Does dietary counseling improve quality of life in cancer patients? A systematic review and meta-analysis

Results have been mixed as to whether dietary counseling improves clinical outcomes in cancer patients. This systematic review and meta-analysis of randomized trials assessed the effect of dietary counseling on quality of life (QOL). It included only randomized trials that focused on dietary counseling and that relied upon a standardized QOL measurement. Five trials that met these and all other a priori eligibility criteria were identified; they are the focus of this meta-analysis. When these five studies were examined in aggregate, the standardized mean difference in QOL scores among patients who received dietary counseling was 0.56 (95% confidence interval,-0.01-1.14; P = 0.06). Dietary counseling does not appear to improve QOL significantly in patients with cancer. However,an observed trend toward benefit underscores the need for further study.     

Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis.

PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.     

Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis

BackgroundMicrosatellite instability (MSI) status in predicting the efficacy of adjuvant chemotherapy in colorectal cancer remains controversial.Materials and methodsStudies were identified through PubMed, Embase and ASCO proceedings with a combination of keywords (colorectal cancer, chemotherapy and MSI).ResultsA MA was performed for treated and non-treated MSI population on seven studies. Statistical calculations were performed on 7 studies representing 3690 patients; mean age: 65.5 years; 810 stage II and 2444 stage III (75%). MSI-high (MSI-H) was found in 454 patients (14% of the global population), and microsatellite stable (MSS) in 2871. A total of 1444 patients received 5-fluorouracil (5FU)-based chemotherapy, whereas 1518 patients did not.For MSI-H patients, there was no statistically significant difference for RFS whether or not they received chemotherapy (5 studies); HR RFS: 0.96 (95% confidence interval (CI): 0.62–1.49); HR OS (6 studies): 0.70 (95% CI: 0.44–1.09; p = 0.12). Elsewhere, we found a significant interaction between MSI status (MSI-H or MSS) and therapeutic status suggesting a lesser benefit for MSI-H than for MSS patients (HR interaction RFS: 0.77 (95% CI: 0.67–0.87)).ConclusionWe found similar RFS for treated and untreated MSI-H patients, showing that MSI-H status, in addition to being a good prognostic factor is also a predictive factor of non response.     

Does sunlight prevent cancer? A systematic review

Accumulating evidence for beneficial effects of sunlight on several types of cancer with a high mortality rate makes it necessary to reconsider the health recommendations on sun exposure, which are now mainly based on the increased risks for skin cancer. We reviewed all published studies concerning sun exposure and cancer, excluding skin cancer. All selected studies on prostate (3 ecologic, 3 case-control and 2 cohort), breast (4 ecologic, 1 case-control and 2 cohort) and ovary cancer (2 ecologic and 1 case-control) showed a significantly inverse correlation between sunlight and mortality or incidence. Two ecologic, 1 case-control and 2 prospective studies showed an inverse relation between sunlight and colon cancer mortality; 1 case-control study found no such association. Ecologic studies on non-Hodgkin lymphoma (NHL) mortality and sunlight gave conflicting results: early studies showing mostly positive and later studies showing mostly negative correlations. Three case-control studies and 1 cohort study found a significant inverse association between the incidence of NHL and sunlight. The question of how to apply these findings to (public) health recommendations is discussed.     

Neoadjuvant treatment in pancreatic cancer: Evidence-based medicine? A systematic review and meta-analysis

Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16–18.26 months); for resected patients OS was 22.78 months (95% CI 20.42–25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84–10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting.     

The local inflammatory response in colorectal cancer – Type,location or density? A systematic review and meta-analysis

IntroductionThe host anti-tumour inflammatory response is a strong prognostic indicator, and tumour infiltrating lymphocytes (TILs) are believed to have a complimentary role alongside TNM assessment in dictating future management. However, there is wide disagreement regarding the most efficacious and cost-effective method of assessment.MethodsA comprehensive literature search was performed of EMBASE, MedLine and PubMed as well as an assessment of references to identify all relevant studies relating to the assessment of the peri-tumoural inflammatory response or TILs and prognosis in colorectal cancer (CRC). A meta-analysis was performed of 67 studies meeting the REMARK criteria using RevMan software.ResultsIntratumoural assessment of both CD3 and CD8 in CRC were significant for disease-free survival (DFS) (combined HRs 0.46; 95%CI: 0.39–0.54 and 0.54; 95%CI: 0.45–0.65), as well as overall survival (OS) and disease-specific survival (DSS). The same was true for assessment of CD3 and CD8 at the invasive margin (DFS: combined HRs 0.45; 95%CI: 0.33–0.61 and 0.51; 95%CI: 0.41–0.62). However, similar fixed effects summaries were also observed for H&E-based methods, like Klintrup-Makinen grade (DFS: HR 0.62; 95%CI: 0.43–0.88). Furthermore, inflammatory assessments were independent of MSI status.ConclusionThe evidence suggests that it is the density of a co-ordinated local inflammatory infiltrate that confers survival benefit, rather than any individual immune cell subtype. Furthermore, the location of individual cells within the tumour microenvironment does not appear to influence survival. The authors advocate a standardised assessment of the local inflammatory response, but caution against emphasizing the importance of any individual immune cell subtype.     

Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer?

BACKGROUND:

To quantify the magnitude of benefit of the addition of hormone treatment (HT) to exclusive radiotherapy for locally advanced prostate cancer, a literature‐based meta‐analysis was conducted.

METHODS:

Event‐based relative risks (RR) with 95% confidence intervals (CIs) were derived through a random‐effect model. Differences in primary (biochemical failure and clinical progression‐free survival) and secondary outcomes (cancer‐specific survival, overall survival [OS], recurrence patterns, and toxicity) were explored. Absolute differences and numbers of patients needed to treat (NNT) were calculated. A heterogeneity test, a metaregression analysis with clinical predictors of outcome, and a correlation analysis for surrogate endpoints were also performed.

RESULTS:

Seven trials (4387 patients) were gathered. Hormone suppression significantly decreased both biochemical failure (RR, 0.76; 95% CI, 0.70‐0.82; P < .0001) and clinical progression‐free survival (RR, 0.81; 95% CI 0.71‐0.93; P = .002), with absolute differences of 10% and 7.7%, respectively, which translates into 10 and 13 NNT. cancer‐specific survival (RR, 0.76; 95% CI, 0.69‐0.83; P < .0001) and OS (RR, 0.86; 95% CI, 0.80‐0.93; P < .0001) were also significantly improved by the addition of HT, without significant heterogeneity, with absolute differences of 5.5% and 4.9%, respectively, which translates into 18 and 20 NNT. Local and distant relapse were significantly decreased by HT, by 36% and 28%, respectively, and no significant differences in toxicity were found. Primary and secondary efficacy outcomes were significantly correlated.

CONCLUSIONS:

Hormone suppression plus radiotherapy significantly decreases recurrence and mortality of patients with localized prostate cancer, without affecting toxicity. Cancer 2009. © 2009 American Cancer Society.     

Retrospective review of genomic testing in breast cancer: Does it improve outcome?

Purpose

Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a “big data” approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA).

Methods

A total of 888 patients with adequate gene expression, disease-free survival (DFS), and overall survival (OS) data were selected for analysis. DFS and OS were calculated for patients with high and low expression of angiopoietin and VEGF pathway genes using TCGA data. Gene-specific thresholds to dichotomize patients into high and low expression were determined and survival plots were generated.

Results

The TCGA cohort was representative of national breast cancer patients with respect to stage, pathology, and survival. High Ang2 gene expression was associated with not only decreased DFS (p = 0.05), but also decreased OS (p < 0.05). High co-expression of Ang2 and its receptor Tie2 was associated with both decreased DFS and OS (p < 0.05). There was strong correlation between angiopoietin and VEGF pathway genes. While high expression of VEGFA alone was not associated with survival, high co-expression with Ang2 was associated with decreased OS.

Conclusions

This study validates TCGA as a representative database providing genomic data and survival outcomes in breast cancer. Our TCGA data support the angiopoietin pathway as a key mediator in the pathologic angiogenic switch in breast cancer.

     

Follow-up in breast cancer: does routine clinical examination improve outcome? A systematic review of the literature

Multiple guidelines exist for the follow-up of breast cancer, with no agreement on frequency or duration. The contribution of routine clinical examination for the detection of potentially treatable relapse, and the impact this has on survival, is unknown. In this study, we systematically review the literature to establish the proportion of potentially treatable locoregional relapses and new contralateral breast cancers detected by clinical examination, mammography and patient self-examination. We analyse whether method of detection of relapse influences outcome. The methods used were systematic review of the literature. MEDLINE, EMBASE, CancerLit, Web of Sciences and EBM reviews were the data sources for the systematic review. All studies with information on proportion of relapses detected by clinical examination, mammography and self-examination were included. A total of 30-40% of potentially treatable relapses are detected by patient self-examination. In studies published before 2000, 15% of such relapse is mammographically detected with 46% detected by routine clinical examination. In those published after 2000, 40% are mammographically detected with 15% detected on routine clinical examination. Patients with ipsilateral breast relapse detected clinically appear to do less well than those with relapse detected by self-examination or mammography. Routine clinical surveillance is responsible for detection of fewer potentially treatable relapses in more modern cohorts as experience with mammography increases. There is no evidence to suggest that clinical examination confers a survival advantage compared with other methods of detection. The data in this analysis suggest that a review of the guidelines on follow-up after breast cancer should be undertaken.     

Should we still use prophylactic drain in gastrectomy for cancer? A systematic review and meta-analysis

Prophylactic drain in gastrectomy for cancer is still widely used, although some evidence has disputed this practice and spreading enhanced recovery protocol has been pushing towards surgical simplification. This study aimed at assessing the impact of drain placement on important clinical outcomes, evaluating the results of randomised controlled trials (RCTs), or cohort studies whenever information provided by the former was scarce.PubMed, PMC, Cochrane Library, CNKI and Wanfang databases were searched from January 1990 to February 2019, both for RCTs and cohort studies comparing use or avoidance of prophylactic drain in gastric cancer patients undergoing gastrectomy. All RCTs and cohort studies were rated according to Jadad score and Newcastle-Ottawa-Scale, respectively. Meta-analysis was separately performed on RCTs and cohort studies. The following clinical outcomes were considered: anastomotic leak, reoperation rate, additional drain procedure, length of stay, postoperative morbidity, postoperative mortality, readmission rate and drain related complications.Overall, 3 RCTs (330 patients) and 7 cohort studies (2897 patients) were included. Seven studies came from Eastern Countries. Meta-analysis on RCTs evidenced that drain avoidance halves overall morbidity (RR = 0.47, 95%CI 0.26–0.86, p = 0.014) and slightly reduces length of stay (SMD -0.24, 95%CI -0.51–0.03, p = 0.083). Only one postoperative death occurred in the drain group. The other outcomes were either not reported or reported just by one RCT each. Meta-analysis on cohort studies, despite higher statistical power, did not highlight any significant difference.This meta-analysis showed that prophylactic drain avoidance can reduce morbidity and length of stay, while not significantly affecting other major surgical outcomes.     

Capecitabine and oxaliplatin in advanced colorectal cancer:A?dose-finding?study

Purpose:Capecitabine and oxaliplatin are both activeanticancer agents in the treatment of patients with advanced colorectalcancer (ACRC). The aim of this dose-finding trial was to determinethe maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs)and the activity of the combination in patients with advanced colorectalcancer. Patients and methods:Twenty-fivechemotherapy-pretreated patients received the combination ofcapecitabine and oxaliplatin. Capecitabine was administered orally twicea day continuously for 14 days in doses ranging from 1650 to 2500mg/m²/d, and oxaliplatin was administered as a two-hourinfusion on day 1 using dose, ranges from 100 to 130 mg/m²repeated every three weeks. Results:Twenty-fivepatients were assessable for toxicity, and DLTs were diarrhea (grade3: 27%) and stomatitis (grade 3: 9%) at dose levelVI. Dose level V (capecitabine 2500 mg/m² and oxaliplatin 120mg/m²) was found to be the MTD. Hematological toxicitywas minimal, overall neurotoxicity (grade 1–4) was 27% with1% grade 3–4. A global response rate was 17%(95% confidence interval (95% CI):2%–32%) and the median overall survival was 12months. Conclusion:The recommended dose for furtherphase II studies is capecitabine 2500 mg/m²/d withintermittent schedule and oxaliplatin 120 mg/m² every threeweeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitisand vomiting. This combination should be studied in phase II trials inadvanced colorectal.     

Should noncurative resection of the primary tumour be performed in patients with stage iv colorectal cancer? A systematic review and meta-analysis

Purpose

Surgical resection of the primary tumour in patients with advanced colorectal cancer (crc) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (qol).

Methods

Reports in the central, medline, and embase databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle–Ottawa Scale. Data were collected and synthesized per protocol.

Results

From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10–30.7 months) in the resection group and 11.4 months (range: 3–22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (ci): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% ci: 0% to 9.7%) and 25.9% (95%ci: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% ci: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 ci: 15.4% to 39.9%). No study provided qol data.

Conclusions

Although this review supports primary tumour resection in advanced crc, the results have significant biases. Randomized trials are warranted to confirm the findings.     

Sentinel lymph node in oesophageal cancer—a systematic review and meta-analysis

Background

Sentinel lymph nodes (SLNs) have been used to predict regional lymph node metastasis in patients with melanoma and breast cancer. However, the validity of the SLN hypothesis is still controversial for oesophageal cancer. We performed this meta-analysis to evaluate the feasibility and accuracy of radio-guided SLN mapping for oesophageal cancer.

Methods

A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate a pooled event rates and 95% confidence interval (95% CI).

Results

The search identified 23 relevant articles. The overall detection rate was 0.93 (95% CI: 0.894-0.950), sensitivity 0.87 (95% CI: 0.811-0.908), negative predictive value 0.77 (95% CI: 0.568-0.890) and the accuracy was 0.88 (95% CI: 0.817-0.921). In the adenocarcinoma cohort, detection rate was 0.98 (95% CI: 0.923-0.992), sensitivity 0.84 (95% CI: 0.743-0.911) and the accuracy was 0.87(95% CI: 0.796-0.913). In the squamous cell carcinoma group, detection rate was 0.89 (95% CI: 00.792-0.943), sensitivity 0.91 (95% CI: 0.754-0.972) and the accuracy was 0.84 (95% CI: 0.732-0.914).

Conclusions

It is possible to identify and obtain a SLN before neoadjuvant therapy in oesophageal cancer. However, further work is needed to optimize radiocolloid type, refine the technique and develop a quick and accurate way to determine SLN status intraoperatively. This technique has to be further evaluated before it can be applied widely.     

Adult weight gain and colorectal adenomas—a systematic review and meta-analysis

BackgroundColorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association.MethodsWe searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose–response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model.ResultsFor colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17–1.65;I²: 43%,N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%–11%;I²: 65%,N = 7 studies). Although there was indication of non-linearity (P_{non-linearity} < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions.ConclusionsEven a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer.