bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of competency-based medical education in a Canadian medical oncology training program: Lessons from our first year.
Authors: Tomiak Anna T. , Linford Geordie , McDonald Micheline , Willms Jane , Hammad Nazik 
Published: March 2020

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.
Choosing oncology as specialization: Medical students' perception after clinical rotation in cancer center.
Authors: Castillo Fernandez Omar Orlando , Lim Maria , Montano Lilian Hayde , Perez-Jimenez Gaspar , Camaño Jhonattan , Mendoza Enrique , Pereira Yamileth 
Published: March 2020

10528 Background: Cancer is a leading cause of death worldwide and the demand for oncologist and palliative care specialists is increasing dramatically. Two years ago, The Universidad de Panama incorporated Oncology in the curriculum in order to face the shortage of professionals involved in cancer care. Little information is available concerning young medical students desire to pursue a career in oncology.The aim of this study is to evalute medical students perception about Oncology as a specialization field. Methods: An electronic survey was sent to medical students from Universidad de Panama after finishing Oncology rotation the last 2 years. Chi square and Mann Whitney U tests were used to compare variables. Results: 145 questionnaries were responded (40%). 60% female and 40% male. Median age was 25 years old. Clinical rotation during Oncology practices were: 37% in Medical Oncology, 24% in Surgical Oncology, 21% in Radiation Oncology and 18% in Palliative Care. 20% (29) of students are highly motivated to pursue a career in Oncology. 8 in Radiation Oncology. 8 in Surgical Oncology, 8 in Medical Oncology and 5 in Palliative Care. Variable associated with a oncology preference were: male gender (p=0.007), lack of human resources (p=0.009), contact with patients and family (p=0.005), good experience with mentor (p=0.002), nature and complexity of disease (p<0.001). Potential emotional burden was negatively asssociated (p=0.004) with oncology preference. 66% of students acknowledged that clinical rotation changed positively their perception about cancer patient care and a third of students haved not rule out the possibility to choose Oncology in the near future. Conclusions: Early exposition to medical student to cancer care might help to reduce the global shortage of oncologist and palliative specialists.
STRASS (EORTC 62092): A phase III randomized study of preoperative radiotherapy plus surgery versus surgery alone for patients with retroperitoneal sarcoma.
Authors: Bonvalot Sylvie , Gronchi Alessandro , Le Pechoux Cecile , Swallow Carol Jane , Strauss Dirk C. , Meeus Pierre , van Coevorden Frits , Stoldt Stephan , Stoeckle Eberhard , Rutkowski Piotr , Sangalli Claudia , Honoré Charles , Rastrelli Marco , Raut Chandrajit , Chung Peter , Fiore Marco , Litiere Saskia , Marreaud Sandrine , Gelderblom Hans , Haas Rick L.M. 
Published: March 2020

11001 Background: The predominant pattern of failure of retroperitoneal sarcoma (RPS), frequently associated with subsequent death, is locoregional recurrence. Unlike in limbs, the efficacy of radiotherapy (RT) combined with surgery is not established. Methods: STRASS is a randomized, multicentre, international trial. Eligible patients had histologically-proven localized primary RPS, operable and suitable for radiotherapy. Patients were randomized 1:1 to preoperative RT (3D-CRT or IMRT) 50.4 Gy followed by surgery (RT/S group) or surgery alone (S group), stratified by hospital and performance status (0-1 vs 2). Primary endpoint is abdominal recurrence-free survival (ARFS; local relapse after complete resection, peritoneal sarcomatosis, R2 surgery, progressive disease during RT or unresectable disease). IDMC recommended a sensitivity analysis in which local progression on RT is not regarded as an event for patients who subsequently achieve complete surgical resection. Secondary endpoints were recurrence-free survival, overall survival, acute toxicity profile of RT, perioperative and late complications, and QoL. The study was designed to provide 90% power to show an increase of 20% in the 5-year ARFS rate, from 50% to 70% (corresponding to a HR of 0.52) at 2-sided 5% significance level. Results: 266 patients from Europe, USA and Canada were randomized between January 2012 and April 2017; 198 patients (74.5 %) had liposarcoma (LPS). Eighteen patients were designated ineligible. Overall rate of re-operation for any complication was 10.1%: 13 (10.9%) and 12 (9.4%) patients in RT/S versus S groups. 19 pts (14%) progressed during RT, 4 of whom did not undergo surgery. 3-year ARFS was 60.4% (95% Confidence interval (CI) 51.4-68.2%) and 58.7% (49.5- 66.7%) (HR = 1.01, 95%CI 0.71-1.44, p=0.954) in RT/S versus S groups. In the sensitivity analysis, 3-year ARFS was 66.0% (57.1-73.5%) and 58.7% (49.5-66.7%) in RT/S versus S groups (HR = 0.84, 95% CI 0.58-1.21, p=0.340). In the LPS subgroup, 3-year ARFS (sensitivity analysis) was 71.6% (61.3-79.6%) and 60.4% (49.8-69.5%) in RT/S versus S groups (HR = 0.64, 95%CI 0.40-1.01, p =0.049). Conclusion: STRASS failed to demonstrate a benefit of pre-operative RT for RPS. In the exploratory analysis, preoperative RT may benefit the LPS subgroup. Funding Source: EORTC and EUROSARC FP7 278472. Clinical trial information: EORTC 62092.
Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma.
Authors: McCabe Martin G. , Moroz Veronica , Khan Maria , Dirksen Uta , Evans Abigail , Fenwick Nicola , Gaspar Nathalie , Kanerva Jukka , Kühne Thomas , Longhi Alessandra , Luksch Roberto , Mata Cristina , Phillips Marianne , Sundby Hall Kirsten , Valverde Morales Claudia Maria , Westwood Andrew J. , Winstanley Mark , Whelan Jeremy , Wheatley Keith ,   Euro Ewing Consortium
Published: March 2020

11007 Background: 5-year survival of RR-ES is about 15%. Several chemotherapy regimens are used, but without robust evidence. rEECur, the first randomised controlled trial in this setting, is defining a standard of care, balancing efficacy and toxicity. Methods: Patients aged 4 to 50 with RR-ES and fit to receive chemotherapy were randomised 2, 3 or 4 ways between topotecan & cyclophosphamide (TC), irinotecan & temolozomide (IT), gemcitabine & docetaxel (GD) or high-dose ifosfamide (IFOS). Primary outcome measure was objective response (OR) after 4 cycles by RECIST 1.1. Secondary outcomes included PFS, OS and toxicity. A probability-based Bayesian approach was used. The first interim assessment to determine which arm should be closed occurred when 50 evaluable patients had been recruited to 3 arms and evaluated for the primary outcome measure. Results: 242 patients (89% RECIST-evaluable) recruited between 18/12/14 and 21/06/18 were randomised to TC (n=75), IT (71), GD (66) and IFOS (30). Median age was 21 years (range 4 to 49). Patients had: refractory ES (20%), 1st recurrence (63%), >1st recurrence (17%); initial primary disease arose in bone in 60%; disease progression sites were primary site (17%), pleuropulmonary (29%) or other metastatic (54%). Median follow up was 11.3 months. Outcomes in the GD arm were: response rate 11.5% (95% CI: 4.4 to 23%), median PFS 3.0 months (95% CI: 1.6 to 8.0), median OS 13.7 months (95% CI: 10.1 to 23.9). The table shows, for each pairwise comparison of GD with the other arms (randomly labelled A, B, C to maintain blinding of open arms), the probabilities given the observed data that OR, PFS and OS were better for GD than for each other arm (RR: relative risk, HR: hazard ratio). For OR and PFS, all comparisons favoured the other arms. There were fewer grade 3/4 adverse events with GD than with the other arms pooled (58% v. 74%). Conclusions: rEECur has shown that GD is a less effective treatment than TC, IT or IFOS in reducing tumour burden or prolonging PFS in RR-ES. Recruitment continues to the remaining arms. Clinical trial information: ISRCTN36453794. [Table: see text]
A phase II randomized study of CMB305 and atezolizumab versus atezolizumab in NY-ESO-1+ soft tissue sarcoma: Analysis of immunogenicity, tumor control, and patient survival.
Authors: Chawla Sant P. , Van Tine Brian Andrew , Pollack Seth , Ganjoo Kristen N. , Elias Anthony D. , Riedel Richard F. , Attia Steven , Choy Edwin , Okuno Scott H. , Agulnik Mark , von Mehren Margaret , Livingston Michael B. , Keedy Vicki Leigh , Verschraegen Claire F. , Philip Tony , Bohac Gerry C. , Yurasov Sergey , Lu Hailing , Chen Michael , Maki Robert G. 
Published: March 2020

11011 Background: CMB305 (C) is an immunotherapy designed to generate an anti-NY-ESO-1 immune response (IR). C consists of a dendritic cell-targeting lentiviral vector encoding NY-ESO-1 gene (LV305), and a TLR-4 agonist NY-ESO-1 recombinant protein plus GLA-SE (G305). A Phase 1 study demonstrated C is safe, generates IR and conveys a median overall survival (mOS) of 23.7 months (15.5, not reached [NR]) for soft tissue sarcomas & 29.2 months (12.2, NR) for synovial sarcoma (SS) (ESMO 2018). We evaluated efficacy and safety of C and atezolizumab (A) vs A alone in NY-ESO-1+ SS and myxoid round cell liposarcoma (MRCL). Methods: A prospective randomized open label phase 2 study of C (LV305 Intradermal Days 0, 14, 42, 70 + G305 Intramuscular Days 28, 56, 84 then q 6wk up to one year (yr)) + A (1200mg IV q3wk) vs A alone in advanced NY-ESO-1+ SS/MRCL. Primary endpoints of OS and progression-free survival (PFS); secondary endpoints of safety, IR, and response rate and post hoc analysis by line of therapy. Results: 88 patients (pts) were enrolled and dosed. Arm C+A: median age 48 yrs, 73% SS, 98% relapsed metastatic, 73% ≥2 prior lines chemotherapy; Arm A: 47 yrs, 67% SS, 84% relapsed metastatic, 53% ≥2 prior lines chemotherapy. Most treatment-related adverse events (TRAE) Grade 1/2, no treatment related deaths. Summary of clinical outcomes. Conclusions: Despite no major differences in PFS and OS between the treatment arms (Arm C+A had more advanced disease and more prior lines of chemotherapy), Arm A +C achieved PRs, a higher level of anti-NY-ESO-1 IR, and pts with IR had numerically superior outcomes. Moreover, the clinical benefit of C+A in earlier lines of therapy warrant further study. Clinical trial information: NCT02609984. [Table: see text]
Interval-compressed vincristine, doxorubicin, cyclophosphamide (VAC), alternating with ifosfamide and etoposide (IE) for adults with Ewing or Ewing-like sarcoma.
Authors: Lu Eric , Ryan Christopher W. , Bassale Solange , Lim Jeong Youn , Davis Lara Emily 
Published: March 2020

11025 Background: In Children’s Oncology Group trial AEWS0031, VAC alternating with IE administered every 2 weeks rather than every 3 weeks resulted in a superior event-free survival (EFS). In the 2-week dosing group, a median interval of 15 days (mean 17.3) was achieved. Only 12% of patients enrolled in the trial were age 18+ and thus the feasibility of interval-compressed VAC/IE in the adult population remains poorly described. We conducted a retrospective analysis of our institutional experience using this regimen. Methods: Pharmacy administration records at Oregon Health and Science University were reviewed to identify patients age 18+ with Ewing and Ewing-like sarcoma who received VAC/IE q2wk, with first dose between January 2011 and March 2018. Results: 24 patients were identified. Median age was 28 (range 18 to 60). At diagnosis, 67% had localized disease. The most common primary sites were extremity (38%) and pelvis (17%); another 25% had extra-osseous primary tumors. Local therapy included surgery in 50% and XRT in 33% of subjects. The median interval between cycles was 16.7 days (mean 17.5). The median number of admissions for toxicity per patient was 2. The median number of dose delays (toxicity prolonging the 2 week interval) per patient was 4. Early treatment discontinuation occurred in 17%. Cumulative doses are outlined in Table. 5-year overall survival was 41%. 5-year EFS was 52% among patients with localized disease and 0% among those with metastatic disease. Conclusions: For adults with Ewing and Ewing-like sarcoma, chemotherapy administered every 2 weeks is a feasible and effective therapy, without significant dose reductions required. Our results are comparable to prior studies involving a primarily pediatric population. [Table: see text]
Neurofibromatosis 1 (NF1) and gastrointestinal stromal tumors (GISTs): Five-year experience from a regional center in United Kingdom.
Authors: Bulusu Venkata Ramesh , Casey Ruth , Giger Olivier , Carroll Nicholas , Maher Eamonn 
Published: March 2020

11035 Background: NF1 is an inherited autosomal dominant condition characterised by multifocal neurofibromas, café au lait spots, Lisch nodules, freckling. GISTs are the most common mesenchymal tumour of the gastrointestinal tract occurring in NF1 patients. We present our 5 year experience of NF1 associated GISTs from a regional centre in United Kingdom. Methods: 15 patients with GISTs associated with NF1 syndrome were identified from the database. Clinical, pathological, molecular and treatment outcomes were analysed. Results: N = 15. Male-3 and female-12. Median age 46 years. 33% were multifocal and 67% unifocal. Primary site Stomach-6.6%, duodenum-33%, small bowel-67%, colon 6.6%. Presenting symptoms: Abdominal pain-47%, anemia/bleed-40% and incidental finding-13%. Tumour size 0.5-23 cm, median 9 cm. Mitotic index 0-15, median 4 mitoses/5mm2. Risk stratification-Low/intermediate risk 60% and high risk 40%. Histology was spindle cell in 87% and mixed in 13%. All GISTs were CD117 and DOG-1 +ve. SDHB expression was preserved in all GISTs. No activation mutations were detected in KIT (exons 9, 11, 13, 17), PDGFRA (exons 12, 14, 18) and BRAF. Treatment: 67% had the primary GIST resected. None had adjuvant imatinib. 6 patients had been treated with tyrosine kinase inhibitors. 1 partial response lasting < 3 months was observed with Imatinib. No durable responses were seen with Imatinib or Sunitinib or Regorafenib. All 5 patients with metastatic disease died within one year of diagnosis. Conclusions: GISTs associated with NF1 syndrome are rare. Median age of diagnosis is a decade earlier than KIT/PDGFRA mutated GISTs. We observed that NF1 associated GISTs occur predominantly in small bowel, are mostly spindle cell histology and have female preponderance. No durable responses were noted with Imatinib or Sunitinib or Regorafenib. There is an urgent need for systematic international collaboration to identify druggable pathways/targets in NF1 GISTs. Any trials should be multicentre/ multinational to expedite recruitment.
Identification of genomic alterations by circulating tumor DNA in leiomyosarcoma: A molecular analysis of 73 patients.
Authors: Arshad Junaid , Roberts Ali , Cotta Jared Addison , Trent Jonathan C. 
Published: March 2020

11044 Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. In contrast to many sarcomas, the genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating Tumor DNA (ctDNA) offers a rapid and non-invasive method of next-generation sequencing (NGS) that could be utilized for diagnosis, therapy and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes utilizing NGS. Blood samples from patients with leiomyosarcoma were analyzed, and results from December 2014-December 2018 were reviewed. Results: Of the 90 samples collected and analyzed, alterations were detected in 73 ctDNA samples. After exclusion of variants of uncertain significance (VUS), 63 ctDNA samples harbored cancer-associated genomic alterations. Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. 76% (45) were female with a median age of 63 (range, 38-87) years. All samples were designated metastatic. The following table shows common alterations and types of mutations. The other alterations included RAF1, ERBB2, MET, PTEN, TERT, APC and NOTCH1. In 24 of the 73 patients (33%) the genomic alterations detected by ctDNA are potentially targetable by an FDA-approved or clinical trial therapy. There were 4 (5%) patients who were found to have incidental germline TP53 mutations. Conclusions: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.[Table: see text]
Clinical outcomes of sunitinib (Su) for patients (pts) with desmoid tumors (DT).
Authors: Miano Salvatora tindara , Francini Guido , Civitelli Serenella , Petrioli Roberto , Francini Edoardo 
Published: March 2020

11052 Background: The incidence of DT is steadily increasing in pts affected by familial adenomatous polyposis (FAP) and represents the first cause of death for pts who underwent preventive proctocolectomy. Currently, there is no standard therapy for DT and Tamoxifen (20 mg once daily) + Meloxicam (15 mg once daily) (TM) is the most commonly used regimen in clinical routine. We sought to evaluate the efficacy of Su, the most active PDGFR TKI, as first-line therapy for pts with DT. Methods: In this phase II IRB approved prospective study, pts with progressive, symptomatic, or recurrent DT were randomized to receive either Su (52 mg once daily) or TM. The primary end point was progression-free survival, defined as time from treatment start to clinical or radiological progression, whichever came first, at 2 years (2yr-PFS). Secondary endpoints were rates of objective response (OR), evaluated per RECIST criteria version 1.1, time to OR (ttOR), and toxicity. Adverse events (AE) were assessed per NCI-CTCAE version 4.02. Results: Of the 32 pts enrolled, 22 received Su and 10 TM. In both groups, median age at diagnosis was 43.5 years No OR was observed in the TM group. In the Su group, 17 pts had a partial response and 5 stable disease and the ORR was 75% (95% CI, 50 to 100). At a median follow-up of 27 months, the 2yr-PFS was 81% (95% CI, 69-96) and 36% (95% CI, 22-57) in the Su cohort and TM cohort, respectively (HR = 0.13; 95% CI, 0.05- 0.31; P<0.001). The median ttOR among pts who had an OR was 24 months. In the TM group, no toxicity was observed. The most frequently reported AE in the Su group were grade 1 or 2 hypothyroidism (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). (HR: 0.260; p = 0.0035). All AE responded to dose reduction (37.5 mg). Conclusions: In a cohort of pts with progressive, recurrent, or symptomatic DT, Su seems to be well tolerated and improve 2yr-PFS and OR rate compared with TM therapy. Further prospective studies with larger samples are needed to verify these results.
Phase 1 combination therapy with pexidartinib (PEX) and sirolimus (S) to target tumor-associated macrophages in pigmented villonodular synovitis, malignant peripheral nerve sheath tumors, and other soft tissue sarcomas.
Authors: Manji Gulam Abbas , Van Tine Brian Andrew , Lee Shing Mirn , Raufi Alexander , Patwardhan Parag , Blumberg Lauren Esther , Sender Naomi , Wang Jennifer , Otap Daniel , Singh-Kandah Shahnaz V. , Do Khanh Tu , Hirbe Angela C. , Bollag Gideon , Schwartz Gary K. 
Published: March 2020

11055 Background: No effective therapy exists for unresectable malignant peripheral nerve sheath tumors (MPNSTs). We previously reported that the combination of PEX and the mTOR inhibitor S synergistically inhibited MPNST growth (CCR 20: 3146, 2014) by depleting M2 TAMs and by inhibiting receptor tyrosine kinases (RTKs), including c-KIT, PDGFR, CSF1R. We characterized the safety, tolerability, recommended phase 2 dose (RP2D) of PEX plus S in all sarcoma sub-types. Methods: Patients (pts) received PEX plus S orally in 28 days cycle as per Table. The RP2D was determined using the time-to-event continual reassessment method (TITE-CRM) in advanced sarcoma who have progressed on standard therapy. DLT was defined as any need for a dose reduction. Results: 24 pts were accrued (Acr) of which 18 were evaluable (MPNST – 6, pigmented villonodular synovitis (PVNS) – 3, leiomyosarcoma – 5, and other – 9). The mean age was 46y, 56% were male, and 67% had greater than 2 prior therapies. Most common ( > 20%) grade 2 or higher TEAEs were anemia (33%), WBC count decrease (28%), fatigue, neutropenia, and lymphopenia (22% each). There were 5 dose limiting toxicities (DLT): 2 for elevated LFTs both of which resolved with dose reduction, 2 for supra-therapeutic S trough levels, and 1 for grade 5 dehydration at dose level (DL) 3. Four subjects experienced a partial response (PR; -44% to -77% by RECIST, 18 – 61 wks on therapy). Seven subjects experienced stable disease (SD; +19.7% to -20.7% by RECIST; 9.4 – 30 wks on therapy). Five subjects progressed on therapy and two subjects experienced early DLTs and did not undergo tumor assessment. The RP2D is DL 3 (S 2mg/PEX 1000mg) with an estimated probability of DLT of 26.7% as determined by TITE-CRM. This recommendation is based on a target DLT rate of 25%. TAMs and immune subtypes from available tissue specimens and historical controls will be presented. Conclusions: 1000mg of PEX in combination with 2mg of S daily has an acceptable safety profile. Objective responses and durable SD was observed in PNVS and MPNST patients justifying proceeding with a multi-center single arm phase 2 study in advanced MPNST. Clinical trial information: NCT02584647. [Table: see text]