tbuckley/cabot-search huggingface dataset:
Abstract P194: Associations of Bone Mineral Density With Blood Pressure and Obesity in Hong Kong Chinese Adults
Authors: Yao Jie Xie, Alice Yuen Loke, Suzanne C. Ho, Marc Ka-chun Chong
Journal: Circulation (2019)

Background: There were conflicting results regarding the association between blood pressure (BP) and bone mineral density (BMD) in previous studies. Obesity, often co-existing with high BP, may explain the discrepancy in those findings. The aim of this study was to examine the association between BP and BMD in Hong Kong Chinese adults, and to determine whether the relationship between BP and BMD differed in subjects with and without obesity. Methods: Eight hundred and one adults aged from 45 to 86 years were recruited at two outpatient clinics in Hong Kong. Data of weight, height, waist circumference, BP, disease diagnosis were extracted from medical records at the clinics. The femur neck total BMD (g/cm 2 ) was measured by dual-energy X-ray absorptiometry (DXA). The demographics, smoking, drinking, and other covariates were collected by a self-administered questionnaire. Osteoporosis, osteopenia, and normal bone mass were classified by BMD T-score for analysis. Results: The average systolic BP was 121.5 mmHg, 123.2 mmHg, and 126.9 mmHg, diastolic BP was 71.9 mmHg, 72.6 mmHg, and 75.8 mmHg among osteoporosis, osteopenia, and normal bone mass groups, respectively. Subjects with osteoporosis had lowest BP level (all P&lt;0.01). In the multiple liner regression analysis, after adjustment of age, gender, BMI, cancer, diabetes, and chronic renal failure, higher systolic BP was associated with higher BMD (B=0.00078, 95%CI: 0.00020 to 0.00136, P&lt;0.01). This association was significant in both males and females (both P&lt;0.05). No significant association was observed between diastolic BP and BMD (P&gt;0.05). When subjects were stratified by obesity status, the non-obese (BMI&lt;25) subjects had a lower BMD for a given level of systolic BP (B=0.00064, 95%CI: 0.00006 to 0.00128, P&lt;0.05), whereas the association was no longer significant among obese (BMI≥25) subjects (P&gt;0.05). Conclusion: Unlike most previous studies, we found a positive association between systolic BP and BMD, which higher systolic BP predicted higher BMD. This association was not significant in obese subjects but existed in non-obese subjects, indicating more studies are needed to explore the mechanisms of BP and obesity on the changes of BMD.
Impact of macrolide therapy in critically ill patients with acute respiratory failure: a desirability of outcome ranking analysis to investigate the OUTCOMEREA database
Authors: Stéphanie Pons, Jean-François Timsit, Stéphane Ruckly, Carole Schwebel, Laurent Papazian, Elie Azoulay, Jean Reignier, Lara Zafrani
Journal: Intensive Care Medicine (2019)
Liver transplantation using hepatitis B core positive grafts with antiviral monotherapy prophylaxis
Authors: Tiffany Cho-Lam Wong, James Yan-Yue Fung, Tracy Yu-Shi Cui, Allan Hoi-Kin Lam, Jeff Wing-Chiu Dai, Albert Chi-Yan Chan, Tan-To Cheung, Kenneth Siu-Ho Chok, Kelvin Kwok-Chai Ng, Chung-Mau Lo
Journal: Journal of Hepatology (2019)
Comparison of DNA hypomethylating agents and low dose cytarabine in elderly acute myeloid leukemia patients: A meta-analysis.
Authors: Nicole Vincelette, Seongseok Yun
Journal: Journal of Clinical Oncology (2015)

e18062 Background: Both DNA hypomethylating agents (HMA) and low dose cytarabine (LDAC) have been widely used for elderly acute myeloid leukemia (AML) patients with intermediate or poor cytogenetic risk who are not eligible for intensive chemotherapy or stem cell transplantation (SCT), however the clinical outcomes have been inconsistent. We performed a meta-analysis to compare the clinical outcomes of HMA vs. LDAC including overall survival (OS) and risk of hematologic adverse events in elderly AML patients. Methods: Relevant articles were searched in PubMed, EMBASE and Cochrane databases. Eligible studies were limited to randomized controlled trials comparing HMAs (azacitidine or decitabine) to LDAC in adult patients with de novo and secondary AML. Relative risk and 95% CI were calculated by using random effect model. Results: Overall survival (OS) was 21.8% for HMA vs. 12.1% for LDAC (RR 0.91, 95% CI 0.85-0.97) and grade 3-4 hematologic adverse events rates were 39.4% vs. 37.8% for (RR 1.07, 95% CI 0.92-1.24) for thrombocytopenia, 63.9% vs. 50.3% (RR 1.15, 95% CI 0.86-1.54) for neutropenia, and 30.3% vs. 28.1% (RR 1.14, 95% CI 0.90-1.44) for anemia in HMA vs. LDAC, respectively. In a subgroup analysis, only azacitidine treatment showed OS improvement (RR 0.66, 95% CI 0.49-0.80) and decitabine was associated with higher risk of neutropenia (RR 1.44, 95% CI 1.21-1.73) compared to LDAC treatment. Conclusions: Collectively, these results suggest that azacitidine over the decitabine may be better choice than LDAC in elderly AML patients who are not eligible to intensive chemotherapy or allogeneic SCT.
Comparing the Risk Factors of Plaque Rupture and Failed Plaque Healing in Acute Coronary Syndrome
Authors: Mark E. Brezinski
Journal: JAMA Cardiology (2019)

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Impact of BRAF mutation in patients with brain metastasis from melanoma.
Authors: Vyshak Alva Venur, Rupesh Kotecha, Zhijian Chen, Samuel T. Chao, Paul Elson, John H. Suh, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2015)

e13016 Background: Melanoma patients with brain metastasis (MBM) have a dismal prognosis.BRAF mutation occurs in approximately 50% of patients with metastatic melanoma; however its impact on MBM outcomes is unknown. We evaluated the prognostic significance of BRAF mutation in MBM at our institution. Methods: With IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify MBM patients. Overall survival (OS) from the diagnosis of MBM was the primary end point. OS was summarized using the Kaplan-Meier method and analyzed using the logrank test. Results: 256 patients with MBM were treated between 2000 and 2013. BRAF status was available for 76 MBM. BRAF mutation was present in 35 patients, 41 had wild type BRAF. V600 mutations were present in 28 patients (21-V600E mutations, 4-V600K). The median interval from melanoma diagnosis to BM was 22.2 months(m). Median age at diagnosis was 63 years (26-85), 65% were male, and 67% were symptomatic at presentation. KPS was 90-100 in 45%, 80 in 28% and < 80 in 27% of MBM. Stereotactic radiation (SRS)± surgery was the initial modality of treatment in 33(43%) and whole brain radiation therapy (WBRT)± surgery in 28 (37%) patients, 18 patients received Vemurafenib (VEM) after BM. Median OS for the 76 patients was 6.2m. OS in BRAF (+) patients was 8.8m while in BRAF (-) was 5.4m. Patients treated with WBRT ± other modalities, the BRAF (+) and BRAF (-) patients had OS of 4.6m and 5.4m respectively. Patients treated with SRS ± other modalities, BRAF (+) had OS of 18.6m while BRAF (-) had 5.5m. Conclusions: In this small cohort of MBM, SRS ± other modalities improved survival in BRAF (+) patients compared to BRAF (-). A prospective trial to validate this is planned. Factor N Median OS in months (95% C.I) p BRAF (-) vs BRAF (+) BRAF(-) 41 5.4(3.9-7.0) 0.19 BRAF(+) 35 8.8(5.5-17.2) BRAF(+) treated with VEM vs BRAF(+) not treated with VEM BRAF(+) with VEM 18 8.8(3.4-27.8) 0.65 BRAF(+)without VEM 17 9.5(5.5-18.6) SRS± other modalities BRAF(-) 19 5.5(3.9-10.8) 0.004 BRAF(+) 14 18.6(7.0-49.4) SRS± other modalities in BRAF(+) treated with VEM vs BRAF(+) not treated with VEM BRAF(+) with VEM 6 44.6(5.3-49.4) 0.37 BRAF(+)without VEM 8 17.2(7.0-18.6)
Antibody-Drug Conjugate-Based Therapeutics: State of the Science
Authors: Michael J Birrer, Kathleen N Moore, Ilaria Betella, Richard C Bates
Journal: JNCI Journal of the National Cancer Institute (2019)

Antibody-drug conjugates (ADCs) are complex engineered therapeutics consisting of monoclonal antibodies, directed toward tumor-associated antigens, to which highly potent cytotoxic agents are attached using chemical linkers. This targeted drug delivery strategy couples the precision of the antibody targeting moiety with the cytocidal activity of the payload, which is generally too toxic on its own to be systemically administered. In this manner, ADCs confer a means to reduce off-target toxicities in patients by limiting the exposure of normal tissues to the payload, thus broadening the potential therapeutic window compared with traditional chemotherapy. The pace of ADC development is accelerating, with the number of investigational agents in human trials having more than tripled over the past 5 years, underscoring the enthusiasm for this transformative approach to cancer treatment. Here, we review the key structural elements of ADC design (antibody, linker, and payload), highlighting critical aspects and technological advances that have affected the clinical effectiveness of this class of biopharmaceuticals. The ADC field continues to evolve, including ongoing efforts aimed at improving target selection, developing payloads with varied mechanisms of action and increased potency, designing innovative bioconjugation strategies, as well as maximizing efficacy and tolerability in patients. An overview of the current clinical trial landscape is provided, with emphasis on the clinical experience of the four ADCs to have received regulatory approval to date, as well as additional promising candidates currently in late-stage clinical development in both solid tumor and hematological malignancies.
Somatic alterations in a seven-gene DDR gene panel predicts platinum sensitivity in advanced prostate cancer patients.
Authors: Panagiotis J. Vlachostergios, Jyothi Manohar, Muhammad Junaid Niaz, Aileen Lee, Amy Hackett, Ana M. Molina, David M. Nanus, Himisha Beltran, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2019)

283 Background: Genomic alterations in the DNA damage response and repair (DDR) pathways are common in advanced PC. Platinum compounds are active in CRPC pts. DDR-defective PC tumors have increased sensitivity to PARP inhibitors (PARPi); the mechanisms involved in sensitivity to platinum and PARPi may be similar but not identical. This study aimed to assess the impact of somatic DDR alterations on clinical outcome of platinum-treated patients with advanced PC. Methods: We reviewed records of advanced PC patients, who received platinum-based chemotherapy with available tumor tissue specimens. We used next generation sequencing (whole exome or targeted) to assess for mutations and copy number alterations in a selected panel of DDR genes, including BRCA1, BRCA2, ATM, ERCC3, ERCC5, TP53 and RB1. We used Kaplan Meier curves to predict PFS and OS after initiation of platinum chemotherapy. Results: Our cohort included 50 men, median age 69.5 years (45-91), median PSA 0.81 (0.008-2291.25), median LDH 264 (109-6714). 39 had visceral metastases (38 liver, 15 lung, 2 adrenal, 2 peritoneal, 1 brain). The majority or pts (33/50) received carboplatin, 17 received cisplatin (2 subsequently also received carbo with initial platinum used for data analysis). Most pts received chemotherapy doublets, and platinum was most frequently combined with etoposide (N=27) and paclitaxel (N=9). 39 pts had tumors harboring at least one DDR alteration. Somatic deletions in BRCA2 gene (N=18) were associated with a significantly longer PFS compared to men with wild-type BRCA2 (median PFS: 6 versus 3 months, P=0.019). No significant associations were identified between somatic DDR alterations and OS. Presence of ≥2 concomitant DDR somatic alterations predicted a favorable PFS compared to single-gene alterations or lack thereof (6 vs 3 months, P=0.006). Conclusions: Our study suggests that presence of ≥2 concomitant DDR somatic alterations from a 7-gene DDR panel, including BRCA1, BRCA2, ATM, ERCC3, ERCC5, TP53, and RB1, may predict longer PFS in pts with advanced PC treated with platinum-based chemotherapy. Further studies are needed to clinically qualify multiplex predictive biomarkers of DDR-defective PCs.
Hyperprogressive disease (HPD) in genitourinary (GU) cancer patients treated with PD-1/PD-L1 inhibitors.
Authors: Inhwan Hwang, Inkeun Park, Shin-Kyo Yoon, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2019)

369 Background: Post immunotherapy response and disease progression pattern are still under investigation. In terms of progression, rapid progression pattern called HPD has been observed during the early cycles of PD-1/PD-L1 inhibitors therapy in patients with various cancers. Data of HPD in patients with GU cancer are limited. Methods: This study included 203 patients with GU cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as greater than 50% increase in tumor burden compared with before-treatment computed tomography (CT) scan and greater than 2-fold increase in tumor growth rate (TGR) compared with previous TGR. Development of extensive new lesions were also regarded as HPD. Response was evaluated by RECIST v1.1 on at least two consecutive CT scan before the initiation of PD-1/PD-L1 inhibitors and one CT scan within 2 months after initiation of PD-1/PD-L1 inhibitors. Results: 102 patients with renal cell carcinoma (RCC) and 101 patients with urothelial cell carcinoma (UCC) were included. Median age was 64 years (range 56-71) and 141 patients (70%) were male. The most common metastatic site was lymph node (66%), followed by lung (51%) and bone (34%). HPD was observed in 13 out of 230 patients (5.7%; 95% CI, 5.0-6.3). Median OS for patients with progressive disease and HPD were 7.3 months and 3.5 months, respectively ( p=0.09). HPD was more frequently found in patients with UCC than RCC (11% vs. 0.9%, p=0.01). In multivariate analysis, patients of UCC ( p &lt;0.001), presence of liver metastasis ( p=0.002), elevated LDH level (&gt; upper normal limit, p=0.01), and hypoalbumimemia (&lt; 3.5 gm/dL, p&lt;0.001) were independent predictive factors for HPD. Conclusions: The incidence of HPD in GU cancer patients seems to be low compared to previous studies (9-10%). The majority of HPD developed in UCC and the incidence in RCC is negligible. Cares should be taken when treating patients with PD-1/PD-L1 inhibitors, especially when patients have UCC and liver metastases, elevated LDH and hypoalbuminemia.
Hypoxia and neoplasms: Sickle cell patients as a living model.
Authors: Katharine Batt, Scott Isom, Andrew Matthew Farland, David Leedy, John Owen, Marcelo Raul Bonomi
Journal: Journal of Clinical Oncology (2015)

e12591 Background: Hypoxia is a hallmark of tumors leading to (mal-) adaptive processes, the development of aggressive phenotypes and treatment resistance. Two types of hypoxia have been studied: acute or 'cycling' hypoxia caused by compromised perfusion or flow stop and chronic hypoxia caused by diffusion limitations. In vitro, hypoxia seems to have significant impacts on tumor cell-type selection and variability; in vivo, the impact of hypoxia is still poorly understood. SCP are prone to frequent sickle pain crises, characterized by vaso-occlusive crises—episodes of localized, acute hypoxia—over their lifetimes. We propose then, that this pathophysiologic phenomenon of SCP can offer insight into understanding the effects of hypoxia on tumorigenesis and neoplastic growth. Methods: In a retrospective review of the Wake Forest Baptist Medical Center (WFBMC) Electronic Data Warehouse (EDW) capturing data from 1980 until present, we compared the prevalence of malignancies across all age ranges in SCP to all ages in the general population (GPop) using ICD-9 codes. Statistical significance was determined using the Fisher’s exact test. Results: Of 3,874 SCP identified in the EDW, 848 (21.89%) were diagnosed with a malignancy while 256,560/2,123,301 (12.08%) of the GPop had a malignancy diagnosis (p < 0.0001). In a subgroup analysis by tumor type, only hematologic malignancy diagnoses had a statistically significant prevalence rate in SCP when compared to GPop: 120/3,874 (3.1%) SCP v 18,829/2,123,301(0.9%) GPop (p < 0.0001). Conclusions: The overall incidence of neoplasms in SCP was increased compared to the GPop; hematologic malignancy was the only tumor subtype with a statistically meaningful difference in prevalence between the two studied populations. These findings suggest that SCP may provide a valid model to evaluate the effects of hypoxia on neoplastic growth and development in tumor cells.
TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Authors: Rachel A. Freedman, Rebecca S. Gelman, Carey K. Anders, Michelle E. Melisko, Heather A. Parsons, Anne M. Cropp, Kelly Silvestri, Christine M. Cotter, Kathryn P. Componeschi, Juan M. Marte, Roisin M. Connolly, Beverly Moy, Catherine H. Van Poznak, Kimberly L. Blackwell, Shannon L. Puhalla, Rachel C. Jankowitz, Karen L. Smith, Nuhad Ibrahim, Timothy J. Moynihan, Ciara C. O’Sullivan, Julie Nangia, Polly Niravath, Nadine Tung, Paula R. Pohlmann, Robyn Burns, Mothaffar F. Rimawi, Ian E. Krop, Antonio C. Wolff, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2019)

Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts.Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m2 twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression.Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B).Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.
Effects of sunitinib and pazopanib on patients physical, social, and emotional function: Result of a prospective patients reported outcome tool.
Authors: Prantik Das, Akram Ali, Karen Simmonds, Lesley Mckenna
Journal: Journal of Clinical Oncology (2019)

667 Background: Sunitinib and pazopanib are are effective treatment options for metastatic Renal cell carcinoma (mRCC) and both may impair patient’s quality of life (QOL). There has been no direct comparison between these agents and their effect on these domains. Methods: A prospective study of mRCC patients who had received Sunitinib or Pazopanib as a first line treatment was conducted. A set of questionnaires has been developed in-house, influenced by existing recognised tools, such as EORTC-C 30 and PHQ-9, and is tailored to focus on relevant QoL issues patients face. This questionnaire named as Patient reported outcome tool. They primarily relate to physical, emotional and social functioning in the quality of life of patients. Each category has 4 questions. The questions are quite generic and allow patients to apply them to what’s important in their lives. Answers are on a scale of 0-10. The purpose of the questionnaire is to assess a balance of physical, cognitive and independence related aspects of their life over the course of their treatment. All patients are asked to complete the baseline questionnaire and then in every clinical visit. Results: Data were collected prospectively of metastatic RCC patients who had received Sunitinib or Pazopanib from May 2017 to Aug 2018. Total 45 patients were included, 23 received Pazopanib and 22 were on Sunitinib. There was a higher rate of significant worsening for the physical well-being subscale for Sunitinib versus Pazopanib. Patients on Sunitinib reported worsening tiredness, skin problems and sleep disturbance. Socially, patients on Sunitinib reported more closer to family, better interaction with friends and more motivated to go out. Problem with feeling sad, fear of death and anxiousness were more pronounced on Pazopanib arm. Conclusions: Our study suggested that there are marked differences between Sunitinib vs Pazopanib and their effects on patients physical, emotional and social wellbeing. Physical function was more influenced by sunitnib while pazopanib has more effect emotional wellbeing. Further studies are warranted to confirm these findings.