Analysis of Oncology and Radiation Therapy Representation on the National Board of Medical Examiners Official Practice Material for the United States National Standardized Medical Board Examinations.

Radiation therapy (RT) is a critical component of multidisciplinary cancer care, but has inconsistent curricular exposure. We characterize the radiation oncology (RO) content on the standardized undergraduate medical examinations by comparing its context and prevalence with other domains in oncology. National Board of Medical Examiners (NBME) self-assessments and sample questions for the United States Medical Licensing Exam (USMLE) Steps 1-3 and NBME clinical science shelf examinations were accessed (n = 3878). Questions were inductively analyzed for content pertaining to oncology and treatment modalities of RT, systemic therapy (ST), and surgical intervention (SI). Questions were coded using USMLE Physician Tasks/Competencies and thematic analysis. Descriptive statistics and analyses using the Kruskal-Wallis test are reported. A total of 337 questions (8.6%) within the USMLE and shelf exams included oncology content, with 101 questions (2.6%) referencing at least one cancer treatment modality (n = 35 RT, 45 ST, 57 SI). Treatment questions were more common on USMLE Step 2 CK (n = 35/101, 32%) compared to Step 1 (n = 23/101, 23%) and Step 3 (n = 8/101, 8%) (p < 0.001). RT was significantly less likely to be the correct answer (2/35, 6%) compared to ST (4/45, 9%) and SI (18/57, 32%) (p = 0.003). Therapeutic oncology questions are uncommon on the examination material, with an under-representation of radiation-related content, and contextual bias favoring surgical approaches. We advocate for greater RO involvement in the content creation of such examinations to help trainees better understand multidisciplinary cancer care.

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.

Modern Perspectives on Radiation Oncology Residency Expansion, Fellowship Evolution, and Employment Satisfaction.

PURPOSE: In an effort to better characterize the extent and impact of residency expansion and job placement, the authors conducted a multilevel survey of radiation oncologists exploring the current state of the radiation oncology employment market. METHODS: A multilevel survey was conducted using the Qualtrics platform in the spring of 2017. Survey participants were categorized into five groups within radiation oncology: (1) chairpersons, (2) program directors, (3) new practitioners (at least 1 year out of residency), (4) new residency graduates (radiation oncology postgraduate year 5 graduates with new jobs), and (5) medical students. The Wilcoxon-Mann-Whitney test was used to compare Likert scale scores. RESULTS: A total of 752 participants were surveyed, with an overall response rate among all five groups of 31% and 92% of those completing the entire survey. Chairpersons were more likely to consider expanding their residency programs compared with program directors. Fellowship remained low on the job search, with less than 10% of new graduates and new practitioners interested in fellowship positions. Job satisfaction was high with 85% of new graduates, and 78% of new practitioners moderately to very satisfied with their future or current employment. The vast majority of both new practitioners (85%) and new graduates (81%) was moderately to very satisfied with their location of practice. CONCLUSIONS: Resident job satisfaction remains high, whereas interest in radiation oncology fellowships remains low. Conflicting perception regarding the job market and residency expansion could have downstream impacts, such as deterring potential applicants.

How many lymph nodes are enough?-defining the extent of lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

BACKGROUND: Surgical resection with lymph node dissection is the primary therapeutic modality for gastric cancer. National Cancer Database (NCDB) was used to determine the extent of lymph nodes (LNs) dissection for gastric cancer. METHODS: The NCDB was queried from 2004-2013 for patients with margin-negative, invasive resected gastric cancer. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Multiple sensitivity analyses were utilized to decrease bias. RESULTS: A total of 17,851 patients were included. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration (<7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cut-off point was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6%±1.6% for 0-9 removed LNs compared to 48.2%±1.2% for 10+ removed LNs (P<0.001) in pN1 disease and 18.3%±1.7% for 0-9 removed LNs compared to 32.6%±1.2% for 10+ removed LNs (P<0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2%±1.3% for 0-19 removed LNs compared to 28.5%±1.7% for 20+ removed LNs (P<0.001). Moreover, the outcome was inferior among patients who had >10% positive dissected LNs (P<0.05). CONCLUSIONS: The extent of dissected lymph nodes of 20 or greater lymph nodes was associated with superior survival. Extended LN dissection is to be considered especially in patients with clinical lymphadenopathy.

Improved Survival With Increased Time-To-Radiation and Sequential Chemotherapy After Surgery for pN2 Non-Small-cell Lung Cancer.

BACKGROUND: Currently, the ideal timing for postoperative radiotherapy (PORT) and chemotherapy is unknown. The present study evaluated their relative timing on overall survival (OS) using the National Cancer Database (NCDB). MATERIALS AND METHODS: The NCDB was queried for patients from 2004 to 2012 with resected non-small-cell lung cancer (NSCLC), pathologically involved N2 (pN2) nodes, and negative margins. All patients underwent adjuvant chemotherapy and external beam radiotherapy. The time to radiation (TTR) was determined from the date of surgery to the start of PORT, with the exclusion of those receiving PORT < 4 weeks or > 24 weeks postoperatively. Early and late TTR was dichotomized at 8 weeks after receiver operating characteristic analysis. Multivariate Cox regression analysis was conducted to predict the variables significantly associated with survival. RESULTS: A total of 1629 patients were eligible for analysis. Of the 1629 patients, 703 had received PORT < 8 weeks and 926 had received PORT ≥ 8 weeks postoperatively. The receipt of PORT after 8 weeks was associated with better OS (P = .0044). No significant differences were found in survival in the concurrent group comparing early and later TTR (P = .9119). However, a significant OS benefit was found for sequential chemotherapy with an increased TTR (P = .0045). Older age, male sex, shorter distance traveled, increased nodal positivity, larger tumor size, higher Charlson/Deyo comorbidity score, and early TTR were associated with inferior survival on multivariate analysis. CONCLUSION: A TTR of ≥ 8 weeks with sequential chemotherapy in the setting of PORT was associated with improved survival in patients with NSCLC with pN2 nodes.

Comparison of Self-Reported Data on Student Doctor Network to Objective Data of the National Resident Matching Program.

PURPOSE: To compare matching outcomes between self-reporting on Student Doctor Network (SDN) and objective data from the National Resident Matching Program (NRMP). MATERIALS AND METHODS: Data were collected from SDN starting in the 2010 to 2011 academic year and extending to the 2015 to 2016 academic year. A total of 193 radiation oncology applicants had reported data during the period. A total of four applicants (2.1%) did not match and were excluded from the analysis. Applicants were compared with the NRMP charting outcomes of 2011, 2014, and 2016. RESULTS: US allopathic seniors comprised a majority of those reporting on SDN (95.2%). The majority of applicants (58.2%) self-reported in the later years between 2014 and 2016. Those reporting on SDN were more likely to be members of Alpha Omega Alpha (39.7% on SDN versus 27.5% in 2016 NRMP, 23.6% in 2014 NRMP, and 31.2% in 2011 NRMP) and had higher mean United States Medical Licensing Examination (USMLE) step 1 and step 2 scores. Of the applicants, 81% matched within their top three ranked residencies on their match list. Common themes associated with reasons for their successful match included research experience, letters of recommendation, and away rotations. Common themes associated with advice given to future applicants were the importance of research, personality, and away rotations. CONCLUSION: Self-reporting on SDN does have a bias toward more successful radiation oncology applicants compared with the objective NRMP data. However, if self-reporting increases, SDN may serve as a reasonably accurate source of information for future applicants.

Matched-Pair Analysis of High Dose Versus Standard Dose Definitive Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: Recent data have called into question the use of dose-escalated radiotherapy for locally advanced non-small-cell lung cancer and the effect of cardiac radiotherapy doses. We compared the outcomes after chemoradiation using standard-dose (SD; ≤ 64 Gy) or high-dose (HD; > 64 Gy) radiotherapy. PATIENTS AND METHODS: A matched-pair analysis was performed of 178 patients with stage IIB-IIIB non-small-cell lung cancer for SD versus HD groups using age ± 5 years, gender, stage, tumor size ± 2 cm, yielding 86 patients. The clinical endpoints were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox regression method. RESULTS: The median follow-up was 16.8 months for the entire cohort (HD, 21.6 months; SD, 12.1 months; P = .06). No significant differences were found in disease stage, histologic type, age, performance status, gender, or tumor size between the 2 groups. The median overall survival was 23.1 months for the HD group (95% confidence interval, 20.6-25.5) versus 13.6 months for the SD group (95% confidence interval, 9.6-17.5; P = .03). The 2-year freedom from locoregional recurrence was 48.7% for the SD and 65.3% for the HD groups (P = .07). The 2-year freedom from distant metastasis was 46.7% for the SD and 70.3% for the HD groups (P = .05). A higher cardiac V30 dose (P = .03) was the strongest predictor of survival besides clinical stage (P = .02). CONCLUSION: Dose-escalated radiotherapy resulted in improved survival and recurrence rates. A higher cardiac dose was a significant predictor of decreased survival.

Stereotactic body radiotherapy for re-irradiation of lung cancer recurrence with lower biological effective doses.

OBJECTIVE: Few studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer. METHODS: Two hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival. RESULTS: Twenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported. CONCLUSION: Patients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.

Differential effects of distinct central nervous system regions on cell migration and axonal extension of neural precursor transplants.

Transplantation of neural precursor cells (NPCs) is a promising therapeutic strategy in CNS injury. However, the adult CNS lacks instructive signals present during development and, depending on the region and type of transplant, may be inhibitory for neuron generation and axonal growth. We examined the effects of the white matter in different regions of the adult CNS on the properties of NPC transplants with respect to cell survival, differentiation, migration, and axonal growth. NPCs were prepared from day 13.5 embryonic spinal cord of transgenic rats that express the human placental alkaline phosphatase (AP) reporter. These NPCs were injected unilaterally into the cervical spinal cord white matter and into the corpus callosum of adult rats and were analyzed immunohistochemically 2 weeks later. NPCs survived in both regions and differentiated into astrocytes, oligodendrocytes, and neurons, with no apparent differences in survival or phenotypic composition. However, in the spinal cord white matter, graft-derived cells, identified as precursors and glial cells, migrated from the injection site rostrally and caudally, whereas, in the corpus callosum, graft-derived cells did not migrate and remained at the injection site. Importantly, graft-derived neurons extended axons from the grafting site along the corpus callosum past the midline, entering into the contralateral side of the corpus callosum. These results demonstrate dramatic differences between white matter regions in the spinal cord and brain with respect to cell migration and axonal growth and underscore the importance of considering the effects of the local CNS environment in the design of effective transplantation strategies.

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.

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.