tbuckley/cabot-search huggingface dataset:
Bladder-preserving therapy using a real-time tumor-tracking radiotherapy system for muscle-invasive bladder cancer.
Authors: Haruka Miyata, Takahiro Osawa, Jun Frumido, Hiroshi Kikuchi, Ryuji Matsumoto, Takashige Abe, Satoru Maruyama, Kentaro Nishioka, Shinichi Shimizu, Takayuki Hashimoto, Hiroki Shirato, Nobuo Shinohara
Journal: Journal of Clinical Oncology (2019)

364 Background: Bladder-preserving therapy with a real-time tumor-tracking radiotherapy system (RTRT system) has been used for muscle-invasive bladder cancer (MIBC) since 1998 in our institution. We evaluate long term outcomes of this therapy. Methods: From 1998 to 2016, 38 patients with a T2-T4N0M0 bladder cancer who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection (TUR) and 40 Gy irradiation to the whole bladder was followed by TUR of the tumor bed (1st Evaluation) and endoscopic implantation of fiducial markers in the bladder wall around the primary tumor. Then, a boost of 25 Gy was made to the primary tumor using RTRT system. Protocol TUR of the tumor bed was performed 6 months later (2nd Evaluation). Patients with adequate renal function (CCR&gt;45ml/min) received concurrent chemoradiotherapy with nedaplatin (cisplatin analog made in Japan, 70mg/m2 intravenously, day1, day22, day50). Results: Median follow-up for surviving patients was 6 yr. 5- and 10-yr OS were 55%, 40%, and 5- and 10-yr PFS were 55% and 39%, respectively. The CR rate at 1st evaluation was 66%, in those patients 5- and 10-yr OS rates were 70% and 61%. Among the patients with non-CR at 1st evaluation, CR rate at 2nd evaluation was 31%. Local recurrence occurred in 13 patients. One of them was performed cystectomy and 9 were performed TUR and/or bladder injection therapy. 11 patients experienced distant recurrence, 2 of those was performed chemotherapy. In univariate analysis, male (OS; HR: 0.33, 95% CI: 0.12-0.92, PFS; HR:0.25, 95% CI: 0.09-0.69) and PS0-1 (OS; HR: 0.26, 95% CI: 0.09-0.79, PFS; HR: 0.29, 95% CI: 0.10-0.85) were significantly associated with good OS and PFS (shown in Table). In multivariate analysis, the both of these covariates were also significantly associated with good OS and PFS (male; OS; HR: 0.31, 95% CI: 0.11-0.88, PFS; HR: 0.21, 95% CI: 0.07-0.62, PS0-1; OS; HR: 0.25, 95% CI: 0.08-0.76, PFS; HR: 0.24, 95%CI: 0.09-0.75). Conclusions: Bladder-preserving therapy is a considerable option in patients medically unfit for or not desiring cystectomy.
Immune infiltrate with CD8 low or PDL1 high associated with metastatic prostate cancer after radical prostatectomy (RP).
Authors: Cecile Vicier, Lillian Werner, Ying Huang, Anis Hamid, Carolyn Evan, Massimo Loda, Christopher Sweeney
Journal: Journal of Clinical Oncology (2019)

86 Background: Given limited information about the prostate cancer (PC) immune infiltrate in men with localized disease, we profiled 6 markers and correlated them with risk of metastases after RP, using a single-institution cohort. Methods: Using a tissue microarray (TMA) with formalin-fixed, paraffin-embedded radical prostatectomy specimens, we performed a multiplex immunohistochemistry (IHC) analysis of immune checkpoint markers (PD1, PDL1), T-cell regulator / helper (FOXP3, CD4) and killer T cells (CD3, CD8). Quantitative multispectral imaging analysis was used to define the “density” of each marker: a ratio between number of positive cells divided by glandular and stromal area. Data collected included patient characteristics, time to biochemical relapse (BCR), time to metastasis (M1) and overall survival (OS). Results: TMA staining resulted data for at least one marker for 129 patients and all 6 markers for 109 patients. Median follow-up for this cohort was 14 years (0.25-27 years). As detailed in the table, either low CD8 or high PDL1 had a statistically significant association with biochemical and metastatic relapse and trend toward poorer OS on univariate analysis (UVA). A risk score of 0, 1 or 2 with CD8 low and PDL1 high each being one point revealed a strong association with higher score and incremental risk of BCR and metastasis. Conclusions: Multiplex IHC profiling of primary prostate cancer revealed high PDL1 and low CD8 density as poor prognostic markers alone and more impactful as part of a risk score for biochemical and metastatic relapse. [Table: see text]
Induction chemotherapy followed by transoral laser microsurgery: A mutimodal approach to improve outcomes for locally advanced laryngeal cancer patients?
Authors: Maria Cossu Rocca, Fausto Maffini, Susanna Chiocca, Mariangela Massaro, Luigi Santoro, Augusto Cattaneo, Elena Verri, Fausto Chiesa, Lorenzo Preda, Franco Nole, Mohssen Ansarin
Journal: Journal of Clinical Oncology (2015)

e17039 Background: The need to combine cure with preservation of laryngeal functions is the challenge in laryngeal cancer treatment. We conducted a randomized phase II study with platinum induction chemotherapy followed by Transoral Laser Microsurgery (TLM) in patients with intermediate laryngeal cancer. The clinical aim was to evaluate feasibility and the research purpose the investigation of new predictive markers. Methods: Between 2006 and 2008, 32 patients (pts) were evaluated and 22 were randomized in the study. All patients had histologically proven diagnosis of squamous cell carcinoma of the glottis in stage T2 N0 M0 (tumor extended to supraglottis and/or subglottis, and/or with impaired vocal cord mobility) or T3 N0 M0 (only tumors limited to the larynx, with invasion of the paraglottic space or with minor thyroid cartilage erosion and without arytenoid fixation). Eleven pts were treated in arm 1 with cisplatin (CDDP) + 5Fluorouracil (5FU) iv 5-days continuous infusion and 11 pts in arm 2 with CDDP + vinorelbine (VNR) + 5FU iv 21-days continuous infusion. TLM was performed within the fourth week from the beginning of the last course of chemotherapy and biological markers were assessed on initial biopsy and further analysed. Results: At 2 years disease free survival (DFS), Overall survival (OS) and organ preservation (OP) were respectively 70%, 100% and 100% with adequate laryngeal function. No patient underwent gastrostomy or tracheostomy. The laryngeal preservation rate at 50 months was 93.75%: only one patient (1/16) lost his larynx due to tumor loco-regional relapse. Among markers investigated, low protein levels of Thymidylate Synthetase (TS) were statistically significant in responder patients Conclusions: Our treatment approach did not worsen DFS and OS compared to the results of standard treatments reported in the Literature. With regards to biological findings, our results could be a good omen for future studies that can direct the course of laryngeal cancer treatment
Clinicopathologic and germline mutation analysis of young patients (age 40 and younger) with pancreatic ductal adenocarcinoma.
Authors: Akihiro Ohmoto, Chigusa Morizane, Emi Kubo, Erina Takai, Kazuaki Shimada, Takuji Okusaka, Shinichi Yachida
Journal: Journal of Clinical Oncology (2015)

e15296 Background: The median age of pancreatic ductal adenocarcinomas (PDAC) patients is approximately 70 years. PDAC rarely affects individuals under the age of 40. We investigated clinicopathologic features and germline mutations of PDAC occurring in young patients ( ≤ 40 years) in order to determine if any difference exists in comparison to those of older patients. Methods: We reviewed a single-institution database of 908 patients with pathologically proven PDAC between 2002 and 2013. We examined the clinicopathologic features in PDAC patients who are less than 40 years of age and compared them to those in older patients ( > 40 years). In addition, we targeted-sequenced 53 genes related to hereditary cancers in 9 patients with available DNA by high throughput platform. Results: Of these 908 patients, a total of 17 patients (1.9%) less than 40 years of age were identified, with a range of 28 to 40 years. There are no differences between groups in terms of gender, smoking, tumor location, UICC stage, morphologic features, a family history of PDAC and a family history of other cancers. In the young patients group, four of them were diagnosed with UICC Stage I-II, four with Stage III, and the remaining nine with Stage IV. Median overall survival in all young patients was 6.7 months, 1-year survival rate; 37.5%. Only one patient had a family history of PDAC. Five of the 17 young patients had a family history of any cancer in first-degree relatives. Targeted-sequencing showed frameshift mutations in MSH6, one of the DNA mismatch repair genes, in two of nine young patients. Sanger sequencing confirmed the presence of these mutations. Conclusions: PDAC patients who are less than 40 years of age are rare (1.9%). The clinicopathologic features in young patients were generally similar to those in older patients. Unexpectedly, almost all young patients had no family history of PDAC, but germline mutations in the MSH6 gene were detected in some cases, suggesting that germline mutations of DNA mismatch repair genes might be related to onset of PDAC at a young age in Japan.
Emerging Real-World Midostaurin Treatment Patterns and Outcomes in FLT3-Mutated Acute Myeloid Leukemia at a Comprehensive Cancer Center
Authors: Connor Willis, Jyothi Menon, Sudhir Unni, Trang Au, Briana Ndife, George J Joseph, Gaetano J Bonifacio, Eytan M. Stein, Srinivas K. Tantravahi, Paul J Shami, Tibor Kovacsovics, Diana Brixner, David Dean Stenehjem
Journal: Blood (2018)
Next generation sequencing of primary prostate cancer tumors to reveal potentially actionable opportunities for clinical management: The UNC experience.
Authors: Daniel James Crona, Anthony Drier, Jing Daisy Zhu, Emily Fox Bell, Margaret Rose Sketch, Amy Garrett, Khalis Mitchell, Scott A Tomlins, Elizabeth Claire Dees, Paul Alphonso Godley, Mary Dunn, Tracy L Rose, Ethan M. Basch, Matthew I. Milowsky, Young E. Whang
Journal: Journal of Clinical Oncology (2019)

305 Background: The Strata trial (NCT03061305) is a multi-institutional precision oncology collaboration structured as an observational protocol that aims to match patients to genomically-guided therapies. Methods: Selected University of North Carolina (UNC) metastatic prostate cancer (mPC) patients were enrolled on this IRB-approved study. Formalin fixed paraffin-embedded primary tumor specimens, without matched germline controls, were sent for targeted next generation sequencing (NGS) to detect actionable variants, including: mutations in 87 genes, copy number variations in 31 genes, and gene fusions in 46 gene drivers. mPC-related genes of particular interest included: AR, ATM, BRCA1/2, ERG, MSH2, MSH6, PTEN, RB1, and TP53. Results: Of the 92 cases sequenced, 5 [5%] failed testing. Of the 87 mPC patients (median age 69 years [47-86]) enrolled: 53 [61%] were white, 28 [32%] were black, 1 [1%] was Asian, and 5 [6%] declined to be identified. NGS data revealed 106 variants in 27 genes: 62 patients (71%) had at least one variant, 21 (24%) had 2 variants, 7 (8%) had 3 variants, and 4 (3%) had 4 variants. Among the 62 patients with at least 1 identified variant, TMPRSS2-ERG fusion occurred most frequently (50%), followed by TP53 (40%), and PTEN (16%). 6% of all sequenced patients had variants in DNA damage repair genes including ATM (3%), BRCA2 (2%) and MSH2 (1%). One patient had a SLC45A3-ERG fusion combined with PTEN deep deletion, which has been associated with a more aggressive phenotype. One patient with a microsatellite-instability high tumor was treated with pembrolizumab. Conclusions: The UNC experience shows that a high proportion of primary prostate cancer tumors from mPC patients have genomic variants, and one patient was treated based on these data. Limited actionability may reflect the landscape of currently FDA approved mPC treatments, and available clinical trials. It may also be due to a short follow-up, and these data could inform treatment planning upon progression.
Abstract P085: Extremes of Sleep Duration and Type II Diabetes in Older Women Participating in the Women’s Health Study
Authors: Jonathan Z Butler, Natalie Slopen, Susan Redline, Mercedes Carnethon, David R Williams, Tiffany M Powell-Wiley, Aruna Pradhan, Julie Buring, Michelle A Albert
Journal: Circulation (2019)

Background: Extreme sleep duration defined as either short (&lt;6 hours) or long (&gt;9 hours) sleep is positively associated with cardiovascular disease (CVD). Because sleep disturbance is prevalent in older women, we evaluated the relationship between extremes of sleep duration and type II diabetes (diabetes) in older women. Methods and Results: In a cross-sectional analysis, we examined the association between self-reported short and long sleep duration and diabetes among 21, 769 older women (mean age = 71. 2 ± 6.0 years old) participating in the ongoing follow-up cohort of the Women’s Health Study. Compared to women with diabetes (N=2539) who slept an average of 6-9 hours, diabetic women who reported short sleep were younger, more likely to be current smokers, less likely to use 1+ drinks/day, were less physically active, had lower annual household income and were less likely to possess a bachelor’s degree. Diabetic women who reported long sleep were older, less likely to be a current smoker, more likely to drink 1+ drinks/day, more likely to have hypertension, depression and anxiety symptoms, were less likely to have a bachelor’s degree, and had a lower annual household income. Logistic regression analyses adjusted for age and race/ethnicity revealed that both short [OR, 95% CI: 1.86 (1.48-2.34)] and long [OR, 95% CI: 1.49 (1.34-1.66)] sleep were significantly associated with a higher odds of diabetes (reference = 6 to 9 hrs sleep). These significant relationships persisted but were somewhat attenuated after control for CVD risk factors and psychological status (i.e., depression and anxiety symptoms) [Short: OR, 95% CI: 1.38 (1.07-1.70); Long: 1.28 (1.14-1.45)]. Conclusion: Extremes of sleep duration were significantly associated with higher odds of diabetes in older women participating in the Women’s Health Study. These hypothesis-generating data suggest that short and long sleep duration might confer key heightened cardiometabolic risk even in older women.
Association of CXCL12 and TNF-α Gene Polymorphisms and Susceptibility to Cervical Cancer.
Authors: Geping Yin, Juan Li, Aifang Wu, Jing Liang, Yuanyuan Zhi
Journal: Journal of Clinical Oncology (2015)

e16531 Background: Further research is required to identify single nucleotide polymorphisms (SNPs) associated with cervical cancer. To assess the association of TNF-α/rs1799724 and CXCL12/rs266085 polymorphisms with susceptibility to cervical cancer in Han Chinese population in Shandong Province. Methods: 348 patients with cervical squamous cell carcinoma, including CIS (121) and invasive carcinoma (227), and 351 healthy controls. Genomic DNA was isolated from peripheral blood and genotyping for TNF-α/rs1799724 and CXCL12/rs266085 was carried out using TaqMan SNP Genotyping Assays. Results: TNF-α/rs1799724 polymorphism showed the C-allele was less prevalent among cases as compared to controls (74.3% vs 92.0%), while the T-allele was more prevalent among cases (P = 0.000, OR = 3.99, 95%C.I.：2.90-5.51). CXCL12/rs266085 polymorphism showed the C-allele was less prevalent among cases as compared to controls （41.2% vs 49.7%), while the T-allele was more prevalent among cases (P = 0.001, OR = 1.41 , 95% C.I.：1.14-1.74). The genotype and allele frequencies of these two SNPs did not differ between CIS and invasive squamous cell carcinoma (P > 0.05). Moreover, the allele frequencies of rs1799724 were significantly different between controls without or with HPV infection (P < 0.05). Neither the genotype nor allele frequencies of rs266085 were statistically different between HPV-negative and positive controls. Conclusions: TNF-α/rs1799724 and CXCL12/rs266085 polymorphisms are associated with cervical cancer. C- > T polymorphism of these two SNPs and HPV infection are linked to high risk for cervical cancer.
Abstract MP48: Control of Cardiovascular Risk Factors Among Older Adults With Incident Diabetes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Gargya Malla, Andrea Cherrington, Sha Zhu, Doyle M Cummings, Olivio Clay, Todd M Brown, Loretta T Lee, Ruth Kimokoti, Mary Cushman, Monika M Safford, April P Carson
Journal: Circulation (2019)

Background: Control of risk factors is important for the primary prevention of cardiovascular disease among adults with diabetes. The objective of this study was to determine whether management of clinical (hemoglobin A1c &lt;8%; BP &lt;130/80 mm Hg; and statin use) and lifestyle factors (not currently smoking; physical activity on 4+ days/week; and moderate or no alcohol use) varied by race and sex among older adults with incident diabetes. Methods: This study included 1,420 Black and White adults from the REGARDS Study with incident diabetes at the follow-up exam (2014-16). Incident diabetes was defined as fasting glucose&gt;=126 mg/dL, random glucose&gt;=200 mg/dL, or use of diabetes medications among those without diabetes at baseline (2003-07). Modified Poisson regression was used to obtain prevalence ratios (PR) for the control of risk factors for Black versus White adults and assess race-sex interactions. Results: The mean age was 71.5 years, 53.6% were female, 46.1% were Black and 85.7% reported they were aware of their diabetes. BP control was lower for Black males than White males (p=0.0036), whereas statin use was lower for Black females than White females (p=0.0241). For lifestyle factors, not smoking was lower for Black males than White males (p=0.0187), whereas moderate or no alcohol use was higher for Black females than White females (p&lt;0.0001). (Figure) Race-sex interactions were not statistically significant. In age and sex-adjusted models, Black adults were less likely to have BP controlled (PR=0.89; 95% CI=0.81, 0.99) or use statins (PR=0.88; 95% CI=0.80, 0.97) and more likely to report moderate or no alcohol use (PR=1.05; 95% CI=1.03, 1.07) than White adults. Control of other factors was similar. Conclusion: Although control of individual risk factors was generally high among older adults with incident diabetes, racial differences in BP control and statin use were apparent. Assessment and management of cardiovascular risk factors in this high-risk population remains important for prevention.
Abstract P155: Smoking, Its Cessation, and Future Risk of Heart Failure: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ning Ding, Amil M Shah, Michael J Blaha, Patricia P Chang, Wayne D Rosamond, Kunihiro Matsushita
Journal: Circulation (2019)

Introduction: Smoking is considered as a major risk factor for cardiovascular disease, including heart failure (HF). Few studies have evaluated the prospective association of detailed smoking parameters (including duration, intensity, and cessation) with incident HF. Hypotheses: These smoking parameters will be associated with incident HF. Methods: In 14,010 ARIC participants free of a history of HF at baseline (1987-89), we quantified the associations of smoking parameters (pack-years, duration, and intensity [pack/day]) with incident HF (hospitalizations with HF diagnosis [ICD-9: 428.0-428.9] or a death certificate ICD-9 code 428.0-428.9 or ICD-10 code I50.0-I50.9) using Cox models. Years since quitting in former smokers (&lt;5, 5-9, 10-19, 20-29, and ≥30 years) were explored as time-varying variables, with time-varying covariates whenever possible. Results: Over a median follow-up of 26 years, there were 3,047 cases of HF. Pack-years was significantly associated with incident HF (HR 1.31 [95% CI 1.28-1.35] per 20 pack-years). Both smoking duration and intensity showed significant associations with HF (HR 1.62 [1.55-1.70] per 20 years of smoking and 1.43 [1.36-1.50] per 1 pack/day). Smoking cessation demonstrated a graded association with HF, with significantly increased risk even after cessation for ≥30 years (1.16 [1.04-1.31]) (Table-Model 2). After further adjusting for incident coronary events, the association was attenuated but remained significant up to cessation for 10-19 years (Table-Model 3). Conclusions: All smoking parameters tested in this study consistently show significant associations with incident HF. The HF risk related to smoking lasted at least 19 years after its cessation. Our results further highlight the importance of smoking prevention and early smoking cessation for the prevention of HF.
Abstract 13502: African Americans with Hypertrophic Cardiomyopathy Manifest a More Myopathic and Less Obstructive Phenotype than Caucasians
Authors: Lars L Sorensen, Aurelio Pinheiro, Veronica Dimaano, Hsin-Yueh Liang, Iraklis Pozios, Hong-Chang Luo, Maria R Abraham, Thomas Fritz-Hansen, Niels T Olsen, Peter Sogaard, Theodore P Abraham
Journal: Circulation (2012)

Background: Hypertrophic Cardiomyopathy (HCM) is an inherited cardiomyopathy known to affect African Americans who may be proportionately at higher risk than other ethnic groups. However, there has...
Early Detection of Hypoglycemia in Type 1 Diabetes Using Heart Rate Variability Measured by a Wearable Device
Authors: Marleen Olde Bekkink, Mats Koeneman, Bastiaan E. de Galan, Sebastian J. Bredie
Journal: Diabetes Care (2019)

OBJECTIVE Changes in heart rate variability (HRV) occur at the initiation of hypoglycemia due to sympathetic nervous system activity. We investigated the use of HRV detection by a wearable device as an early alert for hypoglycemia. RESEARCH DESIGN AND METHODS This proof-of-principle study included 23 patients with type 1 diabetes (14 women, mean age 42 ± 11 years). Patients wore a VitalConnect HealthPatch for 5 days. Hypoglycemia was defined as glucose ≤70 mg/dL (≤3.9 mmol/L) by fingerstick measurement. HRV was analyzed in standardized periods before the hypoglycemic event. RESULTS Sixty-six hypoglycemic events were recorded. Hypoglycemia caused a typical HRV pattern in 36 (55%) of the hypoglycemic events. Eighteen events (27%) showed an atypical pattern. Ten events were unclassified (15%), and two did not display a change in HRV (3%). CONCLUSIONS Hypoglycemia causes early changes in HRV that can be detected by a wearable device. Measuring real-time HRV seems promising for early hypoglycemia detection.