tbuckley/cabot-search huggingface dataset:
Abstract 346: Glucose Inhibits Cardiomyocyte Maturation Through Nucleotide Biosynthesis
Authors: Haruko Nakano, Itsunari Minami, Daniel Braas, Herman Pappoe, Xiuju Wu, Addelynn Sagadevan, Laurent Vergnes, Kai Fu, Marco Morselli, Xueqin Ding, Adam Z Stieg, James K Gimzewski, Matteo Pellegrini, Peter M Clark, Karen Reue, Aldons J Lusis, Bernard Ribalet, Siavash K Kurdistani, Heather Cristofk, Norio Nakatsuji, Norio Nakatsuji, Atsushi Nakano
Journal: Circulation Research (2017)

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is known to be associated with congenital heart disease. However, little is known about the mechanism how blood glucose impacts heart formation. Using a chemically-defined human pluripotent stem cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic and electrophysiological levels via nucleotide biosynthesis through the pentose phosphate pathway. Even though blood glucose level stays stable in utero during normal pregnancy, glucose uptake by fetal cardiac tissue was found drastically reduced at late gestational stages in the mouse. Interestingly, perturbation of glucose dynamics during gestation in a murine model of diabetic pregnancy promoted mitosis and inhibited maturation of fetal cardiomyocytes. Therefore, this observation suggests that the metabolic switch is not only to meet the energy demand but also to induce a genetic program to facilitate cardiac maturation, providing a possible mechanistic basis for the congenital heart disease in diabetic pregnancy.
Assessing trainee’s need and readiness for e-cancer education and training in Africa.
Authors: Omoruyi Credit Irabor, Anouk Berger, Victor Mbarika, Nazik Hammad, Folakemi Odedina, Wilfred Ngwa
Journal: Journal of Clinical Oncology (2018)

11012 Background: As a prerequisite to launching a virtual education and training platform, the African Organization for Research and Training in Cancer (AORTIC) assessed the educational needs and e-Learning readiness of Sub-Sahara African oncology staff before designing ICT support systems. Methods: Using existing assessment models, we developed a self-assessment tool for a cross-sectional survey. Competence areas assessed include basic knowledge, early detection and diagnosis, clinical skill, cancer registry, and cancer management respectively. Components of e-Learning readiness assessed include access to technology, technological skills/competence, capacity for self-directed learning, confidence prerequisite skills, and motivation. We calculated an average score for each component as (Sum of positive response/Sum of responses). Results: There were 128 respondents. 33%, 44%, 48%, 58% and 60% felt they needed further training in the areas of basic knowledge, early detection and diagnosis, clinical skill, cancer registry, and cancer management respectively. Reported internet access for e-Learning is 100%, significantly higher than the 31.2% internet penetration of Sub-Sahara Africa. However, only 15.7% have a bandwidth of quality to support real-time visual learning. Weighted averages for technological access, skill, competence, capacity for self-directed learning, motivation, and prerequisite skills was 69%, 86%, 51% 42% and 80% respectively. Conclusions: There are deficiencies in the training of oncology health professionals in all five competency areas, and e-Learning can supplement ongoing traditional training to meet the gap. The low access to the internet in Africa may not be disruptive to asynchronous oncology training but may limit real-time video-based synchronous learning which involves more intense interaction between trainees and trainers. However, African bandwidth growth trend indicates this limitation is fast diminishing. African oncology health professionals are technologically competent for e-Learning and score high in the prerequisite skills. There is, however, a low ability for self-directed learning, and many may need a support system for the advanced virtual education.
Results of a randomized phase 3 study evaluating the potential benefit of a second-look surgery plus HIPEC in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP- NTC01226394).
Authors: Diane Goere, Olivier Glehen, Francois Quenet, Michel Ducreux, Jean-Marc Guilloit, Matthieu Texier, Ellen Benhamou, Dominique Elias
Journal: Journal of Clinical Oncology (2018)

3531 Background: Complete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) allow to prolong survival in patients with colorectal peritoneal metastases (CRPM), especially with a low tumor burden. The aim of the PROPHYLOCHIP multicentric randomized phase 3 study was to evaluate the potential survival benefit of a systematic second-look surgery plus HIPEC in patients at high risk of developing CRPM. Methods: Patients at high risk of developing CRPM defined as minimal CRPM resected with the primary, or history of ovarian metastases, or perforated primary tumor, were eligible. After 6 months of adjuvant chemotherapy, patients without sign of recurrence were randomized into 2 arms: (1) surveillance, (2) systematic second-look surgery plus HIPEC (intraperitoneal oxaliplatin). The primary end-point was the 3-year disease-free survival (DFS). Secondary end-points included overall survival (OS), peritoneal DFS and postoperative complications. Results: Between 2012 and 2015, 150 patients were randomized. During the second-look laparotomy (n = 71), CRPM was diagnosed in 52%, with a median peritoneal cancer index of 4 [0-26]. No patient died postoperatively and grade 3-4 complications occurred in 41%. After a median follow-up of 51 [47-55] months, the 3-year DFS of 44% [33-56] in the second-look group and of 51% [40-62] in the surveillance group did not differ (p = 0.75). In the surveillance group, a peritoneal relapse occurred in 25 (33%) patients, which was accessible to CRS-HIPEC in 16, whereas in the second-look group, 24 (32%) patients had a peritoneal relapse of whom 2 were treated with a new CRS-HIPEC. The 3-year OS was not significantly different, 80% [69-88] and 79% [68-87] in the surveillance and in the second-look groups, respectively. Conclusions: This study confirms that criteria for high risk of developing PM are strong, and strengthens the role of a peritoneal-centered surveillance in these patients. However, a pro-active strategy including a systematic second-look surgery plus HIPEC failed to improve survival, in comparison to an adequate surveillance. Clinical trial information: NCT01226394.
A multicenter prospective study of image-guided radiofrequency ablation for small breast carcinomas.
Authors: Takayuki Kinoshita, Naoto Yamamoto, Tomomi Fujisawa, Daisuke Takabatake, Noriaki Wada, Norikazu Masuda, Hitoshi Tsuda, Hiroyoshi Doihara, Masato Takahashi
Journal: Journal of Clinical Oncology (2012)

TPS1147 Background: As the management of breast carcinoma evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising noninvasive ablation technique is radiofrequency ablation (RFA), which can effectively kill tumor cells with a low complication rate. Our preliminary studies of RFA followed by standard surgical resection have indicated that this technique is effective for surgical ablation of small (≤ 2cm) breast tumors without extensive intraductal components (EIC). Methods: To determine if RFA is oncologically and cosmetically appropriate for the local treatment of primary breast carcinoma, this multi-center prospective study used RFA as the sole local treatment of breast tumors ≤ 1.5cm in size on ultrasound and MRI. Exclusion criteria include receiving of preoperative chemotherapy, or the presence of invasive lobular carcinoma or invasive ductal carcinoma with suspicious EIC. After confirmation that the standard baseline core biopsy for diagnosis and measurement of tumors markers (ER, PgR, HER-2/neu expression and the presence of the Ki-67 proliferative marker) have been obtained, consent will be obtained and the patient scheduled RFA. All patients received adjuvant radiation therapy. The use and choice of systemic therapy will be based on the information from the baseline core biopsy and imaging studies. The first primary endpoints of this study is successful tumor ablation, as evidenced by negative findings on vacuum-assisted or core biopsies and imaging studies after RFA. The second primary endpoints is the incidence of procedure related adverse events. Forty patients with small tumors that are clearly identifiable and measurable by ultrasound and MRI were enrolled. The response to ablation was evaluated with both vacuum-assisted or core biopsies and imaging studies every 3 months during the first year. The long-term outcomes were assessed using quality of life measurement scales and imaging studies every 6 months thereafter through year 5.
Abstract 11604: The Relationship of Sudden Death and All-cause Mortality to Baseline Values of High-sensitivity Cardiac Troponin T and I in the EVOLVE Trial
Authors: Charles A Herzog, Kate Tsirtsonis, Fred S Apple
Journal: Circulation (2017)

Introduction: High sensitivity cardiac troponin (hs-cTn) levels are strong predictors of adverse outcomes. There is uncertainty regarding their use in end-stage renal disease (ESRD) pts. We analyze...
Prevalence and Significance of Tricuspid Regurgitation Post-Endocardial Lead Placement
Authors: Kalilur Anvardeen, Rajeev Rao, Samir Hazra, Karen Hay, Hongyan Dai, Nik Stoyanov, David Birnie, Girish Dwivedi, Kwan Leung Chan
Journal: JACC. Cardiovascular imaging (2018)
Breast cancer risk perception and adherence to u.s. cancer prevention guidelines.
Authors: Jillian Eckroate, Anees B. Chagpar, Erin Wysong Hofstatter
Journal: Journal of Clinical Oncology (2018)

1554 Background: In the United States, nearly 300,000 cancer diagnoses each year are attributed to poor diet and physical inactivity. We sought to determine whether perceived personal breast cancer risk was associated with adherence to healthy lifestyle habits. Methods: The National Health Interview Survey (NHIS) is conducted annually by the CDC, designed to broadly represent the U.S. civilian population. We utilized data from the 2010 and 2015 NHIS adult and cancer supplements to evaluate fruit/vegetable intake, alcohol use, and exercise habits among women who perceived themselves to be at high risk of developing breast cancer, as compared to those women who perceived themselves to be at average or low risk. Results: In 2010 and 2015, 12,055 and 14,542 women without a history of cancer were surveyed, representing 94,990,140 and 98,404,285 people, respectively. In 2010, those who perceived themselves to be at higher risk of breast cancer were more likely to follow the fruit/vegetable and physical activity guidelines, but less likely to follow the alcohol intake guidelines than those at low to average risk, but these differences were not statistically significant (p = 0.57, 0.15, 0.31 respectively). In 2015, those who perceived themselves to be at high risk were significantly more likely to follow the fruit/vegetable guidelines (p = 0.02) as their low/average risk counterparts, but had similar rates of following alcohol and physical activity guidelines (p = 0.58 and 0.67 respectively). In general, guideline adherence did not improve from 2010 to 2015 (see table). Conclusions: Less than a third of women adhere to nutrition and physical activity guidelines regardless of self-perceived breast cancer risk, a trend that has remained stable over time and indicates a need to educate patients on healthy lifestyle habits. 2010 2015 p-value High Risk—% meeting guidelines Fruit/Veg Intake (³ 5 servings/daily) 4.90% 6.25% 0.25 Alcohol Intake (£ 7/week) 94.22% 95.80% 0.16 Physical Activity (75-150 min vig-mod activity/week) 30.11% 28.97% 0.64 Low/Avg Risk—% meeting guidelines Fruit/Veg Intake (³ 5 servings/daily) 4.42% 3.92% 0.11 Alcohol Intake (£ 7/week) 95.13% 95.35% 0.53 Physical Activity (75-150 min vig-mod activity/week) 27.74% 29.79% 0.01
Facility volume and head and neck squamous cell carcinoma: Trends and effect on survival.
Authors: Roy Xiao, Matthew C Ward, Kailin Yang, David J. Adelstein, Shlomo A. Koyfman, Brandon Prendes, Brian Burkey
Journal: Journal of Clinical Oncology (2018)

e18518 Background: Facility volume has been found to predict improved survival for patients with breast and esophageal cancer. However, the role of facility volume in head and neck squamous cell carcinoma (HNSCC) remains unclear. Methods: We used the National Cancer Database (NCDB) to perform a cohort study of all patients with HNSCC from 2004-2013. During this period, the average annual treatment volume (ATV) was calculated for each reporting facility. The primary outcome was overall survival. Results: Facilities were grouped by ATV into quartiles: Q1 ( < 16.7 ATV, 59,608 patients), Q2 (16.7-33.7 ATV, 60,077 patients), Q3 (33.8-86.0 ATV, 59,785 patients), and Q4 ( > 86.0 ATV, 60,072 patients). Each of the following reported results compared the largest ATV quartile (Q4) to the smallest quartile (Q1) and was found to be statistically significant (p < 0.001). Almost all facilities in Q4 were academic (80.4%), whereas academic facilities were uncommon in Q1 (8.1%). On average, Q4 facilities treated younger patients (61.1 v. 63.7 years). Of note, more Q4 patients had advanced cancer compared to Q1 (47.7% v. 37.8% clinical stage IV). Additionally, on average, Q4 patients traveled further for their care (65.4 v. 17.3 miles) and waited longer for treatment initiation (37.3 v. 29.3 days). Q4 patients were treated more often for oral cavity SCC (34.1% v. 22.5%) and less often for laryngeal SCC (22.9% v. 35.0%). Surgery was more common (58.5% v. 41.6%) while radiation therapy was less common (65.0% v. 78.8%) as components of the treatment regimen among Q4 patients. Kaplan-Meier analysis demonstrated extended 5-year survival for Q4 patients compared to Q1 (81.0 v. 68.7 months), a finding confirmed by Cox proportional hazards regression (HR 0.90, 95% CI 0.88-0.92). Conclusions: Despite having more advanced cancers, traveling further, and waiting longer for treatment, patients with HNSCC treated at the highest volume facilities experience significantly extended survival.
A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without systemic bevacizumab, for patients with advanced cancer and liver involvement.
Authors: Elena Fountzilas, Elangovan Krishnan, Filip Janku, Siqing Fu, Daniel D. Karp, Aung Naing, Vivek Subbiah, David S. Hong, Sarina Anne Piha-Paul, David J Vining, Apostolia Maria Tsimberidou
Journal: Journal of Clinical Oncology (2018)

2527 Background: Hepatic arterial infusion (HAI) of chemotherapy is a treatment option for patients (pts) with cancer metastatic to the liver. We investigated HAI oxaliplatin combined with capecitabine +/- bevacizumab, in advanced cancer with liver involvement. Methods: Pts received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Arm A) or without (Arm B) bevacizumab (10 mg/kg IV). A 3+3 dose design was used, followed by an expansion phase. Results: From 9/2009 to 2/2014, 61 pts (34 men, 27 women) were enrolled (Arm A = 44; Arm B = 17). Pts were treated in Arm B if they had contraindications to bevacizumab (n = 13) or if there was no spot available in Arm A (n = 4). The median age was 60 yrs (range, 20-88). The most common cancers were colorectal (22 pts), liver (13), pancreas (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1-12); 32 (53%) pts had previously oxaliplatin. Grade 3 diarrhea was the only DLT and occurred in 2 pts receiving 1000 mg/m2 capecitabine. Thus, the MTD was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. Common toxicities were anemia, thrombocytopenia, neutropenia, hypomagnesemia, and nausea/vomiting. Outcomes are shown in Table. Eleven (18%) pts remained on treatment for ≥6 months, including 4 (6.6%) pts who remained on treatment for ≥1 year. Conclusions: HAI oxaliplatin combined with capecitabine +/- bevacizumab was well-tolerated and was associated with favorable outcomes in selected pts. Clinical trial information: NCT01213238. Oxaliplatin HAI, Capecitabine, Bevacizumab Oxaliplatin HAI, Capecitabine Total No. of pts 44 17 61 No. of evaluable pts 36 11 47 CR+PR (%) 8 (22) 1 (9) 9 (19) SD (%) 26 (72) 9 (81) 35 (75) SD≥4 months (%) 14 (39) 0 14 (30) Median TTF, months (95% CI) 3 (2.27-3.73) 1.5 (1.0-2.0) 2.7 (2.4-3.0) Median OS, months (95% CI) 7.1 (5.46-8.8) 6.2 (3.16-9.17) 7 (5.57-8.56) Median time on Rx, months (95% CI) (Range) 3 (2.35-3.65) (1-21) 2 (1.56-2.47) (1-15) 3 (2.48-3.53) (1-21) * CR complete response, OS: overall survival, PR: partial response, Rx: treatment, SD: stable disease, TTF: time to treatment failure
Lung cancers with mutations in <i>EGFR</i> exon 18: Molecular characterization and clinical outcomes in response to tyrosine kinase inhibitors.
Authors: Wei-Chu Victoria Lai, Ai Ni, Maria E. Arcila, James Huang, Joshua K. Sabari, Kathryn Cecilia Arbour, Charles M. Rudin, Mark G. Kris, Gregory J. Riely, Helena Alexandra Yu
Journal: Journal of Clinical Oncology (2017)

9029 Background: Little data is available to guide clinical management of individuals with less common oncogenic drivers such as exon 18 mutations (ex18m) in EGFR. To better understand the impact of these rare mutations on treatment outcomes, we reviewed clinicopathologic data in patients (pts) with ex18m treated with tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancers. Methods: Pts with EGFR ex18m were detected via molecular diagnostics using Sequenom™, FoundationOne™ or MSK IMPACT™ NGS testing from 2003-2016. We reviewed their clinical data for molecular alterations in EGFR, treatment outcomes in response to TKI (time on treatment) and median overall survival (OS). Results: We identified mutations in EGFR ex18m in 63 pts. Median age at diagnosis was 68; 63% were women; 29% never smokers. Overall, 74 ex18m were found in 63 pts, including: G719A = 38, G719S = 11, G719C = 8, E709K = 6, E709_T710delinsD = 6, E709A = 3, G719D = 2. E709 and G719 co-mutations in ex18 were found in 9 pts, and 1 pt was found to have 3 separate tumors, each with a distinct ex18m. 29/63 (46%) patients with ex18m had a co-occurring EGFR mutation: 9 with another ex18m; 20 with ex19-21m. Using our IMPACT NGS, the median number of co-mutations was 8 (range 1-17). Two out of 63 pts had a pre-treatment T790M mutation. The 25 pts with non-metastatic disease presented in the following stages: IA = 19; IB = 3; IIB = 1; IIIA = 2; IIIB = 2. 34/38 pts with metastatic disease were treated with the following first-line EGFR-TKIs: erlotinib = 28, afatinib = 5, osimertinib = 1. Median duration on TKI treatment in months was: erlotinib = 10 mo, (range 1-25), afatinib = 3 mo (range 2-9), osimertinib = 4 mo. Median OS from the date of diagnosis of metastatic disease was 22 months (95% CI 18-29). In comparison, a similar cohort of pts with sensitizing EGFR exon19del/L858R mutations had a median OS of 31 months (95% CI 28-33) (Naidoo Cancer2015). Conclusions: Almost half of ex18m occur concurrently with another EGFR mutation. Overall, ex18m pts have a shorter median OS when compared to similar patient cohorts. EGFR-TKIs appear to be an effective treatment for pts with ex18m in EGFR-mutant lung cancers.
The “one airway, one disease” concept in light of Th2 inflammation
Authors: Lisa Giovannini-Chami, Agnès Paquet, Céline Sanfiorenzo, Nicolas Pons, Julie Cazareth, Virginie Magnone, Kévin Lebrigand, Benoit Chevalier, Ambre Vallauri, Valérie Julia, Charles-Hugo Marquette, Brice Marcet, Sylvie Leroy, Pascal Barbry
Journal: European Respiratory Journal (2018)

In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and bronchial cells were collected by brushing from healthy controls (C, n=13), patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry, gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell (Th17) and interferon (IFN) signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose excluded 30% of the initial cohort. All bronchial samples from the AR group were Th2-high. The gene expression profile of nasal samples from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2 response, in particular due to a more robust influence of the IFN response in 14 out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002), while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.
Malignant wounds associated with cancer: Delay in treatment, impairment in quality of life and associated psychosocial and financial burden.
Authors: Brooke E Rosenbaum, Stephen W Dusza, Shari Beth Goldfarb, Christopher Andrew Barker, Alina Markova
Journal: Journal of Clinical Oncology (2018)

e22171 Background: Malignant wounds are a rare complication of advanced cancer in which tumor cells erode the skin. These wounds have a high symptom burden—including exudate, malodor, bleeding, and pain—that negatively impacts patients’ quality of life. While prior studies show that consistent wound care can be palliative, there is limited research on the barriers to receiving such care. Methods: We included cancer patients with malignant wounds managed at MSKCC dermatology clinic. Clinical data obtained from patient charts and QoL accessed via Skindex-16 and WoSSAC surveys. Outpatient medical supply cost data obtained from supplier invoices. Results: We assessed 28 patients with malignant wounds (median f/u 1 yr): 75% were female and 25% male. Median age was 61.4 years. Primary malignancy included breast (68%), lymphoma (18%) and Kaposi sarcoma (7%). Wounds were located on chest (50%), back (21%) and lower extremity (21%). Median time from onset of symptoms to first wound care visit was 6.5 months. Symptoms were exudate (89%), malodor (79%), pain (79%) and pruritus (21%). Wound care regimens required dressing changes 2-3x/week (52%), daily (39%) or > 1x/day (9%). Half of patients required visiting nurse services to assist with dressing changes. Median cost of wound care supplies was $456/month. Patients cited financial hardships (22%) and logistical issues (15%) as barriers to obtaining supplies. Patient surveys showed quality of life was more highly impacted by psychosocial effects of having a malignant wound (e.g., desire to socialize, mood, and self-esteem) than physical symptoms (e.g., pain, malodor, and pruritus). 54% of patients had ≥1 hospitalization for wound-related complications, such as cellulitis (63%), symptomatic anemia (15%) and pain crisis (11%). Eleven patients died during the study period. Conclusions: Malignant wound patients face multiple barriers to receiving wound care, such as delay in presentation, high cost of supplies, psychosocial isolation, and associated morbidities. Research to identify factors that delay presentation and compromise quality of life can help oncologists provide more effective care for patients with malignant wounds.