bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic syndrome and breast cancer: Effects of a 16-week combined exercise intervention.
Authors: Dieli-Conwright Christina Marie , Tripathy Debu , Schroeder E. Todd , Mortimer Joanne E. , Bernstein Leslie 
Published: March 2020

TPS9648 Background: Current evidence suggests that breast cancer treatments such as chemotherapy lead to excessive weight gain, fatigue, physical inactivity, and negative alterations in components of metabolic syndrome (MetS). MetS is associated with increased risk of cancer recurrence, cardiovascular diseases and type 2 diabetes, and is defined by visceral adiposity, insulin resistance, hyperglycemia, hyperinsulinemia, low serum high-density lipoprotein cholesterol, and hypertension. MetS is highly prevalent and present in 25% of American and European adults and higher in minorities. Given that chemotherapy for breast cancer induces many of the components of MetS, an effort to offset these consequences of cancer therapy using exercise/lifestyle intervention could improve breast cancer, cardiovascular and endocrine outcomes. Methods: Our study seeks to determine whether a 16-week exercise intervention induces changes in prognostic components of MetS (waist circumference, blood pressure, serum levels of glucose, insulin, lipids, C-reactive protein and HbA1c) among breast cancer survivors if initiated within 3 months of completion of chemotherapy or radiation therapy. We are currently recruiting women diagnosed with Stage I-III breast cancer from the USC Norris Comprehensive Cancer Center and Los Angeles County Hospital, which cares for a high proportion of minority/underserved patients. Participants are randomized to either the Control (usual care) or the Exercise group. The Exercise group participates in aerobic and resistance exercise sessions 3 times a week for 16 weeks supervised by an exercise specialist at the USC Clinical Exercise Research Center. At baseline and following the study period, all participants are tested for MetS components, muscle strength, body composition, bone density, cardiorespiratory fitness, quality of life, fatigue and shoulder function. We will recruit an additional 85 patients (at present time n=15) over the next 3 years. It is expected that this intervention will improve components of MetS and physical fitness in breast cancer survivors when compared to the Control group, thus defining intervention and biomarker variables for more definitive trials. Clinical trial information: NCT01140282.
Phase III clinical trials with anamorelin HCl, a novel oral treatment for NSCLC cachexia.
Authors: Abernethy Amy Pickar , Temel Jennifer S. , Currow David , Gleich Lyon L. , Friend John 
Published: March 2020

TPS9649 Background: Cancer anorexia/cachexia is a debilitating and life-threatening complication of an underlying malignancy that may develop in up to 80% of terminally ill cancer patients. Cancer cachexia has a multifactorial pathogenesis and is manifested by accelerated losses of skeletal muscle and disproportionate losses of lean body mass (LBM). Anamorelin HCl is a ghrelin receptor agonist that has demonstrated significant increases in LBM, physical strength, and body weight in Phase II trials in patients with cancer cachexia. Through its ghrelin and growth hormone secretagogue activity, it displays both anabolic and appetite stimulating properties – two aspects vital to treating cancer anorexia/cachexia. Methods: HT-ANAM-301 (NCT01387269) and HT-ANAM-302 (NCT01387282), also known as ROMANA 1 and ROMANA 2, are double-blind, placebo-controlled, randomized (2:1 anamorelin HCl vs. placebo) Phase III trials in patients with non-small cell lung cancer (NSCLC) cachexia. Eligible patients must have unresectable Stage III or IV NSCLC and cachexia (weight loss of ≥5% body weight within prior 6 months or BMI <20 kg/m2). Patients receive once daily oral doses of anamorelin HCl (100 mg) or placebo for 12 weeks. Co-primary endpoints are the change from baseline in LBM as measured by DXA and in muscle strength as measured by handgrip strength. Secondary endpoints include change in body weight, overall survival, and quality of life (FACIT-F and FAACT questionnaires). For HT-ANAM-301 only, blood samples are collected at Week 6 for population pharmacokinetics. After 12 weeks of treatment, patients may continue in a separate 12-week safety extension study (HT-ANAM-303 [ROMANA 3] NCT01395914). At their last meeting (August 2012), the Independent Data Monitoring Committee suggested no safety issue and allowed the trials to continue as planned. Clinical trial information: NCT01387269, NCT01387282, NCT01395914.
Management of muscle-invasive bladder cancer with bladder preservation in Russia: A survey-based analysis of current practice and the impact of an educational workshop on clinical expertise.
Authors: Dengina Natalia , Chernich Marina , Usychkin Sergey , Degnin Catherine , Chen Yiyi , Gladkov Oleg , Nosov Dmitry , Tsimafeyeu Ilya , Thomas Charles R. , Tjulandin Sergei , Mitin Timur 
Published: March 2020

10509 Background: Trimodality bladder preservation (BP) is an accepted alternative to radical cystectomy for patients with muscle-invasive bladder cancer (MIBC). The global utilization of BP is variable, and practice patterns have not been previously studied in Russia. During the Russian Annual Oncology Congress, organized by the Russian Society of Clinical Oncology in November 2018, our group has conducted a contouring workshop for Russian radiation oncologists (ROs). We sought to elucidate the contemporary practice patterns in Russia and determine the impact of this workshop on attitudes of Russian ROs towards BP. Methods: Pre- and post-workshop IRB-approved surveys were analyzed to determine baseline clinical experience and patterns of care among Russian ROs. The effect of the contouring workshop on participants’ knowledge and attitudes was performed using tests for paired nominal data. Results: We analyzed 77 pre-workshop and 32 matched post-workshop questionnaires. 56% (43 out of 77) of respondents treated MIBC patients with bladder-directed radiation therapy (RT). Of these, 40% (17 out of 43) treated only inoperable patients, and 60% treated both operable and inoperable MIBC patients. 14% offered RT alone to their patients, while the rest offered concurrent chemoRT. 63% (26 out of 41) offered suboptimal concurrent systemic agents, such as single agents carboplatin or paclitaxel. 63% of respondents felt that BP can only be done in specialized centers with established expertise, but only 10% felt uncomfortable offering an MIBC patient a BP option in their clinic. Prior to workshop, 40% of respondents estimated universal poor bladder and erectile functions after BP. The workshop resulted in dramatic change in participants’ attitudes towards BP long-term urinary (Stuart-Maxwell-test, p < 0.01), and sexual (exact McNemar test, p < 0.01) side-effects. Prior to workshop, only 52% of respondents routinely discussed smoking cessation (SC) with their patients, whereas after workshop almost 90% agreed that SC discussion is mandatory (exact McNemar test, p = 0.04). Conclusions: Bladder preservation is commonly used in Russia in the management of MIBC patients. Our contouring workshop resulted in dramatically improved understanding of long-term BP toxicities and inspired Russian ROs to incorporate smoking cessation counseling into routine clinical practice. International educational efforts are critical to improve multi-disciplinary management of MIBC patients.
Molecular profiling (MP) for malignancies: Knowledge gaps and variable practice patterns among United States oncologists (Onc).
Authors: Singh Bhavana Pendurthi , Britton Susan Lynne , Prins Petra , Yin Chao , Lankford Maria L. , Willey Joanne P. , Buettner Arden , Tiscione Brynn , Scharf Mitchell , Blancato Jan , Marshall John 
Published: March 2020

10510 Background: Clinically impactful therapies for malignancies require the identification of specific molecular alterations. Onc must be aware of these targets and how to interpret them to provide optimum care. The use of MP has become the standard of care for many cancers, and is recently FDA approved. Using 2 data sets, we assessed the current awareness and incorporation of MP in the treatment of cancer; comparing data from community based Onc (C) to academic Onc (A). Methods: C consisted of 292 physicians polled using an audience response system during 6 case-based research events across the US. Questions focused on various aspects of molecular testing. Data for A was obtained from a chart review focused on timing and extent of MP in disease specific academic practices (lung, breast, GI) (N = 59). Results: Within C, 257 (88%) were Onc from community-based practices. The frequency at which Onc ordered MP significantly varied depending on tumor type; 33% in lung cancer (LC), 18% in colorectal cancer (CRC) and less commonly in breast cancer (BC) (8%). In A, MP was ordered more frequently; 74% in LC, 27% in CRC and 0% in BC. These results reflect a gap in practice among community versus academic Onc, as C had lower utilization of MP for both LC and CRC. In C, Onc were also asked to match the molecular alteration with the appropriate targeted therapy. Onc incorrectly matched the molecular alteration to the targeted therapy or marked unknown in up to 69%. This reflects a large knowledge gap among community Onc with regards to the correct application of MP to currently FDA approved targeted therapies. Conclusions: Given the significant knowledge and practice gap, we conclude there is an urgent need for focused educational activities that facilitate improved knowledge of MP and corresponding personalized therapeutic strategies for Onc in the US.
Collaborative learning workshops to optimize integration of cancer immunotherapies in the community setting.
Authors: Shivakumar Latha , Perloff Tara , Lucas Lorna 
Published: March 2020

10535 Background: The expanding armamentarium of immunotherapies available to treat patients with cancer poses a challenge to community practitioners. They need guidance around the practical issues that they must navigate to provide immunotherapy safely and effectively in their own communities. Methods: The Association of Community Cancer Centers (ACCC) implemented collaborative learning workshops focused on best practices for implementing cancer immunotherapies in the community setting with respect to care coordination, monitoring and management of immune-related adverse events (irAEs), and access to care. The workshops were held between April and June of 2018 in community cancer centers. A multidisciplinary steering committee including two medical oncologists, an oncology nurse, and an oncology pharmacist, led this initiative. The workshops started with a 45-minute open discussion section where the faculty posed questions to the learners to understand their specific institutional challenges. The faculty took cues from the initial discussion and focused the remainder of the education on addressing the challenges and barriers that were uncovered, rather than merely summarizing recent clinical data. The faculty discussed clinical case scenarios and presented clinical evidence for the various treatment decisions. At the end of the workshop, the instructors collaborate with the learners to draft an action plan for incorporating changes into their practice. Participants were surveyed at 3 and 6 months following participation in the workshop to report on the status of their action plans. Results: After participating in the workshops, almost 100% of the participants reported being confident in their ability to make changes in their practice. The responses of the participants to the post-activity assessment revealed a 11% relative increase in knowledge and competence and the participants were up to 14.7% more likely to receive evidence-based management with immunotherapies based on effect size calculations. At the 3-month follow-up, the participating sites had already implemented over 30% of the action items listed in their plans and at the 6-month follow-up, 100% of the action items drafted by learners were implemented as planned. Conclusions: The collaborative learning workshops were successful in inducing changes in knowledge, competence, and performance among the intended target audience of community oncology practitioners.
Phase II trial of gemcitabine (G) with pazopanib (P) or gemcitabine with docetaxel (T) in advanced soft tissue sarcoma (STS).
Authors: Somaiah Neeta , Van Tine Brian Andrew , Hill Elizabeth Goodwin , Milhem Mohammed M. , Schuetze Scott , Meyer Christian Frederick , Reuben Daniel Y. , Elias Anthony D. , Read William L. , Chawla Sant P. , Wahlquist Amy E. , Garrett-Mayer Elizabeth , Kraft Andrew S. 
Published: March 2020

11008 Background: P is a multi-tyrosine kinase inhibitor with efficacy in many sarcoma subtypes. We designed a trial to assess the benefit of adding P to G as an alternative regimen to the commonly used combination of G+T in pts with STS (NCT01593748). Methods: We performed an open-label, randomized phase 2 trial enrolling pts with advanced non-adipocytic STS who had received prior anthracycline based therapy. Pts were assigned (1:1 stratified randomization based on leiomyosarcoma and prior pelvic radiation) to receive G 1000 mg/m2 on days 1 and 8 with P 800 mg daily or G 900 mg/m2 on days 1 and 8 and T 100 mg/m2 on day 8, repeated q 3 wks. The primary objectives were estimating median PFS and rate of grade ≥3 adverse events (AEs). Secondary objectives included estimating the hazard ratio (HR) and response rates. Cross-over was allowed for RECIST progression. Sample size of 90 was derived based on the precision of 95% confidence intervals (CI) for reporting toxicity and PFS in each arm. Results: A total of 90 pts enrolled; 45 on each arm. Pt characteristics and results are detailed in Table. Median PFS was 4.1 months for each arm (p= 0.3, based on stratified log-rank test). The clinical benefit rate (PR+SD) was 29% for each arm (p>0.99, based on Fisher’s exact test). The rate of related grade ≥3 AEs were 20.6% with G+T and 19.9% with G+P. Related grade ≥3 AEs (%) occurring in ≥10% of pts (G+T; G+P): anemia (36, 20), fatigue (29; 13), low platelets (56; 51), low neutrophils (20; 49), AST increase (2; 13) and hypertension (2; 20). Conclusions: This study demonstrates comparable efficacy between G+P and G+T, suggesting that G+P can be considered for second-line therapy in advanced non-adipocytic STS. Pt Characteristics and Results. Clinical trial information: NCT01593748. [Table: see text]
A randomized phase II study of nivolumab monotherapy versus nivolumab combined with ipilimumab in advanced gastrointestinal stromal tumor (GIST).
Authors: Singh Arun S. , Chmielowski Bartosz , Hecht J. Randolph , Rosen Lee S. , Chow Warren Allen , Wang Xiaoyan , Brackert Sandra , Adame Carlos , Bovill John , Schink Elena , Douek Michael , Chantharasamee Jomjit , Wong Karlton , Eilber Frederick C. , Glaspy John A. 
Published: March 2020

11017 Background: Most GISTs are driven by mutations in KIT and PDGFRa and secondary mutations are felt to confer resistance to TKIs. In advanced/metastatic GIST, the benefit of second line TKIs and beyond is progressively less after imatinib failure. As such, novel non-TKI approaches are important to explore. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST refractory to at least imatinib were enrolled on a randomized, parallel group, unblinded Phase 2 trial of either nivo (240 mg Q2wks) or nivo (240 mg Q2wks) with ipi (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate(ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Imaging was assessed by investigator and 3 independent radiologists. Patients were randomized 1:1 and were restaged every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: At cutoff, 29 patients (27 evaluable) with a median of 3 (1-7) lines of prior therapies have started on trial. In the nivo only arm, 7/15 pts had a best response of SD for a CBR of 46.7% with the median PFS being 8.57 wks. In the nivo + ipi arm, 1/12 patients had a PR and 2/12 have SD for a CBR of 25.0% (95% exact C.I. 5.5%-57.2%) with a median PFS of 9.1 wks. 8 patients have been on therapy for more than 6 months and two patients with a KIT Exon 17 mutation had radiographic disease shrinkage. Most AEs were grades 1-2 with fatigue (37%) being the most common. 4 Grade 3/4 AEs occurred in the nivo and ipi arm (hyperglycemia, weakness, diarrhea x 2) and 4 grade 3/4AEs occurred in the nivo arm (DKA, hyperglycemia, rash, fatigue). Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, responses and disease control with both nivo and nivo + ipi were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.
Pathologic discordance in sarcomas: Prospective comparison of external and sarcoma center pathologic diagnosis.
Authors: Eckardt Mark A. , Graham Danielle S. , Singh Arun S. , Chmielowski Bartosz , Federman Noah , Kalbasi Anusha , Bernthal Nicholas M. , Bukata Susan V. , Hornicek Francis J. , Yanagawa Jane , Levine Benjamin D. , Motamedi Kambiz , Seeger Leanne L. , Eckardt Jeffrey J. , Eilber Frederick R. , Dry Sarah M. , Nelson Scott D. , Eilber Frederick C. 
Published: March 2020

11020 Background: With more than 80 different histologic subtypes, sarcomas are a unique pathologic challenge. As therapeutic decisions have become histology-specific, obtaining an accurate pathologic diagnosis is critical in guiding treatment decisions. The aim of this study is to determine the discordance between the diagnosis rendered by an external non-specialized pathologist and pathologic re-review by a specialized sarcoma pathologist at a high-volume sarcoma center. Methods: Patients who presented at the UCLA Multidisciplinary Sarcoma Conference (MSC) in 2017 that had a pathologic diagnosis from an outside facility were included in this study. All specimens underwent pathologic re-review at UCLA by an experienced sarcoma pathologist. The pathology was classified as concordant (identical diagnoses), minor discordance (difference with minor impact on prognosis/therapy) and major discordance (difference with significant impact on prognosis/therapy). Results: 1350 patients were presented at the UCLA MSC in 2017. Of the 635 new patients, 196 presented with an outside pathologic diagnosis and underwent pathologic re-review at UCLA. 44% (n = 87) were concordant, 22% (n = 43) had minor discordance, and 34% (n = 66) had major discordance. Major discordance included substantial discrepancies in histologic subtype (n = 24, 36%), benign/malignant mismatch (n = 23, 35%), diagnostic from non-diagnostic (n = 12, 18%) and major grading discrepancy (n = 7, 11%). Major discordance was most often seen in biopsies [needle (n = 27, 32%), incisional (n = 30, 44%)] as compared to resection (n = 9, 21%). Conclusions: 56% of external non-specialized sarcoma pathologic diagnoses were discordant from specialized sarcoma pathologist review, 34% of which were major discordances. Pathologic re-review of a presumed sarcoma by a specialized sarcoma pathologist is critical for both patient care and investigational studies. [Table: see text]
Depletion of mutant IDH1 impairs chondrosarcoma growth by downregulating integrins.
Authors: Li Luyuan , Hu Xiaoyu , Trent Jonathan C. 
Published: March 2020

11031 Background: chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers, including chondrosarcomas. These mutations lead to the inability of IDH to convert isocitrate into α-ketoglutarate (α-KG). Instead, α-KG is reduced into 2-hydroxyglutarate (D-2HG), an oncometabolite. We sought to determine the role of IDH1 mutation in the tumorigenesis of human chondrosarcomas by inactivating mutant IDH1 (mIDH1) using genetic approaches. Methods: we employed two human chondrosarcoma cell lines, JJ012 and HT1080 that carry endogenous IDH1 mutations. D-2HG levels were measured by tandem mass spectrometry. mIDH1 was knocked out via the CRISPR/Cas9 technique. Colony-forming ability and cell migration were evaluated using soft agar assay and Transwell assay, respectively. The effect of mIDH1 on chondrosarcoma growth was analyzed in murine xenograft models. RNA-seq from total RNA was performed to identify differentially expressed genes (DEGs) between the parental and knockout cells. The biological functions of DEGs were identified through Ingenuity pathway analysis. Results: we found that mIDH1 knockout almost completely depleted D-2HG production, dramatically inhibited colony formation by 35% - 60% in JJ012 ( p < 0.01) and by 40% - 80% in HT1080 ( p < 0.01), and significantly reduced the migratory cell numbers by around 40% in both cell lines ( p < 0.01). Moreover, we observed that loss of mIDH1 led to a marked attenuation of chondrosarcoma formation, whereby the mean volume of the tumors derived from mIDH1-knockout cells was approximately 30% of that of control tumors, in both cell lines (JJ012 and HT1080) ( p < 0.01). Interestingly, RNA-seq data showed a significant downregulation of integrin genes such as ITGA10, ITGA5 and ITGB5 in response to mIDH1 knockout (adjusted p < 0.001). These results were confirmed by qRT-PCR and Immunoblotting. Conclusions: our findings demonstrate that mutant IDH1 plays a vital role in chondrosarcoma tumor formation through aberrant activation of integrins.
Racial disparity in incidence and survival for gastrointestinal stromal tumors (GIST): An analysis of SEER database.
Authors: Ulanja Mark Bilinyi , Rishi Mohit , Beutler Bryce , Konam Kenneth , Sharma Mokshya , Ambika Santhosh , Gullapalli Nageshwara , Hinojosa Tomas 
Published: March 2020

11037 Background: Gastrointestinal tumors (GISTs) represent the most common mesenchymal tumors of the gastrointestinal tract. There has been limited data on GISTs incidence and survival disparities between ethnic groups. We assess disparities in incidence and survival among race in the United States in the era of available GIST histologic codes and treatment. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) database for GIST from 2002 to 2015, with diagnostic code 8936. Results: Of the 7,204 patients identified, 4,928 (68.4%) were White; 1,308 (18.2%) African American (AA) and 968 (13.4%) were classified as Other (American Indian/Alaskan Native, Asian/Pacific Islander). The overall incidence rate (IR) was 0.753 per 100,000. IR was highest among AA at 1.372/100,000, but 0.648/100,000 for Whites, 1.075/100,000 for Asians/Pacific Islanders and 0.276/100,000 for American Indians/Alaskan Natives. The GIST incidence was twice as high for AA as for Whites (Rate ratio [RR]: 2.12; 95% CI: 1.98-2.26; p<0.001). Lower proportion of AA underwent surgery as compared to white and Other. Median overall survival (OS) [116 months] and GIST specific survival (GSS) was significantly lower in AA as compared to White and Other. In multivariate Cox model, belonging to Other had better OS (adjusted hazard ratio [aHR]; 0.81, 95% CI: 0.69-0.95, P=0.011) for GIST, but no difference in prognosis and OS for AA and White [(aHR for whites; 0.93, 95% CI: 0.83-1.04, P=0.187), AA=reference]. Conclusions: Significant racial disparity in incidence and survival for GIST exists, and efforts should be made to bridge this gap and improve outcomes for all races. [Table: see text]