A Novel USMLE® Step 1 Based Approach to Introducing Radiation Oncology to Second-Year Preclinical Medical Students.

There is a paucity of formalized exposure to Radiation Oncology (RO) for preclinical medical students across the United States as well as barriers to implementation within undergraduate medical education curriculum at many institutions. We present a novel approach to implementing an introductory RO didactic lecture to second-year medical students by interweaving associated oncological and ionizing radiation content represented on the United States Medical Licensing Exam® (USMLE®) Step 1 examination. Students had synchronous and asynchronous opportunities to engage with the 1.0-h didactic lecture administered by an attending Radiation Oncologist faculty member. Students were electronically invited to anonymously rank the effectiveness of the lecture materials on a 5-point Likert scale. Performance on standardized board-style questions regarding radiation biology and radiation side effects was recorded before and after the lecture and compared to the historic performance of previous institutional second-year medical student cohorts. The lecture material effectiveness received a mean score of 4.50 on a 5-point Likert scale. There was a statistically significant improvement in student performance on a board-style radiation side effect question from 39% on a pretest to 76% on a posttest. A USMLE® topic-based approach may be an effective way to implement a formalized introduction to RO to preclinical medical students while simultaneously improving performance on relevant standardized board-style questions. Providing evidence that RO topics appear on the USMLE® Step 1 examination curriculum was a powerful incentive for implementation when negotiating with curriculum offices.

Experience With Medical Marijuana for Cancer Patients in the Palliative Setting.

OBJECTIVES: Medical marijuana is a symptom treatment option for palliative cancer patients; however, its useful applications remain limited. The goals of this study were to review the characteristics of patients who received medical marijuana under our ambulatory palliative care program and to determine barriers to access and use of medical marijuana in this population. METHODS: This study was a retrospective analysis of patients who were enrolled in the medical marijuana registry through the ambulatory palliative care department at Upstate Cancer Center. Data from June 2017 to June 2020 were analyzed. Patients were included if they had a diagnosis of cancer, were certified by a qualified practitioner in the New York Medical Marijuana Program, and received care at Upstate Medical University. Patients were excluded if no marijuana certificate was found or if they transferred care. RESULTS: The study population was 184 patients. Ninety-three patients (51.5%) received at least one prescription from a New York licensed marijuana dispensary while 72 (39.13%) were certified but never obtained any medical marijuana. For patients who took at least one dose of medical marijuana, 48.14% experienced an improvement in pain, 44.95% used fewer opioids, and 85.11% had an improvement in at least one symptom. Adverse effects were low at 3.72%. CONCLUSION: Medical marijuana has an important role in the palliation of symptoms in advanced cancers with few adverse effects. There are still many barriers to effective use. More prospective research is needed to optimize delivery and dosing.

Radiation oncology education and experience in the undergraduate medical setting.

The goal of this study was to determine the impact and experience of radiation oncology (RO) education in the undergraduate medical experience in the USA. A list of American medical schools was complied from various sources including the Association of American Medical Colleges (AAMC) and American Association of Colleges of Osteopathic Medicine (AACOM) in the summer of 2019. Data was extracted through institution website review, individual phone calls and email distribution. A total of 198 programs (155 allopathic and 43 osteopathic medical schools) were included. Every medical school curriculum had oncology lecture during MS year 1 and 2, although a minimal amount (4%) had a RO-specific lecture during MS year 1 and 2. There were significant differences in the RO education and experience in allopathic (MD) versus osteopathic (DO) programs. Home radiation oncology programs and career advising were associated with a radiation oncology elective during year 3 and 4. Furthermore, RO career advisors and older schools were associated with having one student match into radiation oncology. RO education during the didactic portion of the undergraduate medical experience remains extremely limited. This limitation is even more pronounced in medical schools without RO mentorship and in osteopathic medical schools. This lack of RO exposure perpetuates itself by bringing less students into the field. These issues require attention both on a national and medical-school-specific level.

Stem cell based delivery of IFN-beta reduces relapses in experimental autoimmune encephalomyelitis.

Interferon-beta (IFN-beta), an approved treatment of multiple sclerosis (MS), produces only partial clinical responses. IFN-beta therapy has been limited by its short serum half-life and limited ability to cross the blood brain barrier. We have developed a means of delivering the IFN-beta gene both systemically and into the central nervous system (CNS) using bone marrow stem cells (BMSCs) as a vehicle and examined the therapeutic efficacy of this approach in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. A retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect virus producer PA317 cells to generate retrovirus containing the IFN-beta gene which then was used to transduce BMSCs. IFN-beta engineered BMSCs were transplanted (i.v.) into mice that then were immunized with proteolipoprotein (PLP) to initiate EAE. IFN-beta-engineered BMSCs transplanted mice showed a significant inhibition of EAE onset, and the overall clinical severity was less compared to control groups. IFN-beta delivery strongly reduced infiltration of mononuclear cells possibly by inhibiting cell adhesion molecules. Reduced demyelination and increased remyelination were also observed in the IFN-beta treated group. Furthermore, inhibition of the pro-inflammatory cytokines TNF-alpha, IFN-gamma and IL-12 and enhanced expression of the anti-inflammatory cytokines IL-10, IL-4 and TGF-beta was observed in CNS tissue. In addition, mice receiving IFN-beta had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF. These results suggest that BMSCs can be used as vehicles to deliver the IFN-beta into the CNS. This is a potentially novel therapeutic approach which might be used in MS and other diseases of the CNS in which drug access is limited.

Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis.

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) which includes a neurodegenerative component. Brain derived neurotrophic factor (BDNF) is a neuroprotective agent which might be useful in preventing neurodegeneration but its application has been limited because the blood brain barrier restricts its access to the CNS. We have developed a novel delivery system for BDNF using transformed bone marrow stem cells (BMSC) and undertook studies of EAE to determine whether the delivery of BDNF could reduce inflammation and apoptosis. Mice receiving BDNF producing BMSC had reduced clinical impairment compared to control mice receiving BMSC that did not produce BDNF. Pathological examination of brain and spinal cord showed a reduction in inflammatory infiltrating cells in treated compared to control mice. Apoptosis was reduced in brain and spinal cord based on TUNEL and cleaved Caspase-3 staining. Consistent with the known mechanism of action of BDNF on apoptosis, Bcl-2 and Akt were increased in treated mice. Further studies suggested that these increases could be mediated by inhibition of both caspase dependent and caspase independent pathways. These results suggest that the BDNF delivered by the transformed bone marrow stem cells reduced clinical severity, inflammation and apoptosis in this model.

Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is neuroprotective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the central nervous system (CNS), when delivered peripherally, is limited due to the blood-brain barrier (BBB). We have developed a means of delivering BDNF into the CNS using genetically engineered bone marrow stem cells (BMSCs) as a vehicle, and have explored the clinical effects of BDNF on outcomes in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). BDNF-engineered-BMSCs were transplanted (i.v.) into irradiated 2-week-old SJL/J female mice. Eight weeks after transplantation, mice were immunized with a peptide of proteolipid protein (PLP(139-151)). Mice, which had received BDNFengineered BMSCs, showed a significant delay in EAE onset and a reduction in overall clinical severity compared to mice receiving BMSC transfected with an empty vector lacking the BDNF gene. In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination. Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group. These results support the use of BMSCs as vehicles to deliver BDNF into the CNS of EAE animals. This is a potentially novel therapeutic approach that might be used to deliver BDNF gene or genes for other therapeutic proteins into the CNS in MS or in other diseases of the CNS in which accessibility of therapeutic proteins is limited due to the BBB.