tbuckley/cabot-search huggingface dataset:
State rurality does not increase risk of prostate cancer death.
Authors: Alexander Geoffrey Shaw Anderson, Katie Murray
Journal: Journal of Clinical Oncology (2019)

119 Background: Prostate cancer is the third most common cancer among men. PSA based screening for prostate cancer was introduced in the 1980s and resulted in a significant decline in prostate cancer mortality. Current AUA guidelines recommend PSA screening in average risk patients between the ages of 55 and 69. There are public health concerns in rural areas of the United States (US) potentially due to decreased access of care. In this study, we sought to evaluate the prevalence of prostate cancer screening and death rate in rural communities within the US. Methods: After IRB approval, data was collected from several different sources. Annual prostate cancer death rate (2011-2015) was obtained from the American Cancer Society. Data from the Behavioral Risk Factor Surveillance System regarding prostate cancer screening during this time interval was acquired. Data regarding populations was obtained from the US Census. Descriptive analyses were used to describe the population and Pearson Correlation Coefficient to determine screened, death rates and rurality correlations. All analyses were completed using SPSS. Results: The median percent of US population residing in rural and urban areas was 25.8% (IQR 22.1%) and 73.8% (IQR 22.1%), respectively. The median percent of male patients screened using PSA 50 years and older was 56.2% (IQR 7.0%). The median death rate (per 100,000) from prostate cancer per state was 19.5 (IQR 1.7%). Prostate cancer death rate was found to have no correlation to percent of population screened (p = 0.29) and percent rurality (p = 0.98). The percent rural population versus percent of screened men over the age of 50 was also not significant (p = 0.20). Conclusions: Neither death rate nor screening rate for prostate cancer using PSA demonstrated a significant association with the percent of patient’s living in rural communities. This is evidence that within the US, rural communities are following guidelines for PSA screening for prostate cancer and therefore there is no discrepancy in prostate cancer death in these areas compared to urban. This study is evidence that the barriers that may be associated with living in rural communities, such as decreased access to healthcare do not translate into worse outcomes related to prostate cancer.
Abstract P383: Smoking Cessation and Weight Change in Relation to Cardiovascular Disease Incidence and Mortality Among Patients With Diabetes Mellitus
Authors: Gang Liu, Yang Hu, Geng Zong, Frank B Hu, JoAnn E Manson, Kathryn M Rexrode, Eric B Rimm, Qi Sun
Journal: Circulation (2019)

Introduction: Some studies suggested that smoking cessation could result in short-term weight gain, deterioration in glycemic control, and worsening of some diabetic symptoms. It is unclear whether weight gain following smoking cessation might mitigate the health benefits among adults with diabetes. Hypothesis: Smoking cessation is associated with a lower risk of cardiovascular disease (CVD) incidence and mortality among individuals with diabetes, and weight gain following smoking cessation does not modify the association. Methods: This prospective analysis included 9,780 men and women with type 2 diabetes from the Nurses’ Health Study (1984-2014) and Health Professionals Follow-Up Study (1988-2014). Information on newly diagnosed diseases, medical history, dietary and lifestyle factors, including smoking status and weight change, was updated every two years through validated questionnaires. Results: During 154,825 person-years of follow-up, there were 2,590 incident CVD cases and 3,326 deaths among participants with diabetes. Compared with those who continued to smoke, quitters had a lower risk of CVD incidence, regardless of weight change after quitting. The multivariate-adjusted hazard ratios (95% confidence intervals) for CVD were 0.66 (0.54-0.81) among recent quitters (≤6 years since smoking cessation) without weight gain, 0.69 (0.47-0.99) among recent quitters with weight gain of 0.1 to 5.0 kg, 0.57 (0.37-0.87) among recent quitters with weight gain of more than 5.0 kg, 0.71 (0.60-0.83) among longer-term quitters (&gt;6 years since smoking cessation), and 0.51 (0.45-0.59) among never-smokers. Similar results were observed for CVD, cancer, and all-cause mortality, although the associations did not reach statistical significance among recent quitters with weight gain. Conclusions: Smoking cessation was associated with a lower risk of CVD incidence among men and women with diabetes, even among those who gained weight after quitting. A health benefit of smoking cessation on mortality was also observed.
Genomic concordance between profiling of circulating tumor DNA (ctDNA) and matched tissue in metastatic urothelial carcinoma.
Authors: Gillian Vandekerkhove, Jean-Michel Lavoie, Matti Annala, Nora Sundahl, Takeshi Sano, Werner J. Struss, Tilman Todenhöfer, Piet Ost, Kim N. Chi, Peter C. Black, Bernhard J. Eigl, Alexander William Wyatt
Journal: Journal of Clinical Oncology (2019)

457 Background: Biomarkers are urgently needed to facilitate tumor molecular stratification in metastatic urothelial carcinoma (mUC), thus potentially enabling patient selection for targeted- and immuno-therapies. We aimed to assess concordance for clinically-relevant driver gene alterations between same-patient tumor tissue and ctDNA. Methods: Whole blood samples were collected from 90 mUC patients (162 samples in total) for next-generation sequencing of cell-free DNA (cfDNA) and leukocyte DNA. Deep targeted sequencing was performed across a custom 50 bladder cancer gene panel (median cfDNA depth of 986x). Matched archival primary tissue and/or metastatic tissue biopsy was available from 65 patients, and profiled using the same assay. Results: 81% of mUC patients (73/90) had ctDNA fractions above 2% in at least one blood collection (median ctDNA fraction 22%). A high tumor mutation burden (≥25 mutations per Mb) was observed in ctDNA from 20 patients (27%). From ctDNA, TP53 and ARID1A were mutated in 64% and 29% of patients, respectively. Tissue from distant metastatic lesions was available from 17 patients; 82% (62/76) of coding somatic mutations identified were independently detected in the matched ctDNA sample; however, 7/14 discordant calls were attributable to the paired sample having a low ctDNA fraction. Similarly, 89% (88/99) of coding somatic mutations detected in archival primary tissue (cystectomy or nephrectomy) were present in later cfDNA collections. Sequencing multiple sites from archival cystectomies revealed spatially and genomically distinct subclones in 2/4 cases. Conclusions: In mUC, tumor tissue and ctDNA demonstrate remarkably high concordance; our findings support the use of either approach in the characterization of truncal driver gene alterations.
Bevacizumab (BEV) with or after chemotherapy (CT) for platinum-resistant recurrent ovarian cancer (PROC): Exploratory analyses of the AURELIA trial.
Authors: Aristotelis Bamias, Meletios A. Dimopoulos, Flora Zagouri, Anne-Sophie Veillard, Jens Kosse, Ana Santaballa, Mansoor Raza Mirza, Gianna Tabaro, Ignace Vergote, Haiko Bloemendal, Maria Lykka, Anne Floquet, Chee Lee, Val Gebski, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2015)

5551 Background: In the open-label randomized phase III AURELIA trial, adding BEV to CT for PROC significantly improved progression-free survival (hazard ratio [HR] 0.48; p < 0.001) and response rate (27% vs 12%) vs CT alone, but not overall survival (OS). Methods: Eligible patients (pts) had measurable/assessable OC that had progressed < 6 mo after platinum CT. After CT selection, pts were randomized to CT ± BEV until progression (PD), unacceptable toxicity or consent withdrawal. Crossover to BEV at PD was optional in the CT arm but prohibited in the BEV–CT arm. Exploratory post hoc analyses assessed factors potentially affecting the decision to crossover to BEV, and efficacy and safety according to post-PD BEV. Results: 179 pts were randomized to BEV–CT and 182 to CT alone. 72 pts (40%) in the CT-alone arm crossed over to BEV after PD and 110 never had BEV. There were no significant differences in pt characteristics between these subgroups at baseline but at the time of PD, 51% vs 35%, respectively, had ECOG performance status (PS) 0 (p = 0.034). 3-month landmark analyses, excluding 28 pts who died or were lost to follow-up before this time, showed significantly longer OS in pts who received BEV either with CT (HR 0.72, 95% CI 0.54–0.97) or after PD (HR 0.69, 95% CI 0.48–0.99) vs those who never received BEV. These differences remained significant after adjusting for identified prognostic factors for OS (chosen CT, platinum-free interval, ECOG PS, baseline ascites, baseline CA-125). When analyzed from the time of PD, the OS HR vs never BEV was 0.84 (95% CI 0.62–1.14) for upfront (pre-PD) BEV–CT and 0.55 (95% CI 0.38–0.79) for BEV after PD. Tolerability was similar with pre- vs post-PD BEV. Conclusions: There appears to be no clear difference in OS between upfront vs post-PD BEV therapy. Pts who never received BEV had the worst OS. These analyses of a non-randomized phase of the study with no information on other post-PD therapies do not allow definitive conclusions about upfront vs post-PD BEV efficacy. Nevertheless, as 60% of pts randomized to CT alone never received BEV, upfront treatment with BEV–CT is important, as reserving BEV until after PD may deny some pts the opportunity to benefit from BEV. Clinical trial information: NCT00976911.
Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study
Authors: Funda Meric-Bernstam, Herbert Hurwitz, Kanwal Pratap Singh Raghav, Robert R McWilliams, Marwan Fakih, Ari VanderWalde, Charles Swanton, Razelle Kurzrock, Howard Burris, Christopher Sweeney, Ron Bose, David R Spigel, Mary S Beattie, Steven Blotner, Alyssa Stone, Katja Schulze, Vaikunth Cuchelkar, John Hainsworth
Journal: The Lancet Oncology (2019)
Targeted Delivery of CpG-Mir-146a Mimic Oligonucleotides As a Therapeutic Strategy to Reduce NF-Κb-Mediated Pathogenic Inflammation and Myeloid Leukemia Progression
Authors: Yu-Lin SU, Zhuoran Zhang, Mati Mann, Xiuli Wang, Le Xuan Truong Nguyen, Bin Zhang, Ling Li, Piotr Swiderski, Mark Boldin, Stephen J Forman, Guido Marcucci, Marcin Kortylewski
Journal: Blood (2018)
Initial Opioid Prescriptions among U.S. Commercially Insured Patients, 2012–2017
Authors: Wenjia Zhu, Michael E. Chernew, Tisamarie B. Sherry, Nicole Maestas
Journal: New England Journal of Medicine (2019)

The United States is undergoing a crippling opioid epidemic, spurred in part by overuse of prescription opioids by adults 25 to 64 years of age. Of concern are long-duration and high-dose initial prescriptions, which place the patients and their friends and relatives at heightened risk for long-term opioid use, misuse, overdose, and death.We estimated the incidence of initial opioid prescriptions in each month between July 2012 and December 2017 using administrative-claims data from across the United States (accessed through Blue Cross-Blue Shield [BCBS] Axis); monthly incidence was estimated as the percentage of enrollees who received an initial opioid prescription among those who had not used opioids (i.e., no opioid prescription or a diagnosis of opioid use disorder in the 6 months before a given month). We then estimated the percentage of enrollees initiating opioid therapy who received a long-duration or high-dose initial opioid prescription in each month during this period. We also calculated the number of providers who initiated opioid therapy in any patient who had not used opioids in each month and examined monthly trends in the duration and dose of initial opioid prescriptions in prescriber and patient subgroups. Our study sample included 63,817,512 enrollees who had not used opioids (mean, 15,897,673 per month).The monthly incidence of initial opioid prescriptions among enrollees who had not used opioids declined by 54%, from 1.63% in July 2012 to 0.75% in December 2017. This decline was accompanied by a decreasing number of providers (from 114,043 in July 2012 to 80,462 in December 2017) who initiated opioid therapy in any patient who had not used opioids. Nonetheless, among the shrinking subgroup of physicians who initiated opioid therapy in such patients, high-risk prescribing (i.e., prescriptions for more than a 3-day supply or for a dose of 50 morphine milligram equivalents per day or higher) persisted at a monthly rate of 115,378 prescriptions per 15,897,673 enrollees who had not used opioids.As the opioid crisis progressed between July 2012 and December 2017, many providers stopped initiating opioid therapy. Although the number of initial opioid prescriptions declined, a subgroup of providers continued to write high-risk initial opioid prescriptions. (Funded by the National Institute on Aging and a gift from Owen and Linda Robinson.).
Clinical outcomes of minimally invasive retroperitoneal lymph node dissection and single dose carboplatin for clinical stage IIa seminoma.
Authors: Robert A Huddart, Alison Helen Reid, Erik Mayer, Syed A Sohaib, David Nicol
Journal: Journal of Clinical Oncology (2019)

530 Background: Standard management of Stage 2 seminoma (SEM) is 3 cycles of cisplatin based multi-agent chemotherapy or paraaortic/pelvic radiotherapy. Both treatments have potential short and long term toxicity. We report the use of minimally invasive (robotic or laparoscopic) retroperitoneal lymph node dissection (MI-RPLND) and adjuvant carboplatin. Methods: From 01/2013-04/2017, patients (pt) with SEM and Stage 2a disease on computed tomography (CT) staging scan were considered for MI-RPLND included the radiologically enlarged lymph nodes for Stage 2a SEM. Adjuvant carboplatin (AUC 7) x 1 cycle was administered after confirmation of nodal involvement. Post-operative outcomes including length of stay, Clavien-Dindo 1 complications and pathological staging were recorded. CT was performed at 3 months to verify nodal clearance and then pts monitored with a standard surveillance protocol. Results: Twenty modified unilateral templates were performed. Median and mean post-operative stay was 1 and 1.5 days. One pt required conversion to open surgery and two experienced Clavien-Dindo 1 complications. All pts had preserved ejaculation. Mean number of nodes removed per pt 14.3 (range 5-31) with average 1.75 nodes involved (range 0-5). In 2 pts the enlarged nodes were pN0; they were surveyed and are relapse free at 44+ months. In one case the enlarged lymph node contained embryonal carcinoma (EC) despite primary histology of pure SEM. The remaining 17 pts had confirmed pathological stage 2 SEM. The pt with EC and one pt who had adjuvant carboplatin for stage 1 disease received (B) EP x 2 cycles. 16 patients received a single cycle of adjuvant carboplatin (AUC 7). After median follow-up of 41 months (range 22-70), one patient has relapsed. This occurred at 18 months outside the template of dissection. This patient initially had multifocal disease with 3 pathologically involved nodes. He received BEP X 3 with complete radiological resolution of disease and remains disease free. Conclusions: MI-RPLND in conjunction with a single dose of carboplatin may potentially be an option for the management of Stage 2a SEM. In this series, a subset of pts were overstaged using standard CT imaging.
Impact of non steroidal anti-inflammatory drugs (NSAIDs) in patients with salivary gland tumors.
Authors: Bilal Ahmad, Sobia Nabeel, Haseeb Saeed, Michael Machiorlatti, Sara Vesely, Mohamad Ali Cherry, Wajeeha Razaq, Mohammad Razaq
Journal: Journal of Clinical Oncology (2015)

e17067 Background: Preclinical and recent randomized trials have shown benefit of NSAIDs in inhibition of carcinogenesis mainly in gastrointestinal cancers. Salivary gland tumors comprise a group of heterogeneous tumors making less than 1 % of all the cancers and limited data is available in this regard. We describe a retrospective analysis of adult patients (pts) with salivary gland tumors treated at our institution evaluating impact of NSAIDs. Methods: From Jan 1996 to June 2013, we identified a total of 183 patients of which 137 patients met the inclusion criteria. We divided patients into two groups: Patients with NSAIDS and patients without NSAIDS. We studied outcomes in different stages I, II, III and IV. Kaplan-Meier curves were used to estimate survival rates for categorical variables. A Cox Proportional Hazards model on overall survival (OS) was implemented to assess continuous covariates as well as create a final multivariable model. We assessed interaction between age, gender, NSAIDs use and number of medications according to the stage. Results: A total number of 137 patients were assessed. There were 83 (61%) pts ≥ 60 yrs and 54 (39%) pts < 60 yrs of age. The median age was 66 yrs with 84 (61%) males and 53 (39%) females. On the basis of stage, 19 (14%) pts with Stage I, 32 (23%) Stage II, 34 (25%) Stage III, and 52 (38%) Stage IV. NSAIDs use was reported in 48% (62/137) of pts with 7 patients having unknown status. ‪After adjusting for stage, age, sex, and other covariables, NSAIDs use was significantly (p-value = 0.0401) associated with overall survival (OS). The hazard of death was 2.4 (95% CI 1.04 - 5.54) times higher for those who were not on NSAIDS as compare to pts who were on NSAIDs. Similarly, we found that gender was significantly associated with OS (p = 0.0024), with males having a higher hazard of death relative to females (HR = 3.26 95% CI 1.52-7.00). Conclusions: Patients with Salivary glands tumors who were on NSAIDs had better OS as compare to the pts who were not on NSAIDs regardless of the stage. This supports the fact that NSAIDS might have antitumor properties. Further investigations are needed to study this impact in rare tumors like salivary gland tumors.
Hyperthermic intraperitoneal chemotherapy (secondary cytoreduction CRS + HIPEC) for recurrent epithelial ovarian cancer (EOC): Indian experience.
Authors: S.P. Somashekhar, Prasanna G, Amit Rauthan, Rajshekhar Channabasappa Jaka
Journal: Journal of Clinical Oncology (2015)

e16536 Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has been proposed as treatment for recurrent epithelial ovarian carcinoma. We evaluated the outcomes of CRS+ HIPEC in Recurrent Epithelial Ovarian cancers, in Indian patients. Methods: Prospective non-randomized study February 2013-Jan 2015. 26 patients with advanced Recurrent EOC, with no extra-abdominal disease treated with Secondary CRS + HIPEC in a tertiary care Cancer institution, Southern India, were analyzed. Belmonte dedicated HIPEC machine pump with Cisplatin 100mg/m2, 41.5-43 degree Celsius for 90 minutes, in platinum sensitive cases & Doxorubicin 15 mgs/m2 + Cisplatin 75 mgs/m2 in platinum resistant cases was used Results: 18 upfront & 8 post chemotherapy. Median peritoneal carcinomatosis Index, PCI, was 9.5 (Range 3-19). Average surgery duration 9 hrs (Range 5.5 – 19). No 60 days mortality. Duration of hospital stay (p < 0.001), gastrointestinal recovery (p = 0.039), infection type (p = 0.036), ARDS (p = 0.041) correlates with extent of cytoreduction. 24 patients achieved CC0, and 2 pts CC1. Bowel resection required in 34.6 %. Diaphragm stripping was required in 30.7% with resection in 7.6%. Median hospital stay was 12 days (range: 10-42 days) Bowel fistula happened in 7.6% cases requiring re-exploration, temporary stomas, wound related complications in 26%. At median follow-up of twelve months, 11.5% recurrences ( Both Paltinum resistant cases recurred in peritoneal cavity and one pt also in Liver Parenchyma) and One platinum sensitive pt recurred isolated in Peritoneal cavity. One death (Pulmonary embolism at 5th month of f/u was observes). Remaining 23 patients are disease free till to date. Conclusions: In our Indian study, secondary cytoreduction and HIPEC is shown to be very promising in Recurrent Epithelial Ovarian cancers pts with no extra-abdominal disease & good Performance status and can be done with acceptable morbidity, using dedicated HIPEC machine resulting in good peritoneal control of disease & DFS. The benefit of HIPEC in our study was limited to platinum sensitive recurrent cases only and not to platinum resistant cases.
Multigene profiling in incidentally- and clinically detected prostate cancer.
Authors: Maristella Bianconi, Luca Faloppi, Antonio Zizzi, Roberta Mazzucchelli, Mario Scartozzi, Rodolfo Montironi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2015)

e16107 Background: Many prostate cancers never become clinically evident even in the absence of treatment. Randomized trials have confirmed an early survival advantage for surgery in higher-risk disease. Novel biomarkers can improve prediction and decision making about treatment. One promising tool is the expression of genes related to cell cycle progression (CCP). Analysis of their expression yields a CCP score that is an independent factor in radical prostatectomy (RP) and in transurethral resection of the prostate (TURP) [1]. Information on the expression of such genes in clinically insignificant prostate cancer, present in approximately 40% of men, has never been assessed.We aimed to validate the performance of the CCP score in a small cohort of incidental prostate cancer in comparison with clinically-detected prostate cancer. Methods: We collected specimen of 7 radical prostatectomy, 3 incidentally and 4 clinically detected prostate cancers. Gene profiling analysis was conducted at the Myriad Genetics Laboratory, Salt Lake City, Utah, USA. Samples were taken from the dominant tumor focus. RNA was extracted using miRNeasy (Qiagen, Valencia, CA), and expression levels were determined using TaqMan low-density arrays (Applied Biosystems, Foster City, CA) for a set of 46 predetermined genes (31 CCP and 15 housekeeper genes). All genes were centered by their average expression in a set of commercial prostate tumor samples. Results: Among all 46 studied genes, BIRC5 and FOXM1 showed statistically significant differences in expression according to clinical presentation (p = 0,0286). BIRC5, also known as survivin, is a key player in mitosis. FOXM1 expression in prostate epithelial cells is critical for prostate carcinogenesis. Conclusions: The current study, even though based on a small number of cases shows that there are subtle differences in terms of gene expression between incidental and clinically detected prostate cancers. This investigation may represent a clinical tool to categorize patients with different prognosis. References: 1) Cooperberg MR, Simko JP, Cowan JE, et al. Validation of a Cell-Cycle Progression Gene Panel to Improve Risk Stratification in a Contemporary Prostatectomy Cohort. J Clin Oncol 2013, 31.