A population-based comparison of patients with metastatic esophagogastric carcinoma between Japan and the Netherlands

Purpose: Differences exist between Asian and Western patients with esophagogastric cancer, for example in terms of histological subtype and treatment strategies. This study aimed to compare characteristics and treatment between patients with metastatic esophagogastric cancer from Japan and the Netherlands using nationwide cancer registry data. Methods: Patients diagnosed with metastatic esophageal or gastric cancer were included from the nationwide national cancer registry of Japan (2016–2019) and the Netherlands (2015–2020). Treatment strategies were analyzed using chi-squared tests. Results: The proportion of patients with metastatic esophageal (16.0% vs 34.2%) and gastric cancer (14.9% vs 45.2%) were lower in Japan compared to the Netherlands. Japanese patients with metastatic esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC) or gastric cancer (GC) were more often male and older compared to Dutch patients. Proportion of patients with metastatic disease who received surgical resection was higher in Japan compared to the Netherlands (EAC 9.3 vs 1.4%, p < 0.001; ESCC 10.7% vs 2.3%, p < 0.001; GC 12.0% vs 3.6% p < 0.001). Proportion of patients who received systemic therapy was also higher (EAC 44.8% vs 30.4%, p < 0.001; ESCC 26.6% vs 12.0%, p < 0.001; GC 50.7% vs 35.8% p < 0.001). Conclusions: Japanese patients less often presented with metastatic esophagogastric cancer and more often underwent surgical resection or received systemic therapy compared to Dutch patients. Further investigation should elucidate what the deliberations are in both Japan and the Netherlands and if more patients in the Netherlands could benefit from surgical resection or systemic therapy and whether this would translate in better survival and quality of life

From presentation to paper: gender disparities in oncological research

Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown. We aim to identify gender-based differences in contributions to presentations at two major oncological conferences. Abstracts presented at plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and European Society for Medical Oncology (ESMO) Congresses were collected. Trend analyses were used to analyze female contribution over time. The association between presenter's sex, study outcome (positive/negative) and journals' impact factors (IFs) of subsequently published papers was assessed using Chi-square and Mann-Whitney U tests. Of 166 consecutive abstracts presented at ASCO in 2011-2018 (n = 34) and ESMO in 2008-2018 (n = 132), 21% had female presenters, all originating from Northern America (n = 17) or Europe (n = 18). The distribution of presenter's sex was similar over time (p = 0.70). Of 2,425 contributing authors to these presented abstracts, 28% were women. The proportion of female abstract authors increased over time (p <0.05) and was higher in abstracts with female (34%) compared to male presenters (26%; p <0.01). Presenter's sex was not associated with study outcome (p = 0.82). Median journals' IFs were lower in papers with a female first author (p <0.05). In conclusion, there is a clear gender disparity in research presentations at two major oncological conferences, with 28% of authors and 21% of presenters of these studies being female. Lack of visibility of female presenters could impair acknowledgement for their research, opportunities in their academic career and even hamper heterogeneity in research

Assessing real-world representativeness of prospective registry cohorts in oncology: insights from patients with esophagogastric cancer

OBJECTIVES: This study aimed to explore the real-world representativeness of a prospective registry cohort with active accrual in oncology, applying a representativeness metric that is novel to health care. STUDY DESIGN AND SETTING: We used data from the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) registry and from the population-based Netherlands Cancer Registry (NCR). We used Representativeness-indicators (R-indicators) and overall survival to investigate the degree to which the POCOP cohort and clinically relevant subgroups were a representative sample compared to the NCR database. Calibration using inverse propensity score weighting was applied to correct differences between POCOP and NCR. RESULTS: The R-indicator of the entire POCOP registry was 0.72 95% confidence interval [0.71, 0.73]. Representativeness of palliative patients was higher than that of potentially curable patients (R-indicator 0.88 [0.85, 0.90] and 0.70 [0.68, 0.71], respectively). Stratification to clinically relevant subgroups based on treatment resulted in higher R-indicators of the respective subgroups. Both after stratification and calibration weighting survival estimates in the POCOP registry were more similar to that in the NCR population. CONCLUSION: This study demonstrated the assessment of real-world representativeness of patients who participated in a prospective registry cohort and showed that real-world representativeness improved when the variability in treatment was accounted for

Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma:TRAP Study

PURPOSE: Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC. PATIENTS AND METHODS: Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses. RESULTS: Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively. CONCLUSION: Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively

Incidence, Stage, Treatment, and Survival of Noncardia Gastric Cancer

IMPORTANCE: Gastric cancer is the fifth most common cancer worldwide, and investigating its incidence, characteristics, treatment, and outcomes over the past decades can help in selecting clinical strategies and future research directions. OBJECTIVE: To analyze the trends in incidence, staging, and treatment of gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: This nationwide, population-based cohort study included patients diagnosed with noncardia gastric cancer (NCGC) between 1989 and 2021 in the Netherlands. MAIN OUTCOMES AND MEASURES: Differences in tumor characteristics, treatment, and survival were analyzed per fixed time periods (1989-1993, 1994-1998, 1999-2003, 2004-2008, 2009-2013, 2014-2018, and 2019-2021). RESULTS: In total, 47 014 patients (median [IQR] age, 73 [64-80] years; 28 032 [60%] male patients) were identified with mostly adenocarcinomas of the antrum region (when location was known). Age-standardized incidence decreased from 20.3 to 6.1 per 100 000 person-years between 1989 and 2021. During the study period, unknown T and N stages were recorded less frequently, and metastatic disease was diagnosed more frequently (1989-1993: 2633 of 9493 patients [28%]; 2019-2021: 1503 of 3200 patients [47%] in 2019-2021). Over time, fewer patients with metastatic disease underwent surgery with or without other treatment modalities (68% in 1989-1993 vs 64% in 2019-2021), and palliative chemotherapy in metastatic NCGC increased from 9% to 40%. For patients with nonmetastatic disease, 5-year relative survival improved from 28% (95% CI, 26.5%-29.2%) to 36% (95% CI, 33.5%-37.6%) between 1989 and 2021. For patients with nonmetastatic disease undergoing a resection, 5-year survival increased from 40% (95% CI, 38.3%-41.8%) to 51% (95% CI, 47.9%-53.3%). For patients with metastatic disease, 1-year relative survival increased from 10% (95% CI, 8.7%-11.1%) to 19% (95% CI, 17.2%-21.6%), but 3-year relative survival remained poor at 5% (95% CI, 3.6%-7.5%). CONCLUSIONS AND RELEVANCE: In this nationwide cohort study involving 47 014 patients diagnosed with NCGC (1989-2021), the results showed a decrease in incidence, more accurate staging, a shift in treatment modalities, and improved patient survival

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Conditional survival and cure of patients with colon or rectal cancer: A population-based study

Background: The increasing number of colorectal cancer (CRC) survivors need survival estimates that account for the time already survived. The aim of this population-based study was to determine conditional survival, cure proportions, and time-to-cure (TTC) of patients with colon or rectal cancer. Materials and Methods: All patients with pathologic stage I-III CRC treated with endoscopy or surgery, diagnosed and registered in the Netherlands Cancer Registry between 1995 and 2016, and aged 18 to 99 years were included. Conditional survival was calculated for those diagnosed before and after 2007. Cure proportions were calculated using flexible parametric models. Results: A total of 175,384 patients with pathologic stage I (25%), II (38%), or III disease (37%) were included. Conditional 5-year survival of patients with stage I, II, and III colon cancer having survived 5 years was 98%, 94%, and 92%, respectively. For patients with stage I-III rectal cancer, this was 96%, 89%, and 85%, respectively. Statistical cure in patients with colon cancer was reached directly after diagnosis (stage I) to 6 years (stage III) after diagnosis depending on age, sex, and disease stage. Patients with rectal cancer reached cure 0.5 years after diagnosis (stage I) to 9 years after diagnosis (stage III). In 1995, approximately 42% to 46% of patients with stage III colon or rectal cancer, respectively, were considered cured, whereas in 2016 this percentage increased to 73% to 78%, respectively. Conclusions: The number of patients with CRC reaching cure has increased substantially over the years. This study's results provide valuable insights into trends of CRC patient survival and are important for patients, clinicians, and policymakers