tbuckley/cabot-search huggingface dataset:
Bisphosphonate utilization among men with metastatic castration-resistant prostate cancer (CRPC).
Authors: Alicia Katherine Morgans, Amy J Graves, David F. Penson
Journal: Journal of Clinical Oncology (2015)

e16088 Background: National Comprehensive Cancer Network guidelines recommend monthly zoledronic acid in men with castration-resistant prostate cancer to prevent SREs. We assessed adherence to guideline recommendations by studying bisphosphonate utilization in a population-based cohort of men with metastatic CRPC. Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified men aged > 65 with prostate cancer as a primary cause of death during 2006-2009. Death from prostate cancer was presumed a surrogate for metastatic CRPC because Medicare lacks a diagnosis code for CRPC. We identified doses of bisphosphonates during a 12-month period beginning15 months before death and concluding at SRE or 3 months before death. We used multivariable negative binomial regression with an offset of log follow-up time to identify factors associated with bisphosphonate treatment. Results: Among 9,634 men who died of prostate cancer, 22% received ≥ 1 treatment with bisphosphonates. Bisphosphonate use increased over time, with men dying in 2009 more likely to receive treatment than men dying in 2006 (incidence rate ratio [IRR] 1.88, 95% CI 1.70-2.70). Men age 75-84 and ≥ 85 were less likely than men aged 65-74 to use bisphosphonates (IRR 0.63, 95% CI 0.49-0.78 and IRR 0.34, 95% CI 0.17-0.50, respectively). Black men were less likely than white men to receive treatment (IRR 0.75, 95% CI 0.54-0.95), as were men from areas with lower median income (P = 0.014). Compared with men seeing a urologist only, men seeing a medical oncologist and a urologist (IRR 2.52, 95% CI 2.36-2.38) or a medical oncologist alone (IRR 3.82, 95% CI 3.54-4.09) had higher incidence rate of treatment. Conclusions: Fewer than a quarter of American men dying of prostate cancer receive treatment with bisphosphonates within the final year of their lives, with particularly low rates of treatment among older men, black men, and those living in areas with low median income. Visits with a medical oncologist were associated with increased incidence rate of treatment. Further research is needed to determine why there are disparities in adherence to guidelines by age, race and socioeconomic status, and to identify interventions to eliminate them.
Overall survival by race in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or enzalutamide.
Authors: Megan Ann McNamara, Daniel J. George, Krishnan Ramaswamy, Stanislav Lechpammer, Jack Mardekian, Neil M. Schultz, Li Wang, Onur Baser, Ahong Huang, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2019)

212 Background: Prostate cancer (PC) is the most common malignancy among US men and the 2 nd leading cause of cancer-related death. African Americans (AAs) have higher mortality from mCRPC than Whites (W). Despite this disparity, a small prior study suggested AAs may have better PSA response to abiraterone acetate (ABAC) than Ws, though radiographic progression did not differ. We evaluated overall survival (OS) in AA vs W chemotherapy-naïve (CN) mCRPC patients (Ps) treated with ABAC or enzalutamide (ENZ). Methods: This was a retrospective study that used the Veterans Health Administration (VHA) database. Male PC Ps (≥18 years) who had surgical or medical castration were identified from Apr 1, 2013 to Mar 31, 2018. The index date was the first prescription claim date for ABAC or ENZ following castration. Ps had no chemotherapy for 12 months pre-index date and had continuous VA health plan enrollment for ≥12 months pre- and post-index date. Ps were followed until death or disenrollment. Unadjusted and Kaplan-Meier survival analyses adjusted for demographic and clinical characteristics were used to calculate survival time, and multivariate Cox proportional hazards models assessed the relationship between race and OS. Results: This study included 2,123 W and 787 AA mCRPC Ps with mean ages of 74 and 71 years, respectively. The median follow‐up time was 570 days and 561 days for AA and W, respectively. AA were more prone to comorbid hypertension (77.1% vs 67.1%; p&lt;.0001), type II diabetes (38.1% vs 29.3%; p&lt;.0001), and liver damage or abnormality (8.8% vs 5.2%; p=0.0003) than W . From the unadjusted analysis, the median Kaplan-Meier estimated OS was 910 days for AAs and 784 days for Ws; AAs had better OS than Ws (HR=0.887; 95%CI [0.790-0.996]). From the adjusted analysis, the median Kaplan-Meier estimated OS was 918 days for AAs and 781 days for Ws; AAs still had better OS (HR=0.826; 95%CI [0.732-0.933]). Conclusions: This large retrospective study provides the first evidence that AA CN mCRPC Ps may have better OS with ABAC or ENZ than W Ps. Trials are needed to validate this finding and explore the mechanisms of racial disparities in outcomes with new hormonal therapies.
A multidisciplinary team-based approach to mitigate the impact of androgen deprivation therapy in prostate cancer: A randomized phase II study.
Authors: YaoYao Guan Pollock, Li Zhang, Tammy J. Rodvelt, Brian Ma, Greta Macaire, Rami Weinberg, Stacey Kenfield, June M. Chan, Kimberly Topp, Erin Van Blarigan, Terence W. Friedlander, Amy M. Lin, Lawrence Fong, Won Kim, Jeffrey Hough, Mina Lee, Charles J. Ryan, Eric Jay Small, Rahul Raj Aggarwal
Journal: Journal of Clinical Oncology (2019)

204 Background: Androgen deprivation therapy (ADT) is associated with numerous metabolic toxicities that are potentially modifiable. We sought to evaluate the impact of participation in a multidisciplinary clinic (MDC) designed to provide individualized lifestyle modification and management of ADT-related side effects. Methods: This phase II study recruited men with prostate cancer who had started ADT &lt; 6 months prior to enrollment, and in whom ADT was planned for at least 12 months following enrollment. Patients were randomized in a 1:1 ratio to either the MDC or standard of care (SOC). Patients randomized to the MDC were provided monthly multidisciplinary assessment and counseling on exercise, nutrition, and symptom management for 12 months on a rotating schedule. Endpoints included feasibility endpoints (proportion of visits completed), and efficacy endpoints, including mean change from baseline to 12 months in blood pressure (BP), weight, waist circumference, percent body fat, hemoglobin A1C (HbgA1C), insulin resistance, and fasting lipids. Results: 25 men were randomized to MDC, and 23 were randomized to SOC. Overall 91% (295/325) of MDC visits were completed. 72% (18/25) of patients completed all 12 months of MDC, and 80% (20/25) completed the first 6 months. Compared to SOC, patients in the MDC arm had a trend towards more favorable mean percent change from baseline to 12-month follow up in systolic BP (6.5% vs. 10.3%), diastolic BP (-3.9% vs.10.0%), waist circumference (2.5% vs. 4.0%), HbA1C (-2.4% vs. -1.7%), insulin resistance (0.5% vs. 1.9%), and fasting lipids (total cholesterol: 7.0% vs. 21.8%; LDL: -2.9% vs. 7.6%; triglyceride: 15.5% vs. 37.2%). Conclusions: Individualized and comprehensive management of toxicities of ADT in a multidisciplinary clinic is feasible, and appears to provide some benefit over SOC. Larger randomized studies are warranted to investigate whether this intervention will provide lasting benefit. Clinical trial information: NCT02168062.
Abstract MP50: Regional Income and Relative Individual Income, but Not Income Inequality, is Associated With Cardiovascular Health
Authors: Sarah S Singh, Stephanie J Frisbee
Journal: Circulation (2019)

Background: Result from many studies support that the associations between income, income inequality, and mortality, including CVD mortality, are very complex. Given the urgent need for greater CVD prevention in populations, it is essential to understand how income inequality and income, both in individuals and the regions in which they live, can affect cardiovascular health (CVH). Objective: To examine the associations between regional income and income inequality and individual relative income and individual CVH. Setting: This study was carried out in a nationally representative sample of Canadian adults aged 20 years and older residing in 113 health regions (HR) across Canada. Data and Methods: This study is a cross-sectional design using data from the Canadian Community Health Survey (CCHS) 2015-2016 database. The CCHS is a nationwide, nationally representative survey that collects information on the health status, health care utilization, and health determinants of the Canadian population. The study outcome was individual CVH, defined using the AHA CVH Index (CVHI) and determined using self-reported responses in CCHS. Regional income inequality was measured as the Gini coefficient of the HR. Regional income was measured as the median household income in the HR. Individual income was measured as relative, not absolute, income representing the individual’s household income compared to those in the HR. Multilevel models were used to examine the associations between regional income and income inequality and individual relative income and individual CVH, controlling for individual age, sex, race and education. Analyses were conducted using SAS 9.4 software. Results: The majority of the population were males (51%), aged 40-60 (37%), with tertiary education (64%) and of the White race (79%). Overall, mean CVH for individuals was 4.5. The national average Gini coefficient across HRs was 0.4. The average individual fell within the 6 th decile for relative household income. Living in a HR with greater income inequality was not associated with lower individual CVH (β= -0.04 p-value=0.91), though living in an HR with higher median household income was associated with better individual CVH (β= 0.32 p=0.004). Finally, having higher relative household income was associated with better individual CVH (β= 0.05 p&lt;0.0001), regardless of the median income of the region of residence. Conclusion: While the inequality of income within a HR did not significantly affect CVH, higher regional income and relative individual income was associated with better CVH. Results of this study contribute to the growing body of evidence attempting to disentangle the true associations between income, income inequality, and CVH.
Intensive follow-up for detection of recurrences in resected high risk colorectal cancer patients.
Authors: Luis Felipe Schmidt, Henrique de Araujo Vianna Trasel, Juliano Ce Coelho, Guilherme Geib
Journal: Journal of Clinical Oncology (2015)

e14511 Background: A significant proportion of resected colorectal cancer patients will relapse and, when feasible, surgical resection is the only potentially curative approach. Moreover, early palliative chemotherapy may improve survival. There is no consensus about the best strategy of follow-up, chiefly in high risk cases. We evaluate an intensive follow-up strategy in detection of potentially resectable relapses in high risk colorectal cancer. Methods: A retrospective cohort was performed in a university hospital in Brazil. Patients with stage III colorectal cancer, treated from 2002 to 2013 and at least 18 months of follow-up were included. Data was collected from electronic records. All CT scans of abdomen and chest and Carcinoembrionic antigen (CEA) measurements were computed during five years. Primary outcome was the rate of curative intent resection on first relapse. Total number of recurrences and survival were secondary outcomes. Study was approved by local ethics committee. Results: A total of 314 patients were included in analysis. Median age was 62 years, 51.3% female and colonic primary site in 58.9%. Stage IIIA, IIIB and IIIC were 8.9, 69.1 and 22.0% respectively. Complete adjuvant treatment was done by 72.6%. CEA and abdominal and chest CT rates, adjusted for length of follow-up were, respectively, 2.07, 1.21, 0.73 exams/patient/year. Relapses occurred in 144 patients (45.9%), most (72.8%) in the first two years. Curative intent resection was performed in 45 patients, representing 31.2% of relapses and 14.3% of the cohort. Number of CT scans needed to detect any relapse and a potentially resectable relapse were, respectively, 12 and 39 for entire period and 8 and 35, for the first two years of follow-up. Median overall survival was not reached in salvage resection patients, compared to 20 months in relapsed patients not amenable to rescue surgery (HR 0.19, IC95% 0.09-0.40; p < 0.001). Conclusions: We observed a substantial number of relapses after primary treatment in a cohort of high risk colorectal patients. Rescue surgery in metastatic patients was slightly higher than previous reports. Stage III colorectal cancer patients may benefit from intensive follow-up schedule, particularly in first two years.
The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.
Authors: Onal Cem, Ali Murat Sedef, Fatih KOse, Ezgi Oymak, Ozan Cem Guler, Ahmet Taner Sumbul, Sercan Aksoy, Berna Akkus Yildrim, Ali Ayberk Besen, Sadik Mullaoglu, Huseyin Mertsoylu, Gokhan Ozyigit
Journal: Journal of Clinical Oncology (2019)

308 Background: The aim of this study is to evaluate the prognostic implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and after 4 and 12 weeks of treatment with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively evaluated 102 mCRPC treated with abiraterone either pre- or post-chemotherapy between November 2012 and October 2017 in three institutions. We calculated NLR and PLR at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks. Fifty patients (49%) were treated with abiraterone post-docetaxel, and 52 patients (51%) received abiraterone pre-chemotherapy. Based on receiver operating characteristic analysis, patients were stratified as low NLR ( &lt; 3.1) or high NLR (≥ 3.1), and low PLR ( &lt; 163) or high PLR (≥ 163). The cutoff for anemia was &lt; 12g/dL. Results: Median follow-up times for patients overall and for those who survived were 24.0 months (range, 0.3 – 54.9 months) and 25.5 months (range, 2.8 – 54.9 months), respectively. The median time of abiraterone treatment was 8.1 months (range, 2.4 – 40.1 months). The median overall survival (OS) was 20.8 months (interquartile range: 17.3–24.4). In univariate analysis, NLR, PLR, PSA response, and low hemoglobin (Hgb) were found significantly predictive of OS and progression-free survival (PFS). In multivariate analysis, declines in NLR and PSA of ≥ 90% emerged as significant independent predictors of OS and PFS. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. Patients with baseline Hgb &gt; 12 g/dL had significantly longer median OS compared with patients with Hgb ≤ 12 g/dL; however, the significance of Hgb was lost at 12 weeks. Conclusions: NLR and PSA response to abiraterone was a significant predictor of OS and PFS in mCRPC patients treated with abiraterone delivered either pre- or post-chemotherapy. Furthermore, persistent increase in NLR during abiraterone has prognostic value for OS in patients with mCRPC.
Catheter ablation for atrial fibrillation no better than drug therapy for reducing death or disabling stroke, trial finds
Authors: Susan Mayor
Journal: BMJ (2019)

Catheter ablation achieved no significant reduction in death, disabling stroke, serious bleeding, or cardiac arrest compared with drug treatment in patients with atrial fibrillation (AF) in a large randomised trial.1 But further results2 showed clinically significant improvements in symptoms and quality of life with ablation.

Antiarrhythmic drug therapy has been the primary treatment for AF for decades but limited effectiveness in some patients has led to the development of other strategies to maintain sinus rhythm, including ablation. Although effective in restoring sinus rhythm in AF, the effects of catheter ablation on long term mortality and stroke risk have been unclear.

The new international study, CABANA, randomised 2204 patients to either catheter ablation (pulmonary vein isolation with additional ablation procedures at …
Personalized use of metronomic cyclophosphamide for DNA repair deficient castration-resistant prostate cancer: A phase II trial.
Authors: Cameron Phillips, Giulio Francia, Robert S. Kerbel, Urban Emmenegger
Journal: Journal of Clinical Oncology (2019)

TPS346 Background: There is a continued need to identify novel targets for the treatment of metastatic, castration-resistant prostate cancer (mCRPC). DNA damage repair (DDR) aberrations are emerging as such a target: 20%-30% of mCRPCs harbor DDR gene aberrations, rendering tumors particularly sensitive to DNA damaging agents and poly ADP-ribose polymerase inhibitor (PARPi) therapy. 88% of men with DDR deficient mCRPC responded to the PARPi olaparib in a phase II trial, whereas in unselected mCRPC patients the metronomic use of the DNA damaging agent cyclophosphamide (CPA) resulted in response rates of 25-60%. Intriguingly, in randomized phase II trials of unselected ovarian and triple-negative breast cancer (ie tumor types enriched for DDR defects), metronomic CPA alone was as active as metronomic CPA plus the PARPi veliparib. Based on this we hypothesize that DDR deficient mCRPC is particularly sensitive to metronomic CPA. To the best of our knowledge this is the first attempt to utilize metronomic CPA in a personalized manner. Our study has the potential to define metronomic CPA as an affordable and well-tolerated alternative to PARPi therapy in men with DDR deficient mCRPC. Methods: To study if metronomic CPA achieves a similar response rate (ie ≥85%) in DDR deficient mCRPC as seen with olaparib, men with mCRPC progressing after 1-2 lines of systemic therapy will undergo circulating tumor DNA based testing for BRCA1/2 or ATM aberrations. Patients with such aberrations will proceed with metronomic CPA (50 mg po daily). Primary endpoint: RECIST 1.1 and/or ≥50% PSA response rate at 12 weeks. Secondary endpoints include biochemical, radiological and clinical progression-free survival. Applying the Optimal Simon's Two-Stage design, and using a type I error rate of 0.05 and a power of 0.8, in the first stage we plan to enroll 14 patients. If there are ≤10 or fewer responses, the study will be stopped. Otherwise, another 19 patients will be accrued as part of the second stage.
The use of adjuvant treatment in stage I endometrioid endometrial cancer in the National Cancer Database (NCDB).
Authors: Angela Jain, Elizabeth Handorf, Gina Mantia-Smaldone
Journal: Journal of Clinical Oncology (2015)

5599 Background: Women with Stage I endometrioid endometrial carcinomas (EEC) tumors have excellant long term survival. Women may be offered adjuvant radiation if high-risk features are present in the resected tumor. Whole pelvic radiation (EBRT) or vaginal brachytherapy (VB) reduce local recurrence, but do not improve survival. GOG249 looked at the use of chemotherapy with VB in high-grade tumors (HGT). This is a retrospective study using the National Cancer Database to understand national trends in using surgery, radiation and chemotherapy in Stage I EEC. Methods: We identified women with EEC diagnosed between 1998 and 2012 and treated with surgery and/or chemotherapy and/or radiation using the National Cancer Database, with known grade status. Using Chi-squared tests and multivariate logistic regression, we analyzed pathologic stage of EC by age, grade, histology, facility type, race, payor status, income, location, Charlson score, year of diagnosis and facility location. Due to data availability, survival analysis was restricted to patients diagnosed between 2003 and 2007. We used Kaplan-Meier curves and proportional hazards regression to assess overall survival in patients treated with adjuvant EBRT vs VB. Results: Among 241,350 patients identified, patients with HGT had decreased use of EBRT over time from 17% to 5%; the use of VB increased from 7% to 24% (p = 0.0001). There were no significant changes for the use of radiation in patients with low-grade tumors. Patients with age > 70 were more likely to receive radiation than patients < 70, but less likely to receive chemotherapy (p = 0.0001). The use of chemotherapy in all patients increased from 1% to 14% over time. Multivariate analysis demonstrated that patients with HGT had 84% 5 year survival with VB vs 78% for patients receiving EBRT (HR 0.85 vs 1.16, p = 0.0001). In patients with low grade tumors there was no advantage for the use of VB and ERBT decreased survival. The use of chemotherapy did not improve survival. Conclusions: The use of VB and chemotherapy has been increasing over time for patients with HGT. However, the use of chemotherapy may not improve survival in this highly curable population, while the use of EBRT is demonstrated to decrease survival.
WGS and RNA-Seq Is Superior to Conventional Diagnostic Tests in Multiple Myeloma: Ready for Prime Time?
Authors: Alexander Höllein, Sven O. Twardziok, Wencke Walter, Stephan Hutter, Jesús María Hernández, Manja Meggendorfer, Torsten Haferlach, Wolfgang Kern, Claudia Haferlach
Journal: Blood (2018)
Outcomes of high-dose whole pelvic simultaneous integrated boost IMRT in patients with pelvic lymph node-positive prostate cancer.
Authors: Takashi Mizowaki, Kenji Takayama, Kiyonao Nakamura, Rihito Aizawa, Takahiro Inoue, Toshinari Yamasaki, Takashi Kobayashi, Shusuke Akamatsu, Osamu Ogawa
Journal: Journal of Clinical Oncology (2019)

192 Background: Managements of prostate cancer patients with positive pelvic lymph node (N1M0) have been very challenging. We evaluated the outcomes of high-dose whole pelvic (WP) intensity-modulated radiation therapy (IMRT) by using the simultaneous integrated boost (SIB) technique, combined with long-term androgen deprivation therapy (ADT). Methods: Between May 2005 and November 2013, 52 patients with T2a-T4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Pelvic lymph node metastases were clinically diagnosed based on the following criteria; depicted swollen lymph nodes on diagnostic imaging associated with subsequent shrinkage in size on a follow-up imaging after neoadjuvant ADT (NA-ADT). The median age and initial PSA value were 66 years old (range: 52–79) and 29.7 ng/ml (4.8–251.9), respectively. NA-ADT (median: 8 months, range: 5–20) was given in all cases. SIB WP-IMRT was designed to simultaneously deliver 78 Gy, 66.3 Gy, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes, and the pelvic lymph node region, respectively. Adjuvant ADT (A-ADT) was given in all patients except for one case who developed severe adverse events during NA-ADT. In 9 patients, permanent A-ADT was given due to castration after IMRT (n = 2) and development to castration resistant status during A-ADT (n = 7). The median duration of A-ADT was 24 months (range: 7–71) in the remaining 42 patients. Results: The median follow-up period was 69 months (range: 12–136). Biochemical relapse-free survival rate based on the Phoenix definition and distant metastasis-free survival rates at 5 years were 69% (95% CI = 54%–80%) and 78% (95% CI = 64%–87%), respectively. Overall survival and prostate cancer-specific survival rates at 5 years were 88% (95% CI = 74–94%) and 92% (95% CI = 79–97%), respectively. Loco-regional recurrence was not observed. 5-year cumulative incidence rates of grade 2-3 late GU and GI toxicities were both 2%. No grade 4 acute or late toxicity was observed. Conclusions: High-dose WP SIB-IMRT to patients with N1M0 prostate cancer seems promising, and warrants future prospective studies.