tbuckley/cabot-search huggingface dataset:
Abstract P352: The Anticancer mTOR-Inhibitor Temsirolimus Produces Left Ventricular Dysfunction in Murine Hearts
Authors: Carlo G Tocchetti, Carmela Coppola, Cristina Quintavalle, Antonio Barbieri, Domenica Rea, Giuseppe Palma, Marianna Gala, Antonio Luciano, Aldo Giudice, Nazareno Paolocci, Claudio Arra, Rosario V Iaffaioli, Gerolama Condorelli, Nicola Maurea
Journal: Circulation Research (2011)

Background: Cardiotoxicity is a major drawback and social problem linked to many anticancer treatments. Early identification of signs of this adversity would certainly benefit the management of oncologic patients. The mTOR-inhibitor temsirolimus is currently being evaluated for anticancer efficacy in hundreds of clinical trials and is approved for treatment of advanced renal cell carcinoma. However, the PI3K/Akt pathway converges on mTOR, which is a central regulator of cell growth, including cardiomyocyte growth. Here, we aim at evaluating the cardiac effects of the anticancer mTOR-inhibitor temsirolimus in a mouse model in vivo. Methods: Left Ventricular (LV) fractional shortening (FS) was assessed by M-mode echocardiography in sedated C57BL/6 mice (2–4 mo. old) at day 0, and after 2, 7, 14, 21 days from a single i.p. injection of temsirolimus (0.1mg/kg, a dose comparable to the one used to treat cancer in humans) or vehicle. Doxorubicin (Doxo, 2.17 mg/kg/day for 7 days) was used as a positive control. With Speckle Tracking echocardiography (ST) we also evaluated radial myocardial strain (%), a very sensitive parameter which can detect subtle changes in cardiac function. Results: After 2 days, there was no change in FS with temsirolimus, but FS was already reduced with Doxo: 52±0.2%, p=.0000001 vs sham (60±0.4%). With temsirolimus, FS was reduced only after 21 days: 50±3%, p=.009 vs sham. Interestingly, with Speckle Tracking echocardiography we found that in the temsirolimus group radial strain was already decreased at 7 days: 42±5%, p=.01 vs sham (59±1%). Conclusions: The antineoplastic mTOR-inhibitor temsirolimus induces LV dysfunction in mice. Such dysfunction occurs later than the one observed with Doxo, but speckle tracking echocardiography is more sensitive than conventional echocardiography and can detect early signs of myocardial alteration that may prelude to overt LV dysfunction. The clear mechanisms of temsirolimus cardiotoxicity are to be elucidated in further experimental studies. We also plan to apply speckle tracking echocardiography to clinical studies, in order to evaluate the impact of early identification of temsirolimus cardiotoxicity in the treatment of renal cell carcinoma.
Estimation of distribution of childhood diarrhoea, measles, and pneumonia morbidity and mortality by socio-economic group in low-income and middle-income countries
Authors: Angela Y Chang, Carlos Riumallo-Herl, Stephen C Resch, Stéphane Verguet
Journal: The Lancet Global Health (2017)

BackgroundVaccines are one of the most successful interventions in improving population health in low-income and middle-income countries (LMICs). In addition to the direct improvements in health outcomes, we are interested in their distributional effects—that is, whether vaccines promote or reduce health equity across socioeconomic groups. Empirical data on incidence and mortality of vaccine-preventable diseases across socioeconomic groups is not available. Therefore, we developed a method to estimate the distribution of childhood diseases and deaths across income groups and the benefits of three vaccines—for diarrhoea, measles, and pneumonia—in 41 LMICs.MethodsFor every country and disease (diarrhoea, measles, pneumonia), we estimated the distribution of cases and deaths that would occur in each income quintile had there been no immunisation or treatment programme, using both the prevalence and relative risk of a set of risk and prognostic factors. Building on these baseline estimates, we assessed the effect of three vaccines (first dose of measles vaccine, pneumococcal conjugate vaccine, and rotavirus vaccine) under five scenarios based on sets of quintile-specific immunisation coverage and uptake of disease treatment.FindingsBecause the prevalence of risk factors is higher in the poorest two quintiles than in the rest of the population, more disease cases and deaths would occur in the poorest two quintiles for all three diseases when vaccines or treatment are unavailable. However, we noted that current immunisation coverage and treatment utilisation rates have resulted in greater inequity in the distribution of cases and deaths. Even if in absolute terms the poorest quintiles benefit more from vaccines, the wealthier two quintiles sees a higher percentage decrease in cases and deaths. Thus, in terms of overall distribution of remaining cases and deaths with vaccine coverage, the poorest quintiles would see a higher comparative burden of disease than they would without vaccine coverage. Country-specific context, including how the baseline risks, immunisation coverage, and treatment utilisation are currently distributed across quintiles, affects how different policies translate to improvements in the distribution of cases and deaths.InterpretationOur analysis highlights several factors, including risk and prognostic factors, and vaccine and treatment coverage that would substantially contribute to the unequal distribution of childhood diseases, and we found that merely ensuring equal access to vaccines will not reduce the health outcomes gap between income quintiles. Such information can inform policies and planning of programmes that aim to improve equitable delivery of healthcare services.FundingBill & Melinda Gates Foundation.
Annals Story Slam - Harry and the Dreaded Hat
Authors: Mark Angelo
Journal: Annals of Internal Medicine (2017)

Web Exclusives4 April 2017Annals Story Slam - Harry and the Dreaded HatFREEMark Angelo, MDMark Angelo, MDFrom Cooper University Hospital, Camden, New Jersey.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0034 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Harry and the Dreaded Hat "Harry and the Dreaded Hat," by Dr. Mark Angelo (Duration 8:45)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Cooper University Hospital, Camden, New Jersey.Current Author Address: Mark Angelo, MD, Cooper University Hospital; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 April 2017Volume 166, Issue 7Page: SS1 ePublished: 4 April 2017 Issue Published: 4 April 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
The financial burden of cancer care: Do patients know what to expect?
Authors: Fumiko Chino, Jeffrey M. Peppercorn, James A Tulsky, Peter A Ubel, Deborah Schrag, Christel Rushing, Jonathan Nicolla, Ivy Altomare, Greg Samsa, Amy Pickar Abernethy, Yousuf Zafar
Journal: Journal of Clinical Oncology (2013)

6516 Background: Patients receiving cancer treatment can experience significant financial distress (FD), but little is known about whether patients are adequately informed about costs of care. Methods: This is a planned interim analysis of an ongoing cross-sectional study of insured adults with solid tumors on anticancer therapy for ≥1 month. Consecutive patients were surveyed, in person, at a referral center and 3 rural oncology clinics. Participants were asked about subjective FD (via validated measure), out-of-pocket costs, expected burden, and willingness to accept high out-of-pocket costs. Medical records were reviewed for disease and treatment data. Logistic regression assessed the relationship between FD, expected burden, quality of life (QOL), and willingness to accept high out-of-pocket costs. Results: Among 119 participants (85% response), median age was 60 years (range 27-86), 54% were men, 29% were non-white, 96% had completed high school, and 40% were retired. 81% had incurable cancer. Median income was $50,000/yr. Median out-of-pocket costs were $480/mo. 19% reported high/overwhelming FD. Median time on treatment was 200 days. Compared to anticipated levels of personal financial burden at the start of treatment, 40% were experiencing a higher degree of burden, 24% were experiencing a lower degree of burden, and 32% were experiencing the same degree of burden. In adjusted analyses, both high/overwhelming FD score (OR 4.79; 95% CI 1.64-13.95; p=0.004) and a lower QOL score (OR 0.81; 95% CI 0.67-0.99; p=0.035) were associated with a higher than expected financial burden. The following were not associated with higher than expected financial burden: age, gender, education, cancer stage, cost as a proportion of income, time on treatment, or willingness to accept high out-of-pocket costs. Conclusions: A large portion of insured patients faced out-of-pocket costs that were greater than expected. Those who were least prepared for financial burden reported higher FD and lower QOL. Since patient characteristics could not identify those at highest risk for unexpected cost burden, future research should focus on how to identify patients at risk and better prepare them for potential treatment-related financial burden.
Glioblastoma multiforme metastasis outside the central nervous system: Three case reports and possible mechanisms of escape.
Authors: Edwin Boelke, Christiane Matuschek, Lawrence E. Ginsberg, Sujit S. Prabhu, Wilfried Budach, Anne Hayman, Jackson Hamilton
Journal: Journal of Clinical Oncology (2013)

e13035 Background: Primary brain and central nervous system (CNS) tumor incidence is approximately 19 per 100,000 individuals per year in the United States (US) compared with 7 per 100,000 individuals worldwide. The most common intra-axial tumor is gliomas, which account for 32% of all primary CNS tumors and 80% of all malignant tumors of the CNS.The most common diffuse glioma is grade 4 astrocytoma (glioblastoma, GBM), which makes up 54% of diffuse glial tumors. GBM is also the most aggressive brain tumor with poor prognosis.GBM metastases outside the CNS are rare, so therapeutic experience with these types of tumors is limited. Methods: Herein, we present 3 GBM patients with extra-CNS metastasis. Results: One patient developed GBM metastasis in the lung and pleura 5 years after his GBM diagnosis had been confirmed. Another patient who underwent resection of the primary GBM developed disease that extended through the sphenoid to involve the orbit and skull and subsequently invaded the parotid gland and neck nodes 1 year after diagnosis. A third patient developed GBM metastasis in the skull and L5 vertebra 2 years after her primary brain tumor had been resected. Conclusions: The exact mechanism of GBM metastasis outside the central nervous system is not well understood but likely involves the invasion of structures such as bone, lymphatics, and vasculature, especially veins. Above-average survival time and repeated surgical intervention may place GBM patients at higher risk for these unusual metastases.
INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced esophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG).
Authors: Nick Pavlakis, David Goldstein, Katrin Marie Sjoquist, Andrew Martin, Eric Tsobanis, Sonia Yip, Jenny Shannon, Matthew E. Burge, Michelle F. Cronk, Niall C. Tebbutt, Andrew Strickland, Lara Rachel Lipton, Timothy Jay Price, Louise M. Nott, Dean Laurence Harris, Margot J. Burnell, Thierry Alcindor, Yung-Jue Bang, Yoon-Koo Kang, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2013)

TPS4157 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has a poor prognosis, and there is no established standard treatment following failure of first or second line chemotherapy (CT). Regorafenib (BAY 73-4506)(REG) is an oral multi-kinase inhibitor which targets kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-β, FGFR), and oncogenesis (RAF, RET and KIT), and has shown activity in other solid tumours. Following promising results in colon cancer and GIST, this study will determine if regorafenib has sufficient activity and safety to warrant further evaluation in a phase III trial as a second or third line therapy for AOGC. Methods: International (Australia &amp; New Zealand (ANZ); Canada (NCIC CTG), Korea) randomised phase II, double-blind, placebo-controlled trial with 2:1 (REG:placebo) randomisation and stratification by: (1) Lines of prior chemotherapy for advanced disease (1 vs. 2). (2) Geographic region. Eligible patients with histological confirmation of OGC, with measurable metastatic or locally advanced disease that is refractory to, or relapsed following, first or second line CT, will receive best supportive care plus 160mg REG or matching placebo orally on days 1-21 of each 28 day treatment cycle until disease progression or prohibitive adverse events. Primary endpoint is progression free survival (PFS). Secondary endpoints: PFS by baseline VEGF, response rate, overall survival, safety, quality of life and exploratory plasma angiogenesis and tissue growth factor biomarkers. 150 patients will be randomized in a 2:1 (REG:PBO) ratio. This will provide 90% power to detect a PFS rate at 2 months in the REG arm ≥ 66% versus &lt; 50%. If 16 of 33 (evaluable) REG participants have progressed by 2 months, then the study will be reassessed or stopped. Results: As of January 2013, 19 of 29 planned ANZ sites are open, with 10 patients enrolled. Regulatory approval has been received for 16 sites in Canada and 7 sites in Korea. 4 Korean sites have received ethics approval with recruitment expected to commence in early April 2013. Clinical trial information: ACTRN12612000239864.
Using cancer registry data to improve adherence with breast cancer pathways.
Authors: Karen K. Fields, Alicia Watson, Ashley Durand, Tracy Simpson, Sandra Stewart, JuQing Shi, Jack Liu, Dana Elise Rollison
Journal: Journal of Clinical Oncology (2017)

127 Background: Evidence-based clinical pathways have been shown to improve quality and cost effectiveness. Moffitt Cancer Center (MCC) has developed clinical pathways for more than 50 cancer sites. Using data derived from multiple sources, we performed a series of measurements of adherence to breast cancer (ca) pathways, provided clinician feedback and evaluated changes over time. Methods: We developed an automated method to evaluate pathway adherence for 1 st line systemic treatment (tx) recommendations using data from Stages I-IV analytic breast ca cases presenting to MCC for tx during calendar years (CY) 2013-2015. As a baseline, cases were manually audited for adherence in CY 2012. Data sources included Cancer Registry and electronic health record (EHR). A patient (pt) was considered “On” pathway if the correct tx, including relevant clinical trials, was administered based on various prognostic and clinical factors. Only pts who received all 1 st line systemic tx at MCC were included. Pts who refused txor had contraindications, non-applicable histologies or multiple primary cancers were excluded. The EHR was reviewed to assure the accuracy of “Off” pathway determinations. Results: A total of 3727 analytic breast ca cases were seen at MCC between CY 2012-2015; 873 met all criteria and were eligible for analysis. 80% was set as an institutional target for adherence. The following table displays yearly trends for pts “On Pathway” for all applicable chemotherapy, immunotherapy and hormonal tx. Conclusions: Cancer Registry and EHR data can be used to automate surveillance of pathway adherence creating a feedback loop to clinicians who can, in turn, improve adherence over time. [Table: see text]
Dose escalation of daily carboplatin concurrent with accelerated radiation by delayed concomitant boost for locally advanced head and neck cancer
Authors: K. S. Hu, M. Dietrich, B. Culliney, S. Malamud, J. Cotliar, D. Frank, T. Mirzoyev, I. Jules, M. Persky, L. B. Harrison
Journal: Journal of Clinical Oncology (2004)

5556 Background: Accelerated radiation by delayed concomitant boost (AFX-CB) and concurrent chemoradiation represent two major advances in head and neck cancer treatment; however, the optimal regimen has yet to be defined. We investigated escalating small daily doses of carboplatin prior to each fraction of AFX-CB. Erythropoietin (EPO) was initiated if hemoglobin (Hgb) fell below 12g/dl to minimize the impact of anemia. Methods: 24 patients (18 M: 6 F) with 2002 AJCC Stage II-IVb (15 unresectable and 9 resectable cancers deemed to require total laryngectomy) were treated with AFX-CB to 70Gy/6 weeks (BID RT last 2 wks) with daily doses of carboplatin escalating from 10 to 15mg and given within 1 hour prior to radiation. Dose-limiting toxicity (DLT) was defined as RTOG acute grade(Gr)4 mucositis or NCI Gr 2 hematologic toxicity. Nine patients received EPO. Results: 92%(22/24) completed a full course of chemoradiation. Median treatment time was 43 days (35–46 days). Ten patients were treated at 10mg/day, 12 at 12.5mg and 2 at 15mg. MTD has not been reached. No patient experienced Gr 4 mucositis while Gr2 hematologic toxicities were as follows: leukopenia: 2 pts; anemia:1 pt and thrombocytopenia: 0 pts. EPO raised Hb levels by a median increment of 1.4 g/dl (00.2–3.0g/dl) and above 12g/dl in 7 of 9 pts. Acute Gr 3 toxicities were as follows: 1) mucositis: 54%, 2) dermatitis: 4%. Median weight loss was 2% (0–12%). At a median followup of 11 months, crude local control (LC) was 60% (9/15) among unresectable cancers and 89% (8/9) for organ preservation patients. Actuarial 1 yr LC was 72% and 86%, respectively. Crude overall survival (OS) was 53% (1yr OS 73%) and 100% (1 yr OS 100%), respectively. Conclusions: The addition of carboplatin to AFX-CB is well tolerated up to daily doses of 15mg. Among organ preservation patients, none experienced a DLT; however, no further dose-escalation is planned due to excellent organ preservation rates at tested levels. Dose-escalation will continue for unresectable patients whose outcomes are comparable to other reported experiences. EPO can effectively correct mild anemia during chemoradiation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Ortho Biotech; Bristol-Myers Squibb
Association between caring for a high proportion of older patients and adhering to standard care for younger patients.
Authors: Satoru Kamitani, Tomone Watanabe, Momoko Iwamoto, Takahiro Higashi
Journal: Journal of Clinical Oncology (2017)

41 Background: Multiple comorbidities and physiologic decline often prevent older patients from receiving the same standard care provided to younger patients. Therefore, providers who mainly treat older patients may become accustomed to not adhering to standards and thus might be less likely to provide standard care to younger patients. In this study, we compared the care provided to younger patients between facilities that care for a large number of elderly patients and those that treat relatively few older patients. Methods: We used a nationwide registry-linked claims database of 297 hospitals. Among the quality indicators (QIs) we formerly developed, we selected 2 and 3 QIs for lung cancer and gastric cancer, respectively, based on the variation in adherence across facilities. Facilities were divided into 2 groups based on the proportion of older patients (≥75) with each cancer type. We then compared the QI adherence in treating patients younger than 60 years old between the groups. The difference in adherence to standards of care (quality scores) between the 2 groups of facilities was assessed by using a logistic regression model adjusting for patient age and sex. Results: We analyzed data for 6,708 patients with lung cancer and 26,470 patients with gastric cancer. Respective quality scores for facilities with more older patients versus facilities with fewer older patients were 63.4% versus 66.1% (p=0.439) for the EGFR mutation test before the first chemotherapy among stage IV lung adenocarcinoma patients; 63.2% versus 52.5% (p=0.238) for concurrent chemoradiotherapy (CCRT) for localized small cell lung carcinoma patients; 51.6% versus 46.9% (p=0.229) for HER2 test before the first chemotherapy among patients with unresectable gastric cancer; 81.8% versus 79.7% (p=0.354) for Helicobacter pylori test on patients with gastric cancer who had ESD/EMR; and 60.9% versus 60.7% (p=0.948) for adjuvant chemotherapy within 6 weeks among pathological stage II/III gastric cancer patients. Conclusions: Caring for a high proportion of older patients is not associated with diminished provision of standard care to younger patients.
Are women satisfied after prophylactic mastectomy
Authors: A. M. Geiger, C. N. West, A. I. Liu, G. Wolde-Tsadik
Journal: Journal of Clinical Oncology (2004)

6048 Background: Bilateral prophylactic mastectomy in women with increased breast cancer risk and contralateral prophylactic mastectomy in women with unilateral breast cancer dramatically reduce the risk of subsequent breast cancer. However, little is known about long-term satisfaction with the procedure and related quality of life outcomes. Methods: We mailed surveys to 816 women with bilateral or contralateral prophylactic mastectomy done at six health maintenance organizations between 1979 and 1999. The survey included validated measures of satisfaction, quality of life and concern about breast cancer. The first survey mailing included a $5 cash incentive. Nonrespondents received a second survey mailing and a telephone reminder call. Results: We received completed surveys from 661 (81%) women in our sample; 115 women with bilateral and 546 women with contralateral prophylactic mastectomy. For women with bilateral prophylactic mastectomy the mean age at survey was 57 and the mean years since procedure was 12. For women with contralateral prophylactic mastectomy the mean age at survey was 61 and the mean years since procedure was 10. Over 80% of respondents indicated they are very satisfied with their prophylactic mastectomy yet half remain very concerned about their breast cancer risk, with no differences between the two types of prophylactic mastectomy. Among women with bilateral prophylactic mastectomy 65 (61.3%) reported being quite a bit or very much satisfied with their quality of life, versus 391 (76.2%) of women with contralateral prophylactic mastectomy (chi square p=0.03). Younger women were less satisfied with their procedure and quality of life, and had more concern about their breast cancer risk. Results did not vary by time since procedure. Conclusions: Satisfaction and quality of life after bilateral and contralateral prophylactic mastectomy is high but not universal. Surprisingly, many women remain concerned about breast cancer despite undergoing a procedure that dramatically reduces their risk. These results may be useful for women considering prophylactic mastectomy and their clinicians, whose discussions should include clear information on risk reduction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration National Cancer Institute