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Background: More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs. Methods: This is a prospective, multicenter, open‐label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression‐free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator‐assessed PFS, liver‐specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. Discussion: This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs. [ABSTRACT FROM AUTHOR]

Background: To assess the frequency of patient‐reported outcomes (PROs) and non‐PROs in randomized controlled trials (RCTs) addressing head/neck cancers. Methods: We included RCTs about interventions to treat head/neck cancers. PubMed was searched on September 16, 2022 and included studies published during three periods (2000–2002, 2010–2012, and 2020–2022). Data on types of outcomes and instruments to measure them were extracted and organized into PROs and non‐PROs, and temporal trends for reporting outcomes were determined. Results: There was a reduction in the frequency of non‐PROs (40% to 22%) and an increase in PROs (5% to 19%) over 20 years. The frequency of reporting both non‐PROs and PROs seemed to be stable over the same period (55% to 58%). A great variety of instruments to measure PROs and non‐PROs was identified. Conclusions: There has been a growth in the types of PROs in more recent years, and they were more frequently reported in RCTs. However, head/neck cancer trials with a combination of PROs and non‐PROs were the most prevalent. [ABSTRACT FROM AUTHOR]

Background: Early palliative care (EPC) improves the quality of life but may not be feasible for all patients with advanced cancer. Symptom screening has been suggested to triage patients for EPC, but scant evidence exists for this practice. Methods: We conducted a subgroup analysis of a cluster‐randomized controlled trial of EPC vs. standard oncology care according to patients' baseline symptom scores (high [>23] vs. low [≤23] Edmonton Symptom Assessment System Distress Score [ESAS SDS]). A linear mixed‐effects model was used to account for correlation within clusters, adjusting for the baseline outcome score and all covariates in the original trial. Results: Among the 461 participants, baseline symptom scores were high in 229 patients (127 intervention, 102 control) and low in 232 (101 intervention and 131 control). Among those with high baseline symptoms, there was improved quality of life in the EPC arm compared to controls at 4 months (adjusted difference in primary outcome of FACIT‐Sp change score [95% CI], 8.7 [2.8 to 14.5], p = 0.01; adjusted difference in QUAL‐E, 4.2 [0.9–7.5], p = 0.02); there was also improved satisfaction with care (6.9 [3.8–9.9], p = 0.001) and clinician‐patient interactions (−1.7 [−3.4 to −0.1], p = 0.04), but no significant difference in ESAS SDS (−5.6 [−12.7 to 1.4], p = 0.11). In the low baseline symptom group, there were no significant differences between arms for any outcomes. Conclusion: EPC improved quality of life, satisfaction with care, and clinician‐patient interactions only in those with high baseline symptoms. Symptom severity may be an appropriate criterion to trigger early referrals to palliative care. [ABSTRACT FROM AUTHOR]

Cancer‐related fatigue (CRF) is one of the most common chronic symptoms experienced by cancer patients. As moxibustion is a popular traditional therapy for managing fatigue, it can be an alternative strategy to treat CRF as well. Therefore, we rigorously designed a full‐scale, multicenter, assessor‐blinded, randomized controlled trial to evaluate the efficacy and safety of moxibustion treatment for CRF. Ninety‐six subjects suffering from CRF were recruited and randomly assigned to moxibustion group, sham moxibustion group, or usual care group. Both the moxibustion group and the sham group received moxibustion treatment for 8 weeks and the usual care group did not. Brief fatigue inventory (BFI) score and Functional Assessment of Cancer Therapy‐Fatigue score were used to assess CRF at baseline and weeks 5, 9, and 13. Questionnaires for the assessment of cognitive impairment, quality of life, and Cold–Heat and Deficiency–Excess patterns were also evaluated. BFI scores significantly decreased in moxibustion group compared to the usual care group (mean difference of −1.92, p < 0.001 at week 9 and mean difference of −2.36, p < 0.001 at week 13). Although the sham group also showed significant improvement during the treatment period, only the moxibustion group showed improvement after 4 weeks of follow‐up period (mean difference of −1.06, p < 0.001). There were no serious adverse events. Our findings confirmed the efficacy and safety of moxibustion for CRF compared to usual care. We also found that moxibustion has a prolonged treatment effect during 4 weeks of follow‐up period. [ABSTRACT FROM AUTHOR]

Background: Missing patient reported outcomes data threaten the validity of PRO‐specific findings and conclusions from randomized controlled trials by introducing bias due to data missing not at random. Clinical Research Associates are a largely unexplored source for informing understanding of potential causes of missing PRO data. The purpose of this qualitative research was to describe factors that influence missing PRO data, as revealed through the lived experience of CRAs. Methods: Maximum variation sampling was used to select CRAs having a range of experiences with missing PRO data from academic or nonacademic centers in different geographic locations of Canada. Semistructured interviews were audio‐recorded, transcribed verbatim, and analyzed according to descriptive phenomenology. Results: Eleven CRAs were interviewed. Analysis revealed several factors that influence missing PRO data that were organized within themes. PROs for routine clinical care compete with PROs for RCTs. Both the paper and electronic formats have benefits and drawbacks. Missing PRO data are influenced by characteristics of the instruments and of the patients. Assessment of PROs at progression of disease is particularly difficult. Deficiencies in center research infrastructure can contribute. CRAs develop relationships with patients that may help reduce missing PRO data. It is not always possible to provide sufficient time to complete the instrument. There is a need for field guidance and a motivation among CRAs to contribute their knowledge to address issues. Conclusion: These results enhance understanding of factors influencing missing PRO data and have important implications for designing operational solutions to improve data quality on cancer RCTs. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide a comprehensive evaluation of the impact of angiogenic inhibitors on SCLC survival using network meta‐analysis. Methods: The impact of five angiogenesis inhibitors, that is, vandetanib (Van), bevacizumab (Bev), Rh‐endostatin (End), sunitinib (Sun), and thalidomide (Tha), on progression‐free survival (PFS) and overall survival (OS) was evaluated by conducting a network meta‐analysis. RNA sequencing data were downloaded from publicly available databases. Results: Nine phase II and III randomized controlled trials (RCTs), that involved 1599 participants, that investigated angiogenesis inhibitors in the treatment of SCLC were included in this meta‐analysis. Sun and Bev achieved better PFS than Tha (Bev VS. Tha, HR = 0.88, 95% CI: 0.79‐0.98, Sun VS. Tha, HR = 0.80, 95% CI: 0.65‐1.00). Moreover, Sun and Bev were superior to placebo in terms of PFS (Bev VS. Placebo, HR = 0.89, 95%CI: 0.81‐0.97, Sun VS. Placebo, HR = 0.81, 95% CI: 0.66‐1.00). Based on this study, we found no significant difference of OS of SCLC. The angiogenesis pathway and expression of target genes were globally deactivated in SCLC tissue. Conclusion: Results of this network meta‐analysis indicate that the PFS outcome of SCLC with Sun or Bev drugs is superior to that of Tha. The improved therapeutic impact of angiogenesis inhibitors on SCLC needs more evidence, such as long‐term observation in clinical trials, to be validated. [ABSTRACT FROM AUTHOR]

Abstract: This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. Systematic online searches were performed in PubMed, Web of Sciences, China Knowledge Infrastructure and Weipu from the inception to November 15, 2017. Potential studies were assessed using the Cochrane risk of bias scale. Statistical analyses were performed on Stata 14.0 and RevMan 5.3. Finally, twelve studies entered final qualitative synthesis and quantitative analysis. The GP regimen compared with the FP regimen had significantly higher 1‐year survival rate (relative risk (RR) = 1.07, 95% confidence interval (CI): 1.01‐1.13), significantly better performance in the fixed‐effect model (RR = 1.16, 95%CI: 1.04‐1.30) and significantly higher remission rate (RR = 1.17, 95%CI: 1.05‐1.29). Significant differences between regimens were found in gastrointestinal effects (RR = 0.58, 95%CI: 0.45‐0.74). No significant differences between regimens were found in reduced hemoglobin rate (RR = 0.55, 95%CI: 0.36‐1.21), neutropenia (RR = 1.84, 95%CI: 0.93‐5.02), or reduced platelet (RR = 1.25, 95%CI: 0.85‐1.75) and mucosal inflammation (RR = 0.81, 95%CI: 0.57‐1.16). Sensitivity analysis indicated the results remained stable. The funnel plot indicated some publication bias. In conclusion, the GP regimen outperforms the FP regimen in treatment of advanced nasopharyngeal carcinoma with no difference in adverse effects. We may consider the GP regimen a better choice, but this conclusion should be confirmed by high‐quality trials. [ABSTRACT FROM AUTHOR]

The objective of this review was to analyze trends in outcomes and in the quality of phase III randomized controlled trials on advanced NSCLC published between 2000 and 2012, selecting 76 trials from a total of 122 retrieved in a structured search. Over the study period, the number of randomized patients per trial increased by 14 per year ( P = 0.178). The sample size significantly increased between 2000 and 2012 in trials of targeted agents (460.1 vs. 740.8 patients, P = 0.009), trials of >1 drug (360.4 vs. 584.8, P = 0.014), and those including patients with good performance status (675.3 vs. 425.6; P = 0.003). Quality of life was assessed in 46 trials (60.5%), and significant improvements were reported in 10 of these (21.7%). Platinum-based regimens were the most frequently investigated (86.8% of trials). Molecular-targeted agents were studied in 25.0% of chemotherapy arms, and the percentage of trials including these agents increased each year. The median (interquartile range) overall survival ( MOS) was 9.90 (3.5) months with an increase of 0.384 months per year of publication ( P < 0.001). A statistically significant improvement in MOS was obtained in only 13 (18.8%) trials. The median progression-free survival was 4.9 (1.9) months, with a nonsignificant increase of 0.026 months per year ( P > 0.05). There has been a continuous but modest improvement in the survival of patients with advanced NSCLC over the past 12 years. Nevertheless, the quality of clinical trials and the benefit in outcomes should be carefully considered before the incorporation of novel approaches into clinical practice. [ABSTRACT FROM AUTHOR]

The mechanisms whereby regular exercise reduces chronic inflammation remain unclear. We investigated whether regular aerobic exercise alters basal levels of interleukin ( IL)-10 and IL-4 in two randomized trials of physical activity. The Alberta Physical Activity and Breast Cancer Prevention Trial ( ALPHA, n = 320) and the Breast Cancer and Exercise Trial in Alberta ( BETA, n = 400) were two-center, two-armed randomized trials in inactive, healthy, postmenopausal women. Both trials included an exercise intervention prescribed five times/week and no dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus no activity in the controls. BETA examined dose-response effects comparing 300 ( HIGH) versus 150 ( MODERATE) min/week. Plasma concentrations of IL-10 and IL-4 were measured at baseline, 6, and 12 months. Intention-to-treat ( ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. Circulating anti-inflammatory cytokine levels decreased among all groups, with percent change ranging from −3.4% (controls) to −8.2% ( HIGH) for IL-4 and −1.6% (controls) to −7.5% ( HIGH) for IL-10. No significant group differences were found for IL-4 (ALPHA P = 0.54; BETA P = 0.32) or IL-10 ( ALPHA P = 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by baseline characteristics was found for IL-10 but not for IL-4. Results from these two large randomized aerobic exercise intervention trials suggest that aerobic exercise does not alter IL-10 or IL-4 in a manner consistent with chronic disease and cancer prevention. [ABSTRACT FROM AUTHOR]