Contrasting characteristics of daily physical activity in older adults by cancer history.

BACKGROUND: Using objectively collected physical activity (PA) data from the Baltimore Longitudinal Study of Aging, the authors tested whether patterns of daily activity and sedentary time differed by cancer survivorship in older adults. METHODS: In total, 659 participants (mean age ± standard deviation, 71 ± 10 years; 51% women) who had self-reported information on cancer history were instructed to wear an accelerometer for 7 consecutive days. Accelerometer data were summarized into: 1) PA volume and 2) activity fragmentation (interrupted activity), expressed as both continuous and as dichotomized (low and high) variables. Participants were categorized into 4 groups by cross-classification of dichotomous PA volume and fragmentation. Multiple regression models were used to estimate differences in PA patterns by cancer history. RESULTS: Cancer survivors averaged 0.12 fewer log-transformed activity counts per day (standard error, 0.05; P = .02) than individuals who reported no history of cancer after adjusting for demographics, behavioral factors, and comorbidities. Although fragmentation did not differ by cancer survivorship in the continuous model (P = .13), cancer survivorship was associated with 77% greater odds (odds ratio, 1.77; 95% confidence interval, 1.11-2.82) of having high (vs low) fragmentation and 94% greater odds (odds ratio, 1.94; 95% confidence interval, 1.13-3.33) of having combined low PA/high fragmentation (vs high PA/low fragmentation) relative to those with no cancer history. CONCLUSIONS: The current findings suggest that cancer survivors engage in lower total daily PA and that they perform this activity in a more fragmented manner compared with adults without a history of cancer. These results may reflect the onset and progression of a low-activity phenotype that is more vulnerable to heightened levels of fatigue and functional decline with aging.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted. The objective of this analysis was to describe characteristics and trends of clinical trials funded by the National Institutes of Health over time and by Institutes and Centers of the National Institutes of Health. Methods Interventional studies funded by the National Institutes of Health and registered in ClinicalTrials.gov between 2005 and 2015 were included in the analysis. Trials were identified from the 27 March 2016 Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database. A descriptive analysis of trials by year and National Institutes of Health Institute/Center was performed. Results There were 12,987 National Institutes of Health-funded clinical trials registered between 2005 and 2015. There were 1,580, 1,116, and 930 trials registered in 2005, 2010, and 2015, respectively. The majority were early-development trials (phases 0, 1, or 2; 53%), randomized (61%), and single-center (63%). Trial demographics have remained unchanged over time. Median trial sample size was 64 (interquartile range 29-192) with 10% of trials enrolling ≥500 participants. Most trials were completed within 5 years of enrollment start (69%). Trial characteristics varied considerably across National Institutes of Health Institutes and Centers. Results were reported under the assumptions that most National Institutes of Health-funded trials are registered in ClinicalTrials.gov and that trials are being registered completely and accurately. Conclusion In conclusion, there has been a decline in the number of trials being funded over time, explained in part by a relatively constant budget, increases in trial costs, or other factors that cannot be quantified. National Institutes of Health-funded trials are relatively small and tend to be single-centered. There are substantial differences in the number and types of trials done by Institutes and Centers within the National Institutes of Health.

Chemotherapy regimens for advanced pancreatic cancer: a systematic review and network meta-analysis.

BACKGROUND: Advanced pancreatic cancer confers poor prognosis and treatment advancement has been slow. Recent randomized clinical trials (RCTs) have demonstrated survival benefits for combination therapy compared to gemcitabine alone. However, the comparative benefits and harms of available combination chemotherapy treatments are not clear. We therefore conducted a systematic review and Bayesian network meta-analysis to assess the comparative safety and efficacy of chemotherapy regimens for the treatment of advanced pancreatic cancer. METHODS: MEDLINE, PubMed, EMBASE, Cochrane Central Registry of Clinical trials and abstracts from major scientific meetings were searched for RCTs published from 2002 to 2013. Key outcomes were overall survival (OS), progression free survival (PFS), and safety including grade 3-4 febrile neutropenia, neutropenia, vomiting, diarrhea, fatigue and sensory neuropathy. Bayesian network meta-analyses were conducted to calculate survival and safety outcomes using gemcitabine (GEM) as the reference comparator. Effect estimates and 95% credible intervals were calculated for each comparison. Mean ranks and the probability of being best were obtained for each treatment analyzed in the network meta-analysis. RESULTS: The search identified 23 studies involving 19 different treatment regimens and 9,989 patients. FOLFIRINOX, GEM/cisplatin/epirubicin/5FU (PEFG), GEM/NAB-paclitaxel (NAB-P), GEM/erlotinib+/-bevacizumab, GEM/capecitabine, and GEM/oxaliplatin were associated with statistically significant improvements in OS and PFS relative to gemcitabine alone and several other treatments. They were amongst the top ranked for survival outcomes amongst other treatments included. No significant differences were found for other combination chemotherapy treatments. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Overall, combination therapies had greater risk for evaluated grade 3-4 toxicities over gemcitabine alone. CONCLUSIONS: In the absence of head-to-head comparisons, we performed a mixed-treatment analysis to achieve high-quality information on the effectiveness and safety of each treatment. This study suggests that some combination therapies may offer greater benefits in the treatment of advanced pancreatic cancer than others. To more fully elucidate the comparative benefits and harms of different combination chemotherapy regimens, rigorously conducted comparative studies, or network meta-analysis of patient-level data are required.

Impact of patient selection, disease progression, and adverse events on esophageal cancer outcomes after trimodality therapy.

BACKGROUND: Neoadjuvant chemoradiation followed by surgery (NeoCRT) has been advocated as standard therapy for resectable esophageal cancer. Our objective was to compare oncologic outcomes between NeoCRT and upfront surgical resection (SURG). METHODS: We conducted a single-institution, retrospective review of all potentially resectable esophageal cancer patients treated with NeoCRT or SURG. RESULTS: From 2003 to 2010, 151 patients had NeoCRT (n = 48; 31.8%) or SURG (n = 103; 68.1%). Histology was mostly adenocarcinoma (77.5%) or squamous carcinoma (19.2%). Mean radiation dose was 44 ± 0.1 Gy, and 80.8% received platinum-based doublet chemotherapy. There were more women in the SURG group (23.3% vs 4.2%; p < 0.01) and more cardiovascular comorbidity in the NeoCRT group (39.6% vs 21.4%; p = 0.027). There was no difference in age, histology, R0 resection rate, and treatment-related mortality (NeoCRT = 4.2%; SURG = 3.9%; p = 0.15). Failure to undergo resection after NeoCRT (n = 11; 22.9%) was mainly due to disease progression (n = 6) or treatment-related mortality (n = 4). Resection could not be performed in 4 SURG patients (3.9%; p < 0.001; unresectable = 2; occult metastases = 2). NeoCRT did not improve median survival (NeoCRT = 29 ± 6; SURG = 26 ± 3 months; p = 0.376) or recurrence-free interval (NeoCRT = 25.8 ± 5; SURG = 19.4 ± 2 months; p = 0.19). Complete pathologic response (n = 8; 21.6%) was not associated with improved survival. If we exclude from analysis NeoCRT patients who did not undergo surgery, survival was significantly improved after NeoCRT (NeoCRT = 41 ± 15; SURG = 24 ± 8 months; p = 0.0082). CONCLUSIONS: Patient selection and early assessment of treatment response may be key factors in identifying the best candidates for trimodality therapy.