tbuckley/cabot-search huggingface dataset:
Implementation of competency-based medical education in a Canadian medical oncology training program: Lessons from our first year.
Authors: Anna T. Tomiak, Geordie Linford, Micheline McDonald, Jane Willms, Nazik Hammad
Journal: Journal of Clinical Oncology (2019)

10514 Background: As part of a university wide initiative, CBME was implemented in our MO training program in July 2017. Stages, Entrustable Professional Activity (EPA) assessments and Required Training Experiences established by the Royal College of Physicians and Surgeons of Canada were adopted. MedTech Central, the electronic portfolio developed at our university was used for assessment collection. We share here observations and experiences from our first year of implementation. Methods: Assessment metrics were obtained through MEdTech. Ethics was granted by Queen’s University as part of an ongoing research study on feedback. Lessons learned were compiled from discussions between the Program Director, Residents, Program Administrator, CBME Education Consultant and CBME lead. Results: A total of 195 assessments were completed July 2017-November 2018. 81% were EPA assessments and the remainder multisource feedback, rubrics and field notes. The median number of assessments per faculty was 17 (0-42). 52% of assessments included written “Comments” or “Next steps”. A median of 6 assessments per faculty member included specific or actionable feedback. Lessons learned centered on: 1) Faculty and Resident development and engagement (critical before, during and after implementation); 2) Value of sharing work of CBME (CBME Education Consultant, CBME Lead, Academic Advisors, Competence Committee); 3) Importance of effective communication strategy with stakeholders 4) Importance of collaboration with other training programs at institutional and national levels; 5) Culture change (a slow process); 6) Resident concerns regarding lack of global assessment; 7) Assessment plan challenges (How many observations required?); 8) Burden of CBME (Resident driven assessments or a better balance?) ; 9) Limitations of e-portfolio (How to live track and by whom?); 10) Costs 11) Value of continuous quality assurance and improvement. Conclusions: Our first year of implementation was successful in introducing CBME concepts, work based assessments and e-portfolios. Ongoing work is needed, including increasing the number of assessments and quality of feedback.
Safety, tolerability, and PK of topical calcitriol formulation for treatment of chemotherapy-induced alopecia (CIA) in patients receiving taxane-based regimen: Final results.
Authors: Mario E. Lacouture, Rangaprasad Sarangarajan, Joaquin Juan Jimenez, Michael A. Kiebish, Niven R. Narain, Brian Berman, Shari Beth Goldfarb
Journal: Journal of Clinical Oncology (2019)

11608 Background: Chemotherapy-induced alopecia (CIA) following taxane-based treatment regimen is due to direct toxicity of these agents on rapidly dividing cells within hair follicles. Currently no oral or topical agents have been approved for prevention of CIA. In murine studies, topical calcitriol reduced CIA, likely due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy. Methods: A 3+3 dose-escalation strategy was used in this Phase 1 study with 3-6 patients at six dose levels (5/10/20/40/60/80 μg/mL) were assessed for safety and tolerability of BPM31543. Patients with a diagnosis of breast cancer, gynecologic cancer or sarcomas receiving a taxane-based chemotherapy regimen applied 1mL of the formulation to the scalp BID, ≥ 5 days prior to starting chemotherapy for at least 3 months or until treatment completed. Safety and efficacy assessments included AE monitoring, PK analysis, blinded photographic assessments and patient self-assessment. Results: 22/23 (95.7%) female patients receiving treatment and included in the safety population experienced at least one TEAE. The most frequently experienced TEAEs were alopecia (14 pts; 60.9%), fatigue (11 pts; 47.8%), nausea (9 pts; 39.1%), peripheral sensory neuropathy (7 pts; 30.4%), and maculopapular rash and vitamin D increased each in six patients (26.1%). Of these, elevated vitamin D and rash were possibly or probably related to treatment. Fatigue, nausea, and neuropathy were likely due to chemotherapy. In 18 patients included in the post-dose versus pre-treatment comparison, there was no dose-dependency on systemic levels of calcitriol. Hair loss &lt; 50% from baseline was observed in 8 patients at week 7 that was maintained at week 15 in 2 patients. Conclusions: Study results showed BPM31543 applied topically twice daily to the scalp in patients receiving taxane-based chemotherapy was safe and well-tolerated. No DLT was observed up to 80 µg/mL dose and no MTD level was reached. There was a signal of potential efficacy detected at each dose level. A seamless Phase 2/3 trial strategy for clinical development is planned. Clinical trial information: NCT01588522.
A novel <i>HMGA2-YAP1</i> fusion gene in a patient with aggressive angiomyxoma.
Authors: Brandon Dasilva, Mee-Young Lee, Daniel C. Ramirez, Robert G. Maki
Journal: Journal of Clinical Oncology (2019)

e22514 Background: Aggressive angiomyxoma (AA) is a rare neoplasm typically found in the perineum or pelvis, often with a gelatinous consistency and a highly vascular nature that leads to surgical complications and a high recurrence rate following what otherwise are attempts at curative surgery. For patients with recurrent disease in whom surgery is not indicated or potentially mutilating, estrogen antagonism has been successfully employed. HMGA2 on chromosome 12 has been known to be translocated in this tumor for over a decade, but no partners have been identified for HMGA2 in this tumor type. Methods: A 44-year-old woman with a perineal mass underwent attempted resection, but this was halted due to extensive blood loss after removal of a portion of what proved to be an AA. She was referred for systemic treatment to the sarcoma clinic. A Foundation Medicine Heme test was conducted on the patient's tumor. Results: The patient was treated with leuprolide and anastrozole with a RECIST 1.1 partial response and loss of vascularity consistent with a radiological response. She underwent preoperative radiation therapy and a follow up operation with negative margins. The resection specimen showed evidence of a very good result from systemic therapy and radiation. Molecular testing demonstrated a HMGA2-YAP1 fusion, implying a t(11;12)(q22.1;q14.3) translocation. Conclusions: This is the first demonstration of a partner for the HMGA2 gene in AA. A variety of other translocations have been found in AA, some of which involve chromosome 12. Thus, as with benign lesions such as lipomas, myolipomas, osteochondrolipomas, leiomyomas, pleomorphic adenomas, as well as a smaller number of overt malignancies, there appears to be promiscuity in HMGA2 (or other translocation) fusion products that lead to development of AA. Not all patients with AA respond to estrogen antagonism, or will show evidence of benefit before getting worse, as shown in case series and reports of AA patients. Assessing HMGA2 partners and their outcomes may better stratify future patients with AA with respect to possible benefit of estrogen antagonism.
P14.39 How far should it be removal beyond the Gd-enhanced edge in Glioblastoma cases? -Preoperative removal range identification using Methionine-PET and Thallium-SPECT fusion image
Authors: N Nakayama, H Yano, H Takei, K Miwa, J Shinoda, T Iwama
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Mostly, the removal rate of glioblastoma has been discussed in the Gd enhanced area, but tumor cells are surely infiltrated beyond the Gd enhanced edge. Although Methionine-PET (MET) and Thallium-SPECT (Tl) are useful for preoperative tumor invasion range identification, they are off-label use in most countries, and their respective accumulation ranges do not match completely. In this study, Gd-MRI, MET, and Tl were performed, and the accumulation range was compared from the fusion images, and the prediction method of the tumor cell infiltration range was examined. MATERIAL AND METHODS The mean interval period between MET and Tl administration was 16.3 days in 21 cases of glioblastoma (12 male and 9 female, average age 59.1 ± 17.8 years). Fusion images were generated using iPlan Cranial 3.0.The MET-area, Tl-area, Overlap-area where MET and Tl overlap, and Accumulation-area where MET and Tl are maximally accumulated were measured in the same cross section as the Gd-enhanced maximum area (Gd-area, X cm2) in axial view. Each volume was also measured similarly. RESULTS Gd-area was correlated with all of MET-area, Tl-area, Overlap-area, and Accumulation-area (p ≦0.0001).Gd-volume (X’cm3) showed correlation with all of MET-volume, Tl-volume, Overlap-volume, and Accumulation-volume (p ≦0.0001). The linear approximation was calculated as follows. Overlap-area = 1.942X + 1.0208 (R = 0.937), Accumulation-area = 1.3299X + 6.098 (R = 0.889), Overlap-volume = 1.1539X ‘+ 7.0573 (R = 0.927), Accumulation-volume = 1.8668X ‘+30.06 (R = 0.893). CONCLUSION These linear approximations can be used to predict the tumor invasion range from the Gd-enhanced maximum area or Gd-enhanced volume without using off-label use drugs.
Medicare Drug-Price Negotiation — Why Now . . . and How
Authors: Richard G. Frank, Len M. Nichols
Journal: New England Journal of Medicine (2019)

Interview with Dr. Stacie Dusetzina on three proposals for redesigning the Medicare Part D prescription-drug benefit. (09:54)Download A targeted bargaining strategy using tried and tested arbitration techniques could help Medicare balance drug innovation and affordability. Such negotiation could lower excessively high prices, even as parts of the market where competition works well are left alone.
P14.129 Predicting glioblastoma invasion using multiparametric MRI and a bi-level machine learning approach
Authors: C Li, P Liu, Y Wei, Y Li, C Schönlieb, S J Price
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is characterized by its extensive infiltration into the brain parenchyma, which poses challenges to accurate treatment volume targeting. Current treatment planning is based on the contrast-enhancing images. Tumor invasion, however, is well known beyond the contrast enhancement. Although deep learning shows potential in delineating tumor invasion based on multiparametric MRI, it requires large amount of training data. Image inpainting may reconstruct the lost image information based on image structure and requires less training data. The purpose of this study is to investigate whether a bi-level deep learning approach could integrate conventional neural network (CNN) and image inpainting to delineate tumor invasion based on the multiparametric MRI. MATERIAL AND METHODS A total of 115 patients (mean age 59.3 yrs, range 22 - 76 yrs, 87 males) with supratentorial de novo glioblastoma were recruited for maximal safe tumor resection. Post-operative temozolomide chemoradiotherapy was performed following the Stupp protocol. The Response Assessment in Neuro-oncology criteria was used to evaluate patient response. All MRI sequences were pre-operatively acquired using a 3T scanner, including T2-weighted, post-contrast T1-weighted, FLAIR, dynamic susceptibility contrast (DSC) and diffusion tensor imaging (DTI). The isotropic (p) and anisotropic (q) maps were generated from DTI. The relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) were generated from the DSC images after the leakage correction. All images were coregistered to post-contrast T1W images. Contrast-enhancing (CE) and non-enhancing (NE) regions were semi-automatically segmented and validated by an experienced neuro-radiologist. A tissue segmentation was performed using the FAST (FMRIB’s Automated Segmentation Tool) to segment the normal-appearing brain excluding the above both tumor regions and were classified into three tissue types (grey matter, white matter and CSF). A CNN model was applied to build a classification function between the CE region and the three normal-appearing tissue types based on the multi-parametric MRI. A bespoke inpainting scheme was then applied to predict the tumor invasion area in the NE region. Kaplan-Meier and Cox proportional regression were used to evaluate the significance of the predicted volume. RESULTS The volumes of the contrast-enhancing tumor is 53.6 ± 33.8 cm3. The predicted invasive volume in the non-enhancing region is 31.0 ± 17.7 cm3.The multivariate model shows that the predicted volume was significantly associated with OS (HR = 0.97, P= 0.006). The patient subgroup with a higher predicted volume showed significantly better OS (P= 0.009) and PFS (P= 0.021). CONCLUSION The proposed bi-level deep learning approach may effectively integrate multiparametric MRI for predicting tumor invasio.
Mobile Devices and Health
Authors: Ida Sim
Journal: New England Journal of Medicine (2019)

Interview with Dr. Ida Sim on mobile devices and health. (14:22)Download Mobile health involves sensors, mobile apps, social media, and location-tracking technology used in disease diagnosis, prevention, and management. This article provides an overview of key functional and regulatory aspects; the article is accompanied by an explanatory video, an illustrated glossary, and an audio interview with the author.
Novel methods of analyzing long-term trends in incidence and survival applied to gastroesophageal cancers.
Authors: Zhensheng Wang, Michael Goodman, Hemchandra Mahaseth, Bassel F El-Rayes
Journal: Journal of Clinical Oncology (2012)

e14512 Background: The incidence of esophageal squamous cell (ESC) carcinoma has been decreasing, while incidence of esophageal adenocarcinoma (EA) keeps increasing. The specific time periods during which incidence trends changed have not been examined. Secular trends in survival and changes of those trends need to be investigated. Methods: Incidence and survival were analyzed using joinpoint regression models, which are designed to examine long-term longitudinal data for a change in trend. We identified 75,497 patients with esophageal cancer and adenocarcinoma of the gastric cardia (GCA) in the Surveillance, Epidemiology, and End Results database between 1973 and 2008. Incidence and one-year survival rates for ESC, EA, and GCA were compared by race, gender and stage. Results were expressed in terms of identifiable inflexion points (joinpoints) with before-and-after estimates of annual percent changes (APC) with 95% confidence intervals (CI). Results: Incidence of ESC has demonstrated a clear inflexion point in the mid 1980s with accelerated decrease across race and gender categories. While incidence of EA has been increasing, the increase slowed down in mid 90s in all groups except blacks. For GCA, there was a clear increase in incidence up until early 80s followed by a plateau although in men there was a significant post-87 decrease. One-year survival of ESC patients has been improving; for local/regional disease the trend became less pronounced in late 80s whereas for distant disease the improvement appears to continue without identifiable inflexion points. The patterns of one-year survival for EA and GCA were similar. Local/regional diseases demonstrated a significant improvement in survival without changes in trend while survival of distant diseases showed an inflexion point in the mid 90s followed by a marked improvement. Conclusions: Joinpoint regression analysis is a valuable tool in assessing long-term trends of incidence and survival. The survival of ESC, EA, and GCA demonstrated significant improvement over the last 35 years. The inflexion points reflected introduction of combined modality therapy for regional disease and availability of newer chemotherapy agents for distant disease.
P04.02 Postponing the medical treatment is possible in selected cases of diffuse low-grade glioma with foci of WHO grade III-IV after total or subtotal resection
Authors: A Darlix, V Rigau, J Fraisse, C Gozé, M Fabbro, H Duffau
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Diffuse low-grade gliomas (DLGG) are defined by a continuous growth and an unavoidable malignant transformation. Foci of malignant transformation may be found within DLGG samples obtained from surgical resections. As the medical management is classically based on the higher tumor grade, an immediate adjuvant treatment is usually proposed (radiotherapy [RT] with Temozolomide or PCV), whatever the extent of resection. Yet, early RT has no impact on overall survival compared with late RT, and is associated with cognitive toxicity. An alternative approach consists in postponing the medical treatment in selected patients. MATERIAL AND METHODS We conducted a monocentric retrospective analysis of a consecutive series of patients managed with this conservative approach. Inclusion criteria were: DLGG (WHO 2016 grade II) with at least one focus of malignant transformation (grade III-IV); no previous chemotherapy or RT; no less than a subtotal resection of the FLAIR tumor volume; no intention of treating with immediate adjuvant therapy; at least two years of postoperative follow-up. The time interval to the next medical treatment (chemotherapy and/or radiotherapy) was assessed, as well as the functional and survival results. RESULTS Forty-five DLGG patients, of median age 36.5 years, were included in the analysis (median time interval from diagnosis: 7.3 months). The histo-molecular diagnosis was diffuse astrocytoma, IDH mutant in 46.7% of cases, astrocytoma, IDH wild-type in 13.3% and oligodendroglioma, IDH mutant and 1p/19q codeleted in 40.0%. Ten tumors presented with grade IV foci. The quality of resection was subtotal (FLAIR tumor residue ≤15 cm3) in 73.3%, total (no FLAIR tumor residue) in 24.4% and supratotal in 2.2%. After surgery, patients were managed with regular clinical and radiological follow-up. With a median postoperative follow-up of 6.3 years, 75.5% of patients received a subsequent medical treatment, after a median time interval of 3.7 years. The first treatment after surgery consisted of repeated surgery in 11 patients, Temozolomide in 28 patients, RT in one patient. At the time of analysis, 19 patients (42.2%) had been treated with RT, after a median time interval of 9.5 years. Nine patients (20.0%) had died (median overall survival not reached, 5-years and 7-years survival rates: 95.2% and 67.0%). Most surviving patients were still active professionally (69.4%), with a median Karnofsky performance status of 90, and no or rare seizures. CONCLUSION In this series, total or subtotal resection of DLGG with a least one focus of grade III-IV glioma radically changed the natural history of these tumors and allowed delaying the following medical treatment by several years. This strategy is feasible in selected patients and should be considered on a case-by-case basis in patients with foci of malignant transformation following total or subtotal resection.
Urban green space, tree canopy, and prevention of heart disease, hypertension, and diabetes: a longitudinal study
Authors: Thomas Astell-Burt, Xiaoqi Feng
Journal: The Lancet Planetary Health (2019)

BackgroundWhile many studies suggest there are health benefits of urban green space, relatively few have explored potential for prevention of major non-communicable diseases. Those which have tend to rely on cross-sectional data that is vulnerable to reverse causation and also typically focus on total green space, rather than attempt to tease out which type of green space matters most; a key question among urban planners. The purpose of this longitudinal study was to examine whether urban green space in total, and tree canopy specifically, plays a protective role in prevention of heart disease, hypertension, and diabetes.MethodsIncident doctor diagnosed heart disease, hypertension and diabetes were measured in a residentially stable sample of 46 786 city-dwellers in the Sax Institute's 45 and Up Study (baseline 2006–09; follow-up 2012–15). The odds of incident outcomes were measured in association with total green space and tree canopy within 1·6 km road network buffers using multilevel models adjusted for confounding. These analyses were replicated to check for associations with prevalent outcomes.FindingsThe odds of incident heart disease (odds ratio 0·78, 95% CI 0·65–0·93), hypertension (0·83, 0·72–0·96), and diabetes (0·69, 0·54–0·85) were lower among people with ≥30% tree canopy, compared to 0–9% tree canopy. Evidence was also found to suggest lower odds of prevalent heart disease (0·85, 0·75–0·95), hypertension (0·87, 0·78–0·96), and diabetes (0·62, 0·52–0·75) with ≥30% tree canopy compared with 0–9% tree canopy. Total green space ≥30% compared to 0–4% was associated with lower odds of prevalent diabetes only (0·72, 0·52–0·98).InterpretationThis longitudinal study adds further support for urban greening, and restoration and conservation of urban tree canopy in particular, to be considered as a non-health sector-led strategy for non-communicable disease prevention.FundingThe Hort Frontiers Green Cities Fund and the National Health and Medical Research Council.
Effects of furosemide (40 mg) on nasal mucociliary clearence, mucus contact angle and mucus transportability by cough in young healthy subjects
Authors: D. M. Goto, G. M. Torres, E. S. Aquino, Antonio Carlos Seguro, Paulo Hilário Nascimento Saldiva, Geraldo Lorenzi Filho
Journal: American Journal of Respiratory and Critical Care Medicine (2008)