tbuckley/cabot-search huggingface dataset:
Biweekly oxaliplatin plus capecitabine (OXXEL) versus oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus (OXAFAFU) in metastatic colorectal carcinoma (MCC): Safety interim analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial
Authors: C. Sandomenico, G. Filippelli, B. Massidda, A. Farris, D. Natale, S. Palmeri, L. Maiorino, G. Condemi, S. Leo, E. Greco, A. Gambardella
Journal: Journal of Clinical Oncology (2006)

3590 Background: We have previously reported that OXAFAFU regimen significantly prolonged the overall survival of MCC patients (pts) in comparison with IRIFAFU regimen (Comella, Ann Oncol 2005). Moreover, the OXXEL regimen showed promising activity in phase II study (Comella, Cancer Chemother Pharmacol 2005). Comparison of these two regimens in terms of safety and activity is the aim of the present trial. Methods: Pts with MCC were randomly treated with: oxaliplatin 85 mg/m 2 iv on day (D) 1, levo-folinic acid 250 mg/m 2 plus 5-fluorouracil 850 mg/m 2 bolus iv on D 2 (OXAFAFU); or oxaliplatin 100 mg/m 2 iv on D 1, Xeloda 1,000 mg/m 2 twice daily po from D 1 (evening) to D 11 (morning). Treatment was delivered every 2 weeks up to progression, or for a maximum of 12 cycles. Results: From May 2004 to December 2005, 191 eligible pts were recruited (OXAFAFU, 96 pts; OXXEL, 95 pts). Characteristics of pts were well balanced in OXAFAFU vs OXXEL arm: primary colon, 74% vs 72%; PS 0/1–2, 57/43% vs 65/35%; previous adjuvant CT, 24% vs 20%; liver metastases, 80% vs 83%; ≥ 2 metastatic sites, 54% vs 49%. At this interim analysis, with a median number of 8 (range, 1–12) cycles delivered in both arms, 143 pts (OXAFAFU, 73; OXXEL, 70) were assessed for safety. In OXAFAFU vs OXXEL arm, occurrence of WHO grade ≥ 3 toxicity was: neutropenia, 29% vs 3%; anemia, 2% vs 7%; thrombocytopenia 3% vs 7%; diarrhea, 4% vs 13%; vomiting, 4% vs 3%; hand-foot syndrome, 1% vs 7%. Conclusions: At this interim analysis, the OXXEL regimen appeared to produce significantly less neutropenia than the OXAFAFU regimen, at a price of an acceptable non-hematologic toxicity. Accrual will continue up to reaching the final sample size of 300 pts. No significant financial relationships to disclose.
The development of a financial toxicity patient-reported outcome instrument (PRO) in cancer.
Authors: Jonas A. De Souza, Bonnie Yap, Fay J. Hlubocky, Mark J. Ratain, David Cella, Christopher Daugherty
Journal: Journal of Clinical Oncology (2013)

6612 Background: Considering patients' (pts) subjective experience is essential for optimal decision making and care. However, despite increasing recognition of the impact of costs on oncology care, there is no accepted and validated PRO that specifically describes the financial burdens cancer pts experience. Methods: A financial toxicity PRO in advanced cancer pts undergoing treatment was developed in 3 stages. Stage 1: literature review and semi-structured qualitative interviews with pts for item generation; items were classified into 5 theoretical domains (financial, resources, affect, coping and family); draft items were examined for redundancy. Stage 2: pts assessed the items for readability and importance to their quality of life via two Likert scales (0 – 3 scales) to generate an importance score; items were ranked by decreasing importance score until at least 3 items per theoretical domain had been retained. Stage 3: pilot-testing assessing inter-item (IIC) and item–total (ITC) correlations to identify redundancy (Spearman’s rho &gt;0.7, p&lt;0.05) and statistically unrelated content; items were formatted in accordance with the Functional Assessment of Cancer Therapy (FACT) quality of life measure, with a 7-day time window and a 5-point Likert scale. Subject data on tumor type, age, gender, race, income, insurance type and educational level were collected. Results: 132 pts (20 in stage 1, 45 in stage 2 and 67 in stage 3) were approached and 101 agreed to participate. Stage 1: literature review, 20 pts, and 6 investigators generated 98 items, which were reduced to 58 due to redundancy. Stage 2: 35 pts ranked the items for importance, and 30 items were retained. The mean importance score was 1.83 (range 1.04 – 2.11). Stage 3: 46 pts completed the 30-item instrument. Their mean age was 61 years; 59% were male and 53% had private or employer purchased insurance; 14 items were excluded due to high IIC and 3 were excluded due to non-significant ITC, resulting in a 13-item PRO. The mean IIC and ITC of the final items were 0.373 and 0.645, respectively. Conclusions: A 13-item financial toxicity PRO has been developed in 101 pts with advanced cancers. This instrument will undergo validation as a subscale of the FACT in a larger cohort of cancer pts.
Antineoplastic effects of specific inhibition of Notch-2 in bladder cancer.
Authors: Tetsutaro Hayashi, Kilian Gust, Wolfgang Jaeger, Shannon Awrey, Na Li, Manuel Altamirano-Dimas, Ralph Buttyan, Estelle Li, Ladan Fazli, Peter C. Black
Journal: Journal of Clinical Oncology (2013)

e15590 Background: Notch signaling guides cell fate decisions, establishment of cell lineages, stem cell maintenance and differentiation during early development. Notch is re-activated in many malignancies where it has been shown to regulate tumor growth and progression. We report effects of Notch-2 knockdown and treatment with a specific Notch-2 inhibitor, NRR2Mab, in pre-clinical models of bladder cancer. Methods: UM-UC3, UM-UC13 and UM-UC16 cells, representing invasive bladder cancer cells with high Notch-2 expression, were stably transduced with Notch-2 or non-targeting shRNA in a lentiviral vector. A Notch-2-inactivating monoclonal antibody, NRR2Mab, and an isotype-matched, non-targeting antibody were provided by Genentech, Inc. (San Francisco, CA). Cells were grown under adherent (AH) or anchorage-independent conditions (AI) and the effects of Notch-2 silencing or NRR2Mab inactivation were quantitatively assessed for changes in proliferation, migration and invasive activities using in vitro assays, and for expression of Notch-2 or other common stem cell-related genes using quantitative RT-PCR, Western blotting and immunohistochemistry. In vivo effects were evaluated in an orthotopic bladder cancer xenograft model with bioluminescence imaging. Results: Cells transduced with the Notch-2 shRNA or treated with NRR2Mab demonstrated markedly decreased Notch-2 expression. Both treatments diminished cell proliferation under AI but not AH conditions in UM-UC3 and UM-UC13. When grown in AI conditions, UM-UC3 and UM-UC13 were found to be enriched for expression of stem cell genes. Notch-2 silencing or treatment with NRR2Mab diminished the expression of these genes. Both treatments significantly inhibited cell migration and invasion of these cells. In vivo, stable Notch-2 knockdown significantly inhibited xenograft growth for all 3 cell lines. NRR2Mab treatment also inhibited UM-UC13 xenograft growth and metastasis. Conclusions: Our results provide preclinical evidence that Notch-2 may be a useful target to inhibit growth and progression of bladder cancer. Targeting Notch-2 with a specific inhibitory monoclonal antibody warrants further evaluation in this context.
Thymidine phosphorylase expression in metastatic kidney cancer as a potential predictor of outcome in patients treated with sunitinib.
Authors: Manuela Miscoria, Carla Di Loreto, Fabio Puglisi, Paul Gerard Murray, Laura Deroma, Maizaton Atmadini, Souad Messahel, Gianpiero Fasola, Nicholas David James, Emilio Porfiri
Journal: Journal of Clinical Oncology (2012)

e15091 Background: Aberrant tumour angiogenesis is a hallmark of Renal Cell Carcinoma (RCC). Sunitinib is a small molecule targeting angiogenesis licensed for advanced RCC (aRCC) treatment. Thymidine Phosphorylase (TP) is an enzyme involved in pyrimidine nucleotide metabolism with a role in angiogenesis upregulation in cancer. In RCC, TP expression is associated with poor prognosis. We studied TP immunohistochemical expression in RCC samples and its association with the outcomes in a cohort of aRCC patients treated with sunitinib. Methods: We identified 59 consecutive patients with aRCC treated with sunitinib at our Institution. Nuclear (N) and cytoplasm (C) scoring for TP, using the validated Tsuda scoring, was performed. TP expression and clinico-pathological variables were studied to assess their association with the outcome of S therapy. The log rank test has been used for the univariate analysis and the Cox regression for the multivariate analysis. Results: Thirty-four patients received sunitinib as first line treatment. Fifty patients (84%) had clear cell RCC, 7 (12%) showed sarcomatoid features. Forty-five patients (76%) achieved either an objective response or stable disease. At the time of the analysis 32 patients had died, 46 had progressed and 41 had stopped the treatment. After an average follow up of 21 months, median OS and PFS were 21.2, 12.8 months respectively. N TP staining was positive in 19 patients (32%) and C staining in 36 (61%) patients. A significant association was observed between the N and C expression (p=0.004). The univariate analysis identified an association between N TP expression and longer OS (29.8 vs 17.8 months; p=0.0463) even if the association was not significant in the multivariate analysis (HR=0.56; CI 0.19-1.6). No associations were noted with PFS. Conclusions: In our study TP was overexpressed in a significant percentage of kidney cancers. In patients treated with sunitinib, N TP expression was associated with better OS. The results of the multivariate analysis were probably affected by the limited sample size. Larger and prospective studies are necessary to define the role of TP in RCC.
THE NEUTROPHIL-LYMPHOCYTE RATIO AND SUBCLINICAL CORONARY ARTERY DISEASE: ANALYSIS FROM AN OBSERVATIONAL COHORT STUDY IN PSORIASIS
Authors: Amit Dey, Heather Teague, Justin Rodante, Marcus Y. Chen, Martin Playford, Paul M. Ridker, Nehal Mehta
Journal: Journal of the American College of Cardiology (2020)
Use of cardiopulmonary exercise testing (CPET) to identify patients at high risk for adverse outcome after pancreaticoduodenectomy.
Authors: Ajith K. Siriwardena, Muneer Junejo
Journal: Journal of Clinical Oncology (2013)

e15072 Background: Pancreaticoduodenectomy is the standard of care for tumours confined to the head of pancreas and can be undertaken with low operative mortality. However, the procedure has a high morbidity, particularly in older patient populations with pre-existing co-morbidities. Many of the currently available methods for assessment of pre-operative risk rely on either scoring systems or indirect measures of cardiopulmonary function. In contrast, pre-operative cardiopulmonary exercise testing (CPET) provides a direct functional assessment of integrated cardiac and respiratory performance. This study evaluates the role of pre-operative cardiopulmonary exercise testing (CPET) for prediction of post-operative morbidity and outcome after pancreaticoduodenectomy. Methods: In a prospective cohort undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with co-morbidity) were categorized as high-risk and underwent preoperative assessment by CPET according to pre-defined protocol. Data were collected on functional status, postoperative complications and survival. The predictive potential of CPET-derived markers was assessed. Results: 143 patients underwent preoperative assessment of whom 50 were deemed low-risk for surgery per protocol. Of 93 high-risk patients 64 proceeded to surgery after preoperative CPET. CPET-derived ventilatory equivalent of carbon dioxide (VE/VCO 2 ) at anaerobic threshold (AT) was a predictive marker of postoperative mortality with an AUC of 0.85 (95% CI 0.63 to 1.07, p = 0.020); a threshold of 41 was 75% sensitive and 94.6% specific (PPV 50%, NPV 98.1%). Above this threshold, raised VE/VCO 2 was a predictor of poor long-term survival (HR 1.90, 95%CI: 1.02 to 3.57, p = 0.045). Conclusions: CPET is a useful adjunctive test for predicting post-operative outcome in patients being assessed for pancreaticoduodenectomy. CPET-derived VE/VCO 2 above a threshold of 41 predicts early post-operative death and poor long-term survival. CPET should be considered in the pre-operative work-up prior to pancreaticoduodenectomy.
COMPARISON OF INTRAVASCULAR ULTRASOUND-DERIVED MINIMUM LUMEN AREA AND INSTANTANEOUS WAVE-FREE RATIO IN LEFT MAIN CORONARY ARTERY DISEASE
Authors: Amir Lerman, Takumi Toya, Stephanie El Hajj, Takayuki Warisawa, John Nan, Christopher Cook, Christopher Rajkumar, James Howard, Henry Seligman, Yousif Ahmad, Shunichi Doi, Akihiro Nakajima, Masafumi Nakayama, Sonoka Goto, Rafael Vera-Urquiza, Takao Sato, Yuetsu Kikuta, Yoshiaki Kawase, Hidetaka Nishina, Sunao Nakamura, Hitoshi Matsuo, Javier Escaned, Yoshihiro Akashi, Justin E. Davies
Journal: Journal of the American College of Cardiology (2020)
Abstract 14266: Statins Ameliorates Chronic Stress-Related Vascular Aging and Atherosclerotic Plaque Growth in ApoE-Deficient Mice Fed High Fat-Diet
Authors: Yanna Lei, Limei Piao, Masafumi Kuzuya, Xian Wu Cheng
Journal: Circulation (2019)

Introduction: Emerging evidence has showed that chronic stress plays a more and more important role on various diseases. Stains as traditional anti-atherosclerotic drugs have been used in clinical ...
ASSOCIATION BETWEEN VARIATION OF TROPONIN AND PROGNOSIS OF ACUTE MYOCARDIAL INFARCTION BEFORE AND AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Xiaoxiao Zhao, Ying Wang, Chen Liu, Peng Zhou, Sheng Zhaoxue, Jiannan Li, Jingying Zhou, Runzhen Chen, Yi Chen, Song Li, Hanjun Zhao, Hongbing Yan
Journal: Journal of the American College of Cardiology (2020)
Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020
Authors: Pete Kinross, Carl Suetens, Joana Gomes Dias, Leonidas Alexakis, Ariana Wijermans, Edoardo Colzani, Dominique L Monnet
Journal: Eurosurveillance (2020)

The cumulative incidence of coronavirus disease (COVID-19) cases is showing similar trends in European Union/European Economic Area countries and the United Kingdom confirming that, while at a different stage depending on the country, the COVID-19 pandemic is progressing rapidly in all countries. Based on the experience from Italy, countries, hospitals and intensive care units should increase their preparedness for a surge of patients with COVID-19 who will require healthcare, and in particular intensive care.
Chemotherapy in advanced biliary tract carcinoma (BTC): A comprehensive analysis
Authors: F. Eckel, R. M. Schmid
Journal: Journal of Clinical Oncology (2006)

14036 Background: BTC are uncommon but highly fatal malignancies in the United States and Europe. Unfortunately, most BTC are diagnosed at advanced stages when the tumor is unresectable. Due to the lack of phase III studies there is no standard regimen for palliative chemotherapy of BTC. The aim of this study was to analyze existing data of published clinical trials, even small and non-randomized, and identify superior regimens, which may represent a quasi standard of care of palliative chemotherapy in this disease. Methods: Data for this analysis were identified by searches of PubMed and references from relevant articles using the search terms “biliary tract neoplasms”, “bile duct neoplasms”, “cholangiocarcinoma”, and “gallbladder neoplasms”. Only papers published in English since 1985 were included. Additionally abstracts from ASCO meetings presented since 1999 were included. Results: 88 trials were analyzed. The overall response rates (OR) of this trials were in the range of 0–83%. There were 497 responders out of 2137 patients corresponding to a pooled OR of 23.3% (95%CI 21.5–25.2%). The median progression free survival (PFS) and overall survival (OS) for all patients was 4.1 and 8.0 months, respectively. There was a significant correlation between OR and PFS (r=0.49; p=0.001) and PFS and OS (r=0.76; p=0.000) but not between OR and OS. Gemcitabine (GEM) and platinum analogs (P) had a significant positive impact on OR, whereas the impact of taxanes and irinotecan was negative. OR of subgroups defined by 5-FU, GEM, and P were analyzed in detail. There was only a trend of an increased OR between 5-FU and GEM without P (17 vs 22%). Combination with P increased significantly the OR of 5-FU by 10% (17 vs 27%) and of GEM by 20% (22 vs 42%). Conclusions: The pooled OR of mostly small trials of palliative chemotherapy in BTC is about 23%. With GEM alone no significant improvement could be achieved compared to 5-FU or capecitabine. However, doublets of GEM in combination with P synergistically increased OR. Results of GEM plus P are promising and should be further evaluated by large RCT. In the meantime GEM plus P may represent at least a good option for patients in good general condition. No significant financial relationships to disclose.
MANGANESE-ENHANCED T1 MAPPING IN MYOCARDIAL VIABILITY: VALIDATION WITH 18F-FDG PETMR
Authors: Nick Spath, Nick Spath, Adriana Tavares, Gillian Gray, Marc Dweck, David E. Newby, Phillip C. Yang, Maurits Jansen, Scott Semple
Journal: Journal of the American College of Cardiology (2020)
Investigation of estrogen receptor α phosphorylation in breast cancer
Authors: N. Sarwar, J. Jiang, S. Shousha, R. C. Coombes, S. Ali
Journal: Journal of Clinical Oncology (2006)

20046 Background: Estrogen receptor α (ERα) is an important predictive marker for response to endocrine therapy in breast cancer. Phosphorylation of ERα, in particular on serine 118 (S118), can result in ligand independent activation, thereby possibly contributing to resistance to endocrine therapies. The clinical significance of ERα phosphorylated at serine 118 (P-S118) in breast cancer was examined. Methods: Immunohistochemistry was performed on 301 primary breast tumor biopsies and on a small subset that had become resistant to endocrine therapy. P-S118 levels were scored using the modified McCarty’s H scoring system. Results: 282 (94%) of the 301 tumors were ERα positive. Of the 282 ERα positive patients, 282 (83%) had detectable nuclear staining for P-S118. There was no association between P-S118 staining and tumor size, nodal status, progesterone receptor and c-erbB2 status. There was however a positive correlation of P-S118 with ERα expression, (p &lt; 0.001) and activated (phosphorylated) mitogen-activated protein kinase (MAPK) expression (p &lt; 0.001). There was a clear inverse relationship with tumor grade and P-S118 staining (p &lt; 0.001). Lower grade tumors being associated with higher H-scores for P-S118 staining. There was also some evidence of an association between P-S118 and age (P = 0.08). No association was found between P-S118 expression and survival. There was however a statistically significant difference in the distribution of P-S118 expression before and after becoming resistant to hormonal therapies (z = −2.357 p-value = 0.02). Comparison of H-scores showed that P-S118 levels were elevated following tumor regrowth. Conclusion: This analysis shows that S118 phosphorylation is higher in more differentiated tumors, suggesting that phosphorylation at this site is associated with a better prognosis. However, S118 phosphorylation is elevated in biopsies taken from patients who had relapsed on tamoxifen, compared to pre-treatment biopsies. Collectively these data indicate a complex role for ERα phosphorylation at least at S118, in breast cancer progression. No significant financial relationships to disclose.
Evaluating the accuracy of frozen section in borderline ovarian tumors.
Authors: Natasha Gupta, Tanuja Rajpal, Sameer Sharma
Journal: Journal of Clinical Oncology (2013)

5564 Background: The objective of this study was to evaluate accuracy of frozen section in borderline ovarian tumors and to determine the tumor characteristics that lead to higher likelihood of inaccurate intraoperative diagnosis (IAIOD). IAIOD is a clinical problem that restricts the diagnostic accuracy of frozen section in borderline ovarian tumors. Methods: This was a retrospective chart review of 622 consecutive cases that were diagnosed with pelvic mass and underwent surgery at busy gynecology services of two institutions, between 2006-2011. Of these cases, 52 were diagnosed as borderline ovarian tumors by frozen section. Experienced pathologists performed frozen section with second opinion from specialized gynecologic pathologists as needed. Terms such as “at least borderline” were also evaluated to help stratify patients. Frozen section and final permanent histology reports were compared. Patient and tumor characteristics that may cause IAIOD such as age of patient, histological subtype, size of tumor, bilaterality, CA-125 levels were studied. Staging was performed when borderline or malignant ovarian tumors were identified by frozen section. Results: Agreement of the frozen section results with final pathology was observed in 37 out of 52 patients with a diagnostic accuracy of 71.15 %. Under diagnosis occurred in 12 out of 52 patients and over diagnosis occurred in 3 out of 52 patients. Age &gt;40 years, size of tumor &gt;5 cm, bilaterality of tumors and CA-125 were not found significant in causing IAIOD when chi-square analysis was performed. Characterization by “at-least” borderline terminology at the time of frozen section did not help identify patients with higher likelihood of IAIOD. Conclusions: In our study, the rate of IAIOD was high, at 23% despite experienced pathologists and using “at-least borderline” terminology. Traditionally described features leading to inaccuracy with frozen sections, such as large tumors with mucinous histology did not increase the risk of IAIOD in this study. Patients with unilateral, small tumors and non-mucinous histology had greatest risk for IAIOD. Given this information, full staging of all borderline ovarian tumors identified at time of frozen section should remain the standard of practice.
The relationship between symptom burden and perceived comorbidity in outpatients with common solid tumors.
Authors: Christine Ritchie, Judith Manola, Elizabeth Kvale, Claire Frances Snyder, Michael Fisch
Journal: Journal of Clinical Oncology (2012)

6080 Background: Cancer patients have high symptom burden, but it is unclear whether comorbid conditions are associated with patient-reported symptom burden (the number and severity of symptoms). Methods: The Eastern Cooperative Oncology Group (ECOG) enrolled 3106 patients with invasive cancer of the breast, colon/rectum, prostate and lung, regardless of phase of care or stage of disease. At baseline, patients completed the M.D. Anderson Symptom Inventory (MDASI) and were also asked how bothered they were by difficulties related to health problems other than cancer. Symptom burden (SB) was defined as the number of symptoms scored 7 or higher on the 13-item MDASI physical scale. Variance-weighted least squares regression was used to identify factors associated with increasing levels of being bothered by comorbid conditions. Results: About 65% of patients were at least a little bothered by symptoms associated with comorbidities. There was a strong association between increased bother by comorbidities and increased SB (p&lt;0.0001). Among those not bothered by difficulties related to comorbidities, ≥1 symptom was rated 7 or worse by 29% of patients, compared to 51% in patients bothered by difficulties related to comorbidities (Fisher’s exact p&lt;0.0001). Except for hair loss, the severity of all symptoms was higher in those patients reporting bother due to other perceived comorbidities. Factors associated with increased bother include SB (p&lt;0.0001), taking medications for diabetes (p&lt;0.0001), impaired ECOG performance status (p=0.03), older age (p=0.004), and being perceived by the clinician as having higher degree of difficulty for providing care (p&lt;0.0001). Conclusions: Symptom burden varies significantly according to the degree to which cancer patients perceive bother that they attribute to comorbid health problems. Perception of comorbidity is worth exploring as a stratification factor in symptom research and as an indicator for complexity in patient care.