RESUMO

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r > 0.87 and p-values >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Assuntos

Terapia por Captura de Nêutron de Boro , Modelos Animais de Doenças , Neoplasias de Cabeça e Pescoço/radioterapia , Melanoma/radioterapia , Neoplasias Bucais/radioterapia , Mucosite/radioterapia , Fótons , Animais , Carcinoma de Células Escamosas/radioterapia , Cricetinae , Humanos , Lesões Pré-Cancerosas/radioterapia , Radiometria

RESUMO

PURPOSE: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. METHODS: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. RESULTS: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. CONCLUSIONS: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

Assuntos

Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Pulmonares/radioterapia , Animais , Argentina , Boro/farmacocinética , Boro/uso terapêutico , Compostos de Boro/farmacocinética , Terapia por Captura de Nêutron de Boro/instrumentação , Estudos de Viabilidade , Frutose/análogos & derivados , Frutose/farmacocinética , Humanos , Pulmão/metabolismo , Pulmão/efeitos da radiação , Neoplasias Pulmonares/metabolismo , Modelos Animais , Modelos Biológicos , Fótons , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Ovinos , Fatores de Tempo , Distribuição Tecidual

RESUMO

PURPOSE: The purpose of this study is to assess the potential of dynamic infrared imaging (DIRI) as a functional, noninvasive technique for evaluating the skin acute toxicity and tumor control within the framework of the Argentine boron neutron capture therapy (BNCT) program for cutaneous malignant melanoma. METHODS: Two patients enrolled in the Argentine phase I/II BNCT clinical trial for cutaneous malignant melanoma were studied with DIRI. An uncooled infrared camera, providing a video output signal, was employed to register the temperature evolution of the normal skin and tumor regions in patients subjected to a mild local cooling (cold stimulus). In order to study the spatial correlation between dose and acute skin reactions, three-dimensional representations of the superficial dose delivered to skin were constructed and cameralike projections of the dose distribution were coregistered with visible and infrared images. RESULTS: The main erythematous reaction was observed clinically between the second and fifth week post-BNCT. Concurrently, with its clinical onset, a reactive increase above the basal skin temperature was observed with DIRI in the third week post-BNCT within regions that received therapeutic doses. Melanoma nodules appeared as highly localized hyperthermic regions. 2 min after stimulus, these regions reached a temperature plateau and increased in size. Temperature differences with respect to normal skin up to 10 degrees C were observed in the larger nodules. CONCLUSIONS: Preliminary results suggest that DIRI, enhanced by the application of cold stimuli, may provide useful functional information associated with the metabolism and vasculature of tumors and inflammatory processes related to radiation-induced changes in the skin as well. These capabilities are aimed at complementing the clinical observations and standard imaging techniques, such as CT and Doppler ultrasound.

Assuntos

Terapia por Captura de Nêutron de Boro/métodos , Melanoma/diagnóstico , Melanoma/radioterapia , Radioterapia Assistida por Computador/métodos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/radioterapia , Termografia/métodos , Idoso , Feminino , Humanos , Raios Infravermelhos , Masculino , Resultado do Tratamento

RESUMO

A previous work concerning tumor control and skin damage in cutaneous melanoma treatments with BNCT has been extended to include doses, volumes and responses of 104 subcutaneous lesions from all patients treated in Argentina. Acute skin reactions were also scored for these patients, and cumulative dose-area histograms and dose-based figures of merit for skin were calculated. Broadening the tumor response analysis with the latest data showed that the (minimum or mean) tumor dose is not a good predictor of the observed clinical outcome by itself. However, when the tumor volume was included in the model as second explicative variable, the dose increases its significance and becomes a critical variable jointly with the volume (p-values<0.05). A preliminary analysis to estimate control doses for two groups of tumor sizes revealed that for small tumor volumes (< 0.1cm(3)) doses greater than 20 Gy-Eq produce a high tumor control (> 80%). However, when tumor volumes are larger than 0.1cm(3), control is moderate (< 40%) even for minimum doses up to 40 Gy-Eq. Some quantities based on skin doses, areas and complication probabilities were proposed as candidates for predicting the severity of the early skin reactions. With the current data, all the evaluated figures of merit derived similar results: ulceration is present among the cases for which these quantities take the highest values.

Assuntos

Terapia por Captura de Nêutron de Boro/efeitos adversos , Terapia por Captura de Nêutron de Boro/estatística & dados numéricos , Melanoma/radioterapia , Lesões por Radiação/etiologia , Neoplasias Cutâneas/radioterapia , Relação Dose-Resposta à Radiação , Eritema/etiologia , Humanos , Melanoma/patologia , Valor Preditivo dos Testes , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Úlcera Cutânea/etiologia

RESUMO

We recently initiated a program aimed to investigate the suitability of dynamic infrared imaging for following-up nodular melanoma patients treated with BNCT. The reason that makes infrared imaging attractive is the fact that it constitutes a functional and non-invasive imaging method, providing information on the normal and abnormal physiologic response of the nervous and vascular systems, as well as the local metabolic rate and inflammatory processes that ultimately appear as differences in the skin temperature. An infrared camera, with a focal plane array of 320 x 240 uncooled ferroelectric detectors is employed, which provides a video stream of the infrared emission in the 7-14 microm wavelength band. A double blackbody is used as reference for absolute temperature calibration. After following a protocol for patient preparation and acclimatization, a basal study is performed. Subsequently, the anatomic region of interest is subjected to a provocation test (a cold stimulus), which induces an autonomic vasoconstriction reflex in normal structures, thus enhancing the thermal contrast due to the differences in the vasculature of the different skin regions. Radiation erythema reactions and melanoma nodules possess typically a faster temperature recovery than healthy, non-irradiated skin. However, some other non-pathological structures are also detectable by infrared imaging, (e.g. scars, vessels, arteriovenous anastomoses and injuries), thus requiring a multi-study comparison in order to discriminate the tumor signal. Besides the superficial nodules, which are readily noticeable by infrared imaging, we have detected thermal signals that are coincident with the location of non-palpable nodules, which are observable by CT and ultrasound. Diffuse regions of fast temperature recovery after a cold stimulus were observed between the third and sixth weeks post-BNCT, concurrent with the clinical manifestation of radiation erythema. The location of the erythematous visible and infrared regions is consistent with the 3D dosimetry calculations.

Assuntos

Terapia por Captura de Nêutron de Boro , Raios Infravermelhos , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Termografia/métodos , Idoso , Terapia por Captura de Nêutron de Boro/efeitos adversos , Temperatura Baixa , Eritema/etiologia , Eritema/patologia , Eritema/fisiopatologia , Feminino , Humanos , Perna (Membro) , Masculino , Melanoma/patologia , Melanoma/fisiopatologia , Planejamento da Radioterapia Assistida por Computador , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/fisiopatologia , Fenômenos Fisiológicos da Pele , Temperatura Cutânea , Fatores de Tempo

RESUMO

As part of phase I/II melanoma BNCT clinical trial conducted in Argentina in a cooperative effort of the Argentine Atomic Energy Commission (CNEA) and the Oncology Institute Angel H. Roffo (IOAHR), 7 patients (6 female-1 male) received eight treatment sessions covering ten anatomical areas located in extremities. Mean age of the patients was 64 years (51-74). The treatments were performed between October 2003 and June 2007. All patients presented multiple subcutaneous skin metastases of melanoma and received an infusion containing approximately 14 gr/m(2) of (10)borophenyl-alanine (BPA) followed by the exposition of the area to a mixed thermal-epithermal neutron beam at the RA-6 reactor. The maximum prescribed dose to normal skin ranged from 16.5 to 24 Gy-Eq and normal tissue administered dose varied from 15.8 to 27.5 Gy-Eq. Considering evaluable nodules, 69.3% of overall response and 30.7% of no changes were seen. The toxicity was acceptable, with 3 out of 10 evaluable areas showing ulceration (30% toxicity grade 3).

Assuntos

Terapia por Captura de Nêutron de Boro/métodos , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Idoso , Argentina , Compostos de Boro/uso terapêutico , Feminino , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador

RESUMO

A Phase I/II protocol for treating cutaneuos melanomas with BNCT was designed in Argentina by the Comisión Nacional de Energía Atómica and the medical center Instituto Roffo. The first of a cohort of thirty planned patients was treated on October 9, 2003. This article depicts the protocol-based procedure and describes the first clinical case, treatment regime and planning, patient irradiation, retrospective dosimetric analysis and clinical outcome. Considering the low acute skin toxicity and the complete response in 21 of the 25 subcutaneous melanoma nodules treated, a second irradiation was performed in a different location of the extremity of the same patient. The corresponding clinical outcome is still under evaluation.

Assuntos

Terapia por Captura de Nêutron de Boro , Frutose/análogos & derivados , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Argentina , Boro/sangue , Boro/farmacocinética , Compostos de Boro/farmacocinética , Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro/métodos , Protocolos Clínicos , Feminino , Frutose/farmacocinética , Frutose/uso terapêutico , Humanos , Melanoma/metabolismo , Melanoma/secundário , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/secundário , Resultado do Tratamento

RESUMO

This article reports on the progress of the modeling and experimental characterization of the RA-6 reactor neutron beam, designed for the upcoming BNCT clinical trials of skin melanoma, and presents the first theoretical analysis of such beam performance. The aspects relating to surface source modeling and assessment, beam dosimetry, treatment planning system calibration, and treatment planning optimization are presented herein. Several methods and criteria were established in order to provide guidance for future clinical studies conducted in this facility. Following a realistic model, the theoretical analysis was based on a clinical case of malignant melanoma in extremities. Owing to the complex geometry of the tumor, this particular clinical case represents one of the most difficult lesions to be treated. This article discusses the thorough evaluation stage that has led to the optimization of the treatment planning procedure. Two candidate plans were proposed, and dose-volume distributions in the target volume were evaluated on the basis of the application of a series of criteria that define the critical normal structures which limit the dose delivered. In spite of the complexity of the clinical case under review, results showed that only 4% of the tumor volume is underdosed in cases of mean blood 10B concentration values, even in the most unfavorable analysis. The overall results suggest that this BNCT facility is prepared to rigorously explore the clinical efficacy of the RA-6 beam and the BNCT treatment modality for peripheral melanomas.

Assuntos

Terapia por Captura de Nêutron de Boro/métodos , Nêutrons Rápidos , Melanoma/radioterapia , Planejamento da Radioterapia Assistida por Computador , Neoplasias Cutâneas/radioterapia , Idoso , Ensaios Clínicos como Assunto , Feminino , Humanos , Perna (Membro)/patologia , Dosagem Radioterapêutica

RESUMO

Nuestra serie de 113 pacientes operados por litiasis coraliformes por vía abierta, con seguimiento promedio de 41,3 meses (6-150) entre enero/1980 a diciembre/1995. Se evaluó a lar go plazo la función renal en relación al uso de isquemia y protección renal durante la cirugía, la presencia de litiasis e ITU en la evolución. 94 (83,2 por ciento) pacientes presentaban fx renal preoperatoria normal y 19 presentaban fx renal alterada preoperatoria. Deterioro de la función renal se observó en 14 pacientes (12,4 por ciento). Al evaluar la fx renal al lar go plazo, se evidencia que todos los factores analizados se asocian a deterioro de la fx renal, pero sólo la ITU y la ITU asociada a litiasis en la evolución presenta diferencias estadísticamente significativas (p

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cálculos Urinários/cirurgia , Nefrostomia Percutânea/métodos , Nefrectomia , Cálculos Urinários , Evolução Clínica , Seguimentos , Nefrostomia Percutânea/efeitos adversos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias , Estudos Retrospectivos

RESUMO

Es conocida en la literatura médica la baja incidencia de la patología suprarrenal. Constituyendo hoy en día un capítulo urológico fascinante. El objetivo de este trabajo es presentar la experiencia clínico-quirúrgica de la patología suprarrenal en nuestro hospital. Material y Métodos: Se revisaron 76 operados por patología suprarrenal primaria entre enero de 1969 y mayo de 1996. Resultados: de los 76 pacientes, 28 (36,8 por ciento) fueron feocromocitomas, seguidos por hiperaldosteronismo en 13 pacientes (17 por ciento), hipercortisolismo en 1 1 pacientes (14,5 por ciento). 5 pacientes (6,5 por ciento) se operaron por cáncer suprarrenal, 4 (5,2 por ciento) por metástasis, 4 (5,2 por ciento) fueron adenomas corticales, 3 hiperplasia nodulares, 2 hematomas, 2 linfangiomas quísticos, 2 angiomiolipomas, 1 paciente con tuberculosis y otro con lipoma periadrenal. De esto 76 pacientes 42 (55 por ciento) fueron mujeres y 34 varones. La edad promedio fue de 55,2 años, 50 pacientes (66 por ciento) se presentaron con clínica y/o laboratorio propios de su patología. El estudio endocrino, cuando se usó, permitió sospechar la patología en la mayoria de los casos 26 pacientes (34 por ciento) fueron nódulados no funcionables con tamaño promedio de 3,5 cm. siendo hallazgo por ECO y/o TAC en 16 casos (61,5 por ciento) distribuidos como 4 (25 por ciento) metástasis, 3 (19 por ciento) hiperplasias nodulares,3 (19 por ciento) adenomas corticales, 2 feocromocitomas, 1 cáncer, 1 an giomiolipoma, 1 hematoma y 1 linfangioma quístico. La TAC,ECO, cintigrafía, arteriografía y venografía permitieron (usando 1, 2 ó más de estos) el hallazgo o confirmación del diagnóstico, siendo la TAC el método más efectivo 10050 en los que se usó. El diagnóstico definitivo lo dió la histología en todos. El abordaje quirúrgico más usado fue la lumbotomía (87 por ciento) exepto para los feocromocitomas en los que se usó abordaje anterior. No hubo mortalidad operatoria y la morbilidad fue baja (2 por ciento). Concluciones: nuestra serie confinna que el diagnóstico de la patología adrenal puede ralizarse con bastante certeza en el preoperatorio. La TAC es el método de estudio de mayor rendimiento. Como procedimiento quirúrgico reglado, esta cirugía puede ser practicada con una baja morbimortalidad apoyada por un manejo perioperatorio adecuado estimulando su práctica como tratanúento electivo en diversas patologías adrenales

Assuntos

Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adrenalectomia , Hiperfunção Adrenocortical/cirurgia , Hiperaldosteronismo/cirurgia , Feocromocitoma/cirurgia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia/efeitos adversos , Hiperfunção Adrenocortical/diagnóstico , Hiperaldosteronismo/diagnóstico , Complicações Pós-Operatórias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X