Risks of hypertension and thromboembolism in patients receiving bevacizumab with chemotherapy for colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three-drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first-line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life-threatening side effects such as severe hypertension (HTN) (5%-18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%-4.6%), and gastrointestinal perforation (0.3%-2.4%). This meta-analysis aims to evaluate the additive risk of BVZ-induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. METHODS: Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ-chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. RESULTS: The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy-only group. CONCLUSION: BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy-only group. Our findings are significant as they provide vital information in analyzing the risk-benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities.

Respondent Driven Sampling Method of Recruitment for a Case Control Study of Gastric Cancer Risk.

OBJECTIVE: Gastric cancer (GC) disproportionately affects ethnic minorities in the US including Asians and Pacific Islanders. Research with minority groups who are at high risk are needed to provide more effective treatment. Successful recruitment of minorities to research must overcome obstacles of language, access, fear and mistrust. Respondent Driven Sampling (RDS) is a sampling strategy designed to recruit underrepresented minority populations using social networks. However, there are no reports of RDS being used for a case-control study. METHODS: Our pilot study examined the feasibility of using RDS as a recruitment strategy to enroll a large number of participants to develop a GC screener. Our preliminary work showed that 750 cases and 5,250 controls would be needed to fully develop this tool. GC cases, who also served as the seeds, were asked to refer 2 more people to participate as controls in our study. Our pilot goal was to recruit 8 GC cases (as seeds) and 112 controls using three waves of referrals and recruitment. RESULTS: Twenty-seven GC cases were contacted of which 10 refused, 4 expressed interested to participate in the survey but were unwilling to recruit controls. Thirteen cases were recruited but only 5 Complete the survey. Of these 5, 3 cases did not pass on referral coupons and only 2 of the participants gave coupons to 3 potential controls. CONCLUSION: Our study revealed the limitations of using RDS with cancer patients to support recruitment. GC patients' constrained social networks, inadequate incentives or other factors may have contributed to the lack of success with using RDS in this setting.

A qualitative analysis of patients' experiences with an emergency department diagnosis of gastrointestinal cancer.

OBJECTIVES: Optimally, cancer is diagnosed through periodic screening or detection of early symptoms in primary care settings. However, an estimated 23%-52% of gastrointestinal (GI) cancers are diagnosed in the emergency department (ED). Cancer diagnosed in the ED has been associated with worse clinical and patient-reported outcomes even after adjustment for cancer stage. We sought to explore patients' accounts of patient and health care system factors related to their diagnosis in the ED and their lived experience of receiving a diagnosis in this setting. METHODS: Patients with an ED visit during or within 30 days of their GI cancer diagnosis at an urban academic hospital serving a largely disadvantaged population were recruited. Interviews were coded in NVivo 12 and analyzed using a thematic analysis approach. RESULTS: Patient-reported factors associated with their experiences included denial and avoidance of symptoms, mistrust of the health system, and lack of cancer screening knowledge. Health care system factors included misdiagnosis and delayed access to specialty care or tests. Experiences receiving a cancer diagnosis in the ED were overwhelmingly negative. CONCLUSIONS: This study highlights the unmet needs in identifying and diagnosing patients who ultimately present to the ED for evaluation and eventual diagnosis of cancer. Our results shed light on several modifiable factors, including the need for increased public awareness of the asymptomatic nature of cancer and the importance of cancer screening. Additionally, health care systems modifications beyond the ED are needed to improve access to timely care when symptoms arise.

Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.

BACKGROUND: Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer. METHODS: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 µg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported. RESULTS: Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%). CONCLUSIONS: Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer. IMPACT: PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.

Socioeconomic Disparities in Gastric Cancer and Identification of a Single SES Variable for Predicting Risk.

INTRODUCTION: Socioeconomic status (SES) is a known risk factor for gastric cancer (GC). This study seeks to examine education, income, and occupation variables separately to identify the single variable that can be best used to assess SES risk for GC. METHODS: Data from a case-control survey study were used. Logistic regression models were created for education, income, and occupation adjusted for age, sex, and race. Models were compared using AIC, c-statistics, and pseudo-R square to determine the model that had the highest risk predictive ability. RESULTS: GC cases had lower education levels and more commonly held jobs in unskilled labor. Annual household income was lower in cases compared to controls. Age, gender, race, education, and occupation were associated with increased risk of GC. The education model adjusted for age, gender, and race found < high school (HS) education to have an OR of 3.18 (95% CI 1.09-9.25) for GC compared to > HS education. The occupation model demonstrated that employment in unskilled labor had OR of 4.32 (95% CI 1.05-17.76) for GC compared to professional occupation. Model fit was best for the education model (AIC: 113.583, lower AIC is better) compared to income (117.562) or occupation (117.032). Education contributed the most to model variability (% delta pseudo-R square (4.7%)) compared to occupation (4.0%) or income (3.8%). CONCLUSION: Education level was the single most reliable measure of GC risk among 3 SES variables and can be employed as an ideal single indicator of SES-related GC risk when multiple SES factors cannot be obtained.