Vegetation biomass and topography are associated with seasonal habitat selection and fall translocation behavior in Arctic hares.

Habitat selection theory suggests that environmental features selected at coarse scales reveal fundamental factors affecting animal fitness. When these factors vary across seasons, they may lead to large-scale movements, including long-distance seasonal migrations. We analyzed the seasonal habitat selection of 25 satellite-tracked Arctic hares from a population on Ellesmere Island (Nunavut, Canada) that relocated over 100 km in the fall. Since no other lagomorph is known to perform such extensive movements, this population offered an ideal setting to test animal movement and habitat selection theory. On summer grounds hares selected low elevation areas, while on winter grounds they selected high vegetation biomass, high elevation, and steep slopes. During fall relocation, they alternated between stopover and traveling behavioral states (ratio 2:1). Stopover locations were characterized by higher vegetation heterogeneity and lower rugosity than traveling locations, while vegetation biomass and elevation interacted to explain stopover locations in a more complex way. The selected combination of environmental features thus varied across seasons and behavioral states, in a way broadly consistent with predictions based on the changing food and safety needs of hares. Although causality was not demonstrated, our results improve our understanding of long-distance movements and habitat selection in Arctic hares, as well as herbivore ecology in the polar desert. Results also provide strong support to animal movement and habitat selection theory, by showing how some important hypotheses hold when tested in a species phylogenetically distinct from most animal models used in this research field.

The bioequivalence study design recommendations for immediate-release solid oral dosage forms in the international pharmaceutical regulators programme participating regulators and organisations: differences and commonalities.

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug's pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2.

Warming in the land of the midnight sun: breeding birds may suffer greater heat stress at high- versus low-Arctic sites.

Rising global temperatures are expected to increase reproductive costs for wildlife as greater thermoregulatory demands interfere with reproductive activities. However, predicting the temperatures at which reproductive performance is negatively impacted remains a significant hurdle. Using a thermoregulatory polygon approach, we derived a reproductive threshold temperature for an Arctic songbird-the snow bunting (Plectrophenax nivalis). We defined this threshold as the temperature at which individuals must reduce activity to suboptimal levels (i.e. less than four-time basal metabolic rate) to sustain nestling provisioning and avoid overheating. We then compared this threshold to operative temperatures recorded at high (82° N) and low (64° N) Arctic sites to estimate how heat constraints translate into site-specific impacts on sustained activity level. We predict buntings would become behaviourally constrained at operative temperatures above 11.7°C, whereupon they must reduce provisioning rates to avoid overheating. Low-Arctic sites had larger fluctuations in solar radiation, consistently producing daily periods when operative temperatures exceeded 11.7°C. However, high-latitude birds faced entire, consecutive days when parents would be unable to sustain required provisioning rates. These data indicate that Arctic warming is probably already disrupting the breeding performance of cold-specialist birds and suggests counterintuitive and severe negative impacts of warming at higher latitude breeding locations.

A Survey of the Criteria Used for the Selection of Alternative Comparator Products by Participating Regulators and Organizations of the International Pharmaceutical Regulators Programme.

The safety and efficacy of a generic product are partly based on demonstrating bioequivalence to the innovator product; however, when the innovator product is no longer available as a comparator product, a survey conducted within the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP) indicated that the criteria for selecting an alternative comparator product varies. For most members of the BEWGG, an existing marketed generic that was approved based on a comparison with the locally registered innovator product can be used, contingent on criteria that ranges from allowing any generic to be used, to allowing only specific criteria-defined generics to be used. Notwithstanding the acceptability of a generic as an alternative comparator, it is not always the preferred comparator for several jurisdictions. Some jurisdictions require the use of a locally sourced alternative innovator comparator (e.g., the same medicinal ingredient manufactured by a different company) or a foreign innovator comparator. Unlike the other members of the BEWGG, the European Union (EU) has no such options available, rather mechanisms are in place to allow manufacturers to develop a new comparator. The criteria described herein regarding the use of an alternative comparator product can also be applied to scenarios where a specific strength of a series of strengths or an innovative fixed dose combination are discontinued. The results of the survey demonstrate that while criteria for selecting alternative comparator products are not harmonized among the BEWGG participants, the common concern for all jurisdictions is to select a comparator product that meets the safety and efficacy standards of the original innovator product.

Evaluation of subcutaneous daratumumab injections in the ambulatory care setting.

INTRODUCTION: Subcutaneous daratumumab is non-inferior to intravenous daratumumab for the treatment of multiple myeloma and significantly reduced incidence of systemic reactions. However, manufacturer for subcutaneous daratumumab has not provided guidance regarding optimal methods for monitoring for hypersensitivity reactions following subcutaneous daratumumab administration. METHODS: A retrospective analysis was performed in two cohorts of patients who received at least two doses of subcutaneous daratumumab for the treatment of plasma cell disorders: patients with previous exposure to intravenous daratumumab (dara-exposed) and patients without history of intravenous daratumumab (dara-naïve). The primary outcome was incidence of systemic and injection-site reactions following first dose of subcutaneous daratumumab. Secondary analysis included time to systemic and injection-site reactions, grading of adverse reaction, and incidence of second systemic reaction. RESULTS: Thirty-one patients were dara-naïve and 49 patients were dara-exposed. Differences in incidence of systemic (dara-naïve: 9.7% vs dara-exposed: 6.1%, p = 0.67) and injection-site reactions (dara-naïve: 12.9% vs dara-exposed: 14.3%, p = 0.99) did not reach statistical significance. Difference in median time to systemic reaction (dara-naïve: 3 h vs dara-exposed: 12 h, p = 0.18) was clinically important but did not reach statistical significance. Median time to injection-site reactions (dara-naïve: 6 h vs dara-exposed: 24 h, p = 0.03) was shorter in the dara-naïve cohort. No clinically meaningful difference was observed for incidence of second systemic reaction. CONCLUSION: Most reactions were mild and did not require medical intervention. Following first subcutaneous daratumumab dose, monitoring for 3 h for dara-naïve patients and no monitoring time for dara-exposed patients for hypersensitivity reactions may be a safe and reasonable practice.

Impact of Extended-Interval Versus Standard Dosing of Zoledronic Acid on Skeletal Events in Non-Small-Cell Lung Cancer and Small-Cell Lung Cancer Patients With Bone Metastases.

BACKGROUND: Zoledronic acid every 4 weeks (Q4wk) reduces the incidence of skeletal-related events (SREs) in patients with metastatic lung cancer. Lung cancer patients were excluded from extended-interval dosing trials (every 12 weeks [Q12wk]) that demonstrated noninferiority of the 2 dosing schemes. To date, the optimal dosing of zoledronic acid in metastatic lung cancer remains unknown. OBJECTIVE: To determine whether zoledronic acid dosed Q12wk is similar to Q4wk dosing for prevention of SRE in patients with metastatic lung cancer. METHODS: A retrospective analysis was performed in patients with non-small-cell lung cancer and small-cell lung cancer with bone metastases who received Q12wk and Q4wk zoledronic acid. The primary outcome was incidence of SRE at 1 year. Secondary analyses included time to first SRE, overall survival (OS), incidence of osteonecrosis of the jaw (ONJ), kidney dysfunction, and hypocalcemia. RESULTS: A total of 34 patients received Q12wk and 46 patients received Q4wk zoledronic acid. Incidence of SRE at 1 year (Q12wk, 23.5%, vs Q4wk, 23.9%; 95% CI = -0.184 to 0.192; P = 0.968) and median time to SRE (not reached for either cohort; P = 0.530) did not differ. The Q12wk cohort had longer median OS (24.00 vs 8.97 months; P = 0.022). There were no differences in incidence of ONJ, kidney dysfunction, and hypocalcemia. CONCLUSION AND RELEVANCE: This is the first report examining extended-interval dosing of zoledronic acid in metastatic lung cancer. Incidence and time to SRE at 1 year were similar. This extended-interval dosing may be safe and reasonable for patients with lung cancer with bone metastases.

A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme.

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members.  Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.

Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities.

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

Robotic partial nephrectomy: The current status.

INTRODUCTION: Since its introduction, robotic partial nephrectomy (RPN) has become increasingly popular, in part as a result of several advances in technique. The purpose of this paper is to review these techniques as well as the perioperative, functional, and oncologic outcomes after RPN and compare these outcomes to those after laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN). METHODS: A literature review was performed to identify papers and meta-analyses that compared outcomes after RPN to OPN or LPN. All meta-analyses were included in this review. RESULTS: Technical advances that have contributed to improved outcomes after RPN include the first-assistant sparing technique, the sliding clip technique, early unclamping, and selective arterial clamping. All five meta-analyses that compared LPN to RPN found that RPN was associated with a shorter warm ischemia time (WIT), but that there were no differences in estimated blood loss (EBL) or operative times. Those meta-analyses that compared intraoperative and postoperative complications, conversion to open or radical nephrectomy, length of stay (LOS), and postoperative estimated glomerular filtration rate (eGFR) either found no difference or favored RPN. Four meta-analyses compared RPN to OPN. All four found that EBL, LOS, and postoperative complications favor RPN. There were no significant differences in intraoperative complications, conversion to radical nephrectomy, or positive surgical margin rates. One meta-analysis found that eGFR was better after RPN. Operative time and WIT generally favored OPN. CONCLUSIONS: Several techniques have been described to improve outcomes after RPN. We believe that the literature shows that RPN is as good if not better than both LPN and OPN and has become the preferred surgical approach.

The Requirements for Additional Strength Biowaivers for Immediate Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities.

In relation to the registration of generic products, waivers of in vivo bioequivalence studies (biowaivers) are considered in three main cases: certain dosage forms for which bioequivalence is self-evident (e.g. intravenous solutions), biowaivers based on the Biopharmaceutics Classification System and biowaivers for additional strengths with respect to the strength for which in vivo bioequivalence has been shown. The objective of this article is to describe the differences and commonalities in biowaivers for additional strengths of immediate release solid oral dosage forms between the participating members of the International Pharmaceutical Regulators Program (IPRP). The requirements are based on five main aspects; the pharmacokinetics of the drug substance, the manufacturing process, the qualitative and quantitative composition of the different strengths, and the comparative dissolution profiles. For the pharmacokinetic aspects, many regulators/agencies have the same requirements. All strengths must be manufactured with the same process, although a few regulators/agencies accept small differences. In relation to the formulation aspects, the data required breaks down into three major approaches based initially on one of those of the EU, the USA or Japan, but there are some differences in these three major approaches with some country specific interpretations. Most regulators/agencies also have the same requirements for the dissolution data, though there are some notable exceptions.

Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis.

Branching morphogenesis in the mammary gland is achieved by the migration of epithelial cells through a microenvironment consisting of stromal cells and extracellular matrix (ECM). Here we show that galectin-1 (Gal-1), an endogenous lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes, induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D organotypic cultures. Surprisingly, Gal-1's effects on mammary patterning were independent of its glycan-binding ability and instead required localization within the nuclei of mammary epithelia. Nuclear translocation of Gal-1, in turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end buds. Specifically, α2,6-sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Conversely, unsialylated LacNAc glycans, enriched in the epithelial ducts, sequestered Gal-1 in the extracellular environment, ultimately attenuating invasive potential. We also found that malignant breast cells possess higher levels of nuclear Gal-1 and α2,6-SA and lower levels of LacNAc than nonmalignant cells in culture and in vivo and that nuclear localization of Gal-1 promotes a transformed phenotype. Our findings suggest that differential glycosylation at the level of tissue microanatomy regulates the nuclear function of Gal-1 in the context of mammary gland morphogenesis and in cancer progression.

Variation in the use of active surveillance for low-risk prostate cancer.

BACKGROUND: This study assessed the use of active surveillance in men with low-risk prostate cancer and evaluated institutional factors associated with the receipt of active surveillance. METHODS: A retrospective, hospital-based cohort of 115,208 men with low-risk prostate cancer diagnosed between 2010 and 2014 was used. Multivariate and mixed effects models were used to examine variation and factors associated with active surveillance. RESULTS: During the study period, the use of active surveillance increased from 6.8% in 2010 to 19.9% in 2014 (estimated annual percentage change, +28.8%; 95% confidence interval [CI], + 19.6% to + 38.7%; P = .002). The adjusted probability of active-surveillance receipt by institution was highly variable. Compared with patients treated at comprehensive community cancer centers, patients treated at community cancer programs (odds ratio [OR], 2.00; 95% CI, 1.50-2.67; P < .001) and academic institutions (OR, 2.47; 95%, CI, 1.81-3.37; P < .001) had higher odds of receiving active surveillance. Compared with patients treated at very low-volume facilities, patients treated at very high-volume facilities had higher odds of receiving active surveillance (OR, 3.57; 95% CI, 1.94-6.55; P < .001). Patient and hospital characteristics accounted for 60.2% of the overall variation, whereas the treating institution accounted for 91.5% of the unexplained variability. CONCLUSIONS: Within this hospital-based cohort, the use of active surveillance for low-risk prostate cancer increased significantly over time. Significant variation was found in the use of active surveillance. Most of the variation was attributable to facility-related factors such as the facility type, facility volume, and institution. Policies to achieve consistent and higher rates of active surveillance, when appropriate, should be a priority of professional societies and patient advocacy groups. Cancer 2018;124:55-64. © 2017 American Cancer Society.

Changes observed in prostate biopsy practices in an inner city hospital with a high risk patient population following the 2012 uspstf psa screening recommendations.

INTRODUCTION: We compared characteristics of patients undergoing prostate biopsy in a high-risk inner city population before and after the 2012 USPSTF recommendation against PSA based prostate cancer screening to determine its effect on prostate biopsy practices. MATERIALS AND METHODS: This was a retrospective study including patients who received biopsies after an abnormal PSA measurement from October 2008-December 2015. Patients with previously diagnosed prostate cancer were excluded. Chi-square tests of independence, two sample t-tests, Mann-Whitney U tests, and Fisher's exact tests were performed. RESULTS: There were 202 and 208 patients in the pre-USPSTF and post-USPSTF recommendation cohorts, respectively. The post-USPSTF cohort had higher median PSA (7.8 versus 7.1ng/mL, p=0.05), greater proportion of patients who were black (96.6% versus 90.5%, p=0.01), and greater percentage of biopsy cores positive for disease (58% versus 29.5%, p<0.001). Multivariable analysis supported that the increase in PSA was independent of the increase in the proportion of patients who were black. The proportion of patients who were classified as D'Amico intermediate and high-risk disease increased in the post-USPSTF cohort and approached statistical significance (70.1% versus 58.8%, p=0.12). CONCLUSIONS: Our study suggests that the USPSTF recommendations may have led to na increase in pre-biopsy PSA as well as greater volume of disease. Also, a greater proportion of patients were being classified with intermediate or high risk disease. While the clinical significance of these findings is unknown, what the data suggests is somewhat troubling. Future research should further examine these changes in a larger cohort as well as resultant long-term outcomes.

Notch1 and Notch2 receptors regulate mouse and human gastric antral epithelial cell homoeostasis.

OBJECTIVE: We tested the ability of Notch pathway receptors Notch1 and Notch2 to regulate stem and epithelial cell homoeostasis in mouse and human gastric antral tissue. DESIGN: Mice were treated with the pan-Notch inhibitor dibenzazepine (DBZ) or inhibitory antibodies targeting Notch1 and/or Notch2. Epithelial proliferation, apoptosis and cellular differentiation were measured by histological and molecular approaches. Organoids were established from mouse and human antral glands; growth and differentiation were measured after treatment with Notch inhibitors. RESULTS: Notch1 and Notch2 are the predominant Notch receptors expressed in mouse and human antral tissue and organoid cultures. Combined inhibition of Notch1 and Notch2 in adult mice led to decreased epithelial cell proliferation, including reduced proliferation of LGR5 stem cells, and increased apoptosis, similar to the response to global Notch inhibition with DBZ. Less pronounced effects were observed after inhibition of individual receptors. Notch pathway inhibition with DBZ or combined inhibition of Notch1 and Notch2 led to increased differentiation of all gastric antral lineages, with remodelling of cells to express secretory products normally associated with other regions of the GI tract, including intestine. Analysis of mouse and human organoids showed that Notch signalling through Notch1 and Notch2 is intrinsic to the epithelium and required for organoid growth. CONCLUSIONS: Notch signalling is required to maintain gastric antral stem cells. Notch1 and Notch2 are the primary Notch receptors regulating epithelial cell homoeostasis in mouse and human stomach.

Association Between Recurrence and Re-Excision for Close and Positive Margins Versus Observation in Patients with Benign Phyllodes Tumors.

BACKGROUND: Breast lesions not sampled prior to surgery or initially diagnosed as fibroepithelial lesions on core biopsy may have a diagnosis of phyllodes tumor (PT) on excision. Historically, re-excision for close or positive margins has been the standard of care. We examined the rate of re-excision for close or positive margins in patients with benign phyllodes and compared recurrence rates among those undergoing re-excision versus observation. METHODS: We identified all patients with phyllodes tumor diagnosed between 2003 and 2013. Operative and surgical pathology reports were reviewed for clinical, pathologic, and follow-up data. RESULTS: Among 246 cases, 216 (88%) were benign PT and 30 (12%) borderline/malignant tumors. In the group of benign PT (n = 216), margins were negative in 64 patients (29.6%), 50 (23%) were close, and 102 (47%) were positive. Of those with close margins, 22 (44%) underwent reexcision and residual benign PT was found in 2 (9%). In patients with positive margins, 45 (44%) had re-excision and residual benign PT was detected in 4 (8.8%). After a median follow-up of 35.5 months, there were 4 (1.9%) recurrences among patients with benign PT. There was no difference in recurrence among patients who had re-excision for positive or close margins versus observation (p = 0.7 and 0.21, respectively). CONCLUSIONS: Among patients with close or positive margins, there was no significant difference in disease recurrence between patients who underwent reexcision and those who were observed. Based on these results, it may be reasonable to manage these patients conservatively with close follow-up.

Evaluation of the first open-access hepatitis B and safe injection online training course for health professionals in China.

BACKGROUND: Despite the high prevalence of chronic hepatitis B virus (HBV) infection in China, HBV infection prevention and long-term care knowledge of health professionals is inadequate. To address this knowledge gap, we developed an open-access evidence-based online training course, "KnowHBV", to train health professionals on prevention of HBV transmission and safe injections. We conducted an evaluation of the course with health professionals in China to examine its effectiveness in improving knowledge and learner's satisfaction of the course. METHODS: Between July and December 2011, 1015 health professionals from selected hospitals and disease control institutions of Shandong province registered for the course and 932 (92 %) completed the three-module course. Participants' demographic information, pre- and post-course knowledge test results and learner's feedback were collected through the course website. RESULTS: Pre-course knowledge assessment confirmed gaps in HBV transmission routes, prevention and long-term care knowledge. Only 50.4 % of participants correctly identified all of the transmission routes of HBV, and only 40.7 % recognized all of the recommended tests to monitor chronically infected persons. The number of participants that answered all six multi-part multiple-choice knowledge questions correctly increased from 183 (19.7 %) before taking the course to 395 (42.4 %) on their first attempt upon completion of the course. Over 90 % of the 898 participants who completed the learner-feedback questionnaire rated the course as 'good' or 'very good'; over 94 % found the course instructional design helpful; 57.5 %, 65.7 % and 68.5 % reported that half or more than half of the course content in modules 1, 2 and 3 respectively provided new information; and 93.2 % of the participants indicated they preferred the online learning over traditional face-to-face classroom learning. CONCLUSIONS: The "KnowHBV" online training course appears to be an effective online training tool to improve HBV prevention and care knowledge of the health professionals in China.

Grade 5 Radiation Necrosis After Whole-Brain Radiation Therapy.

Whole-brain radiation treatment is often considered for patients with leptomeningeal disease. There are limited reports of the development of radiation necrosis after whole-brain radiation treatment and fewer associating the presence of germline mutations with risk. We present a case report to highlight the need for consideration of radiosensitizing mutations when recommending radiation therapy.

Experience From an Early Exposure Education Program in Radiation Oncology for High School and Undergraduate Students.

Exposure to radiation oncology (RO), which is a small and highly subspecialized field of oncology, during undergraduate or medical education is often limited. Coupled with reduced elective exposures during the COVID-19 pandemic, unsubstantiated concerns regarding the RO job market have led to a noticeable decline in residency applications and medical students who express an interest in the field. Here, we describe a summer education program piloted in our RO department at a comprehensive cancer center to provide premedical school students (ranging from high school to postbaccalaureate) early exposure to the specialty through clinical shadowing, research opportunities, journal club, and formal didactic lectures. Pre- and postprogram surveys were administered to these students to evaluate the change in knowledge in RO. A total of 8 students participated in the program. We found an increase in understanding of the specialty, high levels of interest in considering RO as a career, and positive feedback regarding the program overall. This study supports the role of early exposure and education in stimulating interest in future medical students to pursue RO as a career. Future efforts are needed to further develop and evaluate these education programs as well as disseminate the program more broadly.

Perception and Utilization of Cannabinoids in Patients Undergoing Radiation Treatment: Our Patients Are Curious.

PURPOSE: Limited studies have described the utilization of cannabinoids among patients with cancer. This survey study aimed to characterize utilization patterns and perceptions of cannabinoid use for treatment-related side effects among patients receiving radiation treatment. METHODS AND MATERIALS: This was an anonymous survey study of patients who were undergoing or recently completed radiation treatment at a comprehensive cancer center. Data on cannabinoid use during cancer treatment, reasons for the use of cannabinoids, perceived effects of cannabinoids, and formulations of usage were collected and summarized using descriptive statistics. RESULTS: Of the 431 respondents, 111 (25.8%) patients reported cannabinoid use since their cancer diagnosis. Among the cannabinoid users, a majority (73.9%) experienced improvement in symptoms; 38.7% had better relief of cancer-treatment symptoms from cannabinoids in comparison to their prescription medications, and 16.2% lowered the amount of prescription pain medications needed after using cannabinoids. Cannabinoids appeared to be most effective in helping patients manage sleep (76.6%) and anxiety (72.1%). When asked about whether physicians should be discussing cannabinoid use, 45.1% of cannabinoid users wanted to speak with their doctors regarding its utilization. For patients who did not report cannabinoid use, a large majority (83.1%) never had discussions with their doctors regarding its utilization as part of their cancer care, and 34.8% wanted to learn more about cannabinoids from their doctors. CONCLUSIONS: About 1 in 4 patients with cancer reported cannabinoid use to assist in symptom control. A majority had subjective alleviation of treatment-related symptoms from cannabinoid use. Regardless of cannabinoid use, a sizable percentage of patients never had any discussions about cannabinoids with their oncologists, with some expressing interest in learning more. Guidelines are needed to assist radiation oncologists on how cannabinoids may play a role in caring for patients.

Current Status and Future Directions of Image-Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer.

PURPOSE: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. METHODS: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". DISCUSSION: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. CONCLUSIONS: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy.