Small static radiosurgery field dosimetry with small volume ionization chambers

Purpose: To evaluate the response of the four smallest active volume thimble type ionization chambers commercially available (IBA-dosimetry RAZOR Nano Chamber, Standard Imaging Exradin A16, IBA-dosimetry CC01 and PTW T31022) when measuring SRS cone collimated Flattening Filter Free (FFF) fields. Methods: We employed Monte Carlo simulation for calculating correction factors as defined in IAEA TRS-483. Monte Carlo simulation beam model and ion chamber geometry definitions were supported by an extensive set of measurements. Type A and B uncertainty components were evaluated.Results: Commissioning of Monte Carlo 6 MV and 10 MV FFF beam models yielded relative differences between measured and simulated dose distributions lower than 1.5%. Monte Carlo simulated output factors for 5 mm SRS field agree with experimental values within 1% local relative difference for all chambers. Smallest active volume ion chamber (IBA-dosimetry RAZOR Nano Chamber) exhibits smallest correction, being compatible with unity. Correction factor combined uncertainties range between 0.7% and 0.9%. Smallest uncertainties were recorded for smallest and largest active volume ion chambers, although the latter exhibited largest correction factor. Highest contribution to combined uncertainty was type B component associated with beam model initial electron spatial Full Width Half Maximum (FWHM) uncertainty. Conclusions: Among the investigated chambers, the IBA RAZOR Nano Chamber was found to be an excellent choice for narrow beam output factor measurement since it requires minimum correction (in line with IAEA TRS-483 recommendations). This is caused by its tiny size and tissue equivalence materials which produce minimum volume averaging and fluence perturbationS

Lat-1 and glut-1 carrier expression and its prognostic value in gastroenteropancreatic neuroendocrine tumors

Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors.This work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041, PI16-02091 and PI19-00584 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), GETNE G1707 and GCI1901 (funded by Grupo Español de Tumores Neuroendocrinos y Endocrinos) and cofinanced by FEDER funds to M.M. Proyectos de Investigación en Salud (FIS) PI19/01316-FEDER (funded by Instituto de Salud Carlos III), given to J.C.T. Grants from the Ministerio de Economia y Competitividad (SAF2016-76815 and SAF2017-90794-REDT), and Fundació La Marato de TV3 (534/C/2016) ceded to J.A

Intraosseous Squamous Cell Carcinoma Associated with Denosumab-Induced Osteonecrosis of the Jaw

Medication-related osteonecrosis of the jaw (MRONJ) has been associated with the use of different drugs administered in the treatment of malignant neoplasms or metastases and in antiresorptive therapies. Since 2010, denosumab, a monoclonal antibody whose mechanism of action is to prevent the activation of the RANK receptor on the surface of osteoclasts, has been associated with osteonecrosis of the jaw. Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare neoplasm characterised by the presence of squamous cells within the maxillary or mandibular bone without an initial clinical association with the oral mucosa. We present a case of a PIOSCC in an osteonecrosis of the jaw related to a patient who received antiresorptive treatment with denosumab outlining the clinical and histopathological features of MRONJ and PIOSCC

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

[Antonio García Teijeiro (Barcelona.1991)]

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