PURPOSE:To explore the cancer-related fatigue(CRF) trajectories and their predictors of gastric cancer patients undergoing 6-cycle chemotherapy, and to identify subgroup characteristics of patients with different CRF trajectories. METHODS:A prospective longitudinal study was conducted between November 2020 and December 2021, involving 189 first-time chemotherapy gastric cancer patients at a tertiary general hospital in Chengdu, Sichuan Province, China. Data were collected 7 times within 6 chemotherapy cycles (before the first cycle(T0), and within 1 week after the end of each cycle (T1∼T6)).The CRF level was assessed by the Cancer Fatigue Scale. Growth mixture modeling was used to identify the latent classes of CRF trajectories. Group differences analyses were performed to determine characteristics of patients with different CRF trajectories, and multivariate regression analysis was adopted to identify predictors of CRF trajectories. RESULTS:The overall CRF level increased over time, with the greatest change from T0 to T1. Three CRF trajectories were identified: the acute fatigue group(Class1:23.8 %), the low fatigue group(Class2:59.8 %), and the gradually worsening fatigue group(Class3:16.4 %). Patients with pain or depression were more likely to be in the acute fatigue group, and female were more likely to be in the gradually worsening fatigue group, compared with the low fatigue group. CONCLUSIONS:The overall CRF trajectory and three sub-trajectories were identified. Patients with pain, depression, and being female are prone to CRF deterioration. Since CRF level increases fastest from T0 to T1, early prevention and management of CRF should be implemented in gastric cancer patients undergoing chemotherapy.

Background Family caregivers play a crucial caregiving role for colorectal cancer patients undergoing chemotherapy, and the emotional states of both patients and caregivers can influence each other. A high prevalence of depression and anxiety exists among both patients and caregivers, with their emotional states mutually influencing each other. This significantly impacts the quality of life for both parties. However, there is limited research on the bidirectional relationship between depression and anxiety in both groups. Objective This study aims to investigate the longitudinal bidirectional relationship between depression and anxiety in colorectal cancer patients and their family caregivers using a cross-lagged panel model. Method A total of 244 pairs of colorectal cancer patients undergoing chemotherapy and their family caregivers were assessed using the Hospital Anxiety and Depression Scale. Data collection was conducted at four time points: the initial chemotherapy session and 1-, 3-, and 6- months post-chemotherapy. A cross-lagged panel model was employed to analyze the longitudinal interrelationship between depression and anxiety within and between the two groups. Result The study found high prevalence rates of depression and anxiety in both colorectal cancer patients and their caregivers. The cross-lagged model revealed a dynamic, bidirectional relationship between depression and anxiety in patients and caregivers from the second wave onwards ( P < 0.05). Conclusion The emotional states of depression and anxiety in colorectal cancer patients and their caregivers show dynamic changes and are longitudinally interrelated. These findings underscore the importance of early psychological assessment and interventions targeting both patients and caregivers.

BackgroundRadiotherapy is an effective curative treatment option for intermediate- to high-risk localized prostate cancer. According to the HYPO-RT-PC trial (ISRCTN45905321), there was no significant difference in 5 years of follow-up in terms of failure-free survival, overall survival, urinary toxicity, and bowel toxicity, while erectile function decreased between ultra-hypofractionated radiotherapy with conventionally fractionated radiotherapy, except that the incidence of urinary toxicity in ultra-hypofractionated radiotherapy was higher at 1 year of follow-up. We evaluated the cost-effectiveness of ultra-hypofractionated radiotherapy and conventionally fractionated radiotherapy for intermediate- to high-risk localized prostate cancer from the Chinese payer's perspective. MethodsWe developed a Markov model with a 15-year time horizon to compare the cost and effectiveness of ultra-hypofractionated radiotherapy with those of conventionally fractionated radiotherapy for localized intermediate- to high-risk prostate cancer. The outcomes were measured in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and willingness-to-pay (WTP). Univariable and probability sensitivity analyses were performed to evaluate the robustness of the Markov model. ResultsBased on the Markov model, conventionally fractionated radiotherapy yielded 2.32 QALYs compared with 2.14 QALYs in ultra-hypofractionated radiotherapy in China. The cost of ultra-hypofractionated radiotherapy was found to be decreased by about 14% folds ($4,251.04) in comparison with that of conventionally fractionated radiotherapy. The ICER of conventionally fractionated radiotherapy versus that of ultra-hypofractionated radiotherapy was $23,616.89 per QALY in China. The failure-free survival with grade 2 or worse urinary toxicity and the discount rate per annum were the most sensitive parameters utilized in ultra-hypofractionated radiotherapy. The cost-effectiveness acceptability curve showed that conventionally fractionated radiotherapy had 57.7% probability of being cost-effective under the Chinese WTP threshold. ConclusionFrom the perspective of Chinese payers, ultra-hypofractionated radiotherapy was not a cost-effective strategy compared with conventionally fractionated radiotherapy for patients with localized intermediate- to high-risk prostate cancer. Nevertheless, reduction of the grade 2 or worse urinary toxicity of ultra-hypofractionated radiotherapy could alter the results.

Introduction The type of extended adjuvant endocrine therapy is not clear, nor is the optimum duration of extended adjuvant endocrine therapy for patients with early breast cancer. Our study aims to satisfy the requirements for systematically identifying and synthesising the available evidence on the clinical safety and efficacy of extended adjuvant endocrine therapy for patients with hormone receptor-positive early breast cancer. Methods and analysis A comprehensive electronic literature database search will be performed using three electronic databases: PubMed, Cochrane Library and Embase (Ovid interface). Our main outcomes of interest were overall survival, disease-free survival, relapse-free survival, invasive contralateral breast cancer, acceptability and grades 3 and 4 non-haematological toxicities in this study. We will assess the risk of bias and overall quality of evidence using the Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation, respectively. We will perform subgroup and sensitivity analyses in the selected trials. We will assess the three key assumptions of network meta-analysis: transitivity, consistency and homogeneity. Ethics and dissemination The protocol was preregistered in the International Prospective Register of Systematic Reviews (PROSPERO) database. Ethics approval and patient consent are not required for the network meta-analysis. The final results of this network meta-analysis will be disseminated through national and international conferences and published in a peer-reviewed journal. PROSPERO registration number CRD42021278271.

Abstract Background: Radiotherapy is an effective curative treatment option for intermediate-to-high-risk localized prostate cancer. Given that no significant difference was observed in survival and toxicities, we evaluated the cost-effectiveness of ultra-hypofractionated radiotherapy and conventionally fractionated radiotherapy for intermediate-to-high-risk localized prostate cancer from the Chinese payer perspective.Methods: We developed a Markov model with a 15-year time horizon to compare the cost and effectiveness of ultra-hypofractionated radiotherapy with those of conventionally fractionated radiotherapy for localized intermediate-to-high-risk prostate cancer. Outcomes were measured in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and willingness-to-pay (WTP). Univariable and probability sensitivity analyses were performed to evaluate the robustness of the Markov model.Results: Based on the results of our Markov model, the conventionally fractionated radiotherapy yielded 2.32 QALYs compared with 2.14 QALYs in the ultra-hypofractionated radiotherapy in China. The cost of ultra-hypofractionated radiotherapy was found to be decreased by about 14% folds ($4251.04) in comparison to that of conventionally fractionated radiotherapy. The ICER of conventionally fractionated radiotherapy vs the ultra-hypofractionated radiotherapy was $23,616.89 per QALY in China. The most sensitive parameters were the ultra-hypofractionated radiotherapy utility of failure-free survival (FFS) with grade two or worse urinary toxicity and discount rate per annum. The cost effectiveness acceptability curve showed that conventionally fractionated radiotherapy had a 57.7% probability of being cost-effective at the Chinese WTP threshold.Conclusion: The ultra-hypofractionated radiotherapy was not a cost-effective strategy compared with conventionally fractionated radiotherapy in patients with localized intermediate-to-high-risk prostate cancer from the perspective of the Chinese payers. However, steep reductions in the grade two or worse urinary toxicity of the ultra-hypofractionated radiotherapy could alter the results.

INTRODUCTION:It is currently unclear which cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, combined with endocrine therapy, is the preferred treatment approach in patients with hormone receptor (HR)-positive, human epidermal receptor-2 (HER2) negative metastatic breast cancer. The aim of this study was to evaluate the existing evidence for the comparative efficacy, safety and cost-effectiveness of different CDK4/6 inhibitors for metastatic breast cancer in first-line and second-line settings. METHODS AND ANALYSIS:We will systematically conduct a literature search in Embase, PubMed and the Cochrane Library and additional searches by handsearching citations of previous systematic reviews. We will also screen major conference proceedings (American Society of Clinical Oncology, European Society of Medical Oncology and San Antonio Breast Cancer Symposium). Preliminary scoping searches were conducted in July 2021, but the search will be updated when new trials are available. The primary outcome was progression-free survival. The secondary outcomes were overall survival, objective response rates, grade 3-4 haematological and non-haematological toxicities, quality-adjusted life years and incremental cost-effectiveness ratios. The risk of bias will be assessed by Cochrane risk of bias tools, and the quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation. Subgroup analyses and sensitivity analyses will be performed to further confirm our findings. In addition, one-way sensitivity analysis and probabilistic sensitivity analyses will be conducted to determine uncertainty. ETHICS AND DISSEMINATION:This study does not require ethics approval as only secondary data will be collected. The results of our study will provide an overview of the current level of CDK4/6 inhibitors for patients with HR-positive, HER2-negative metastatic breast cancer, and undertake subgroup analyses to explore variables that might affect these effects. The results of this study will be presented at an international clinical conference and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER:CRD42021266597.

Background : The optimal management strategy for patients with left-sided obstructive colon cancer remains unclear. The aim of this study is to compare the efficacy and safety of emergency resection (ER), self-expanding metallic stents (SEMS) and decompressing stoma (DS) for left-sided obstructive colon cancer. Methods : Electronic searches by titles/abstracts of ER, SEMS and DS for left-sided obstructive colon cancer will be performed using the following electronic bibliographic databases: PubMed, Cochrane Library, Embase and clinical trials. The protocol of this network meta-analysis has been registered on PROSPERO (CRD42021243097). The primary outcomes are the oncological outcomes such as local recurrence rate and overall and disease-free survival. Secondary outcomes of this study include peri- and postoperative outcomes, successful primary anastomosis, temporal and permanent stoma. Included randomized controlled trials will be evaluated on their risk of bias with the Cochrane Collaboration’s risk of bias tool. The quality of observation studies will be assessed using Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. The overall quality of the evidence will be judged based on Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in the network meta-analysis. Heterogeneity, publication bias, subgroup analysis and sensitivity analysis will be explored. Discussion : Considering the importance of acute intestinal obstruction in left-sided colon cancer, we hope that this network meta-analysis can aid and accelerate the consolidation of evidence, such that health-care professionals and patients are provided with high-quality evidence to facilitate decisions on how to manage patients with left-sided obstructive colon cancer. We will conduct subgroup and sensitive analysis to determine the potentially appropriate population for either ER or a bridge to surgery (SEMS or DS) and provide a foundation for future studies from our network meta-analysis.

Background: This is an updated meta-analysis comparing the postoperative complications observed with robotic versus laparoscopic surgery (LS) for the treatment of rectal cancer. Methods: Cochrane central, MEDLNE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica dataBASE), Google Scholar, Web of Science and were searched for studies (published after the year 2015), comparing robotic versus LS for the treatment of rectal cancer. The postoperative outcomes were considered as the endpoints in this analysis. RevMan 5.4 was used to carry out the statistical analysis. Risk ratio (RR) with 95% confidence intervals (CI) were used to represent the results following data analysis. Results A total number of 22,744 participants were included in this study whereby 9178 participants were assigned to the robotic surgery and 13,566 participants were assigned to the LS group. The time period of patients' enrollment varied from years 2007 to 2017. Our results showed that overall complications (RR: 0.91, 95% CI: 0.71-1.17; P = .45), wound complications (RR: 0.81, 95% CI: 0.64-1.04; P = .09), anastomotic leak (RR: 1.12, 95% CI: 0.88-1.42; P = .37), anastomotic bleeding (RR: 0.88, 95% CI: 0.29-2.64; P = .82), stoma-related complications (RR: 0.88, 95% CI: 0.24-3.21; P = .85), intra-abdominal abscess (RR: 0.53. 95% CI: 0.22-1.31; P = .17), urinary tract infection (RR: 0.94, 95% CI: 0.53-1.66; P = .83), enterocolitis (RR: 1.35, 95% CI: 0.38-4.71; P = .64), reoperation (RR: 0.85, 95% CI: 0.46-1.54; P = .58), and mortality (RR: 0.75, 95% CI: 0.34-1.62; P = .46) were not significantly different between robotic-assisted versus LS for rectal cancer. Postoperative ileus (RR: 1.21, 95% CI: 0.81-1.81; P = .34), readmission (RR: 1.17, 95% CI: 0.75-1.83; P = .48), and urinary retention (RR: 0.51, 95% CI: 0.21-1.23; P = .14) were also similarly manifested. Conclusions: In this updated meta-analysis, both robotic and laparoscopic surgeries were equally effective for the treatment of rectal cancer. Similar postoperative complications were observed. However, our analysis was restricted only to postoperative outcomes, parameters such as duration of surgery were not taken into consideration.

Background: Identifying the genes and signaling pathways related to chemoresistance might facilitate the development of novel therapeutic strategies for colon cancer. In this study, we aimed to investigate the biological functions and underlying mechanisms of action of miR-19b and NR3C1, as well as their effects on chemosensitivity to oxaliplatin and prognosis of colon cancer patients. Methods: Reverse transcription–polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining were used to analyze the expression of miR-19b and NR3C1. Dual firefly luciferase reporter gene analysis was used to identify miR-19b target genes. Associations of miR-19b and NR3C1 with survival were estimated by the Kaplan–Meier method and Cox regression analyses. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis were used to measure cell viability, cytotoxicity, cell cycle phase, and apoptosis, respectively. The effect of miR-19b on cell proliferation was investigated in vivo. Results: The miR-19b was overexpressed and NR3C1 was decreased in colon cancer tissue and cell lines (SW480 and DLD-1). The miR-19b inhibition and NR3C1 overexpression inhibited cell proliferation, and induced G1/S cell cycle blockade, apoptosis, and chemosensitivity to oxaliplatin in vitro. The miR-19b inhibition suppressed subcutaneous tumorigenesis in vivo. Increased miR-19b and decreased NR3C1 in colon cancer were correlated with poor prognosis. In addition, our results confirmed NR3C1 was directly targeted by miR-19b. Thus, miR-19b might inhibit apoptosis and enhance oxaliplatin chemoresistance via the PI3K/AKT/mTOR pathway. Conclusions: Our study revealed that miR-19b promotes cell survival and chemoresistance to oxaliplatin via the PI3K/AKT/mTOR pathway by downregulating NR3C1 in colon cancer. miR-19b and NR3C1 might be potential intervention targets for chemoresistance of colon cancer.

Purpose: High rate of perineal surgical site infection (SSI) is the most common complication following abdominoperineal resection (APR), especially for extralevator abdominoperineal excision (ELAPE). The purpose of this study was to investigate the effect of continuous negative pressure drainage combined with intermittent irrigation (CNPDCII) in the presacral space on the perineal SSI following laparoscopic ELAPE for low rectal cancer. Patients and Methods: The clinical data of 99 patients with low rectal cancer who underwent laparoscopic ELAPE surgery were retrospectively analyzed. Among the 99 patients, 46 patients received CNPDCII and 53 patients received conventional drainage in the presacral space after ELAPE. Self-made irrigation drainage tube: took a silicone drainage tube, cut 3 side holes at every 2cm intervals at the front end, and fixed a flexible tube of an intravenous needle at the front end of the silicone drainage tube. The conventional drainage tube or self-made irrigation drainage tube was placed in the presacral space and poked out from the inside of the ischial tuberosity. The incidence of SSI and other perioperative indicators between the two groups was compared within 30 days after surgery. Results: There was no statistical difference in clinicopathological features between the two groups of patients (p>0.05). A statistically lower rate of SSI was found in CNPDCII group (17.4%, 8/46) than the conventional drainage group (35.8%, 19/53). The drainage tube retention time (7.8 +/- 1.2 d VS 9.4 +/- 1.6 d) and the postoperative hospital stay (9.7 +/- 1.4 d VS 11.9 +/- 2.3 d) in CNPDCII group were significantly shortened than the conventional drainage group. There was no statistical difference in operating theatre time and intraoperative blood loss between the two groups. Multivariate analysis confirmed that CNPDCII was an independent protective factor for SSI after ELAPE. Conclusion: CNPDCII can effectively reduce the incidence of SSI following laparoscopic ELAPE, which is simple, safe and effective.

Introduction Controversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers. Methods and analysis Electronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA. Ethics and dissemination Ethics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports. Trial registration number CRD42019139109.

Introduction Different maintenance strategies have shown efficacy in patients with advanced ovarian cancer, but without drawing any conclusion on which strategy is preferred. Therefore, we will conduct a network meta-analysis and cost-effectiveness analysis to investigate maintenance strategies containing chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and anti-angiogenesis therapy for patients with advanced ovarian cancer. Methods and analysis The search strategy to identify potentially relevant studies will include hand searches in EMBASE, PubMed, Cochrane library and Web of science. The primary outcome is progression-free survival, defined as the date of randomisation to the date of progression or death. The secondary outcome is overall survival (calculated from the time from randomisation to death from any cause), grade 3–4 haematological and non-haematological toxicities, quality-adjusted life years and incremental cost-effectiveness ratios. Two steps of meta-analysis will be carried out, traditional pair-wise meta-analysis and network meta-analysis. Methodological quality, risk of bias and the strength of evidence from randomised controlled trials (RCTs) will be proposed to assess the quality of RCTs. Heterogeneity, publication bias, subgroup analysis and sensitivity analysis will be explored. Ethics and dissemination The purpose of our study is to perform a comprehensive efficacy, safety and cost-effectiveness analysis of all maintenance strategies in patients with advanced ovarian cancer. The results will be disseminated through international conference reports and peer-reviewed manuscripts. Ethics approval is not required for network meta-analysis and cost-effectiveness analysis. PROSPERO registration number CRD42021231814.

microRNA-190b (miR-190b) is abnormally expressed in multiple types of cancer, however, its role in colorectal cancer (CRC) is largely unknown. In the present study, it was demonstrated that miR-190b expression was upregulated in CRC cell lines compared with the normal epithelial colon cell line. Knockdown of miR-190b decreased proliferation, colony formation and invasion, and increased apoptosis of CRC cells. Furthermore, forkhead box protein P2 (FOXP2) was predicted as a target of miR-190b and further validated by luciferase activity reporter assay and western blotting. Rescue experiments showed that knockdown of FOXP2 reversed the inhibitory effects of miR-190b inhibitor on the behavior of the CRC cell lines. Taken together, the present study demonstrated the oncogenic role of miR-190b in CRC through regulation of FOXP2 expression.