pinecone/core-2020-05-10-deduplication huggingface dataset:
Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

BACKGROUND: Evidence from experimental animal and cell line studies supports a beneficial role for vitamin D in prostate cancer (PCa). Although the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. This study assessed the associations of circulating 25-hydroxyvitamin D (25(OH)D) and common variations in key vitamin D-related genes with fatal PCa. METHODS: In a large cohort consortium, 518 fatal cases and 2986 controls with 25(OH)D data were identified. Genotyping information for 91 single-nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (vitamin D receptor, group-specific component, cytochrome P450 27A1 [CYP27A1], CYP27B1, CYP24A1, CYP2R1, and retinoid X receptor α) was available for 496 fatal cases and 3577 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of 25(OH)D and SNPs with fatal PCa. The study also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. RESULTS: No statistically significant relationship was observed between 25(OH)D and fatal PCa (OR for extreme quartiles, 0.86; 95% CI, 0.65-1.14; P for trend = .22) or the main effects of the SNPs and fatal PCa. There was evidence suggesting that associations of several SNPs, including 5 related to circulating 25(OH)D, with fatal PCa were modified by 25(OH)D. Individually, these associations did not remain significant after multiple testing; however, the P value for the set-based test for CYP2R1 was .002. CONCLUSIONS: Statistically significant associations were not observed for either 25(OH)D or vitamin D-related SNPs with fatal PCa. The effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration
Health-related quality-of-life results from PALETTE: A randomized, double-blind, phase 3 trial of pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or after prior chemotherapy-a European Organization for research and treatment of cancer soft tissue and bone sarcoma group global network study (EORTC 62072)

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                  152958.pdf (publisher's version ) (Open Access)BACKGROUND: Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global, double-blind, randomized, phase 3 trial of pazopanib 800 mg versus placebo as second-line or later treatment for patients with advanced soft tissue sarcoma (N = 369). In that trial, progression-free survival was significantly improved in the pazopanib arm (median, 4.6 vs 1.6 months; hazard ratio, 0.31; P < .001), and toxicity of pazopanib consisted mainly of fatigue, diarrhea, nausea, weight loss, and hypertension. METHODS: HRQoL was assessed using the 30-item core European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol. The primary HRQoL endpoint was the EORTC QLQ-C30 global health status scale. RESULTS: Compliance with HRQoL assessments was good, ranging from 94% at baseline to 81% at week 12. Differences in scores on the EORTC QLQ-C30 global health status subscale between the 2 treatment arms were not statistically significant and did not exceed the predetermined, minimal clinically important difference of 10 points (P = .291; maximum difference, 3.8 points). Among the other subscales, the pazopanib arm reported significantly worse symptom scores for diarrhea (P < .001) loss of appetite (P < .001), nausea/vomiting (P < .001), and fatigue (P = .012). In general, HRQoL scores tended to decline over time in both arms. CONCLUSIONS: HRQoL did not improve with the receipt of pazopanib. However, the observed improvement in progression-free survival without impairment of HRQoL was considered a meaningful result. The toxicity profile of pazopanib was reflected in the patients' self-reported symptoms but did not translate into significantly worse overall global health status during treatment. Cancer 2015;121:2933-2941. (c) 2015 American Cancer Society
Psychometric properties of an Australian supportive care needs assessment tool for Indigenous patients with cancer

BACKGROUND\ud
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There are significant disparities in cancer outcomes between Indigenous and non-Indigenous Australians. Identifying the unmet supportive care needs of Indigenous Australians with cancer is imperative to improve their cancer care.  The purpose of this study was to test the psychometric properties of a supportive care needs assessment tool for Indigenous Australian (SCNAT-IP) cancer patients.\ud
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METHODS\ud
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The SCNAT-IP was administered to 248 Indigenous Australians diagnosed with a range of cancer types and stages, and received treatment in one of four Queensland hospitals. All 39 items were assessed for ceiling and floor effects and analysed using exploratory factor analysis (EFA) to determine construct validity. Identified factors were assessed for internal consistency and convergent validity to validated psychosocial tools. \ud
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RESULTS\ud
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EFA revealed a four-factor structure (physical and psychological, hospital care, information and communication, and practical and cultural needs) explaining 51% of the variance. Internal consistency of four subscales was good, with Cronbach Alpha reliability coefficients ranging from 0.70-0.89. Convergent validity was supported by significant correlations between the SCNAT-IP with the Distress Thermometer (r=0.60, p<0.001), and The Cancer Worry Chart (r=0.58, p<0.001) and a moderately strong negative correlation with Assessment of Quality of Life questionnaire (r=-0.56, p<0.001). \ud
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CONCLUSION\ud
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These data provide initial support for the SCNAT-IP a measure of multiple supportive care needs domains specific to Indigenous Australian cancer patients undergoing treatment
Investigating the relationship between vitamin D and cancer requires dosing the bio-available non-hydroxylated vitamin D storage in cancer tissues

International audienceIn a recent article published in CancerShui et al. observed no statistically significant relationship between circulating 25-hydroxyvitamin D (25(OH)D) and fatal prostate cancer (PCa) 1. However, an association between CYP2R1 SNPs and fatal PCa is found 1. CYP2R1 is the hydroxylase involved in the conversion of vitamin D into 25(OH)D. In the classical vitamin D endocrine system,activation of vitamin D into 1,25(OH)2D requires two successive hydroxylation steps. The first one is catalyzed by CYP2R1 in the liver and the second one by CYP27B1 in the kidneys. Then, 1,25D is released in the blood circulation and behaves as an endocrine hormone. The conversion of 25(OH)Dinto the active hormone 1,25(OH)2D by CYP27B1 is under stringent control. However, the first hydroxylation step catalyzed in the liver by CYP2R1 is constitutive and is not believed to be subjected to tight regulation. This has two important consequences: i) the regulation of liver CYP2R1 has retained little attention, and ii) circulating non-hydroxylated vitamin D is rapidly metabolized by liver CYP2R1. Therefore, 25(OH)D concentrations are considered to reflect vitamin D inputsand are used to determine the vitamin D status. A major breakthrough in our understanding on the nonskeletal effects of vitamin D is the recent discovery of autocrine/paracrine vitamin D systemsin many tissues 2 .This autocrine/paracrine signalingensures the local bioactivation of 25(OH)D into 1,25(OH)2D by extra-renal CYP27B1. In autocrine/paracrine vitamin D systems, the vitamin D metabolites are produced, act and are degraded locally without affecting serum 25(OH)D levels. Shui and coll rightly pointed out that local synthesis of 1,25(OH)2D from 25(OH)D can occur,because CYP27B1 is expressed in the prostate. However, the authors do not mention that CYP2R1 is also expressed in prostate tissue
The first comprehensive report on Indigenous Australian women's inequalities in cervical screening: a retrospective registry cohort study in Queensland, Australia (2000-2011)

BACKGROUND: The Australian National Cervical Screening Program, introduced more than 20 years ago, does not record the Indigenous status of screening participants. This article reports the first population-based estimates of participation in cervical screening for Indigenous and non-Indigenous Australian women. METHODS: This was a retrospective, population-based study of 1,334,795 female Queensland residents, aged 20 to 69 years, who participated in cervical screening from 2000 to 2011; 26,829 were identified as Indigenous through linkage to hospitalization records. Participation rates were calculated as the number of women screened divided by the average estimated resident population, with adjustments made for hysterectomies, for each 2-, 3-, and 5-year screening period. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), which were adjusted for age group, place of residence, and socioeconomic disadvantage. RESULTS: In 2010-2011, the 2-year participation rate was 55.7% (95% CI, 55.6%-55.9%) for non-Indigenous women and 33.5% (95% CI, 32.9%-34.1%) for Indigenous women; this represented a decrease from 2000-2001 (57.7% [95% CI, 57.6%-57.9%] and 35.3% [95% CI, 34.5%-36.1%], respectively). The difference between Indigenous and non-Indigenous women was greatest for those aged 45 to 49 years. The 3- and 5-year participation rates were higher within both groups, and the absolute differences between the 2 groups were larger. Significant interactions between the Indigenous status and the place of residence and socioeconomic disadvantage highlight that the Indigenous/non-Indigenous differential was evident in all places of residence except for very remote areas (OR, 0.99; 95% CI, 0.95-1.02) and was greatest in the most affluent areas (OR, 0.26; 95% CI, 0.24-0.27). CONCLUSIONS: Indigenous Australian women participate less than non-Indigenous women, and this gap has not closed. These results provide important benchmarks for the new Australian cervical screening program commencing in 2017, which will provide opportunities to reduce inequities for Indigenous women and address longstanding data deficiencies in the collection of the Indigenous status. Cancer 2016;122:1560-9. VC 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Lisa J. Whop, Gail Garvey, Peter Baade, Joan Cunningham, Kamalini Lokuge, Julia M. L. Brotherton, Patricia C. Valery, Dianne L. O, Connell, Karen Canfell, Abbey Diaz, David Roder, Dorota Gertig, Suzanne P. Moore and John R. Condo
Significant impact of biochemical recurrence on overall mortality in patients with high-risk prostate cancer after carbon-ion radiotherapy combined with androgen deprivation therapy

BACKGROUNDWhether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials.METHODSIn the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D\u27Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate.RESULTSThe median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM.CONCLUSIONSBR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies
Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial

Background: The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, improved clinical outcomes in patients with platinum-sensitive relapsed ovarian cancer, when used with chemotherapy and continued as maintenance therapy. This study describes health-related quality-of-life (QoL) during the first year of treatment. Methods: 456 women were randomly allocated to either receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib concurrently and continued as maintenance. Patients completed QoL questionnaires until disease progression, 3-weekly during chemotherapy and then 6-weekly to one year. Patients alive with disease progression completed a QoL form at one year from randomisation. The primary QoL end point was the global score from the EORTC QLQ-C30 at one year, comparing the standard chemotherapy group with the concurrent plus maintenance cediranib group. Results: Questionnaire compliance was 90% at baseline, and 76% at one year, similar across the three groups. Mean global QoL score at one year was 62.6 points in the standard chemotherapy group and 68.7 points in the concurrent plus maintenance group (+4.5, 95% CI -2.0 to 11.0, p = 0.18). Sensitivity analyses suggest this finding is robust to the effect of missing data, and the improvement became statistically significant after adjusting for self-reported diarrhoea. Conclusion: ICON6 showed a significant improvement in PFS using cediranib as concurrent and maintenance therapy. We report no QoL detriment with cediranib one year after commencing treatment. Maintained QoL, alongside prolonged cancer control, suggest cediranib has a valuable role in the treatment of relapsed ovarian cancer
The association between complications and quality of life after mastectomy and breast reconstruction for breast cancer

BACKGROUND: Medical treatment for breast cancer is associated with substantial toxicity and patient burden. There is less known about the impact of surgical complications. Understanding this impact could provide important information for patients when they are considering surgical options. METHODS: Between 2008 and 2009, the UK National Mastectomy and Breast Reconstruction Audit recorded surgical complications for a prospective cohort of 17,844 women treated for breast cancer at 270 hospitals; 6405 of these women were surveyed about their quality of life 18 months after surgery. Breast appearance, emotional well‐being, and physical well‐being were quantified on 0‐ to 100‐point scales. Linear multiple regression models, controlling for a range of baseline prognostic factors, were used to compare the scores of patients who had complications with the scores of those who did not. RESULTS: The overall complication rate was 10.2%. Complications were associated with little or no impairment in women undergoing mastectomy without reconstruction or with delayed reconstruction. The association was much larger for flap‐related complications suffered during immediate reconstruction. The breast‐appearance scores (adjusted mean difference, –23.8; 95% confidence interval [CI], –31.0 to –16.6) and emotional well‐being scores (adjusted mean difference, –14.0; 95% CI, –22.0 to –6.0) of these patients were much lower than those of any other patient group. Implant‐related complications were not associated with a lower quality of life in any surgical group. CONCLUSIONS: There is a strong case for prospectively collecting flap‐complication rates at the surgeon and surgical unit level and for allowing patients to access these data when they make choices about their breast cancer surgery
Empowerment in adolescents and young adults with cancer: Relationship with health-related quality of life

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                  177580.pdf (publisher's version ) (Open Access)BACKGROUND: The difficulties adolescents and young adults (AYAs) encounter during a cancer experience may result in a reduction in or absence of empowerment. The aims of the current study were to assess levels of empowerment and associated (demographic, clinical, or psychological) factors and examine the association between empowerment and health-related quality of life (HRQOL) among AYA patients with cancer. METHODS: Patients aged 18 to 35 years at time of cancer diagnosis and who were seen by 1 of the members of the specialized multidisciplinary AYA team of the Radboud University Medical Center were invited to complete questionnaires regarding empowerment; HRQOL; and sociodemographic, clinical, and psychological characteristics (autonomy, coping, unmet social support needs, and psychological distress). Results : A total of 83 AYA patients completed the questionnaires. The mean age of the participants at the time of diagnosis was 27.5 years. The vast majority had been treated with chemotherapy (86%), had a more advanced stage of disease, and had completed treatment at the time of participation (74%). The mean empowerment level was 154.1 (standard deviation, 17.8) with a range of 114 to 200. Multivariate analysis demonstrated that the autonomy subscales of self-awareness (beta = .35), capacity for managing new situations (beta = .19), and social support (beta = .35) were found to be positively associated with empowerment. Coping difficulties (beta = -.19) were found to be negatively associated with empowerment. Empowerment was independently associated with physical (beta = .31), psychological (beta = .50), social (beta = .39), religious (beta = .33), and total HRQOL (beta = .52; all P<.01). CONCLUSIONS: Low levels of empowerment were associated with low levels of autonomy and social support, female sex, and coping difficulties among AYA patients with cancer. Recognizing these patients as candidates for empowerment interventions ultimately could help to improve HRQOL in late adolescence and young adulthood. Cancer 2017;123:4039-47. (c) 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes
A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10-year outcomes for efficacy and toxicity

© 2017 American Cancer Society BACKGROUND: Concurrent-adjuvant chemoradiotherapy (CRT) became a recommended treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) with the first report of a significant survival benefit from the Intergroup 0099 study. However, data on late toxicities are lacking. Previous reports from the current NPC-9901 trial have raised concerns about a failure to improve overall survival (OS) because of an inadequate impact on distant control and increases in toxicities/noncancer deaths. Validation of the long-term therapeutic ratio is needed. METHODS: In this phase 3, randomized trial, patients with nonkeratinizing NPC (stage T1-4/N2-3/M0) were randomly assigned to radiotherapy alone (176 patients) or to CRT (172 patients) with concurrent cisplatin followed by adjuvant cisplatin plus fluorouracil. RESULTS: The early findings of significant improvements in tumor control were maintained: the CRT group achieved significantly higher 10-year overall failure-free (62% vs 50%; P =.01) and progression-free survival rates (56% vs 42%; P =.006) because of superior locoregional control (87% vs 74%; P =.003), whereas the impact on distant control remained insignificant (68% vs 65%; P =.24). The initial differences in toxicities diminished with longer follow-up: 52% versus 47% at 10 years for late toxicities (P =.20), 4.1% versus 2.8% for deaths due to treatment toxicity, and 15.1% versus 13.1% for deaths due to incidental/unknown causes. The OS rate for the CRT group reached statistical superiority at 10 years (62% vs 49%; P =.047). CONCLUSIONS: Long-term results have confirmed that CRT can significantly improve OS without excessive late toxicities for patients with regionally advanced NPC. However, more potent therapy is needed for improving distant control, especially for patients with stage IVA/B disease. Cancer 2017;123:4147–4157. © 2017 American Cancer Society.Link_to_subscribed_fulltex
Comparative effectiveness of prostate cancer screening between the ages of 55 and 69 years followed by active surveillance

BACKGROUND: Because of the recent grade C draft recommendation by the US Preventive Services Task Force (USPSTF) for prostate cancer screening between the ages of 55 and 69 years, there is a need to determine whether this could be cost-effective in a US population setting. METHODS: This study used a microsimulation model of screening and active surveillance (AS), based on data from the European Randomized Study of Screening for Prostate Cancer and the Surveillance, Epidemiology, and End Results Program, for the natural history of prostate cancer and Johns Hopkins AS cohort data to inform the probabilities of referral to treatment during AS. A cohort of 10 million men, based on US life tables, was simulated. The lifetime costs and effects of screening between the ages of 55 and 69 years with different screening frequencies and AS protocols were projected, and their cost-effectiveness was determined. RESULTS: Quadrennial screening between the ages of 55 and 69 years (55, 59, 63, and 67 years) with AS for men with low-risk cancers (ie, those with a Gleason score of 6 or lower) and yearly biopsies or triennial biopsies resulted in an incremental cost per quality-adjusted life-year (QALY) of $51,918 or $69,380, respectively. Most policies in which screening was followed by immediate treatment were dominated. In most sensitivity analyses, this study found a policy with which the cost per QALY remained below $100,000. CONCLUSIONS: Prostate-specific antigen–based prostate cancer screening in the United States between the ages of 55 and 69 years, as recommended by the USPSTF, may be cost-effective at a $100,000 threshold but only with a quadrennial screening frequency and with AS offered to all low-risk men. Cancer 2018;124:507-13