Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT).

The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3-5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis.

The first tenet of medicine, primum non nocere or first, do no harm , is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers

The Rise of Blockchain Internet of Things (BIoT): Secured, Device-to-Device Architecture and Simulation Scenarios

Most Internet of Things (IoT) resources are exposed to security risks due to their essential functionality. IoT devices, such as smartphones and tablets, have a limited network, computation, and storage capacity, making them more vulnerable to attacks. In addition, the huge volume of data generated by IoT devices remains an open challenge for existing platforms to process, analyze, and discover underlying trends to create a convenient environment. As a result, to deliver acceptable services, a new solution is necessary to secure data accountability, increase data privacy and accessibility, and extract hidden patterns and usable knowledge. Moving the Internet of Things to a distributed ledger system might be the most effective way to solve these issues. One of the most well-known and extensively utilized distributed ledger systems is the blockchain. Due to its unique properties, such as privacy, accountability, immutability, and anonymity, blockchain technology has recently attracted a lot of interest. Using IoT in conjunction with blockchain technology can bring several benefits. This paper reviews the current state of the art different BIoT architectures, with a focus on current technologies, applications, challenges, and opportunities. The test findings prove that the decentralized authentication platform-based blockchain-based IoT (BIoT) device-to-device architecture has a significantly higher throughput than the gateway-based architecture. To encrypt the elliptical curve cryptographic (ECC) and to generate keys, the Chinese remainder theorem (CRT)-based scheme is proposed and compared with the secure hash algorithm (SHA-256). Finally, ECC-CRT is used to access system performance in terms of latency, throughput, and resource consumption, simulated through the Contiki Cooja (CC) simulator, and alter orderer and peer nodes for performance study in BIoT. A comprehensive analysis and simulation results show that the proposed scheme is secure against a variety of known attacks, including the man-in-the-middle (MiM) attack, and outperforms the SHA-256 cryptographic algorithm. Moreover, the significance of blockchain and IoT, as well as their analysis of proposed architecture, is discussed. This paper will help readers and researchers understand the IoT and its applicability to the real world

Clinical Study Evaluation of Diabetic Patients with Breast Cancer Treated with Metformin during Adjuvant Radiotherapy

. Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients ( value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication ( value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication ( value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Relationship between Industry Payments on Research Productivity and Career Success of Academic Radiation Oncologists

The Physician Payments Sunshine Act in 2010 required industry funding of physicians to be publically reported, now enabling assessment of the effects of industry funding on physician productivity in the field of radiation oncology. The goal of this paper is to further investigate whether there is a direct correlation between industry payments and physician productivity and success, as defined by total publications, h-index, or academic rank, for academic radiation oncologists. This study examined the relationship between industry payments, research productivity, and academic title in academic radiation oncologists. Industry payments data was obtained from the Center for Medicare and Medicaid Services Open Payment database, and bibliometric data was obtained from Scopus. Statistical analyses were performed using on Stata/IC 15.1. Significance was defined as p \u3c 0.05. The annual mean general payments to Professors, Associate Professors, Assistant Professors, and Instructors were $3626,$1293, $622, and$217 respectively. The annual mean research payments were $15813,$7022, $1616, and$293 respectively. Our analysis revealed a significant direct correlation between industry funding and H-index for associate professors, assistant professors, and clinicians/other, but this relationship was not significant for professors and instructors. While both general and research payments was significantly associated with H-index when examined separately, this association was insignificant for general payments when controlling for academic rank, region, degrees, research payments, and gender. A multivariate model showed that an increase in $10,000 annually in research payments was associated with a 1.19-times increase in odds to be in the top quartile of publications and a 1.10-times increase in odds to be in the top quartile of h-index. Increased research productivity is significantly associated with increased academic rank and industry payments. However, when controlling for confounding variables, research payments, and not general payments, are a significant driver of this relationship