tbuckley/cabot-search huggingface dataset:
The elephant in the room: Facilitating conversations about advanced cancer between patients and their spouses.
Authors: Laura S. Porter, Laura FIsh, Hope Elizabeth Uronis, Yousuf Zafar, Karen E. Steinhauser
Journal: Journal of Clinical Oncology (2016)

233 Background: Interventions to enhance couples’ communication about cancer-related issues can lead to benefits for patients, spouses, and their relationships. We recently conducted a pilot study testing a couples communication skills training (CCST) intervention targeted to couples in which one partner had advanced GI cancer, a population who may need particular help addressing difficult and emotionally-laden topics related to life-limiting illness. Results of quantitative analyses suggested that the intervention was effective in improving relationship satisfaction for these couples. The objective of the current study was to analyze intervention session conversation content to identify themes that couples addressed spontaneously, with the ultimate goal of determining whether an intervention that more specifically guides couples to discuss issues related to end of life and the life-limiting nature of the patient’s illness would be acceptable. Methods: 12 couples (10 male and 2 female patients and their spouses) completed the 6 session CCST intervention which provided training in communication skills for sharing thoughts and feelings and making decisions, and gave couples the opportunity to use these skills to discuss cancer-related issues of their choosing. We conducted qualitative content analysis of the 72 audio-recorded sessions, and coded common and recurrent topics raised by patients and spouses. In addition to identifying breadth of topics, we used theme frequency as an initial gauge of theme importance and acceptability. Results: The most common themes identified were prognosis, treatment, emotional intimacy, completion, spouse’s life after the death of the patient, roles, communication, sublimating needs, emotional support, and family. These represent themes previously identified as important to patients at end of life, as well as themes unique to dyads in intimate relationships. Conclusions: These findings support the feasibility of conducting an intervention that combines training in communication skills with guidance for using these skills to discuss topics that are potentially most meaningful to couples facing advanced illness.
Role of HFE in Hepatic Iron Overload: Novel Findings Demonstrate Direct Effects of Mutant C282Y on Hepcidin and Calreticulin mRNA Expression.
Authors: Jorge P. Pinto, Pedro Ramos, Sergio de Almeida, Susana Oliveira, Laura Breda, Marek Michalak, Stefano Rivella, Maria de Sousa
Journal: Blood (2006)
A mapping algorithm of health preferences from EORTC QLQ C30 to health utility index mark 3 (HUI3) in advanced colorectal cancer.
Authors: Kelvin K. Chan, Dongsheng Tu, Christopher J. O'Callaghan, Heather-Jane Au, Natasha B. Leighl, Michael Donald Brundage, Derek J. Jonker, Christos Stelios Karapetis, Jolie Ringash, John Raymond Zalcberg, Jeffrey S. Hoch, Niall C. Tebbutt, Jeremy Shapiro, Timothy Jay Price, Nick Pavlakis, Guy A. Van Hazel, Nicole Mittmann
Journal: Journal of Clinical Oncology (2014)

547 Background: The National Cancer Institute of Canada CO17 study, which showed that patients with advanced colorectal cancer had improved overall survival and derived health related quality of life benefits (measured with EORTC QLQ C30) when treated with cetuximab, collected health preferences with HUI3 prospectively. We examined the relationship between baseline health utilities and quality of life, and constructed a mapping algorithm to derive health utilities from EORTC QLQ C30. Methods: Data from 545 patients including baseline characteristics (age, gender, treatment arm, K-ras, ECOG PS, etc.), health preferences (HUI3), EORTC QLQ C30 five function scales, a two-item global health status (GHS) scale, three symptom scales, and six single items were obtained from the CO17 dataset. Correlations among HUI3 and EORTC QLQ C30 scales and baseline characteristics were examined. Multivariable linear regression model was constructed to develop a mapping algorithm to derive HUI3 from EORTC QLQ C30 scales and/or baseline characteristics. Leave-one-out cross validation (LOOCV) mean absolute error (MAE) and root mean square error (RMSE) were calculated to examine predictive ability. Results: The mean HUI3 was 0.717 (SD = 0.235). HUI3 was significantly correlated with baseline ECOG PS, number of disease sites and the presence of liver metastasis, but not with age, gender, treatment arms or K-ras. HUI3 was also significantly correlated with all EORTC QLQ C30 scales except the diarrhea scale. Multivariable regression showed that HUI3 remained significantly associated with four of the five functional scales (physical, role, cognitive and emotional), the pain scale and the GHS scale. A mapping algorithm consisting of these 6 scales resulted in a model with an adjusted R2 of 0.61, and LOOCV mean error of -0.00014, MAE of 0.11, and RMSE of 0.15. Conclusions: Health preferences as measured by HUI3 are significantly associated with HRQL as measured by EORTC QLQ C30 in patients with advanced refractory colorectal cancer. Our mapping will allow for the generation of health preference values in advanced colorectal cancer when only EORTC QLQ C30 results exist in order to conduct cost-effectiveness analysis.
Potential synergistic effects of bisphosphonates with sorafenib on renal cell carcinoma with bone metastases.
Authors: Ye Ding-Wei, Zhang Hai-Lang
Journal: Journal of Clinical Oncology (2015)

496 Background: We evaluated the role of bisphosphonates in conjunction with sorafenib in improving progression-free survival (PFS) and overall survival (OS) in bone metastatic renal cell carcinoma (mRCC) patients. Methods: A total of 81 sorafenib-treated patients were retrospectively divided into 3 groups at our single study center: Group 1 (n=26, sorafenib single agent); Group 2 (n=26, sorafenib plus oral Bonefos); Group 3 (n=29, sorafenib plus intravenous zoledronic acid). Alkaline phosphatase (ALP) before and 12 weeks after treatment were evaluated as prognostic factor for PFS and OS. Results: The majority of the patients were males (67.9%) with mean age of 57.2 ± 11.2 years. Baseline demographic characteristics were similar across the 3 study groups, and the known prognostic factors were balanced across the cohort. There was no significant difference observed in the objective response between the 3 study groups (Group 1 vs. 2 vs. 3; p=0.659); partial remission (8% vs. 8% vs. 10%), stable disease (65% vs. 80% vs. 66%), progressive disease (27% vs. 12% vs. 24%). Median PFS was significantly higher in Group 2 vs 1 vs 2 (18.7 vs. 6.7 vs. 10.5 months; p=0.024). Median OS was 16.8, 22.1, and 20.7 months; p=0.052 in Group 1, 2 and 3, respectively. Multivariate analysis demonstrated that bisphosphonate use (hazard ratio [HR]=0.36, p=0.006), Memorial Sloan Kettering Cancer Center (MSKCC) score (HR=4.10, p&lt;0.001), non-clear cell subtype (HR=1.26, p=0.039), and elevated ALP after 12 weeks’ treatment (HR=3.53, p&lt;0.001) were associated with PFS. MSKCC score (HR=5.24, p&lt;0.001), elevated ALP after 12 weeks’ treatment (HR=4.71, p&lt;0.001), and metastatic organs (HR=1.93, p=0.008) were associated with OS. Bisphosphonates use was not an independent predictor of OS (HR=0.55, p=0.160). Conclusions: Bisphosphonates administered with sorafenib could synergistically improve PFS and OS in RCC with bone metastases, with the benefit of being more efficacious and safer than intravenous zoledronic acid. Elevated ALP following the treatment could be an independent predictor for both PFS and OS in bone mRCC.
The role of FSH in castration-induced adipogenesis and cardiovascular diseases: Highlighting differences between orchiectomy, GNRH agonists, and antagonists.
Authors: Jehonathan H. Pinthus, Sarah Hopmans, Geoff Werstuck, Wilhelmina CM Duivenvoorden
Journal: Journal of Clinical Oncology (2014)

191 Background: Androgen deprivation therapy (ADT) is associated with weight gain and development of the metabolic syndrome (MS). Different modes of ADT can achieve castration but with different affects on serum FSH levels. Inspired by the observation that adiposity accompanies the incremental increase in serum follicle stimulating hormone (FSH) levels in menopause, we hypothesized that gonadotrophin-releasing hormone (GnRH) antagonists which maximally inhibit FSH levels will associate with reduced adiposity and MS development compared to GNRH analogues and orchiectomy. Methods: In-vitro models of adipocyte differentiations were used to investigate FSH effects on lipid accumulation and expression of the rate limiting enzyme in this process-FAS. In-vivo models for adipogenesis and MS (LDL receptor KO mice) were used to investigate and compare the effects of orchiectomy (n=12), sham surgery (control, n=12), sham surgery plus GNRH antagonist (Degarelix, n=12) and sham surgery plus GNRH agonist (Enanton, n=12). Mice were also manipulated by two nutritional conditions (normal/high fat diet). Longitudinal weight gain (four month), visceral fat accumulation (CT measurements), fasting blood glucose, two hours glucose tolerance tests, serum triglycerides, FSH, LH, and testosterone levels were studied along with number and characteristics of aortic atherosclerotic plaques. Results: The lowest and highest serum FSH levels were recorded in mice treated with degarelix versus orchiectomy and significantly lower levels of FSH and LH in mice treated with degarelix versus enanthon were recorded. Mice treated with enantone gained significantly more weight and visceral fat compared to mice treated with degarelix. Significant lower levels of serum triglycerides and better response to glucose loading were recorded in mice treated with degarelix. Data on atherosclerotic plaques is currently processed and will be discussed, but preliminary analysis reveal lower plauque size in mice treated with degarelix. Conclusions: Usage of GNRH antagonists as ADT attenuates weight gain and development of the MS in preclinical models.
Factors that influence genetic testing outcomes in high-risk breast/ovarian families
Authors: C. I. Herold, K. L. Goldfeder, J. Tigges, J. E. Stopfer, B. L. Weber, S. M. Domchek
Journal: Journal of Clinical Oncology (2005)

9616 Background: Individuals with a family history of both breast cancer (BC) and ovarian cancer (OV) are at high risk of carrying deleterious mutations in BRCA1 and BRCA2 (BRCA1/2). As effective interventions exist to prevent OV and BC in women with BRCA1/2 mutations, genetic testing is very useful in identifying individuals appropriate for risk reduction strategies. In families with negative BRCA1/2 testing, counseling can be much more challenging. Here we report our genetic testing experience in families with both BC and OV. Methods: Charts were reviewed from 304 families with at least one case each of BC and OV in a single lineage and tested for BRCA1/2 mutations. Familial characteristics, pathology reports and BRCA1/2 mutation status were reviewed. P-values were obtained by Z-test. Results: Of the 304 families, 171 (56%) had deleterious mutations in BRCA1/2. As expected, mutations were more commonly found in the 256 families in which an affected individual (BC and/or OV) was tested, compared to the 48 families in which an unaffected individual was tested (152/256 (59%) vs. 19/48 (40%) (p=0.015)). Of the 125 families who had at least one individual with both BC and OV, affected individuals were tested in 107 (86%) –73% had BRCA1/2 mutations. Mutations were more common in women with both BC/OV (50/63, 79%); OV (95/123, 77%); BC diagnosed before age 39 (78/101, 77%) than in women with BC over age 50 (26/56, 46%), or age 40–49 (51/92, 55%) (p<0.002). Pathologic confirmation of ovarian cancer was available in 85/304 (28%) families. In 57/85 (67%) with pathological documentation of ovarian cancer, BRCA1/2 mutations were detected, vs. 114/219 (52%) of those with no pathological documentation (p=0.018). Conclusions: Genetic testing was informative for 56% of breast/ovarian families regardless of the characteristics of the individual tested but is particularly useful when an affected individual is tested and OV pathology is confirmed (72%). For families with uninformative genetic testing, possible explanations include inability to test affected individuals, phenocopy effects, incorrect ovarian cancer diagnosis in which pathological documentation is not available, in addition to the inherent limitations of current genetic testing. No significant financial relationships to disclose.
The association of baseline anxiety and depression with overall survival (OS) in colorectal cancer (CRC).
Authors: Pierre Y. Cheung, Tian Yang Darren Liu, Jason D. Kim, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2015)

706 Background: Patient-reported measures such as psychosocial wellbeing and quality of life have been reported to correlate with cancer survival, but the specific factors within these constructs that associate with outcomes remains poorly defined. Our aim was to examine the effect of baseline anxiety and depression on OS in a population-based cohort of CRC patients. Methods: Patients diagnosed with CRC in 2008, referred to any 1 of 5 regional cancer centers in British Columbia, and who completed a baseline questionnaire to evaluate anxiety and depression were reviewed. We developed a scoring system based on these patient-reported survey data to characterize intensity and subsequently categorized patients as having no, mild, moderate or severe anxiety and/or depression. Vital statistics were captured by medical records. Unadjusted Kaplan-Meier methods and multivariate Cox regression models that controlled for additional socio-demographic and clinical characteristics were constructed to correlate anxiety and depression with OS. Results: A total of 449 patients were included: median age was 66 years (range 26-92), 52% were men, and 69% were white. A significant proportion of respondents reported anxiety (58%) or depression (45%) at baseline. Among them, the majority indicated their anxiety and depressive symptoms were severe (43% and 43%, respectively). Women and those who were single or unmarried were more likely to have anxiety and depression (p&lt;0.001 and p=0.02, respectively). In unadjusted analyses, we observed a trend where increased severity of anxiety (p=0.07) and depression (p=0.04) correlated with worse outcomes. In Cox regression that considered other prognostic factors, however, this observation failed to persist, and neither anxiety nor depression associated with OS (Table). Conclusions: The impact of psychosocial wellbeing and quality of life on CRC outcomes that have been previously described in the literature are unlikely to be mediated through baseline anxiety or depression. [Table: see text]
Alteration of recurrence patterns and prognostic factors by adjuvant S-1 monotherapy in patients with stage II/III gastric cancer.
Authors: Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Naoki Iwata, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2016)

90 Background: Survival benefit of adjuvant S-1 monotherapy among East Asian patients with stage II/III gastric cancer (GC) has been demonstrated by the ACTS-GC trial. Little is known about the changes in prognostic factors and recurrence patterns after it has become widespread as a standard of care. Methods: We enrolled 171 patients with stage II/III GC, 92 patients who underwent gastrectomy alone, and 79 patients treated with S-1 adjuvant. To balance more strictly the essential variables including stage of progression, we conducted propensity score analysis and 70 pairs of patients were generated from each group. Prognostic factors were compared between the groups and initial recurrence patterns were investigated to explore reasons for the change. Results: In concordance with the previous phase 3 trial, overall and recurrence-free survival were better for the S-1 adjuvant group. In the surgery alone group, carcinoembryonic antigen &gt; 5 ng/mL, total gastrectomy, vessel invasion, pT4, and stage 3 were identified as significant prognostic factors. In striking contrast, macroscopic tumor size &gt; 50 mm was the only significant prognostic factor for the S-1 adjuvant group. The lower overall recurrence rate of the S-1 adjuvant group was attributable mainly to a significant decrease of peritoneal recurrence. Conclusions: Prognostic factors changed substantially after implementation of S-1 adjuvant treatment. Macroscopic tumor size should be considered for patient stratification and selection of treatment options for patients with stage II/III GC.
Characteristics of patients referred to embedded rapid access supportive care clinic.
Authors: Sriram Yennu, Zhanni Lu, Janet L. Williams, Joseph Anthony Arthur, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

141 Background: ASCO recommends Palliative care and Oncology integration to improve quality care outcomes. There is limited data on the patient (pt) characteristics (PC) for those who access integrated care. Our center created a pilot rapid access supportive care clinic (RASCC) to facilitate same-day consultation. The aim of this study was to determine the PC of pts referred (R) and not referred (NR) to RASCC. We also examined the PC of those who referred early[ER] (within 12 weeks of diagnosis or registration) vs those who have referred late [LR]. Methods: We reviewed pt medical records of all pts R and NR during the pilot period (Aug 01, 2012 to June 30, 2013). To be eligible all pts had advanced Stage IV non-small cell lung cancer with oncologist estimated overall survival (OS) of ≤ 6 months. Results: Of a total of 419 eligible pts seen at the thoracic oncology clinic, 157 (37%) pts were referred to RASCC. R group had a higher symptom distress scores, SDS (Table 1), weight loss, worse PS and OS compared to NR. There was no difference in PC between ER and LR except in the ESAS symptoms and SDS scores were higher in ER than LR, 40(29.5,52) vs 31.5(22.25,40.125), P &lt; .001. Conclusions: R pts had higher symptom burden and worse OS. Similarly ER had a higher SDS than LR suggesting referrals to RASCC were primarily based on symptom burden. [Table: see text]
Ibrutinib-Based Therapy in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia
Authors: Alexey Kuvshinov, Sergei Voloshin, Irina Martynkevich, Ludmila Martynenko, Andrei Garifullin, Elizaveta Kleina, Vasily Shuvaev
Journal: Blood (2016)
Combination therapy of bevacizumab with rapamycin in antitumor activity.
Authors: Lisa A. McPhatter, Zahid N. Rabbani, Pierre Sonveaux, Matthew E. Hardee, Zeljko Vujaskovic, Herbert I. Hurwitz, Mark W. Dewhirst
Journal: Cancer Research (2006)

5707  The extension of the tumor vascular network during angiogenesis is essential for tumor growth, and the persistent immaturity of the resulting neovessels facilitates metastasis. For these reasons and based on its peculiarities, disrupting tumor angiogenesis is a promising antitumor strategy. An efficient approach is to inhibit the proangiogenic activity of the vascular endothelial growth factor (VEGF), which can be done by means of Bevacizumab/rhuMab, a humanized anti-VEGF monoclonal antibody. However, upon VEGF inactivation, the VEGF-activated PI3K/Akt/mTOR promitotegenic pathway is rescued by other tumor microenvironmental factors. Based on this observation, we reasoned that combining Bevacizumab to Rapamycin, an immunosuppressive drug binding to mTOR, would have superior antitumor activity compared with either agent alone. Utilizing an in vivo xenograft model of colon adenocarcinoma (HT29) in nude mice, 200-300 mm3 HT29 flank tumors were randomized to the following treatments: [1]Rapamycin alone (1.5 mg/Kg/day), [2] Bevacizumab alone (3x(100 μg/Kg)/week), [3] Bevacizumab + Rapamycin combined [4] Saline was used as control. The animals were followed until they reached 4x the initial treatment volume. Using immunohistochemistry, we observed lower VEGF expression in mouse tumors treated with the combination and bevacizumab alone treatments versus control and rapamycin alone. This decrease in VEGF abundance was confirmed via ELISA at the molecular level. The combination and bevacizumab alone therapies significantly decreased angiogenesis (CD31 staining) and tumor cell proliferation (Ki67 staining), and increased tumor cell apotosis (in situ caspase 3 activation assay). Furthermore, a decrease in tumor hypoxia (measured via CAIX staining) was observed. These important changes in the tumor microenvironment prompted us to test the combination strategy in tumor growth delay experiments. Our results showed a more than additive effects (longer tumor doubling time and increased mean tumor regrowth delays) for animals treated with Bevacizumab + Rapamycin (8.6±0.6 and 3.4±0.6 days) versus Bevacizumab (6.6±0.8 and 1.4±0.8 days) or Rapamycin alone (5.4± 0.5 and 0.2± 0.5 days). Collectively, our findings demonstrate potential for a significant therapeutic gain when combining Bevacizumab with Rapamycin for cancer treatment, particularly if combined with other cytotoxic therapies. The increase in oxygenation may lead to tumor radio- and/or chemosensitization. Future studies will investigate this possibility.
Unplanned visits to hospital emergency for oropharynx patients undergoing radiation therapy in Ontario.
Authors: Eric Gutierrez, Nicoda Foster, Elizabeth Lockhart, Rebecca Comrie, Jennifer Stiff, Rebecca Anas, Padraig Richard Warde
Journal: Journal of Clinical Oncology (2014)

267 Background: Radiation therapy (RT) with or without concurrent chemotherapy is the standard of care for patients with oropharyngeal cancer. The acute toxicity of treatment is well recognized and highlights the need for a multidisciplinary approach to management. In 2009, a Head and Neck Organizational Guideline was published by Cancer Care Ontario (CCO) which emphasizes the need for a multidisciplinary team approach of surgical, medical and radiation oncologists; supportive care professionals, including speech language pathologists, dieticians, social workers; and others to support the care of this population. In order to assess the availability of appropriate supportive care for this patient group, the percentage of patients who visited an Emergency Department (ED) during their course of RT and the causes for these visits were assessed. Methods: Patients with a diagnosis of oropharyngeal cancer receiving radical RT in Ontario (10 Cancer Centres) between the period of April 1, 2011 and March 31, 2013 were identified from CCO’s Activity Level Reporting ( ALR ) database. These patients were then linked to the National Ambulatory Care Reporting System ( NACRS ) administrative dataset from the Canadian Institute for Health Information ( CIHI ) which allowed identification of patients that visited ED during their course of RT as well the reasons for the visits. Data on the use of concurrent chemotherapy was not available. Results: Over the two year period, 885 patients in Ontario had radical RT (+ concurrent chemotherapy) for oropharyngeal cancer of which 261 (29.5%) visited an ED at least once during their treatment (range of 22% to 36% across the 10 centres). The main reasons for the ED visits were dehydration and neutropenia, although coding for reason of visit was incomplete in 16% of cases. Conclusions: The high proportion of patients attending an ED while receiving daily RT would suggest that the supportive care needs of this population are not being regularly met. Further work is necessary to understand the reasons for ED visits in this group of patients and the substantial variation seen between centres would suggest this metric may be useful as a new quality of care indicator.