bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insomnia among elderly men and risk of prostate cancer.
Authors: Sigurdardottir Lara , Valdimarsdottir Unnur Anna , Mucci Lorelei , Fall Katja , Rider Jennifer R. , Schernhammer Eva S. , Czeisler Charles A , Launer Lenore , Harris Tamara B. , Stampfer Meir J. , Gudnason Vilmundur , Lockley Steven W. 
Published: February 2017

78 Background: While a large number of studies have reported a positive association between sleep disruption and breast cancer, little is known about its potential role in prostate cancer. Methods: Within the prospective AGES-Reykjavik cohort study, we followed 2102 men from 2002-2006 until the end of 2009. The men answered questions on sleep disturbances, which were combined in various ways to reflect onset and/or maintenance insomnia. Information on the occurrence of prostate cancer was obtained through record-linkages across the Icelandic Cancer and Causes of Death Registers. We used Cox regression models with 95% confidence intervals [CIs] to estimate age- and multivariable adjusted hazard ratios [HR] of prostate cancer by symptoms of insomnia. Results: During follow-up, 135 men (6,4%) were diagnosed with prostate cancer. Compared to men without insomnia, men with severe onset and maintenance insomnia and very severe insomnia were at increased risk of total prostate cancer with HR 1.9 (CI 1.2, 3.0) and 2.2 (CI 1.3, 3.8), respectively. For advanced prostate cancer, the corresponding HRs were 2.3 (CI 0.9-6.2) and 3.7 (CI 1.4-9.9), respectively. Conclusions: These data suggest that insomnia may confer an increased risk of prostate cancer. Reduced melatonin levels represent a plausible biological explanation, although additional studies using biomarkers and longer follow-up times are needed to further clarify the underlying mechanisms.
Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis
Authors: D’Angelo Sandra P. , Larkin James , Sosman Jeffrey A. , Lebbé Celeste , Brady Benjamin , Neyns Bart , Schmidt Henrik , Hassel Jessica C. , Hodi F. Stephen , Lorigan Paul , Savage Kerry J. , Miller Wilson H. , Mohr Peter , Marquez-Rodas Ivan , Charles Julie , Kaatz Martin , Sznol Mario , Weber Jeffrey S. , Shoushtari Alexander N. , Ruisi Mary , Jiang Joel , Wolchok Jedd D. 
Published: February 2017

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti–programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.
Predictors of and Trends in High-Intensity End-of-Life Care Among Children With Cancer: A Population-Based Study Using Health Services Data
Authors: Kassam Alisha , Sutradhar Rinku , Widger Kimberley , Rapoport Adam , Pole Jason D. , Nelson Katherine , Wolfe Joanne , Earle Craig C. , Gupta Sumit 
Published: February 2017

Purpose Children with cancer often receive high-intensity (HI) medical care at the end-of-life (EOL). Previous studies have been limited to single centers or lacked detailed clinical data. We determined predictors of and trends in HI-EOL care by linking population-based clinical and health-services databases. Methods A retrospective decedent cohort of patients with childhood cancer who died between 2000 and 2012 in Ontario, Canada, was assembled using a provincial cancer registry and linked to population-based health-care data. Based on previous studies, the primary composite measure of HI-EOL care comprised any of the following: intravenous chemotherapy < 14 days from death; more than one emergency department visit; and more than one hospitalization or intensive care unit admission < 30 days from death. Secondary measures included those same individual measures and measures of the most invasive (MI) EOL care (eg, mechanical ventilation < 14 days from death). We determined predictors of outcomes with appropriate regression models. Sensitivity analysis was restricted to cases of cancer-related mortality, excluding treatment-related mortality (TRM) cases. Results The study included 815 patients; of these, 331 (40.6%) experienced HI-EOL care. Those with hematologic malignancies were at highest risk (odds ratio, 2.5; 95% CI, 1.8 to 3.6; P < .001). Patients with hematologic cancers and those who died after 2004 were more likely to experience the MI-EOL care (eg, intensive care unit, mechanical ventilation, odds ratios from 2.0 to 5.1). Excluding cases of TRM did not substantively change the results. Conclusion Ontario children with cancer continue to experience HI-EOL care. Patients with hematologic malignancies are at highest risk even when excluding TRM. Of concern, rates of the MI-EOL care have increased over time despite increased palliative care access. Linking health services and clinical data allows monitoring of population trends in EOL care and identifies high-risk populations for future interventions.
Tumor Deposits in Colorectal Cancer: Improving the Value of Modern Staging—A Systematic Review and Meta-Analysis
Authors: Nagtegaal Iris D. , Knijn Nikki , Hugen Niek , Marshall Helen C. , Sugihara Kenichi , Tot Tibor , Ueno Hideki , Quirke Philip 
Published: February 2017

Purpose Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The role of tumor deposits (TDs) in staging remains debated. We have assessed the relation of TDs with metastatic pattern to evaluate whether TDs might add significant new information to staging. Methods We performed a systematic literature search that was focused on the role of TDs in CRC. Studies with neoadjuvant-treated patients were excluded. Data on stage, histologic factors, and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TDs, lymph node metastases (LNMs), and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes. Results Of 10,106 included patients with CRC, 22% presented with TDs. TDs are invariably associated with poor outcome. Presence of TDs was associated with presence of LNMs and EMVI. In a pairwise comparison, effects of TD were stronger than those of both LNMs and EMVI. In the logistic regression model, TDs in combination with LNMs is the strongest predictor for liver (odds ratio [OR], 5.5), lung (OR, 4.3) and peritoneal metastases (OR, 7.0). Presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases. Conclusion We have shown that TDs are not equal to LNMs or EMVI with respect to biology and outcome. We lose valuable prognostic information by allocating TDs into nodal category N1c and only considering TDs in the absence of LNMs. Therefore, we propose that the number of TDs should be added to the number of LNMs to derive a final N stage.
Lung Cancer Risk Prediction Model Incorporating Lung Function: Development and Validation in the UK Biobank Prospective Cohort Study
Authors: Muller David C. , Johansson Mattias , Brennan Paul 
Published: February 2017

Purpose Several lung cancer risk prediction models have been developed, but none to date have assessed the predictive ability of lung function in a population-based cohort. We sought to develop and internally validate a model incorporating lung function using data from the UK Biobank prospective cohort study. Methods This analysis included 502,321 participants without a previous diagnosis of lung cancer, predominantly between 40 and 70 years of age. We used flexible parametric survival models to estimate the 2-year probability of lung cancer, accounting for the competing risk of death. Models included predictors previously shown to be associated with lung cancer risk, including sex, variables related to smoking history and nicotine addiction, medical history, family history of lung cancer, and lung function (forced expiratory volume in 1 second [FEV1]). Results During accumulated follow-up of 1,469,518 person-years, there were 738 lung cancer diagnoses. A model incorporating all predictors had excellent discrimination (concordance (c)-statistic [95% CI] = 0.85 [0.82 to 0.87]). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected c-statistic = 0.84). The full model, including FEV1, also had modestly superior discriminatory power than one that was designed solely on the basis of questionnaire variables (c-statistic = 0.84 [0.82 to 0.86]; optimism-corrected c-statistic = 0.83; pFEV1 = 3.4 × 10−13). The full model had better discrimination than standard lung cancer screening eligibility criteria (c-statistic = 0.66 [0.64 to 0.69]). Conclusion A risk prediction model that includes lung function has strong predictive ability, which could improve eligibility criteria for lung cancer screening programs.
Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
Authors: Davids Matthew S. , Roberts Andrew W. , Seymour John F. , Pagel John M. , Kahl Brad S. , Wierda William G. , Puvvada Soham , Kipps Thomas J. , Anderson Mary Ann , Salem Ahmed Hamed , Dunbar Martin , Zhu Ming , Peale Franklin , Ross Jeremy A. , Gressick Lori , Desai Monali , Kim Su Young , Verdugo Maria , Humerickhouse Rod A. , Gordon Gary B. , Gerecitano John F. 
Published: February 2017

Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion. Results NHL subtypes included mantle cell lymphoma (MCL; n = 28), follicular lymphoma (FL; n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL arising from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenström macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Venetoclax was generally well tolerated. Clinical tumor lysis syndrome was not observed, whereas laboratory tumor lysis syndrome was documented in three patients. Treatment-emergent adverse events were reported in 103 patients (97%), a majority of which were grade 1 to 2 in severity. Grade 3 to 4 events were reported in 59 patients (56%), and the most common were hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Overall response rate was 44% (MCL, 75%; FL, 38%; DLBCL, 18%). Estimated median progression-free survival was 6 months (MCL, 14 months; FL, 11 months; DLBCL, 1 month). Conclusion Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently achieve durable response in MCL. Additional investigations including combination therapy to augment response rates and durability are ongoing.
Pilot Survey of Breast Cancer Management in Sub-Saharan Africa
Authors: Vanderpuye Verna D.N.K. , Olopade Olufunmilayo I. , Huo Dezheng 
Published: February 2017

Purpose To understand the current state of breast cancer management in sub-Saharan Africa. Methods We conducted an anonymous online survey of breast cancer management among African Organization for Research and Treatment in Cancer (AORTIC) members by using a 42-question structured questionnaire in both English and French in 2013. Results Twenty members from 19 facilities in 14 countries responded to the survey. Twelve members (60%) belonged to a multidisciplinary breast cancer team. Radiotherapy equipment was available in seven facilities (36%), but equipment had down time at least once a week in four facilities. Available chemotherapy drugs included methotrexate, cyclophosphamide, fluorouracil, anthracyclines, and vincristine, whereas trastuzumab, taxanes, vinorelbine, and gemcitabine were available in few facilities. Core-needle biopsy was available in 16 facilities (84%); mammogram, in 17 facilities (89%); computed tomography scan, in 15 facilities (79%); magnetic resonance imaging, in 11 facilities (58%); and bone scans, in nine facilities (47%). It took an average of 1 to 3 weeks to report histopathology. Immunohistochemistry was available locally in eight facilities (42%), outside hospitals but within the country in seven facilities (37%), and outside the country in four facilities (21%). Thirteen facilities (68%) performed axillary node dissections as part of a breast protocol. Neoadjuvant chemotherapy was the most common therapy for locally advanced breast cancer in 13 facilities (68%). In three facilities (16%), receptor status did not influence the prescription of hormone treatment. Conclusion This pilot survey suggests that AORTIC members in sub-Saharan Africa continue to make gains in the provision of access to multidisciplinary breast cancer care, but the lack of adequate pathology and radiotherapy services is a barrier. Focused attention on in-country and regional training needs and improvement of health systems deliverables is urgently needed.
Model for Estimating Power and Downtime Effects on Teletherapy Units in Low-Resource Settings
Authors: McCarroll Rachel , Youssef Bassem , Beadle Beth , Bojador Maureen , Cardan Rex , Famiglietti Robin , Followill David , Ibbott Geoffrey , Jhingran Anuja , Trauernicht Christoph , Balter Peter , Court Laurence 
Published: February 2017

Purpose More than 6,500 megavoltage teletherapy units are needed worldwide, many in low-resource settings. Cobalt-60 units or linear accelerators (linacs) can fill this need. We have evaluated machine performance on the basis of patient throughput to provide insight into machine viability under various conditions in such a way that conclusions can be generalized to a vast array of clinical scenarios. Materials and Methods Data from patient treatment plans, peer-reviewed studies, and international organizations were combined to assess the relative patient throughput of linacs and cobalt-60 units that deliver radiotherapy with standard techniques under various power and maintenance support conditions. Data concerning the frequency and duration of power outages and downtime characteristics of the machines were used to model teletherapy operation in low-resource settings. Results Modeled average daily throughput was decreased for linacs because of lack of power infrastructure and for cobalt-60 units because of limited and decaying source strength. For conformal radiotherapy delivered with multileaf collimators, average daily patient throughput over 8 years of operation was equal for cobalt-60 units and linacs when an average of 1.83 hours of power outage occurred per 10-hour working day. Relative to conformal treatments delivered with multileaf collimators on the respective machines, the use of advanced techniques on linacs decreased throughput between 20% and 32% and, for cobalt machines, the need to manually place blocks reduced throughput up to 37%. Conclusion Our patient throughput data indicate that cobalt-60 units are generally best suited for implementation when machine operation might be 70% or less of total operable time because of power outages or mechanical repair. However, each implementation scenario is unique and requires consideration of all variables affecting implementation.
Presentation, Treatment, and Outcomes of Haitian Women With Breast Cancer in Miami and Haiti: Disparities in Breast Cancer—A Retrospective Cohort Study
Authors: Gomez Alexandra , DeGennaro Vincent , George Sophia H.L. , Reis Isildinha M. , Santamaria Estefania , Westin Gustavo Figueiredo , Gabriel Dieudina , Hurley Judith 
Published: February 2017

PurposeWe compared a cohort of Haitian immigrants with residents in Haiti with breast cancer (BC) to evaluate the effects of location on presentation, treatment, and outcomes.Patients and MethodsParticipants were Haitian women with BC living in Miami who presented to the University of Miami/Jackson Memorial Hospital and women with BC living in Haiti who presented to the Innovating Health International Women’s Cancer Center. The primary outcome was the relationship between location, cancer characteristics, and survival. The secondary objective was to compare our results with data extracted from the SEER database. Cox regression was used to compare survival.ResultsOne hundred two patients from University of Miami/Jackson Memorial Hospital and 94 patients from Innovating Health International were included. The patients in Haiti, compared with the patients in Miami, were younger (mean age, 50.2 v 53.7 years, respectively; P = .042), presented after a longer duration of symptoms (median, 20 v 3 months, respectively; P < .001), had more advanced stage (44.7% v 25.5% with stage III and 27.6% v 18.6% with stage IV BC, respectively), and had more estrogen receptor (ER) –negative tumors (44.9% v 26.5%, respectively; P = .024). The percentage of women who died was 31.9% in Haiti died compared with 17.6% in Miami. Median survival time was 53.7 months for women in Haiti and was not reached in Miami. The risk of death was higher for women in Haiti versus women in Miami (adjusted hazard ratio, 3.09; P = .0024).ConclusionWomen with BC in Haiti experience a significantly worse outcome than immigrants in Miami, which seems to be related to a more advanced stage and younger age at diagnosis, more ER-negative tumors, and lack of timely effective treatments. The differences in age and ER status are not a result of access to care and are unexplained.
Awareness and Perception About Cancer Among the Public in Chennai, India
Authors: Elangovan Vidhubala , Rajaraman Swaminathan , Basumalik Barsha , Pandian Dhivya 
Published: February 2017

Purpose Cancer-related stigma influences the way people perceive cancer, which renders cancer control—beginning with prevention and proceeding to palliation—a challenging task. This study aimed to assess the current levels of awareness and perceptions about cancer among people with various socioeconomic status and diverse backgrounds in the city of Chennai, India. Patients and Methods The sample population (N = 2,981; 18 to 88 years of age) was stratified into four groups: patients (n = 510), caregivers (n = 494) consulting at the Cancer Institute (Women Indian Association), college students (n = 978), and general public (n = 999). Fourteen statements related to cancer stigma or myths were identified and categorized by awareness (10 items) or perception (4 items). Responses to those statements were recorded by using a Likert scale (yes, no, and don’t know). The data were described by frequency analysis and χ2 test using SPSS Version 13 (SPSS, Chicago, IL). Results More than 70% of the study participants were aware that cancer is curable, that cancer is not contagious, and that cancer is not a curse or a death sentence. However, only approximately half believed that surgery or biopsy do not cause cancer to spread to other organs or that radiation therapy does not consist of receiving an electric shock. Higher education, younger age, male sex, personal experience with cancer (either as a patient or caregiver), and high socioeconomic status were the categories of people with increased awareness about cancer. Conclusion These factors need to be taken into consideration in tailoring information, education, and communication campaigns. Resource allocation for these campaigns is an investment in cancer control.
Ipilimumab in Pretreated Patients With Advanced Malignant Melanoma: Results of the South African Expanded-Access Program
Authors: Rapoport Bernardo L. , Vorobiof Daniel A. , Dreosti Lydia M. , Nosworthy Adam , McAdam Georgina , Jordaan Johan P. , Miller-Jansön Helen , de Necker Margreet , de Beer Janetta C. , Duvenhage Hennie 
Published: February 2017

Purpose The primary objective of this study was to evaluate 1- and 2-year survival rates and durable remissions in pretreated patients with advanced (unresectable or metastatic) malignant melanoma treated with ipilimumab in a South African expanded-access program (SA-EAP). Patients and Methods This multicenter, retrospective study obtained data from pretreated patients with advanced malignant melanoma who were eligible for the ipilimumab SA-EAP. Ipilimumab was administered at a dose of 3 mg/kg intravenously every 3 weeks for four cycles to adults with advanced melanoma for whom at least one line of treatment for metastatic disease had failed. Data from the medical records of 108 patients treated within the SA-EAP were collected and statistically analyzed to determine overall (OS) and progression-free survival (PFS) at 1 and 2 years. Results In the population of 108 patients, a median OS of 8.98 months (95% CI, 7.47 to 10.79 months) was observed. One-year OS was 36% (95% CI, 26% to 45%), and 2-year survival was observed as 20% (95% CI, 12% to 27%). The median survival without progression (ie, PFS) was 3.44 months (95% CI, 2.98 to 4.16 months), and 1- and 2-year PFS were 22% (95% CI, 14% to 29%) and 14% (95% CI, 8% to 21%), respectively. The longest recorded survival was 3.4 years. No independent prognostic variables were identified to predict for OS by multivariate Cox proportional hazards model. Conclusion In this multicenter South African setting, ipilimumab at a dose of 3 mg/kg was an effective treatment with long-term OS in a subset of patients with pretreated advanced malignant melanoma.