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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. 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. 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. 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.

BackgroundHealth-related quality of life (HRQoL) assessments are increasingly incorporated into oncological randomized controlled trials (RCTs). The quality of HRQoL reporting in RCTs concerning palliative systemic treatment for advanced esophagogastric cancer is currently unknown. Therefore, we conducted a systematic review to investigate the quality of HRQoL reporting over time. MethodsPubMed, CENTRAL and EMBASE were searched for RCTs concerning systemic treatment for advanced esophagogastric cancer up to February 2017. The Minimum Standard Checklist for Evaluating HRQoL Outcomes in Cancer Clinical Trials was used to rate the quality of HRQoL reporting. Univariate and multivariate generalized linear regression analysis was used to investigate factors affecting the quality of reporting over time.ResultsIn total, 37 original RCTs (N = 10,887 patients) were included. The quality of reporting was classified as ‘very limited’ in 4 studies (11%), ‘limited’ in 24 studies (65%), and ‘probably robust’ in 9 studies (24%). HRQoL reporting did not improve over time, and it did not improve following the publication of the CONSORT-PRO statement in 2013. The publication of HRQoL findings in a separate article and second-line treatment were associated with better reporting.ConclusionsHRQoL reporting in RCTs concerning palliative systemic therapy for advanced esophagogastric cancer is limited and has not improved over time. This systematic review provides specific recommendations for authors to improve HRQoL reporting: formulate hypotheses a priori, clearly describe instrument administration, and handle missing data and interpret findings appropriately.

Gallbladder cancer (GBC) is rare in Western populations and data about treatment and outcomes are scarce. This study aims to analyze survival and identify opportunities for improvement using population-based data from a low-incidence country. GBC patients diagnosed between 2005 and 2016 with GBC were identified from the Netherlands Cancer Registry. Patients were grouped according to time period (2005–2009/2010–2016) and disease stage. Trends in treatment and overall survival (OS) were analyzed. In total 1834 patients were included: 661 (36%) patients with resected, 278 (15%) with non-resected non-metastatic, and 895 (49%) with metastatic GBC. Use of radical versus simple cholecystectomy (12% vs. 26%, p < 0.001) in early (pT1b/T2) GBC increased. More patients with metastatic GBC received chemotherapy (11% vs. 29%, p < 0.001). OS improved from 4.8 months (2005–2009) to 6.1 months (2010–2016) (p = 0.012). Median OS increased over time (2005–2009 vs. 2010–2016) in resected (19.4 to 26.8 months, p = 0.038) and metastatic (2.3 vs. 3.4 months, p = 0.001) GBC but not in unresected, non-metastatic GBC. In early GBC, patients with radical cholecystectomy had a median OS of 76.7 compared to 18.4 months for simple cholecystectomy (p < 0.001). Palliative chemotherapy showed superior (p < 0.001) survival in metastatic (7.3 versus 2.1 months) and non-resected non-metastatic (7.7 versus 3.5 months) GBC. In conclusion, survival of GBC remains poor. Radical surgery and palliative chemotherapy appear to improve prognosis but remain under-utilized.

Despite an aging population and underrepresentation of elderly patients in clinical trials, studies on elderly patients with metastatic pancreatic cancer are scarce. This study investigated the use of chemotherapy and survival in elderly patients with metastatic pancreatic cancer. From the Netherlands Cancer Registry, all 9407 patients diagnosed with primary metastatic pancreatic adenocarcinoma in 2005–2013 were selected to investigate chemotherapy use and overall survival (OS), using Kaplan–Meier and Cox proportional hazard regression analyses. Over time, chemotherapy use increased in all age groups (<70 years: from 26 to 43%, 70–74 years: 14 to 25%, 75–79 years: 5 to 13%, all P < 0.001, and ≥80 years: 2 to 3% P = 0.56). Median age of 2,180 patients who received chemotherapy was 63 years (range 21–86 years, 1.6% was ≥80 years). In chemotherapy‐treated patients, with rising age (<70, 70–74, 75–79, ≥80 years), microscopic tumor verification occurred less frequently (91‐88‐87‐77%, respectively, P = 0.009) and OS diminished (median 25‐26‐19‐16 weeks, P = 0.003). After adjustment for confounding factors, worse survival of treated patients ≥75 years persisted. Despite limited chemotherapy use in elderly age, suggestive of strong selection, elderly patients (≥75 years) who received chemotherapy for metastatic pancreatic cancer exhibited a worse survival compared to younger patients receiving chemotherapy. Data on elderly patients with metastatic pancreatic cancer are scarce. With rising age, palliative chemotherapy use decreased until <5% in octogenarians. Following chemotherapy, patients over 75 years of age had a worse survival.

Background: Real-world data on treatment and outcomes in patients with synchronous metastatic disease compared with patients with metachronous metastatic disease in esophagogastric cancer have not been published before. The aim of our study was to explore treatment, overall survival (OS), and time to treatment fialure (TTF) in patients with synchronous and metachronous metastatic esophagogastric adenocarcinoma. Methods: Patients with synchronous metastatic disease (2015–2017) and patients with metachronous metastatic disease initially treated with curative intent for nonmetastatic disease (2015–2016) were selected from the Netherlands Cancer Registry. OS and TTF were assessed from metastatic diagnosis for patients with synchronous, early metachronous (⩽6 months) or late metachronous (>6 months) metastatic disease using Kaplan–Meier curves with two-sided log-rank test. Results: Median OS was 4.2, 2.1, and 4.4 months in patients with synchronous, early metachronous, and late metachronous metastatic disease, respectively (p < 0.001). The proportion of patients receiving systemic treatment was 41.3%, 21.5%, and 32.5% for synchronous, early metachronous, and late metachronous metastatic disease, respectively (p = 0.001). Among patients receiving systemic treatment, median OS was 8.8, 4.5, and 9.1 months (p < 0.001) and median TTF was 6.1, 3.8, and 5.7 months (p < 0.001) in synchronous, early metachronous, and late metachronous metastatic disease, respectively. Conclusion: Patients with early metachronous metastatic disease have a worse survival compared with patients with synchronous or late metachronous metastatic disease. These patients less often receive systemic treatment, and even when treated, survival is worse compared with patients with synchronous or late metachronous metastatic disease, suggesting a more aggressive tumor behavior.

Prediction models are only sparsely available for metastatic oesophagogastric cancer. Because treatment in this setting is often preference-based, decision-making with the aid of a prediction model is wanted. The aim of this study is to construct a prediction model, called SOURCE, for the overall survival in patients with metastatic oesophagogastric cancer. Data from patients with metastatic oesophageal (n = 8010) or gastric (n = 4763) cancer diagnosed during 2005–2015 were retrieved from the nationwide Netherlands cancer registry. A multivariate Cox regression model was created to predict overall survival for various treatments. Predictor selection was performed via the Akaike Information Criterion and a Delphi consensus among experts in palliative oesophagogastric cancer. Validation was performed according to a temporal internal-external scheme. The predictive quality was assessed with the concordance-index (c-index) and calibration. The model c-indices showed consistent discriminative ability during validation: 0.71 for oesophageal cancer and 0.68 for gastric cancer. The calibration showed an average slope of 1.0 and intercept of 0.0 for both tumour locations, indicating a close agreement between predicted and observed survival. With a fair c-index and good calibration, SOURCE provides a solid foundation for further investigation in clinical practice to determine its added value in shared decision making.

The feasibility, generalizability, and validity of randomized controlled trials (RCTs) may be compromised when patients have preferences for specific trial arms. The patient preference trial (PPT) design, which assigns at least a subset of the patients based on their preference rather than randomization, has been proposed as an alternative. The aim of this review was to provide an overview of the application of the PPT design in oncological research, with a particular focus on PPTs designed to assess the effectiveness of an intervention and provide recommendations on reporting. We performed a scoping review including all prospective oncological studies where trial arm allocation for part or all of the patients was based on patients’ preferences. Retrieved information included research objectives, motivation for the design choice, baseline covariate adjustments, and sample size calculations. We identified 44 PPTs, of which 34 (77%) aimed to investigate intervention effectiveness and were reviewed in more detail. Of these 34 effectiveness PPTs, 24 (71%) studies were completed trials, while 10 were protocols. The most frequently indicated rationale behind opting for the PPT design was the perceived infeasibility of an RCT (17 [50%] studies). Baseline covariate adjustment was performed in 18 (53%) studies. Fourteen out of 24 completed trials reported an unequal allocation ratio across trial arms not anticipated during the design. This review identified several challenges for PPTs in oncology. Future PPTs should take bias due to confounding and unequal group sizes arising from the preferential allocation into account and report on these issues, as these aspects are crucial for the validity and statistical power of the study. •Patient preference trials assign patients to trial arms based on their preference.•This emerging design may serve as an alternative if an RCT is not feasible.•Our literature review identified 44 patient preference trials in oncology.•Future PPTs must address bias due to confounding and unequal group sizes.

Background The anticancer drug paclitaxel is primarily metabolized in the liver. Previous studies have indicated a correlation between impaired liver function and paclitaxel toxicity, which may indicate dose reduction. Since the evidence is limited, the aim of this study was to investigate the effect of impaired liver function on the hematological toxicity of paclitaxel, dose modifications and overall survival (OS). Methods For this single-center retrospective observational study, patients treated with paclitaxel for breast, esophageal and ovarian cancer at the University Medical Centre Utrecht between 2011 and 2022 were identified from the Utrecht Patient Oriented Database (UPOD). Based on regression analysis, the risk of developing Grade 3/4 hematological toxicity was compared between patients with normal and impaired (based on the NCI criteria for bilirubin and ASAT (aspartate aminotransferase) concentrations) liver function. Additionally, differences in the occurrence of toxicity-related dose modifications and OS were evaluated between the two groups. Results A total of 569 patients were included. Breast cancer patients who were receiving advanced treatment and had mildly impaired liver function (ASAT ≤ 2x ULN, bilirubin ≤ ULN) had an increased risk of developing grade 3/4 neutropenia (HR = 4.39, 95% CI 1.20-16.02; p  = 0.03). In addition, patients with impaired liver function treated according to the advanced ovarian cancer regimen had an increased risk of developing grade 3/4 leukopenia (HR = 12.64, 95% CI 2.12–75.22, p  = 0.01) and dose modification (treatment discontinuation) (HR = 3.91, 95% CI 1.74–8.79, p  < 0.01). Impaired liver function was also associated with decreased OS in inoperable esophageal and advanced ovarian cancer patients (HR = 7.65, 95% CI 2.54–23.1, p  < 0.01 and HR = 2.98, 95% CI 1.36–6.54, p  < 0.01, respectively). The risk of developing grade 3/4 hematological toxicity during lower-dose paclitaxel treatment protocols was not significantly different in patients with impaired liver function. Conclusions This study revealed that patients with impaired liver function treated with paclitaxel for breast and ovarian cancer in an advanced setting are at greater risk of developing hematological toxicity than patients with normal liver function at the start of therapy. Furthermore, in patients with ovarian (advanced) or inoperable esophageal cancer, impaired liver function is associated with decreased OS. Within these groups of patients, it is important to weigh the risk of upfront paclitaxel dose modifications versus an adaptive strategy.

Background For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood. Methods Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT. Results Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection ( p -value = 0.001), higher ypT stage ( p -value = 0.004), ypN + ( p -value = 0.008), and non-response ( p-value = 0.012). Conclusion A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.

Purpose To investigate the effect of systemic therapy on health-related quality of life (HRQoL) in patients with advanced esophagogastric cancer in daily clinical practice. This study assessed the HRQoL of patients with esophagogastric cancer during first-line systemic therapy, at disease progression, and after progression in a real-world context. Methods Patients with advanced esophagogastric cancer (2014–2021) receiving first-line systemic therapy registered in the Prospective Observational Cohort Study of Oesophageal-gastric cancer (POCOP) were included ( n  = 335). HRQoL was measured with the EORTC QLQ-C30 and QLQ-OG25. Outcomes of mixed-effects models were presented as adjusted mean changes. Results Results of the mixed-effect models showed the largest significant improvements during systemic therapy for odynophagia (− 18.9, p  < 0.001), anxiety (− 18.7, p  < 0.001), and dysphagia (− 13.8, p  < 0.001) compared to baseline. After progression, global health status (− 6.3, p  = 0.002) and cognitive (− 6.2, p  = 0.001) and social functioning (− 9.7, p  < 0.001) significantly worsened. At and after progression, physical (− 9.0, p  < 0.001 and − 8.8, p  < 0.001) and role functioning (− 15.2, p  = 0.003 and − 14.7, p  < 0.001) worsened, respectively. Trouble with taste worsened during systemic therapy (11.5, p  < 0.001), at progression (12.0, p  = 0.004), and after progression (15.3, p  < 0.001). Conclusion In general, HRQoL outcomes in patients with advanced esophagogastric cancer improved during first-line therapy. Deterioration in outcomes was mainly observed at and after progression. Implications for cancer survivors Identification of HRQoL aspects is important in shared decision-making and to inform patients on the impact of systemic therapy on their HRQoL.