Background: Beyond first-line palliative systemic treatment can be beneficial to selected oesophagogastric cancer patients, but experience with its administration may be limited and vary among hospitals. In a population-based study, we analysed the association between hospital systemic treatment volume and administration of beyond first-line treatment
Background: Results of CheckMate 577 show an improved disease-free survival for patients with resected esophageal or gastroesophageal junction cancer treated with adjuvant nivolumab compared with placebo (22.4 versus 11.0 months). Population-based data can provide insights in outcomes from clinical practice. The aim of our study was to investigate disease-free and overall survival in a nationwide population aligned with the inclusion criteria of CheckMate 577. Patients and Methods: Resected patients with stage II/III esophageal or gastroesophageal junction cancer (2015–2016) treated with neoadjuvant chemoradiotherapy were selected from the Netherlands Cancer Registry. Patients with cervical esophageal cancer, irradical resection, or complete pathological response were excluded. Disease-free and overall survival were assessed from 12 weeks after resection using Kaplan-Meier methods. In addition, to adjust for differences in characteristics between CheckMate 577 and our population-based cohort, a matching-adjusted indirect comparison was performed for pathological lymph node status and pathological tumor status. Results: We identified 634 patients. Sixty percent of patients were diagnosed with recurrence or were deceased at the end of follow-up. Median disease-free survival was 19.7 months and median overall survival was 32.2 months. After the matching procedure, the median disease-free survival was 17.2 months and median overall survival was 28.2 months. Conclusions: Disease-free survival in our population-based study was considerably longer than the placebo population of CheckMate-577 (19.7 versus 11.0 months). Possible explanations are differences in characteristics, quality of esophageal cancer care, or differential strategies for evaluation of recurrence. In the Netherlands postoperative imaging is not part of the standard follow-up as opposed to the standard postoperative imaging in the CheckMate 577 trial. The difference in postoperative imaging could partially explain the longer disease-free survival observed in our study. Quality and optimization of current treatment modalities remain important aspects of esophageal cancer care.
246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.
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.
261 Background: Recent clinical trials of novel systemic therapies showed improved survival of patients with metastatic esophageal cancer (EC) and gastric cancer (GC). Survival improvements observed in clinical trials might be unrepresentative for the total population as the percentage of patients whom participate in clinical trials is limited and more than half of all patients receive best supportive care (BSC). The aim of our study is to assess the best-case, typical and worst-case survival scenarios in patients with metastatic esophagogastric cancer. Methods: We selected patients with metastatic EC (including junction) or GC diagnosed in 2006-2019 from the Netherlands Cancer Registry. Survival scenarios were calculated based on percentiles of the survival curve stratified by tumor location and treatment (tumor-directed therapy or BSC). Survival scenarios were calculated for the 10th (best-case), 25th (upper-typical), 75th (lower-typical) and 90th (worst-case) percentiles. Linear trend analysis was performed to test if changes in survival over the diagnosis years were significant. Results: We identified 12739 patients with EC and 6833 patients with GC. Percentage of patients receiving tumor-directed therapy increased from 34% to 47% and 30% to 45% for patients with EC and GC, respectively. The median survival remained unchanged for patients with EC (5.0 months) and improved slightly for patients with GC (3.1 to 3.7 months; P=0.006). For patients with EC survival of the best-case scenario improved (17.4 to 22.8 months; P=0.001), whereas the other scenarios remained unchanged: upper-typical 11.2 to 11.7 (P=0.11), lower-typical 2.1 to 2.0 (P=0.10) and worst-case 0.9 to 0.8 months (P=0.22). For patients with GC survival improved for the best-case (13.1 to 19.5; P=0.005) and upper-typical scenario (6.7 to 10.6 months; P=0.002), whereas the lower-typical (1.2 to 1.4 months; P=0.87) and worst-case (0.6 to 0.6 months; P=0.60) remained unchanged. For patients with EC receiving tumor-directed therapy survival in all scenarios remained unchanged while for patients receiving BSC survival decreased: best-case 11.8 to 9.8 (P=0.005), upper-typical 6.0 to 5.0 (P=0.002), lower-typical 1.4 to 1.0 (P=0.003) and worst-case 0.7 to 0.5 months (P=0.03). For patients with GC receiving tumor-directed therapy survival improved for all scenarios: best-case 19.8 to 30.4 (P=0.005), upper-typical 6.4 to 10.3 (P=0.002), lower-typical 3.6 to 5.4 (P<0.001) and worst-case 1.4 to 2.6 months (P<0.001), and for patients receiving BSC survival for all scenarios remained unchanged. Conclusions: The proportion of patients with EC and GC receiving tumor-directed therapy increased over time. Despite the fact that survival improvements were not observed across all scenarios, at least an increase in survival was observed in certain subgroups of patients.
Enterococcus faecium is a commensal of the mammalian gastrointestinal tract, but is also found in non-enteric environments where it can grow between 10 °C and 45 °C. E. faecium has recently emerged as a multi-drug resistant nosocomial pathogen. We hypothesized that genes involved in the colonization and infection of mammals exhibit temperature-regulated expression control and we therefore performed a transcriptome analysis of the clinical isolate E. faecium E1162, during mid-exponential growth at 25 °C and 37 °C. One of the genes that exhibited differential expression between 25 °C and 37 °C, was predicted to encode a peptidoglycan-anchored surface protein. The N-terminal domain of this protein is unique to E. faecium and closely related enterococci, while the C-terminal domain is homologous to the Streptococcus agalactiae surface protein BibA. This region of the protein contains proline-rich repeats, leading us to name the protein PrpA for proline-rich protein A. We found that PrpA is a surface-exposed protein which is most abundant during exponential growth at 37 °C in E. faecium E1162. The heterologously expressed and purified N-terminal domain of PrpA was able to bind to the extracellular matrix proteins fibrinogen and fibronectin. In addition, the N-terminal domain of PrpA interacted with both non-activated and activated platelets.
308 Background: Similarities between esophageal and gastric adenocarcinomas have been identified in terms of genomic characteristics. There is however no consensus on the combined or stratified inclusion of esophageal adenocarcinoma (EAC) within gastric cancer (GC) clinical trials. The aim of our study was to compare patient and tumor characteristics, first-line treatment regimens and overall survival (OS) of patients with EAC and GC. Methods: We selected patients with unresectable advanced and/or synchronous metastatic EAC (n = 1554) or GC (including junction tumors; n = 2095) diagnosed in the period 2015-2017 from the nationwide Netherlands Cancer Registry. Patients with a positive HER2 test result and/or receiving trastuzumab as a first-line treatment were excluded. Data on OS were analyzed using Kaplan-Meier curves with Log-Rank test. Results: The EAC patient population had significantly more male patients (83% vs 66%), lower median age (68 vs 71 years) and higher median BMI (25.4 vs 24.5). Significant differences in location of metastases were identified, with higher percentages in non-regional lymph nodes (48% vs 28%), liver (50% vs 35%), lung (21% vs 9%) and bone (19% vs 7%) and lower in peritoneum (5% vs 42%), in EAC versus GC patients respectively. EAC patients more often received any type (supportive or active systemic) of treatment (76% vs 60%). Median OS was longer in EAC than GC patients (EAC: 4.8 vs GC: 4.1 months; p < 0.01). The percentages of patients receiving first-line systemic treatment were equal in both groups (43%). The number of patients receiving CapOx or FOLFOX was not significantly different (43% vs 47%). Carboplatin+paclitaxel was more frequently given in EAC versus GC (34% vs 3%), while EOX or ECC was given less frequently (12% vs 30%). No significant difference was observed in median OS between EAC and GC patients receiving first-line active systemic treatment (8.0 vs 7.6 months; p = 0.28). Conclusions: Patient characteristics, tumor characteristics, treatment regimens and OS differ between EAC and GC patients. Despite these differences, in patients receiving first-line active systemic treatment no significant differences in OS were found.
Background: Population-based predictive factors for the effectiveness of secondline palliative systemic therapy in gastro-oesophageal cancer are not available. This study investigates the predictive value of effectiveness of first-line treatment for second-line treatment outcomes in gastro-oesophageal cancer in a real-world setting. Methods: Patients with metastatic gastro-oesophageal cancer diagnosed in 2010e2017 who were treated with second-line therapy after disease progression on first-line therapy were identified from the Netherlands Cancer Registry. Patients were divided into four groups as per duration of time to treatment failure (TTF) of the first line (0e3, 3e6, 6e9 and >9 months),
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