tbuckley/cabot-search huggingface dataset:
Tumor testing in men with prostate cancer to predict for germline DNA-damage repair mutations.
Authors: Maria Isabel Carlo, Yelena Kemel, Kelsey Breen, Karen Anne Cadoo, Michael Francis Walsh, Wassim Abida, Karen A. Autio, Daniel Costin Danila, Lewis J. Kampel, Michael J. Morris, Dana E. Rathkopf, Susan F. Slovin, David B. Solit, Kenneth Offit, Zsofia Kinga Stadler, Howard I. Scher, Mark E. Robson
Journal: Journal of Clinical Oncology (2019)

229 Background: Current guidelines recommend genetic testing for patients (pts) who have BRCA1/2 mutations on tumor-only testing, where germline is not subtracted. The clinical utility of this approach, and possible inclusion of other DDR genes associated with cancer susceptibility, has not been examined in men with prostate cancer. Methods: Pts with mostly advanced prostate cancer were prospectively enrolled to a matched tumor-germline DNA sequencing protocol and consented for disclosure of germline results. Germline analysis was done with an institutional, CLIA-certified next generation sequencing (NGS) platform (MSK-IMPACT) and analyzed for likely pathogenic or pathogenic germline mutations in at least 76 cancer susceptibility genes. Clinical data was retrieved from the medical record. We report on the frequencies in the germline and in the tumor of a subset of DDR genes. Results: 1243 men had analysis of both germline and tumor. Median age 64 (range 35-90). 12% had a second malignancy and 40% reported a relative with prostate cancer. 19% were of Ashkenazi Jewish (AJ) descent. 330 (27%) had any mutation in BRCA1/2, ATM, CHEK2, PALB2, RAD51C, RAD51D, MSH2, MSH6, MLH1, PMS2. 127 (10%) had a germline mutation, of which 36% were AJ founder mutations. For each gene, the percentage of mutations found in germline and tumor is shown in the table. Conclusions: Of prostate cancer pts found to have any DDR mutation on tumor-germline testing, 29% had a germline mutation. Proportion of germline mutations was highest for PALB2, CHEK2 and BRCA2. These findings not only support germline testing when BRCA1/2 mutations are found tumor-only sequencing, but also support germline testing when other DDR mutations are seen. Clinical trial information: NCT01775072. [Table: see text]
Prediction of lymph node involvement in breast cancer using RNA-sequencing and microRNA expression profile.
Authors: Agust Barnadas, Laura Lopez-Vilaro, Cristina Arqueros, Teresa Ramon y Cajal, Eleonor Paola Murata, Joan Duch, Antonio Moral, Josefina Mora, Maitane Perez-Olabarria, Tania Vazquez, Barbara Garcia Valdecasas, Enrique Lerma, Daniel Escuin
Journal: Journal of Clinical Oncology (2015)

e12558 Background: Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We profiled the expression of miRNAs in paired breast tumor samples and SLNs, and correlate the results with the metastatic lymph node status and the outcome of axillary lymph node dissection (ALND). Methods: we compared 60 paired primary tumor and OSNA-diagnosed SLN from patients with breast cancer. We extracted total RNA and analyzed the miRNA expression profile using RNA-sequencing (MiSeq Illumina). Significant differential expression of miRNAs were tested using the Limma package. The Benjamini-Hochberg method was used to control the false discovery rate. Statistical significance was tested using the square root transformed tpm expression values of the 5p and 3p miRNA transcripts. We used the package Dchip to calculate absolute correlations using analysis of variance with P ≤ 0.01. Gene lists were used to classify samples by linear discriminant analysis and cluster analysis. Gene lists and classification results were chosen according to the highest classification accuracy after cross validation. Results: median age was 64 years (range, 26-88 years). Fifteen patients (25%) had tumor stage I and 43 (72%) had stage II tumors. Twenty patients (33%) had SLN-positive micrometastasis and 20 (33%) SLN-positive macrometastasis. Twenty patients underwent ALND and 5 (25%) had axillary LN metastatic disease. Twenty-six (43%) patients were treated with mastectomy and 31(57%) with lumpectomy. All 60 tumors were invasive ductal carcinomas, 46 (77%) were hormone positive, 9 were HER2-positive and 5 were triple negative tumors. We anticipated that primary tumors with positive SLNs share a particular miRNA expression profile that predicts the outcome of ALND. We are currently analyzing our data analysis to identify the deregulated miRNAs and their association with specific biological pathways. Conclusions: miRNA expression profiling has the potential to identify biomarkers predictive of SLN metastasis and the outcome of ALND in breast cancer.
Molecular characterization of longitudinally tracked prostate cancer foci in men on active surveillance for low-risk disease.
Authors: Jeffrey J. Tosoian, Simpa Samuel Salami, Srinivas Nallandhighal, Tonye A. Jones, Komal R. Plouffe, Fuad F. Elkhoury, Todd Matthew Morgan, Chia-Jen Liu, Lakshmi Priya Kunju, Jeffrey S. Montgomery, Shyam Natarajan, Anthony Sisk, Scott A. Tomlins, Ganesh S. Palapattu, Leonard S. Marks
Journal: Journal of Clinical Oncology (2019)

56 Background: The biological trajectory of Gleason score 6 (GS6) prostate cancer (PCa) in men on active surveillance (AS) is unknown. We herein evaluate the potential for high grade PCa to arise clonally from GS 6 disease and determine the capacity of tissue-based biomarkers to predict grade progression. Methods: Men on AS with GS6 PCa who underwent magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy on two occasions from 2012 through 2017 were enrolled. Tumor foci were tracked and re-sampled using the MRI/US fusion biopsy platform. ERG immunohistochemistry (IHC) and DNA/RNA next generation sequencing (NGS) were performed on formalin-fixed paraffin-embedded (FFPE) initial and repeat biopsy specimens to assess tumor clonality and evaluate candidate molecular markers of PCa grade progression. Results: Sixty-seven men of median age 64 years (IQR 59-69) and PSA 4.9 ng/ml (IQR 3.3-6.4) underwent repeat sampling of a single tracked tumor focus using MRI/US fusion biopsy. The median interval to repeat biopsy was 11 months (IQR 6-13). On repeat biopsy, 31 (46%) men progressed to high-grade (GS≥7) disease (n = 24, GS 3+4 = 7; n = 7, GS ≥4+3 = 7). Among the 67 subjects, ERG IHC status was concordant between initial and repeat biopsy in 64 (96%). Of 134 total specimens obtained (67 initial + 67 repeat biopsies), ERG status determined by NGS was concordant with ERG status by IHC in 132 (99%). Comparing the initial biopsy specimens in men who did versus did not undergo grade progression on follow up biopsy, derived cell cycle progression (CCP) scores (median 57.3 vs. 44.0, p = 0.11) and genomic prostate scores (GPS; median 73.8 vs. 64.4, p = 0.15) were not significantly different. Similarly, expression of FOLH1, PCAT4, SCHLAP1, and SPINK1 on initial biopsy did not significantly differ among men who did and did not undergo grade progression. Conclusions: Use of MRI/US fusion biopsy facilitated resampling of the same clonal focus of cancer over time, with high concordance of ERG status determined by both IHC and NGS. Derived genomic classifiers and candidate individual gene expression markers measured on initial biopsy tissue were not significantly different between patients who progressed and those who did not.
Abstract P355: Religious Attendance, Educational Attainment, and Hypertension. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Ana C Varella, Isabela M Bensenor, Rosane Griep, Maria-Jesus Fonseca, Alexandre C Pereira, Paulo A Lotufo
Journal: Circulation (2019)

Introduction: The relationship between the level of religiosity and health-adverse outcomes has been controversial. One reason should be that how "religiosity" is measured or by a self-declaration (meaning more a cultural variable than a manifestation of the spirituality) of by regular religious practices attendance. Several studies pointed out that educational attainment has a close relationship with the practice of religion. In Brazil, the non-practice religious persors have a higher level of formal education than the general population. Therefore, researchers have focused on risk factors, such as hypertension, studying the effect of religious service attendance, besides other religious dimensions, on blood pressure. Hypothesis: This study has a premise that attending to religious ceremonies are associated with hypertension according to levels of education. Methods: At baseline of the ELSA-Brasil study (15105 adults aged 35-74years old), we asked about the frequency of attendance to religious services. Hypertension was defined as systolic or diastolic blood pressures higher than 140/90 mm Hg or under antihypertensive drugs. Educational attainment was categorized as less or more than high school.Logistic regression models were used to obtain odds ratio (OR) and 95% confidence intervals (95%CI) for the association between frequency of attendance and hypertension adjusted for age, sex, race, income, physical activity and salt consumption (estimated by 12-hour urinary sodium excretion). Further, we added variables that are potential mediators of the religion-hypertension association as smoking, alcohol consumption and body-mass index, depending on the level of education. Results: Three-quarters (76.9%) of the participants reported to be religious (mean age of 51.6 years, 58.7% women; 51.8% white), and 49.8% of them declared religious attendance at least weekly. For those with a higher educational level, no association was found an inverse association between frequent religious service attendance and the presence of hypertension, also concerning sociodemographic variables, and between religious practice attendance and hypertension after adjusting for covariates (OR = 1.10, 95% CI 0.98-1.23). However, for subjects with lower educational attainment, religious attendance was inversely associated with hypertension (OR = 0.71, 95%CI 0.53-0.96), after adjusting for covariates. We did not find differences in each educational attainment strata related to association religious attendance and hypertension when stratified by gender, race, family income, and to be Roman Catholic and non-Roman Catholic. Conclusion: The effects of religious involvement on hypertension seem to diverge according to socioeconomic status, represented here by educational attainment.
Adjuvant chemotherapy using s-1 improves survival in patients with resected advanced extra-hepatic bile duct cancer: A propensity score matching analysis.
Authors: Yoshikazu Toyoki, Keinosuke Ishido, Daisuke Kudo, Norihisa Kimura, Kenichi Hakamada
Journal: Journal of Clinical Oncology (2015)

e15170 Background: Complete surgical tumor resection is the only curative treatment option for extra-hepatic bile duct cancer (EHBDC), but the prognosis of this disease is still poor. The necessity for adjuvant therapy is considered after curative resection. However there are very few reports of effective adjuvant therapy for resected advanced EHBDC until now. This study aimed to evaluate adjuvant chemotherapy using S-1 for patients with EHBDC by a propensity score matching analysis. Methods: From January 2004 to December 2012, 154 patients who had curative resection for EHBDC were classified into two groups: A, 99, surgery alone, and B, 55, surgery with S-1 adjuvant chemotherapy. Patients with pathological stage II, III, or IVa BTC (according to JSBS) who underwent radical resection received oral S-1 (80 mg/m2/day) for 2 consecutive weeks every 3 weeks (1 cycle). The patient underwent surgery with S-1 was matched to patient underwent surgery alone using nearest-neighbor matching without replacement. Propensity scores were matched using caliper width 1/5 logit of the SD, thirty three and exact matches were performed on age, gender, tumor location, operative time, intraoperative blood loss, transfusion, lymph nodes metastasis, curability, clinocopathological factors. Results: There were no differences in characteristics between patients of S-1 group and no S-1 group for age, gender, tumor location, T factor, lymph nodes metastasis, curability, clinocopathological factors, intraoperative blood loss and operative time. The 3, 5-year DFS rate after surgery in no S-1 group were 29.6 and 22.2%. On the other hands, in S-1 group were 59.5 and 47.6% (p = 0.023). The 3, 5-year OS rate after surgery in no S-1 group were 42.3 and 25.0%. On the other hands, in S-1 group were 74.8 and 52.5% (p = 0.005). Conclusions: As a results of propensity score matching analysis, we believe that adjuvant chemotherapy using S-1 has potential benefits for resected advanced EHBDC patients because of the associated improved prognosis.
Risk factors for venous thromboembolism (VTE) during chemotherapy in patients with germ cell tumors (GCT).
Authors: Cassia R Griswold, Erin B. Bailey, Jessica Campaign Mauser, Kenneth M. Boucher, Neeraj Agarwal, Sumati Gupta, Benjamin Louis Maughan
Journal: Journal of Clinical Oncology (2019)

520 Background: The Khorana score is the primary tool utilized to predict VTE risk in patients with cancer. This score incorporates primary cancer site, pretreatment hematologic parameters, and body mass index. GCT are considered high-risk for VTE. However, risk factors for VTE not included in the Khorana Score have been reported for GCT including retroperitoneal lymph node (RPLN) size, elevated LDH, and poor risk disease. Methods: A retrospective chart review was conducted to correlate known VTE risk factors with VTE incidence in male patients with GCT undergoing first-line chemotherapy. Variables included venous access type, RPLN size, LDH, chemotherapy regimen, procedure history, cancer stage and histology, Khorana risk factors, and pertinent demographics. VTE and superficial vein thrombosis (SVT) events that occurred within 1 month prior through 6 months after start of chemotherapy were recorded. Fisher’s Exact test was used for univariate analysis and logistic regression for multivariate analysis of the relationship between predictors and thrombosis. P-values are two-sided at an alpha level of 0.05. Results: 47 patients with GCT were identified. 12 VTE occurred (overall incidence 25.5%), 11 in patients with central lines (39.3% incidence) and 1 with a peripheral line (5.3% incidence). SVT were observed in 5 patients with peripheral lines compared to 1 patient with a central line (26.3% vs. 3.6%). Central line access was the primary variable associated with VTE risk in both univariate and multivariate analysis (p=0.01 and p=0.03, respectively). Conclusions: Venous access type is a significant but modifiable factor that can be targeted to reduce VTE risk. Due to small sample size there is limited statistical power to detect potentially meaningful differences in known risk factors. If validated, these results may identify specific patients to be treated with prophylactic anticoagulation. [Table: see text]
Mini‐Generator Based on Reciprocating Vertical Motions Driven by Intracorporeal Energy
Authors: Lina Zhang, Mengjiao Cheng, He Luo, Haibo Zhang, Guannan Ju, Peng Liu, Yifeng Zhou, Feng Shi
Journal: Advanced Healthcare Materials (2019)

Abstract Most implantable devices rely on a power supply from batteries and require replacement surgeries once the batteries run low. Mini‐generators that harvest intracorporeal energy available in the human body are promising replacements of batteries and prolong the lifetime of implantable devices, thus reducing surgery pain, risks, and cost. Although various sources of energy available in the human body are used for electricity generation using piezoelectric and triboelectric materials or intravascular turbines, concerns about material durability or thrombus risks remain, and developing novel strategies to fabricate a mini‐generator to harvest the intracorporeal energy is still challenging. Herein, a mini‐generator system is designed by exporting the systolic/diastolic blood pressure from the femoral artery of a sheep to trigger the pressure‐responsive reciprocating vertical motions of a conductor. By applying a magnetic field, an induced voltage of 0.32 V and a stable output power of 13.86 µW are obtained, which is promising to power a state‐of‐the‐art pacemaker (8–10 µW). The noncontact electricity generation strategy provides a novel avenue to sustainable power supply for implantable devices.
Generating and visualizing breast re-excision rate from registry and administrative data.
Authors: Ravi V Atreya, Mia Alyce Levy
Journal: Journal of Clinical Oncology (2015)

e17624 Background: Monitoring quality metrics in near real time can help healthcare providers and organizations improve care delivery, engage patients, and comply with reporting requirements of accreditation bodies. However, use of registry data alone limits the ability to provide near real time quality metrics, while clinical and administrative data may be incomplete or biased. In this study, we focus on generating breast cancer re-excision rates in an automated fashion and visualizing surgical treatment paths in novel ways. Methods: This study used surgical registry codes and administrative CPT codes for women diagnosed with stage I-III breast cancer between 2000 and 2012 at a comprehensive cancer center. We measured the re-excision rate for this patient population and used the Chi-square test for trends to compare the CPT rates against the registry rates. We also used Sankey diagrams to represent surgical paths. Results: 1582 patients had 3208 surgical events in the tumor registry. Corresponding CPT codes were missing for 28% of the 3208 surgical events, most of which were for the first surgical event in the sequence (see table). Based on registry data, 890 of the 1582 patients had a breast conserving surgery as their first surgical event. Of those, 68% did not require any additional surgery, 20% required a re-excision, and 11% advanced to receive a mastectomy. There was no significant difference in the annual re-excision rates between both data sets while there was a significant reduction in re-excisions over time in both. Finally, we developed intuitive Sankey diagrams to illustrate the progression of the surgical course. Conclusions: We were able to calculate similar re-excision rates from manually curated registry data as well as near real time administrative data. Our analysis showed that despite the missing CPT data, administrative and clinical data could be used to generate quality metrics and visualize data in a more real time fashion to help patients and providers make data informed decisions. Number of missing CPT codes at different positions in the surgical event sequence. Position in Surgical Sequence Total # of CPT Codes # of Missing CPT Codes % of Missing Codes in Position 1 2830 771 27.2% 2 612 108 17.6% 3 135 8 5.9% 4 17 0 0.0% 5 1 0 0.0%
Testosterone-guided schedule of androgen deprivation therapy (ADT) as an alternative to a fixed schedule in management of prostate cancer.
Authors: Saroj Niraula, Francisco Emilio Vera Badillo, Arnoud J. Templeton, Anna Dodd, Zoann Nugent, Ian Tannock
Journal: Journal of Clinical Oncology (2015)

5039 Background: ADT with LHRH agonists that reduce testosterone production is effective initial therapy for treatment of men with advanced prostate cancer. LHRH agonists are usually administered indefinitely at a fixed interval despite their cost and serious toxicity. Methods: We recruited men with prostate cancer who had been on fixed-schedule injections of a LHRH agonist (most commonly given as 12 weekly injections) for at least one year and had castrate levels of serum testosterone ( < 1.7 mmol/l). We measured their serum testosterone at 6-week intervals, and men resumed their injections only when their serum testosterone was ≥ 1.7mmol/l. We calculated median time to reinstitution of ADT by the Kaplan Meier method and used Cox regression analyses to identify factors predicting delay in reinstitution of treatment. Influence of this approach on quality of life (QoL) was measured by the Expanded Prostate Index Composite (EPIC). Results: From November 2009 to May 2014, a total of 82 men were enrolled. Median age at diagnosis was 68 years (range, 51-83 years). Median time to testosterone recovery after the last injection was 30.8 weeks (Inter-quartile range 17-65 weeks). Lower level of baseline testosterone ( ≤ 1 versus > 1 mmol/l) [Hazard Ratio (HR) 0.32; p = 0.004] and longer duration of disease ( > 5 versus ≤ 5 years) [HR 0.38; p = 0.03] were independent predictors for prolonged time to testosterone recovery. Statistically significant improvement from baseline was noted in the hormonal domain of EPIC (p = 0.002) but not in overall score. Drug costs (LHRH agonist alone) dropped from a median of $4,550 to $1,900 per patient per year. Conclusions: Implementing a testosterone-guided approach to ADT results in a substantial reduction in exposure to, and symptoms from ADT. Drug cost is reduced by > 60% while still maintaining castrate levels of testosterone. Testosterone-guided approach to ADT can have major public health benefits. This approach should be discussed with men on ADT and be considered as the replacement of fixed schedule treatment by physicians and policy makers. Clinical trial information: NCT01007825.
Outcomes in patients (pts) with advanced renal cell carcinoma (aRCC) who discontinued (DC) first-line nivolumab + ipilimumab (N+I) or sunitinib (S) due to treatment-related adverse events (TRAEs) in CheckMate 214.
Authors: Nizar M. Tannir, Robert J. Motzer, Elizabeth R. Plimack, David F. McDermott, Philippe Barthelemy, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Christian K. Kollmannsberger, Howard Gurney, Asim Amin, Marc-Oliver Grimm, Brian I. Rini, Yoshihiko Tomita, M. Brent McHenry, Sabeen Fatima Mekan, Bernard Escudier, Hans J. Hammers
Journal: Journal of Clinical Oncology (2019)

581 Background: The phase 3 CheckMate 214 trial demonstrated superior efficacy for N+I vs S in aRCC, although more patients discontinued N+I compared with S due to TRAEs. This is a post hoc analysis of outcomes in pts who DC N+I or S due to TRAEs. Methods: Untreated pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3Wx4 (induction) and then N 3 mg/kg Q3W (maintenance), or S 50 mg daily for 4 wk on, 2 wk off (6-wk cycles). This analysis includes all pts who DC due to TRAEs reported during extended follow-up (≤100 d after last study dose). Results: Of 550 N+I randomized pts, 135 (25%) DC due to TRAEs, most commonly increased ALT, diarrhea, and increased AST (all 3%); 64 (12%) of 535 S randomized pts DC due to TRAEs, most commonly increased ALT, diarrhea, and pancreatitis (all 1%). In N+I pts who DC due to TRAEs, 47% DC during N+I induction, 7% completed induction but no N maintenance, and 46% completed induction and received N maintenance (median [range] 8 [1–47] doses). At 30-mo minimum follow-up, ORR per investigator, CR rate, and 24-mo OS rate were higher in pts who DC N+I vs S due to TRAEs. Outcomes in pts who DC S due to TRAEs were similar to those in all S ITT pts and worse than in N+I pts who DC due to TRAEs (Table). At 24 mo, 42% of pts who DC N+I due to TRAEs were alive and free from second-line therapy. Consistent outcomes were seen in pts who DC N+I due to TRAEs across IMDC risk groups (data to be presented). Pts who DC N+I due to TRAEs experienced more immune-related select TRAEs and received more high-dose steroids (≥40 mg prednisone daily or equiv.), but times to onset and resolution and resolution rates of select TRAEs were similar vs all treated N+I pts. Conclusions: Discontinuation of first-line N+I due to TRAEs did not result in impaired outcomes, and a high proportion of pts remain alive and free from second-line therapy. Clinical trial information: NCT02231749. [Table: see text]