bluuebunny/crossref_metadata_2025_split huggingface dataset:
Working together in cancer care: An academic community partnership for a diverse patient population.
Authors: Ko Naomi , Burgess Mayah , Demers Lindsay , Sanchorawala Vaishali , Gignac Gretchen , Drake Frederick Thurston , Cassidy Michael Ryan , Baiyee Emily , Lee Stephanie , Moy Beverly 
Published: March 2020

10525 Background: The Massachusetts General Hospital Cancer Care Equity Program conducted a qualitative survey health assessment in the inner-city communities of Boston to study Black Bostonian patients’ perceptions of the barriers to cancer care. Findings revealed a level of mistrust toward large cancer centers and a request for more interactions with their trusted community health providers. At a subsequent community forum geared toward soliciting solutions to improve relationships with academic medical centers, community members recommended that academic oncologists increase engagement with their community health center (CHC) clinicians with a cancer lecture series. Methods: Academic oncologists from Massachusetts General Hospital and Boston Medical Center met with the leadership at two CHCs prior to the creation of the cancer lecture series. Feedback on how to best support CHC providers was established and a cancer care lecture series was created with continuing medical education (CME) credit provided. Five in-person lectures were given at each CHC. Topics included: Consultative Hematology, Breast Cancer, Prostate Cancer, Thyroid Cancer, Colon Cancer and Adrenal Masses. Survey evaluations (summative and formative) were distributed to all participants. An online portal was established to provide ongoing CME to providers. Results: Six academic physicians specializing in cancer care provided lectures at two CHCs. Currently, we have 176 surveys completed from both CHCs. Thus far, 98.3% surveys have indicated that the lectures have been “Excellent” or “Above Average,” and all participants have responded that the objectives of each presentation have been met. We have developed a website to provide ongoing CME for the lectures that were given: http://bucme.org/cancercare . Conclusions: This project aims to improve cancer care education and communication between providers from academic cancer centers and primary care providers at CHCs that care for a diverse and vulnerable patient population.
Enhancing evidence-based medicine skills in oncology training with cognitive technology.
Authors: Chen Chun-You , Hung Hui-Chun , Chiu Hsin-Yi , Wei Po-Li , Kuo Pih-Lian , Chiou Jeng-Fong , Preininger Anita , Dankwa-Mullan Irene , Kefayati Sarah , Solomon Metasebya , Jackson Gretchen , Rhee Kyu , Yen Yun 
Published: March 2020

10532 Background: Evidence-based medicine (EBM) requires applying literature evidence to inform practice. Students from Taipei Medical University Hospital, trained in EBM concepts, participated in a preliminary study using Watson for Oncology (WfO), an evidence-based decision-support system to enhance the EBM skills of medical students. Methods: A class of 50 medical students compared traditional search methods (TSM) and WfO in a workshop divided into 2 sequential sessions on colon and lung cancer, respectively. All students were trained on WfO, and 2 groups of 25 students each were randomly assigned to either TSM or WfO in the first session. Those groups were then assigned to the alternate approach in the second session. Students completed a profile that included their clinical experience with each cancer type. Students used either WfO or TSM to help answer a series of questions related to colon or lung cancer. Students then completed a survey of attitudes towards the technology, followed by a constructed-response learning assessment without the aid of TSM or WfO. Assessments were scored and results compared using a Mann-Whitney U Test; outcomes at two different experience levels, based on student profiles, were compared using a Kruskal-Wallis test. Results: In this preliminary study, more than 70% of students reported limited clinical experience with either cancer. On the colon cancer assessment, students in the WfO group performed significantly better than the TSM group ( p = 0.0001); there was no significant difference detected for lung cancer. Students with more clinical experience felt that TSM was easier to learn than WfO ( p= 0.005); students with less experience felt that WfO was clearer and more understandable than TSM ( p= 0.002). Conclusions: These preliminary results are consistent with better learning outcomes for students using WfO in the colon cancer module. Students with more clinic experience reported that TSM was easier to learn than WfO, however it is unknown if this might be due to a potentially greater familiarity with TSM in this more experienced group. More studies are needed to determine what features, if any, of WfO can facilitate EBM approaches in oncology education.
A phase I/II study of pembrolizumab (Pem) and doxorubicin (Dox) in treating patients with metastatic/unresectable sarcoma.
Authors: Pollack Seth , Redman Mary Weber , Wagner Michael , Loggers Elizabeth Trice , Baker Kelsey K. , McDonnell Sabrina , Gregory Jeffrey , Copeland Vanessa C. , Hammer Kathryn J. , Johnson Rylee , Moore Roxanne , Shahnazari Michael , Townson Steven Matthew , Jones Robin Lewis , Cranmer Lee D. 
Published: March 2020

11009 Background: Patients with advanced soft tissue sarcomas (STS) treated with single agent Dox have a median progression-free survival (PFS) of 4.6 months (mo) and response rate (RR) of 14%. Dox sensitizes tumors to Pem through calreticulin release and killing of immunosuppressive cells. Thus we hypothesize that combining Dox + Pem will improve patient outcomes. Methods: A phase I/II trial (NCT02888665) evaluating Dox+Pem was designed for Dox naïve STS and select bone sarcomas with a 1° endpoints of safety (CTCAE v4.03) and response rate (RR) by RECIST 1.1. Patients received one “priming” dose of Pem (200mg IV) prior to starting Dox+Pem Q3wks. Dox+Pem was continued for up to 6 cycles, followed by Pem monotherapy for up to 2 years or progression. The phase I portion used a 3+3 design with 2 Dox doses (45 & 75 mg/m2), followed by a Simon 2-stage expansion. A retrospective study of patients treated at our center on non-ifosfamide containing Dox trials (DoxT) was performed in order to compare our observed PFS with a comparable historic population. Results: Treatment was well tolerated; detailed safety data will be presented. No additional cardiac risk was observed. No DLTs were observed during phase I and 75mg/m2 was selected as the phase 2 Dox dose. The study met criteria for expansion to the 2nd stage. Though the planned enrollment was 41, the study closed after 37 as it was clear that the RR (22% , including phase I patients) would not meet the phase 2 RR target of 29%. However, 59% of patients had stable disease (disease control rate = 81%) with tumor regression in a majority of patients. The median PFS on Dox + Pem was 8.1 mo (95% CI: 6.3, 10.8). Patients treated with Dox + Pem had a significantly longer median PFS compared to the DoxT cohort (4.1 mo, 95%CI 3.0 – 6.6, p < 0.001). Conclusions: Dox+Pem is well-tolerated. While this study failed to meet its 1° RR endpoint, a highly significant improvement in PFS was observed compared with historical controls. This is consistent with findings in other cancers, such as head & neck, where improved clinical outcomes were observed without significant increase in RR by RECIST. A randomized trial of Dox +/- Pem should be carefully considered in light of recent negative trials in STS. Clinical trial information: NCT02888665.
SAINT: Results of a phase 1/2 study of safety/efficacy using safe amounts of ipilimumab, nivolumab, and trabectedin as first-line treatment of advanced soft tissue sarcoma.
Authors: Gordon Erlinda Maria , Chua-Alcala Victoria S. , Kim Katherine , Liu Seiya , Angel Nicole , Baby Rekha , Brigham Don , Tseng William W. , Pollack Seth , Jones Robin Lewis , Federman Noah , Srikureja Amor M. , Jalas John , Chawla Sant P. 
Published: March 2020

11016 Background: Sarcoma cells are most immunogenic earlier in the disease course and prior to treatment when the immune system can recognize and destroy them. Hypothesis: Immune checkpoint inhibitors would be most effective when given as first line therapy. Methods: This is an IRB-approved dose-seeking Phase 1/2 protocol using defined doses of I (1 mg/kg i.v. q 12 weeks), N (3 mg/kg i.v. q 2 weeks) and escalating doses of T (1.0, 1.2, 1.5 mg/m2 i.v. q 3 weeks), employing the “Cohort of Three” design, followed by a Phase 2 using the MTD of trabectedin. Results: Nine subjects were treated in Phase 1 of the study, and 31 subjects in Phase 2. Safety analysis: at Dose 1: Grade 3 treatment-related adverse events (TRAEs) included fatigue (n = 1), increased TSH (n = 1). At Dose 2, Grade 4 TRAEs included thrombocytopenia with bleeding, DLT (n = 1), increased CK (n = 1); Grade 3 TRAEs included anemia (n = 1), myalgia (n = 1), increased TSH (n = 1), decreased TSH (n = 1), increased AST (n = 1). Efficacy analysis (evaluable patients): At Dose 1: Disease Control Rate (DCR = CR, PR, SD) was 67%, median PFS, 18 weeks; median OS, 50 weeks; At Dose 2: PR (n-1), DCR 60%, median PFS, 24 weeks; median OS, > 46 weeks. At Phase 2, MTD Dose 2 (PUPs): Safety analysis (n = 31): Grade 3 TRAEs included fatigue (n = 2), increased ALT (n = 6), increased AST (n = 4), hypernatremia (n = 1), hyponatremia (n = 1), dehydration (n = 1), rash (n = 1), port cellulitis (n = 1), psoriasis exacerbation (n = 1), increased TSH (n = 1), decreased hemoglobin (n = 2), neutropenia (n = 1). Efficacy analysis (N = 23 evaluable): PR (n-5; 2 UPS, 1 synovial sarcoma, 1 liposarcoma, 1 leiomyosarcoma,), BORR 22%, DCR 96%. Median PFS and OS not yet reached. After 4 treatment cycles, one resected tumor showed 80% necrosis and a greater number (30%) of CD8+ killer T cells, in the TME compared to archived pre-treatment tumor. Conclusions: These data suggest that the SAINT protocol (1) is safe with manageable adverse events, with no additive toxicity, and (2) may control tumor growth. Phase 2 of the study is on-going. Clinical trial information: NCT03138161.
Precision oncology in sarcoma drug development: Impact of genomic matching on response, clinical benefit, and survival in sarcoma patients on phase 1 trials.
Authors: Sen Shiraj , Pestana Roberto , Hess Kenneth R. , Hong David S. , Janku Filip , Naing Aung , Falchook Gerald Steven , Conley Anthony Paul , Patel Shreyaskumar , Meric-Bernstam Funda , Subbiah Vivek 
Published: March 2020

11018 Background: Genomic analyses have revealed many potentially actionable mutations across sarcoma subtypes. Whether sarcoma patients enrolled on genomically matched early phase trials have improved clinical outcomes over patients enrolled on non-genomically matched trials remains unclear. Methods: We analyzed clinical and next gen sequencing data from sarcoma patients on phase 1 trials at MD Anderson Cancer Center (MDACC) and performed logistic and Cox proportional hazards regression analyses to compare response rate (RR), median time to progression (mTTP), clinical benefit rate (CBR = CR, PR, or SD > 6 months), and median overall survival (mOS) between patients treated on genomically-matched and non-genomically matched trials. Results: Among the 406 patients with advanced sarcomas (321 soft tissue sarcoma [STS], 85 bone sarcomas) treated on phase 1 trials at MDACC from May 2006 to May 2018, median age was 53 (range 11-84), 48% were female, and patients had a median 3 prior lines of therapy (range 0-9). The most commonly treated STS subtypes were leiomyosarcoma (n = 66; 16%), liposarcoma (n = 52; 13%), GIST (n = 44; 11%), and synovial sarcoma (n = 11; 3%) and most commonly treated bone sarcomas were osteosarcoma (n = 34; 8%), chondrosarcoma (n = 28; 7%), and Ewing's sarcoma (n = 25; 6%). 23% (n = 93) of sarcoma patients treated on phase 1 trials were treated on genomically-matched trials. RR on non-genomically matched trials was 6% compared to 11% on genomically-matched trials, OR 1.97 (95% CI 0.88, 4.44), p = 0.10. Responses on genomically-matched trials were seen with novel agents targeting TRK, LRRC15, cMET, mTOR, VEGF, MDM2, KIT/PDGFRA, and FGFR. mTTP on non-genomically matched trials was 2.7 months compared to 3.7 months on genomically-matched trials, HR 0.72 (95% CI 0.57, 0.91), p = 0.0048. CBR on non-genomically matched trials was 19% compared to 41% on genomically-matched trials, OR 2.91 (95% CI 1.77, 4.80), p < 0.0001. mOS on non-genomically matched trials was 15.5 months compared to 22.1 months on genomically-matched trials, HR 0.70 (95% CI 0.50,0.98), p = 0.031. Conclusions: Enrollment on genomically-matched phase 1 trials is associated with an improvement in clinical benefit rate, time to progression, and overall survival in heavily pretreated, metastatic sarcoma patients. While RR remained low, we report the mutations associated with responses on genomically-matched trials. A prospective, biomarker-driven genomically-matched basket trial for these alterations is warranted in advanced sarcomas.
Angiosarcoma of bone: A European Muscoloskeletal Oncology Society (EMSOS) multicenter, retrospective study.
Authors: Palmerini Emanuela , Leithner Andreas , Windhager Reinhard , Gosheger Georg , Boye Kjetil , Laitinen Minna , Hardes Jendrik , Traub Frank , Jutte Paul , Willegger Madeleine , Casanova Jose' , Setola Elisabetta , Righi Alberto , Picci Piero , Donati Davide Maria , Ferrari Stefano 
Published: March 2020

11046 Background: Angiosarcoma of bone (B-AS) is an exceedingly rare malignant tumor of vascular origin. The aim of this EMSOS retrospective study is to report on natural history, type of treatment and prognosis of B-AS. Methods: Patient data were collected according to the national rules for observational studies through electronic dataset available on EMSOS WEBsite. Results: 80 patients (51 male and 29 female, median age 54 years, range 17 to 92 years, 56% with localized disease, 44% metastatic) from 8 EMSOS Centers were collected. Surgery of the primary tumor was performed in 76% of patients (amputation in 30%), with intralesional margins in 26%. A surgical complete remission status (SCR) was achieved in 47% of the patients. Radiotherapy (RT) was delivered in 41% of the patients (in 15 patients as definitive local treatment), chemotherapy (CT) in 47% (56% in metastatic and 41% in localized cases). With a median follow-up of 31 months (range 40 to 309 months), 68% of patients died, 16% were disease-free, 12% were alive with disease and 4% dead for other causes. The 5-year overall survival (OS) was 27% (95%CI 16-30): 41% (95%CI 25-56) for localized patients (45% SCR, 17% no SCR, p = 0.03) and 8% (95%CI 0-20) for metastatic patients (p = 0.002). Among metastatic patients, 29/35 have died, with a median time to death of 6 months (1-45), while 6 patients were alive with a median follow-up of 22 months (8-106). Improved survival was observed for male patients (30% vs 8%, p = 0.04), while type of treatment (surgery, chemotherapy, radiation), pattern of metastases and age did not affect outcome. In 18 metastatic patients who underwent chemotherapy partial respo nse (PR) was documented in 1/3 patients after paclitaxel (RR 33%), and stable disease (SD) in 5 patients (2/2 with gemcitabine, 2/8 with doxorubicin/ifosfamide, and 1/4 with osteosarcoma-like chemotherapy). In localized patients, the 5-year OS was significantly better for age ≤ 50 years (68% vs 34%, p = 0.02) and extremity and central tumor as compared with pelvis/sacral location (50% vs 58% vs 0%, p = 0.008), with improved disease-free survival (DFS) after chemotherapy (49% vs 33%, p = 0.04). Conclusions: Metastatic B-AS is a fatal disease and inclusion in experimental trials is warranted. In localized patients, a better probability of survival is expected in younger and surgically treated patients. The use of chemotherapy was associated with improved DFS.
Metagenomic discovery of a distinct inflammatory subtype of human angiosarcoma associated with human herpesvirus 7.
Authors: Chan Jason Yongsheng , Lim Jing Quan , Ravi Vinod , Guan Peiyong , Tay Timothy Kwang Yong , Selvarajan Sathiyamoorthy , Ong Choon Kiat , Huang Dachuan , Jing Tan , Ng Cedric Chuan Young , Sung Ken Wing-Kin , Harunal Rashid Mohamad Farid Rin , Quek Richard Hong Hui , Tan Ngian Chye , Teo Melissa Ching Ching , Rozen Steven , Tan Patrick , Futreal Andrew , Teh Bin Tean , Soo Khee Chee 
Published: March 2020

11047 Background: Angiosarcomas are rare, clinically-aggressive endothelial tumors with remarkable heterogeneity in terms of anatomical and etiological origins, amongst which UV-radiation and oncogenic viruses have been implicated. Methods: The genomic and transcriptomic landscapes of human angiosarcomas were examined using whole genome sequencing (n = 18) and RNAseq (n = 14). Results were validated in an extended cohort of FFPE tissue (n = 57) on various platforms. Results: We observed recurrent mutations in known angiosarcoma-associated genes including TP53, KDR, POT1 and PTPRB. The median tumor mutation burden (TMB) was 1.95 mutations per megabase and was highest in a subset of head and neck angiosarcomas (HN-AS, n = 6) harboring UV signatures. The remaining cases, including seven HN-AS, contained a significantly lower TMB (5.04 vs 0.91, p= 0.0007). In corroboration, UV exposures were validated by cyclobutane pyrimidine dimer immunohistochemistry in 15 of 35 (42.9%) HN-AS and cutaneous angiosarcomas, but not in visceral or breast angiosarcomas. Gene set enrichment analysis (GSEA) revealed upregulation of “cell cycle” and “inflammation” pathways in angiosarcomas. Notably, drug inhibition of overexpressed kinases including aurora kinase, polo-like kinase and checkpoint kinase-1 potently reduced viability in two angiosarcoma cell lines, achieving IC50s of < 1µM. Metagenomic analysis detected viral reads mapping to the human herpesvirus-7 (HHV-7) genome, which were verified by PCR and immunohistochemistry. Genomic integration of HHV-7 was demonstrated at its flanking DRR telomeric repeat sequence adjoining the subtelomeric region of chromosome 17p. Overall, HHV-7 was detected in 38 of 57 (66.7%) angiosarcomas and inversely correlated with UV exposure ( p= 0.01). GSEA and Nanostring IO360 profiling showed that “inflammation” pathways were enriched in viral-positive angiosarcomas, while “cell cycle” pathways were enriched in viral-negative cases. Compared with HHV-7 negative cases, HHV-7 positive angiosarcomas were associated with high tumor inflammation scores (TIS ≥ median 6.74) (73.3% vs 25.0%, p = 0.02). Conclusions: We identified distinct subtypes of angiosarcoma characterized by HHV7-positive “inflammation” and UV-associated “cell cycle” phenotypes.
Low-dose chemotherapy with methotrexate and vinblastine for patients with refractory desmoid tumors: A second report of relationship between efficacy and various factors.
Authors: Nishida Yoshihiro , Sakai Tomohisa , Shimizu Koki , Urakawa Hiroshi , Arai Eisuke , Ikuta Kunihiro , Ando Yuichi , Ishiguro Naoki 
Published: March 2020

11050 Background: Efficacy of low-dose chemotherapy with methotrexate (MTX) and vinblastine (VBL) for desmoid-type fibromatosis (DF) has been reported and approved by many physicians. However, significant factors including biomarker could not be identified to better predict the efficacy of this chemotherapy. Since 2003, meloxicam, which is a selective COX-2 inhibitor, has been applied consecutively as a first line treatment. We applied the low-dose chemotherapy with MTX+VBL for refractory patients. The aim of this study was to reveal the clinical outcome of low-dose chemotherapy with MTX+VBL, and determine the useful factors to predict the efficacy including CTNNB1 mutation status. Methods: Since 2003, 167 cases were histologically diagnosed as DF. Among them, 36 cases were treated with MTX (30mg/M2) +VBL (6mg/M2) chemotherapy. Treatment interval was basically 2 weeks according to our previous study. Effectiveness was evaluated with MRI and/or CT every 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST). Frozen or FFPE (Formalin-Fixed Paraffin-Embedded) specimens obtained at biopsy or previous surgery were subjected to the analyses for CTNNB1 mutation status by Sanger method. Clinical outcome and factors correlating with the efficacy were analyzed. Results: Among 36 cases with this chemotherapy, male was 13, mean age at the treatment was 36±18 years. Mean maximum diameter of tumor was 15±18 cm. Twenty-nine cases (81%) harbored CTNNB1 or APC mutation. Mean treatment duration and cycles of MTX+VBL were 20 months and 29 cycles, respectively. According to RECIST, PD in 2, PR 1n 15, and SD in 19. According to CTCAE, Grade 3 or more adverse events were observed in only one case. CTNNB1 mutation status, gender, age, size, and location did not affect the outcome of RECIST. Longer treatment duration and cycles of chemotherapy were significantly associated with the outcome (P = 0.002 and 0.004, respectively). In 15 cases of PR, recurrent tumors significantly took longer time to get efficacy (P = 0.027), and tumors arising in trunk and extremities tended to take longer time (P = 0.1). Conclusions: Low-dose MTX+VBL chemotherapy is effective and feasible treatment for refractory DF regardless of CTNNB1 mutation status. Occasionally it takes time to obtain objective response.
Use of cardioprotective dexrazoxane and myelotoxicity in anthracycline-treated soft tissue sarcoma patients.
Authors: Silletta Marianna , Spalato Ceruso Mariella , Napolitano Andrea , Mazzocca Alessandro , Valeri Sergio , Improta Luca , Santini Daniele , Tonini Giuseppe , Vincenzi Bruno 
Published: March 2020

11053 Background: Dexrazoxane (DEX) is indicated as a cardioprotective agent for patients receiving doxorubicin, who are at increased risk for cardiotoxicity. Concerns have been raised on the use of DEX, particularly in the adjuvant setting, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when DEX is used. No data in soft-tissue sarcoma (STS) patients is available, so far. Here, we retrospectively analyzed a cohort of our Institute database to assess whether the addition of DEX causes more bone marrow suppression in STS patients receiving Anthracycline-Ifosfamide (AI) combination in perioperative and advanced setting. Methods: 133 patients who received AI between January 2006 and December 2017 were included. 46 of them received DEX concurrently with the AI treatment. Hospital records were reviewed and available for all patients (the accessibility of all the data was an inclusion criterion). Compared to the non-DEX group, patients who received DEX were more frequently treated in the context of a perioperative setting (respectively 27.3 vs 38.8%). No other differences in terms basal patient features were recorded. Significantly, all patients received similar post-medication after each cycle. Results: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of G3/4 hematological side effects: leucopenia (28.7 vs 56.5%, p value=0.0014); neutropenia (35.6 vs 69.6%, p value=0.0002); anemia (28.7 vs 41.3%, p value=0.1758); thrombocytopenia (32.1 vs 54.3%, p value=0.0159). Similarly, compared to the non-DEX group, there were more hospitalizations for febrile neutropenia (37.9 vs 63.0%, p value=0.0066) and dose reductions (19.5 vs 39.1%, p value=0.0221) in the DEX group, above all in perioperative setting (15.6 vs 58.3%, p value=0.0085); but no significant difference in the incidence of treatment delays or interruption. Conclusions: Adding DEX to Anthracycline-based chemotherapy in soft-tissue sarcoma patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions.