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Abstract: Purpose: Quercetin (3, 3,′ 4′, 5, 7 – five-flavonoids) is one of the main components of flavonoids, with multifunctions on immune function, anti-oxidation, anti-viral, anti-inflammatory, and cardiovascular protection. We hypothesize that a combination of quercetin with radiation would increase tumor radiosensitivity. To test this hypothesis, we conducted in vitro and in vivo studies. Methods and materials: The in vitro radio-sensitization activity of quercetin was tested in DLD1, HeLa and MCF-7 tumor cell lines by colony formation assays. The in vivo activity was assessed in the DLD-1 human colorectal cancer xenograft model in nude mice. Mechanistic studies were conducted in several cell lines using Western blot analysis and immunofluorescence microscopy. Results: We found that quercetin can significantly increase tumor radiosensitivity both in vitro and in vivo. The in vitro Sensitizing Enhancement Ratios in DLD1, HeLa and MCF-7 cells were 1.87, 1.65, and 1.74, respectively. The mean doubling time of tumor xenografts was significantly increased in irradiated mice treated with quercetin. At the cellular level, exposure to quercetin resulted in prolonged DNA repair. The mechanistic studies demonstrated that quercetin induced radio-sensitization is through inhibiting the ATM kinase, one of the critical DNA damage response proteins. Conclusion: We demonstrate both in vitro and in vivo evidence that combination of quercetin with radiotherapy can enhance tumor radiosensitivity by targeting the ATM-mediated pathway in response to radiation. [Copyright &y& Elsevier]

Abstract: The 2012 Radiation Oncology Workforce survey was conducted to assess the current state of the entire workforce, predict its future needs and concerns, and evaluate quality improvement and safety within the field. This article describes the dosimetrist segment results. The American Society for Radiation Oncology (ASTRO) Workforce Subcommittee, in conjunction with other specialty societies, conducted an online survey targeting all segments of the radiation oncology treatment team. The data from the dosimetrist respondents are presented in this article. Of the 2573 dosimetrists who were surveyed, 890 responded, which resulted in a 35% segment response rate. Most respondents were women (67%), whereas only a third were men (33%). More than half of the medical dosimetrists were older than 45 years (69.2%), whereas the 45 to 54 years age group represented the highest percentage of respondents (37%). Most medical dosimetrists stated that their workload was appropriate (52%), with respondents working a reported average of 41.7 ± 4 hours per week. Overall, 86% of medical dosimetrists indicated that they were satisfied with their career, and 69% were satisfied in their current position. Overall, 61% of respondents felt that there was an oversupply of medical dosimetrists in the field, 14% reported that supply and demand was balanced, and the remaining 25% felt that there was an undersupply. The medical dosimetrists׳ greatest concerns included documentation/paperwork (78%), uninsured patients (80%), and insufficient reimbursement rates (87%). This survey provided an insight into the dosimetrist perspective of the radiation oncology workforce. Though an overwhelming majority has conveyed satisfaction concerning their career, the study allowed a spotlight to be placed on the profession׳s current concerns, such as insufficient reimbursement rates and possible oversupply of dosimetrists within the field. [Copyright &y& Elsevier]

Purpose: The recently activated Radiation Therapy Oncology Group (RTOG) studies of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC) require tissue density heterogeneity correction, where the high and intermediate dose compliance criteria were established based on superposition algorithm dose calculations. The study was aimed at comparing superposition algorithm dose calculations with Monte Carlo (MC) dose calculations for SBRT for NSCLC and to evaluate whether compliance criteria need to be adjusted for MC dose calculations. Methods and Materials: Fifteen RTOG 0236 study sets were used. The planning tumor volumes (PTV) ranged from 10.7 to 117.1 cm3. SBRT conformal treatment plans were generated using XiO (CMS Inc.) treatment planning software with superposition algorithm to meet the dosimetric high and intermediate compliance criteria recommended by the RTOG 0813 protocol. Plans were recalculated using the MC algorithm of a Monaco (CMS, Inc.) treatment planning system. Tissue density heterogeneity correction was applied in both calculations. Results: Overall, the dosimetric quantities of the MC calculations have larger magnitudes than those of the superposition calculations. On average, R 100% (ratio of prescription isodose volume to PTV), R 50% (ratio of 50% prescription isodose volume to PTV), D 2cm (maximal dose 2 cm from PTV in any direction as a percentage of prescription dose), and V 20 (percentage of lung receiving dose equal to or larger than 20 Gy) increased by 9%, 12%, 7%, and 18%, respectively. In the superposition plans, 3 cases did not meet criteria for R 50% or D 2cm. In the MC-recalculated plans, 8 cases did not meet criteria for R 100%, R 50%, or D 2cm. After reoptimization with MC calculations, 5 cases did not meet the criteria for R 50% or D 2cm. Conclusions: Results indicate that the dosimetric criteria, e.g., the criteria for R 50% recommended by RTOG 0813 protocol, may need to be adjusted when the MC dose calculation algorithm is used. [Copyright &y& Elsevier]

Abstract: Purpose: Providing adequate dosimetric coverage of elongated, curvilinear incisions during adjuvant intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) creates technical challenges. We explored high-dose-rate (HDR) surface brachytherapy to supplement dose to multiple curvilinear incisions. This modality circumvents the technical limitations of relying on multiple en face electron fields while minimizing dose to adjacent normal tissues. Methods and Materials: A 59-year-old man presented with a left-sided, Stage III, T3N2M0, epithelioid MPM. After undergoing a left EPP, adjuvant IMRT was recommended to improve local control. An eight-field IMRT plan was designed to encompass the postoperative hemithorax. Incisional scars were lengthy and extended beyond the hemithoracic target volume. Both en face electron and surface HDR plans were prepared and evaluated based on dosimetric coverage of the incisional scars, dose to normal tissues, reliability of setup, and treatment delivery. Results: HDR was preferred. The patient was planned and treated in the right lateral decubitus position. HDR source catheters were placed along the incisions atop 5-mm bolus. A composite plan including IMRT and brachytherapy dose contributions was produced. Boosts of incisional scars were performed in six fractions (three fractions per week) of 3Gy prescribed to 12mm from the catheter. HDR brachytherapy was well tolerated. Conclusions: Surface HDR brachytherapy is a viable option for supplemental dose to incisional scars at risk of local recurrence after EPP for MPM. Advantages over electron beam therapy include avoidance of field abutments and feathering, less tissue–bone interface dose uncertainty and reproducibility of treatment delivery. [Copyright &y& Elsevier]