bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Medications for Treating Anxiety and Depression in Cancer Survivors in the United States
Authors: Hawkins Nikki A. , Soman Ashwini , Buchanan Lunsford Natasha , Leadbetter Steven , Rodriguez Juan L. 
Published: February 2017

Purpose This study used population-based data to estimate the percentage of cancer survivors in the United States reporting current medication use for anxiety and depression and to characterize the survivors taking this type of medication. Rates of medication use in cancer survivors were compared with rates in the general population. Methods We analyzed data from the National Health Interview Survey, years 2010 to 2013, identifying cancer survivors (n = 3,184) and adults with no history of cancer (n = 44,997) who completed both the Sample Adult Core Questionnaire and the Adult Functioning and Disability Supplement. Results Compared with adults with no history of cancer, cancer survivors were significantly more likely to report taking medication for anxiety (16.8% v 8.6%, P < .001), depression (14.1% v 7.8%, P < .001), and one or both of these conditions combined (19.1% v 10.4%, P < .001), indicating that an estimated 2.5 million cancer survivors were taking medication for anxiety or depression in the United States at that time. Survivor characteristics associated with higher rates of medication use for anxiety included being younger than 65 years old, female, and non-Hispanic white, and having public insurance, a usual source of medical care, and multiple chronic health conditions. Survivor characteristics associated with medication use for depression were largely consistent with those for anxiety, with the exceptions that insurance status was not significant, whereas being widowed/divorced/separated was associated with more use. Conclusion Cancer survivors in the United States reported medication use for anxiety and depression at rates nearly two times those reported by the general public, likely a reflection of greater emotional and physical burdens from cancer or its treatment.
CpG Methylation Signature Predicts Recurrence in Early-Stage Hepatocellular Carcinoma: Results From a Multicenter Study
Authors: Qiu Jiliang , Peng Baogang , Tang Yunqiang , Qian Yeben , Guo Pi , Li Mengfeng , Luo Junhang , Chen Bin , Tang Hui , Lu Canliang , Cai Muyan , Ke Zunfu , He Wei , Zheng Yun , Xie Dan , Li Binkui , Yuan Yunfei 
Published: February 2017

Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed increasingly, and in one half of diagnosed patients, recurrence will develop. Thus, it is urgent to identify recurrence-related markers. We investigated the effectiveness of CpG methylation in predicting recurrence for patients with E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four independent centers were sorted by three phases. In the discovery phase, 66 tumor samples were analyzed using the Illumina Methylation 450k Beadchip. Two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to select significant CpGs. In the training phase, penalized Cox regression was used to further narrow CpGs into 140 samples. In the validation phase, candidate CpGs were validated using an internal cohort (n = 141) and two external cohorts (n = 191 and n =104). Results After combining the 46 CpGs selected by the Least Absolute Shrinkage and Selector Operation and the Support Vector Machine-Recursive Feature Elimination algorithms, three CpGs corresponding to SCAN domain containing 3, Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1, and peptidase inhibitor 3 were highlighted as candidate predictors in the training phase. On the basis of the three CpGs, a methylation signature for E-HCC (MSEH) was developed to classify patients into high- and low-risk recurrence groups in the training cohort ( P < .001). The performance of MSEH was validated in the internal cohort ( P < .001) and in the two external cohorts ( P < .001; P = .002). Furthermore, a nomogram comprising MSEH, tumor differentiation, cirrhosis, hepatitis B virus surface antigen, and antivirus therapy was generated to predict the 5-year recurrence-free survival in the training cohort, and it performed well in the three validation cohorts (concordance index: 0.725, 0.697, and 0.693, respectively). Conclusion MSEH, a three-CpG–based signature, is useful in predicting recurrence for patients with E-HCC.
Beyond Positive Margins and Extracapsular Extension: Evaluating the Utilization and Clinical Impact of Postoperative Chemoradiotherapy in Resected Locally Advanced Head and Neck Cancer
Authors: Trifiletti Daniel M. , Smith Andrew , Mitra Nandita , Grover Surbhi , Lukens John N. , Cohen Roger B. , Read Paul , Mendenhall William M. , Lin Alexander , Swisher-McClure Samuel 
Published: February 2017

Purpose To examine recent utilization and survival outcomes associated with use of adjuvant chemoradiotherapy (CRT) for patients with resected locally advanced head and neck cancer (LAHNC) with negative surgical margins (SM negative) and no extracapsular extension (ECE). Materials and Methods We conducted a retrospective observational cohort study using the National Cancer Database evaluating patients diagnosed in 2004 to 2012 with AJCC stage III to IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx treated with definitive surgery and adjuvant radiotherapy (RT) or CRT. We identified a subset of patients with SM negative and no ECE (n = 10,870). We determined factors associated with CRT use and examined overall survival of patients receiving CRT versus RT. We further evaluated survival outcomes by number of lymph nodes involved to assess whether this was associated with benefit from CRT. Results Among patients with resected LAHNC with SM negative and no ECE, 47% received adjuvant CRT. The use of CRT varied substantially according to several factors, including patient age, contralateral/bulky neck disease, increasing number of positive lymph nodes, and lower neck disease. CRT was associated with a statistically significant improvement in overall survival compared with RT alone (hazard ratio, 0.90; 95% CI, 0.86 to 0.94; P < .001). Survival benefits of CRT versus RT alone increased in patients with multiple positive lymph nodes. Conclusion The use of adjuvant CRT in patients with resected LAHNC with SM negative and no ECE is common. Substantial practice variation as well as the survival differences observed in this study support the conduct of additional research to guide personalized treatment approaches in this setting. The number of positive lymph nodes seems to be an appropriate selection factor for further investigation of CRT in such patients.
Economic Burden of Chronic Lymphocytic Leukemia in the Era of Oral Targeted Therapies in the United States
Authors: Chen Qiushi , Jain Nitin , Ayer Turgay , Wierda William G. , Flowers Christopher R. , O’Brien Susan M. , Keating Michael J. , Kantarjian Hagop M. , Chhatwal Jagpreet 
Published: February 2017

Purpose Oral targeted therapies represent a significant advance for the treatment of patients with chronic lymphocytic leukemia (CLL); however, their high cost has raised concerns about affordability and the economic impact on society. Our objective was to project the future prevalence and cost burden of CLL in the era of oral targeted therapies in the United States. Methods We developed a simulation model that evaluated the evolving management of CLL from 2011 to 2025: chemoimmunotherapy (CIT) as the standard of care before 2014, oral targeted therapies for patients with del(17p) and relapsed CLL from 2014, and for first-line treatment from 2016 onward. A comparator scenario also was simulated where CIT remained the standard of care throughout. Disease progression and survival parameters for each therapy were based on published clinical trials. Results The number of people living with CLL in the United States is projected to increase from 128,000 in 2011 to 199,000 by 2025 (55% increase) due to improved survival; meanwhile, the annual cost of CLL management will increase from $0.74 billion to $5.13 billion (590% increase). The per-patient lifetime cost of CLL treatment will increase from $147,000 to $604,000 (310% increase) as oral targeted therapies become the first-line treatment. For patients enrolled in Medicare, the corresponding total out-of-pocket cost will increase from $9,200 to $57,000 (520% increase). Compared with the CIT scenario, oral targeted therapies resulted in an incremental cost-effectiveness ratio of $189,000 per quality-adjusted life-year. Conclusion The increased benefit and cost of oral targeted therapies is projected to enhance CLL survivorship but can impose a substantial financial burden on both patients and payers. More sustainable pricing strategies for targeted therapies are needed to avoid financial toxicity to patients.
Obesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities
Authors: Jiralerspong Sao , Goodwin Pamela J. 
Published: February 2017

Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes. This is most clearly established for estrogen receptor–positive breast cancer, with the relationship in triple-negative and human epidermal growth factor receptor 2–positive subtypes less well established. A range of biologic mechanisms that may underlie this association has been identified. Weight loss and lifestyle interventions, as well as metformin and other obesity-targeted therapies, are promising avenues that require further study. Conclusion Obesity is associated with inferior survival in breast cancer. Understanding the nature and mechanisms of this effect provides an important opportunity for interventions to improve the diagnosis, treatment, and outcomes of obese patients with breast cancer.
Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101–Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity
Authors: Pituskin Edith , Mackey John R. , Koshman Sheri , Jassal Davinder , Pitz Marshall , Haykowsky Mark J. , Pagano Joseph J. , Chow Kelvin , Thompson Richard B. , Vos Larissa J. , Ghosh Sunita , Oudit Gavin Y. , Ezekowitz Justin A. , Paterson D. Ian 
Published: February 2017

Purpose The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2–overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity. Patients and Methods In this double-blinded, placebo-controlled trial, patients with HER2-positive early breast cancer were randomly assigned to receive treatment with perindopril, bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy. Patients underwent cardiac magnetic resonance imaging at baseline and post–cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF. Results Thirty-three patients received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline demographic, cancer, and cardiovascular profiles were similar between groups. Study drugs were well tolerated with no serious adverse events. After 17 cycles of trastuzumab, indexed left ventricular end diastolic volume increased in patients treated with perindopril (+7 ± 14 mL/m2), bisoprolol (+8 mL ± 9 mL/m2), and placebo (+4 ± 11 mL/m2; P = .36). In secondary analyses, trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients (−1 ± 5%) relative to the perindopril (−3 ± 4%) and placebo (−5 ± 5%) groups ( P = .001). Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis. Conclusion Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy–related declines in LVEF; however, trastuzumab-mediated left ventricular remodeling—the primary outcome—was not prevented by these pharmacotherapies.
Cetuximab Plus Chemoradiotherapy in Immunocompetent Patients With Anal Carcinoma: A Phase II Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group Trial (E3205)
Authors: Garg Madhur K. , Zhao Fengmin , Sparano Joseph A. , Palefsky Joel , Whittington Richard , Mitchell Edith P. , Mulcahy Mary F. , Armstrong Karin I. , Nabbout Nassim H. , Kalnicki Shalom , El-Rayes Bassel F. , Onitilo Adedayo A. , Moriarty Daniel J. , Fitzgerald Thomas J. , Benson Al B. 
Published: February 2017

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus–associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.
Weight Loss Randomized Intervention Trials in Female Cancer Survivors
Authors: Chlebowski Rowan T. , Reeves Marina M. 
Published: February 2017

Purpose Observational study evidence has associated overweight/obesity with decreased survival in women with breast cancer and with several other cancers. Although full-scale, definitive weight loss adjuvant intervention trials with cancer end points remain to be conducted, a number of randomized controlled trials have evaluated weight loss interventions in survivors of cancer in women. Findings from these trials in breast, endometrial, and ovarian cancer are reviewed. Methods A systematic review of randomized controlled clinical trials evaluating weight loss interventions was updated (for studies published 2013 to 2016), and clinical trials registers were searched for ongoing trials. Results Six new randomized trials in breast cancer survivors and two randomized trials in endometrial cancer survivors were identified. Evidence from these trials and the 10 earlier randomized trials in female cancer survivors provide support for the feasibility of recruiting women closer to the cancer diagnosis and efficacy for achieving weight loss, in particular with telephone-based interventions, and have identified the challenge of achieving significant weight loss in African American cancer survivors and of maintaining weight loss in any cancer survivor group. Seven ongoing randomized trials are evaluating the influence of weight loss interventions on cancer end points (five in breast cancer, one in ovarian cancer, and one in endometrial cancer). Conclusion After a decade of preliminary studies, ongoing randomized, controlled clinical trials will potentially provide definitive assessment of whether weight loss can improve breast cancer clinical outcome. Longer-term interventions (> 2 years’ duration) may be needed to optimize weight loss maintenance and any potential benefits on cancer end points.
Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma
Authors: Seisen Thomas , Krasnow Ross E. , Bellmunt Joaquim , Rouprêt Morgan , Leow Jeffrey J. , Lipsitz Stuart R. , Vetterlein Malte W. , Preston Mark A. , Hanna Nawar , Kibel Adam S. , Sun Maxine , Choueiri Toni K. , Trinh Quoc-Dien , Chang Steven L. 
Published: February 2017

Purpose There is limited evidence to support the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Patients and Methods Within the National Cancer Database (2004 to 2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW) –adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the two treatment groups. In addition, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathologic stage (pT3/T4N0, pT3/T4Nx and pTanyN+), and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation, respectively, after RNU. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation (47.41 [interquartile range,19.88 to 112.39] v 35.78 [interquartile range, 14.09 to 99.22] months; P < .001). The 5-year IPTW-adjusted rates of OS for AC versus observation were 43.90% and 35.85%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit (hazard ratio, 0.77 [95% CI, 0.68 to 0.88]; P < .001). This benefit was consistent across all subgroups examined (all P < .05), and no significant heterogeneity of treatment effect was observed (all Pinteraction > .05). Conclusion We report an OS benefit in patients who received AC versus observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.
Cardiac Toxicity After Radiotherapy for Stage III Non–Small-Cell Lung Cancer: Pooled Analysis of Dose-Escalation Trials Delivering 70 to 90 Gy
Authors: Wang Kyle , Eblan Michael J. , Deal Allison M. , Lipner Matthew , Zagar Timothy M. , Wang Yue , Mavroidis Panayiotis , Lee Carrie B. , Jensen Brian C. , Rosenman Julian G. , Socinski Mark A. , Stinchcombe Thomas E. , Marks Lawrence B. 
Published: February 2017

Purpose The significance of radiotherapy (RT) –associated cardiac injury for stage III non–small-cell lung cancer (NSCLC) is unclear, but higher heart doses were associated with worse overall survival in the Radiation Therapy Oncology Group (RTOG) 0617 study. We assessed the impact of heart dose in patients treated at our institution on several prospective dose-escalation trials. Patients and Methods From 1996 to 2009, 127 patients with stage III NSCLC (Eastern Cooperative Oncology Group performance status, 0 to 1) received dose-escalated RT to 70 to 90 Gy (median, 74 Gy) in six trials. RT plans and cardiac doses were reviewed. Records were reviewed for the primary end point: symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, pericarditis, significant arrhythmia, and heart failure). Cardiac risk was assessed by noting baseline coronary artery disease and calculating the WHO/International Society of Hypertension score. Competing risks analysis was used. Results In all, 112 patients were analyzed. Median follow-up for surviving patients was 8.8 years. Twenty-six patients (23%) had one or more events at a median of 26 months to first event (effusion [n = 7], myocardial infarction [n = 5], unstable angina [n = 3], pericarditis [n = 2], arrhythmia [n = 12], and heart failure [n = 1]). Heart doses (eg, heart mean dose; hazard ratio, 1.03/Gy; P = .002,), coronary artery disease ( P < .001), and WHO/International Society of Hypertension score ( P = .04) were associated with events on univariable analysis. Heart doses remained significant on multivariable analysis that accounted for baseline risk. Two-year competing risk–adjusted event rates for patients with heart mean dose < 10 Gy, 10 to 20 Gy, or ≥ 20 Gy were 4%, 7%, and 21%, respectively. Heart doses were not associated with overall survival. Conclusion Cardiac events were relatively common after high-dose thoracic RT and were independently associated with both heart dose and baseline cardiac risk. RT-associated cardiac toxicity after treatment of stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized.