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1.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639218

RESUMO

Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells. This database was then read by the FLUKA Monte Carlo transport code, thus allowing us to calculate the Relative Biological Effectiveness (RBE) for dicentric induction along therapeutic C-ion beams. A comparison with previous results showed that, while in the higher-dose regions (e.g., the Spread-Out Bragg Peak, SOBP), the RBE for dicentrics was lower than that for cell survival. In the lower-dose regions (e.g., the fragmentation tail), the opposite trend was observed. This work suggests that, at least for some irradiation scenarios, calculating the biological effectiveness of a hadrontherapy beam solely based on the RBE for cell survival may lead to an underestimation of the risk of (late) damage to healthy tissues. More generally, following this work, BIANCA has gained the capability of providing RBE predictions not only for cell killing, but also for healthy tissue damage.


Assuntos
Morte Celular , Aberrações Cromossômicas/efeitos da radiação , Radioterapia com Íons Pesados/efeitos adversos , Linfócitos/patologia , Método de Monte Carlo , Neoplasias/radioterapia , Eficiência Biológica Relativa , Biofísica , Humanos , Linfócitos/efeitos dos fármacos
2.
Lancet Oncol ; 22(9): e391-e399, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34478675

RESUMO

The number of patients with cancer in Africa has been predicted to increase from 844 279 in 2012 to more than 1·5 million in 2030. However, many countries in Africa still lack access to radiotherapy as a part of comprehensive cancer care. The objective of this analysis is to present an updated overview of radiotherapy resources in Africa and to analyse the gaps and needs of the continent for 2030 in the context of the UN Sustainable Development Goals. Data from 54 African countries on teletherapy megavoltage units and brachytherapy afterloaders were extracted from the Directory for Radiotherapy Centres, an electronic, centralised, and continuously updated database of radiotherapy centres. Cancer incidence and future predictions were taken from the GLOBOCAN 2018 database of the International Agency for Research on Cancer. Radiotherapy need was estimated using a 64% radiotherapy utilisation rate, while assuming a machine throughput of 500 patients per year. As of March, 2020, 28 (52%) of 54 countries had access to external beam radiotherapy, 21 (39%) had brachytherapy capacity, and no country had a capacity that matched the estimated treatment need. Median income was an important predictor of the availability of megavoltage machines: US$1883 (IQR 914-3269) in countries without any machines versus $4485 (3079-12480) in countries with at least one megavoltage machine (p=0·0003). If radiotherapy expansion continues at the rate observed over the past 7 years, it is unlikely that the continent will meet its radiotherapy needs. This access gap might impact the ability to achieve the Sustainable Development Goals, particularly the target to reduce preventable, premature mortality by a third, and meet the target of the cervical cancer elimination strategy of 90% with access to treatment. Urgent, novel initiatives in financing and human capacity building are needed to change the trajectory and provide comprehensive cancer care to patients in Africa in the next decade.


Assuntos
Recursos em Saúde/tendências , Necessidades e Demandas de Serviços de Saúde/tendências , Radioterapia/tendências , África/epidemiologia , Previsões , Recursos em Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Agências Internacionais , Neoplasias/epidemiologia , Neoplasias/radioterapia , Radioterapia/estatística & dados numéricos , Desenvolvimento Sustentável
3.
Phys Med ; 89: 93-103, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358755

RESUMO

INTRODUCTION: Monte Carlo (MC) algorithms provide accurate modeling of dose calculation by simulating the delivery and interaction of many particles through patient geometry. Fast MC simulations using large number of particles are desirable as they can lead to reliable clinical decisions. In this work, we assume that faster simulations with fewer particles can approximate slower ones by denoising them with deep learning. MATERIALS AND METHODS: We use mean squared error (MSE) as loss function to train networks (sNet and dUNet), with 2.5D and 3D setups considering volumes of 7 and 24 slices. Our models are trained on proton therapy MC dose distributions of six different tumor sites acquired from 50 patients. We provide networks with input MC dose distributions simulated using 1 × 106 particles while keeping 1 × 109 particles as reference. RESULTS: On average over 10 new patients with different tumor sites, in 2.5D and 3D, our models recover relative residual error on target volume, ΔD95TV of 0.67 ± 0.43% and 1.32 ± 0.87% for sNet vs. 0.83 ± 0.53% and 1.66 ± 0.98% for dUNet, compared to the noisy input at 12.40 ± 4.06%. Moreover, the denoising time for a dose distribution is: < 9s and  < 1s for sNet vs. < 16s and  < 1.5s for dUNet in 2.5D and 3D, in comparison to about 100 min (MC simulation using 1 × 109 particles). CONCLUSION: We propose a fast framework that can successfully denoise MC dose distributions. Starting from MC doses with 1 × 106 particles only, the networks provide comparable results as MC doses with1 × 109 particles, reducing simulation time significantly.


Assuntos
Neoplasias , Terapia com Prótons , Algoritmos , Humanos , Método de Monte Carlo , Neoplasias/radioterapia , Redes Neurais de Computação , Imagens de Fantasmas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
4.
Anticancer Res ; 41(8): 3759-3767, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281835

RESUMO

BACKGROUND/AIM: The purpose of this study was to assess patients' use of a crowdfunding platform to raise funds for radiation treatment and to better understand the direct and indirect costs associated with treatments. MATERIALS AND METHODS: The GoFundMe crowdfunding database was queried for four unique categories related to radiation treatment campaigns. Covariates identified included clinical and demographic variables, and associations between amount raised and these predictors were analyzed using a generalized linear model. RESULTS: While 56% percent of campaigns cited direct costs associated with treatment, 73.4% of campaigns cited indirect costs related to treatment. Indirect expenses related to travel (31.7%) as well as living expenses (29.2%) were cited most often across all four treatment categories. CONCLUSION: This study enhances understanding regarding patients use of crowdfunding for radiation treatment. Increased focus should be placed on discussing the indirect costs of care with patients and their families.


Assuntos
Crowdsourcing/estatística & dados numéricos , Custos de Cuidados de Saúde , Neoplasias/radioterapia , Radioterapia/economia , Adolescente , Crowdsourcing/economia , Família , Humanos , Cobertura do Seguro , Neoplasias/economia , Terapia com Prótons/economia , Estados Unidos , Adulto Jovem
5.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199667

RESUMO

Nanoparticles (NPs) with a high atomic number (Z) are promising radiosensitizers for cancer therapy. However, the dependence of their efficacy on irradiation conditions is still unclear. In the present work, 11 different metal and metal oxide NPs (from Cu (ZCu = 29) to Bi2O3 (ZBi = 83)) were studied in terms of their ability to enhance the absorbed dose in combination with 237 X-ray spectra generated at a 30-300 kVp voltage using various filtration systems and anode materials. Among the studied high-Z NP materials, gold was the absolute leader by a dose enhancement factor (DEF; up to 2.51), while HfO2 and Ta2O5 were the most versatile because of the largest high-DEF region in coordinates U (voltage) and Eeff (effective energy). Several impacts of the X-ray spectral composition have been noted, as follows: (1) there are radiation sources that correspond to extremely low DEFs for all of the studied NPs, (2) NPs with a lower Z in some cases can equal or overcome by the DEF value the high-Z NPs, and (3) the change in the X-ray spectrum caused by a beam passing through the matter can significantly affect the DEF. All of these findings indicate the important role of carefully planning radiation exposure in the presence of high-Z NPs.


Assuntos
Cobre/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neoplasias/radioterapia , Radiossensibilizantes/uso terapêutico , Bismuto/química , Bismuto/uso terapêutico , Cobre/química , Relação Dose-Resposta a Droga , Humanos , Nanopartículas Metálicas/química , Método de Monte Carlo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Óxidos/química , Óxidos/uso terapêutico , Radiossensibilizantes/química , Dosagem Radioterapêutica
6.
Cancer Radiother ; 25(6-7): 554-564, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34272182

RESUMO

In the current spectrum of cancer treatments, despite high costs, a lack of robust evidence based on clinical outcomes or technical and radiobiological uncertainties, particle therapy and in particular proton therapy (PT) is rapidly growing. Despite proton therapy being more than fifty years old (first proposed by Wilson in 1946) and more than 220,000 patients having been treated with in 2020, many technological challenges remain and numerous new technical developments that must be integrated into existing systems. This article presents an overview of on-going technical developments and innovations that we felt were most important today, as well as those that have the potential to significantly shape the future of proton therapy. Indeed, efforts have been done continuously to improve the efficiency of a PT system, in terms of cost, technology and delivery technics, and a number of different developments pursued in the accelerator field will first be presented. Significant developments are also underway in terms of transport and spatial resolution achievable with pencil beam scanning, or conformation of the dose to the target: we will therefore discuss beam focusing and collimation issues which are important parameters for the development of these techniques, as well as proton arc therapy. State of the art and alternative approaches to adaptive PT and the future of adaptive PT will finally be reviewed. Through these overviews, we will finally see how advances in these different areas will allow the potential for robust dose shaping in proton therapy to be maximised, probably foreshadowing a future era of maturity for the PT technique.


Assuntos
Previsões , Neoplasias/radioterapia , Terapia com Prótons/tendências , Institutos de Câncer , Ciclotrons , Humanos , Análise de Ativação de Nêutrons , Tratamentos com Preservação do Órgão/instrumentação , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco , Terapia com Prótons/economia , Terapia com Prótons/instrumentação , Terapia com Prótons/métodos , Garantia da Qualidade dos Cuidados de Saúde , Radioterapia Guiada por Imagem/tendências , Síncrotrons
7.
J Appl Clin Med Phys ; 22(7): 177-187, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34101349

RESUMO

Rigorous radiotherapy quality surveillance and comprehensive outcome assessment require electronic capture and automatic abstraction of clinical, radiation treatment planning, and delivery data. We present the design and implementation framework of an integrated data abstraction, aggregation, and storage, curation, and analytics software: the Health Information Gateway and Exchange (HINGE), which collates data for cancer patients receiving radiotherapy. The HINGE software abstracts structured DICOM-RT data from the treatment planning system (TPS), treatment data from the treatment management system (TMS), and clinical data from the electronic health records (EHRs). HINGE software has disease site-specific "Smart" templates that facilitate the entry of relevant clinical information by physicians and clinical staff in a discrete manner as part of the routine clinical documentation. Radiotherapy data abstracted from these disparate sources and the smart templates are processed for quality and outcome assessment. The predictive data analyses are done on using well-defined clinical and dosimetry quality measures defined by disease site experts in radiation oncology. HINGE application software connects seamlessly to the local IT/medical infrastructure via interfaces and cloud services and performs data extraction and aggregation functions without human intervention. It provides tools to assess variations in radiation oncology practices and outcomes and determines gaps in radiotherapy quality delivered by each provider.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Documentação , Humanos , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador , Software
9.
J Med Imaging Radiat Oncol ; 65(4): 410-417, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33973359

RESUMO

The rapid rise in cancer incidence within the world's poorest nations highlights the need for equitable access to evidence-based cancer care. It has been previously demonstrated that radiotherapy is a cost-effective and necessary tool in cancer treatment. However, globally there is a growing divide between demand and supply of radiotherapy services. In low- and middle-income countries, this resource gap is particularly problematic. By region, the Asia-Pacific has been demonstrated to have the highest absolute deficit in radiotherapy services. Radiation oncologists in Australia and New Zealand are geographically well positioned to assist departments within the Asia-Pacific to help to reduce these inequities. The Asia-Pacific Radiation Oncology Special Interest Group (APROSIG) aims to support oncology professionals in the Asia-Pacific to develop safe and sustainable cancer services. Members have already contributed to multiple projects throughout the region, supported by grants and departmental funding. However, the backbone of support comes from volunteers sharing their time and expertise. The Australasian oncological community has the skills and knowledge to help not only those within our borders but also beyond. Such efforts provide the potential to develop valuable clinical, educational, research and leadership experiences whilst establishing networking opportunities throughout the most populated regions of the world. More options for growth and work in global health must be investigated, encouraging future trainees to consider a role within the global cancer community. Without prompt and continued action, the resource deficit is likely to grow and the inequity in accessing radiotherapy and other cancer services further magnified.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Ásia , Países em Desenvolvimento , Humanos , Neoplasias/radioterapia , Radio-Oncologistas
11.
Radiother Oncol ; 160: 236-239, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33992629

RESUMO

Radiotherapy interventions are rapidly evolving and improving, holding promise for better patient outcomes, yet at the possible detriment of higher societal costs. The ESTRO-HERO value-based radiotherapy project aims to develop a framework defining and assessing the value of radiotherapy innovations, to support clinical implementation and equitable access, within a sustainable healthcare system.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Custos e Análise de Custo , Atenção à Saúde , Humanos , Neoplasias/radioterapia , Radioterapia
12.
PLoS One ; 16(4): e0249452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793680

RESUMO

The dose uniformity and penumbra in the treatment field are important factors in radiotherapy, which affects the outcomes of radiotherapy. In this study, the integrated depth-dose-distributions (IDDDs) of 190 MeV/u and 260 MeV/u carbon beams in the active spot-scanning delivery system were measured and calculated by FLUKA Monte Carlo simulation based on the Heavy Ion Medical Machine (HIMM). Considering the dose distributions caused by secondary particles and scattering, we also used different types of pencil beam (PB) models to fit and compare the spatial distributions of PB. We superposed a bunch of PB to form a 20×20 cm2 treatment field with the double Gaussian and double Gaussian logistic beam models and calculated the influence of beam delivery error on the field flatness and penumbra, respectively. The simulated IDDDs showed good agreement with the measured values. The triple Gaussian and double Gaussian logistic beam models have good fitness to the simulated dose distributions. There are different influences on dose uniformity and penumbra resulting from beam uncertainties. These results would be helpful for understanding carbon ion therapy, and physical therapists are more familiar with beam characteristics for active scanning therapy, which provides a reference for commissioning and optimization of treatment plans in radiotherapy.


Assuntos
Radioterapia com Íons Pesados/métodos , Dosagem Radioterapêutica , Radioterapia com Íons Pesados/instrumentação , Humanos , Método de Monte Carlo , Neoplasias/radioterapia , Distribuição Normal
13.
Anticancer Res ; 41(4): 1971-1974, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813403

RESUMO

BACKGROUND/AIM: Oncological care has faced several challenges during the COVID-19 pandemic, e.g. treatment delay and worsening symptoms. Patient-reported anxiety, depression and sleep quality might have changed due to these special circumstances. Therefore, we analyzed the symptom burden of patients treated with palliative radiotherapy at our center. PATIENTS AND METHODS: A retrospective study was performed of 50 consecutive patients and the results were compared to those obtained in a previous pre-COVID study. The Edmonton Symptom Assessment Scale was employed to assess the preradiotherapy symptoms. RESULTS: The highest mean scores were reported for pain in activity (3.2) and dry mouth (3.1). Regarding anxiety, sadness/depression and sleep, the corresponding scores were 1.5, 1.2 and 2.7, respectively. Compared to the previous study, no significant increases were found. Most items had numerically lower mean values, e.g. anxiety (1.5 vs. 2.7). Both study populations had comparable median age (70.5 vs. 70 years), gender distribution and proportion of patients with bone metastases. However, there were two significant imbalances, namely a lower proportion of patients with prostate cancer (12 vs. 30%, p=0.02) and breast cancer (0 vs. 12%, p=0.02). CONCLUSION: In patients who showed up for radiation treatment planning, the suspected increase in anxiety, sadness/depression and sleep disturbance was not demonstrable. It is not known whether or not patients with substantial worries chose to decline referral to palliative radiotherapy. Therefore, comprehensive large-scale studies of patterns of care are needed to fully understand the impact of COVID-19-related measures.


Assuntos
COVID-19/epidemiologia , Efeitos Psicossociais da Doença , Neoplasias/radioterapia , Cuidados Paliativos/métodos , Pandemias , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Ansiedade/etiologia , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Dor do Câncer/diagnóstico , Dor do Câncer/epidemiologia , Dor do Câncer/etiologia , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/patologia , Noruega/epidemiologia , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Análise de Sobrevida , Avaliação de Sintomas
14.
JCO Glob Oncol ; 7: 410-415, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33760639

RESUMO

PURPOSE: The COVID-19 pandemic significantly disrupted cancer care in Africa, further exposing major health disparities. This paper compares and contrasts the experiences of 15 clinicians in six different African cancer centers to highlight the positive aspects (silver linings) in an otherwise negative situation. METHODS: Data are from personal experience of the clinicians working at the six cancer centers blended with what is available in the literature. RESULTS: The impact of COVID-19 on cancer care appeared to vary not only across the continent but also over cancer centers. Different factors such as clinic location, services offered, available resources, and level of restrictions imposed because of COVID-19 were associated with these variations. Collectively, delays in treatment and limited access to cancer care were commonly reported in the different regions. CONCLUSION: There is a lack of data on cancer patients with COVID-19 and online COVID-19 and cancer registries for Africa. Analysis of the available data, however, suggests a higher mortality rate for cancer patients with COVID-19 compared with those without cancer. Positive or silver linings coming out of the pandemic include the adoption of hypofractionated radiation therapy and teleoncology to enhance access to care while protecting patients and staff members. Increasing collaborations using online technology with oncology health professionals across the world are also being seen as a silver lining, with valuable sharing of experiences and expertise to improve care, enhance learning, and reduce disparities. Advanced information and communication technologies are seen as vital for such collaborations and could avail efforts in dealing with the ongoing pandemic and potential future crises.


Assuntos
COVID-19 , Institutos de Câncer , Neoplasias , África/epidemiologia , COVID-19/epidemiologia , Institutos de Câncer/organização & administração , Institutos de Câncer/tendências , Acesso aos Serviços de Saúde , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias/virologia
15.
J Natl Compr Canc Netw ; 19(4): 421-431, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33578375

RESUMO

BACKGROUND: Understanding the sources of variation in the use of high-cost technologies is important for developing effective strategies to control costs of care. Palliative radiation therapy (RT) is a discretionary treatment and its use may vary based on patient and clinician factors. METHODS: Using data from the SEER-Medicare linked database, we identified patients diagnosed with metastatic lung, prostate, breast, and colorectal cancers in 2010 through 2015 who received RT, and the radiation oncologists who treated them. The costs of radiation services for each patient over a 90-day episode were calculated, and radiation oncologists were assigned to cost quintiles. The use of advanced technologies (eg, intensity-modulated radiation, stereotactic RT) and the number of RT treatments (eg, any site, bone only) were identified. Multivariable random-effects models were constructed to estimate the proportion of variation in the use of advanced technologies and extended fractionation (>10 fractions) that could be explained by patient fixed effects versus physician random effects. RESULTS: We identified 37,361 patients with metastatic lung cancer, 3,684 with metastatic breast cancer, 5,323 with metastatic prostate cancer, and 8,726 with metastatic colorectal cancer, with 34%, 27%, 22%, and 9% receiving RT within the first year, respectively. The use of advanced technologies and extended fractionation was associated with higher costs of care. Compared with the patient case-mix, physician variation accounted for a larger proportion of the variation in the use of advanced technologies for palliative RT and the use of extended fractionation. CONCLUSIONS: Differences in radiation oncologists' practice and choices, rather than differences in patient case-mix, accounted for a greater proportion of the variation in the use of advanced technologies and high-cost radiation services.


Assuntos
Neoplasias , Cuidados Paliativos , Padrões de Prática Médica , Radio-Oncologistas , Fracionamento da Dose de Radiação , Humanos , Medicare , Neoplasias/radioterapia , Programa de SEER , Estados Unidos/epidemiologia
16.
JCO Glob Oncol ; 7: 311-323, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33617304

RESUMO

PURPOSE: There has been noteworthy concern about the impact of COVID-19 pandemic on health services including the management of cancer. In addition to being considered at higher risk for worse outcomes from COVID-19, people with cancer may also experience disruptions or delays in health services. This systematic review aimed to identify the delays and disruptions to cancer services globally. METHODS: This is a systematic review with a comprehensive search including specific and general databases. We considered any observational longitudinal and cross-sectional study design. The selection, data extraction, and methodological assessment were performed by two independent reviewers. The methodological quality of the studies was assessed by specific tools. The delays and disruptions identified were categorized, and their frequency was presented. RESULTS: Among the 62 studies identified, none exhibited high methodological quality. The most frequent determinants for disruptions were provider- or system-related, mainly because of the reduction in service availability. The studies identified 38 different categories of delays and disruptions with impact on treatment, diagnosis, or general health service. Delays or disruptions most investigated included reduction in routine activity of cancer services and number of cancer surgeries; delay in radiotherapy; and delay, reschedule, or cancellation of outpatient visits. Interruptions and disruptions largely affected facilities (up to 77.5%), supply chain (up to 79%), and personnel availability (up to 60%). CONCLUSION: The remarkable frequency of delays and disruptions in health care mostly related to the reduction of the COVID-19 burden unintentionally posed a major risk on cancer care worldwide. Strategies can be proposed not only to mitigate the main delays and disruptions but also to standardize their measurement and reporting. As a high number of publications continuously are being published, it is critical to harmonize the upcoming reports and constantly update this review.


Assuntos
COVID-19 , Atenção à Saúde/métodos , Neoplasias/terapia , Assistência Ambulatorial , Estudos Transversais , Atenção à Saúde/organização & administração , Atenção à Saúde/estatística & dados numéricos , Humanos , Neoplasias/radioterapia , Neoplasias/cirurgia
17.
Phys Med Biol ; 66(4): 045016, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33561008

RESUMO

PURPOSE: Nanoparticles (NPs) with radioactive atoms incorporated within the structure of the NP or bound to its surface, functionalized with biomolecules are reported as an alternative to low-dose-rate seed-based brachytherapy. In this study, authors report a mathematical dosimetric study on low-dose rate brachytherapy using radioactive NPs. METHOD: Single-cell dosimetry was performed by calculating cellular S-values for spherical cell model using Au-198, Pd-103 and Sm-153 NPs. The cell survival and tumor volume versus time curves were calculated and compared to the experimental studies on radiotherapeutic efficiency of radioactive NPs published in the literature. Finally, the radiotherapeutic efficiency of Au-198, Pd-103 and Sm-153 NPs was tested for variable: administered radioactivity, tumor volume and tumor cell type. RESULT: At the cellular level Sm-153 presented the highest S-value, followed by Pd-103 and Au-198. The calculated cell survival and tumor volume curves match very well with the published experimental results. It was found that Au-198 and Sm-153 can effectively treat highly aggressive, large tumor volumes with low radioactivity. CONCLUSION: The accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumor repopulation rate is important for the calculation of cell survival curves. Self-absorption of emitted radiation and dose enhancement due to AuNPs must be considered in the calculations. Selection of radionuclide for radioactive NP must consider size of tumor, repopulation rate and radiosensitivity of tumor cells. Au-198 NPs functionalized with Mangiferin are a suitable choice for treating large, radioresistant and rapidly growing tumors.


Assuntos
Braquiterapia/métodos , Simulação por Computador , Doses de Radiação , Radioisótopos/química , Radioisótopos/uso terapêutico , Radioisótopos de Ouro/química , Radioisótopos de Ouro/uso terapêutico , Método de Monte Carlo , Neoplasias/radioterapia , Paládio/química , Paládio/uso terapêutico , Radiometria , Dosagem Radioterapêutica , Samário/química , Samário/uso terapêutico
18.
Sci Rep ; 11(1): 3533, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574390

RESUMO

Proton minibeam radiotherapy (pMBRT) is a spatial fractionation method using sub-millimeter beams at center-to-center (ctc) distances of a few millimeters to widen the therapeutic index by reduction of side effects in normal tissues. Interlaced minibeams from two opposing or four orthogonal directions are calculated to minimize side effects. In particular, heterogeneous dose distributions applied to the tumor are investigated to evaluate optimized sparing capabilities of normal tissues at the close tumor surrounding. A 5 cm thick tumor is considered at 10 cm depth within a 25 cm thick water phantom. Pencil and planar minibeams are interlaced from two (opposing) directions as well as planar beams from four directions. An initial beam size of σ0 = 0.2 mm (standard deviation) is assumed in all cases. Tissue sparing potential is evaluated by calculating mean clonogenic cell survival using a linear-quadratic model on the calculated dose distributions. Interlacing proton minibeams for homogeneous irradiation of the tumor has only minor benefits for the mean clonogenic cell survival compared to unidirectional minibeam irradiation modes. Enhanced mean cell survival, however, is obtained when a heterogeneous dose distribution within the tumor is permitted. The benefits hold true even for an elevated mean tumor dose, which is necessary to avoid cold spots within the tumor in concerns of a prescribed dose. The heterogeneous irradiation of the tumor allows for larger ctc distances. Thus, a high mean cell survival of up to 47% is maintained even close to the tumor edges for single fraction doses in the tumor of at least 10 Gy. Similar benefits would result for heavy ion minibeams with the advantage of smaller minibeams in deep tissue potentially offering even increased tissue sparing. The enhanced mean clonogenic cell survival through large ctc distances for interlaced pMBRT with heterogeneous tumor dose distribution results in optimum tissue sparing potential. The calculations show the largest enhancement of the mean cell survival in normal tissue for high-dose fractions. Thus, hypo-fractionation or even single dose fractions become possible for tumor irradiation. A widened therapeutic index at big cost reductions is offered by interlaced proton or heavy ion minibeam therapy.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons/normas , Hipofracionamento da Dose de Radiação/normas , Dosagem Radioterapêutica , Sobrevivência Celular/efeitos da radiação , Fracionamento da Dose de Radiação , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Prótons/efeitos adversos
19.
JAMA Netw Open ; 4(2): e2034074, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33599771

RESUMO

Importance: The adoption of alternative fractionated radiotherapy regimens for the treatment of patients with cancer and comorbid collagen vascular disease (CVD) is controversial among oncologists because of concerns about potentially severe toxic effects; however, the association between fractionated radiotherapy and toxic effects in the modern era has not been well studied. Objective: To compare acute and late toxic effects among patients with cancer and comorbid CVD who received dose-fractionated radiotherapy. Design, Setting, and Participants: This retrospective cohort study examined 197 adult patients with cancer and CVD who received radiotherapy at a single-institution tertiary academic center over a 12-year period (February 1, 2007, to April 30, 2019), with a median follow-up of 23 months (range, 0-108 months). Data were analyzed from February 1 to August 31, 2020. Exposures: Three dose-fractionated radiotherapy regimens: conventional fractionation (CF; ≤2 Gy per fraction), moderate hypofractionation (MH; >2 Gy to <5 Gy per fraction), and ultrahypofractionation (UH; ≥5 Gy per fraction). Main Outcomes and Measures: The main outcomes were the incidence and severity of acute and late radiotherapy-associated toxic effects, which were assessed separately by dose-fractionation regimen. Toxic effects occurring within 90 days after radiotherapy completion were considered acute, and toxic effects occurring after that 90-day period were considered late. Secondary goals were to identify covariates associated with toxic effects and to characterize the incidence of CVD symptom flares (defined as worsening clinical symptoms and/or worsening results [transient or permanent] on associated blood tests compared with baseline, as documented by managing physicians) after radiotherapy. Results: Of 197 patients with cancer and comorbid CVD (mean [SD] age, 69 [12] years; 134 women [68.0%]; and 149 White participants [75.6%]), 80 patients (40.6%) received CF radiotherapy, 55 patients (27.9%) received MH radiotherapy, and 62 patients (31.5%) received UH radiotherapy. The most common CVD diagnoses were rheumatoid arthritis (74 patients [37.6%]), psoriasis (54 patients [27.4%]), systemic lupus erythematosus (34 patients [17.3%]), and scleroderma (8 patients [4.1%]). The most common radiotherapy sites were the breast (48 patients [24.4%]), thorax (25 patients [12.7%]), central nervous system (24 patients [12.2%]), and prostate (23 patients [11.7%]). Data on acute toxic effects were available for 188 patients (95.4%) and missing for 9 patients (4.6%). Data on late toxic effects were available for 142 patients (72.1%) and missing for 55 patients (27.9%). Over 12 years, the unadjusted incidences of severe acute toxic effects associated with CF, MH, and UH radiotherapy were 5.4% (95% CI, 0.3%-10.5%), 7.4% (95% CI, 0.4%-14.4%), and 1.7% (95% CI, 0%-5.0%), respectively. The incidences of severe late toxic effects associated with CF, MH, and UH radiotherapy were 8.3% (95% CI, 1.3%-15.3%), 0%, and 2.2% (95% CI, 0%-6.4%), respectively. No significant associations were found between severe acute or late toxic effects by dose fractionation regimen. In the multivariable analysis, MH radiotherapy was associated with a lower likelihood of developing late toxic effects (odds ratio [OR], 0.21; 95% CI, 0.05-0.83; P = .03) compared with CF radiotherapy. Those who received UH radiotherapy had a lower likelihood of experiencing late toxic effects (OR, 0.22; 95% CI, 0.04-1.21; P = .08). A total of 19 of 80 patients (23.8%), 15 of 55 patients (27.3%), and 10 of 62 patients (16.1%) experienced CVD symptom flares after receiving CF, MH, and UH radiotherapy, respectively (P = .33). Conclusions and Relevance: In this study, the incidences of unadjusted severe toxic effects over 12 years were less than 10% and were not significantly associated with dose fractionation. When clinically indicated, patients with cancer and comorbid CVD may not require immediate exclusion from the receipt of currently used hypofractionated radiotherapy regimens.


Assuntos
Doenças do Tecido Conjuntivo/epidemiologia , Neoplasias/radioterapia , Lesões por Radiação/epidemiologia , Radioterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Neoplasias da Mama/radioterapia , Comorbidade , Fracionamento da Dose de Radiação , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Incidência , Neoplasias Pulmonares/radioterapia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias da Próstata/radioterapia , Psoríase/epidemiologia , Hipofracionamento da Dose de Radiação , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Escleroderma Sistêmico/epidemiologia
20.
Radiat Res ; 195(3): 293-300, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33400779

RESUMO

Numerous studies have strongly supported the application of gold nanoparticles (GNPs) as radio-enhanced agents. In our previous study, the local effect model (LEM I) was adopted to predict the cell survival for MDA-MB-231 cells exposed to 150 kVp X rays after 500 µg/ml GNPs treatment. However, microdosimetric quantities could not be obtained, which were correlated with biological effects on cells. Thus, we developed microdosimetric kinetic model (MKM) for GNP radio-enhancement (GNP-MKM), which uses the microdosimetric quantities such as dose-mean lineal energy with subcellular domain size. Using the Monte Carlo simulation tool Geant4, we estimated the dose-mean lineal energy with secondary radiations from GNPs and absorbed dose in the nucleus. The variations in MKM parameters for different domain sizes, and GNP concentrations, were calculated to compare the survival fractions predicted by both models. With a domain radius of 500 nm and a threshold dose of 20 Gy, the sensitizer enhancement ratio predicted by GNP-MKM and GNP-LEM was 1.41 and 1.29, respectively. The GNP-MKM predictions were much more strongly dependent on the domain size than were the GNP-LEM on the threshold dose. These findings provide another method to predict survival fraction for the GNP radio-enhancement.


Assuntos
Nanopartículas Metálicas/química , Neoplasias/radioterapia , Radiossensibilizantes/farmacologia , Ouro/química , Humanos , Cinética , Método de Monte Carlo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Radiossensibilizantes/química , Raios X
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