tbuckley/cabot-search huggingface dataset:
Safety and tolerability of adjuvant dose dense chemotherapy in elderly patients with node-positive early breast cancer.
Authors: Vasilios Karavasilis, Dimitrios G. Pectasides, Christos A. Papadimitriou, Helen Gogas, George Kouvatseas, Christos Christodoulou, Angelos Koutras, George E. Pentheroudakis, Helena Linardou, Evangelia Razis, Gerasimos Aravantinos, Meletios A. Dimopoulos, George Fountzilas
Journal: Journal of Clinical Oncology (2013)

1093 Background: Intensive chemotherapy confers benefit to older and younger patients with early breast cancer (BC). We aim to characterize the feasibility and toxicity profile of adjuvant dose-dense chemotherapy (ADDC) in older women with early node positive (BC). Methods: Available data from women who received ADDC for BC within three randomized trials between 1997 and 2008 were retrieved from our electronic database. These trials included HE 10/97: epirubicin and cyclophosphamide, methotrexate and fluorouracil (CMF) with or without paclitaxel, HE 10/00: epirubicin and concurrent or sequential paclitaxel and CMF and HE 10/05: a sequential three arm study of epirubicin, paclitaxel and CMF compared with epirubin, CMF and either weekly paclitaxel or docetaxel. We identified women aged &gt;65 years and we looked at differences in tolerability and delivery of chemotherapy, toxicity, and treatment outcome. Results: From a total of 2,640 patients with a median age of 52 years, who received ADDC, we identified 453 patients (17%) &gt; 65 years, hormonal positive in 76%, all node negative. At least 90% of the planned doses were delivered in 37% of the elderly, compared to 49% of the younger patients (p &lt; 0.0001). Grade 3 and 4 hematological toxicity was observed in 32% of elderly patients compared to 21% of younger (p &lt; 0.0001). Febrile neutropenia occurred in 4.5% of elderly patients as opposed to 2% of younger (p &lt; 0.002). Elderly patients experienced more frequently grade 3 and 4 fatigue, mucositis and sensory neuropathy, though the incidence of these toxicities was relatively low (all p &lt; 0.0001). Relative dose intensities were significantly lower in elderly patients, mainly affected docetaxel and paclitaxel administration. Treatment discontinuation, regardless causality, was not different in both groups. At a median follow-up of 120 months, there was no significant difference in disease free survival. Conclusions: Elderly node positive BC patients treated with ADDC derive comparable clinical benefit as younger patients, mainly in the cost of increased risk of hematological toxicity. This should be taken into account in decision making and treatment individualization in high risk BC patients.
Efficacy and safety of epoetin beta 30,000 IU once weekly in patients with solid tumors and chemotherapy-induced anemia
Authors: P. Heras, A. Hatzopoulos, S. Karagiannis
Journal: Journal of Clinical Oncology (2006)

18620 Background: Anemia is common in patients receiving chemotherapy, causing a multitude of symptoms which have a major impact on quality of life (QoL). Epoetin beta rapidly increases hemoglobin (Hb) levels and improves QoL in anemic patients with a variety of tumors. In patients with lymphoid malignancies, once-weekly epoetin beta 30,000 IU has comparable efficacy to the three-times weekly 10,000 IU regimen (Cazzola et al. Br J Haematol 2003; 122: 386–393). Methods: This was a randomized, double-blind, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumors receiving chemotherapy. Adult patients with anemia (Hb levels &lt;11 g/dl) were randomized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks. All patients received oral iron supplementation. Hb levels, transfusion need and QoL (Functional Assessment of Cancer Therapy-fatigue subscale score [FACT-fatigue]) were assessed at regular intervals. Results: Fifty patients were randomized; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly. Mean (± SD) increase in Hb from baseline to week 12 was 1.75 ± 2.15 g/dl in the 30,000 IU group (p = 0.008 vs baseline) and 1.04 ± 1.75 g/dl in the 20,000 IU group (p = non-significant). Hb response (increase in Hb level ≥2 g/dl from baseline) was observed in 78.3% of patients receiving epoetin beta 30,000 IU and 66.7% receiving epoetin beta 20,000 IU. Improvements in FACT-fatigue were significantly (p &lt; 0.001) correlated with increases in Hb level. Transfusion use was low during the study in both groups. Both epoetin beta regimens were well tolerated and there were no dose-dependent adverse events. Conclusion: Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anemia in patients with solid tumors. No significant financial relationships to disclose.
A case of checkpoint inhibitor-induced celiac disease
Authors: Dana Alsaadi, Neil J. Shah, Aline Charabaty, Michael B. Atkins
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immune checkpoint inhibitors (ICIs) have now become standard of care treatment for many malignancies. ICIs are associated with unique immune mediated adverse events (irAEs) due to dysregulation of immune activation. As treatment with ICIs is becoming more common, rare irAEs are also being recognized. Here we report a case of ICI-induced celiac disease. <h3>Case</h3> A 74-year-old Caucasian female with metastatic renal carcinoma received second line nivolumab (anti-PD1 antibody) after initial disease progression on sunitinib. Ipilimumab was added after she failed to respond to six cycles of nivolumab monotherapy. One week after her first cycle of combination treatment, she presented with nausea, vomiting, grade 1 diarrhea, and weight loss. She underwent endoscopy, which showed bile stasis in the stomach, normal appearing stomach mucosa, and nonbleeding erythematous mucosa in the duodenal bulb. Stomach biopsy showed moderate active chronic gastritis. Duodenal biopsy showed moderate chronic active duodenitis with focal neutrophilic cryptitis, mucosal erosions, villous atrophy, mildly increased intraepithelial lymphocytes, and moderate chronic inflammation in the lamina propria pathognomonic of celiac disease. Symptoms improved with gluten-free diet, twice-daily omeprazole and anti-emetics and she was able to continue on treatment. <h3>Conclusions</h3> There has been only one published case reporting ICI-induced celiac disease. Our case report highlights a rare irAE (celiac disease) associated with ICI treatment. It is unclear whether the patient had previously undiagnosed celiac disease or whether ICIs triggered her enteritis. Our patient was able to continue treatment with ICIs with dietary modifications, suggesting correct diagnosis is critical for optimal patient outcome.
Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC)
Authors: H. D. Brooks, B. Glisson, C. Lu, A. Sabichi, F. Johnson, L. Ginsberg, B. Bekele, V. Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2009)

6022 Background: Dasatinib is a potent inhibitor of src-family kinases, ephA2, PDGFR, Abl, and c-kit. A single-center, open-label, phase II trial was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of dasatinib in recurrent or metastatic HNSCC. Methods: Pts with measurable disease by RECIST, who received 0 or 1 prior regimen for recurrent or metastatic HNSCC with an ECOG performance status 0–1 and tumor tissue appropriate for IHC and FISH were eligible. Dasatinib 100 mg bid was given for 28-day cycles. Primary endpoints were 12-wk progression-free survival (PFS) and objective response rate (ORR). Pts who took at least 1 dose of dasatinib and who died or left study before 12 wks were counted as progressive disease (PD). A 2 stage design, closure after accrual of 15 pts was required if PFS was 45% or less and ORR was 0. Otherwise, planned accrual was 35. Response was assessed at 4 and 12 wks. PK was studied in pts receiving dasatinib per PEG. Biomarkers relevant to Src pathway were planned in tissue and blood. Results: Fifteen pts were accrued. To date, 13 pts are evaluable for response, and 15 pts for toxicity. No grade 3/4 hematologic toxicities were noted. Grade 2–4 nonhematologic toxicities(n): pleural effusion(2), nausea/vomiting(2), dehydration(1), diarrhea(1), dyspnea(1). Toxicity led to hospitalization of 4 pts and drug discontinuation in 5 pts. ORR was 0. One pt was stable at 12 wks (PFS: 7.6%). This pt stopped drug at 15 wks due to toxicity, but also had PD. One pt died on study and cause was deemed unlikely related. Conclusions: Dosed at 100mg bid, dasatinib led to a characteristic toxicity profile in this pt population. Rates of hospitalization and discontinuation for toxicity were fairly high. Final efficacy parameters are pending evaluation of 2 pts. Evaluation of PK and tissue/blood biomarkers is ongoing. No significant financial relationships to disclose.
Abstract MP71: Ten Year Predicted Cardiovascular Disease Risk in Young Women With Adverse Pregnancy Outcomes
Authors: Janet M Catov, Becky McNeil, Philip Greenland, Noel Bairey Merz, Deborah Ehrenthal, Corrette B Parker, William A Grobman
Journal: Circulation (2018)

Introduction: Cardiovascular disease (CVD) is the leading cause of death among women. In stark contrast to mortality declines in other groups, CVD deaths to young women are increasing. CVD prediction in this group is imprecise, and how adverse pregnancy outcomes (APO) may unmask risk during the reproductive years is unknown. Hypothesis: Women with APO will have higher 10-year predicted CVD risk within 7 years following a first pregnancy compared to women with no APO. Study design: We enrolled 10,038 women at 8 sites in their first pregnancy and followed 4,500 through a CVD visit 2-7 years later. Presented here are results for the first 2,705 with lab results and no hypertension or diabetes before pregnancy. The Atherosclerotic CVD (ASCVD), American Health Association Healthy Heart, Pathobiological Determinants of Atherosclerosis in Youth (PDAY), and Reynolds risk scores were compared in women with preterm birth (PTB), preeclampsia/gestational hypertension (PE/GH), gestational diabetes (GDM), small for gestational age (SGA), and no adverse outcomes (no APO, referent). Results: As expected, 10-year predicted CVD risk was very low in women at a median age of 30, although differences at the tail of the distribution were detected based on APO history. Women with no APO had the lowest CVD risk. Women with PTB, PE/GH, GDM, or SGA had higher 10-year CVD risk as predicted by the ASCVD score compared to women with no APO (p&lt;0.05 for PTB and PE/GH). Six to 10% of women with these APOs had ASCVD scores greater than 5%. The PDAY score that predicts risk of coronary artery calcification in young adults was also higher in women with PE/GH or GDM than in those with no APO. Risk factors perturbed after delivery in women with APOs were blood pressure, BMI, waist circumference, HDL-cholesterol, triglycerides, glucose, and HbA1c. Conclusion: While risk scores customized for women of reproductive age are needed, those with a first pregnancy complicated by PTB, PE/GH or GDM have modest but detectable predicted 10-year CVD risk as soon as 2-7 years after delivery.
Bias in reporting of endpoints of efficacy and toxicity in randomized clinical trials (RCTs) for women with breast cancer (BC).
Authors: Francisco Emilio Vera Badillo, Roman Shapiro, Alberto Ocana, Eitan Amir, Ian Tannock
Journal: Journal of Clinical Oncology (2012)

6043 Background: Phase III RCTs are designed to assess clinically important differences in endpoints that reflect benefit to patients. Accurate and unbiased reporting is essential to guide rational therapy. Here we evaluate the quality of reporting of the primary endpoint (PE) and of toxicity in RCTs for BC. Methods: PUBMED was searched from 1995-2011 to identify RCTs for BC. Scales for assessing bias in reporting of the PE and of toxicity were developed. For the PE, scales assessed whether the concluding statement of the abstract (CSAbs) was (a) based on the PE, (b) described appropriately a statistically positive or negative result for the PE, or (c) was based on secondary endpoints. Bias and completeness of reporting of toxicity was assessed using a hierarchy scale of whether reporting occurred in the CSAbs, elsewhere in the abstract, in the discussion of the article or only in the results. Association of bias with Journal Impact Factor (JIF); changes in the PE compared to protocol information in clinicaltrials.gov and funding source was also evaluated. Results: 164 trials were evaluated; 33% showed bias in reporting of the PE. The PE was more likely to be reported in the CSAbs if statistically significant [OR 5.2, 95% CI 1.9-14.3, p=0.001]. A statistically negative PE was not reported in the CSAbs in 27% of trials. Of the 30 trials where protocol information was available in clinicaltrials.gov, there were non-significant associations for the PE to show a positive result if had been changed, and for greater bias in reporting the PE if it was unchanged. 67% of studies showed bias in reporting of toxicity. Only 14% mentioned toxicity in CSAbs. When the PE was positive, bias in reporting of toxicity was more common [OR 2.0, 95% CI 1.0-3.9, p=0.04]. There was no apparent association between bias in reporting of either the PE or toxicity and JIF or funding source, but a non-significant association between change in the PE and industry funding. Conclusions: Bias in reporting of the PE is common especially for studies with a negative PE. Reporting of toxicity is poor especially for studies with a positive PE. Changing of the PE appears to be a strategy to increase the likelihood of observing a statistically significant result.
Multivisceral resections of gastrointestinal stromal tumors
Authors: Y. Zhou, C. Du, H. Fu, G. Zhao, Y. Shi
Journal: Journal of Clinical Oncology (2007)

20523 Background: Gastrointestinal stromal tumors (GISTs) with positive kit staining, although rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. We present our experience in the treatment of disease involving adjacent organs with multivisceral resections. Methods: The clinicopathologic records of twenty-two patients with multivisceral resection, among 170 patients suffered from GISTs treated in our hospital from 1994 to 2005, were retrospectively reviewed. Nine primary tumors originated from the stomach, 4 from the small intestine, 6 from the colorectum, 1 from abdominal cavity, and 2 from the retroperitoneal area. Meanwhile complete follow-up records were available in 15 patients with median 5-year follow-up. Results: The patients included 9 men and 13 women, from 36 to 77 year old. The largest tumor diameter ranged from 2 to 20 cm. The types of multivisceral operation comprised splenectomy (n=8), coloectomy (n=6), nephrectomy (n=5), partial hepatectomy (n=1), duodenectomy (n=1), oophorectomy (n=1), pancreatectomy (n=1), and adrenalectomy (n=1). None of lymph node metastatsis was found in 7 patients with lymph node dissection with gastric GISTs (n=5) or small intestinal GISTs (n=2). The involved organs confirmed by the pathologic diagnosis included kidney (n=2), spleen (n=2), pancreas (n=2), mesentery (n=1), and omentum (n=1). There was no perioperative mortality in this series. Among follow up patients, 9 were alive and 5 were died from the tumor recurrence or metastasis. Among them, one person with gastrectomy, pancreatectomy, adrenalectomy is still alive under 2 year follow-up by imatinib mesylate therapy postoperatively. Conclusions: Complete surgical resection with a negative gross margin by en bloc resection of the involved organs remains the standard treatment for non-metastatic GISTs. Imatinib mesylate represents a major breakthrough in the treatment of advanced GISTs and is the first effective systemic therapy for the disease. No significant financial relationships to disclose.
Toward Portable Artificial Kidneys: The Role of Advanced Microfluidics and Membrane Technologies in Implantable Systems
Authors: Bac Van Dang, Robert A. Taylor, Alexander J. Charlton, Pierre Le-Clech, Tracie Jacqueline Barber
Journal: IEEE Reviews in Biomedical Engineering (2019)

Globally, around 2.6 million people receive renal replacement therapy (RRT), and a further 4.9-9.7 million people need, but do not have access to, RRT [1]. The next generation RRT devices will certainly be in demand due to the increasing occurrence of diabetes, atherosclerosis and the growing population of older citizens. This review provides a comprehensive, yet concise overview of the cleared and remaining hurdles in the development of artificial kidneys to move beyond traditional dialysis technology-the current baseline of renal failure treatment. It compares and contrasts the state-of-the-art in `cell-based' and `non-cell-based' approaches. Based on this study, a new engineering perspective on the future of artificial kidneys is described. This review suggests that stem-cell-based artificial kidneys represent a long-term, complete solution but it can take years of development due to the limitations of current cell seeding technology, viability and complicated behaviour control. Alternatively, there is much potential for near- and medium- term solutions with the development of non-cell-based wearable and implantable devices to support current therapies. Based on recent fundamental advances in microfluidics, membranes and related research, it may be possible to integrate these technologies to enable implantable artificial kidneys (iAK) in the near future.
Effect of a Professional Coaching Intervention on the Well-being and Distress of Physicians
Authors: Liselotte N. Dyrbye, Tait D. Shanafelt, Priscilla R. Gill, Daniel V. Satele, Colin P. West
Journal: JAMA Internal Medicine (2019)

Burnout symptoms among physicians are common and have potentially serious ramifications for physicians and their patients. Randomized studies testing interventions to address burnout have been uncommon.To explore the effect of individualized coaching on the well-being of physicians.A pilot randomized clinical trial involving 88 practicing physicians in the departments of medicine, family medicine, and pediatrics who volunteered for coaching was conducted between October 9, 2017, and March 27, 2018, at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Statistical analysis was conducted from August 24, 2018, to March 25, 2019.A total of 6 coaching sessions facilitated by a professional coach.Burnout, quality of life, resilience, job satisfaction, engagement, and meaning at work using established metrics. Analysis was performed on an intent-to-treat basis.Among the 88 physicians in the study (48 women and 40 men), after 6 months of professional coaching, emotional exhaustion decreased by a mean (SD) of 5.2 (8.7) points in the intervention group compared with an increase of 1.5 (7.7) points in the control group by the end of the study (P < .001). Absolute rates of high emotional exhaustion at 5 months decreased by 19.5% in the intervention group and increased by 9.8% in the control group (-29.3% [95% CI, -34.0% to -24.6%]) (P < .001). Absolute rates of overall burnout at 5 months also decreased by 17.1% in the intervention group and increased by 4.9% in the control group (-22.0% [95% CI, -25.2% to -18.7%]) (P < .001). Quality of life improved by a mean (SD) of 1.2 (2.5) points in the intervention group compared with 0.1 (1.7) points in the control group (1.1 points [95% CI, 0.04-2.1 points]) (P = .005), and resilience scores improved by a mean (SD) of 1.3 (5.2) points in the intervention group compared with 0.6 (4.0) points in the control group (0.7 points [95% CI, 0.0-3.0 points]) (P = .04). No statistically significant differences in depersonalization, job satisfaction, engagement, or meaning in work were observed.Professional coaching may be an effective way to reduce emotional exhaustion and overall burnout as well as improve quality of life and resilience for some physicians.ClinicalTrials.gov identifier: NCT03207581.
Haploidentical Stem Cell Transplantation Attenuates the Prognostic Impact of FLT3-ITD in Acute Myeloid Leukemia
Authors: Jonathan Canaani, Myriam Labopin, Xiao Jun Huang, William Arcese, Fabio Ciceri, Didier Blaise, Giuseppe Irrera, Lucia Lopez Corral, Benedetto Bruno, Stella Santarone, Maria Teresa van Lint, Antonin Vitek, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Journal: Blood (2017)
The biochemical basis for cancer diagnosis by optical spectroscopy
Authors: James P. Freyer, Susan Carpenter, Anabel Guerra, Kurt Short, Pratima Kunapareddy, Judith R. Mourant
Journal: Cancer Research (2005)

5738  A very promising optical technique for non-invasive cancer diagnosis involves absorption or vibrational spectroscopy, typically either by fourier-transform infrared (FTIR) absorption or Raman scattering techniques. Although differences in optical spectra for normal and malignant tissues have been reported, there is little understanding of the underlying biochemical alterations that account for these spectral differences. One important cellular characteristic, which is often not considered in interpreting optical spectra of tissues or cells, is the cellular proliferative status. We have been using an in vitro, two-step rat fibroblast carcinogenesis model to directly address the biochemical basis for changes in both FTR and Raman spectra. Two different immortalized but non-tumorigenic cell lines derived from primary rat fibroblasts were compared with two tumorigenic cell lines produced by c-myc transfection of each non-tumorigenic cell line. Cells were cultured as monolayers and harvested either during exponential growth (proliferating) or at confluence (non-proliferating). Cell suspensions were analyzed by both FTIR and Raman spectroscopy under conditions that maintained viability of the cultures throughout analysis. The cell spectra were fit to a set of five basis spectra (protein, lipid, DNA, RNA and glycogen) in order to derive estimates of the biochemical composition of the cultures. Relative composition estimates from optical spectra were compared to protein, DNA, RNA and glycogen contents determined both by standard biochemical analysis and by flow cytometry. We found that the composition estimates from FTIR and Raman spectroscopy agreed very well, although both techniques had difficulty extracting relative amounts of DNA and RNA due to overlapping resonances and the fact that these are minor components of cells. The flow cytometric and biochemical analysis of the cultures also agreed well with estimates obtained from fitting optical spectra. The most diagnostic biochemical ratios that could be derived from the optical spectra were protein/lipid and nucleic acid/lipid. Comparison of proliferating tumorigenic cells (as a model of a malignant tumor) to non-proliferating immortalized cells (as a model of a normal tissue) showed that both optical spectroscopy techniques could differentiate normal from malignant conditions with a high degree of statistical significance. These ratios were also significantly different when comparing proliferating to nonproliferating cells of each cell type. These results demonstrate that FTIR and Raman spectroscopy can be used to non-invasively estimate the biochemical composition of cells. Importantly, optical spectroscopy could differentiate a ‘normal’ from a malignant culture based on estimates of biochemical composition rather than by direct comparison of the spectra, as is commonly done. We are currently extending this work into an epithelial carcinogenesis system.