS AND MATERIALS: Thirty-three American Society for Radiation Oncology consensus-suitable/cautionary APBI candidates were treated using a passively scattered proton beam between 2010 and 2014 to 34 Gy relative biological effectiveness in 10 fractions twice daily. All patients were immobilized in a Vac-Lok cradle, typically with the arm down, and adducted to mound the breast and facilitate multiple, optimal en face beams. Radiopaque wires were placed on the surgical scar and 3 markers separate from the scar were placed elsewhere on the breast. All markers were used for each setup and removed before treatment. Marker displacement, wire rotation, and wire displacement were recorded from 10 random patients (100 orthogonal films). A 15-mm expansion was made to the tumor bed to obtain a clinical target volume, and followed by a 5-mm skin contraction and exclusion of the chest wall. A radial planning target volume margin of 5 mm was used. RESULTS: Across 100 pretreatment images, median displacement of 3 distinct skin set-up markers was 3, 4, and 3 mm. Displacement of the scar wire in the X and Y direction was 0 and 1 mm, respectively. Among 28 verification scans performed, only 1 resulted in adaptive planning because of the initial presence of an air pocket in the lumpectomy cavity that resolved spontaneously during treatment. CONCLUSIONS: APBI proton treatment using a supine approach was largely reproducible. Inter-fraction variation demonstrates 5-mm radial planning margins were adequate; however, outliers do occur and films should be reviewed critically and in real time. This technique is straightforward and could be used at any proton facility without the need for specialized equipment.
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Neoplasias da Mama/radioterapia , Posicionamento do Paciente/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Mama/fisiologia , Feminino , Humanos , Reprodutibilidade dos Testes , Decúbito DorsalRESUMO
BACKGROUND: As the number of proton therapy centers increases, so does the need for studies which compare proton treatments between institutions and with photon therapy. However, results of such studies are highly dependent on target volume definition and treatment planning techniques. Thus, standardized methods of treatment planning are needed, particularly for proton treatment planning, in which special consideration is paid to the depth and sharp distal fall-off of the proton distribution. This study presents and evaluates a standardized method of proton treatment planning for craniospinal irradiation (CSI). METHODS: We applied our institution's planning methodology for proton CSI, at the time of the study, to an anatomically diverse population of 18 pediatric patients. We evaluated our dosimetric results for the population as a whole and for the two subgroups having two different age-specific target volumes using the minimum, maximum, and mean dose values in 10 organs (i.e., the spinal cord, brain, eyes, lenses, esophagus, lungs, kidneys, thyroid, heart, and liver). We also report isodose distributions and dose-volume histograms (DVH) for 2 representative patients. Additionally we report population-averaged DVHs for various organs. RESULTS: The planning methodology here describes various techniques used to achieve normal tissue sparing. In particular, we found pronounced dose reductions in three radiosensitive organs (i.e., eyes, esophagus, and thyroid) which were identified for optimization. Mean doses to the thyroid, eyes, and esophagus were 0.2%, 69% and 0.2%, respectively, of the prescribed dose. In four organs not specifically identified for optimization (i.e., lungs, liver, kidneys, and heart) we found that organs lateral to the treatment field (lungs and kidneys) received relatively low mean doses (less than 8% of the prescribed dose), whereas the heart and liver, organs distal to the treatment field, received less than 1% of the prescribed dose. CONCLUSIONS: This study described and evaluated a standardized method for proton treatment planning for CSI. Overall, the standardized planning methodology yielded consistently high quality treatment plans and perhaps most importantly, it did so for an anatomically diverse patient population.