辛伐他汀用于结直肠癌治疗的系统综述

“药物再利用”或“药物再定位”是肿瘤学领域热度上升的话题,指寻找某种适应症并非癌症却具有抗癌活性的上市药物,并将其与常规癌症治疗手段相结合以期为患者带来生存获益。辛伐他汀,临床常用于治疗高脂血症、预防心血管疾病,研究发现其用于结直肠癌治疗潜力巨大,已有不少临床研究尝试将辛伐他汀作为辅助用药治疗转移性结直肠癌。     

Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review

BackgroundThe optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear.Materials and methodsWe systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes.ResultsThe search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy.ConclusionsThese findings support the introduction of an approved agent such as trifluridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second-line treatment.     

结直肠癌患者的营养治疗专家共识

结直肠癌是常见肿瘤之一,结直肠癌患者经常出现营养不良和体重丢失,受摄入减少、肠梗阻和吸收不良的影响, 营养不良在结直肠癌患者中比在非胃肠道肿瘤中更常见。 结直肠癌患者应通过营养风险筛查 2002(NRS 2002)与患者主观整 体评估(PG-SGA)进行营养评估。 欧洲肠外肠内营养学会(ESPEN)强烈推荐对于所有接受根治性或姑息性手术的肿瘤患者 采取加速康复外科(ERAS)方案。 ERAS 可降低结直肠手术后的并发症发生率、促进康复和缩短住院时间。 在 ERAS 方案中, ESPEN 推荐每例患者都应进行营养风险筛查,如果存在营养风险,则给予额外的营养治疗;严重营养不良的患者,术前应进行 10~ 14 d 的营养干预,甚至以延迟手术为代价。 不同手术方式的选择会对结直肠癌患者的术后并发症发生率、病死率与 3 年 长期存活率等方面产生不同的影响。 临床医师应关注患者出院后的营养状态,合理进行营养干预,有计划地对出院时存在营 养风险的患者进行随诊。     

Long-term prognostic value of preoperative anemia in patients with colorectal cancer: A systematic review and meta-analysis

Objective

To evaluate the long-term prognostic factor of preoperative anemia in colorectal cancer patients.

Prognostic models for outcome following liver resection for colorectal cancer metastases: A systematic review

Background

Liver resection provides the best chance for cure in colorectal cancer (CRC) liver metastases. A variety of factors that might influence survival and recurrence have been identified. Predictive models can help in risk stratification, to determine multidisciplinary treatment and follow-up for individual patients.

Aims

To systematically review available prognostic models described for outcome following resection of CRC liver metastases and to assess their differences and applicability.

Methods

The Pubmed, Embase and Cochrane Library databases were searched for articles proposing a prognostic model or risk stratification system for resection of CRC liver metastases. Search terms included ‘colorectal’, ‘liver’, ‘metastasis’, ‘resection’, ‘prognosis’ and ‘prediction’. The articles were systematically reviewed.

Results

Fifteen prognostic systems were identified, published between 1996 and 2009. The median study population was 305 patients and the median follow-up was 32 months. All studies used Cox proportional hazards for multi-variable analysis. No prognostic factor was common in all models, though there was a tendency towards the number of metastases, CRC spread to lymph nodes, maximum size of metastases, preoperative CEA level and extrahepatic spread as representing independent risk factors. Seven models assigned more weight to selected factors considered of higher predictive value.

Conclusion

The existing predictive models are diverse and their prognostic factors are often not weighed according to their impact. For the development of future predictive models, the complex relations within datasets and differences in relevance of individual factors should be taken into account, for example by using artificial neural networks.     

A systematic review of the relation between interleukin-2 schedule and outcome in patients with metastatic renal cell cancer

In Europe, interleukin 2 (IL-2) is one of the two treatment modalities officially approved for patients with metastatic renal cell cancer. Traditionally, IL-2 has been administered by three different routes: intermittent bolus injection (BIV), continuous intravenous infusion (CIV) and subcutaneous injection (SC). There have been few randomized trials designed to compare these routes of administration. This paper describes a systematic review of the literature in which an attempt has been made to determine which schedule of administration is superior. Heterogeneity of the data makes firm conclusions difficult. It appears that the number of complete remissions (CR) is similar between BIV and SC routes and that these are higher than for CIV schedules. The durability of the CRs induced by BIV appeared superior to those induced by SC IL-2 and definitely higher than with CIV protocols. This analysis highlights some of the difficulties of using evidence-based medicine to determine standard of care when the clinical-trial data are heterogeneous. These data emphasize the importance of randomized clinical trials in determining what should be regarded as optimum therapy.     

Smoking and survival of colorectal cancer patients: systematic review and meta-analysis

Smoking is a risk factor for colorectal cancer (CRC) incidence and mortality. However, little is known on smoking and its association with survival after CRC diagnosis. We conducted a systematic review and meta-analysis to summarize current evidence. A systematic literature search was carried out in MEDLINE and ISI Web of Science. We included studies that analyzed recurrence-free survival, disease-free survival, all-cause, and CRC-specific mortality according to smoking status. Data were extracted in duplicate. Standard methods of meta-analysis were applied. Sixteen studies from 11 countries were identified, comprising a total sample size of 62 278 CRC patients. Overall, in the 16 included studies, current smoking and, to a lesser extent, former smoking were rather consistently associated with a poorer prognosis compared with never smokers. Meta-analyses yielded random-effects hazard ratio estimates (95% confidence intervals) for all-cause mortality of 1.26 (1.15–1.37) and 1.11 (0.93–1.33) for current and former smokers, compared with never smokers, respectively. In particular, 30-day mortality was found to be increased by between 49% and 100% among current compared with never smokers. Our results support the existence of detrimental effects of smoking on survival also after CRC diagnosis. Perspectives for enhancing prognosis of CRC patients by smoking abstinence deserve increased attention in further research and clinical practice.     

Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review

BackgroundFluoropyrimidine-based chemotherapy is considered standard treatment of advanced colorectal cancer. Recent studies indicate benefit to the addition of bevacizumab, a recombinant monoclonal antibody targeting vascular endothelial growth factor.MethodsMedline, EMBASE, Cochrane Library, and conference proceedings were searched to identify randomized trials in advanced colorectal cancer comparing chemotherapy plus bevacizumab with chemotherapy alone. A meta-analysis of published data was carried out.ResultsFive trials comparing chemotherapy plus bevacizumab with chemotherapy alone as first- or second-line treatment were identified. Our meta-analysis indicates an advantage in favor of the addition of bevacizumab to chemotherapy in terms of overall survival (OS) [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.90; P = 0.0005], progression-free survival (PFS) (HR 0.63; 95% CI 0.49–0.81, P = 0.0004), and response rate (RR 1.50; 95% CI 1.06–2.10, P = 0.02). The most commonly observed adverse effects related to bevacizumab included hypertension, proteinuria, bleeding, and thrombosis. Gastrointestinal perforation and poor wound healing were also observed; however, their incidence was rare.ConclusionsFor patients with advanced colorectal cancer receiving first- or second-line fluoropyrimidine-based chemotherapy, the addition of bevacizumab improves PFS and OS at the expense of increased incidence of toxicity. The magnitude of benefit may differ based on the chemotherapy regimen with which bevacizumab is partnered.     

Surgical treatment of stage IV colorectal cancer with synchronous liver metastases: A systematic review and network meta-analysis

BackgroundThe ideal treatment approach for colorectal cancer (CRC) with synchronous liver metastases (SCRLM) remains debated. We performed a network meta-analysis (NMA) comparing the ‘bowel-first’ approach (BFA), simultaneous resection (SIM), and the ‘liver-first’ approach (LFA).MethodsA systematic search of comparative studies in CRC with SCRLM was undertaken using the Embase, PubMed, Web of Science, and CENTRAL databases. Outcome measures included postoperative complications, 30- and 90-day mortality, chemotherapy use, treatment completion rate, 3- and 5-year recurrence-free survival, and 3- and 5-year overall survival (OS). Pairwise and network meta-analysis were performed to compare strategies. Heterogeneity was assessed using the Higgins I² statistic.ResultsOne prospective and 43 retrospective studies reporting on 10 848 patients were included. Patients undergoing the LFA were more likely to have rectal primaries and a higher metastatic load. The SIM approach resulted in a higher risk of major morbidity and 30-day mortality. Compared to the BFA, the LFA more frequently resulted in failure to complete treatment as planned (34% versus 6%). Pairwise and network meta-analysis showed a similar 5-year OS between LFA and BFA and a more favorable 5-year OS after SIM compared to LFA (odds ratio 0.25–0.90, p = 0.02, I² = 0%), but not compared to BFA.ConclusionDespite a higher tumor load in LFA compared to BFA patients, survival was similar. A lower rate of treatment completion was observed with LFA. Uncertainty remains substantial due to imprecise estimates of treatment effects. In the absence of prospective trials, treatment of stage IV CRC patients should be individually tailored.     

Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer: A systematic review and pooled analysis

The last two decades have seen intensive efforts devoted to the development of compounds that target angiogenesis for the treatment of metastatic colorectal cancer (mCRC). In this review, we describe supporting evidence and ongoing development of angiogenesis inhibitors in the second-line treatment of mCRC, and summarize relevant randomized trials to help therapeutic decision-making in daily practice.     

血清超氧化物歧化酶和结直肠癌患者营养水平的关联性分析

目的:探讨血清超氧化物歧化酶（SOD）和结直肠癌患者营养水平的相关性。方法:选取2015年7月至2018年7月间,我院收治的结直肠癌患者120例和肠道息肉患者86例病例资料。比较两组患者血清SOD水平和总蛋白（TP）、白蛋白（ALB）、前白蛋白（PA)、血红蛋白（HGB）、淋巴细胞（LY）等营养指标,多因素分析结直肠癌患者营养水平下降的危险因素,并分析血清SOD水平与各营养指标之间的关系。结果:肠息肉组患者SOD、ALB、HGB、LY指标均明显高于结直肠癌组患者（P＜0.05）;结直肠癌NRS评分<3分的患者SOD、ALB、HGB指标均明显高于NRS评分=3分的患者（P＜0.05）;低SOD、低ALB、低HGB为结直肠癌患者营养状况下降的危险因素（P＜0.05）。相关分析显示,结直肠癌患者血清TP、ALB、PA、HGB、LY等指标与SOD水平均呈正相关（P＜0.05）。结论:结直肠癌患者血清SOD和营养状况明显下降,且疾病分期越晚下降幅度越大。患者营养状况与血清SOD水平呈正相关。     

Patients’ preferences for surgical and adjuvant systemic treatment in early breast cancer: A systematic review

Purpose

Treatment decisions in early breast cancer can revolve around type of surgery and whether or not to have adjuvant systemic therapy. This systematic review aims to give an overview of patient self-reported factors affecting preferences for breast conserving surgery (BCS) versus mastectomy (MAST), the minimal benefit patients require from adjuvant chemotherapy (aCT) and/or adjuvant hormonal therapy (aHT) to consider it worthwhile, and factors influencing this minimally-required benefit.

Methods

PubMed and EMBASE were searched for relevant articles. Two reviewers independently selected articles and extracted data.

Results

We identified 15 studies on surgical and six on adjuvant systemic treatment decision-making. Factors affecting patient preference for BCS most frequently related to body image (44%), while factors influencing preference for MAST most often related to survival/recurrence (46%). To make adjuvant systemic therapy worthwhile, the median required absolute increase in survival rate was 0.1–10% and the median required additional life expectancy was 1 day to 5 years. The range of individual preferences was wide within studies. Participants in the aHT studies required larger median benefits than those in the aCT studies. Factors associated with judging smaller benefits sufficient most often (44%) related to quality of life (e.g., less treatment toxicity).

Conclusion

Decisive factors in patients’ preferences for surgery type commonly relate to body image and survival/recurrence. Most participants judged small to moderate benefits sufficient to consider adjuvant systemic therapy worthwhile, but individual preferences varied widely. Clinicians should therefore consider the patient’s preferences to tailor their treatment recommendations accordingly.     

Dealing with indeterminate pulmonary nodules in colorectal cancer patients; a systematic review

IntroductionIndeterminate pulmonary nodules (IPNs) are frequently encountered on staging computed tomography (CT) in colorectal cancer (CRC) patients and they create diagnostic dilemmas. This systematic review and pooled analysis aims to estimate the incidence and risk of malignancy of IPNs and provide an overview of the existing literature on IPNs in CRC patients.Materials and methodsEMBASE, Pubmed and the Cochrane database were searched for papers published between January 2005 and April 2020. Studies describing the incidence of IPNs and the risk of malignancy in CRC patients and where the full text was available in the English language were considered for inclusion. Exclusion criteria included studies that used chest X-ray instead of CT, liver metastasis cohorts, studies with less than 60 CRC patients and reviews.ResultsA total of 18 studies met the inclusion criteria, involving 8637 patients. Pooled analysis revealed IPNs on staging chest CT in 1327 (15%) of the CRC patients. IPNs appeared to be metastatic disease during follow up in 16% of these patients. Regional lymph node metastases, liver metastases, location of the primary tumour in the rectum, larger IPN size and multiple IPNs are the five most frequently reported parameters predicting the risk of malignancy of IPNs.ConclusionA risk stratification model for CRC patients with IPNs is warranted to enable an adequate selection of high risk patients for IPN follow up and to diminish the use of unnecessary repetitive chest CT-scans in the many low risk patients.     

Viral infections and colorectal cancer: A systematic review of epidemiological studies

Numerous studies have found the presence of viral DNA in colorectal tumor tissues. However, whether viral infections contribute to the risk of colorectal cancer (CRC) is still under debate. We aimed to provide an overview of published epidemiological studies on the association between viral infections and CRC. A systematic literature search was performed in PubMed to find relevant studies published until 8 May 2014. Information collected included study population, sample type, laboratory method and prevalence of viral infection in cancer or precancer patients and controls. We found 41 studies that fulfilled the selection criteria, all of which had cross‐sectional or case‐control designs, and most of which were of small to moderate size. Viral infections included human papillomaviruses (HPV), human polyomaviruses, human herpesviruses, human bocavirus and Inoue‐Melnick virus. Inconsistent results were observed across studies. Many studies reported higher viral DNA prevalence in tumor tissues than in normal noncancerous tissues either in the same patients or in CRC‐free controls. However, potential contamination or temporal sequence of the infection and cancer development were often unclear. Seroprevalence studies assessing antibody titers indicative of viral infections did not find statistically significant differences between CRC cases and healthy controls. Overall published evidence on the role of viral infections in CRC etiology remains limited. Given the potential importance of viral infections and their implication for prevention, there is a strong need for large, methodologically rigorous epidemiological studies.     

Determinants of delay and association with outcome in head and neck cancer: A systematic review

IntroductionHead and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures.MethodsA search strategy was conducted according to PRISMA guidelines to search electronic databases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible.ResultsFifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined.ConclusionRace, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined.