A Comprehensive Analysis of the Relationship Between Dose Rate and Biological Effects in Preclinical and Clinical Studies, From Brachytherapy to Flattening Filter Free Radiation Therapy and FLASH Irradiation.

PURPOSE: For many years, the effect of dose rate (DR) was considered negligible in external beam radiation therapy (EBRT) until very-high DR (>10 Gy/min) became possible and ultrahigh DR (>40 Gy/s) showed dramatic protection of normal tissues in preclinical experiments. We propose a critical review of preclinical and clinical studies to investigate the biological and clinical effects of DR variation in the range covering brachytherapy to flattening filter free EBRT and FLASH. METHODS AND MATERIALS: Preclinical and clinical studies investigating biological and clinical DR effects were reviewed extensively. We also conducted an in silico study to assess the effect of pulse DR (DRp), taking into account the mean time between 2 tracks during the pulse. RESULTS: Preclinical studies have shown that an increase in DR in the range of 0.01 to 20 Gy/min (not including ultralow or ultrahigh DR) resulted in decreased survival of both normal and tumor cells. This effect was attributed primarily to increasingly unrepaired "sublethal" DNA damage with increasing the DR. However, the models and irradiation conditions have often been very different from one radiobiological study to another. Moreover, the physical parameters on the spatial and temporal microstructure of the beam were not considered systematically. In particular, the DRp was rarely mentioned. The in silico studies showed that for the same average DR, increasing DRp induced an increase of mean track rates. These results could explain the presence of more complex damage when the DRp was increased within the range of DR considered, in relation to the time-dependent probability of accumulating unrepaired, "sublethal" DNA lesions in close proximity. CONCLUSIONS: Knowledge of the beam microstructure is critical to understanding the biological impact and the clinical outcomes of radiation at the DR commonly used in radiation therapy.

The European Joint Research Project UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates.

UHDpulse - Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates is a recently started European Joint Research Project with the aim to develop and improve dosimetry standards for FLASH radiotherapy, very high energy electron (VHEE) radiotherapy and laser-driven medical accelerators. This paper gives a short overview about the current state of developments of radiotherapy with FLASH electrons and protons, very high energy electrons as well as laser-driven particles and the related challenges in dosimetry due to the ultra-high dose rate during the short radiation pulses. We summarize the objectives and plans of the UHDpulse project and present the 16 participating partners.

Experimental comparison of high-density scintillators for EMCCD-based gamma ray imaging.

Detection of x-rays and gamma rays with high spatial resolution can be achieved with scintillators that are optically coupled to electron-multiplying charge-coupled devices (EMCCDs). These can be operated at typical frame rates of 50 Hz with low noise. In such a set-up, scintillation light within each frame is integrated after which the frame is analyzed for the presence of scintillation events. This method allows for the use of scintillator materials with relatively long decay times of a few milliseconds, not previously considered for use in photon-counting gamma cameras, opening up an unexplored range of dense scintillators. In this paper, we test CdWO4 and transparent polycrystalline ceramics of Lu2O3:Eu and (Gd,Lu)2O3:Eu as alternatives to currently used CsI:Tl in order to improve the performance of EMCCD-based gamma cameras. The tested scintillators were selected for their significantly larger cross-sections at 140 keV ((99m)Tc) compared to CsI:Tl combined with moderate to good light yield. A performance comparison based on gamma camera spatial and energy resolution was done with all tested scintillators having equal (66%) interaction probability at 140 keV. CdWO4, Lu2O3:Eu and (Gd,Lu)2O3:Eu all result in a significantly improved spatial resolution over CsI:Tl, albeit at the cost of reduced energy resolution. Lu2O3:Eu transparent ceramic gives the best spatial resolution: 65 µm full-width-at-half-maximum (FWHM) compared to 147 µm FWHM for CsI:Tl. In conclusion, these 'slow' dense scintillators open up new possibilities for improving the spatial resolution of EMCCD-based scintillation cameras.

Perfil epidemiológico da comunidade pertencente à área de risco na cidade de Fortaleza-CE / Epidemiological profile of a community belonging to the risk area in the city of Fortaleza-CE

A pesquisa tem como objetivo geral a análise do perfil epidemiológico dos usuários cadastrados na microárea de risco tipo 1, na cidade de Fortaleza-Ceará. Trata-se de um estudo do tipo transversal e analítico, com abordagem quantitativa, realizado no Centro de Saúde da Família da Secretaria Executiva Regional IV da Prefeitura Municipal de Fortaleza-CE., no período de agosto de 2006 a agosto de 2007. Aplicou-se um formulário semiestruturado como instrumento de pesquisa, a fim de coletar as informações. Utilizou-se o programa EXCELL e o programa Preditictive Analitics Software for Windows (PASW), versão 17.0, para o tratamento dos dados. Utilizou-se a técnica de análise descritiva na base de exploração dos dados, além do teste do qui-quadrado, para verificar a existência de associação entre as variáveis envolvidas no estudo, ao nível de significância de 5%. Os resultados apontaram uma comunidade ganhando de um a dois salários mínimos (230 - 55,8%); apenas 50 (10,6%), com ocupação formal; condições sanitárias e habitacionais precárias (159 - 38,6%); elevada quantidade de crianças fora da creche/escola (113 - 35,9%); e prevalência de doenças crônico-degenerativas entre os idosos (45 - 49,5%). Não foi identificada significância estatística, com uma confiabilidade de 95% entre as categorias apresentadas: não adulto e adulto e os tipos de ocupações (p?0,001); faixa etária escolar das crianças e sexo (p=0,060). Porém observou-se a existência de associação altamente significativa (p?0,001) entre as categorias da faixa etária escolar e a frequência à escola. A faixa etária dos idosos não se apresentou significativa quando relacionada com sexo (p=0,932), ocupação (p=0,200) e tipo de doença (p=0,281). Conclui-se que o retrato epidemiológico oriundo do estudo aponta suscetibilidade multifatorial elevada da comunidade a patologias e agravos à saúde com flagrante dependência de políticas públicas intersetoriais, para modificação do quadro negativo atual.

The research aims to analyze the epidemiological profile of registered users in the type 1 risk micro-area in the city of Fortaleza, Ceará. This is a cross-sectional, analytical study with a quantitative approach, performed at the Center for Family Health of the Region IV Executive Secretariat of the City of Fortaleza-CE, during the period August 2006 to August 2007. We applied a semi-structured questionnaire as a research tool in order to collect the information. We used the Excel program and the Predictive Analytics SoftWare (PASW) for Windows, version 17.0, to process the data. We used the technique of descriptive analysis based on data mining, and the chi-square test, to verify the existence of an association between the variables involved in the study, at a significance level of 5%. Results showed: a community with 230 (55.8%) earning one to two minimum wages, with only 50 (10.6%) having formal employment, 159 (38.6%) with poor sanitary and living conditions, 113 (35.9%) with high number of children without daycare / school attendance, and a prevalence of chronic diseases among the elderly of 45 (49.5%). No statistical significance was identified, with a reliability of 95%, between the categories: non-adult/adult and the types of occupations (p?0,001), nor children?s school age and gender (p = 0.060). However, the existence of a highly significant association (p?0,001) was observed between the categories school age and school attendance. The age of the elderly did not appear significant when compared to gender (p = 0.932), occupation (p = 0.200), and type of disease (p = 0.281). We conclude that the picture coming from the epidemiological study indicates high multifactorial susceptibility of the community to diseases and health problems, with a clear reliance on intersectoral public policies, to change the current negative picture.

Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer.

PURPOSE: The aim of this prospective study was to analyze the safety of methylene blue dye (MBD) and compare its efficacy with that of isotopic mapping for sentinel lymph node (SLN) identification in breast cancer. PATIENTS AND METHODS: The SLN procedure, involving isotopic mapping and MBD (subareolar intraparenchymal injections of 2 mL, 10 mg/mL), was performed on 100 patients with early breast cancer. RESULTS: The procedure was safe with a success rate of 99%; SLNs were, respectively, found in 65% by MBD, in 73% by lymphoscintigraphy and in 94% by gamma-probe. Out of 40 metastatic SLNs, 37 were "hot" and 32 stained. Digital examination allowed the detection of 2 additional metastatic LNs. CONCLUSION: MBD is safe and combination mapping associated with digital examination is the superior method. Modification of the procedure, favouring injections of dilute MBD (4 mL, 1.25 mg/mL) increases MBD efficiency (90%) and maintains low rates of complications.

A new intraoperative gamma camera for the sentinel lymph node procedure in breast cancer.

AIM: This study aimed at evaluating the performance of an intraoperative gamma camera, named CarolIReS, to detect axillary drainage and to assess the removal of sentinel lymph nodes (SLN) in breast surgery. PATIENTS AND METHODS: SLN biopsy was performed on 25 patients and the CarolIReS camera was used preoperatively to localize SLNs. During surgery, individual removal of SLNs was performed using a gamma probe and their activity was measured with a gamma ray counter. At the end of surgery, the CarolIReS camera was used again to check the quality of surgery which was followed by surgical excision for remaining SLNs. RESULTS: The detection efficiency of the CarolIReS camera was 2.2 cps/kBq for 99"Tc activity in SLNs. In one case, it allowed the detection of a residual SLN with a low activity (0.5 kBq) which was massively metastatic. CONCLUSION: Intraoperative cameras could be used to improve the efficiency of the SLN procedure.

Optimization of sentinel lymph node biopsy in breast cancer using an operative gamma camera.

BACKGROUND: Sentinel lymph node (SLN) procedure is now a widely accepted method of LN staging in selected invasive breast cancers (unifocal, size

Precise localization of sentinel lymph nodes and estimation of their depth using a prototype intraoperative mini gamma-camera in patients with breast cancer.

UNLABELLED: The aim of this study was to evaluate the ability of a prototype intraoperative mini gamma-camera, the CarolIReS, with a 50 x 50 mm field of view, to precisely localize sentinel lymph nodes (SLNs) and to determine their depth in a series of patients with infiltrative breast cancer requiring SLN excision. METHODS: With the use of phantoms, the broadness of the signal of an acquired projection was shown to linearly depend on its distance from the collimator. A preclinical ex vivo study of 25 excised SLNs demonstrated that SLN size did not influence depth estimation. The minimum activity threshold for successful use of the proposed method was determined. After a preoperative radioisotope injection and lymphoscintigraphy, the SLN was localized in a series of 11 patients using both the mini gamma-camera and a gamma-probe. During surgery, a ruler was used to measure the depth of all SLNs before their excision. RESULTS: Using the measured linear dependence of image broadness, we found that the expected SLN anatomic depth was compatible with its measured depth during surgery. CONCLUSION: This study showed that the mini gamma-camera efficiently estimated the location of SLNs in 3 dimensions.