tbuckley/cabot-search huggingface dataset:
Spirituality and quality of life among caregivers of advanced cancer patients.
Authors: Tai Chung Lam, Tracy A. Balboni, Michael J. Balboni, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2014)

9559 Background: Religion and/or spirituality (R/S) is important to most advanced cancer patients, and often upholds patient quality of life (QoL) within illness. However, the role of R/S within the caregiving experience has not been adequately studied. Methods: Data from 570 caregiver-patient dyads participating in the Coping with Cancer study were included. Caregivers completed R/S measures on R/S importance, positive and negative religious coping, and degree of spiritual support from medical teams and religious communities. The correlations of caregiver R/S variables to patient R/S were assessed. Multivariable models (MVA) were employed to assess relationships of caregiver R/S measures with their QoL (SF-36 questionnaire) and perceptions of care-giving experience, controlling for confounding factors (e.g., sociodemographic factors, self efficacy). Results: Caregivers (median age 53 years, 51% spouses) largely reported religion to be important (85%). Most (85%) endorsed at least some positive religious coping, and 31% endorsed at least some negative religious coping. Thirty-nine percent and 17% of caregivers reported being highly supported by R/S communities and medical system, respectively. Caregivers' R/S variables were correlated with patient R/S, including religiosity (r=.24, p<.001), positive religious coping (r=.41, p<.001) and negative religious coping (r=.21, p<.001). In MVA assessing relationship of R/S variables to caregiver QOL, negative religious coping was significantly related to lower caregiver QoL (SF-36 mental component summary, β=-2.2, p<.001). In MVAs of the relationship of R/S to perceptions of care-giving experience, greater positive religious coping (OR 1.95, p=.04) and greater medical team spiritual support (OR 2.02, p=.01), were related to more positive perceptions of the caregiving experience. Conclusions: R/S is important to most caregivers and is correlated with patient R/S. Caregiver negative religious coping is associated with poorer QoL. Caregiver positive religious coping and spiritual support from medical teams are related to caregivers' positive perceptions of caregiving experience. Results suggest approaches to improve caregiver QoL should involve intervention on R/S.
Feasibility study of neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group study JCOG0206
Authors: T. Onda, T. Kamura, T. Hirakawa, K. Kuzuya, M. Hatae, T. Iwasaka, I. Konishi, N. Katsumata, H. Fukuda, H. Yoshikawa
Journal: Journal of Clinical Oncology (2006)

15020 Background: Retrospective analyses revealed that survival of ovarian cancer patients treated with NAC followed by IDS was comparable with those treated by standard treatment starting with primary debulking surgery. The purpose is to assess the safety and efficacy of the NAC setting treatment and also to know whether we can accurately diagnose the cancer by imaging studies, cytologic findings and tumor markers without diagnostic laparoscopy (DLS). Methods: The study was performed as a multi-institutional non-randomized phase II trial. Eligibility included stage III/IV müllerian carcinoma (MC) such as ovarian, tubal and peritoneal carcinomas diagnosed by imaging studies (CT and/or MRI), cytology of ascites, pleural effusions or fluids obtained by tumor centesis, CA125 &gt;200 U/ml and CEA&lt;20 ng/ml. After study enrollment, DLS is performed to confirm tumor origin, histology and stage. Four cycles of combination of paclitaxel (175 mg/m 2 , 3h) and carboplatin (AUC 6) are administered as NAC, followed by IDS and additional 4 cycles of chemotherapy. Primary endpoint is proportion of clinical complete remission (% cCR) with CA 125&lt;20 U/ml among all stage III/IV MC confirmed by DLS (expected % cCR of 40% and threshold % cCR of 20%). Major secondary endpoint is positive predictive value (PPV) of clinical diagnoses concerning origin, histology and stage (expected PPV&gt;90%, then DLS will be omitted in the next phase III study). The planned sample size was 56 eligibles, which gives 10% or lower Bayesian posterior probability that PPV is &lt; 90% in case of three false positives. Results: Fifty six patients were enrolled between Jan/2003 and Feb/2004. All patients had accurate pre-DLS diagnosis concerning origin and histology. In 53 (PPV 94.6%) of 56 patients, tumor stage was accurately diagnosed. Twenty nine (62%) of 47 patients who underwent IDS had complete resection without residual tumors. Nineteen (%cCR 36%) among 53 patients with stage III/IV MC achieved cCR at completion of planned treatment. Conclusions: NAC starting without DLS followed by IDS for advanced MC is a promising treatment to be compared with the current standard treatment in a phase III study. [Table: see text]
Use of a nomogram to quantify overall survival (OS) benefit in patients with metastatic renal cell carcinoma (mRCC) receiving bevacizumab (BEV) with interferon (IFN) versus IFN alone.
Authors: P. Karakiewicz, M. Sun, V. Sneller, B. Escudier
Journal: Journal of Clinical Oncology (2010)

4592 Background: BEV + IFN is an established first-line therapy for mRCC. Using data from a randomized, double-blind, phase III trial (AVOREN) of first-line BEV + IFN vs IFN + placebo, we developed a nomogram for prediction of OS and compared it to the Motzer score. Methods: All pretreatment parameters were considered in a Cox regression nomogram predicting OS at 6, 12, 18 and 24 months. To control for type I error and for overfit bias, the nomogram was internally validated (200 bootstrap resamples). The concordance index and measures of calibration were used. Nomogram accuracy was compared to the 1999, 2002 and 2004 Motzer score predictions (DeLong method for related AUCs). Results: 541 patients were included. The most accurate nomogram relying on 14 variables was 85.5, 83.5, 81.4, and 79.6% accurate at 6, 12, 18 and 24 months vs 83.0, 79.0, 77.3 and 75.6% for a simpler, 5 variable nomogram. The 1999 Motzer score was 71.7, 69.9, 65.1 and 63.7% accurate vs 70.7, 68.3, 66.4 and 63.5% for the 2002 score vs 72.3, 71.0, 66.0 and 64.3% for the 2004 score at 6, 12, 18 and 24 months. All accuracy comparisons between the three Motzer score and both nomogram predictions were significant at p≤0.002. Using the 5 variable nomogram, for an individual with KPS of 80%, albumin of 35g/L, creatinine of 155μ mol/L, 5 metastatic sites and LDH >1.5x upper limit of normal, the 6 months nomogram-predicted OS was 81% with BEV + IFN and 68% with IFN alone (13% benefit), 61 and 40% at 12 months, 40 and 25% at 18 months, and 25 and 15% at 24 months. Conclusions: Compared to Motzer score, the nomogram quantifies OS more accurately (8–16% better). Moreover, it illustrates individual OS gains when BEV + IFN is used instead of IFN alone and can help clinicians identifying patients who benefit the most from BEV + IFN versus IFN alone. This tool awaits external validation in an independent sample. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche GlaxoSmithKline, Novartis, Pfizer, Roche Roche
Investigation of constitutive and cytokine-induced expression of pSTAT 1, 3, and 5 in PBL of breast cancer patients
Authors: G. Konjevic, S. Stankovic, T. Srdic, S. Jelic, M. Inic
Journal: Journal of Clinical Oncology (2009)

3042 Background: Although cytokines mediate their effects by latent transcription factors, STATs, their dysregulation has not been much investigated in peripheral blood lymphocytes (PBL) of breast cancer patients. As alterations in the JAK-STAT pathway contribute to immunosuppression in cancer patients in this study, aside from baseline-level, we investigated the level and cytokine-mediated activation of STAT1, 3, and 5 in healthy controls and breast cancer patients. Methods: PBL (5x10 6 /ml) of breast cancer patients in all four clinical stages, as well as healthy controls, were treated in vitro with culture medium (CM) alone, IFNα (250 IU/ml CM) and IL-2 (500 IU/ml) for 24h at 37°C. Induction of phosphorylated STAT proteins was assessed in cellular lysates by Western blotting using monoclonal anti-STAT1, 3, and 5 antibodies. Treated PBL were also analyzed for IFNγ using an intracellular flow cytometry assay. Results: Our results indicate that untreated PBL of breast cancer patients, compared to healthy controls, express a significantly lower baseline level of pSTAT1, 3, and 5. The induction of pSTAT1 expression by IFNα, similar to the induction of pSTAT3 and pSTAT5 by IL-2, is significant for healthy controls and breast cancer patients, although the effect in patients is significantly below that for healthy controls. Moreover, the induction of pSTAT5 by IL-2 is of a higher magnitude than pSTAT3. PBL of breast cancer patients, compared to healthy controls, have a lower level of IFNγ. The production of IFNγ in PBL is enhanced by IFNα, as well as IL-2, although in breast cancer patients to a much lower level than in healthy controls. Conclusions: These results provide evidence that evaluation of STAT expression in PBL of breast cancer patients could be of diagnostic and therapeutic significance for cytokine-based therapy. No significant financial relationships to disclose.
Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline <i>Bap1</i> Mutations
Authors: Yuwaraj Kadariya, Mitchell Cheung, Jinfei Xu, Jianming Pei, Eleonora Sementino, Craig W. Menges, Kathy Q. Cai, Frank J. Rauscher, Andres J. Klein-Szanto, Joseph R. Testa
Journal: Cancer Research (2016)

Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of benign and malignant tumor types, including malignant mesothelioma, melanoma, and kidney carcinoma. However, evidence to support a tumor-suppressive role for BAP1 in cancer remains contradictory. To test experimentally whether BAP1 behaves as a tumor suppressor, we monitored spontaneous tumor development in three different mouse models with germline heterozygous mutations in Bap1, including two models in which the knock-in mutations are identical to those reported in human BAP1 cancer syndrome families. We observed spontaneous malignant tumors in 54 of 93 Bap1-mutant mice (58%) versus 4 of 43 (9%) wild-type littermates. All three Bap1-mutant models exhibited a high incidence and similar spectrum of neoplasms, including ovarian sex cord stromal tumors, lung and mammary carcinomas, and spindle cell tumors. Notably, we also observed malignant mesotheliomas in two Bap1-mutant mice, but not in any wild-type animals. We further confirmed that the remaining wild-type Bap1 allele was lost in both spontaneous ovarian tumors and mesotheliomas, resulting in the loss of Bap1 expression. Additional studies revealed that asbestos exposure induced a highly significant increase in the incidence of aggressive mesotheliomas in the two mouse models carrying clinically relevant Bap1 mutations compared with asbestos-exposed wild-type littermates. Collectively, these findings provide genetic evidence that Bap1 is a bona fide tumor suppressor gene and offer key insights into the contribution of carcinogen exposure to enhanced cancer susceptibility. Cancer Res; 76(9); 2836-44. ©2016 AACR.
New Strategies for Effective Therapeutics in Critically Ill Patients
Authors: Michael A. Matthay, Kathleen D. Liu
Journal: JAMA (2016)

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The Authors' reply
Authors: W. Laleman, F. Nevens
Journal: Gut (2011)

We read with interest the comments raised by Gleeson et al .1 We thank the authors for their valuable remarks.

The aim of our prospective study was not to investigate the natural history of alcoholic steatohepatitis (ASH). Therefore, patients were not selected based on the presence or absence of ASH. The primary aim of the study was to elucidate whether acute-on-chronic liver failure (ACLF), as defined in the literature,2–4 really exists as a clinical identity and more specifically as a complication of cirrhosis. We could demonstrate that among those with symptomatic cirrhosis (70/250 patients with alcoholic cirrhosis), there is a subgroup of patients which …
Association Between Hospital Process Composite Performance and Patient Outcomes After In-Hospital Cardiac Arrest Care
Authors: Monique L. Anderson, Graham Nichol, David Dai, Paul S. Chan, Laine Thomas, Sana M. Al-Khatib, Robert A. Berg, Steven M. Bradley, Eric D. Peterson
Journal: JAMA Cardiology (2016)

Survival rates after in-hospital cardiac arrest (IHCA) vary significantly among US centers; whether this variation is owing to differences in IHCA care quality is unknown.To evaluate hospital-level variation to determine whether hospital process composite performance measures of IHCA care quality are associated with patient outcomes.Using data from the American Heart Association's Get With the Guidelines-Resuscitation (GWTG-R) program, we analyzed 35 283 patients 18 years or older with IHCA treated at 261 US hospitals from January 1, 2010, through December 31, 2012. We calculated the hospital process composite performance score for IHCA using 5 guideline-recommended process measures. Opportunity-based scores were calculated for all patients, aggregated at the hospital level, divided into quartiles, and then associated with risk-standardized survival and neurologic status by a test for trend. The scores were then evaluated through hierarchical logistic regression and reported as odds ratios per 10% increment in hospital process composite performance.Acute care treatments for IHCA.The primary outcome was survival to discharge measured as risk standard survival rates, and the secondary outcome was favorable neurologic status at hospital discharge.Of the 35 283 adults included in this study, the median age was 67 years (interquartile range [IQR] 56-78 years), and 57.9% were male. The median IHCA hospital process composite performance was 89.7% (interquartile range, 85.4%-93.1%) and varied among hospital quartiles from 82.6% (lowest) to 94.8% (highest). The IHCA hospital process composite performance was linearly associated with risk-standardized hospital survival to discharge rates: 21.1%, 21.4%, 22.8%, and 23.4% from lowest to highest performance quartiles, respectively (P < .001). After adjustment, each 10% increase in a hospital's process composite performance was associated with a 22% higher odds of survival (adjusted odds ratio, 1.22; 95% CI, 1.08-1.37; P = .01). Hospital process composite quality performance was also associated with favorable neurologic status at discharge (P = .004).The quality of guideline-based care for IHCA varies significantly among US hospitals and is associated with patient survival and neurologic outcomes.
Adjuvant chemotherapy with temozolomide and radiation therapy in patients with high grade gliomas
Authors: R. Pedersini, E. Vattemi, M. Lusso, S. Baier, M. Campello, M. Broger, A. Schwarz, M. Maffei, P. Lukas, C. Graiff
Journal: Journal of Clinical Oncology (2007)

12534 Background: Temozolomide, a novel alkylating agent, has shown activity in the treatment of patients with high-grade gliomas. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant chemo- radiotherapy according to Stupp regimen. Methods: We reviewed our experience with a combination of radiotherapy (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). Results: 43 patients , median ECOG PS= 0, were treated with concomitant RT and Temozolomide at our institution since March 2004. Median age was 63 (range 33–73), with 62% over 60 years. All patients had histologically confirmed high grade gliomas: glioblastoma multiforme (32), grade III oligodendroglioma (3), grade III oligoastrocytoma (2), grade III astrocytoma (6). 2/43 patients underwent only a biopsy, the remaining underwent debulking surgery. At a median follow-up of 17 months, the median progression-free survival (PFS) was 6 mo and median overall survival (OS) was 12 mo. Median PFS and median OS were similar in elderly ( = 60 years). Treatment was well tolerated. Only one patient had grade IV haematological toxicity. One patient discontinued treatment due to hepatotoxicity. Conclusions: Our findings confirm the results of the EORTC trial(Stupp R et al., 2005) No significant financial relationships to disclose.
In vitro study of the antioxydant properties of the nimesulide and 4OH nimesulide : effect on HRP- and luminol-dependent chemiluminescence produced by human chondrocytes
Authors: Yves Henrotin, SX Zheng, Ange Mouithys-Mickalad, G Deby-Dupont, C Deby, Maurice Lamy, Jean-Michel Crielaard, Jean-Yves Reginster
Journal: Annals of the Rheumatic Diseases (2000)
Rates of appropriate genetic testing referral for breast cancer patients treated in a multidisciplinary cancer care setting.
Authors: Caitlin Laurel Gomez, Nicole Ann Dawson, Robyn Lynn Dvorak, Nova Foster, Anne Hoyt, Sara A. Hurvitz, Amy Kusske, Charles Y. Tseng, Susan Ann McCloskey
Journal: Journal of Clinical Oncology (2014)

45 Background: Approximately 5% to 10% of women diagnosed with breast cancer have a genetic predisposition, which can affect management recommendations. The National Comprehensive Cancer Network (NCCN) has established guidelines for genetics referral and testing, however recent publications have indicated low rates of family history documentation and appropriate genetics referral. We sought to assess the impact of standardized family history documentation on rates of appropriate genetics referral in a multidisciplinary breast clinic (MDC) setting. Methods: In advance of MDC consultation, women with newly diagnosed breast cancer complete an intake questionnaire which includes documentation of Ashkenazi Jewish ancestry along with a thorough family history. We retrospectively analyzed family history documentation to inform eligibility for genetic testing and rates of appropriate genetics referral. Results: Between June 2012 and April 2014, 202 women with newly diagnosed, nonmetastatic breast cancer were seen in MDC. We noted 100% compliance with family history documentation. Per NCCN Guidelines, genetic testing was indicated in 52% (106 patients), of which 77% were appropriately referred to a genetic counselor for evaluation. All patients who met criteria based on personal history factors including age ≤ 45, triple-negative disease under age 60, or two or more breast primaries under age 50 were appropriately referred. Patients who were eligible but not referred ranged in age from 46 to 93 and were eligible for testing based on Ashkenzi Jewish ancestry (3 patients) or family history factors including a relative with ovarian cancer (3 patients), ≥2 relatives with breast cancer (5 patients), or a relative with breast cancer &lt; age 50 (7 patients). Conclusions: Compared with recently published national averages, rates of appropriate family history documentation and genetic testing referrals are significantly higher in our MDC setting. However, this analysis has identified significant opportunity for improvement via identification of overlooked referral indications. Initiatives are underway to improve future compliance.
Abstract 14318: Collagen Cross-Linking but not Collagen Amount Associates with Elevated Filling Pressures in Heart Failure Patients of Hypertensive Origin. Potential Role of Lysyl Oxidase
Authors: Begoña LÓpez, Arantxa González, RamÓn Querejeta, Mariano Larman, Javier DÍez
Journal: Circulation (2012)

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures (FPs) in 38 hypertensive patients with stage C chronic heart failure (HF). FPs were ...
Phase II trial of high-dose weekly topotecan in patients with relapsed small-cell lung cancer (SCLC)
Authors: D. Shipley, D. R. Spigel, J. D. Hainsworth, R. C. Whorf, T. M. Markus, M. Kuzur, J. R. Infante, D. A. Yardley, H. A. Burris, F. A. Greco
Journal: Journal of Clinical Oncology (2008)

19073 Background: Topotecan is FDA approved for the treatment of sensitive relapse SCLC using a 5-day IV schedule. A 4 mg/m2 weekly IV schedule studied by our group was associated with low grade (G) 3/4 toxicity (17% neutropenia, 21% thrombocytopenia, and 16% fatigue), however the objective response rate (ORR) was < 10% (JCO 24: 7083, 2006). We hypothesized that a higher topotecan dose could improve the ORR without significantly increasing toxicity. Methods: This multicenter community-based phase II trial had a 2-stage design with a primary aim to achieve an ORR of 25% (α .04, β .20). Patients (pts) with sensitive or refractory relapsed SCLC, ECOG PS 0–1, measurable disease, and signed informed consent were eligible. All pts received topotecan 6mg/m2 IV weekly for 6 weeks (8 week cycle). Pts were restaged every 8 weeks (per RECIST criteria). Results: 38 pts were enrolled from 5/06 to 10/07. Baseline characteristics: median age 64 years (range 35-82 years); male, 53%; ECOG PS 0/1, 26%/74%, and sensitive relapse, 50%. The median follow-up is 5 months (range 2 - 16 months). No pts were able to receive all planned treatment - 84% due to hematologic toxicity. The average weekly dose delivered over 6 weeks, after adjusting for dose reductions and breaks, was 3.8mg/m2. 1 complete response and 2 partial responses were seen (ORR 8%, 95% CI 2% - 23%). 9 pts (24%) had stable disease and 24 pts (65%) had progressive disease. 2 pts were not evaluable due to hematologic toxicity (1) and unconfirmed data (1). The median time to progression and overall survival were 1.8 months and 3.7 months, respectively. G 3/4 non-hematologic toxicity occurring in > 1 pt was limited to fatigue, 3 pts (8%). G3/4 hematologic toxicity included anemia (14%), neutropenia (50%), and thrombocytopenia (33%). Febrile neutropenia was limited to 2 pts (6%). There were no treatment-related deaths. Conclusions: Weekly administration of topotecan at 6 mg/m2 is not feasible because of hematologic toxicity; and does not improve efficacy in pts with relapsed SCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech GlaxoSmithKline Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, sanofi-aventis