tbuckley/cabot-search huggingface dataset:
Nine-year follow-up for a study of diffusion-weighted MRI in a prospective active surveillance cohort for prostate cancer.
Authors: Daniel Robert Henderson, Nandita M DeSouza, Karen Thomas, Veronica A Morgan, Sophie F Riches, Syed A Sohaib, David Paul Dearnaley, Chris Parker, Nicholas John Van As
Journal: Journal of Clinical Oncology (2015)

5043 Background: Active surveillance (AS) for untreated prostate cancer requires accurate selection of patients unlikely to need treatment in their lifetime. Most studies have selected patients on biopsy and PSA criteria alone, but show a significant number requiring treatment for disease progression. Lower tumour apparent diffusion coefficient (ADC) values, derived from diffusion-weighted MRI (dwMRI), are associated with higher risk disease. We hypothesised that ADC values could aid selection of patients for AS. Early results from this study were published in 2009; we now present findings with the benefit of long-term follow up. Methods: We analysed a subset of patients having pre-enrolment dwMRI in a prospective research study of AS. Inclusion criteria: untreated prostate cancer, T1/T2a/N0M0, Gleason ≤ 3+4, PSA < 15. Protocol follow up was by biopsy at 18-24 months, then every 24 months, along with regular PSA. To avoid influencing treatment decisions, results of dwMRIs were not available to the AS study investigators. Baseline data including PSA, biopsy grade, and T stage, along with ADC value, were analysed with respect to the outcomes of: time to adverse histology (TAH; primary Gleason ≥ 4, ≥ 50% positive cores) and time to deferred radical treatment (TRT). Results: Eighty six patients were included (90% Gleason 6; 86% cT1). Median follow up was 9.5 years. Forty six patients developed adverse histology, and 59 received deferred radical treatment (2 due to patient choice). In univariate analysis, ADC below the median was associated with shorter TAH and TRT with hazard ratios of 2.13 (CI: 1.17-3.89; p < 0.014) and 2.54 (CI: 1.49-4.32; p < 0.001), respectively. Median TRT in patients with ADC above the median was 9.3 years (CI: 7.0-11.6) but 2.4 years (CI: 1.5-6.0) for those below the median. For TRT, addition of ADC to a multivariate model of baseline variables resulted in a significant improvement in model fit (HR: 1.33, CI: 1.14-1.54, p < 0.0001). ROC analysis for TRT: AUC 0.80 (CI: 0.70-0.88). Conclusions: Long-term follow up for this study provides strong evidence that ADC is a useful marker when selecting patients for AS. Routine dwMRI is now included in our ongoing prospective AS study.
A Single Center Experience of Cladribine, Cytarabine, Filgrastim and Mitoxantrone (CLAG-M regimen) in High-Risk or Relapsed/Refractory, Acute Myeloid Leukemia (AML)
Authors: Valérie Vidal, Laila Hamri, Alice Marceau-Renaut, Flore Sicre De Fontbrune, Virginie Eclache, Nevine Osman, Benjamin Papoular, Daniel Lusina, Sabine Brechignac, Regis Peffault De Latour, Claude Preudhomme, Claude Gardin, Thorsten Braun
Journal: Blood (2018)
Monitoring minimal residual disease (MRD) by <i>KRAS</i> mutation burden in urinary or plasma circulating tumor (ct) DNA in colorectal cancer (CRC) patients with resectable liver metastases.
Authors: Cecile Rose T. Vibat, Vlada Melnikova, Marek Minarik, Barbora Belsanova, Saege Hancock, Latifa Hassaine, Errin Samuelsz, Timothy T. Lu, Mark G. Erlander, Lucie Benesova
Journal: Journal of Clinical Oncology (2015)

3594 Background: Over half of patients with CRC will develop liver metastases. Surgical resection greatly improves outcomes in these patients. Non-invasive markers are needed to better monitor treatment responses and guide complex treatment decisions. This study evaluated the utility of quantifying KRAS mutation burden in urine and plasma ctDNA for monitoring MRD in surgical CRC patients with liver metastases. Methods: A blinded retrospective ctDNA analysis was conducted in 20 Stage I-IV CRC patients with KRAS positive primary tumor, 16 of whom had undergone curative or palliative intent surgical resection of primary tumor or liver metastases in combination with various systemic therapies. Urine and plasma specimens were collected prior, during, immediately after surgery, and at additional time points post-surgery. 193 matched urine and plasma specimens (archived 3-5 years) were tested using a novel, NGS-based method for quantitative detection of KRAS mutations in ctDNA. Results: In a blinded analysis, a KRAS mutation that correlated with KRAS mutation in tissue was identified in 95% of evaluable baseline plasmas (19 of 20) and 92% of evaluable baseline urines (11 of 12). 12 of 12 (100%) matched urine and plasma pairs at baseline were concordant (11 KRAS positive and 1 KRAS negative). Analysis of 193 archival longitudinal urine and plasma samples demonstrated a clear correlation and highly comparable fold change between plasma and urinary ctDNA KRAS levels on treatment. Significantly, in 5 of 5 patients with curative intent surgery, urine or plasma ctDNA KRAS levels were undetectable at 7 days post-surgery. In contrast, ctDNA KRAS remained detectable or increased after surgery in 10 of 11 patients with incomplete, palliative surgery. Conclusions: We demonstrate for the first time a clear correlation between the dynamics of urine and plasma KRAS ctDNA changes, and clinical applicability of ctDNA for assessing post-surgery MRD in CRC patients. A prognostic significance of post-surgical KRAS levels and the overall survival in Stage IV CRC patients with liver metastases is being evaluated in a larger cohort. Supported by IGA MZ Grant 13660.
Trends in complementary and alternative medicine use among newly diagnosed prostate cancer patients.
Authors: Kyle Brian Zuniga, Shoujun Zhao, Benjamin E Cedars, Janet E. Cowan, Stacey Kenfield, Erin Van Blarigan, Jeanette M Broering, Peter Carroll, June M. Chan
Journal: Journal of Clinical Oncology (2019)

92 Background: Complementary and alternative medicine (CAM) use is common among prostate cancer (PCa) patients. The benefits and risks of the majority of CAM is inconclusive, and thus understanding trends in use is necessary to guide future research. We sought to investigate the prevalence of CAM use and trends in newly diagnosed PCa patients using the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Methods: Between 1996-2017, 7,989 CaPSURE subjects completed questionnaires on use of over 50 CAM types. For prevalence, subjects were identified as users if they ever indicated CAM use. We then performed univariate analyses to examine associations between sociodemographic and clinical characteristics with CAM use using chi-squared tests. To observe trends in CAM use among newly diagnosed patients, we limited subject responses to questionnaires completed within 24 months of diagnosis (7,358 subjects). We then grouped subjects by diagnosis year and calculated percent change in use. Results: Overall, 56% of subjects reported any CAM use. Commonly used CAM were multivitamins (40% of participants) and essential fatty acids and omega-3 (24% of participants). Compared to non-CAM users, a greater proportion of CAM users were college-educated, had a higher household income, and lived in the West and Midwest regions of the U.S (all p &lt; 0.01). In exploring trends, we found that overall CAM use increased by +203% (19% to 56%) between those diagnosed in 1996-1999 and 2010-2017. Between those diagnosed in 2005-2009 and 2010-2017, the largest changes in use were seen in acupuncture (+289%), Vitamin D (+204%), selenium (-59%), and vitamin E (-39%). Conclusions: PCa patients reported widespread CAM use in 1996-2017. Multivitamins were the most prevalent CAM, and use of acupuncture and Vitamin D increased dramatically. This information may help to prioritize research needs and reinforces the importance of discussing CAM use with patients, with referral to specialists (e.g., nutritionists) when indicated.
Comparative performance analysis between two types of liquid-based endometrial cytology to detect endometrial cancer.
Authors: Yoshika Akizawa, Yasuo Hirai, Hideo Matsui
Journal: Journal of Clinical Oncology (2015)

e16526 Background: In Japan, endometrial cytology by intrauterine sampling is one of the most common tests for evaluating the status of the endometrium. This method is usually applied for the initial pathological evaluation and often for endometrial cancer screening tests, together with cervical cytology. We have developed a very practical and easy endometrial cancer screening system using two types of LBC together with unique safe and painless sampling devices by which even a nurse or smear taker can work for effective intrauterine sampling. The following clinical data are collected. Methods: 85 endometrial samples obtained from Tokyo women’s medical university hospital were analyzed. All samples were obtained directly from the intrauterine cavity using a Uterobrush or Honestbrush N, and processed in a different type of two LBC methods(SurePath and TACAS). Histological samples were obtained by endometrial biopsy or from operated material. Sample collection for histological examination and cytological tests was performed simultaneously. For cytological evaluation, our study group newly devised cytological diagnostic criteria: the Osaki Study Group (OSG) method. In this study, histological diagnosis was considered as the gold standard for cytological diagnosis. A descriptive reporting format was used in this study. Results: Of the 85 cases, 6 specimens were judged as unsatisfactory, all of which were due to scant cellularity. Two detect endometrial carcinoma, the sensitivity and specificity of two types of endometrial cytology were 100% and 100% respectively. Conclusions: These data indicate that both two types of liquid based endometrial cytology is acceptable for clinical usage. Since these two LBC methods seems to provide greater ease and standardization of preparation, liquid based endometrial cytology, coupled with the newly devised cytological diagnostic criteria(OSG method) and descriptive reporting format, may be an acceptable and reliable diagnostic method not only for Japan, but also for the rest of the world.
Benefit of perioperative systemic therapy in patients with colorectal liver metastases (CRLM) undergoing liver-directed therapy (LDT).
Authors: Kaihong Mi, Michael J. McNamara, Paul Elson, Shiva Shrotriya, Katherine Glass, Cristiano Quintini, Federico Aucejo, Eren Berber, Alok A. Khorana
Journal: Journal of Clinical Oncology (2015)

e14529 Background: The benefit of perioperative systemic therapy in CRLM patients with LDT has only been tested in limited clinical trials, but is frequently administered. We therefore evaluated the impact of perioperative systemic therapy in patients with CRLM undergoing LDT at our institution. Methods: Perioperative chemotherapy information and clinicopathologic factors were collected through an electronic medical records review in CRLM patients who underwent LDT from 2/2006 to 2/2014 at Cleveland Clinic. Preoperative and adjuvant chemotherapy were defined as treatment delivered before or after 3 months of LDT, respectively. Overall survival (OS) and liver-specific PFS (LPFS) were analyzed and summarized by using the Kaplan-Meier method. The logrank test was used to compare patient groups. Results: The study population comprised 214 patients. Median age was 60 years (range 27-88) and 59% with synchronous disease. Approximately 70% developed recurrent disease, of which 85% occurred in the liver. Surgical resections were performed more frequently than RFA (67% vs 33%). Median OS and LPFS were 43.8 and 23.7 months, respectively. Preoperative therapy and adjuvant therapy were given in 61% and 50% of patients, respectively; 25% of patients had both. The primary chemotherapy backbone was either FOLFOX or FOLFIRI in over 70% of patients. In patients treated with a targeted agent (34% in preoperative and 47% in adjuvant therapy), bevacizumab was used in 77%. Patients were further evaluated using the MSKCC-CRC score. There was no OS benefit treated preoperatively in patients with either a low (0-2) or high (3-5) score. Patients with adjuvant therapy had significantly improved OS (55.8 vs 37.4 months, p = 0.008). This was predominantly due to its benefit in high risk patients (58.5 vs 36.6 months, p = 0.02). A significant benefit in LPFS with adjuvant therapy was also observed (27.8 vs 19.7 months, p = 0.04). Conclusions: Our data suggests a benefit associated with the administration of adjuvant chemotherapy for patients with CRLM who undergo LDT. This benefit is predominantly observed in patients with a high risk MSKCC-CRC score; future studies could target high-risk patients specifically.
Abstract P248: Increased Arterial Stiffness Measures in Morbidly Obese Patients After Bariatric Surgery
Authors: Frances Wang, Chao Yang, Hirofumi Tanaka, Josef Coresh, Chiadi Ndumele, Kunihiro Matsushita
Journal: Circulation (2019)

Introduction: The association between obesity and arterial stiffness is complex and has been reported to be modified by age, with a positive association in older adults and an inverse association in younger adults. Additionally, several diet and exercise-based programs have demonstrated conflicting results regarding changes in arterial stiffness before and after weight reduction. However, few have explored arterial stiffness outcomes in bariatric surgery patients. Objective: To characterize changes in arterial stiffness after bariatric surgery. Methods: In 72 morbidly obese patients, we evaluated two measures of arterial stiffness, cardio-ankle vascular index (CAVI) and heart-ankle pulse wave velocity (haPWV), ~1 month prior to and 6 and 12 months after bariatric surgery. Arterial stiffness measures were assessed twice at each visit and averages were reported. Paired t-tests were used to evaluate the significance of changes after bariatric surgery. Results: The mean age of our study sample was 44.5 years (SD 11.2), and 72.2% were female. Average BMI substantially decreased after bariatric surgery (from 47.1 to 34.8 kg/m 2 ). Similarly, systolic blood pressure declined after surgery (from a mean of 143.0 to 131.7 mmHg) whereas diastolic blood pressure did not significantly differ. Both arterial stiffness measures, CAVI and haPWV, were significantly elevated after bariatric surgery (Figure, p&lt;0.001). CAVI increased from baseline by an average of 0.64 (95% confidence interval [CI]: 0.42-0.87) at 6-month follow-up and 0.80 (95% CI: 0.53-1.07) 1 year after surgery. A similar pattern was observed for haPWV. Conclusions: Despite favorable changes in body weight and blood pressure, arterial stiffness measures were elevated after bariatric surgery. Although this observation is in line with an inverse association between obesity and arterial stiffness in younger adults, future studies are necessary to explore the underlying mechanisms and clinical implications of increased arterial stiffness after bariatric surgery.
Radiogenomic characterization of multifocal prostate cancer.
Authors: Simpa Samuel Salami, Jeremy B Kaplan, Srinivas Nallandhighal, Mandeep Takhar, Jeffrey J. Tosoian, Matthew Lee, Junhee Yoon, Daniel H Hovelson, Komal R. Plouffe, Samuel D. Kaffenberger, Arvin Koruthu George, Jeffrey Scott Montgomery, Matthew Davenport, Sungyong You, Scott A. Tomlins, Nicole E Curci, Hyung Lae Kim, Daniel Eidelberg Spratt, Aaron M. Udager, Ganesh S. Palapattu
Journal: Journal of Clinical Oncology (2019)

126 Background: Up to 20% of patients with negative multiparametric magnetic resonance imaging (MRI) harbor Gleason score ≥7 prostate cancer (PCa). We sought to elucidate the molecular basis of and determine the prognostic significance of PCa visibility on MRI. Methods: We identified a retrospective cohort of patients who underwent MRI prior to prostatectomy with both MRI visible (PIRADS 3 – 5) and invisible PCa. MRI for each patient was re-reviewed and co-registered with whole-mount histopathology. DNA and RNA were co-isolated from all tumor foci pre-identified on FFPE specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA) and a custom targeted RNAseq panel assessing PCa relevant alterations. A multigene RNAseq model was developed and validated in two independent cohorts to predict MRI visible PCa and to determine the prognostic significance of MRI visibility. Results: A total of 26 primary tumor foci from 10 patients were analyzed. Of the 14 (54%) invisible lesions on MRI, 5 (36%) were Gleason 3+4 = 7 and the remainder were Gleason 6. We detected high-confidence prioritized PCa relevant mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in MRI invisible lesions. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, and TP53. A 9-gene RNA signature, the majority of which were under-expressed cellular organization and structure genes, was developed to predict MRI visibility with an AUC of 0.89. Validation of this signature in an independent data set (n = 16) yielded an AUC of 0.88 with a specificity of 100% for predicting MRI visible tumors. Using this signature in a cohort of 375 patients with clinical follow up, we found that predicted MRI visibility status was not an independent predictor of biochemical recurrence, metastasis-free survival, or PCa specific mortality (all p &gt; 0.05). Conclusions: We observed under-expression of cellular organization and structural genes in MRI visible tumors compared to MRI invisible cancer foci. Using our validated signature to predict MRI visibility status, we found that MRI visibility is not a significant predictor of oncological outcomes.
Adipolin/CTRP12 protects against pathological vascular remodelling through suppression of smooth muscle cell growth and macrophage inflammatory response
Authors: Hayato Ogawa, Koji Ohashi, Masanori Ito, Rei Shibata, Noriyoshi Kanemura, Daisuke Yuasa, Takahiro Kambara, Kazuhiro Matsuo, Satoko Hayakawa, Mizuho Hiramatsu-Ito, Naoya Otaka, Hiroshi Kawanishi, Shukuro Yamaguchi, Takashi Enomoto, Takaya Abe, Mari Kaneko, Mikito Takefuji, Toyoaki Murohara, Noriyuki Ouchi
Journal: Cardiovascular Research (2019)

Secreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodelling.Adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Adipolin deficiency also led to a reduction in transforming growth factor-β (TGF-β) 1 protein levels in injured arteries. Treatment of cultured macrophages with adipolin protein led to a reduction in lipopolysaccharide-stimulated expression of inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin (IL) 6, and monocyte chemotactic protein (MCP)-1. These effects were reversed by inhibition of TGF-β receptor II (TGF-βRII)/Smad2 signalling. Adipolin also reduced platelet-derived growth factor (PDGF)-BB-stimulated proliferation of vascular smooth muscle cells (VSMCs) through a TGF-βRII/Smad2-dependent pathway. Furthermore, adipolin treatment significantly increased TGF-β1 concentration in media from cultured VSMCs and macrophages.These data indicate that adipolin protects against the development of pathological vascular remodelling by attenuating macrophage inflammatory responses and VSMC proliferation.
Anti-cancer effects of zoledronic acid on human cancer cells.
Authors: Pengfei Jiang, Rajesh Mukthavaram, Natsuko Nomura, Sandeep C. Pingle, Santosh Kesari
Journal: Journal of Clinical Oncology (2015)

e13042 Background: Zoledronic Acid (Zole) is a potent nitrogen-containing bisphosphonates (NBP) has been extensive used to limit bone turnover in a various diseases including tumors. Recently, clinical trails of Zoledronic Acid demonstrated direct anti-cancer effects as well as the skeletal-related events. Methods: We investigated the effect of 4 NBPs on human tumor cell proliferation. We found Zole is the most potent NBP for serum GBM tumor cell lines, breast cancer cell lines and as well for patient-derived GBM stem-cell-like cells. Zole also effectively inhibited GBM tumor growth in mouse model. Zole stimulated strong autophagy but not apoptotic signals in all tested cells. Only one intermediate product of cholesterols synthesis pathway----geranylgeranyl diphosphate (GGPP) rescued cells from the cytotoxicity of Zole. Knock-down of RABGGTA, which encodes a subunit of the Rab geranylgeranyl-transferase proteins, but not FNTA induced a similar effect as Zoledronic Acid in cancer cell lines. Results: Zoledronic acid potentially inhibits human cancer cell proliferation including primary human tumor cells derived from GBM patients. The rescue experiments indicated that the RABGGTase mediates the cell cytotoxic effect of zoledronic acid. Conclusions: These data suggested great potential for Zoledronic Acid against human cancer mediated by the ablation of Rab protein functions.
Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults
Authors: Vasanti S. Malik, Yanping Li, An Pan, Lawrence De Koning, Eva Schernhammer, Walter C. Willett, Frank B. Hu
Journal: Circulation (2019)

Background: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of mortality is of public health interest. Methods: We examined associations between consumption of SSBs and ASBs with risk of total and cause-specific mortality among 37 716 men from the Health Professional’s Follow-up study (from 1986 to 2014) and 80 647 women from the Nurses’ Health study (from 1980 to 2014) who were free from chronic diseases at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. Results: We documented 36 436 deaths (7896 cardiovascular disease [CVD] and 12 380 cancer deaths) during 3 415 564 person-years of follow-up. After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality; pooled hazard ratios (95% confidence intervals) across categories (&lt;1/mo, 1–4/mo, 2–6/week, 1-&lt;2/d, and ≥2/d) were 1.00 (reference), 1.01 (0.98, 1.04), 1.06 (1.03, 1.09), 1.14 (1.09, 1.19), and 1.21 (1.13, 1.28; P trend &lt;0.0001). The association was observed for CVD mortality (hazard ratio comparing extreme categories was 1.31 [95% confidence interval, 1.15, 1.50], P trend &lt;0.0001) and cancer mortality (1.16 [1.04, 1.29], P trend =0.0004). ASBs were associated with total and CVD mortality in the highest intake category only; pooled hazard ratios (95% confidence interval) across categories were 1.00 (reference), 0.96 (0.93, 0.99), 0.97 (0.95, 1.00), 0.98 (0.94, 1.03), and 1.04 (1.02, 1.12; P trend = 0.01) for total mortality and 1.00 (reference), 0.93 (0.87, 1.00), 0.95 (0.89, 1.00), 1.02 (0.94, 1.12), and 1.13 (1.02, 1.25; P trend = 0.02) for CVD mortality. In cohort-specific analysis, ASBs were associated with mortality in NHS (Nurses’ Health Study) but not in HPFS (Health Professionals Follow-up Study) ( P interaction, 0.01). ASBs were not associated with cancer mortality in either cohort. Conclusions: Consumption of SSBs was positively associated with mortality primarily through CVD mortality and showed a graded association with dose. The positive association between high intake levels of ASBs and total and CVD mortality observed among women requires further confirmation.