tbuckley/cabot-search huggingface dataset:
End-of-life care resource utilization: A single provider perspective
Authors: J. A. Stewart, D. Runde, K. Rovick, J. Cleary, J. Grossman
Journal: Journal of Clinical Oncology (2006)

16022 Background: Most cancer physicians are aware that significant resources are spent in the last year of life but they are provided little feedback on cost or yield of care. Awareness of resource allocation for patients near the end of life may influence physician conversation with patients and families, treatment recommendations, and hospice referral. Methods: UWHealth cancer registry data were used to identify 90 patients who had died in a recent three year period and were cared for at least in part by the medical oncologist being evaluated. Health services utilization within UWHealth (hospital and hospital based clinic sites) was assessed for the last 6 months of life in 66 patients where a clear date of death could be identified. Data included in- and out-patient, pharmacy, laboratory, radiation and imaging services. Hospice charges are not included. Results: In the last 6 months of life, radiology, radiation therapy and pharmacy charges made up 52% of the total. Use of CT, MRI and palliative radiation increased near the end of life. In the last two months of life, 47% of the entire pharmacy charges were spent. In-patient services were greatly increased in the last month of life. Overall charges and more expensive services were highest in the last month of life. Conclusions: Care near the end of life is expensive. This review targeting patients affiliated with one medical oncologist at a large academic health center showed that radiology, radiotherapy, and pharmacy charges involved more than half the total accrued in the last 6 months of life. Feedback such as this if routinely provided to individual oncologists and disease oriented teams may generate strategies for improving end of life care. Even if expensive, some services may be helpful and necessary, others may not. Discussion regarding accountability for resource allocation within the multidisciplinary setting of cancer care may aid in developing improved end of life approaches for patients. No significant financial relationships to disclose.
Somatostatin receptor (SSTR) expression and proliferative index (Ki 67) in 100 patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs): Clinical-pathological correlation.
Authors: Juan Manuel O'Connor, Veronica Pesce, Guillermo Ariel Mendez, Claudia Bestani, Fabiana Marmissolle, Nora Giacomi, Susana Belli, Enzo Domenichini, Matias Chacon, Victor Zamora, Ana Cabanne, Enrique Luis Roca
Journal: Journal of Clinical Oncology (2012)

e14598 Background: Somatostatin receptor expression (SSTR), mainly subtypes 2 and 5, is a feature of well differentiated GEP-NETs. Such expression has a prognostic and predictive value for the use of somatostatin analogs.Ki 67, present during the cycle phases (G1, S, G2 y M) is a nuclear antigen associated with cell proliferation. The correlation between both clinical and pathological factors is under active investigation in patients with GEP-NETs. Methods: An analysis including 100 patients in the database of the Argentum Group was performed. Consecutive patients were included during the 2006-2007 period. In all cases, a centralized revision of the sample was conducted for diagnosis confirmation.The study of SSTR receptors in tissue and Ki67 was conducted using IHQ.The Kaplan-Meier method was used to analyse survival. Log-rank test was used for the comparative analysis of the variables of interest. Results: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. The univariate analysis showed significant differences in the expression of SSTR2 (a) but not in the expression of SSTR 5.The expression of the proliferative index (Ki 67) was associated with significant differences in relation to OS at 5 years, 84% (Ki 67 under or equal to 2%), 66% (Ki 67 between 3 and 15%) and 13% (Ki 67 over 15%). The OS at 5 years in patients with SSTR 2/5 positive and Ki 67 under 2% was 86%, 64% in pts. with SSTR 2/5 positive and Ki 67 over 2% and 20 % in pts. with SSTR 2/5 negative, independent Ki 67 (p .0023). Conclusions: The expression of at least one of the SSTRs 2 (a) or 5 was found in 86% and 62% of cases respectivevly in this population. In the population with GEP-NETs under study, a subgroup of patients with a better prognosis was identified in association with the expression of SSTR 2/5 and Ki67 below 2%. The assessment of SSTR 2(a) and 5 in tissues, together with the study of the proliferative index are a useful tool for prognosis assessment in these patients.
Phase II trial of preoperative irinotecan-cisplatin (IC) followed by concurrent IC and radiotherapy (IC/RT) for locally advanced gastric and esophago-gastric junction adenocarcinoma (LA-G/EGJ-A)
Authors: M. E. Vega-Villegas, M. C. Galán-Guzmán, J. Gallego-Plazas, A. Cervantes, P. Escudero, J. Tabernero, B. Massutí, V. Alonso-Orduña, D. Asensio, F. Rivera
Journal: Journal of Clinical Oncology (2006)

4059 Background: Long-term survival for LA-G/EGJ-A is poor and could be improved by preoperative chemoradiotherapy. We performed a phase II trial to evaluate IC followed by IC/RT in this setting. Methods: Patients with locally advanced (stage II-IV, M0) G/EGJ-A were included. Main objective was pathological complete response (pCR). Secondary objectives were toxicity, response to preoperative treatment and resection rate. Pretreatment staging included an esophagogram, EUS and CT scan. Two courses of IC (Irinotecan 65mg/m 2 and Cisplatin 30mg/m 2 d 1 and 8, each 21 d) were given and pts without progression received IC/RT: daily RT (180cGy fractions, total dose: 5040cGy) with concurrent IC (Irinotecan 65mg/m 2 and Cisplatin 30mg/m 2 d 1, 8, 15 and 22 of RT). Response to preoperative treatment was evaluated with EUS and CT scan 3–4 weeks after the end of radiotherapy. Five to 8 weeks after RT, surgical resection was performed if feasible. Results: Between 2003 and 2005, 40 pts were included: 32 men; median age 65 (45–80); PS (ECOG): 0: 38%, 1: 59%, 2: 3%; Location and resectability: Esophago-gastric Junction: 16 pts (resectable: 11 pts), Stomach: 24 pts (resectable: 13 pts); Stage: II: 13 pts, III: 15 pts, IV: 12 pts. Grade 3–4 toxicity of IC (40 pts evaluable): neutropenia 22 % (febrile 5%), diarrhoea 8%, emesis 5%, asthenia 3%. One pt (3%) died during IC due to progression. All the 33 pts who received IC/RT were evaluable for toxicity (G-3–4): neutropenia 39% (febrile 0%), diarrhoea 0%, emesis 6%, asthenia 26%, thrombocytopenia 6%. Four pts (12%) died during IC/RT (toxicity: 2 pts, progression: 2 pts). Response to preoperative treatment: PR: 6 pts, SD: 21 pts, Prog: 6 pts, No Evaluated: 7 pts. R0 resections were performed in 12 out of 24 (50%) initially resectable pts (pCR: 2 pts) and in 4 out of 16 (25%) initially non-resectable pts (pCR: 0 pts). One pt died during the first 30 days after resection. With a median follow-up of 12 months, 16 pts (40%) are alive with disease, 10 (25%) pts are alive and disease free and 14 pts (35%) have died. Conclusions: Preoperative IC&gt; IC/RT obtained moderate response and resection rates with mild toxicity in LA-G/EGJ-A. Supported by a grant from Prasfarma/Almirall Prodesfarma. [Table: see text]
The long tail of significantly mutated genes in prostate cancer.
Authors: Joshua Armenia, Stephanie Anne Mullane, JianJiong Gao, Debyani Chakravarty, Ritika Kundra, Franklin W. Huang, G. Celine Han, Dan Robinson, Levi A. Garraway, Peter Nelson, Mark A. Rubin, Mary-Ellen Taplin, Wassim Abida, Charles L. Sawyers, Arul M. Chinnaiyan, Philip W. Kantoff, Johann S. De Bono, Nikolaus Schultz, Eliezer Mendel Van Allen
Journal: Journal of Clinical Oncology (2017)

131 Background: The mutational landscapes of primary and metastatic PCa have been robustly analyzed in multiple whole exome sequencing (WES) studies. We hypothesized that an aggregate, uniform analysis of all data generated to date would enable discovery of new significantly mutated genes and pathways not previously associated with PCa, and shed more light onto the genetic differences between primary and metastatic PCa. Methods: We assembled and uniformly analyzed a cohort of 1,021 tumor and matched germline primary and metastatic PCa whole exomes (686 primary, 335 metastatic), and performed mutational significance analysis using statistical and biological approaches to determine which genes and pathways are recurrently altered. Results: We identified 117 significantly mutated genes (Mutsig q&lt;0.1) in PCa, which included many novel genes and pathways. These include epigenetic modifiers [KMT2C (6%), KMT2D (6%), and KDM6A (2.7%)], regulators of the SWI/SNF complex [SMARCA1 (1.1%), ARID1A (1.5%), ARID1B (1.3%), ARID2 (1.3%), and PBRM1 (0.7%)], and the splicing pathway [SF3B1 (1.1%) and U2AF1 (0.5%)]. In addition, we identified mutations in FUBP1 (0.4%), a splicing regulator involved in the regulation of MDM2 splicing. We also found truncating mutations in SPEN, a hormone inducible transcriptional repressor, in 2.8% of samples, similar to the frequency observed in breast tumors. Finally, a comparison of primary and metastatic samples enabled discovery of a genetic profile associated with metastatic disease, including AR amplifications and mutations, and loss of TP53, PTEN, and RB1. At lower frequency, metastatic tumors showed enrichment in mutations in MLLs (KMT2C/D), APC, CDK12, BRCA2, CTNNB1, and amplifications of MYC and CCND1. Conclusions: Through aggregation and uniform genomic analysis, we refined the map of somatic mutations in PCa and identified cancer genes and pathways not previously associated with this disease. Our findings may inform patient stratification and translational investigation.
Results of the GETUG-AFU 19 trial: A randomized phase II study of dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with or without anti-epidermal growth factor receptor (EGF-R) monoclonal antibody panitumumab (PANI) in advanced transitional cell carcinoma (ATCC).
Authors: Stephane Culine, Aude Flechon, Gwenaelle Gravis, Guilhem Roubaud, Yohann Loriot, Florence Joly, Philippe Barthelemy, Elias Assaf, Hakim Mahammedi, Philippe Beuzeboc, Sylvie Van Hulst, Frederic Rolland, Aline Guillot, Marine Gross-Goupil, David Kayat, Sophie Tartas, Mathilde Deblock, Muriel Habibian, Simon Thezenas, Yves Allory
Journal: Journal of Clinical Oncology (2017)

307 Background: Frequent overexpression and correlation with stage and survival has been reported with the EGF-R pathway in ATCC. Methods: 93 patients (pts) with locally advanced or metastatic bladder or upper urinary tract (UUT) transitional cell carcinoma were planned with a 1:2 randomisation ratio. Patients with K-Ras or H-Ras mutations were excluded. dd-MVAC included M 30 mg/m 2 d1, V 3 mg/m 2 d2, D 30 mg/m 2 d2 and cisplatin 70 mg/m 2 d2 (d1 = d14) with G-CSF support. PANI 6 mg/kg was given on d2. The number of pts was determined from the 9-month median progression-free survival (PFS) rate reported with dd-MVAC. Using a one stage Fleming design, the dd-MVAC+PANI combination will be considered to be active if at least 37 patients among 70 do not show tumor progression at 9 months (p0 = 0.50, p1 = 0.70, alpha = 0.08 and beta = 0.03). As basal-like subtype might be related to Anti-EGFR treatment response, the phenotype was determined using a Keratin 5/6 and GATA3 double immunostaining (8 basal like among 58 cases tested). Results: From September 2010 to November 2015, 96 patients (bladder 68, UUT 21, both 8) received dd-MVAC (33) or dd-MVAC+PANI (63). No significant difference was observed among baseline characteristics and prognostic factors. The median number of cycles was 6 (1-6) in both arms. At least one grade &gt; 2 toxicity was observed in 79% and 76% of patients in the dd-MVAC and PANI arms, respectively. More dermatological adverse events were observed in the PANI arm. Objective responses were reported in 23 (70%) pts in the dd-MVAC arm and 30 pts (48%) in the PANI arm. With a median follow-up of 27 months, PFS was 6.8 months and 5.7 months in the dd-MVAC and PANI arms respectively; OS was 20.2 months and 12.5 months in the dd-MVAC and PANI arms, respectively. No association was observed between PFS and basal-like feature for patients treated by MVAC+PANI. Molecular subtyping is in progress to confirm this observation at mRNA level. Conclusions: When combined with dd-MVAC, PANI does not seem to improve efficacy in pts with ATCC. Clinical trial information: NCT02818725.
An assessment of the mating motive explanation of the beauty premium in market-based settings
Authors: Enrichetta Ravina
Journal: Behavioral and Brain Sciences (2017)

Abstract Labor market and real-life studies were not designed to discriminate between evolutionary and taste-based and stereotype explanations for the beauty premium, have too many confounding effects, and lack crucial information. Smaller-stake and experimental studies provide more compelling evidence in favor of mating motives and suggest the direction of future research for the economists' field studies.
Initial salvage therapy in first relapse AML: A phase IIb study of CPX-351 versus investigator’s choice—A subset analysis by prognostic group.
Authors: Stuart Goldberg, Jorge E. Cortes, Eric Jay Feldman, David Rizzieri, Hagop Kantarjian, Sora Limor, Arthur Chin Louie, Jonathan E. Kolitz
Journal: Journal of Clinical Oncology (2012)

6525 Background: CPX-351 encapsulates cytarabine and daunorubicin within liposomes at a 5:1 molar ratio, shown in vitro to maximize synergy. Liposomal encapsulation enables preferential uptake of drug within leukemic blasts followed by intracellular release enhancing efficacy in AML. A randomized Phase 2b study in 1 st relapse AML completed 1-year follow up with improvement in event free (EFS) and overall survival (OS). This report describes patient outcomes with a focus on the unfavorable subset per the European Prognostic Index (EPI) (Breems DA, et al. J Clin Oncol, 2005 Mar 20;23:1969-1978). Methods: Patients (pts) ≤65yo in 1 st relapse AML after an initial CR &gt;1 month, ECOG PS= 0-2, serum creatinine&lt; 2.0 mg/dL, total bilirubin &lt; 2.0 mg/dL, ALT/AST &lt; 3 x ULN, and LVEF &gt;50% were eligible. Pts with APL, daunorubicin exposure &gt;368 mg/m 2 (or other anthracycline equivalent), active CNS leukemia, uncontrolled infections were excluded. Pts were randomized 2:1 to receive up to 2 inductions and 2 consolidation courses of CPX-351 (100 u/m 2 ; D 1, 3, 5) or investigators choice of intensive salvage treatment. Post remission allo-transplantation was permitted. 126 pts were stratified by EPI into favorable, intermediate, and unfavorable groups (with projected 1-year OS of 70%, 49%, and 16%). The primary efficacy endpoint was % survival at 1-year. Results: CPX-351 increased the rate of morphologic leukemia-free state (77% vs. 60%), the rate of CR + CRi (51% vs. 41%), and the median EFS (4.0 vs. 1.4 mo) and OS (8.5 vs. 6.3 mo) in the overall patient population. Significant survival improvement occurred amongst those with unfavorable EPI scores (HR=0.55, p-value=0.02) with improved 1-year survival (29% vs. 10%). CPX-351 treatment resulted in more prolonged cytopenias with increased febrile neutropenia and grade 3-4 infections, but not in the D 60 mortality (overall: 15% vs. 16%; unfavorable: 16% vs. 24%). Conclusions: CPX-351 is highly active in AML and induces remission even in patients with prior cytarabine and anthracycline exposure. Efficacy was evident in every prognostic group, particularly in the unfavorable EPI group where a statistically significant improvement in 1-year survival was observed.
Perceptions of clinical trials in gastrointestinal/hepatobiliary cancer patients: A comprehensive survey in a Korean tertiary hospital.
Authors: Lee Chun Park, Jeeyun Lee, Hee Young Kim, Moon Ki Choi, Jung Yong Hong, Silvia Park, Chi Hoon Maeng, Ingu Do, Se Hoon Park, Joonoh Park, WonKi Kang, Hoyeong Lim, Young Suk Park
Journal: Journal of Clinical Oncology (2012)

e13094 Background: In the past few years, the volume of clinical trials has increased rapidly in East Asia, especially in Asian prevalent cancer types such as gastric cancer, hepatobiliary cancer. The actual degree of understanding or perceptions of clinical trials by cancer patients have been rarely studied in East Asian countries. Methods: Between July 1 st 2011 and November 30 th 2011, we conducted a prospective survey study regarding cancer patient’s awareness and willingness to participate a clinical trial. The questionnaire consisted of 21 questions based on an Index of Clinical Trial Understanding. Patients with gastrointestinal/hepatobiliary cancer who visited the Hemato-Oncology outpatient clinic at Samsung Medical Center and signed informed consent form were enrolled. The survey was conducted by a well-trained research nurse and statistical analysis was analyzed at the biostatistics core at SMC. Results: In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trial was substantially higher in patients with higher level of education (p&lt;.001), married (p=.004), and higher economic status (p=.001). Nevertheless, willingness to participate the clinical trial was not significantly increased by higher level of education (p=.286), married (p=.685) and higher income (p=.310). The most common source for acquisition of clinical trial was attending physicians (52.0%) followed by mass media (36.6%), other patients (6.39%), internet (3.3%) and others (1.5%). The most influential factors for patient’s willingness to participate were physician’s opinion (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations towards new anti-cancer drug (n=142, 21.0%). Patients were likely to refuse to participate a clinical trial due to unverified treatment modality (n=320, 47.4%) and negativity for clinical trials (n=193, 28.6%). Conclusions: We surveyed a large patient cohort to specifically inquire willingness and awareness of clinical trial in Asian-prevalent cancer types. Further correlative analyses with various variable will be presented at the meeting.
Breast cancer screening controversy: Impact on other cancer screening programs.
Authors: Jérôme Viguier, Xavier B. Pivot, Chantal Touboul, François Eisinger, Jean-Yves Blay, Yvan Coscas, Christine Lhomel, Jean-François Morère
Journal: Journal of Clinical Oncology (2014)

e12507 Background: The breast cancer screening (BCS) controversy following the Cochrane meta-analysis has affected women’s perception and understanding of BCS. We speculated that this controversy may influence cancer screening for other locations. This analysis looks at the potential collateral effect of the BCS controversy on the population’s perception of and intention to participate in colorectal and cervical cancer screening programs. Methods: A nationwide, observational study, recorded in the EDIFICE iterative surveys, on a representative sample of 451 women (age 40-75 years) living in France, was conducted in January 2013, using the method of quotas. The survey questionnaire was administered via the computer-assisted telephone interviewing technique 3 months after the start of the controversy. Attitudes toward different cancer location screening were studied. Results: Of the 405 women with no history of cancer, 69 (17%) were aware of the controversy. Among this latter group, 8% declared their intention to undergo mammograms less frequently and 9%, that the controversy would have an impact on their participation in other cancer screening programs. The concept of BCS being “more reassuring than worrying” was significantly less prevalent among women in the “aware of the controversy” group than in the group without awareness (57% vs.77%, P<0.05), and the same tendency was observed for colorectal cancer screening (56% vs. 70%, P<0.05) and cervical cancer screening (59% vs.72%, P<0.05), respectively. Conclusions: Few women were aware of the controversy, and its impact on the intention to undergo screening in the overall population of our sample is very low (1%). However, for women who are mindful of the controversy, we observed a deterioration in the level of confidence in cancer screening, and this effect was not limited to BCS but also extended to colorectal and cervical cancer screening.
Mortality in Patients with the Acquired Immunodeficiency Syndrome Treated with either Foscarnet or Ganciclovir for Cytomegalovirus Retinitis
Journal: New England Journal of Medicine (1992)

We performed a multicenter, randomized, unblinded clinical trial (the Foscarnet—Ganciclovir Cytomegalovirus Retinitis Trial) designed to compare ganciclovir with foscarnet in the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Of 234 patients, 127 were randomly assigned to ganciclovir and 107 to foscarnet; the study drugs were administered according to a common protocol at the 11 participating clinical centers. Antiretroviral therapy (with zidovudine, didanosine, or dideoxycytidine) was given as dictated by best medical judgment. The patients were followed for the progression of retinitis, visual loss, and death.
Can focal therapy impact perioperative, oncological, and functional outcomes in men who underwent focal therapy salvage robotic-assisted radical prostatectomy? A retrospective matched-pair comparative study.
Authors: Igor Nunes-Silva, Eric Barret, Victor Srougi, Mohammed Baghdadi, Silvia Garcia Barreras, Paolo Capogrosso, Gregory Rembeyo, Arie Carneiro, Rafael Sanchez-Salas, François Rozet, Marc Galiano, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

76 Background: Salvage surgery is an option for recurrent prostate cancer(PCa) after focal therapy(FT). This is the first study to assess the impact of FT on surgical outcomes comparing salvage robotic-assisted radical prostatectomy(S-RARP) versus primary-RARP(P-RARP). We aimed to compare the impact of FT on perioperative, oncological and functional outcomes in men underwent S-RARP versus P-RARP. Methods: Prospective data of 2775 men underwent RARP for localized PCa from 2000 to 2016 were reviewed. Twenty-five men underwent S-RARP after FT failure(S-RARP group). Total 2750 underwent RARP as primary treatment. Matched-pair 1:2 selection of 44 out of 2750 patients by age, IPSS and IIEF5 defined P-RARP group. Primary endpoint was between-groups differences on functional outcomes. Secondary endpoint was oncological data. p &lt; 0.05 was significant. Results: Surgical time, transfusion and complication rates were comparable(p &gt; 0.05). Rates of continence probability[49.5%(SE 0.13) versus 62.4%(SE 0.08), p = 0.8 and 73%(SE 0.14) versus 76.5%(SE 0.07), p = 0.8, at 1 and 2 years, respectively] and the chance for achieving continence[HR 1.062, 95%CI 0.54-2.08, p = 0.861] were comparable between-groups. Potency recovery was significant lower on S-RARP[3±2 versus 9.22±6.55, p = 0.008]. S-RARP showed significant lower rates of cumulative BCR-free survival probability[67.6%(SE 0.12) versus 95.1%(SE 0.03), p = 0.001 and 56.3%(SE 0.15) versus 92.4%(SE 0.04), p = 0.001, at 1 and 2 years, respectively]. S-RARP presented significant increased risk of BCR[HR 4.8, 95%CI 1.67-13.76, p = 0.004]. Upstaging was an independent predictor factor for BCR on S-RARP[HR 14.65, 95%CI 1.46-146.37, p = 0.022] (Table 1). Conclusions: Salvage-RARP following FT failure is feasible and safe with acceptable complications rates. Patients assigned to FT should be previously advised about lower erectile recovery rates in case of a salvage surgery. Urologists may be warned about the risk of undertreatment in patients presenting failure along FT follow-up.
A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin
Authors: Keum-Yong Seong, Min-Soo Seo, Dae Youn Hwang, Eoin D. O'Cearbhaill, Seamus Sreenan, Jeffrey M. Karp, Seung Yun Yang
Journal: Journal of Controlled Release (2017)