bluuebunny/crossref_metadata_2025_split huggingface dataset:
MUTYH-related polyposis syndrome associated with a variant of uncertain significance mutation: A new pathogenic mutation?
Authors: Picanço-Albuquerque Clarissa Gondim , Sant'Ana Rosane Oliveira , Luciano Maria Claudia dos Santos , Bezerra Maria Júlia Barbosa , Bitencourt Flávio da Silveira , Barbosa Oliveira Francisca Fernanda , Souza Thuany Pinto Rocha de , Silva Paulo Goberlânio de Barros , Lima Marcos Venício Alves , Silva-Fernandes Isabelle Joyce de Lima 
Published: June 2022

e22528 Background: The familiar history is indispensable to clinical investigation during genetic counseling and the new molecular techniques allowed the identification of hereditary cancer predisposition syndromes (CPS). However, the classification systems of these syndromes are difficulty and very complex. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases to reduce the subjectivity bias of mutation variants classified as risk. Methods: To show the difficulty of classification of these variants we describe a case report of a family from countryside of Brazil in which there is a high rate of inbreeding. This family has three brothers with polyposis and colorectal cancer between 51 and 60 years-old. Results: The index-case had multiple polyps, developed colorectal cancer at 51 years-old and had a familiar history of two brother dead by colorectal cancer after polyposis and nine brother without familiar history of cancer, a father dead at 38 years-old by non-specific lung-disease and a mother alive at 83 years-old. There was no description of other cases of cancer among uncles and grandparents. The index-case performe a NSG genetic painel to CPS and showed a homozygosis variant in MUTYH gene: NM_001048174.1: c.253T > C:p.(Trp85Arg), that was classified as variant of uncertain significance (VUS). MUTYH is a base excision repair enzyme, it plays a crucial role in the correction of DNA errors and may be considered a cell protective factor and is associated with MUTYH-related polyposis (MAP). MAP is an autosomal recessive CPS and presents a phenotype that overlaps attenuated polyposis and familial adenomatous polyposis, increasing the risk of colorectal cancer in 43-63% up to 60 years or 80% if there is no surveillance/tracking. In view of the family history that suggests autosomal recessive inheritance, with a homozygous variant absent in the database of population controls (gnomAD) and in which in silico predictors indicate the effect of this variant as deleterious, the management of this family must be carried out considering it as a potential high-risk pathogenic variant. Conclusions: While the classification criteria for the variants are being refined, we reinforce the importance of a careful family history in the approach to CPS in order to offer an appropriate clinal conduct in the prevention of hereditary cancer.
Reduction in local tumor recurrence in a murine R2 resection model comparing locally administered docetaxel-releasing product, OncoPLEX, versus systemic docetaxel.
Authors: Emanuel Noam , Nedvetzki Shlomo , Rosenfeld Yosef , Kozloski Goldi A. , Reichart Malka , Senagore Anthony J. 
Published: June 2022

e22530 Background: Local recurrence (LR) negatively impacts long-term survival and patients’ quality of life in many solid tumor malignancies, despite advances in surgical techniques and neoadjuvant and adjuvant treatments. Systemic treatment-related morbidity and mortality remains an unmet need, especially if only an R2 resection is achievable. OncoPLEX is a biodegradable, extended-release formulation of docetaxel that is applied in the form of a paste to the resection bed at surgery. We evaluated OncoPLEX efficacy in preventing local recurrence in an R2 tumor resection model generated with cell lines that exhibit high or low docetaxel sensitivity. Methods: Cell lines sensitivity to free docetaxel and OncoPLEX-released docetaxel were determined in a cytotoxic assay. CT26 (murine colorectal carcinoma--resistant) and U-87 (human primary glioblastoma—sensitive) were tested. A murine subcutaneous (SC) tumor resection model using a predetermined tumor size (400-600 mm3) and a standardized R2 resection (̃90%) was developed. OncoPLEX was applied once on the tumor bed post-resection, docetaxel was IV injected every 4 days (6 times total), and animals were followed for tumor regrowth. The overall docetaxel dose in OncoPLEX (0.78 mg docetaxel) is lower than the maximal tolerated dose and non-lethal reported dose (TAXOTERE [10 mg/kg IV]; prescribing information). Results: The IC50 concentrations of free docetaxel in CT26 and U-87 cell lines indicated resistance and sensitivity to docetaxel respectively (112.6 nM vs 4.2 nM). The cytotoxic potency of OncoPLEX-released docetaxel exhibited a similar relationship with greater potency (IC50 values in CT26 56.7 vs. 1.2 nM in U-87). At the completion of the CT26 SC study (37 days), there were more tumor-free animals in the OncoPLEX group (6/8, 75%) compared with the control IV docetaxel treated (3/8, 38%) or the untreated control (0/8, 0%). A similar trend was observed in the U-87 study; OncoPLEX (4/10, 40%), Control intraperitoneal-injected taxel (2/10, 20%), and untreated control (0/10, 0%). In both studies, the average tumor volume was significantly smaller with either OncoPLEX or systemic treatment compared with untreated controls (CT26: 375 mm3, 485 mm3 and 1500 mm3 (p<0.05); U-87, 403 mm3, 780 mm3 and 2059 mm3; p<0.001). There was no effect on behavior or weight in the OncoPLEX treated animals. Conclusions: Locally administered OncoPLEX in this R2 resection model reduced local tumor recurrence and systemic adverse outcomes. OncoPLEX offers a potentially enhanced local adjuvant chemotherapy option with reduced side effects for solid tumors, independent of the tumor sensitivity or resistance to docetaxel.
Treatment advances in metastatic triple-negative breast cancer (TNBC): Addressing the knowledge gap.
Authors: Heller Elizabeth Jean , Smith Keira P , Williams Sarah L 
Published: June 2022

e23006 Background: The dearth of effective treatment options for patients with metastatic TNBC has enabled the rapid development of more effective treatments for this condition, but research indicates that clinicians face challenges in maintaining a working knowledge of evolving data. This study was conducted to determine if an online, case-based continuing medical education (CME)/nursing continuing professional development (NCPD)–approved activity could identify and address gaps in clinicians’ knowledge regarding the personalized care of patients with metastatic TNBC. Methods: The activity, Metastatic Triple-Negative Breast Cancer: Applying Treatment Advances to Personalized Care, chaired by Sara A. Hurvitz, MD, FACP, was made accessible starting on July 23, 2021. Learners participated in a 1-hour activity that highlighted emerging therapeutic targets in TNBC, with an emphasis on current challenges and new opportunities in the management of metastatic disease. Learners completed a repeated-pairs pre- and post-activity assessment consisting of case-based questions that gauged their ability to apply emerging data to clinical decision making. Knowledge gaps and learning gains were calculated based on percentages of learners obtaining correct responses on the pre- and post-activity assessments. Significance was assessed using a chi-squared test. Results: As of February 2, 2022, 632 clinicians had completed the activity for credit. Baseline assessment data revealed gaps in knowledge regarding emerging actionable targets and management of treatment-related adverse events (Table). The activity resulted in significant gains in knowledge and competence related to these topics, with P < 0.0001 for all learning gains. Conclusions: These data indicate that a substantial knowledge gap exists regarding the latest developments in the treatment of metastatic TNBC. They also demonstrate that online, case-based CME/NCPD-approved activities can result in statistically significant improvements in clinicians’ knowledge of therapeutic advances and management of treatment-related adverse events for patients with metastatic TNBC. Acknowledgements: This activity was supported by an independent educational grant from Merck.[Table: see text]
Engaging continuing medical education in evaluating knowledge gaps and preferences in advanced BRAF+ melanoma.
Authors: Robinson Katie , Scavone Jillian L , Scully Emily , Lewis Emily , Esgro Robert A. , Kirkwood John M. 
Published: June 2022

e23007 Background: Given the rapid evolution of treatments for advanced melanoma, oncology providers are challenged to stay current on evidence-based recommendations for optimal patient care. Integrating practice-based polling into continuing medical education (CME) activities is a proven way to increase engagement, address knowledge gaps, and assess attitudes on specific topics. Methods: We provided a CME activity designed to educate oncology and dermatology providers on the latest advances regarding the management of advanced BRAFmut+ melanoma. Interspersed engagement opportunities further assessed practice preferences and elucidated persisting educational needs. The CE activity was available for credit from December 31, 2020 to December 30, 2021. Results: 305 medical oncology or dermatology providers who each see an average of 25 patients with melanoma per month participated. These providers scored an average 38% on pretest topics related to the use of triple therapy and patient and/or tumor characteristics that guide clinical decision-making. Post-learning, providers scored 84%, highlighting the impact of the education on knowledge gaps. Notably, while 51% of these providers indicated that they were guessing on the pre-test, the percentage of those who were confident and correct on the post-test rose from 3% to 28%, demonstrating a rise in confidence among participants. While 50% of participants noted a positive perception of triple therapy (BRAF inhibitor + MEK inhibitor + anti-PD1) in the front-line setting, case-based polling questions showed that providers lack consensus regarding the use of combinations of treatments in other clinical scenarios. While 45% would recommend triple therapy in the first-line setting, dual checkpoint inhibitor (CPI)-based treatment is preferred after progression on a first-line CPI or dual-targeted therapy. Conclusions: CME is a useful method to address knowledge gaps regarding evolving treatment options. As data regarding the use of triple therapy for patients with BRAF+ melanoma emerges, oncology and dermatology providers will require further education on how to apply these options in practice.[Table: see text]
Educational impact of inpatient hematology-oncology service structure.
Authors: Cooperrider Jennifer H. , Patel Anand Ashwin , Brondfield Sam 
Published: June 2022

e23013 Background: Literature suggests that inpatient hematology-oncology (heme-onc) clinical experiences may have a deleterious impact on trainee interest in heme-onc. However, the impact of inpatient heme-onc service structure on trainee education is not known. To delineate the factors affecting trainee education, we aimed to characterize the structure of inpatient heme-onc services at comprehensive cancer centers (CCCs) and the associated impact on trainees. Methods: We designed a survey with Likert-type and open-ended questions using established procedures. We surveyed heme-onc fellowship program directors (PDs) at all 50 U.S. CCCs with fellowship programs. We performed point biserial and Pearson correlations on Likert-type responses and content analysis on open-ended responses. Results: Eighteen out of 50 (36%) PDs responded and described 117 services. Services were either primary (35%), consult (44%), or both (21%). Fellows were present on 93% and residents on 54% of services. PDs rated the educational value of most inpatient services as either “very high” or “somewhat high” for both fellows (73% very high, 13% somewhat high) and residents (49% very high, 33% somewhat high). PDs perceived that fellows derived greater educational value from consult-only vs primary/mixed services [R(105) = 0.25, p= 0.01] and provided greater reciprocal benefit to consult-only vs primary/mixed services [R(100) = 0.28, p= 0.004]. Hospital type (county, university, or veteran’s) and the presence or absence of a formal curriculum on the service did not correlate with perceived educational benefit. Multiple open-ended comments suggested that heme-onc attendings and fellows should be consultative rather than primary service providers, programs should separate teaching and non-teaching services, and service/education balance optimization should be prioritized. Inadequate service staffing and lack of institutional support were identified as barriers to inpatient education. Conclusions: PDs felt that inpatient heme-onc services had high educational value for trainees, particularly for fellows. Both fellows and services may derive mutual benefit from fellow participation on inpatient consult services structured separately from non-teaching primary services. Hospital type and the presence or absence of a structured curriculum may not be critical for education on inpatient heme-onc services. Appropriate service/education balance, staffing, and institutional support are crucial to optimize inpatient education. Future studies should explore the trainee perspective around the educational value of inpatient clinical experiences. PDs and institutions can use the study findings to craft beneficial inpatient educational experiences for heme-onc trainees.
Improving resident education on the inpatient solid tumor oncology rotation through development of an asynchronous video curriculum.
Authors: Walsh Laura , Agarwal Parul , Brondfield Sam , Chida Natasha , Donehower Ross C. , Marrone Kristen 
Published: June 2022

e23014 Background: As the oncology patient population grows, continued recruitment of talented individuals is essential. Meaningful and highly educational clinical exposures play a crucial role in a resident’s decision to pursue fellowship in oncology. Currently, the majority of oncology exposure occurs in the inpatient setting, where trainees are confronted with many competing clinical demands, leaving minimal time for teaching. Prior work has demonstrated that dedicated time for teaching supplemented with high-yield educational material improves trainee satisfaction and interest in a particular field. We hypothesize that implementing an asynchronous inpatient video oncology curriculum will improve resident clinical competency and satisfaction. Methods: This is an ongoing, single institution educational intervention using the Kern method for curriculum development in the Johns Hopkins Osler Internal Medicine Residency (IRB00307077). A targeted needs assessment has been developed to identify gaps in medical knowledge, assess preparedness in managing common solid tumor inpatient diagnoses, and explore satisfaction with prior educational experiences on this service. Based on these results, ten educational videos will be created by content experts and aligned with the learning objectives of the Osler residency program and ABIM blueprint. Trainees will have dedicated time to watch the videos during their solid tumor rotation. We plan to evaluate effectiveness of our curriculum by measuring completion rates and pre- and post-video multiple choice responses. We will also assess knowledge retention and resident satisfaction at three and six months post-rotation with online questionnaires. Results: Annual Osler program ACGME survey data review revealed a high level of resident dissatisfaction with the oncology clinical experience compared with other rotations. While 83.3% of residents rated their general internal medicine experience as “excellent,” only 52.4% rated their oncology experience as “excellent.” Needs assessment data collection has been delayed by the COVID-19 pandemic but is ongoing. Following topic selection, videos will be created in April 2022 with plans for video curriculum implementation in July 2022. Conclusions: In order to attract and retain trainees in the field of oncology, it is imperative that educational curricula adapts to meet learners’ needs. Efficient, evidence-based instructional strategies designed to promote clinical competency for internal medicine residents on an inpatient solid tumor service may foster engagement and rotation satisfaction. We are currently evaluating how an asynchronous video inpatient oncology curriculum may significantly improve the inpatient internal medicine trainee experience. If successful, this curriculum can be adapted for other trainees and practitioners new to the field of oncology.
Heterogeneity in treatment regimens for AYA bone sarcomas: A comparison of outcomes at a single sarcoma center.
Authors: Espejo-Freire Andrea P. , Campoverde Leticia , Kropotova Yana , Statz-Geary Kurt , Costa Philippos Apolinario , Barreto Coelho Priscila , Bialick Steven , D'Amato Gina Z. , Jonczak Emily , Trent Jonathan C. , Dhir Aditi 
Published: June 2022

e23508 Background: Bone sarcomas account for about 5% of cancers in adolescents and young adults (AYA). Outcomes in this population are consistently inferior than children. It is poorly understood whether this is related to the tumor biology or the therapeutic approach. In addition, regimens used in AYAs are heterogeneous due to poor tolerance of pediatric regimens and lack of clinical trials specific to this population. We sought to study the therapeutic regimes and outcomes of AYA bone sarcoma patients (pts) to understand the optimal therapeutic approach better. Methods: From our institutional database, we extracted data of pts with the diagnosis of “osteosarcoma” (OS) and “Ewing sarcoma” (ES) in the AYA (15-39 yo) population from 2011-21. We included only pts with efficacy documented to different regimens. Descriptive statistics were used for patient demographics, presentation, regimens, and outcomes (Table). Objective response rate (ORR) was defined as the number of patients achieving a partial or complete response. Relapse rate (RR) was calculated for the pts that progressed after undergoing definitive curative intent treatment. Survival comparison between groups was made using the Kaplan Meier method and Log Rank Test. We used Fisher's exact test to compare differences in ORR between treatment groups. Results: We identified 30 ES and 44 OS pts. For both ES and OS, Kaplan Meier survival analysis showed no difference in presentation adjusted overall survival between treatment groups; ( x2 .351, p .55) for ES and ( x2 1.94 p .378) for OS. Importantly, in OS, ORR difference between Adria/IVCis and Adria/IACis was statistically significant ( p .0188). Conclusions: Our study shows the heterogeneity in first-line treatment strategies for AYA pts with bone sarcomas. For ES, response rates for VAC/IE and VAI were similar. In the OS cohort, we found ORR for Adria/IACis was 81% which was statistically different to pts receiving Adria/IVCis (ORR 30%). However, we saw relapses in 43% of pts treated with Adria/IACis. This indicates that the intra-arterial approach could be helpful for limb preservation but suggests the need for intense adjuvant chemotherapy to prevent relapses. There were no statistically significant differences in the survival outcomes of AYA bone sarcoma pts treated with pediatric versus adult regimens.[Table: see text]
Primary site and survival in osteosarcoma: A National Cancer Database (NCDB) analysis.
Authors: Eaton Vincent , Tupper Connor , Silberstein Peter T. 
Published: June 2022

e23512 Background: Osteosarcoma (OSC) is the most common primary bone tumor and typically affects the appendicular skeleton (specifically, the long bones of the upper and lower extremities). However, this cancer can affect other regions of the body as well, such as the skull, mandible, ribs, vertebral column, and other areas involving bone and/or any articular cartilage and, to the author’s knowledge, all possible primary sites have not been investigated. The aim of this study is to see whether or not the primary site of the tumor in OSC patients may have an effect on survival outcomes. Methods: Using the NCDB, patients diagnosed with OSC between 2004-2018 were identified using ICD-O-3 histology codes 9180 through 9193. The cohort was analyzed to investigate survival outcomes in different primary sites. Univariate analysis was then performed assessing patient length of survival for each primary site subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 9826 patients with known primary site that had survival data were included. The site with the best survival was the lower limb which had significantly better survival than all other primary sites. Tumors of the upper limb had highest median survival (153 months) of those with median survival reported (which was all except for lower limb). Patients with primary tumor of ribs, sternum, clavicle had a significantly better survival than both vertebral column and pelvis/sacrum/coccyx (all p < .01). Upper limb patients survived significantly longer than all groups other than the skull, face, and mandible (p < .05). The labeled primary site with the highest mean survival was the lower limb at 123.1 months and the lowest survival was the pelvis, sacrum, and coccyx, with a median survival of 54.6 months. Conclusions: This study found numerous survival differences between patients diagnosed with OSC of different primary sites. Labeled primary sites of the lower limb and upper limb were associated with best survival while the pelvis, sacrum, and coccyx were associated with worst survival. Future studies should be done to investigate variables that may impact the survival of different primary sites, including staging, treatments, time from diagnosis to treatment, socioeconomic factors, and insurance status.[Table: see text]