bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase Ib/II study of selinexor in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST): SeliGIST/GEIS-41 trial.
Authors: Serrano Cesar , Valverde Claudia , Cruz Jurado Josefina , Martinez-Trufero Javier , Guri Xavier , Giuppi Martina , Redondo Andrés , Suarez-Paniagua Beatriz , Romagosa Cleofe , Martinez Virginia 
Published: June 2021

11534 Background: KIT or PDGFRA oncogenic activation drives GIST progression throughout the disease course. Accordingly, currently approved agents in metastatic GIST focus on the therapeutic suppression of these receptors. However, the clinical benefit after imatinib (IM) progression is still modest, suggesting the co-operation of KIT/PDGFRA-independent mechanisms in GIST cell survival. Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, and preclinical studies evidenced antitumoral activity in GIST as single agent and in combination with IM in both IM-sensitive and IM-resistant models. Methods: The phase Ib portion studied IM 400 mg daily plus weekly selinexor in patients (pts) with IM-resistant, advanced GIST. Prior intolerance to IM was not allowed. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D) of this combination. Investigator-assessed response was evaluated every 8 weeks using RECIST 1.1. Results: At data cutoff of Sep 25, 2020, 12 pts were enrolled and received treatment with IM 400 mg and selinexor once weekly at dose levels (DL) 1 (60 mg), DL2 (80 mg) and DL3 (100 mg). Median age 57 (range 46-77), 42% female, median prior therapies 4 (range 2-7). Although only 1/6 pts developed a dose limiting toxicity (DLT) at DL3, the RP2D was defined at DL2 (IM 400 mg daily and selinexor 80 mg once weekly) based on activity data in the DL2 and the need for dose reductions in 5/6 pts at DL3 after the DLT window. All pts were evaluable for toxicity and response. One DLT occurred at DL3 (G3 nausea). Non-DLT G3/4 toxicities were anemia (1/12 pts), neutropenia (1/12 pts), vomiting (1/12 pts) and fatigue (2/12 pts). Common G1/2 toxicities were nausea (11/12 pts), vomiting (10/12 pts), neutropenia (5/12 pts) and anemia, fatigue, diarrhea, and periorbital edema (4/12 pts each). No unexpected toxicities were observed. Overall response rate in the 12 pts evaluable for response was 67% (95% CI 0.349-0.901), with 2 pts achieving PR (17%) and 6 pts SD (50%) as the best response. Clinical benefit rate (CBR = CR, PR, SD) ≥ 16 weeks was 42% (95% CI 0.157-0.723). Median progression free survival was 3.5 months (95% CI 1.7-7.3). Four pts remain on trial at data cutoff. Conclusions: IM and selinexor combination is well-tolerated and has clinical activity in heavily pretreated GIST pts. The trial is currently exploring selinexor as single agent in the IM-resistant GIST population. Clinical trial information: NCT04138381.
Next generation sequencing of sarcomas: Response to crizotinib in two cases with MET amplification.
Authors: Victor Adrienne I. , Alvarez Olga , Baumgart Megan Ann , Goyal Gaurav , Sahasrabudhe Deepak M. 
Published: June 2021

11538 Background: Sarcoma subtypes are often defined by recurrent molecular alterations. The purpose of this study is to review the utility of next generation sequencing (NGS) in sarcoma patients and report clinical outcomes to matched therapies. Methods: The records of all patients seen at the University of Rochester Medical Center (URMC) with sarcoma and NGS profiling between 8/2013 and 3/2020 were reviewed. Responses to agents targeting reported alterations were analyzed. In patients with fluorescent-in-situ hybridization (FISH) testing, fusion events by NGS were compared with FISH results. All highlighted pathogenic alterations on the NGS profile report as well as variants of uncertain significance (VUS) were recorded. Results: Seventy-five patients met inclusion criteria. Of these, 25 received a treatment based on identified alterations; 1 had a complete response (CR), 4 had partial responses (PR), and 4 experienced disease stabilization (SD). We identified two patients with MET amplified sarcoma that responded to treatment with crizotinib. One other patient with a diagnosis of leiomyosarcoma was found to have an unusually high total mutational burden (TMB) and experienced complete pathologic response to dual checkpoint blockade. In 4 cases, testing resulted in a change in subtype diagnosis. Several rare and novel fusions were identified; a sarcoma with TPM4-NTRK3 fusion responded to larotrectinib, while a sarcoma with PML-JAK1 fusion did not respond to ruxolitinib, and a sarcoma with IL7R-BCL2 fusion progressed on venetoclax. Table summarizes matched therapies in responders. Conclusions: NGS profiling led to a targeted therapy with a clinical benefit rate of 12% in this cohort. NGS profiling led to a change in diagnosis in 5% of this cohort. Multi-institutional collaborations to track outcomes of matched therapy would help determine the utility of therapies in rare cancers and unusual alterations.[Table: see text]
VAC temporization pending final margins after suprafascial myxofibrosarcoma excision to reduce the rate of local recurrence.
Authors: Fourman Mitchell Stephen , Ramsey Duncan C. , Kleiner Justin , Daud Anser , Newman Erik T. , Schwab Joseph H. , Chen Yen-Lin , DeLaney Thomas F. , Mullen John Thomas , Raskin Kevin , Lozano-Calderon Santiago 
Published: June 2021

11573 Background: The microinvasive nature of suprafascial myxofibrosarcoma complicates the accuracy of intraoperative margin assessment, and tumor bed resections after soft tissue reconstruction are unreliable. For the past 3 years we have temporized the excised tumor bed with a wound VAC, delaying soft tissue coverage until final negative margins were achieved. Here, we compare the oncologic/surgical outcomes of suprafascial myxofibrosarcomas managed with VAC temporization (VT) with single-stage excision/reconstruction (SS). Methods: We retrospectively studied suprafascial myxofibrosarcomas managed from 1/1/2000 to 1/1/2019 who received neoadjuvant or adjuvant radiation and had at least 2-years of oncologic follow-up at a tertiary referral cancer center. Our primary outcome was local recurrence. Comparisons were performed using Fisher’s Exact Test or Students t-test. A p-value < 0.05 was considered significant. Results: Fifty-three patients (18 VAC temporized, 35 single stage) were included. While VT patients were older (74.9 ± 10.2 vs. 63.9 ± 13.6, p = 0.003), treatment groups did not significantly differ with respect to comorbidity, tumor volume, stage and grade. VT patients had significantly fewer local recurrences (5.6% vs. 28.6% after SS, p = 0.048) and R1 resections that required an unplanned readmission for tumor bed re-excision (0% vs. 37.1% after SS, p = 0.002). VT required more total surgeries (2.8 ± 0.9 vs. 1.8 ± 0.9 for SS, p = 0.0002). Post-operative infectious and wound complications were equivalent (Table). Conclusions: Our VAC temporization strategy had a significantly lower LR than SS treatment. While high quality multi-institutional validation is required, VT may represent a paradigm shift in the management of myxofibrosarcoma.[Table: see text]
Does early palliative care reduce end-of-life hospital costs? A propensity-score matched, population-based, cohort study.
Authors: Seow Hsien , Sutradhar Rinku , Barbera Lisa Catherine , Guthrie Dawn , McGrail Kim , Burge Fred , Peacock Stuart , Chan Kelvin K. 
Published: June 2021

12006 Background: Few studies describe how early versus late palliative care affects end-of-life health services costs. The aim of this study was to investigate the impact of early vs not-early palliative care among cancer decedents on the combined costs of receiving aggressive care (ED/hospitalization) and supportive care (home care/physician home visit). Methods: Using linked administrative databases, we created a retrospective cohort of cancer decedents between 2004 -2014 in Ontario, Canada. We identified those who received “early” palliative care (palliative care service used in the hospital or community 12 to 6 months before death [exposure]). We used propensity score matching to identify a control group of “not-early” palliative care, hard matched on age, sex, cancer type and stage. The propensity score included region, year, treatment, etc. We examined differences in median costs (including hospital, ED, physician, and home care costs) between pairs in the last month of life. Results: We identified 144,306 cancer decedents, of which 37% received early palliative care in the exposure period. After propensity score matching, we created 36,238 pairs of decedents who received early and not-early palliative care. After matching the early and not-early groups had equal distributions of age, sex, cancer type (24% lung cancer) and stage (25% stage 3 or 4). Among those who received early palliative care, 56.3% used hospital in-patient care in the last month, whereas 66.7% of the control group (not-early palliative care) used in-patient care; considering only inpatient hospital costs, those receiving early palliative care used a median of $2,894 in the last month of life compared to the control group of $5,311 (p < 0.001). Overall median costs in the last month of life for patients in the early palliative care vs the control group was $11,129 vs. $10,598 (p < 0.001). Conclusions: In our population-based, propensity-score matched, cohort study of cancer decedents, receiving early palliative care reduced the median overall health system costs, especially via avoiding hospitalizations in the last month of life.
The impact of advance care planning on hope among patients with advanced cancer.
Authors: Cohen Michael , Althouse Andrew , Chu Edward , Arnold Robert M. , White Douglas B. , Rosenzweig Margaret Q. , Bulls Hailey W. , Smith Kenneth , Schenker Yael 
Published: June 2021

12029 Background: Providers often cite a fear of “giving up hope” as a reason they defer advance care planning (ACP) among patients with advanced cancer. We sought to determine whether engagement in ACP impacts patient’s hope. Methods: This is a secondary analysis of a randomized controlled trial of primary palliative care in advanced cancer. Patients who had not completed ACP at baseline were included in the analysis. ACP was assessed in the forms of an end of life conversation with one’s oncologist (EOL conversation) and completion of a living will/advance directive (AD). Measurements were obtained at baseline and 3 months. Hope was measured using the Herth Hope Index (HHI, range 12-48, higher scores indicate higher hope). ACP was measured with patient responses to a validated ACP questionnaire that queried (1) if they had had an EOL conversation with their provider and (2) if they had completed a living will or advance directive. Multivariate regression was performed to control for baseline HHI score, study randomization and age, religious importance, education, marital status, socioeconomic status, time since cancer diagnosis, pain/symptom burden (ESAS), and anxiety/depression score (HADS)—all variables known to be associated with ACP and/or hope. Results: A total of 672 patients with advanced cancer were enrolled in the overall study. The mean age was 69±10, and the most common cancer types were lung (36%), GI (20%) and breast/GYN (16%). In this group, 378 (56%) had not had an EOL conversation at baseline, of whom 29% (111/378) reported having an EOL conversation by 3 months. Hope was not different between patients who had or did not have an EOL conversation over the study period (ΔHHI 0.20 ± 5.32 vs -0.53 ± 3.80, p=0.136). After multivariable adjustment, hope was significantly increased in patients who had engaged in an EOL conversation (adjusted mean difference in ΔHHI 0.95 (95%CI 0.08-1.82), p=0.032). Similarly, of 216 (32%) patients without an AD at baseline, 31% (67/216) patients had subsequently completed one. Unadjusted hope was not different between those who had and had not completed an AD (ΔHHI 0.20 ± 3.89 vs -0.91 ± 4.50, p=0.085). After adjustment, hope was significantly higher in those who completed an AD (adjusted mean difference in ΔHHI 1.31 (95%CI 0.13-2.49), p=0.030), (Table). Conclusions: Our results demonstrate that hope is not decreased after engagement in ACP and may, in fact, be increased. These findings may provide reassurance to providers who are apprehensive about having these important and difficult conversations. Unadjusted and adjusted change in hope for those patients who had and had not had completed an EOL conversation or AD.[Table: see text]
Overall and progression-free survival in young breast cancer patients with low muscle mass and density.
Authors: Greiner Rebecca Sheaff , Flores Matthew , Boselli Danielle , Stone Taylor , Hadzikadic-Gusic Lejla , Hecksher Anna , Bailey-Dorton Chasse Margot , Wang Eric , Walsh Declan 
Published: June 2021

12052 Background: Low muscle mass (skeletal muscle index, SMI) and density (skeletal muscle density, SMD) are associated with chemotherapy toxicity and shorter survival in women with breast cancer. This has not been studied specifically in women ≤ 40 years at diagnosis. They have different body compositions and more aggressive cancers than older women. We compared pre-treatment muscle measures in survivors and non-survivors and investigated their association with overall survival (OS) and progression-free survival (PFS). Methods: This case-control study included 112 women aged ≤ 40 years at diagnosis. Women with pre-treatment CT scans from 2009-2018 were identified; non-survivors were matched with survivors by age, year of diagnosis and disease characteristics. Body composition was determined by CT analysis. Measures were compared between the groups using Kruskal-Wallis tests. Kaplan-Meier methods summarized OS and PFS and the associations of muscle characteristics with OS and PFS were examined by univariate Cox proportional hazard models. Results: Median age was 35 years; median follow-up was 8.2 years. 75% had Stage II or III disease and 21% Stage IV disease. 33% were sarcopenic (SMI < 40) and 16% had low SMD (HU <37.8). Non-survivors had more intermuscular fat (IMAT), reduced SMD, and reduced skeletal muscle gauge (SMG). Sarcopenia was not associated with OS; however, sarcopenia was associated with shorter PFS. The median skeletal muscle gauge was 1973; low skeletal muscle gauge (SMG <1973) was associated with both shorter OS and PFS. Median IMAT was 1.6, and high IMAT (≥1.6) was associated with shorter OS and PFS. Conclusions: Low muscle mass (sarcopenia) at breast cancer diagnosis was associated with shorter PFS and low muscle density (low SMG and higher IMAT) was associated with shorter OS and PFS in women ≤ 40 years. These sub-optimal muscle characteristics may indicate an overall reduced state of health and/or decreased ability to tolerate treatment, thus reducing survival. Future research should determine the significance of muscle changes throughout treatment and establish standards for improved muscle health.[Table: see text]
Predictors of receiving survivorship care plans and visits.
Authors: Duffy Christine M. , Saiganesh Harish , Chrysanthopoulou Stavroula , Higel-Mcgovern Camille , Dizon Don S. 
Published: June 2021

12055 Background: While the Commission on Cancer has eliminated strict quotas for accreditation, Survivorship Care Plans (SCPs) and/or Survivorship Care Visits (SCV) at treatment completion are encouraged. However, who receives a SCP or SCV, whether it impacts care, and impact of distress on care is unknown. We examined the provision of survivorship care at the Lifespan Cancer Institute (LCI) to determine (1) clinical and distress thermometer scores (DTS) association with SCPs and SCVs; (2) impact of SCV visits on specialty referrals, and (3) demographic and clinical predictors of receipt of SCP and SCV. Methods: We retrospectively reviewed EMR records on 1,960 patients at LCI between 2014-2017 for SCPs and SCVs and extracted demographics, treatment variables, and distress scores. We used T-test or Wilcoxon rank test and Chi-square tests for evaluating the bivariate associations of SCP and SCV with continuous and categorical factors respectively. We fit logistic regression models to assess the adjusted effect of these factors on receipt of SCP and SCV independently. All analyses were performed in R v4.0.2. Results: The mean age was 63.9 (SD=11.8), 67% were female, 51.2% were married or partnered. Breast (38.8%), lung (17.6%), and prostate (13.7%) were the most common cancers. DTS were recorded in 64% with mean of 3.88(SD=3.05): distress was higher in women (4.36, SD=3.01), breast cancer pts (4.53, SD=3.07), gyn (4.22, SD=3.07), pancreatic (4.12, SD=3.41) and anal cancers (4.52, SD=3.47) and in those with Stage IV disease (5.33, SD=3.43). SCPs were completed in 740 (37.8%) patients and of those 65.9% had a SCV. SCV were associated with more specialty referrals for psychiatry, physical therapy, nutrition, and sexual health but not smoking cessation or fiscal services. DTS were associated with increased referral to psychiatry only. The adjusted models (table) showed odds of receiving a SCP were higher in those younger, and having breast cancer v all other cancers, with prostate having lowest odds. For receipt of SCV, odds were higher in those younger, female, and having breast cancer, with prostate and lung having the lowest odds. Conclusions: Gender, age and type of cancer are significant predictors of receipt of SCP and SCV. SCP and SCV patterns may represent patient preferences, but practice patterns and unconscious biases may also play a part suggesting areas for further research and outreach.[Table: see text]
Multifactorial analysis of cancer patients’ willingness for COVID-19 vaccination.
Authors: Kosmidis Paris A. , Lagogianni Christie , Kosmidis Thanos 
Published: June 2021

12062 Background: Public health authorities advocate vaccinations for the general population, including cancer patients and survivors. Since the onset of the COVID-19 pandemic, its vaccine has been eagerly awaited, but the extent of cancer patients’ willingness to get vaccinated is not clear. As health promotion is crucial for these individuals, it is important to measure and analyze their willingness to receive the vaccine. Methods: A few days after the regulatory approval for the first COVID-19 vaccine, the CareAcross online interactive platforms were used to evaluate the willingness of patients to get vaccinated. Through an online survey, within a few hours, 1106 cancer patients selected either “Yes, I plan to get the vaccine” or “No, I will not get the vaccine”. The patients were from the UK, Germany, France, Spain or Italy; they had been diagnosed with breast, lung, prostate or colorectal cancer. Their responses were analyzed to determine how their cancer diagnosis (including date, metastatic status, and other aspects), and their country of origin, affected their reported willingness to get vaccinated. Results: Overall, 70.6% of patients indicated willingness to get the vaccine (WTV), and 29.4% reported the opposite (NWTV). The strongest determinant of WTV was the patient’s country of origin: patients in the UK, Spain, Italy, Germany and France reported WTV of 84.1%, 64.2%, 58.7%, 47.4% and 38.3%, respectively. The next strongest determinant was the time elapsed since the patient’s diagnosis: for the largest population with available diagnosis date (451 UK patients), the average time since diagnosis for patients with WTV vs NWTV was: breast, 3.5 vs 2.5 years; lung, 1.6 vs 1.4 years; prostate, 2.4 vs 3.3 years; colorectal, 1.9 vs 1.5 years. Among patients from other countries with available diagnosis date: as the time since diagnosis increased, among 148 Italian patients WTV gradually increased; among 94 Spanish patients, WTV substantially decreased; among 85 French patients, WTV gradually decreased; among 50 German patients, WTV substantially increased. There was no significant correlation of WTV percentages with cancer type; metastatic status; triple negative vs non-triple negative among breast cancer patients; non-small cell vs small cell among lung cancer patients. Conclusions: Despite long-standing efforts of the scientific community for health promotion through the COVID-19 vaccine, a substantial percentage of cancer patients reported no willingness to get vaccinated. This appeared to depend on each patient’s country of origin, and the time elapsed since their diagnosis. This patient input was collected shortly after the first vaccine’s approval. With increasing evidence of efficacy and safety through more vaccinations of citizens and patients, willingness is expected to increase. We are in the process of conducting a follow-up survey to track these changes and update the results to be reportable during ASCO.
Treatment-specific risk of second malignancies in five-year survivors of diffuse large B-cell lymphoma.
Authors: Geurts Yvonne M. , Neppelenbroek Suzanne I.M. , So-Osman Cynthia , Vermaat Joost S.P. , van Spronsen Dick Johan , Plattel Wouter J. , de Weijer Roel J. , Verschueren Karijn M.S. , Zijlstra Josée M. , Koene Harry R. , Nijziel Marten R. , Schimmel Erik C. , Böhmer Lara H. , Ong Francisca , Visser Hein , van Kampen Daphne , Kersten Marie José , Aleman Berthe M.P. , Van Leeuwen Flora , Schaapveld Michael 
Published: June 2021

12072 Background: Due to the historically less favorable prognosis of diffuse large B cell lymphoma (DLBCL), the burden of second malignant neoplasms (SMNs) has been rarely studied in DLBCL survivors. However, radiotherapy and chemotherapy may increase SMN risk among DLBCL patients. Anthracyclines may increase the risk of hematological malignancies, but it is not clear whether they also increase solid cancer risk. Methods: We established a multicenter cohort of 2,384 5-year DLBCL survivors treated at ages 15-60 years with radiotherapy and/or immuno-chemotherapy between 1989 and 2012. Observed numbers of SMNs were compared with expected cancer incidence in the general population to compute standardized incidence ratios (SIRs), absolute excess risks (AERs, per 10.000 person-years) and cumulative incidence. Treatment specific incidence was compared with general population rates and assessed within the cohort using Cox regression. Results: Most DLBCL patients received alkylating agents (95%), anthracycline-containing chemotherapy (95%) or radiotherapy (61%); 46% received rituximab. Median follow-up was 13.3 years; 17% of patients was followed ≥20 years. In total, 308 5-year survivors developed an invasive SMN (SIR 1.6; 95% confidence interval (CI), 1.4 to 1.8), translating into 56.2 excess cancers per 10.000 person-years (see Table for specific sites). In 20-year survivors of DLBCL, the SIR was 1.8 (95% CI 1.3-2.6). The 20-year cumulative incidence of any SMN was 18.7% (95% CI 16.5-21.0%). The SIR for any SMN was higher in patients <40 years at first treatment (SIR ≤40 years: 2.8, SIR >40 years: 1.4; p<0.001). Treatment specific results will be presented at ASCO21. Conclusions: DLBCL survivors experience higher risk of SMNs than the general population. Identification of patients at increased risk could improve follow-up care.[Table: see text]