tbuckley/cabot-search huggingface dataset:
Cell-free DNA (cfDNA) whole genome bisulfite sequencing in patients with muscle-invasive bladder cancer patient treated with cystectomy with curative intent.
Authors: Yi-Tsung Lu, Gerald C Gooden, Ben Yi Tew, David Buckley, Kimberly Siegmund, Siamak Daneshmand, Bodour Salhia, Amir Goldkorn
Journal: Journal of Clinical Oncology (2019)

359 Background: Muscle invasive bladder cancer (MIBC) frequently recurs despite radical cystectomy, and new biomarkers are needed to guide treatment. DNA methylation plays a key regulatory role in cancer initiation and progression and has been correlated with prognosis in multiple cancer types. We hypothesized that methylation patterns in cfDNA can predict recurrence after curative cystectomy. Methods: Using a clinically annotated USC bladder cancer tissue archive under an IRB approved protocol, we selected 40 patients whose cancer relapsed within 3 years of radical cystectomy, as well as 46 age-matched and stage-matched patients who did not recur after 3 years of follow-up. cfDNA was extracted from the archival plasma, and samples were pooled for whole genome bisulfite sequencing (WGBS) based on pathologic stages (T2a, T2b, T3a, T3b, and T4/N+) and recurrence status. Results: Extracted cfDNA and sequencing met QC criteria, and differentially methylated regions (DMRs) were called by metlene and filtered based on &gt; 10% methylation difference (recurrence vs. cured) and p value &lt; 0.01. Pooled analysis across stages yielded 729 DMRs, of which 487 (67%) were hypomethylated in the recurrence groups. Unsupervised clustering of these DMRs accurately distinguished the recurrence groups. Stage-specific DMRs were also called and used to generate a list of differentially methylated genes shared across stages. Methylation by stage and pooled across stage in our recurrence groups was directly correlated with methylation in tumor tissue in publically available datasets (Basespace Correlation Engine) and was inversely correlated with TCGA expression datasets. Conclusions: WGBS was successfully performed in MIBC using cfDNA extracted from archival plasma. Methylation patterns were concordant with publically available datasets, and cfDNA hypomethylation pre-cystectomy was associated with cancer recurrence in our cohort. Additional data filtering and annotation is ongoing and will be used to define a methylation signature for validation as a biomarker predictive of recurrence in MIBC.
Abstract P239: Sugar-Sweetened Beverage Consumption and Risk of Type 2 Diabetes in African Americans: Findings From the Jackson Heart Study
Authors: Chandra L Jackson, Arnita F Norwood, Mario Sims, W. Braxton Jackson, Adolfo Correa, Vasanti Malik, Katherine L Tucker
Journal: Circulation (2019)

Background: There is a paucity of data investigating whether consumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of type 2 diabetes (T2D) among African Americans. OBJECTIVE: To determine, in a prospective analysis, whether SSB consumption is associated with increased risk of T2D among African Americans. RESEARCH DESIGN AND Methods: Using a community-based prospective investigation of Jackson Heart Study adult participants from 2004 to 2010, we estimated risk of T2D by frequency of SSB consumption adjusting for age, sex, marital status, CVD, total energy intake, physical activity, smoking status, alcohol consumption, socioeconomic status, and body mass index (BMI) as a potential mediator. Results: Among 3,223 study participants, the mean age was 53±12.5 years, 63% were women, and 66% had at least a college education. Total energy intake, and intakes of carbohydrates, fat, sugar and caffeine increased with increasing SSB consumption, and 21% of participants consumed ≥1 SSB per day. Mean follow-up was 7.5 years with 24,124 person-years, and there were 561 cases of incident diabetes. After age and sex adjustment, SSB consumption was not significantly associated with T2D risk: hazard ratio (HR): 1.61 [95% confidence interval (CI): 0.58-4.48] for 1-4 times/month, HR: 1.77 [95%CI: 0.66-4.76] for 2-6 times/week, and HR: 1.81 [95%CI: 0.67-4.85] for ≥ 1/day (p for trend=0.291) compared to &lt;1/month. In fully-adjusted models, associations remained positive but non-significant and adjustment for BMI attenuated the associations minimally (≤3%). Conclusions: Although HRs tended to increase with higher intake, the frequency of SSB intake was not significantly associated with risk of T2D in African Americans. Larger studies in this population with consideration of other aspects of the diet are warranted.
Characterization and predictors of sleep disturbance in patients with relapsed/refractory chronic lymphocytic leukemia (r/r CLL).
Authors: Travis D Westbrook, Kami J. Maddocks, Barbara L. Andersen
Journal: Journal of Clinical Oncology (2015)

e18021 Background: Sleep disturbances are common complaints among cancer patients, and are linked to poorer quality of life and cellular immunity, as well as alterations in inflammatory/angiogenic markers. Disturbances may persist for years, particularly when disease is managed with ongoing therapy. CLL is the most prevalent adult leukemia, and often requires lifelong treatment to delay disease progression. Prevalence and predictors of sleep disturbance in CLL have not been examined. The current study describes sleep disturbance among patients with r/r CLL and examines predictors (i.e., cancer-specific stress, depressive symptoms, and pain) of its severity. We hypothesized that predictor variables would positively relate to severity of sleep disturbance. Methods: A cross-sectional design was used. R/r CLL patients (N = 147; 71% male; mean age = 64 years) completed psychological assessments of sleep disturbance, cancer-specific stress, depressive symptoms, and pain at screening for enrollment in a phase II trial of targeted therapy ibrutinib. Sleep disturbance was operationalized as a composite of symptoms including difficulty falling or staying asleep, having restless or non-restorative sleep, and daytime drowsiness due to inadequate sleep. Hierarchical multiple linear regression was used. All analyses controlled for age, gender, smoking status, medical comorbidities, and number of prior CLL therapies. Results: More than 41% of patients felt their sleep was inadequate and only 42% reported achieving 7-8 hours of sleep per night. Rates of daytime tiredness, restlessness during sleep, and non-restorative sleep were elevated in comparison to population norms. Snoring and headaches/breathlessness upon waking were equivalent to population norms. Depressive symptoms, pain, and cancer-specific stress significantly predicted severity of sleep disturbance (ps < .001, R2 values = 0.20, 0.13, and 0.12, respectively). Conclusions: Sleep disturbance is a common burden among patients with CLL. This is the first study to provide insight into psychological mechanisms of sleep disturbance in this population, which may better orient intervention development.
Abstract 14852: Clinical Significance of Non-culprit Plaque Regression Following Acute Coronary Syndrome: A Serial Intravascular Ultrasound Study
Authors: Hirohisa Endo, Tomotaka Dohi, Katsumi Miyauchi, Jun Shitara, Hideki Wada, Shinichiro Doi, Ryo Naito, Hirokazu Konishi, Shuta Tsuboi, Manabu Ogita, Yoshiteru Kato, Iwao Okai, Miho Yokoyama, Hiroshi Iwata, Takatoshi Kasai, Takayuki Yokoyama, Shinya Okazaki, Kikuo Isoda, Kazunori Shimada, Satoru Suwa, Hiroyuki Daida
Journal: Circulation (2017)

Background: Recently, the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis has offered valuable insight into plaque regression/progression. However, the benefic...
Single institutional experience of bevacizumab-based regimens in treatment of hepatocellular carcinoma.
Authors: Reham Abdel-Wahab, Manal Hassan, Kanwal Pratap Singh Raghav, Ahmed S Shalaby, Gehan Botrus, Lianchun Xiao, Jeffrey Morris, Robert A. Wolff, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2015)

e15138 Background: Hepatocellular carcinoma (HCC) is a highly vascular tumors and angiogenesis play an important role in HCC prognosis and treatment response. Our study aim to evaluate the efficacy of bavacizumab based regimens in treatment of HCC patients. Methods: We reviewed records of 148 patients who had advanced HCC; Child Pugh score A or B; Performance status ≤ 2; treated with bevacizumab alone or in combination with Erlotinib; either as first or second line therapy. Univariate analysis was done using the c2 or Fisher’s exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Kaplan-Meier method used to estimate the median overall survival (OS), progression free survival (PFS), time to progression (TTP) and the log rank test was performed to compare subgroups of patients according to the treatment modalities. Results: Among first line treated patients OS was 14.7 (95% confidence interval (CI); 10.8 – 19.6) and median PFS16 was 8.1 months (95% CI; 6.1 – 9.8). While, second line treated patients had OS 11.3 month (95%CI; 8 – NA) and median PFS16 4.9 months (95% CI; 2.01 – NA). Only 1 Patient achieved complete response (0.7%); 15 patients achieved partial response (10.1%); 69 patients had stable disease (46.6%); 49 patients had disease progression (33.1%); 14 has no available date (9.5%); with 10.8% response rate and 57.4% disease control rate. TTP was 6.9 (95% CI 5.3 – 8.6) and median OS was 17.97 months (95% CI; 15.4 -20.6). Prospective trials data from 103 patients showed grade 3 to 4 including fatigue 26 (21.1%), diarrhea 14 (11.4%), hypertension 14 (11.4%), elevated transaminases 11 (8.9%) and gastrointestinal bleeding 11 (8.9%) Conclusions: Bevacizumab alone or in combination with Erlotinib showed a promising results in advanced HCC. Future second-line trials are needed to compare it with best supportive care. Randomized front-line trial against sorafenib is ongoing. Bevacizumab N = 16 Bevacizumab + Erlotnib N = 132 P- value Median OS (95%CI) 20.2 (13.8 – 26.7) 17.7 (14.9 – 20.5) 0.6 Median PFS16 (95%CI) 12 (4.4 – 7.9) 6.1 (4.4 – 7.9) 0.1 Median TTP (95%CI) 11.9 (1.5 – 22.3) 6.8 (5.1 – 8.5) 0.2
Updated analysis of progression-free survival with first subsequent therapy (PFS2) and safety in the SPARTAN study of apalutamide (APA) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Eric Jay Small, Fred Saad, Simon Chowdhury, Stephane Oudard, Boris A. Hadaschik, Julie Nicole Graff, David Olmos, Paul N. Mainwaring, Ji Youl Lee, Hiroji Uemura, Angela Lopez-Gitlitz, Byron M. Espina, Youyi Shu, Wayne R. Rackoff, Oliver Brendan Rooney, Anil Londhe, Shinta Cheng, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2019)

144 Background: In the phase 3 SPARTAN study, compared with placebo (PBO), APA, a next-generation androgen receptor inhibitor, decreased the risk of distant metastasis or death by 72% (hazard ratio [HR], 0.28; p &lt; 0.0001) in men with high-risk nmCRPC. After 1 year of additional follow-up, PFS2 and safety were reevaluated to ensure maintenance of benefit against potential harm. Methods: Pts with nmCRPC and prostate-specific antigen doubling time of ≤ 10 mos were randomized 2:1 to APA (240 mg QD) + androgen deprivation therapy (ADT) or PBO + ADT. All pts who developed distant metastasis, determined by blinded independent central review, were eligible to receive subsequent therapy including open-label treatment with abiraterone acetate + prednisone, provided by the sponsor. The exploratory PFS2 end point (time from randomization to disease progression on subsequent anticancer therapy or death) was evaluated, as was incidence of treatment-emergent adverse events (TEAEs). Results: Median treatment duration with APA was 25.7 mos; with PBO, 11.5 mos (original analysis, mos: APA, 19.2; PBO, 11.2). Pts randomized to APA continued to show significant benefit in PFS2 (HR, 0.5; 95% CI, 0.39-0.63; p &lt; 0.0001) vs PBO (APA median time to PFS2 not reached vs PBO 39.3 mos). At a median follow-up of 32 mos, 51.3% of pts receiving APA, 8% of the 75 pts who crossed over from PBO to APA, and 99.7% of remaining PBO pts had discontinued study treatment. Rates of discontinuations due to progressive disease and AEs were 27.3% and 12.7%, respectively, in the APA group and 73.4% and 8.4% in the PBO group. There was no substantial change in the incidence of TEAEs in the APA group at the 1-year update. With regard to drug specific TEAEs, there were no grade 4 or 5 events; grade 3 TEAEs consisted of rash, 5.2%; falls, 2.4%; fractures, 3.1%; hypothyroidism, 0%; and seizures, 0%. Conclusions: APA was previously shown to result in an improvement in metastasis-free survival and symptomatic progression. With a median APA treatment duration of 25.7 mos, APA continues to show significant benefit in PFS2, and its safety profile remains unchanged. Clinical trial information: NCT01946204.
Xenon-129 MRI detects ventilation deficits in paediatric stem cell transplant patients unable to perform spirometry
Authors: Laura L. Walkup, Kasiani Myers, Javier El-Bietar, Adam Nelson, Matthew M. Willmering, Michael Grimley, Stella M. Davies, Christopher Towe, Jason C. Woods
Journal: European Respiratory Journal (2019)

Background Early detection of pulmonary morbidity following haematopoietic stem cell transplantation (HSCT) remains an important challenge for intervention, primarily due to the insensitivity of spirometry to early change, and in paediatrics, patient compliance provides additional challenges. Regional lung ventilation abnormalities in paediatric HSCT patients were quantified using hyperpolarised xenon-129 ( 129 Xe) magnetic resonance imaging (MRI) and compared to spirometry. Methods Medically stable, paediatric allogeneic HSCT patients (n=23, ages 6–16 years) underwent an outpatient MRI scan where regional ventilation was quantified with a breath-hold of hyperpolarised 129 Xe gas. Ventilation deficits, regions of the lung that ventilate poorly due to obstruction, were quantified as a ventilation defect percentage (VDP) and compared to forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity (FVC) ratio, and forced expiratory flow at 25–75% of FVC (FEF 25–75% ) from spirometry using linear regression. Results The mean± sd 129 Xe VDP was 10.5±9.4% (range 2.6–41.4%). 129 Xe VDP correlated with FEV 1 , FEV 1 /FVC ratio and FEF 25–75% (p≤0.02 for all comparisons). Ventilation deficits were detected in patients with normal spirometry ( i.e. FEV 1 &gt;80%), supporting the sensitivity of 129 Xe MRI to early obstruction reported in other pulmonary conditions. Seven (30%) patients could not perform spirometry, yet ventilation deficits were observed in five of these patients, detecting abnormalities that otherwise may have gone undetected and untreated until advanced. Conclusion Lung ventilation deficits were detected using hyperpolarised 129 Xe gas MRI in asymptomatic paediatric HSCT patients and in a subgroup who were unable to perform reliable spirometry. 129 Xe MRI provides a reliable imaging-based assessment of pulmonary involvement in this potentially difficult to diagnose paediatric population.
Occurrence and Severity of DLI Associated Chronic Gvhd Influence the Clinical Outcomes in Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Wenjing Yu, Xiao-Dong Mo, Xiaohui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kaiyan Liu, Xiaojun Huang
Journal: Blood (2018)
The Ayushman Bharat Pradhan Mantri Jan Arogya Yojana and the path to universal health coverage in India: Overcoming the challenges of stewardship and governance
Authors: Blake J. Angell, Shankar Prinja, Anadi Gupt, Vivekanand Jha, Stephen Jan
Journal: PLoS Medicine (2019)

In an Essay, Blake Angell and colleagues discuss ambitious reforms planned to expand coverage of the health system in India.
Sentinel lymph node biopsy in papillary thyroid cancer: Reliability in decision for selective lateral neck dissection.
Authors: Ivan Markovic, Radan Dzodic, Merima Oruci, Marko Buta, Igor Djurisic, Gordana Pupic, Srdjan Nikolic, Zorka Inic, Nada Santrac, Marija Markovic, Milan Kocic, Zorica Tomasevic
Journal: Journal of Clinical Oncology (2015)

e17022 Background: The incidence of occult lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) reaches 80%, still their surgical management in clinically node negative (cN0) patients remains controversial and ranges from
A phase I and randomized phase II study of cabozantinib plus docetaxel and prednisone (C+DP) versus docetaxel and prednisone (DP) alone in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Munjid Al Harthy, Ravi Amrit Madan, Fatima Karzai, Daniel Peter Petrylak, Joseph W. Kim, Philip M. Arlen, Marc Robert Theoret, Jenn Marte, Marijo Bilusic, Anna Couvillon, Guinevere Chun, Helen Owens, Amy Hankin, Lisa M. Cordes, William Douglas Figg, James L. Gulley, William L. Dahut
Journal: Journal of Clinical Oncology (2019)

173 Background: A phase I study of Cabozantinib (C) in combination with docetaxel (D) and prednisone (P) in patients (pts) with mCRPC determined that 40 mg daily was the maximum tolerated dose of C in combination with D and P (C+DP). We report a pooled analysis of the phase I and randomized phase II study comparing C+DP to DP alone. Methods: Eligible pts had mCRPC without prior chemotherapy in the castrate setting. All pts received a fixed dose of D (75 mg/m 2 IV day one of each 21 day cycle) and P (5 mg PO twice daily), and in the C+DP group, C at three escalating dose levels: 20 mg, 40 mg, or 60 mg in the phase I cohort (all PO daily) and 40 mg daily in the phase II cohort. Results: A total of 32 pts received C+DP (19 pts in phase I and 13 pts in the phase II cohort). 12 pts received DP alone. Baseline characteristics for C+DP vs DP included median age 69 (45 – 84) vs 69 (50-83) and median PSA 74.8 ng/ml (0.01-4093.7) vs 309.5 ng/ml (94.6 – 2649) respectively. Clinical trial information: NCT01683994. 18/32 C+DP pts had previous enzalutamide or abiraterone, with a median PFS of 13.6 months (95% CI: 5.2 – 21.0). 23/32 pts (72%) treated with C+DP required dose reduction or discontinuation of C, and 10/32 (31%) required C discontinuation. 2/32 patients (6%) in the C+DP group died on protocol, possibly related to study drug (sudden death NOS/venous thromboembolism). Grade 4 adverse events (AEs) in the C+DP group included: neutropenia (28%), leukopenia (6%), pulmonary embolism (3%), and mucositis (3%) and in DP: hyperglycemia (8%). Grade 3 AEs (&gt;10%) in C+DP included: neutropenia (31%), febrile neutropenia (16%), leukopenia (13%), hypophosphatemia (13%) and in DP: anemia (17%). Conclusions: In pts with mCRPC, C+DP is associated with a greater PFS and PSA responses compared to DP alone. Toxicities with the combination were manageable. Further study is required to better define the potential benefits of C+DP in mCRPC.[Table: see text]
Pilot study of dual imaging with 89Zr-IAB2M and 68Ga-PSMA-11 PET/CT prior to prostatectomy.
Authors: Muhammad Junaid Niaz, Yuliya Jhanwar, Thomas Flynn, Shankar Vallabhajosula, Francesca Khani, Brian D. Robinson, Scott T. Tagawa, Neil Harrison Bander, Douglas Scherr
Journal: Journal of Clinical Oncology (2019)

90 Background: Due to high expression of Prostate Specific Membrane Antigen (PSMA), it’s an excellent candidate for targeted molecular imaging. 89 Zr-df-IAB2M is a J591 antibody derived minibody and 68 Ga-PSMA-11 is a PSMA small molecule. Methods: Patients with clinically significant (defined as: ≥ 0.5 cm3 with Gleason pattern ≥ 4) localized prostate cancer (PCa) on conventional imaging modalities who planned to undergo surgery were imaged by PET/CT 1-3 hours after 5±2mCi of 68 Ga-PSMA-11 injection and 89 Zr-IAB2M PET 2-4 days after 10mg IAB2M labeled with 2.5 mCi of 89 Zr injection. Image results were interpreted by a central reader without knowledge of the surgical pathology, mapped and the mapped findings later compared with surgical pathology map. Results: 9 patients having clinically localized PCa with median age 65 (46-79) and PSA 8.42 (1.6-12.2) were enrolled. All dominant PCa lesions, which had a median Gleason score 8 (6-9), were detected by both IAB2M and PSMA-11. The smallest of these dominant lesions was 8mm in size. Median SUVmax for dominant lesions was 3.3 (2.3-7.5) on IAB2M and 7.1 (1.6-23.2) on PSMA-11; median MR PIRADS was 4 (4-5). Of 9 Gleason 6 lesions identified on pathology, PSMA-11 detected 3 and IAB2M detected 2. Four extra-prostatic lesions in one patient were detected by both PET agents, 3 were confirmed by surgical pathology and 1 confirmed on bone scan 2 months post-op. A total of 8 lesions reported on scans were not reported by path: 3 were false positive on both scans, 3 were false positive on IAB2M scan only and 2 were false positive on PSMA-11 scan only. 5 Gleason 6 and 2 Gleason 3+4 lesions on pathology were missed by both PET agents and could be considered false negatives. Conclusions: In this small pilot series, performance of the both PET agents was very similar. An advantage of IAB2M is its hepatobiliary clearance rather than renal/urinary, which makes it potentially easier to visualize the PCa and/or pelvic disease; an advantage of PSMA-11 is the ability to image within 1 hour. Clinical trial information: NCT03675451.
A randomized trial comparing fluorocholine-PET/CT with conventional imaging in prostate cancer.
Authors: Scott Williams, Jean-Mathieu Beauregard, Peter Roselt, Kate Moody, Richard Fisher, Elizabeth Drummond, Rodney J Hicks
Journal: Journal of Clinical Oncology (2019)

2 Background: We conducted a randomised trial comparing 18 Flourocholine-PET/CT (FCH) to Computed Tomography (abdomen and pelvis) plus 99m Tc-Whole Body Bone Scan (Conventional Imaging [CIm]) to determine imaging performance in prostate cancer (PC). Methods: This prospective two-arm 1:1 randomised trial enrolled men with newly diagnosed or biochemically recurrent PC to first-line imaging (FLI) with either CIm or FCH. Participants without evidence of metastases proceeded to second-line imaging (SLI) using the alternative imaging strategy. The primary aim was to determine whether FCH was more effective as a FLI approach in changing management. Secondary endpoints included incremental utility of SLI and negative predictive value (NPV) based on progression-free survival (PFS). Australian New Zealand Clinical Trials Registry ACTRN12608000641392. Results: 108 men were enrolled; 44% were for staging of newly-diagnosed PC and median follow-up 43 months. Imaging impacted clinical management in 32.4% of men (95% CI=23.7-42.1%), mostly with FLI (n=30). High-impact management changes occurred in 27.8% (95% CI=16.5-41.6%) of FCH cases compared with 11.1% (95% CI=4.2-22.6%) in the CIm arm (p=0.032). The final management plan was derived using FCH in 98.1% (95% CI = 90.1-100%) of cases and 92.6% (95%CI = 82.1-97.9%) of CIm cases (p=0.242). FLI with FCH showed unequivocally N1 or M1 disease in 22.2% (95% CI = 12-35.6%), and 16.7% (95% CI = 7.9-29.3%; p= 0.531) of CIm cases. The overall NPV for stage TxN0M0 (from all imaging) was 26.3% (95% CI: 13.9 - 41.2%), with no significant difference between arms (p=0.9). For N1M0 cases, the NPV was 14.3% (95% CI: 7.1 - 35.7%). The identification of N1M0 by FCH resulted in a longer time to identification of progressive disease, with a median PFS of 32 months (95% CI=2-68months) compared with 3 months (95% CI=1-16 months) in the CIm N1M0 cohort (p=0.05). Conclusions: FCH-PET/CT identifies more high-clinical-impact lesions than CIm as first-line imaging. All imaging modalities were poor at predicting subsequent progressive disease. Isolated node-positive disease seen with FCH is associated with a longer time to - but similarly high rates of - recurrence, suggesting a lead-time bias. Clinical trial information: ACTRN12608000641392.