tbuckley/cabot-search huggingface dataset:
Cytoreductive surgery (CRC) and heated intraperitoneal chemotherapy (HIPEC) in patients with platinum resistant epithelial ovarian cancer (PROC).
Authors: Hatem M. El Halabi, Sybilann Williams, Harold Theodore Huss, Samuel C. Bieligk, Rod Flynn, Giuseppe Del Priore, Digant Gupta, Mahdi Taha, David A. Litvak, Maurie Markman, Laura Gilmore, Charles K. Brown
Journal: Journal of Clinical Oncology (2015)

e16545 Background: Patients with platinum resistant epithelial ovarian cancer (PROC) have generally poor prognosis and poor response to systemic and targeted therapy. We evaluated cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) in patients with PROC. Methods: Retrospective analysis of all PROC patients, treated with HIPEC at a national network of 5 tertiary care cancer hospitals from 2009 to 2013. Survival analyses were performed Results: of 53 patients that had CRS and HIPEC for EOC,forty patients had PROC. Average age was 52 ±10 years. The median overall survival was 26 (14.7-36.2) months. It was 30 months for patients with R0 resection and 15 (5.4-24.9) months for patients with R1 resection (p = 0.044). Median PFS was 16 (12.6-19.2) months for R0 resection and 8 (1.4-14.5) months for R1 resection (p = 0.038). Median survival was 30 months for patients with peritoneal carcinomatosis index (PCI) less than 19, and 18 months for patients with PCI greater or equal to 19 p = 0.05. There was zero ninety days mortality and 42% morbidity. The median progression free survival (PFS) was 10.3 months post HIPEC compared to 4.4 months for the penultimate treatment immediately prior to HIPEC (p < 0.001). Conclusions: CRS and HIPEC is feasible and safe in this population of patients with PROC and seems to be associated with meaningful long term survival. HIPEC clinically prolonged DFS longer than did the penultimate chemotherapy in this heavily pretreated patient population. Prospective studies are warranted to further investigate CRS and HIPEC in the treatment of PROC.
Intratumoral heterogeneity of cancer driver genomic alterations across several tumor types.
Authors: Kai Wang, Adrienne Johnson, Depinder Khaira, James Sun, Bati Katzman, Timothy Brennan, Caitlin McMahon, Kyle Gowen, Sohail Balasubramanian, Siraj Mahamed Ali, Julia Andrea Elvin, Doron Lipson, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross, Roman Yelensky
Journal: Journal of Clinical Oncology (2015)

1558 Background: Intratumoral heterogeneity (ITH) or variations in genomic alterations (GA) between different areas of primary tumors or in their metastases has been an area of intense investigation and is often cited as a reason for failure of targeted therapies. We used an NGS-based comprehensive genomic profiling assay (CGP) to examine 5 tumor types across 10 tissue sections in 5 patients each to determine the impact of ITH on GA relevant to cancer biology (cancer “drivers”). Methods: 250 FFPE 40u sections from 25 patients were obtained from 2 separate non-adjacent blocks at levels throughout the entire block thickness. CGP was performed at Foundation Medicine, as previously described (PMID: 24142049). 245/250 sections were processed successfully, obtaining coverage depth > 700x, with all classes of GA (substitutions, indels, copy number alterations - CNA) assessed. Heterogeneity in cancer driver GA was evaluated including raw data review, and associated with clonal architecture. Results: 837 total substitutions or indels (short variants – SV) were observed in 245 sections, with 217 assessed to be subclonal based on mutant frequency (MAF) and tumor content. Only 20 SV were not detected in paired sections from same PT, for a discordance rate of 2.3% (20/857). All discordances were in subclonal variants, with avg MAF < 6%. CNA concordance was 90.2%, with half of discordances associated with low tumor purity or coverage bias. Findings were similar across tumor types (Table), with key targetable GA including EGFR mutation in lung cancer and ERBB2 amplification in breast cancer concordant across all sections. Conclusions: Our analysis reveals that intratumoral heterogeneity of cancer driver GA is limited. The data supports CGP of a single biopsy section as appropriate in most patients with advanced solid tumors, provided sufficient sensitivity is attained for sub-clonal events in impure clinical tissue. Concordance Breast Invasive Duct Carcinomas Colorectal Adenocarcinomas Head and Neck Squamous Cell Carcinomas Renal (1 oncocytoma + 1 chromophobe, 1 urothelial and 2 unclassified carcinomas Lung (3 adenocarcinomas + 2 squamous cell carcinomas) Short Variant GA 95.0% 98.5% 99.4% 96.0% 98.1% CNA 96.3% 86.4% 88.2% 80.0% 90.0%
Maintenance bevacizumab versus stop and go therapy after induction therapy in first-line treatment of stage IV colorectal cancer: Pooled analysis of randomized clinical trials.
Authors: Emiliano Tamburini, Britt Rudnas, Stefania Nicoletti, Carlotta Santelmo, Manuela Fantini, Claudio Ridolfi, Fabrizio Drudi, Lucia Stocchi, Valentina Arcangeli, Giuseppe Pasini, Maximilian Papi, Eleonora Barzotti, Lorenzo Gianni, Davide Tassinari
Journal: Journal of Clinical Oncology (2015)

e14622 Background: In stage IV colorectal cancer, Bevacizumab maintenance therapy or stop and go therapy is considered the gold standard approach after first line induction chemotherapy. However, there are no clear data about which approach is preferable. Methods: All randomized phase III trials comparing maintenance bevacizumab based chemotherapy (MB) versus stop and go therapy (ST) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the reccomandations of the Cochrane collaboration and the Quality of Reporting of Meta-Analysis Guidelines. Results: 1289 patients of three trials were included into the analysis. A significant improvement in TFS (HR 0,79; CI 95% 0,7-0,9 p = 0,0005) and PFS (HR 0,56; CI 95% 0,44-0,71 p < 0,00001) were observed in favour of MB versus ST. An advantageous trend, but not statistically significant, for MB versus ST were also observed for OS (HR 0,88; CI 95% 0,77-1,01, p = 0,08). Conclusions: Our data suggest that use of MB approach increases TFS, PFS versus ST. Despite not observing any statistically advantage, it should be highlighted that MB versus ST showed a strong trend in favour of MB. MB should probably be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy.
Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity
Authors: Iago Pinal‐Fernandez, David R. Amici, Cassie A. Parks, Assia Derfoul, Maria Casal‐Dominguez, Katherine Pak, Richard Yeker, Paul Plotz, Jose C. Milisenda, Josep M. Grau‐Junyent, Albert Selva‐O'Callaghan, Julie J. Paik, Jemima Albayda, Andrea M. Corse, Thomas E. Lloyd, Lisa Christopher‐Stine, Andrew L. Mammen
Journal: Arthritis & Rheumatology (2019)

Objective Although more than a dozen myositis‐specific autoantibodies ( MSA s) have been identified, most patients with myositis are positive for a single MSA . The specific overexpression of a given myositis autoantigen in myositis muscle has been proposed as initiating and/or propagating autoimmunity against that particular autoantigen. The present study was undertaken to test this hypothesis. Methods In order to quantify autoantigen RNA expression, RNA sequencing was performed on muscle biopsy samples from control subjects, MSA ‐positive patients with myositis, regenerating mouse muscles, and cultured human muscle cells. Results Muscle biopsy samples were available from 20 control subjects and 106 patients with autoantibodies recognizing hydroxymethylglutaryl‐coenzyme A reductase (n = 40), signal recognition particles (n = 9), Jo‐1 (n = 18), nuclear matrix protein 2 (n = 12), Mi‐2 (n = 11), transcription intermediary factor 1γ (n = 11), or melanoma differentiation–associated protein 5 (n = 5). The increased expression of a given autoantigen in myositis muscle was not associated with autoantibodies recognizing that autoantigen (all q &gt; 0.05). In biopsy specimens from both myositis muscle and regenerating mouse muscles, autoantigen expression correlated directly with the expression of muscle regeneration markers and correlated inversely with the expression of genes encoding mature muscle proteins. Myositis autoantigens were also expressed at high levels in cultured human muscle cells . Conclusion Most myositis autoantigens are highly expressed during muscle regeneration, which may relate to the propagation of autoimmunity. However, factors other than overexpression of specific autoantigens are likely to govern the development of unique autoantibodies in individual patients with myositis.
Factors associated with perceptions of breast radiologists regarding the accuracy and usefulness of mammography audits.
Authors: Katherine Y Tossas-Milligan, Garth H Rauscher, Bethliz Irizarry, Ashley Nicole Czworniak, Anne Marie Murphy
Journal: Journal of Clinical Oncology (2015)

e12613 Background: Little is known about the extent to which radiologists actually use mammography audit reports to improve performance, or their association with attitudes or practices. As part of a statewide mammography quality assurance program in Illinois, radiologists were recruited to participate in a survey regarding their personal and work background, work activities, mammography performance and related factors. Methods: Of 342 radiologists who completed the survey, 304 responded to questions about mammography audits at their practicing institution. Radiologists were asked if they agreed with these three statements: I trust the accuracy of the reports; audit reports prompt me to review cancers missed on mammography; and audit reports prompt me to improve my interpretive performance. Each were presented on a 5-point Likert scale and categorized as agree versus not agree, and each were examined for associations with fellowship training, academic affiliation, years practicing, mammography volume, (mis)use of BIRADS 3 and BIRADS 4/5 categories when interpreting screening mammograms, and level of agreement with the statement: “MQSA should require segregation of screening from diagnostic mammograms at audit.” Results: Radiologists with more comprehensive audits were more likely to trust (p = 0.11) and use the reports to improve performance ( ≤ 0.015). Radiologists (mis)using BIRADS 3,4,5 codes for screening interpretation were less likely to trust and use the reports to improve performance. Radiologists who agreed audits should segregate screening from diagnostic mammograms are more likely to trust and use the reports to improve performance. Conclusions: Results suggest that more comprehensive audits are more likely to be trusted and used by radiologists to modify screening interpretation. Radiologists who understand the vital importance of segregating screening and diagnostic mammograms are much more likely to trust in and rely on the audit for feedback.
TGF-β Signaling in Fetal Mesenchymal Progenitor Cells Plays an Essential Role in the Emergence of Bone Marrow Hematopoietic Niches
Authors: Grazia Abou Ezzi, Teerawit Supakorndej, Jingzhu Zhang, Joseph R. Krambs, Hamza Celik, Daniel C. Link
Journal: Blood (2018)
Abstract TS2-1: The complexity of targeting PI3K for cancer therapy
Authors: L Cantley
Journal: Cancer Research (2019)

Abstract Phosphoinositide 3-Kinase (PI3K) is activated by insulin and other growth factors to mediate cell growth. The PI3K enzyme encoded by the PIK3CA gene is one of the most frequently mutated oncogenes in human cancer. This same enzyme mediates insulin responses in liver, muscle, fat and other tissues. The most common mutations in this gene enhance the ability of PI3K to be activated by insulin. Since breast cancers typically express relatively high levels of the insulin receptor, high serum insulin levels are likely to enhance activation of PI3K in breast cancers. PI3K inhibitors that target PIK3CA have the expected physiological effect of raising serum glucose and insulin levels and the elevated insulin is likely to compromise the effectiveness of therapy. Data will be presented showing that in mouse models of human breast cancers and other cancers, dietary interventions and pharmaceutical interventions that limit elevation of serum insulin during PI3K therapy improve responses to PI3K inhibitors. Citation Format: Cantley L. The complexity of targeting PI3K for cancer therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS2-1.
Application to international guidelines in treatment of thromboembolic events in cancer patients: A hospital-based cohort study in Paris, France.
Authors: Isabelle Mahe, Hortense Puget, Jean Chidiac, Andrey Strukov, Jean-Claude Buzzi, Helene Helfer, Michele Lamuraglia, Anne Perozziello
Journal: Journal of Clinical Oncology (2015)

e12647 Background: low-molecular-weight heparin (LMWH) treatment was recommended by international guidelines for a period of 3-6 months in patients with cancer-associated thromboembolism. The aims of our work was to assess the implementation in daily clinical practice. Methods: Using the PMSI (prospective payment system) databases, all hospitalizations from January to December 2012, in three department medicine, surgery and gynecology-obstetrical (MCO) APHP (Assistance Publique Hôpitaux de Paris) hospitals were retrospectively analyzed to look for patients with the reported diagnosis of cancer and venous thromboembolism (VTE) (as a primary or secondary diagnosis). Compliance with guidelines was assessed by comparing the treatment received by the patient at the time of hospitalization to guidelines. T1 was defined as the first ten days after VTE diagnosis, T2 the period from 10 days to 3 months, T3 the period between 3 and 6 months, and T4 after 6 months. Results: 219 therapeutic strategies were assessed among 240 included patients. Adhesion to guidelines was 56% among patients during T1, but decreased during T2 and T3 (33% and 11% respectively). In T4, 65% of patients had an appropriate treatment due to less restrictive recommendations after 6 months. The overall compliance was estimated at 52% for all periods. Patients with special conditions (renal failure, thrombocytopenia, VTE recurrence on anticoagulation) had less often a treatment in accordance with recommendations (46%). Overall, 60% of all cancers were at a metastatic stage, and patients with an advanced cancer had more often a treatment in accordance with guidelines (58%). Patients who experienced pulmonary embolism were more often adequately treated (60%) than patients with deep venous thrombosis (40%). Conclusions: Adhesion to guidelines for VTE treatment in cancer is low, with only half patients with an adequate treatment. Compliance dropped significantly after the first 10 days of treatment. Only the cancer stage seems to impact physician’s prescription. Our study underlies the need to further promote adequate therapeutic strategies in usual care in VTE cancer patient.
Abstract P400: Household Salt Intake Level is Associated With All-Cause, Cardiovascular and Stroke Mortality: A 24-Year Follow-Up of Nippon Data80
Authors: Azusa Shima, Naomi Miyamatsu, Katsuyuki Miura, Naoko Miyagawa, Nagako Okuda, Nobuo Nishi, Katsushi Yoshita, Aya Kadota, Harumitsu Suzuki, Keiko Kondo, Tomonori Okamura, Akira Okayama, Hirotsugu Ueshima
Journal: Circulation (2019)

Background: Dietary salt intake is associated with the risk of raised blood pressure and cardiovascular diseases (CVD). In Asian countries, a major source of salt intake is seasoning or table salt from cooking at home. However, little is known about the relationship between salt intake level of the entire household and CVD mortality risk. Objective: We aimed to investigate the relationship between household salt level and mortality from all-causes, CVD, stroke and subtypes of stroke in a 24-year follow-up study of a Japanese representative population (NIPPON DATA80). Methods: NIPPON DATA80 is a cohort study based on the National Nutrition Survey and the National Survey on Circulatory Disorders conducted by Japanese government in 1980. A total of 8,702 individuals (56% women) who were living with someone such as family were included in this analysis. Participants were 30-79 years old and none had a history of myocardial infarction or stroke. Household salt level was evaluated as the amount of salt consumption (g) per 1000 kcal of total energy intake in each household. The amount of salt consumption and total energy intake were evaluated using 3-day weighed food records at baseline. We used Cox proportional hazards models to evaluate the effect of household salt level for each mortality. Multivariable-adjusted hazard ratios (HRs) and confidence intervals (CIs) for a salt increment of 2g/1000 kcal (1 standard deviation) were calculated after adjusting for sex, age, body mass index, smoking status, drinking status, daily physical activity level, household-based potassium, household-based saturated fatty acid and household-based long-chain n-3 polyunsaturated fatty acid. Results: In 186,186 person-years of follow-up, there were 27.1% (2360 of 8702) deaths, among which CVD were 787 (9.0%), and stroke were 361 (4.1%). Household salt level was 6.25 (±2.02) mg/1000 kcal. Multivariable-adjusted HRs for a 2g/1000 kcal increment in household salt level were 1.07 (1.02-1.11) for all-causes mortality, 1.11 (1.03-1.19) for CVD mortality and 1.12 (1.00-1.25) for stroke mortality. In the analysis for subtypes of stroke, the relative risk of mortality from cerebral hemorrhage was significantly increased (p for trend = 0.024); the HR (95%CI) for a 2g/1000 kcal increment of household salt level was 1.28 (1.03-1.59). However, the association for mortality from cerebral infarction was not significant (HR 1.05; 95% CI 0.91-1.22). Conclusion: Household salt level was associated with long-term risk of all-cause, CVD and stroke mortality in a representative population of Japanese men and women. The association was stronger for mortality risk from cerebral hemorrhage.
Non-invasive ventilation in acute respiratory failure
Authors: S Mehta, N S Hill
Journal: Thorax (2002)

Noninvasive PPV has been employed for decades in patients with chronic respiratory failure. Increasing use in patients with acute respiratory failure is a more recent phenomenon, mainly because of advances in noninvasive interfaces and ventilator modes. Noninvasive PPV delivered by nasal or oronasal mask has been demonstrated to reduce the need for endotracheal intubation, decrease lengths of stay in the ICU and hospital, and possibly reduce mortality. In the acute care setting, evidence now demonstrates the efficacy of noninvasive PPV for acute exacerbations of COPD, pulmonary edema, pulmonary contusions, and acute respiratory failure in patients who decline or who are not believed to be candidates for intubation. No firm conclusions can yet be made regarding patients with respiratory failure due to other causes, but studies suggest that noninvasive PPV may also be of benefit in patients with postoperative respiratory insufficiency, chest wall disease, and cystic fibrosis. Several factors are vital to the success of this therapy, including careful patient selection, properly timed intervention, a comfortable, well-fitting interface, patient coaching and encouragement, and careful monitoring. Noninvasive ventilation should be used as a way to avoid endotracheal intubation rather than as an alternative. Accordingly, a trial of noninvasive ventilation should be instituted in the course of acute respiratory failure before respiratory arrest is imminent, to provide ventilatory assistance while the factors responsible for the respiratory failure are aggressively treated. Moreover, the authors favor conservative management with expeditious intubation in patients who have other conditions that place them at risk during use of noninvasive ventilation or in patients failing to respond to noninvasive PPV. Noninvasive PPV clearly represents an important addition to the techniques available to manage patients with acute respiratory failure; however, because most studies have been retrospective and uncontrolled, many issues remain unresolved. Further controlled studies are needed to confirm the safety and efficacy of noninvasive PPV, evaluate the most appropriate selection of patients and timing of intervention, define the best type of interface, and assess the costs of noninvasive PPV in comparison with conventional therapy.
The UCLA Histo-Genetic Risk Classification (U-HGRC) to predict outcomes of localized clear cell renal cell carcinoma.
Authors: Cedric Michel Lebacle, Aydin Pooli, Nagesh Rao, Erika Louise Wood, Nils Kroeger, Hyun J. Kim, Izak Faiena, Sandy Liu, Karim Chamie, Arie S. Belldegrun, Brian Shuch, Alexandra Drakaki, Allan J. Pantuck
Journal: Journal of Clinical Oncology (2019)

627 Background: Thirty percent of patients with localized clear cell renal cell carcinoma (ccRCC) will ultimately develop recurrence (local or metastatic) after nephrectomy. Current risk stratification systems still misclassify patients. We have developed a novel classification integrating cytogenetic findings to better stratify the risk of recurrence and overall survival (OS) after surgery for localized ccRCC. Methods: A total of 646 patients from UCLA with ccRCC and tumor cytogenetic analysis, were included in this study. After a selection of histologic parameters using logistic regression and cytogenetic parameters using principal component analysis a CHAID decision tree and Kaplan Meier analysis were used to build the UCLA Histo-Genetic Risk Classification (U-HGRC). Survival analyses of the model were validated on two random samples of 323 patients. Recurrence was defined as any local recurrence or development of new metastasis after surgery. Results: The T-stage, tumor size, presence of sarcomatoid features, gain of chromosome 5q, loss 10q, or loss X/Y were used to stratify the risk of recurrence of ccRCC into three U-HGRC groups of low (1), intermediate (2) or high-risk (3). After a mean follow-up of 55 months, risk of recurrence (HR = 2.44, p = .001 for U-HGRC 2; HR = 9.90, p &lt; .0001 for U-HGRC 3), disease-free survival (DFS) (Log-rank p &lt; .0001), risk of death (HR = 1.72, p = .033 for U-HGRC 2; HR = 4.74, p &lt; .0001 for U-HGRC 3) and OS (Log-rank p &lt; .0001) were significantly different between groups. These findings were validated on two random samples. For high-risk group, median DFS and OS were 2.7 and 6.3 years, respectively. The 5-year risks of recurrence for U-HGRC group 1, 2 and 3 were 9%, 25% and 62%, respectively. The AUC of the model was significantly improved comparing to the current UISS system (0.72 for U-HGRC vs 0.65 for UISS, p = .008) with an accuracy of 82.8% for the U-HGRC high-risk group. Conclusions: The U-HGRC, which integrates genomic alterations with clinical and pathologic features, allowed a better stratification of recurrence risk and overall survival that could help to select appropriate patients for surveillance and adjuvant therapy protocols.