In a multicenter study, we determined the expression profiles of 863 microRNAs by array analysis of 454 blood samples from human individuals with different cancers or noncancer diseases, and validated this 'miRNome' by quantitative real-time PCR. We detected consistently deregulated profiles for all tested diseases; pathway analysis confirmed disease association of the respective microRNAs. We observed significant correlations (P = 0.004) between the genomic location of disease-associated genetic variants and deregulated microRNAs.
ancreatic cancer is characterized by aggressive tumor growth with early metastases (1, 2). Further, cancer cachexia and sarcopenia are both ubiquitous characteristics which limit the ability to perform daily activities, compromise patients' quality of life (QoL), and have been associated with poor overall survival (3,4). Therefore, preservation of physical functioning and health-related QoL are the main treatment goals of supportive cancer care.Patient QoLvaries significantly depending on stage of disease and treatment phase. Thus, patients in a metastatic disease situation were found to have a lower QoL compared to surgically treated patients (5). Furthermore, patients shortly after surgery have a lower QoL than patients at two months after surgery SummaryBackground: Improving quality of life (QoL) is an important treatment goal in pancreatic cancer patients. Although the beneficial effects of exercise on QoL are well understood, few studies have investigated more aggressive cancers such as pancreatic cancer.Methods: Within a randomized trial, we assessed the efficacy of 6-month resistance training on physical functioning (primary outcome) and further QoL-related outcomes. 65 pancreatic cancer patients were assigned to home-based training, supervised training, or a usual care control group. Analysis-of-covariance models on changes from baseline to 6 and 3 months were applied.Results: 47 patients completed the intervention period. After 6 months, no effects of resistance training were observed. However, after 3 months, explorative analyses showed significant between-group mean differences (MD) in favor for resistance training for physical functioning (pooled group: MD=11.0; p=0.016; effect size[ES]=0.31), as well as for global QoL (MD=12.1; p=0.016; effect size=0.56), and other outcomes, such as sleep problems and fatigue. Multiple imputation analyses yielded similar results. Home-based and supervised training performed similarly. Conclusion:This first randomized resistance training trial in pancreatic cancer patients indicated clinically relevant improvements in QoL after 3 but not after 6 months. Given the severity of pancreatic cancer, exercise recommendations may already commence at surgery.
4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P<0.001. 9 out of the 51 neoadjuvant patients included in the safety set reported 12 serious adverse events of grade 3 or above. Conclusions: There was no difference in resection rate between arms, however neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Clinical trial information: 89500674 .
Objectives Maintaining or improving muscle mass and muscle strength is an important treatment goal in pancreatic cancer (PC) patients because of high risk of cachexia. Therefore, we assessed feasibility and effectivity of a 6-month progressive resistance training (RT) in PC patients within a randomized controlled trial. Methods Sixty-five PC patients were randomly assigned to either supervised progressive RT (RT1), home-based RT (RT2), or usual care control group (CON). Both exercise groups performed training 2 times per week for 6 months. Muscle strength for knee, elbow, and hip extensors and flexors and cardiorespiratory fitness and body weight were assessed before and after the intervention period. Results Of 65 patients, 43 patients were analyzed. Adherence rates were 64.1% (RT1) and 78.4% (RT2) of the prescribed training sessions. RT1 showed significant improvements in elbow flexor/extensor muscle strength and in maximal work load versus CON and RT2 (P < 0.05). Further, knee extensors were significantly improved for RT1 versus CON (P < 0.05). Body weight revealed no significant group differences over time. Conclusions Progressive RT was feasible in PC patients and improved muscle strength with significant results for some muscle groups. Supervised RT seemed to be more effective than home-based RT.
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