RESUMO
Carbon ion radiotherapy (CIRT) has garnered interest for the treatment of locoregional rectal cancer recurrence. No study has compared CIRT and X-ray radiotherapy (XRT) for reirradiation (reRT) in such cases. We analyzed and compared the clinical outcomes such as local control, overall survival, and late toxicity rate between CIRT and XRT, for treating locoregional rectal cancer recurrence. Patients with rectal cancer who received reRT to the pelvis by CIRT or XRT from March 2005 to July 2019 were included. The CIRT treatment schedule was 70.4 Gy (relative biological effectiveness) in 16 fractions. For the XRT group, the median reRT dose was 50 Gy (range 25-62.5 Gy) with a median of 25 fractions (range 3-33). Thirty-five and 31 patients received CIRT and XRT, respectively. Tumour and treatment characteristics such as recurrence location and chemotherapy treatment differed between the two groups. CIRT showed better control of local recurrence (adjusted hazard ratio [HR] 0.17; p = 0.002), better overall survival (HR 0.30; p = 0.004), and lower severe late toxicity rate (HR 0.15; p = 0.015) than XRT. CIRT was effective for treating locoregional rectal cancer recurrence, with high rates of local control and survival, and a low late severe toxicity rate.
Assuntos
Radioterapia com Íons Pesados , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Neoplasias Retais/radioterapia , Terapia por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Radioterapia com Íons Pesados/efeitos adversos , Radioterapia com Íons Pesados/mortalidade , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Reirradiação/efeitos adversos , Reirradiação/mortalidade , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Seul , Fatores de Tempo , Resultado do Tratamento , Terapia por Raios X/efeitos adversos , Terapia por Raios X/mortalidadeRESUMO
The treatments available for disseminated superficial actinic porokeratosis (DSAP) have been limited and have variable efficacy. We report the largest case series to date of the use of Grenz ray therapy in 17 patients with DSAP. There was at least 50% improvement in DSAP lesions in all cases. Erythema, itching and burning were common side effects of Grenz ray therapy. We believe that Grenz ray therapy may be an effective treatment option for patients with DSAP.
Assuntos
Poroceratose/radioterapia , Terapia por Raios X , Adulto , Idoso , Eritema/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Prurido/etiologia , Terapia por Raios X/efeitos adversosRESUMO
Introduction: Radiotherapy is one of the methods used as a treatment for malignant tumors in the head and neck region and it can cause tissue damage in the irradiated areas. In head and neck radiotherapy, teeth are often included within the irradiation area and, consequently, the dental pulp; which receives high doses of radiation. Objective: To evaluate the effects of ionizing radiation on the pulp tissue of rat teeth. Methodology: A double-blind experimental assay with 35 Albinus Wistar rats divided into seven groups was performed; one control group, three groups irradiated with 15 Gy, and three groups irradiated with 25 Gy. The irradiated groups were submit-ted to a single dose of radiation and sacrificed 24 hours, 7 days, and 22 days after irradiation, respectively. The samples were evaluated for the morphological presence of inflammatory infiltrate, edema, necrosis, fibrosis, and degeneration of blood vessels. Statistical analysis was performed using the Kruskal-Wallis and Dunn tests with p < 0.05. Results: Hyaline degeneration of the pulp blood vessels in the irradiated teeth was statistically signifi-cant in all irradiated groups. Inflammatory infiltrate, edema, necrosis or fibrosis was not observed. Conclusion:A single X-radiation dose is not able to affect the dental pulp connective tissue in the long term with no clinical damage.
Introdução: A radioterapia é um dos métodos utilizados como tratamento para tumores malignos em região de cabeça e pescoço e que pode causar danos aos tecidos nas áreas irradiadas. Na radioterapia de cabeça e pescoço, os dentes são comumente incluídos dentro da área de radiação e, consequentemente, a polpa dentária, recebe altas doses de radiação. Objetivo: Avaliar os efeitos da radiação ionizante no tecido pulpar de dentes de ratos. Metodologia: Foi realizado um ensaio experimental duplo-cego com 35 ratos Albinus Wistar divididos em sete grupos: um grupo controle, três grupos irradiados com 15 Gy e três grupos irradiados com 25 Gy. Os grupos irradiados foram submetidos a uma dose única de radiação e sacrificados 24 horas, 7 dias e 22 dias após a irradiação, respectivamente. As amostras foram avaliadas quanto à presença morfológica de infiltrado inflamatório, edema, necrose, fibrose e degeneração nos vasos sanguíneos. A análise estatística foi realizada por meio dos testes de Kruskal-Wallis e Dunn com p < 0.05. Resultados: Degeneração hialina nos vasos sanguíneos pulpares dos dentes irradiados foi estatisticamente significante em todos os grupos irradiados. Não foi observado infiltrado inflamatório, edema, necrose ou fibrose. Conclusão: Uma dose única de radiação X não é capaz de afetar o tecido conjuntivo da polpa dentária a longo prazo sem danos clínicos.
Assuntos
Animais , Ratos , Radiação Ionizante , Terapia por Raios X/efeitos adversos , Polpa Dentária , HialinaRESUMO
To clarify the health risks of internal radiation exposure, it is important to investigate the radiological effects of local exposure at cell levels from radioactive materials taken up by organs. Focusing on the response of cell populations post-irradiation, X-ray microbeams are very effective at reproducing the effects of local exposure within an internal exposure in vitro. The present study aims to clarify the effects of local exposure by investigating the response of normal human cell (MRC-5) populations irradiated with X-ray microbeams of different beam sizes to DNA damage. The populations of MRC-5 were locally irradiated with X-ray microbeams of 1 Gy at 0.02-1.89 mm2 field sizes, and analyzed whether the number of 53BP1 foci as DSB (DNA double strand break) per cell changed with the field size. We found that even at the same dose, the number of DSB per cell increased depending on the X-irradiated field size on the cell population. This result indicated that DNA damage repair of X-irradiated cells might be enhanced in small size fields surrounded by non-irradiated cells. This study suggests that X-irradiated cells received some signal (a rescue signal) from surrounding non-irradiated cells may be involved in the response of cell populations post-irradiation.
Assuntos
Proliferação de Células/efeitos da radiação , Radioisótopos de Césio/toxicidade , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Terapia por Raios X/efeitos adversos , Raios X/efeitos adversos , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Humanos , Pulmão/patologia , Pulmão/efeitos da radiaçãoRESUMO
In the last 25 years microbeam radiation therapy (MRT) has emerged as a promising alternative to conventional radiation therapy at large, third generation synchrotrons. In MRT, a multi-slit collimator modulates a kilovoltage x-ray beam on a micrometer scale, creating peak dose areas with unconventionally high doses of several hundred Grays separated by low dose valley regions, where the dose remains well below the tissue tolerance level. Pre-clinical evidence demonstrates that such beam geometries lead to substantially reduced damage to normal tissue at equal tumour control rates and hence drastically increase the therapeutic window. Although the mechanisms behind MRT are still to be elucidated, previous studies indicate that immune response, tumour microenvironment, and the microvasculature may play a crucial role. Beyond tumour therapy, MRT has also been suggested as a microsurgical tool in neurological disorders and as a primer for drug delivery. The physical properties of MRT demand innovative medical physics and engineering solutions for safe treatment delivery. This article reviews technical developments in MRT and discusses existing solutions for dosimetric validation, reliable treatment planning and safety. Instrumentation at synchrotron facilities, including beam production, collimators and patient positioning systems, is also discussed. Specific solutions reviewed in this article include: dosimetry techniques that can cope with high spatial resolution, low photon energies and extremely high dose rates of up to 15 000 Gy s-1, dose calculation algorithms-apart from pure Monte Carlo Simulations-to overcome the challenge of small voxel sizes and a wide dynamic dose-range, and the use of dose-enhancing nanoparticles to combat the limited penetrability of a kilovoltage energy spectrum. Finally, concepts for alternative compact microbeam sources are presented, such as inverse Compton scattering set-ups and carbon nanotube x-ray tubes, that may facilitate the transfer of MRT into a hospital-based clinical environment. Intensive research in recent years has resulted in practical solutions to most of the technical challenges in MRT. Treatment planning, dosimetry and patient safety systems at synchrotrons have matured to a point that first veterinary and clinical studies in MRT are within reach. Should these studies confirm the promising results of pre-clinical studies, the authors are confident that MRT will become an effective new radiotherapy option for certain patients.
Assuntos
Terapia por Raios X/métodos , Humanos , Radiometria , Planejamento da Radioterapia Assistida por Computador , Segurança , Microambiente Tumoral/efeitos da radiação , Terapia por Raios X/efeitos adversosRESUMO
The ventricular-subventricular zone (V-SVZ) of the mammalian brain is a site of adult neurogenesis. Within the V-SVZ reside type B neural stem cells (NSCs) and type A neuroblasts. The V-SVZ is also a primary site for very aggressive glioblastoma (GBM). Standard-of-care therapy for GBM consists of safe maximum resection, concurrent temozolomide (TMZ), and X-irradiation (XRT), followed by adjuvant TMZ therapy. The question of how this therapy impacts neurogenesis is not well understood and is of fundamental importance as normal tissue tolerance is a limiting factor. Here, we studied the effects of concurrent TMZ/XRT followed by adjuvant TMZ on type B stem cells and type A neuroblasts of the V-SVZ in C57BL/6 mice. We found that chemoradiation induced an apoptotic response in type A neuroblasts, as marked by cleavage of caspase 3, but not in NSCs, and that A cells within the V-SVZ were repopulated given sufficient recovery time. 53BP1 foci formation and resolution was used to assess the repair of DNA double-strand breaks. Remarkably, the repair was the same in type B and type A cells. While Bax expression was the same for type A or B cells, antiapoptotic Bcl2 and Mcl1 expression was significantly greater in NSCs. Thus, the resistance of type B NSCs to TMZ/XRT appears to be due, in part, to high basal expression of antiapoptotic proteins compared with type A cells. This preclinical research, demonstrating that murine NSCs residing in the V-SVZ are tolerant of standard chemoradiation therapy, supports a dose escalation strategy for treatment of GBM. Stem Cells 2019;37:1629-1639.
Assuntos
Quimiorradioterapia/efeitos adversos , Ventrículos Laterais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Temozolomida/efeitos adversos , Terapia por Raios X/efeitos adversos , Animais , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Quimiorradioterapia/métodos , Quebras de DNA de Cadeia Dupla , Reparo do DNA/genética , Modelos Animais de Doenças , Resistência a Medicamentos/fisiologia , Feminino , Glioblastoma/patologia , Glioblastoma/terapia , Ventrículos Laterais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Temozolomida/farmacologia , Terapia por Raios X/métodosRESUMO
Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.
Assuntos
Arritmias Cardíacas/radioterapia , Miocárdio/patologia , Miócitos Cardíacos/efeitos da radiação , Terapia por Raios X/efeitos adversos , Animais , Arritmias Cardíacas/patologia , Ablação por Cateter/efeitos adversos , Coração/efeitos da radiação , Frequência Cardíaca/efeitos da radiação , Íons Pesados/efeitos adversos , Humanos , Miócitos Cardíacos/patologia , Radiação não Ionizante/efeitos adversos , Radiocirurgia/efeitos adversos , Técnicas Estereotáxicas/tendências , SuínosAssuntos
Carcinoma Basocelular/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Neoplasias Primárias Múltiplas/etiologia , Segunda Neoplasia Primária/etiologia , Couro Cabeludo , Neoplasias Cutâneas/etiologia , Terapia por Raios X/efeitos adversos , Idoso , Criança , Feminino , Humanos , Tinha do Couro Cabeludo/radioterapiaRESUMO
INTRODUCTION: Li-Fraumeni syndrome (LFS), due to TP53 germline mutations, is characterised by a remarkably high incidence of multiple primary cancers (MPCs), and the key role of p53 in response to DNA damage questions the contribution of anticancer treatments to MPCs development. MATERIALS AND METHODS: We first evaluated genotoxicity of X-rays and different classes of conventional chemotherapies, thanks to genotoxicity assays, based on the measurement of transcriptional response to DNA damage and performed in murine splenocytes, either exposed ex vivo or extracted from exposed mice. We then exposed a total of 208 Trp53Δ/Δ, wt/Δ or wt/wt mice to clinical doses of X-rays or genotoxic or non-genotoxic chemotherapies. Tumour development was monitored using whole-body magnetic resonance imaging and pathological examination at death. RESULTS: X-rays and conventional chemotherapies, except mitotic spindle poisons, were found to be genotoxic in both p53 genotoxicity assays. Exposition to X-rays and the topoisomerase inhibitor etoposide, analysed as genotoxic anticancer treatment, drastically increase the tumour development risk in Trp53Δ/Δ and wt/Δ mice (hazard ration [HR] = 4.4, 95% confidence interval [CI] [2.2-8.8], p < 0.001*** and HR = 4.7, 95% CI [2.4-9.3], p < 0.001***, respectively). In contrast, exposure to the non-genotoxic mitotic spindle poison, docetaxel, had no impact on tumour development. CONCLUSIONS: This study shows that radiotherapy and genotoxic chemotherapies significantly increase the risk of tumour development in a LFS mice model. These results strongly support the contribution of genotoxic anticancer treatments to MPC development in LFS patients. Therefore, to reduce the risk of MPCs in germline TP53 mutation carriers, radiotherapy should be avoided whenever possible, surgical treatment prioritised, and non-genotoxic treatments considered.
Assuntos
Antineoplásicos/toxicidade , Mutação em Linhagem Germinativa , Síndrome de Li-Fraumeni/genética , Neoplasias Primárias Múltiplas/genética , Proteína Supressora de Tumor p53/genética , Terapia por Raios X/efeitos adversos , Animais , Antineoplásicos/uso terapêutico , Predisposição Genética para Doença/genética , Humanos , Síndrome de Li-Fraumeni/diagnóstico por imagem , Síndrome de Li-Fraumeni/terapia , Imageamento por Ressonância Magnética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias Primárias Múltiplas/etiologia , Fatores de Risco , Análise de Sobrevida , Irradiação Corporal Total/efeitos adversos , Terapia por Raios X/métodosRESUMO
PURPOSE: To analyze the effects of micro-beam irradiation (MBI) on the normal tissues of the mouse ear. METHODS AND MATERIALS: Normal mouse ears are a unique model, which in addition to skin contain striated muscles, cartilage, blood and lymphatic vessels, and few hair follicles. This renders the mouse ear an excellent model for complex tissue studies. The ears of C57BL6 mice were exposed to MBI (50-µm-wide micro-beams, spaced 200 µm between centers) with peak entrance doses of 200, 400, or 800 Gy (at ultra-high dose rates). Tissue samples were examined histopathologically, with conventional light and electron microscopy, at 2, 7, 15, 30, and 240 days after irradiation (dpi). Sham-irradiated animals acted as controls. RESULTS: Only an entrance dose of 800 Gy caused a significant increase in the thickness of both epidermal and dermal ear compartments seen from 15 to 30 dpi; the number of sebaceous glands was significantly reduced by 30 dpi. The numbers of apoptotic bodies and infiltrating leukocytes peaked between 15 and 30 dpi. Lymphatic vessels were prominently enlarged at 15 up to 240 dpi. Sarcomere lesions in striated muscle were observed after all doses, starting from 2 dpi; scar tissue within individual beam paths remained visible up to 240 dpi. Cartilage and blood vessel changes remained histologically inconspicuous. CONCLUSIONS: Normal tissues such as skin, cartilage, and blood and lymphatic vessels are highly tolerant to MBI after entrance doses up to 400 Gy. The striated muscles appeared to be the most sensitive to MBI. Those findings should be taken into consideration in future micro-beam radiation therapy treatment schedules.
Assuntos
Orelha/efeitos da radiação , Lesões Experimentais por Radiação/etiologia , Síncrotrons , Terapia por Raios X/efeitos adversos , Terapia por Raios X/instrumentação , Animais , Relação Dose-Resposta à Radiação , Orelha/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Lesões Experimentais por Radiação/patologia , Fatores de TempoRESUMO
BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a rare keratinization disorder with potential malignant transformation, for which present treatment strategies show limited success. AIM: To evaluate the response of DSAP lesions to grenz ray radiotherapy (RTx). METHODS: Data of patients treated with RTx at University Hospital Zurich, Switzerland, between 2004 and 2015, were reviewed. Patients with DSAP, who received at least 1 RTx treatment session and who had been followed up for at least 4 weeks were included in the further data analysis. RESULTS: The study cohort consisted of 8 patients with a median age of 73 years (range 54-84). All were treated with grenz rays for DSAP. Most (7/8) patients showed complete clinical clearing of the lesions. All patients experienced temporary side effects of RTx, which resolved within 4 weeks after the last irradiation. CONCLUSION: We suggest radiotherapy with grenz rays as a treatment option for DSAP.
Assuntos
Poroceratose/radioterapia , Terapia por Raios X , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Retratamento , Resultado do Tratamento , Terapia por Raios X/efeitos adversosRESUMO
The ionizing radiation received by patients and health workers due to radiological imaging may increase the risks of radiation effects, such as cancer and cataracts. We have investigated the dose received by specific areas around the head and related this to DNA damage in the blood lymphocytes of subjects exposed to interventional imaging. The entrance surface doses (ESD) to the forehead, neck, and shoulder were measured with a thermoluminescence dosimeter (CaSO4 disc or polycrystalline powder of lithium tetraborate doped with Mn) and compared with that of dose area product (DAP). DNA damage was measured by γ-H2AX, p53ser15, chromosomal aberration (CA), and micronucleus (MN) assays in lymphocytes of patients (n=75), before and 2 and 24h after exposure. The measured ESD values were 230.5±4.9, 189.5±3.55 and 90.7±3.4mGy for the forehead, neck, and shoulder, respectively. The DAP varied from 1.8 to 2047 Gy*cm2, showing a correlation with fluoroscopy time (r=0.417). Received doses did not increase early markers of DNA damage (γ-H2AX and p53ser15 assays), but residual damage (CA and MN frequencies) showed a significant (p<0.001) increase at 2 and 24h post-exposure compared to pre-imaging, despite poor correlation with DAP (r=0.1). Our results show that interventional imaging procedures deliver significant radiation doses and induce measurable DNA damage in lymphocytes of subjects, highlighting the need for rigorous patient safety protocols.
Assuntos
Dano ao DNA , Linfócitos/efeitos da radiação , Radiografia Intervencionista/efeitos adversos , Terapia por Raios X/efeitos adversos , Raios X/efeitos adversos , Adolescente , Adulto , Idoso , Ensaio Cometa , Relação Dose-Resposta à Radiação , Feminino , Histonas/genética , Humanos , Linfócitos/patologia , Masculino , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Testes para Micronúcleos , Pessoa de Meia-Idade , Doses de Radiação , Proteína Supressora de Tumor p53/genética , Adulto JovemRESUMO
Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Comportamento Animal/efeitos dos fármacos , Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Metaloporfirinas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Comportamento Animal/efeitos da radiação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Terapia Combinada , Irradiação Craniana , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Feminino , Humanos , Metaloporfirinas/administração & dosagem , Metaloporfirinas/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Nus , Atividade Motora/efeitos dos fármacos , Atividade Motora/efeitos da radiação , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Temozolomida , Terapia por Raios X/efeitos adversosRESUMO
BACKGROUND: The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. MATERIAL AND METHODS: CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days). For the acute skin reaction, non-tumor bearing CDF1 mice were irradiated with a comparable radiation scheme, and monitored for acute skin damage between Day 7 and 40. Late RIF was assessed in the irradiated mice. RESULTS: The TCD50 (dose producing tumor control in 50% of mice) values with 95% confidence interval were 29.7 (25.4-34.8) Gy for C ions and 43.9 (39.2-49.2) Gy for photons, with a corresponding Relative biological effectiveness (RBE) value of 1.48 (1.28-1.72). For acute skin damage the MDD50 (dose to produce moist desquamation in 50% of mice) values with 95% confidence interval were 26.3 (23.0-30.1) Gy for C ions and 35.8 (32.9-39.0) Gy for photons, resulting in a RBE of 1.36 (1.20-1.54). For late radiation-induced fibrosis the FD50 (dose to produce severe fibrosis in 50% of mice) values with 95% confidence interval were 26.5 (23.1-30.3) Gy for carbon ions and 39.8 (37.8-41.8) Gy for photons, with a RBE of 1.50 (1.33-1.69). CONCLUSION: The observed RBE values were very similar for tumor response, acute skin damage and late RIF when irradiated with large doses of high- linear energy transfer (LET) carbon ions. This study adds information to the variation in biological effectiveness in different tumor and normal tissue models.
Assuntos
Carbono/uso terapêutico , Carcinoma/radioterapia , Radioterapia com Íons Pesados , Neoplasias Mamárias Experimentais/radioterapia , Lesões Experimentais por Radiação/etiologia , Pele/efeitos da radiação , Tela Subcutânea/patologia , Animais , Carbono/efeitos adversos , Feminino , Fibrose , Íons Pesados/efeitos adversos , Membro Posterior , Camundongos , Transplante de Neoplasias , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Tela Subcutânea/efeitos da radiação , Terapia por Raios X/efeitos adversos , Raios X/efeitos adversosRESUMO
Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.
Assuntos
Neoplasias Esofágicas/terapia , Traumatismos Cardíacos/etiologia , Lesão Pulmonar/etiologia , Terapia com Prótons/efeitos adversos , Lesões por Radiação/etiologia , Terapia por Raios X/efeitos adversos , Quimiorradioterapia/efeitos adversos , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prótons/efeitos adversos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Resultado do Tratamento , Carga Tumoral/efeitos da radiação , Raios X/efeitos adversosRESUMO
PURPOSE: To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions. METHODS: Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP). RESULTS: For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SS plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100-4.49/100) to 6.05/100 (range 1.38/100-11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100-11.5/100) for Cone and 5.22/100 (range 1.37/100-8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322). CONCLUSIONS: For treating peripheral brain lesions--where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy--the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (<7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (<70 MeV) is a major technological challenge in commercially available proton therapy systems.
Assuntos
Neoplasias Encefálicas/cirurgia , Terapia com Prótons/métodos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/efeitos da radiação , Encéfalo/cirurgia , Neoplasias Encefálicas/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Risco , Terapia por Raios X/efeitos adversos , Terapia por Raios X/métodos , Adulto JovemRESUMO
BACKGROUND: Grenz ray therapy (GRT) has been used for inflammatory and neoplastic dermatologic diseases for over 100 years. Its use is declining, possibly because of the difficulties maintaining radiation certification and insurance coverage. OBJECTIVE: The aim of this study is to evaluate the safety and effectiveness of GRT in chronic inflammatory dermatoses of the hands and feet. METHODS: We performed a retrospective chart review of patients treated with GRT at the Oregon Health & Science University from 2006 to 2009. Candidates identified for the study were then mailed questionnaires to supplement data acquired from chart review. RESULTS: Most patients (73%; 95% confidence interval [CI], 65%-80%) experienced at least moderate improvement. This improvement persisted for at least 1 month in 66% of patients (95% CI, 57%-74%), with 18 patients (23%; 95% CI, 15%-33%) clear for over 1 year. Minimal adverse effects were reported, and most patients (63%; 95% CI, 52%-72%) stated that they would repeat GRT if available. CONCLUSIONS: Grenz ray therapy seems to be a safe and effective modality for chronic hand and foot dermatoses with some patients experiencing prolonged remissions. Grenz ray therapy, when available, should be considered before the use of systemic agents, which are often associated with higher costs and potential toxicities.
Assuntos
Dermatoses do Pé/radioterapia , Dermatoses da Mão/radioterapia , Terapia por Raios X/métodos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Dosagem Radioterapêutica , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Terapia por Raios X/efeitos adversosAssuntos
Radioterapia com Íons Pesados , Neoplasias/radioterapia , Carbono/química , Ensaios Clínicos Fase III como Assunto , Terapia Combinada/métodos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA , Radioterapia com Íons Pesados/economia , Radioterapia com Íons Pesados/instrumentação , Radioterapia com Íons Pesados/métodos , Humanos , Internacionalidade , Neoplasias/tratamento farmacológico , Neoplasias/economia , Neoplasias/genética , Oxigênio/metabolismo , Terapia com Prótons , Terapia por Raios X/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: To investigate the cytogenetic damage of the intrachange type in peripheral blood lymphocytes of patients treated for prostate cancer with different radiation qualities. MATERIAL AND METHODS: Prostate cancer patients were enrolled in a clinical trial based at the Heidelberg University Hospital and at the GSI Helmholtz Centre for Heavy Ion Research in 2006. Patients were treated either with intensity-modulated radiation therapy (IMRT) alone or with a carbon-ion boost followed by IMRT. Blood samples were collected at the end of the therapy and the mBAND technique was used to investigate the cytogenetic damage of the inter and intrachange types. Moreover, the mBAND analysis was performed on healthy donor cells irradiated in vitro with X-rays or C-ions. RESULTS: Our results show no statistically significant differences in the yield and the spectrum of chromosome aberrations among patients treated only with IMRT and patients receiving the combined treatment when similar target volumes and doses to the target are compared. CONCLUSION: The study suggests that the risks of normal tissue late effects and second malignancies in prostate cancer patients are comparable when heavy ions or IMRT radiotherapy are applied.