bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of glyoxalase-1 in trabectedin-resistant myxoid liposarcoma.
Authors: Simonetti Sonia , Iuliani Michele , Pantano Francesco , Ribelli Giulia , Napolitano Andrea , Santini Daniele , Tonini Giuseppe , Vincenzi Bruno 
Published: May 2020

e23566 Background: Glyoxalase-1 (Glo1) is involved in the detoxification of the endogenous reactive metabolite, methylglyoxal (MG), whose abnormal accumulation increases adduct levels and induce cell apoptosis. Previous studies demonstrated that increased Glo-1 expression was associated with cancer chemotherapy resistance. We performed bioinformatics analyses finding that Glo-1 mRNA over-expression was correlated with worse prognosis in patients affected by Soft Tissue Sarcoma (STS). On the bases of these evidences, we investigated the potential role of Glo1 expression as biomarker of tumor growth and drug resistance in STS. Methods: Trabectedin and MG cytoxicity was evaluated by MTT viability assay measured at spectrofluorometer. Apoptosis was analyzed by flow cytometry using Annexin V antibody and propidium iodide. Glo-1 expression analysis was performed by Western Blot using a mouse monoclonal anti-human Glo-1 antibody (NBP1-19015). Synergy analysis was calculated using Combenefit software and statistical analysis was performed by Student-t test using the program GraphPad-Prism. Results: As STS trabectedin resistant model, we used a myxoid-liposarcoma cell line (402-91 ET cells) that are not responsive to clinical doses of trabectedin contrary to the parental sensitive cell line (402-91 WT cells). Intriguingly, we found higher Glo-1 protein levels in 402-91 ET cells compared to 402-91 WT cells. The treatment of 402-91 ET cells with the specific Glo1 inhibitor S-p-bromobenzylglutathione cyclopentyl diester (BBGC), in combination with trabectedin (PharmaMar), significantly inhibited cell viability and increased apoptosis than trabectedin alone. In particular, the addition of BBGC reduced trabectedin EC50 (half-maximal effective concentration) from 20.4nM to 5.92nM in 402-91 ET cells, similar to that observed in 402-91 WT cells (4.92nM). To investigate if cell death was induced by MG accumulation following Glo1 inhibition, we evaluated 402-91 ET cell viability after treatment with different doses of MG in combination with trabectedin. The addition of MG restored sensitivity to trabectedin in 402-91 ET cells as well as BBGC. Conclusions: Our results highlight a new potential mechanism of trabectedin resistance mediated by Glo-1 over-expression. The use of the specific Glo-1 inhibitor, BBGC, restores trabectedin sensitivity in resistant cells leading to MG accumulation that, in turn, promotes cell death and apoptosis. These data provide a strong rationale to investigate Glo-1 inhibition strategy, in combination with trabectedin, in STS in vivo models.
Effect of beta blocker use in soft tissue sarcomas.
Authors: De Leo Edward , Hanayneh Wissam , Shah Chintan , Wang Yu , Lee Ji-Hyun , Close Julia Lee , Dang Nam H. 
Published: May 2020

e23571 Background: Soft tissue sarcomas (STS) are a rare, heterogenous group of cancers that tend to have a poor prognosis and few effective treatment strategies. Beta blockers (BB), in particular non-selective BB such as propranolol, have been shown to have an antitumor effect in different malignancies, including breast, colon, and angiosarcomas. The underlying mechanism is unclear but it is thought to be related to the inhibition of beta receptors on malignant cells, which leads to decrease in tumor vascularity and hematogenous spread. In this retrospective analysis, we examined the effect of BB on the outcomes of STS at a tertiary referral center. Methods: Adult patients from 2000 through 2019 with a diagnosis of STS with adequate follow up were included, and were divided into 2 groups: patients on BB at any point during treatment and/or up to 6 months prior to diagnosis, and patients without BB. The patient and tumor data were extracted and analyzed. The primary outcome was overall survival (OS). Statistical methods included descriptive analysis, univariable and multivariable Cox proportional hazard regression analyses and Kaplan-Meier survival plots. Results: 448 patient charts were analyzed. Median age at diagnosis was 55 (range 18-89). 54% were male. 4.9% of patients were diagnosed with stage 4 disease. Histologies included: undifferentiated pleomorphic sarcoma 26.1%, leiomyosarcoma 10%, synovial sarcoma 9.2%, liposarcoma 7.8%, osteosarcoma 2.7%, Ewing sarcoma 2% and others 42.2%. 18.1% of patients were on BB during treatment, with metoprolol the most commonly used (59%). 96% of patients on BB had HTN and 44% had coronary artery disease. Patients on BB were less likely to receive adjuvant therapy (18% vs 26%). Patients on BB were more likely to have stage 4 disease at presentation (9.9% vs 3.8%). Multivariate analysis showed there was no significant difference in overall survival between patients on BB and those not on BB, HR 1.3 (CI 0.8-2.1, p = 0.24). Conclusions: There is no difference in overall survival in patients on beta blockers during treatment for STS after controlling for stage, comorbidities, smoking, and age. Further studies are needed to evaluate the effect of specific beta blocker drugs on soft tissue sarcoma outcomes.
Qualitative patient interviews on symptoms and impacts in metastatic synovial sarcoma (mSS).
Authors: Becker Brandon , Eliason Laurie , Culver Kenneth W. , Arbuckle Rob , Francis Anya , Pokras Shibani 
Published: May 2020

e23576 Background: Synovial sarcoma (SS), a soft tissue sarcoma, is a rare and aggressive malignancy, with significant morbidity and mortality associated with mSS. There are currently no patient-reported outcome (PRO) instruments specific to mSS patients and little qualitative research to understand impacts on mSS patients’ health-related quality of life (QoL). The objective of this study was to characterize the symptoms and impacts experienced by mSS patients to inform the selection of content-valid PRO instruments for use in investigational trials in mSS patients. Methods: This was a non-interventional, qualitative interview study of adult participants in the United States (US) with physician-confirmed mSS. Participants were consented from a large private practice in the US. Six semistructured concept elicitation interviews (60–90m by telephone) were conducted by trained interviewers. Participants were asked to describe their mSS symptoms and their impact on functioning in an open-ended fashion with follow-up probes. Verbatim transcripts were analyzed using thematic analysis methods and Atlas.Ti software. Socio-demographics and clinical characteristics were collected by the site. The study received Institutional Review Board (IRB) approval from Western IRB. Results: Among the 6 participants, average age was 45y (range 21–61y) and 2 were female. All 6 participants had pulmonary metastasis, 1 participant had a liver metastasis, and 1 participant had a mediastinal mass. The most common symptoms participants spontaneously identified were pain (n = 6), fatigue (n = 6), coughing (n = 5, with 2 upon probing), shortness of breath (n = 4), phlegm/mucus in the lungs (n = 3), coughing up blood (n = 2), and gastrointestinal complications (n = 2). Nerve/shooting/burning pain (n = 5) was mentioned upon probing. Participants also reported impacts of their disease on sleep (quantity and quality) (n = 6), physical activity (n = 6), social life (n = 6), daily activities (n = 5), emotions (n = 5), loss of appetite (n = 3), and finances (n = 1). Although not spontaneously reported, global ratings of overall health and QoL were considered relevant by all participants. Conclusions: This is the first study to identify patient-relevant symptoms and impacts associated with mSS. Further interviews with additional participants are ongoing, and we will analyze these data to identify appropriate PRO instruments for use in investigational trials in mSS patients. Funding: GlaxoSmithKline (209386).
End-of-life care in the immune checkpoint inhibitor era.
Authors: Buckenheimer Alyssa , Dothard Andy Shipe , Russell Gregory , Grey Carl , Petty William J. , Lycan Thomas 
Published: May 2020

e24003 Background: Immune checkpoint inhibitors (ICI) can lead to durable responses in some patients with advanced non-small cell lung cancer (NSCLC) with less toxicity than chemotherapy. However, ICI can cause idiosyncratic adverse effects and radiographic responses can be difficult to interpret, making prognostication difficult and potentially impeding a timely transition to hospice. Our purpose was to explore end of life (EOL) outcomes in NSCLC patients treated with ICI. Methods: Retrospective data were collected on all patients with NSCLC started on ICI at single center (2014-2018) and who died before last known follow-up. EOL outcomes included hospitalizations, ICU admissions, timing/location of hospice referral and death. Charts were reviewed to identify barriers to hospice referrals or enrollment. Outcomes were compared to published data of similar cohort (2008-2010) from same institution treated with chemotherapy. Results: Out of 143 patients who died, 83 (58%) had internal hospice referral by cancer center; 15 (11%) were referred by external provider. Hospitalization frequency was associated with higher likelihood of internal hospice referral (p 0.04). Internal hospice referral was not associated with differences in age, sex, race, ethnicity, smoking history, cancer subtype, treatment response/toxicity, or overall survival. Internal hospice referral was associated with decreased rates of death on the hospital floor (p < 0.001) and the intensive care unit (ICU, p < 0.001). When compared to chemotherapy cohort, there was similar rate of hospice referral (68% vs. 74%, p 0.33) but higher rates of starting new systemic therapy within 30 days of death (17% vs. 6%, p 0.001) and last dose within 14 days of death (13% vs. 5%, p 0.005). Other EOL outcomes (hospitalization frequency, death in ICU) were similar, although ICI cohort trended towards a lower rate of death on the floor than chemotherapy cohort (16% vs. 25%, p 0.06). Barriers to hospice referral were not well documented by providers but lack of family support for home EOL care was a common reason patients declined hospice. Conclusions: ICI was associated with a higher rate of systemic treatment at EOL as compared to a historical chemotherapy cohort, although the rates of hospice referral and other outcomes were similar.
Predictive role of Vulnerable Elders Survey-13 screen tool for elder cancer patients in final oncology treatment plan.
Authors: Almugbel Fahad , Timilshina Narhari , AlQurini Naser , Jin Rana , Berger Arielle , Romanovsky Lindy , Puts Martine , Loucks Allison , Alibhai Shabbir M.H. 
Published: May 2020

e24020 Background: The Vulnerable Elders Survey (VES-13) is one of several tools that can identify older patients who are vulnerable (if the score is ≥ 3 out of 10) and more likely to benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cutpoint of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive scores (7-10) will have a higher likelihood of a change in the final oncologic treatment plan compared to low positive patients (score 3-6). Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment (solid tumor and lymphoma) in the geriatric oncology clinic at the Princess Margaret Cancer Centre from June 2015 to June 2019. Various VES-13 score cutpoints were compared with the final treatment plan to identify those individuals whose treatment was modified after CGA. Area under the curve was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by type of patient. Results: 386 patients with mean age 81, 58% males were included. Gastrointestinal cancer was the most common site 31% and 60% were planned to receive curative treatment. The final treatment plan was modified in 50% with VES-13 scores 7-10, 46.7% with scores 3-6 and 26.8 % for scores < 3 (P = 0.002; Table). The optimal VES-13 cutoff was between 3-6 (C-statistics 0.57-0.59).The VES-13 performed similarly in those considering local treatment (surgery with/without radiation) vs. chemotherapy. Modified final treatment for local therapy with VES-13 scores < 3 was 11.4 % compared to 42.9% with scores ≥ 3 was 42.9% (p-value < 0.001), whereas for systemic therapy it was 32.4% and 62.5%, respectively (p-value = 0.002). Conclusions: Although high positive VES-13 scores (7-10) had slightly higher likelihood of having the final oncologic treatment plan modified, there was no strong advantage compared to the conventional cutpoint of 3 or higher. The VES-13 performed similarly in predicting treatment change after CGA for local and systemic treatment plans. Further studies are required to identify the optimal frailty screening tool and cutpoint. [Table: see text]
Enhancing safety of exercise for individuals with bone metastases: Screening recommendations developed through Delphi consensus process.
Authors: Campbell Kristin L. , Weller Sarah , Cormie Prue , Lane Kirstin N. , Rauw Jennifer Marie , Goulart Jennifer 
Published: May 2020

e24042 Background: Exercise has been shown to improve physical function and quality of life in individuals with bone metastases. To facilitate better integration of exercise services into clinical care for these more complex patients, the purpose was to understand the current views of an expert panel on the appropriate exercise screening approach for adults with bone metastases. Methods: Physicians, physical therapists and exercise physiologists with clinical or research expertise in providing medical and/or exercise advice to individuals with bone metastases were identified. A 3-round modified online Delphi survey was used to establish a consensus, with a priori consensus set to 70%. Results: Response rates were 68% (73/107), 81% (59/73) and 97% (57/59) for each Delphi round. Key consensus points were: a) medical guidance (i.e. communication and medical information from a physician) is recommended prior to commencing structured exercise for all individuals with bone lesions (90% consensus) and is required when individuals present with bone pain, have received past medical treatment for bone pain, or have a history of disease-related fractures (90% consensus); b) the primary objective of exercise professionals for seeking medical guidance is to obtain medical information (e.g., bone scan reports) to guide clinical decision making for exercise prescription (93% consensus) and for bi-directional communication (i.e., for overall patient care and safety) (75% consensus) versus requiring a direct referral from a physician for liability coverage (39% consensus); c) the physician group that exercise professionals most commonly approach for medical guidance are medical oncologists (84% consensus) or radiation oncologists (63% consensus) compared to primary care providers (33% consensus), orthopedic surgeons (40% consensus) or physiatrists (16%); d) as part of pre-exercise screening by an exercise professional, information should be collected on the number, location and type of bone lesion(s), level of bone pain and any other bone-related symptom (100% consensus). Conclusions: This represents the current views of a range of physicians, physical therapists, exercise physiologists and researchers who provide medical and/or exercise advice to adults with bone metastases. These findings will inform the work of the International Bone Metastases Exercise Working Group to establish the first exercise guidelines for adults with bone metatases.
Self-reported memory problems in adult-onset cancer survivors in the United States with or without: Type 2 diabetes mellitus, hypertension and hyperlipidemia.
Authors: Thimothee Valerie , Kendall Alexis , Perez Ashley , Friar Elora , Rothman Catherine , Carpenteiri Francesca , Winters Paul , Robinson Temple , Jean-Pierre Pascal 
Published: May 2020

e24062 Background: Cancer and chronic diseases (CD) are independent predictors of cognitive dysfunction, especially memory problems that can impact patients’ psychosocial functioning and quality of life. We examined the prevalence of memory problems in cancer patients with or without CD, including Type 2 Diabetes mellitus (DM), hypertension (HTN) and hyperlipidemia (HLD). Methods: We examined data from people who completed the US National Health and Nutrition Examination Survey from 2009 to 2016 to determine the prevalence of memory problems in cancer survivors vs. non-cancer survivors with and without a history of CD. Participants answered the ‘yes’ or ‘no’ question: “Are you limited in any way because of difficulty remembering or because you experience periods of confusion?” History of Cancer, DM, HTN and HLD were self-reported. We used Rao-Scott Modified Chi-Square Test (X2test) for cross-classified categorical data from complex sample survey. Age, sex, race-ethnicity, education, poverty, and general health were controlled using logistic regression. Results: The sample included 21813 adults, ³ 20 years old, and ≈52% female. There were 40% Whites, 22% Blacks, 25% Mexican American/Other Hispanics, and 13% other race/multi-racial. About 46% graduated high School/had a GED (21.2%) or completed less than high school (24.4%). Of those with cancer ( N= 2025), memory problems were associated with DM (17.72%; X2test, p= 0.003) and (HTN, 13.42%; X2test, p= 0.007), but not HLD (11.66%; X2test, p= 0.786). Of those without cancer, memory problems were associated with DM, HTN and HLD (all p< 0.0001). Prevalence of CD was much greater in cancer survivors with memory problems ( p< .05). Conclusions: Strategies to mitigate memory problems in cancer survivors should consider the implications of DM, HTN and HLD, particularly given the prevalence of these chronic morbidities in cancer populations.
Hypothyroidism and its impact on outcomes in head and neck cancer.
Authors: Srinivas Sujay , Noronha Vanita , Patil Vijay Maruti , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar 
Published: May 2020

e24066 Background: Hypothyroidism is a known late side effect of chemo-radiation in head and neck cancer. Hypothyroidism has been known to be associated with improved outcomes in renal cell carcinoma. Whether such a phenomenon exists in head and neck cancer is unknown. Methods: We performed a phase 3 study evaluating the role of Nimotuzumab in head and neck squamous cell cancers (HNSCC). In this study adult HNSCC patients treated with Cisplatin and radiation were randomly assigned to receive Nimotuzumab or not. The data of this study has been utilized for this analysis. Hypothyroidism was defined as TSH level more than 4.95 U/L. The cumulative incidence of hypothyroidism and its impact on PFS (progression free survival), OS (overall survival) and loco-regional control (LRC) was evaluated using binary regression analysis. To study the impact of hypothyroidism in outcomes a landmark analysis was performed. Results: 176/536 patients analyzed developed hypothyroidism with a cumulative incidence of 33%. Hypothyroidism showed a favorable impact on PFS, OS and LRC. Median PFS was 19.5 months while median OS was 22.2 months in the euthyroid subgroup vs not reached (NR) for both in the hypothyroid subgroup. The respective hazard rates (HR) for PFS and OS was 0.37 (95% CI: 0.27 - 0.52) and 0.15 (95% CI: 0.11 - 0.23). The LRC was also better with its median duration being 39.2 months vs NR in the euthyroid and hypothyroid subgroups respectively; HR for LRC being 0.40 (95% CI: 0.28 - 0.58). Conclusions: Thus development of hypothyroidism is associated with improved outcomes in HNSCC in terms of LRC and survival.
Cancer survivors with multiple chronic conditions: A rising challenge—Trend analysis from National Health Interview Survey.
Authors: Jiang Changchuan , Wang Haowei , Wang Qian , Zheng Binbin , Shapiro Charles L. 
Published: May 2020

e24089 Background: Cancer survivors are disproportionally influenced by chronic/comorbid diseases, which were linked to more psychological distress, increased healthcare service use, higher medical costs, adverse clinical outcomes, and financial hardship in cancer survivors. However, the trend in chronic diseases remains unknown among cancer survivors. Methods: We conducted a population-based study using serial samples of the National Health Interview Survey (NHIS) from 2002 through 2018. The outcomes include hypertension, diabetes, stroke, coronary artery disease (angina pectoris, coronary heart disease, heart attack), other heart diseases, COPD (emphysema, chronic bronchitis in the past 12 month), hepatitis, arthritis, morbid obesity (BMI > 40 or BMI > 35 with obesity-related diseases), asthma attack within 12 months, weak/failing kidney, any liver disease. We included adults who 1) have a history of cancer for except non-melanoma skin cancer; 2) report outcomes of diseases. Multiple chronic conditions(MCC) were defined as three or more non-cancer chronic conditions. Multivariable logistics regression was used to estimate the annual percent change(APC) in prevalence from 2002 to 2018, using SAS 9.4 and accounting for the design of NHIS. Results: 30728 adult cancer survivors and 485233 adults without a history of cancer were included in the final analysis. We found increasing prevalence in hypertension, diabetes, kidney disease, liver diseases and morbid obesity from 2002 to 2018, and decreasing prevalence in heart diseases, COPD, and hepatitis. The prevalence of MCC increased significantly in cancer survivors from 23.6% in 2002 to 29.6% in 2018 (APC 0.9%, p trend < 0.01). This was especially evident in younger patients aged 18 to 44 (APC 4.4%, p trend < 0.01) and African-American patients (APC 2.2%, p trend = 0.01). Conclusions: Our findings suggest that comorbid illnesses, especially MCC, have become an emerging public health burden for cancer survivors, which requires attention and more effective risk factors interventions. Future studies are needed to identify a better strategy to modify risk factors and prevent long term comorbidities for cancer survivors. It is also important to call for public health planning given severe chronic diseases burden for this rapid-growing but vulnerable community.