tbuckley/cabot-search huggingface dataset:
End-of-life chemotherapy use in metastatic breast cancer.
Authors: Tala Achkar, Mini Jacob, Vipin Villgran, Shira Abberbock, Margaret Quinn Rosenzweig, Shannon Leigh Huggins-Puhalla, Adam Brufsky, Aju Mathew
Journal: Journal of Clinical Oncology (2015)

e20505 Background: End-of-life chemotherapy (EOLC) use in metastatic breast cancer (MBC) is poorly described. We aimed to estimate the prevalence and identify the predictors of EOLC in MBC. Methods: We conducted a single institution retrospective chart review of women with MBC who died between 1/1/10 and 9/30/14. Demographic information, tumor characteristics, and survival were obtained. Dates of last chemotherapy administration were confirmed through patient charts. EOLC use was defined as receipt of chemotherapy within 4 weeks of death. The non-end-of-life chemotherapy group (non-EOLC) included all patients who did not belong to the EOLC category. Bivariate associations between multiple clinical characteristics and EOLC were tested for statistical significance using chi-square/Fisher’s exact or Wilcoxon Rank sum tests. Significant predictors for EOLC vs. non-EOLC were determined using a logistic regression model. p-values ≤ 0.025 were considered statistically significant. Results: 274 patients with MBC were analyzed. 10.2% received EOLC within 2 weeks of death, and 22.6% received EOLC within 4 weeks of death. Patients receiving EOLC were younger than non-EOLC. Patients with MBC involvement of multiple organ systems and patients treated with more lines of chemotherapy were more likely to receive EOLC compared with non-EOLC (p < 0.001). Breast cancer tumor subtype was not significantly associated with EOLC. In a multivariate analysis of EOLC versus non-EOLC, we found a 49% reduction in EOLC among subjects with CNS disease compared to those without; OR (95% CI): 0.51 (0.26-1.01); p = 0.05. Women with de novo MBC were 56% less likely to receive EOLC compared with those who progressed after early-stage breast cancer; OR (95% CI): 0.44 (0.18 – 1.06); p = 0.07. Conclusions: More EOLC was used in younger women and those with greater disease burden. Tumor subtype was not a predictor for increased EOLC use. Less EOLC use was noted among patients with CNS disease and de novo metastatic disease, although these associations were not statistically significant.
Ethnicity and hepatocellular carcinoma risk factors in New Mexico: A retrospective analysis over a 12-year period.
Authors: Khine Zar Win, Diaa Osman, Ruofei Du, Yehuda Z. Patt
Journal: Journal of Clinical Oncology (2017)

269 Background: Common hepatocellular carcinoma (HCC) risk factors, such as hepatitis C virus (HCV) and hepatitis B virus infections, heavy exposure to alcohol and non-alcoholic steatohepatitis (NASH), vary in relation to gender, ethnicity, and geographic regions. New Mexico (NM) has the highest adjusted risk ratio of 1.27 for HCC when compared with other US geographic regions. The population of Hispanic Whites (HW), non-Hispanic Whites (NHW) and American Indians (AI) in NM provides a unique opportunity to study the prevalence of the known HCC risk factors among different ethnicities. Methods: We identified about 550 patients who were diagnosed and/or received treatment for HCC at the University of New Mexico (UNM) Hospital and the UNM Cancer Center from 2003 to 2015, using ICD 9/10 codes. Following approval by institutional review board, a retrospective chart review was conducted to correlate the known HCC risk factors and ethnicity of patients. This is a preliminary report of the findings in a randomly selected 226 of the 550 patients, and we expect to complete the analysis by the time of the GI ASCO symposium. A logistic regression with pairwise comparison was conducted to determine the distribution of the HCC risk factors among different ethnicities. Results: Among NHW, HCV is the most prevalent risk factor for HCC. AI have lower proportion of HCV infection, compared to NHW (35% vs 74%; P= 0.0008). However, DM and NASH were more frequently observed among AI than NHW, 54% vs 27% and 27% vs 9% ( P= 0.025 and 0.038) respectively. Table 1: Proportion of HCV, diabetes, NASH among AI, NHW and HW and pairwise comparison between ethnic groups. Conclusions: Among AI, the major risk factors for HCC seem diabetes mellitus and NASH. However, among NHW, chronic HCV infection is the most prevalent risk factor for HCC.[Table: see text]
Survival in patients with BRCA mutation-positive platinum-sensitive recurrent ovarian cancer.
Authors: Ceri Hirst, David Parry, Kathryn Alsop, Anna deFazio, Sian Fereday, Gillian Mitchell, David Bowtell, Catherine Emmanuel
Journal: Journal of Clinical Oncology (2014)

e16519 Background: Olaparib is in development for maintenance treatment in patients with BRCA mutation positive (BRCAm) platinum sensitive recurrent (PSR) ovarian cancer. A phase 2 trial, NCT00753545, has shown superior progression free survival versus placebo, but overall survival comparison was not powered and, as in many cancer trials, was confounded by multiple subsequent therapy lines and crossover. The primary objective of this study was to estimate survival in patients with BRCAm PSR ovarian cancer unexposed to olaparib, to provide a context for outcomes in exposed patients. Methods: Between 2002 and 2006, the observational Australian Ovarian Cancer Study (AOCS) analysed BRCAm status, treatments and survival of 1001 women with nonmucinous ovarian cancer. This post-hoc analysis describes the clinical features and Kaplan Meier survival of a subcohort of BRCAm patients who met the same eligibility criteria as used in the olaparib trial (PSR defined as >6 months between the end of platinum therapy and documented response to next platinum therapy) but were unexposed to olaparib. Descriptive comparison with the olaparib-exposed arm of the clinical trial, conducted 2008-2012, was undertaken. Results: 41 BRCAm PSR AOCS patients met the inclusion criteria and were compared with 74 global olaparib-arm trial patients. Baseline characteristics were well matched for patient age, race, tumor grade, stage, and platinum sensitive interval. Response (complete/partial) to prior therapy was not analysable from AOCS. Median overall survival measured after treatment for PSR was 21.9 months in the AOCS subcohort and 34.9 months in the olaparib patients. Conclusions: After PSR, the AOCS subcohort had a shorter median survival than olaparib trial patients. Measured baseline characteristics were similar between groups. However, adjusted analyses for unmeasured confounders that may impact survival, such as prior treatment complete or partial response and time-specific factors, have not been performed. Median survival was also longer in the BRCAm trial placebo-arm (31.9 months; post-trial PARPi exposure in 23%). Thus these early findings should be interpreted with caution. Clinical trial information: NCT00753545.
Individual insulin use and the risk of breast cancer: An international clinical epidemiology study.
Authors: Lamiae Grimaldi-Bensouda, David A. Cameron, Michel Marty, Anthony H Barnett, Frederique Penault-Llorca, Michael N. Pollak, Bernard Charbonnel, Matthew Riddle, Laurent Mignot, Jean-Francois Boivin, Artak Khachatryan, Michel Rossignol, Jacques Benichou, Annick Alperovitch, Lucien Abenhaim
Journal: Journal of Clinical Oncology (2013)

1578 Background: The association between individual insulin use and cancer risk has been previously considered with studies reporting higher breast cancer incidence for insulin glargine. Objective: To assess the relative risk of breast cancer associated with individual insulin use (glargine, human insulin, insulin analogs aspart and lispro). Methods: Systematic case-control study of incident breast cancer occurring in women with diabetes from across the United Kingdom, Canada and France. Participants and Settings: 775 case-patients with diabetes and primary invasive or in situ carcinoma of the breast (diagnosed between 1 January, 2008 and 30 June, 2009) selected from 39,958 incident breast cancer patients from 92 large oncology clinics; and 3,050 control-patients with diabetes selected from 580 general practices and matched on country, age, date, type of diabetes (1 or 2), and management by diabetologist or general practitioner. Data on exposure: Data was collected from physicians and patients. Statistical analysis: The main risk model was a multivariable conditional logistic regression including individual insulin use, 8 years preceding the index date, and controlling for past use of any insulin, oral antidiabetic drug use, reproductive factors, lifestyle, education, hormone replacement therapies and contraceptive use, body mass index, comorbidities, diabetes duration, and annual number of physician visits. Results: Adjusted odds ratios of breast cancer were: 1.04 [95% Confidence Interval: 0.76-1.44] for glargine; 1.23 [0.79-1.92] for lispro; 0.95 [0.64-1.40] for aspart; 0.81 [0.55-1.20] for human insulin. Similar results were observed in new insulin users. No effect of dose or duration of use was observed for glargine on the risk of breast cancer. Conclusions: This first international case-controlled study found no difference in the risk of developing breast cancer among patients according to individual insulin use.
Extensive lymph node dissection in the era of increasing perioperative chemotherapy for muscle-invasive urothelial carcinoma of the bladder.
Authors: Dara Denise Holder, James Lin, Micheal Whalen, James M. McKiernan, Guarionex DeCastro
Journal: Journal of Clinical Oncology (2012)

e15018 Background: The efficacy of perioperative chemotherapy (CHT) in the management of muscle invasive urothelial carcinoma of the bladder (UCB) has been attributed to its ability to eliminate occult disease, which when coupled with a cystectomy can reduce recurrence. The therapeutic role of lymphadenctomy (LND), with an appropriate template and nodal yield, during radical cystectomy (RC) is well established. To date, there have been no studies examining the integrative effect of an extended LND and the use of perioperative CHT for patients with muscle-invasive UCB. As such we examined the interaction between survival and extent of LND based on whether patients received perioperative CHT or RC only. Methods: Review of our urologic oncology database yielded 314 patients with cT 2-4 N 0 M 0 UCB who underwent RC with and without perioperative CHT between 1990- 2011. Extended lymph node dissection was defined as the removal of ≥11 nodes. Clinical and pathological variables were analyzed using Cox Hazard and Kaplan Meier models. The primary endpoints examined were overall (OS) and disease-specific (DSS) survival. Results: Two hundred and four (65%) patients were identified who underwent RC only, while 110 (35%) patients received perioperative CHT and RC. There was no significant difference between the 2 groups in common demographic and pathologic variables. Fifty-one percent of patients who underwent CHT and RC and 42% who underwent a RC only had an extensive LND (p=0.16), with a mean nodal yield of 9. Extended LND was associated with a non-significant decreased risk of death in the RC-only group (HR=0.54, CI: 0.23-1.20, p=0.14), and a non-significant increase in patients who underwent perioperative CHT (HR=1.25, CI: 0.71-2.81, p=0.56). Kaplan Meier analysis showed an increase in the probability of DSS at 2 years in the RC-only group who underwent an extended LND vs. a standard LND (0.96 vs. 0.84, p= 0.12) while no such trend was observed in the perioperative CHT patients (0.75 vs. 0.75, p=0.35). Conclusions: Surgical management of occult micrometastatic disease through extended LND improves survival in patients undergoing RC only, but offers no additional benefit over perioperative CHT.
Risk factor analyses of severe cicatricial stricture after chemoradiotherapy for stage II/III (T3) esophageal carcinoma.
Authors: Natsuko Tsushita, Yoshitaka Honma, Kengo Nagashima, Takahiro Miyamoto, Shoko Nakamura, Rei Umezawa, Yoshinori Ito, Hirokazu Shoji, Atsuo Takashima, Satoru Iwasa, Ken Kato, Tetsuya Hamaguchi, Jun Itami, Narikazu Boku
Journal: Journal of Clinical Oncology (2017)

190 Background: Severe benign cicatricial stricture (SBCS) is a major complication after chemoradiotherapy (CRT) for esophageal carcinoma (EC), and causes oral intake impairment leading to deterioration of quality of life even after being cured. Aim of this study was to investigate risk factors of SBCS. Methods: The subjects of this study were patients with stage II/III (T3) EC who received CRT and achieved complete response (CR) between 2000 and 2011. SBCS was determined as disability of passage by diameter-9mm endoscope. Results: Among 197 patients with Stage II/III (T3) treated by CRT, CR was obtained in 91 patients, who were included in this analysis. The median age was 63 years. Fifteen patients (16.5%) were female. The median follow-up time was 5.1 years. The cumulative incidence of SBCS was 15.0% (95%CI 9.0-24.5). Significant risk factors of SBCS were female (hazard ratio (HR) 3.3 (95%CI 1.1-10.0), p = 0.04), requirement of diced/liquid meal (HR 5.7 (95%CI 1.8-18.2), p = 0.003), tumor occupying 3/4 or grater of esophageal perimeter (HR 7.4 (95%CI 1.3-42.9), p = 0.03) and disability of endoscope passage (HR 12.7 (95%CI 4.2-38.5), p &lt; 0.001) in univariate analysis. Hypoalbuminemia increased the risk of SBCS (HR 2.4 (95%CI 0.8-7.1), p = 0.12) marginally. As for the factors during CRT, grade 2-4 esophagitis significantly increased the risk of SBCS (HR 6.2 (95%CI 1.5-25.7), p = 0.01). Multivariate analysis showed that hypoalbuminemia (HR 3.5 (95%CI 1.1-11.1), p = 0.03) and disability of endoscope passage (HR 14.8 (95%CI 4.3-51.3), p &lt; 0.001) were the significant risk factors of SBCS. Female (HR 1.5 (95%CI 0.5-4.9), p = 0.51) was not a significant risk factor in multivariate analysis. Conclusions: Obstructions before CRT, hypoalbuminemia and severe esophagitis during CRT are considered as risk factors of SBCS. Because SBCS occurred after completion of CRT, prophylactic treatment should be established especially for esophageal carcinoma patients with risk factors of SBCS.
Progression of castrate-resistant (CR) disease in nonmetastatic (M0) prostate cancer (PC) patients: A retrospective cohort study using data from the Henry Ford Health System (HFHS).
Authors: Jennifer Beebe-Dimmer, Karynsa Cetin, Cecilia Yee, Lois Lamerato, Scott Stryker, Alexander Liede, Kendra L. Schwartz, Vahakn B. Shahinian
Journal: Journal of Clinical Oncology (2012)

e15147 Background: Androgen deprivation therapy (ADT) is the cornerstone treatment of advanced PC, but is frequently used in the M0 setting. After a variable period of hormone-sensitivity, most patients develop CR disease (rising prostate-specific antigen [PSA] despite ongoing ADT). These men are at increased risk of developing bone metastases (BMT), particularly in those with higher serum PSA and shorter PSA doubling time (DT). The epidemiology and natural history of M0 CRPC has not been well-studied in a population-based setting. Methods: A retrospective cohort study was conducted using HFHS administrative data and included 691 men diagnosed with M0 PC between 1996 and 2005, who received ADT, with serial PSA measurements to determine CR. Patient records through 12/31/2008 were reviewed for outcomes of interest. CRPC was defined as 2 consecutive PSA rises, with “high risk” defined as PSA ≥8 ng/mL or PSA DT ≤10 months (mos) after the development of CRPC (Smith MR et al. Lancet 379:39-46, 2012). The risk of BMT was estimated for the entire cohort and for the CRPC and high-risk CRPC subsets. Results: Of the 691 patients included in the cohort (median age: 73 years, 48% African American), 98% received only GnRH agonists and 2% had orchiectomy. Median follow-up for the entire cohort after ADT initiation was 49 mos (IQR=45). 101 patients (15%) met criteria for CRPC during follow-up, with a median of 18 mos on active ADT prior to CRPC development (IQR=14). Of CRPC patients, 85% met criteria for high-risk (of those, 16% had PSA ≥8 ng/mL, 12% had PSA DT ≤10 mos, and 72% had both). Among all patients, 12% (n=82) developed BMT during follow-up, with 42% (n=36) of the high-risk CRPC subset developing BMT. Median time from high-risk CRPC to BMT was 9 mos (IQR=17). Conclusions: The HFHS resource allowed for our investigation of PSA characteristics corresponding to disease progression in a racially diverse patient population. A substantial proportion of M0 PC patients on ADT will eventually develop CR disease. Once a patient has CRPC, the risk of BMT is relatively high.
Cougar-02: A randomized phase III study of docetaxel versus active symptom control in patients with relapsed esophago-gastric adenocarcinoma.
Authors: Natalie Cook, Andrea Marshall, Jane M. Blazeby, John A. Bridgewater, Jonathan Wadsley, Fareeda Y. Coxon, Wasat Mansoor, Srinivasan Madhusudan, Stephen Falk, Gary William Middleton, Daniel Swinson, Ian Chau, Joyce Thompson, David Cunningham, Paula Kareclas, Janet A. Dunn, Hugo Ford
Journal: Journal of Clinical Oncology (2013)

4023 Background: Survival in patients who relapse after first-line chemotherapy (CT) for advanced esophago-gastric adenocarcinoma (EGC) is poor though recently randomised trials (RCT) have suggested a small benefit for second line chemotherapy with taxanes or irinotecan. There is very little data on health related quality of life (HRQL) or overall survival (OS), particularly in patients who progress shortly after first-line therapy. Methods: COUGAR-02 was a multicentre open-label, phase III RCT for patients with locally advanced or metastatic EGC of performance status (PS) 0-2 who had progressed within 6 months of previous platinum/fluoropyrimidine CT. Patients were randomised (1:1) to receive either docetaxel 75mg/m 2 every 3 weeks for up to 6 cycles or active symptom control (ASC). The primary endpoint was OS. The secondary endpoint of HRQL, assessed using EORTC QLQ-C30 and QLQ-ST022, was analysed using standardised area under a curve and compared using Wilcoxon rank sum test. Sensitivity analysis adjusting for dropouts due to death were performed using quality adjusted survival. Results: 168 patients (84 patients in each arm) were recruited between April 2008 and April 2012. Median age was 65 years (range 28-84); 81% were males. PS at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. 86% had metastatic disease. 43% progressed during previous CT, 28% progressed within 3 months of end of previous CT and 29% progressed between 3 and 6 months. Median number of cycles of docetaxel was 3. 23% completed 6 cycles. Docetaxel was well tolerated and resulted in a significantly improved OS over ASC alone (HR=0.67 (95% CI 0.49-0.92); p=0.01). Objective response rate was 7%. For QLQ-C30, patients on docetaxel arm reported significantly less pain (p=0.0008) and trend for less nausea and vomiting (p=0.02) and constipation (p=0.02) than those on ASC arm. Similar global HRQL seen (p=0.53).For QLQ-ST022, trend seen for less dysphagia (p=0.02) and pain symptoms (p=0.01) for patients on docetaxel arm than ASC Conclusions: Docetaxel provided a significant OS benefit over ASC with improvements in symptom scores and no loss in overall HRQL. Docetaxel can be considered a standard of care in this setting. Clinical trial information: NCT00978549.
Phase II trial of neoadjuvant gemcitabine (G) and cisplatin (C) with sunitinib in patients (pts) with muscle-invasive bladder cancer (MIBC).
Authors: Arjun Vasant Balar, Gopa Iyer, Andrea Borghese Apolo, Ashley Marie Regazzi, Ilana Rebecca Garcia-Grossman, Deepa Pendse, Irina Ostrovnaya, Joanne F. Chou, Bernard Bochner, Guido Dalbagni, Harry W. Herr, Matthew I. Milowsky, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2012)

4581^ Background: Response to neoadjuvant chemotherapy (NC) prior to radical cystectomy (RC) predicts improved overall survival (OS) in MIBC. Associations with enhanced survival include complete pathologic response (pT0; Grossman, NEJM 2003) and eradication of the muscle-invasive component (&lt;pT2; Splinter, J Urol 1992). Sunitinib (S) is active in pretreated pts with advanced disease. We tested if S added to GC was safe, improved the rate of pT0, and improved the rate of &lt;pT2. Methods: Cisplatin-eligible pts with cT2-4aN0 bladder cancer received G 1000 mg/m 2 and C 35 mg/m 2 on day (D) 1 and D8 with S 25 mg orally daily D1-14 of a 21D cycle for 4 cycles. RC plus pelvic lymph node dissection was required to assess response of pT0 or &lt;pT2. A Simon’s Minimax 2-stage design was used to test a null (H0) pT0 rate ≤ 20% against alternative (H1) pT0 rate ≥ 40% with Type I and II error rates of 0.05 and 0.10 respectively. Enrollment to the 2 nd stage of 45 patients was planned if ≥ 6 of the initial 24 evaluable pts achieved pT0. Primary endpoint was pT0N0 and secondary endpoints were: response defined as &lt;pT2N0; safety; time to progression (TTP), and OS. Results: 18 pts (15M, 3F), median age 63 (54-76) were enrolled from 6/09 and 10/11 after which financial support was withdrawn. 3 pts were inevaluable for response endpoints due to: 1.) withdrawal of consent, 2.) declining any surgery, 3.) partial cystectomy instead of RC. All 18 were evaluable for safety, TTP and OS. 1 of 15 pts had pT0N0 (6.6%; 95% CI 0.34 – 29.8%) and 5 had &lt;pT2N0 (33%; 95% CI 15-58%). 4 of 5 pts with status &lt;pT2N0 were pTisN0. Median TTP was 10 months (95% CI 3.5-NR). 3 pts were deceased at time of analysis; median OS not reached. Neutropenia due to the 3 drug combination required routine GCSF support on day 8 of each cycle. Grade 3/4 toxicities were anemia (11 pts), neutropenia (6), thromboembolic events (2), febrile neutropenia (2) and infection (2). Conclusions: Despite incomplete accrual, the pT0 rate was low suggesting that S does not add to GC. Residual non-invasive disease (&lt;pT2) was common, including a large proportion of pts with pTisN0. Given these findings, response criteria for future NC studies should consider either &lt;pT2 or &lt; pTis as the primary endpoint.
Tunnel-and-bridge strategy for rectal endoscopic submucosal dissection: tips to allow strong countertraction without clip and line
Authors: Mathieu Pioche, Jérôme Rivory, Vincent Lépilliez, Jean-Christophe Saurin, Thierry Ponchon, Jérémie Jacques
Journal: Endoscopy (2017)

Endoscopic submucosal dissection (ESD) is the reference method for curative resection of rectal tumors, reducing the rate of recurrence and allowing complete specimen assessment [1]. Nevertheless, it is technically challenging and new strategies to reduce the procedure time and difficulty, and to improve learning are needed [2] [3] [4].