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Despite evidence-based guidelines, variation in esophageal cancer care exists in daily practice. Many oncology networks deployed regional agreements to standardize the patient care pathway and reduce unwarranted clinical variation. The aim of this study was to explore the trends in variation of esophageal cancer care between participating hospitals of the Managed Clinical Network (MCN) in the Netherlands. Patients with esophageal cancer diagnosed from 2012 to 2016 were selected from the Netherlands Cancer Registry. Variation on treatment strategies, lead time to start of treatment, and 2-year survival, were calculated and compared between five clusters of hospitals within the network. A total of 1763 patients, diagnosed in 17 hospitals, were included. 71% of all patients received treatment with a curative intent, which ranged from 69% to 77% between the clusters of hospitals in 2015–2016. Although variation in treatment modalities between the clusters was observed in 2012–2014, no significant variation existed in 2015–2016, except for patients receiving no treatment at all. The 2-year overall survival of patients receiving treatment with a curative intent did not vary significantly between the clusters of hospitals (range: 56%–63%). Nevertheless, the median lead time before patients started treatment with a curative intent varied between clusters of hospitals in 2015–2016 (range: 34–47 days; p < 0.001). Limited variation in esophageal cancer treatment between clusters of hospitals in the MCN existed. This study shows that oncology networks can promote standardization of cancer care and reduce variation between hospitals through insight into variation. [ABSTRACT FROM AUTHOR]

In patients with gastric or gastroesophageal junction (GEJ) cancer treated with curative intent, distant interval metastases may be detected after start of neoadjuvant chemotherapy or during surgery. The aim of this study was to explore characteristics, allocated treatment and overall survival (OS) in gastric/GEJ cancer patients with interval metastases, and to compare OS with synchronous metastatic gastric/GEJ cancer patients who started palliative chemotherapy. Patients with interval metastases were selected from the Netherlands Cancer Registry by including patients with potentially curable gastric/GEJ adenocarcinoma (2010–2018) who started chemotherapy without concurrent radiotherapy. The OS since start of neoadjuvant treatment of patients with interval metastases was compared with a propensity score-matched cohort of patients with synchronous metastases who received palliative systemic treatment. 164 patients with interval metastases diagnosed in 2010–2018 were included. Metastases were most frequently detected during surgery (83%) and most frequently located in the peritoneum (77%). Peritoneal interval metastases were observed in 63% and 80% of the patients who did and did not have a diagnostic laparoscopy prior to neoadjuvant treatment, respectively (P = 0.041). Median OS was 8.9 months (IQR 5.5–13.4), compared to 8.0 months (IQR 4.1–14.1) in matched synchronous metastatic patients calculated from start of neoadjuvant and palliative systemic treatment, respectively (P = 0.848). This population-based study shows that gastric/GEJ cancer patients who started neoadjuvant treatment and were diagnosed with interval metastases most frequently suffered from peritoneal metastases detected during (exploratory) surgery, even when a diagnostic laparoscopy was performed before start of treatment. OS was comparable to patients with synchronous metastatic gastric/GEJ cancer. [ABSTRACT FROM AUTHOR]

In esophageal cancer patients, distant metastases develop between the start of neoadjuvant chemoradiotherapy and planned surgery, so-called interval metastases. The primary aim of this study was to assess management, overall survival (OS), and prognostic factors for OS in these patients. A secondary aim was to compare OS with synchronous metastatic patients. Esophageal cancer patients with interval distant metastases were identified from the Netherlands Cancer Registry (2010 to 2017). Management was categorized into metastasis-directed therapy (MDT), primary tumor resection, or best supportive care (BSC). The OS was calculated from the diagnosis of the primary tumor. Prognostic factors affecting OS were studied using Cox proportional hazard models. Propensity score-matching (1:3) generated matched cases with synchronous distant metastases. In all, 208 patients with interval metastases were identified: in 87 patients (42%) MDT was initiated; in 10%, primary tumor resection only; in 7%, primary tumor resection plus MDT; and in 41%, BSC. Median OS was 10 months (interquartile range, 8.6 to 11.1). Compared with BSC, superior OS was independently associated with MDT (hazard ratio [HR] 0.36; 95% confidence interval [CI], 0.26 to 0.49), primary tumor resection (HR 0.55; 95% CI, 0.33 to 0.94), and primary tumor resection plus MDT (HR 0.20; 95% CI, 0.10 to 0.38). Worse OS was independently associated with signet ring cell carcinoma (HR 1.92; 95% CI, 1.12 to 3.28) and poor differentiation grade (HR 1.96; 95% CI, 1.35 to 2.83). The OS was comparable between matched patients with interval and synchronous distant metastases (10.2 versus 9.4 months, P =.760). In esophageal cancer patients treated with neoadjuvant chemoradiotherapy with interval distant metastases, the OS was poor and comparable to that of synchronous metastatic patients. [ABSTRACT FROM AUTHOR]

Studies have shown that multidisciplinary team meetings (MDTM) improve diagnostic work-up and treatment-decisions. This study aims to evaluate the influence of implementing a regional-video-Upper-GI-MDTM (uMDTM) for oesophageal cancer (OC) on the number of patients discussed, treatment-decisions, perspectives of involved clinicians and overall survival (OS) in the Eindhoven Upper-GI Network consisting of 1 resection hospital and 5 referring hospitals. Between 2012 and 2018, patients diagnosed with OC within this region, were selected from the Netherlands Cancer Registry(n = 1119). From 2014, an uMDTM was gradually implemented and a mixed-method quantitative and qualitative design was used to analyse changes. Quantitative outcomes were described before and after implementation of the uMDTM. Clinicians were interviewed to assess their perspectives regarding the uMDTM. After participation in the uMDTM more patients were discussed in an MDTM (80%–89%, p < 0.0001) and involvement of a resection centre during the uMDTM increased (43%–82%, p < 0.0001). The proportion of patients diagnosed with potentially curable OC (cT1-4a-x, any cN, cM0) remained stable (59%–61%, p = 0.452). Endoscopic or surgical resections were performed more often (28%–34%, p = 0.034) and the use of best supportive care decreased (21%–15%, p = 0.018). In the qualitative part an improved knowledge, collaboration and discussion was perceived due to implementation of the uMDTM. Three-year OS for all OC patients increased after the implementation of the uMDTM (24%–30%, p = 0.025). Implementation of a regional Upper-GI MDTM was associated with an increase in patients discussed with a resection centre, more curative resections and a better OS. It remains to be elucidated which factors in the clinical pathway explain this observed improved survival. • A regional Upper-GI video MDTM was associated with more patients discussed with a resection centre. • Overall clinicians participating in the regional MDTM were satisfied with the organization. • Implementation of a regional Upper-GI video MDTM was associated with an improved overall survival. [ABSTRACT FROM AUTHOR]

Surgical resection is the cornerstone of curative treatment for gastric cancer. The aim of this study was to evaluate reasons for and patient- and tumor characteristics that are associated with refraining from surgical resection in patients with potentially curable gastric cancer. Between 2015 and 2017, all patients with potentially curable gastric adenocarcinoma (cT1-4a-x, cN0-3-x, cM0) were included from the Netherlands Cancer Registry (NCR). Patients were divided into a resection (RG) and a no-resection group (nRG). Reasons for not undergoing resection as registered by the NCR were evaluated. Using multivariable logistic regression analyses, patient and tumor characteristics associated with refraining from resection were assessed. Of the 1679 analyzed patients with potentially curable disease, 1127 patients (67%) underwent resection, and 552 patients (33%) did not. Most common registered reasons for refraining from surgery were patient refusal (25%), low performance status (23%), comorbidity and extent of disease (both 10%). Factors associated with not undergoing resection were: age ≥80 years (OR 4.77, [95%CI 2.27–10.06], p < 0.001), low Social-Economic-Status (SES) (OR 2.68 [95%CI 1.31–5.46], p = 0.007), WHO performance status 3–4 (OR 10.48 [95%CI 2.41–45.73], p = 0.002) with several accompanying comorbidities, unclassified Lauren classification (OR 3.93 [95%CI 1.61–9.56], p = 0.003) and overlapping/diffuse tumors (OR 3.51, [95%CI 1.54–8.05], p = 0.003). A third of patients with potentially curable gastric cancer did not undergo resection. Most frequent registered reasons for refraining from surgery were patient refusal, performance status, comorbidity and extent of disease. Additionally, multivariable analyses identified higher age, lower SES, and poor tumor characteristics as associated factors. • Of patients with potentially curable gastric cancer, 33% does not undergo surgery. • Most common reasons are patient refusal, worse performance status and comorbidity. • These reasons may reflect shared decision-making and practice variations. • Discrepancy between reason and patient features calls for accurate patient selection. [ABSTRACT FROM AUTHOR]

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 in oesophagogastric adenocarcinoma, as well as the effect on overall survival (OS). Synchronous metastatic oesophagogastric adenocarcinoma patients (2010–2017) were selected from the Netherlands Cancer Registry. Hospitals were categorised in volumes quartiles. The association between hospital systemic treatment volume and the use of beyond first-line treatment was assessed using trend and multivariable logistic regression analyses. OS was compared between hospitals with high and low beyond first-line treatment administration and treatment strategies using Kaplan–Meier curves with log-rank test and multivariable Cox proportional hazard regression. Beyond first-line treatment was administered in 606 of 2,466 patients who received first-line treatment, and increased from 20% to 31% between 2010 and 2017 (P < 0.001). The lowest hospital volumes were independently associated with lower beyond first-line treatment administration compared to the highest volume (OR 0.62, 95% CI 0.39–0.99; OR 0.67, 95% CI 0.48–0.95). Median OS was higher in all patients treated in hospitals with a high versus low beyond first-line treatment administration (7.9 versus 6.2 months, P < 0.001). Second-line paclitaxel/ramucirumab was administered most frequently and independently associated with longer OS compared to taxane monotherapy (HR 0.74, 95% CI 0.59–0.92). Higher hospital volume was associated with increased beyond first-line treatment administration in oesophagogastric adenocarcinoma. Second-line paclitaxel/ramucirumab resulted in longer survival compared to taxane monotherapy. • Beyond first-line treatment use in oesophagogastric cancer increased between 2010 and 2017. • Higher hospital volume is associated with increased beyond first-line treatment use. • Patients treated in high-volume beyond first-line treatment hospitals have better OS. • Second-line paclitaxel/ramucirumab resulted in longer OS than a taxane alone. [ABSTRACT FROM AUTHOR]

In several Western European countries it is recommended to treat gastric cancer patients with perioperative chemotherapy if they are eligible for surgery. However, little is known about its use in daily clinical practice. This study examines the use of perioperative treatment and its impact on survival in the Netherlands. Patients diagnosed with potentially resectable gastric cancer (cT1N+/cT2-T3,X any cN, cM0,X) between 2006 and 2014 were selected from the Netherlands Cancer Registry (N = 5824). Treatment trends were examined. Propensity score matching was used to create a subsample to reduce selection bias. Cox regression analysis was used to assess differences in overall survival. The percentage of patients treated with perioperative treatment increased from 3% in 2006 to 26% in 2014 and the use of only surgery decreased from 60% to 26%. 35% of all patients did not undergo surgery. Of the patients who underwent preoperative chemotherapy and surgery, 43% did not commence postoperative treatment. Cox regression analysis showed a better overall survival for patients who underwent perioperative treatment compared to patients who underwent preoperative treatment only (HR = 0.80 95%CI 0.70–0.93; propensity matched sample: HR = 0.84 95%CI 0.71–0.99), whereas survival was comparable for patients who underwent preoperative chemotherapy versus surgery alone (HR = 0.89 95%CI 0.77–1.02, propensity matched sample: HR = 0.85 95%CI 0.72–1.01). This population-based study highlights that a significant proportion of the patients did not receive perioperative treatment. More research is necessary to elucidate the importance of the individual components of perioperative treatment. [ABSTRACT FROM AUTHOR]

As previous studies showed significant hospital variation in curative treatment of esophagogastric cancer, this study assesses the association between this variation and overall, cancer-specific and recurrence-free survival, and Health-Related Quality of Life (HRQoL). Patients diagnosed with potentially curable esophageal or gastric cancer between 2015 and 2018 as registered in the Netherlands Cancer Registry were included. Data on overall survival was available for all patients, data on cancer-specific and recurrence-free survival and HRQoL was available for subgroups. Patients were classified according to diagnosis in hospitals with low, medium or high probability of treatment with curative intent (LP, MP or HP). Multivariable models were used to assess the association between LP, MP and HP hospitals and HRQoL and survival. This study includes 7,199 patients with esophageal, and 2,407 with gastric cancer. Overall and cancer-specific survival was better for patients diagnosed in HP versus LP hospitals for both esophageal (HR = 0.82, 95%CI:0.77–0.88 and HR = 0.82, 95%CI:0.75–0.91, respectively), and gastric cancer (HR = 0.82, 95%CI:0.73–0.92 and HR = 0.74, 95%CI:0.64–0.87, respectively). These differences disappeared after adjustments for treatment. Recurrence-free survival was worse for gastric cancer patients diagnosed in HP hospitals (HR = 1.50, 95%CI:1.14–1.96), which disappeared after adjustment for radicality of surgery. Minor, but no clinically relevant, differences in HRQoL were observed. Patients diagnosed in hospitals with a high probability of treatment with curative intent have a better overall and cancer-specific but not recurrence-free survival, while minor differences in HRQoL were observed. [ABSTRACT FROM AUTHOR]

Multidisciplinary team meetings (MDTM) and especially MDTMs in which expert centres are involved (expert MDTMs) are a key element in adequate cancer care. However, variation among hospitals in the proportion of patients presented during an expert MDTM has been described. This study aims to investigate national practice variation in the proportion of patients with oesophageal or gastric cancer being discussed during an expert MDTM. Patients diagnosed with oesophageal or gastric cancer in 2018–2019 were selected from the Netherlands Cancer Registry (n = 6,921). Multilevel logistic regression analyses were used to analyse the association between patient, and tumour characteristics, and the probability to be discussed in an expert MDTM. Variation was analysed according to the hospital and region of diagnosis for: all patients, patients with a potentially curable (cT1-4A cTX, any cN, cM0) or incurable tumour stage (cT4b and/or cM1). In total, 79% of patients were discussed during an expert MDTM, of whom 84% (n = 3,424) and 71% (n = 2,018) with potentially curable, or incurable oesophageal or gastric cancer, respectively. The proportion of patients discussed during an expert MDTM ranged from 54% to 98%, and 17% to 100% between hospitals for potentially curable and incurable patients, respectively (all p < 0.0001). Adjusted analyses showed significant hospital (all p < 0.0001), but no regional variation regarding the patients discussed during an expert MDTM. For patients with oesophageal or gastric cancer the probability of being discussed during an expert MDTM varies considerably according to the hospital of diagnosis. [ABSTRACT FROM AUTHOR]

Background This study aims to provide insight in the quality of current daily practice in clinical lymph node staging in colorectal cancer (CRC) in the Netherlands. Methods Data of the nationwide population-based Netherlands Cancer Registry between 2003 and 2014 were used to analyze lymph node staging for cM0 CRC patients. Accuracy of clinical lymph node staging was calculated for the period 2011–2014. Analyses were performed for patients without preoperative treatment or treated with short-course radiotherapy (SCRT) followed by resection. Results 100,211 patients were included for analysis. The proportion clinically positive lymph nodes increased significantly between 2003 and 2014 (6%–22% for colon cancer; 7%–53% for rectal cancer). The proportion histological positive lymph nodes remained stable (±35% colon, ±33% rectum). Data from 2011 to 2014 yielded a sensitivity, specificity, positive and negative predictive value of 41%, 84%, 59% and 71% for colon cancer, respectively (n = 21,629). This was 38%, 87%, 56%, 76% for rectal cancer without SCRT, (n = 2178) and 56%, 67%, 47% and 75% for rectal cancer with SCRT (n = 3401), respectively. Conclusion Accuracy of clinical lymph node staging in colorectal cancer patients is about as accurate as flipping a coin. This may lead to overtreatment of rectal cancer patients. Acceptable specificity and NPV limit the risk of undertreatment. [ABSTRACT FROM AUTHOR]

Background The aim of this population-based cohort study was to determine whether the addition of neoadjuvant chemoradiotherapy (nCRT) to surgery is associated with improved pathologic outcomes and survival in patients with cT2N0M0 esophageal cancer. Methods Patients who underwent nCRT followed by surgery or surgery alone for cT2N0M0 esophageal cancer were identified from The Netherlands Cancer Registry database (2005–2014). Accuracy of clinical staging was assessed using the resection specimen as gold standard. After propensity score matching, influences of both treatment strategies on radical resection (R0) rates and overall survival were compared. Results In total 533 patients were included; 353 underwent nCRT followed by surgery and 180 underwent surgery alone. In the nCRT group 32% of patients achieved a pathologic complete response. Clinical understaging was observed in 62% of the patients in the surgery alone group based on pT-stage (n = 30, 27%), pN-stage (n = 26, 23%), or both (n = 55, 50%). Propensity score matching resulted in 78 patients who underwent nCRT plus surgery versus 78 who underwent surgery alone. In the nCRT group radical resections were more frequently observed (99% vs. 89% p = 0.031) and resulted in improved 5-year overall survival (46% vs. 33%, p = 0.017). Conclusion In this population-based study, clinical staging of cT2N0M0 esophageal cancer was highly inaccurate. Compared to surgery alone, neoadjuvant chemoradiotherapy was associated with higher radical resection rates and improved overall survival. [ABSTRACT FROM AUTHOR]

Background Young patients with rectal cancer tend to present with more advanced-stage disease and unfavourable tumour morphology. The effects of these tumour characteristics on survival in this particular patient group are unclear. Methods Population-based data from the Netherlands Cancer Registry (NCR) were used. Data from patients diagnosed with rectal cancer between 1989 and 2010 were selected. Younger patients (⩽40 years) were compared with middle-aged patients (41–70 years) with respect to disease stage, tumour characteristics, treatment and outcomes. Patients aged older than 70 years were excluded. Relative excess risk (RER) models were used to perform uni- and multivariate survival analyses. Findings A total of 37.056 patients were included (⩽40 years n = 1.102). Compared with middle-aged patients, young patients were more likely to have stage III (33.8% versus 27.8%) and stage IV (24.3% versus 19.6%) disease ( p < 0.001). Young patients also presented more frequently with mucinous tumours (10.8% versus 9.0%), signet cell carcinomas (2.6% versus 0.6%) and poorly differentiated tumours (16.6% versus 12.3%) ( p = 0.001). The treatment of stage I–III patients did not differ between the two groups, except regarding adjuvant chemotherapy, which was more often given to young patients (24.3% versus 14.4%, p < 0.001). Young age was a prognostic factor for better survival in stage I–III patients (RER 0.82 CI 0.71–0.94). Adjuvant chemotherapy was associated with improved survival in stage I–III patients (RER 0.76, 95%CI 0.70–0.83). In an exploratory analysis, adjuvant chemotherapy in young stage III and pN1 patients was associated with improved survival. Concluding statement Young patients present with more advanced disease and have more unfavourable tumour characteristics compared with middle-aged patients. Despite these characteristics, survival rates are equal, and young age is a prognostic factor for better survival. Although the use of adjuvant chemotherapy is controversial, a positive correlation with survival was found in this study. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Until recently, peritoneal metastases (PM) were regarded as an untreatable condition, regardless of the organ of origin. Currently, promising treatment options are available for selected patients with PM from colorectal, appendiceal, ovarian or gastric carcinoma. The aim of this study was to investigate the incidence, treatment and survival of patients presenting with PM in whom the origin of PM remains unknown. Methods: Data from patients diagnosed with PM of unknown origin during 1984–2010 were extracted from the Eindhoven Cancer Registry. European age-standardised incidence rates were calculated and data on treatment and survival were analysed. Results: In total 1051 patients were diagnosed with PM of unknown origin. In 606 patients (58%) the peritoneum was the only site of metastasis, and 445 patients also had other metastases. Chemotherapy usage has increased from 8% in the earliest period to 16% in most recent years (p =.016). Median survival was extremely poor with only 42days (95% confidence interval (CI) 39–47days) and did not change over time. Median survival of patients not receiving chemotherapy was significantly worse than of those receiving chemotherapy (36 versus 218days, p <.0001). Conclusion: The prognosis of PM of unknown origin is extremely poor and did not improve over time. Given the recent progress that has been achieved in selected patients presenting with PM, maximum efforts should be undertaken in order to diagnose the origin of PM as accurately as possible. Potentially effective treatment strategies should be further explored for patients in whom the organ of origin remains unknown. [Copyright &y& Elsevier]

Abstract: Background: The reported annual incidence of adrenocortical carcinoma (ACC) is 0.5–2.0 cases per million individuals. Updated population-based studies on incidence are lacking. The aim of this nationwide survey was to describe the incidence and survival rates of ACC in the Netherlands. Secondary objectives were to evaluate changes in both survival rates and the number of patients undergoing surgery. Methods: All ACC patients registered in the Netherlands Cancer Registry (NCR) between 1993 and 2010 were included. Data on demographics, stage of disease, primary treatment modality and survival were evaluated. Results: Included were 359 patients, 196 of whom were female (55%). Median age at diagnosis was 56years (range 1–91). The 5-year age-standardised incidence rate decreased from 1.3 to 1.0 per one million person-years. Median survival for patients with stage I–II, stage III and stage IV disease was 159months (95% confidence interval (CI) 93–225months), 26months (95% CI: 4–48months) and 5months (95% CI: 2–7months), respectively (P <0.001). Improvement in survival was not observed, as reflected by the lack of association between survival and time of diagnosis. The percentage of patients receiving treatment within 6months after diagnosis increased significantly from 76% in 1993–1998 to 88% in 2005–2010 (P =0.047), mainly due to an increase in surgery for stage III–IV patients. Conclusion: These nationwide data provide an up-to-date survey of the epidemiology of ACC in the Netherlands. A trend towards a decreasing overall incidence rate was observed. Survival rates did not change during this period despite an increased number of surgical procedures. [Copyright &y& Elsevier]

Among them, 4.632 (57%) patients had an intestinal type carcinoma, 3.149 (39%) patients had a diffuse type carcinoma and 359 (4%) had a mixed type carcinoma. Compared to diffuse type carcinomas, the intestinal type carcinomas metastasised more frequently to the liver (56% versus 20%, p<0.0001) and lungs (13% versus 7%, p<0.0001), whereas diffuse type carcinomas metastasised more often to the peritoneum (55% versus 27%, p<0.0001), bones (9% versus 5%, p<0.0001) and ovaries (3% versus 1%, p<0.0001). The median survival for patients with metastatic intestinal type gastric adenocarcinoma was 4.3 months versus 3.9 months for patients with a metastatic diffuse type gastric carcinoma (p<0.0001). [Extracted from the article]

Colorectal cancers (CRCs) are rare in adolescents and adults ages 25 years or younger. We analyzed clinical, pathology, and molecular features of colorectal tumors from adolescents and young adults in an effort to improve genetic counseling, surveillance, and, ultimately, treatment and outcomes. We analyzed clinical data and molecular and genetic features of colorectal tumor tissues from 139 adolescents or young adults (age, ≤25 y; median age, 23 y; 58% male), collected from 2000 through 2017; tumor tissues and clinical data were obtained from the nationwide network and registry of histopathology and cytopathology and The Netherlands Cancer Registry, respectively. DNA samples from tumors were analyzed for microsatellite instability, mutations in 56 genes, and genome-wide somatic copy number aberrations. Mucinous and/or signet ring cell components were observed in 33% of tumor samples. A genetic tumor risk syndrome was confirmed for 39% of cases. Factors associated with shorter survival time included younger age at diagnosis, signet ring cell carcinoma, the absence of a genetic tumor risk syndrome, and diagnosis at an advanced stage of disease. Compared with colorectal tumors from patients ages 60 years or older in the Cancer Genome Atlas, higher proportions of tumors from adolescents or young adults were microsatellite stable with nearly diploid genomes, or contained somatic mutations in TP53 and POLE , whereas lower proportions contained mutations in APC. We found clinical, molecular, and genetic features of CRCs in adolescents or young adults to differ from those of patients older than age 60 years. In 39% of patients a genetic tumor risk syndrome was identified. These findings provide insight into the pathogenesis of CRC in young patients and suggest new strategies for clinical management. Performing genetic and molecular analyses for every individual diagnosed with CRC at age 25 years or younger would aid in this optimization. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy (CRT) is increasingly used as a nonsurgical treatment for esophageal cancer. In Japanese studies, salvage endoscopic resection (ER) has emerged as a promising strategy for local failure after definitive CRT. We aimed to evaluate the safety and efficacy of salvage ER in a Western setting. Gastroenterologists from Europe and the United States were invited to submit their experience with salvage endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) after definitive CRT. Participating gastroenterologists completed an anonymized database, including patient demographics, clinicopathologic variables, and follow-up on survival and recurrence. Gastroenterologists from 10 endoscopic units in 6 European countries submitted information on 25 patients. A total of 35 salvage ER procedures were performed, of which 69% were ESD and 31% EMR. Most patients had squamous cell carcinoma (64%) of the middle or lower esophagus (68%) staged as cT2-3 (68%) and cN+ (52%) before definitive CRT. The median time from end of definitive CRT to ER was 22 months (interquartile range, 6-47). The en-bloc resection rate was 92% for ESD and 46% for EMR. During a median of 24 months (interquartile range, 12-59) of follow-up after salvage ER, 52% developed a recurrence (11 locoregional, 2 distant). The 5-year recurrence-free survival, overall survival, and disease-specific survival were 36%, 52%, and 79%, respectively. No major intra- or postprocedural adverse events, such as bleeding or perforation, were reported. In carefully selected esophageal cancer patients, salvage ER is technically feasible after definitive CRT. Further prospective research is recommended to validate the safety and effectivity of salvage ER for the management of local failure. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this nationwide cohort study was to examine the course of symptoms and trajectories of health-related quality of life (HR-QoL) and psychological distress during follow-up and to identify vulnerable patients. Patients with pathological stage I–III colorectal cancer (CRC) between 2013 and 2018 were included. Baseline characteristics were collected from the Netherlands Cancer Registry, and patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30/CR29, Hospital Anxiety and Depression Scale and low anterior resection syndrome (LARS) questionnaires at the baseline and subsequently at 3, 6, 12, 18 and 24 months. Latent class growth and multinomial logistic regression analyses were performed to outline 24-month trajectories in HR-QoL and distress and to identify predictive factors. : A total of 1535 patients with colon cancer or rectal cancer were included. Trajectory analysis of HR-QoL identified three patient classes: high HR-QoL (62.7%), improving HR-QoL (29.0%) and low HR-QoL (8.3%). The following patient groups were identified with having low distress (64.0%), moderate distress (26.9%) and high distress (9.1%). Around 13% of the total cohort had either persistent low HR-QoL or high psychological distress throughout follow-up. Patients belonging to this vulnerable group were significantly more likely to be female, to be younger aged, to have lower education, to have disease stage II–III or to have major LARS. Although most patients treated for stage I–III CRC fared well, a small but significant proportion of around 13% did not recover during follow-up and reported low HR-QoL and/or high psychological distress levels throughout. This study's findings should be taken into account when organising and selecting patients for tailored follow-up. • The number of patients with colorectal cancer (CRC) requiring follow-up increased. • Quality of life (QoL) and distress among recently diagnosed patients with CRC are unclear. • Most patients with stage I–III CRC did well and reported high QoL and low distress. • Trajectory analysis revealed vulnerable patient groups and identified predictive factors. • Patient-reported outcome measures should be used when personalising CRC follow-up. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy (dCRT) is a treatment option with curative intent for patients with esophageal cancer that could result in late toxicities and affect health-related quality of life (HRQoL). This study aimed to review the literature and perform a meta-analysis to investigate the effect of dCRT on late toxicities and HRQoL in esophageal cancer. A systematic search was performed in MEDLINE, EMBASE, and PsychINFO. Prospective phase II and III clinical trials, population-based studies, and retrospective chart reviews investigating late toxicity or HRQoL after dCRT (≥50 Gy) were included. The HRQoL outcomes were analyzed using linear mixed-effect models with restricted cubic spline transformation. Any HRQoL changes of ≥10 points were considered clinically relevant. The risk of toxicities was calculated using the number of events and the total study population. Among 41 included studies, 10 assessed HRQoL and 31 late toxicity. Global health status remained stable over time and improved after 36 months compared with baseline (mean change, +11). Several tumor-specific symptoms, including dysphagia, eating restrictions, and pain, improved after 6 months compared with baseline. Compared with baseline, dyspnea worsened after 6 months (mean change, +16 points). The risk of any late toxicity was 48% (95% CI, 33%-64%). Late toxicity risk of any grade for the esophagus was 17% (95% CI, 12%-21%), pulmonary 21% (95% CI, 11%-31%), cardiac 12% (95% CI, 6%-17%), and any other organ 24% (95% CI, 2%-45%). Global health status remained stable over time, and tumor-specific symptoms improved within 6 months after dCRT compared with baseline, with the exception of dyspnea. In addition, substantial risks of late toxicity were observed. [ABSTRACT FROM AUTHOR]

Although curative treatment options are identical for male and female gastroesophageal cancer patients, access to care and survival may vary. This study aimed to compare treatment allocation and survival between male and female patients with potentially curable gastroesophageal cancer. Nationwide cohort study including all patients with potentially curable gastroesophageal squamous cell or adenocarcinoma diagnosed between 2006 and 2018 registered in the Netherlands Cancer Registry. The main outcome, treatment allocation, was compared between male and female patients with oesophageal adenocarcinoma (EAC), oesophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC). Additionally, 5-year relative survival with relative excess risk (RER), that is, adjusted for the normal life expectancy, was compared. Among 27,496 patients (68.8% men), most were allocated to curative treatment (62.8%), although rates dropped to 45.6%>70 years. Curative treatment rates were comparable among younger male and female patients (≤70 years) with gastroesophageal adenocarcinoma, while older females with EAC were less frequently allocated to curative treatment than males (OR = 0.85, 95% confidence interval [CI] 0.73–0.99). For those allocated to curative treatment, relative survival was superior for female patients with EAC (RER = 0.88, 95% CI 0.80–0.96) and ESCC (RER = 0.82, 95% CI 0.75–0.91), and comparable for males and females with GAC (RER = 1.02, 95% CI 0.94–1.11). While curative treatment rates were comparable between younger male and female patients with gastroesophageal adenocarcinoma, treatment disparities were present between older patients. When treated, the survival of females with EAC and ESCC was superior to males. The treatment and survival gaps between male and female patients with gastroesophageal cancer warrant further exploration and could potentially improve treatment strategies and survival. • Nationwide study (n = 27,496) showing sex disparities in gastroesophageal cancer. • 63% of patients with potentially curative disease received treatment (♂ 64%, ♀ 59%). • Sex disparities in treatment allocation were mostly present for patients>70 years. • When treated, female patients with EAC and ESCC had superior survival. • The treatment and survival gaps between sexes warrant further consideration. [ABSTRACT FROM AUTHOR]

This population-based cohort study analysed treatment, overall survival (OS), and independent prognostic factors for OS in gastric cancer patients with liver metastases. Between 2015 and 2017, patients with synchronous metastatic gastric or gastroesophageal junction adenocarcinoma limited to the liver were included from the prospectively maintained population-based Netherlands Cancer Registry. Liver oligometastatic disease (OMD) was defined as ≤3 liver metastases. The primary outcome was OS. Independent prognostic factors for OS were analysed using multivariable Cox regression analysis. A total 295 patients with metastases limited to the liver were included. The primary tumour was resected in four patients (1.4%). Treatment for liver metastases consisted of chemotherapy alone (28.1%), trastuzumab plus chemotherapy (4.7%), surgery (1.0%), or best supportive care (67.5%). Median OS across all included patients was 4.0 months (95% confidence interval [CI]: 3.1–4.5). Liver OMD was detected in 77 patients (26%). Treatment for liver OMD consisted of chemotherapy alone (24.6%), trastuzumab plus chemotherapy (5.2%), surgery (3.9%), or best supportive care (67.5%). Median OS among patients with liver OMD was 5.7 months (95% CI: 4.8–7.5). Across all patients, better OS was independently associated with liver OMD (hazard ratio [HR] 0.66, 95% CI: 0.50–0.87), trastuzumab (HR 0.41, 95% CI: 0.23–0.72) but not with triplet compared with doublet chemotherapy (HR 0.94, 95% CI: 0.57–2.87). Worse OS was independently associated with unknown nodal stage versus cN0 (HR 1.74, 95% CI: 1.17–2.60), diffuse-type versus intestinal-type adenocarcinoma (HR 2.06, 95% CI: 1.32–3.20), and monotherapy or best supportive care versus doublet chemotherapy (HR 1.72, 95% CI: 1.03–2.87, and HR 3.61, 95% CI: 2.55–5.10, respectively). In this population-based cohort study, liver OMD was detected in 26% of patients. Liver OMD and trastuzumab treatment were independently associated with better OS while triplet as compared with doublet chemotherapy was not. OS among patients with liver OMD nevertheless remained poor. The concept of OMD and the benefit of resection of liver OMD may still have been relatively unknown in this disease type during the study inclusion years. [Display omitted] • 26% of patients with metastatic disease limited to the liver had liver OMD. • Liver OMD was independently associated with superior overall survival. • Overall survival in patients with liver OMD was nevertheless poor. [ABSTRACT FROM AUTHOR]

Previous studies showed that the incidence of early-onset colorectal cancer (EO-CRC, diagnosis <50 years) is rising in Western countries. Additionally, young patients present with more advanced disease. Integrated nationwide assessment of epidemiologically and clinically relevant trends would provide more insight into this specific group of patients with CRC. We aimed to provide an analysis of trends in age- and stage-specific incidence, characteristics, treatment and relative survival of patients with EO-CRC in the Netherlands and compare these with 50- to 59-year-old patients. Data from 1989 to 2018 were retrieved from the Netherlands Cancer Registry. Non-standardised age-specific incidence rates were calculated, and trends were assessed using Joinpoint regression. Treatment and 5-year relative survival trends were provided and compared between EO-CRC and 50- to 59-year-old patients. The EO-CRC incidence annually increased with 0.7–2.1% over the last decades. CRC incidence for the 50- to 59-year-old population annually increased with 0.8–1.7% until 2006 and showed a major increase in incidence after the introduction of nationwide screening in 2014. Stage III and Stage IV CRC primarily increased across the studied age groups, while Stage I and Stage II CRC did not. Patients with EO-CRC received multimodal treatment more often than 50- to 59-year-old patients, but differences were minor. Relative survival increased over time and showed little differences between EO-CRC and 50- to 59-year-old patients. Only few epidemiological and clinical differences were found between EO-CRC and 50- to 59-year-old patients; hence, the urge for a specific approach of EO-CRC in screening and treatment guidelines might be tempered. • Early-onset colorectal cancer (EO-CRC) incidence increased in the Netherlands with 0.7–2.1% over the last decades. • This increase in incidence was highly comparable to the 50- to 59-year-old population. • EO-CRC treatment and relative survival differed slightly from 50- to 59-year-old patients with CRC. • The urge for a specific approach of EO-CRC in guidelines might be tempered. [ABSTRACT FROM AUTHOR]

Population-based predictive factors for the effectiveness of second-line 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. Patients with metastatic gastro-oesophageal cancer diagnosed in 2010–2017 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 (0–3, 3–6, 6–9 and >9 months), and the association with overall survival (OS) and second-line TTF was assessed using Kaplan-Meier curves and two-sided multivariable regression models. Median OS since the start of the second line of patients (n = 611) with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 4.0, 4.1, 5.5 and 7.1 months, respectively (P < 0.001). Median second-line TTF of patients with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 2.8, 2.4, 3.0 and 4.5 months, respectively (P < 0.001). Patients with first-line TTF of >9 months showed a longer OS than patients with first-line TTF of 0–3 months (adjusted hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.46–2.47), 3–6 months (adjusted HR 1.88; 95% CI 1.47–2.39) and 6–9 months (adjusted HR 1.31; 95% CI 1.04–1.65). Results for second-line TTF were similar. This study shows a positive correlation between effectiveness of first-line therapy and outcomes of second-line therapy in gastro-oesophageal cancer. Physicians should take duration of the first line into account when considering second-line palliative systemic therapy. • First-line time to treatment failure (TTF) is predictive for second-line TTF. • First-line TTF is predictive for second-line overall survival. • Clinicians should consider TTF when discussing the second line with patients. [ABSTRACT FROM AUTHOR]

The clinical significance of tumor-positive peritoneal cytology (CYT+) in gastric cancer (GC) patients is unclear. This nationwide cohort study aimed to i) assess the frequency of cytological analysis at staging laparoscopy; ii) determine the prevalence of CYT+GC; and iii) compare overall survival (OS) in CYT+ patients versus those with (PM+) and those without (PM-) macroscopic peritoneal disease. All patients diagnosed with cT1–4, cN0–2 and M0 or synchronous PM GC between 2016–2021 were identified in the Netherlands Cancer Registry database and linked to the nationwide pathology database. A total of 4397 patients was included, of which 40 % underwent cytological assessment following staging laparoscopy (863/1745). The prevalence of CYT+ was 8 %. A total of 69 patients had CYT+(1.6 %), 789 (17.9 %) had PM+ and 3539 (80.5 %) had PM- disease. Hazard ratio for OS in CYT+ versus PM+ was 0.86 (95 %CI 0.64–1.17, p-value=0.338), and in PM- versus PM+0.43 (95 %CI 0.38–0.49, p-value<0.001). No survival difference was found between systemic chemotherapy versus surgical resection in CYT+ patients. In this nationwide study, OS for gastric cancer patients with CYT+ was equally unfavorable as for those with PM+ and significantly worse as compared to those with PM-. The optimal treatment strategy has yet to be established. [Display omitted] • Tumor-positive peritoneal cytology and PM in GC had a comparable dismal survival. • Surgery and systemic treatment in CYT+ patients showed equal survival figures. • Staging laparoscopy including cytology improves patient selection for GC therapy. [ABSTRACT FROM AUTHOR]

It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging. [ABSTRACT FROM AUTHOR]

To investigate the nationwide time trends in incidence and survival of oesophageal and gastric adenocarcinomas according to the Laurén classification (intestinal, diffuse and mixed type). All patients diagnosed in the Netherlands with oesophageal or gastric adenocarcinoma between 1989 and 2015 were included. A syntax was developed to determine the histological subtype based on pathology reports as archived in the Dutch pathology registry. These reports were linked to individual data from the Netherlands Cancer Registry. Relative survival was used to assess survival. The histological subtype could be determined in 18.691 (84.1%) oesophageal and in 32.312 (83.5%) gastric adenocarcinomas. Among these, 79% were intestinal and 21% diffuse type in oesophageal cancers, compared to 55% intestinal and 44% diffuse type in gastric cancers. Relative median survival of intestinal type tumours was longer than that of diffuse type tumours, that is, 12.1 versus 9.4 months for oesophageal carcinomas, and 10.1 versus 7.6 months for gastric carcinomas, respectively. Between 1989 and 2015, the relative median survival of non-metastatic intestinal and diffuse type oesophageal adenocarcinoma improved from 12.0 to 30.0 months, and from 12.0 to 19.2 months, respectively. The same was true for intestinal type gastric carcinoma (from 22.8 to 27.6 months) but for diffuse type gastric carcinoma, the increase was less (from 16.8 to 18.0 months). In this nationwide study, histological subtypes of oesophageal and gastric adenocarcinomas differed in incidence and survival times. These findings may call for a differentiated treatment approach. • The Laurén classification is prognostic for survival in oesophagogastric cancer. • Intestinal type tumours are associated with a better survival. • Survival of oesophageal adenocarcinoma improved over the years. • Survival of diffuse type gastric carcinoma remained relatively unchanged. [ABSTRACT FROM AUTHOR]

Background Induction chemotherapy (IC) for clinically node-positive bladder cancer is applied without clinical evidence of improved outcome. Our objective was to compare complete pathological downstaging (pCD) and overall survival (OS) for IC versus upfront radical cystectomy (RC) in cT1-4aN1-3M0 urothelial carcinoma (UC). Methods This population-based study included 659 cN+ patients treated with RC between 1995 and 2013. IC was applied in 212 (32%) patients. We defined pCD as ≤(y)pT1N0 at RC. Multivariable analyses were preformed to identify independent predictors of pCD and OS. Results In cN1 and cN2–3 patients, 31% and 19% of patients proved to be pN0 at upfront RC. In cN1, pCD was achieved in 39% following IC versus 5% for upfront RC (P < 0.001). In cN2–3 UC, rates were 27% versus 3% (P < 0.001). Three-year OS for pCD and ypCD were 81% and 84%, respectively. Three-year OS rates were 66% versus 37% (cN1) and 43% versus 22% (cN2-3), again in favour of IC (P < 0.001). In multivariable analyses, IC was associated with pCD (Odds ratio, 14; 95% confidence interval [CI], 7.4–25) and a 53% decreased risk of death (Hazard ratio [HR], 0.47; 95% CI, 0.36–0.61). Indication bias and unequal distributions of factors associated with OS (e.g. patients proceeding to RC) limit interpretation of our results. Conclusions Patients with clinical nodal involvement should not be neglected. Up to 1/4 of patients with cN+ disease had pN0 at upfront RC. Moreover, IC followed by RC for clinically node-positive UC was associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial. Take home message IC followed by RC for clinically node-positive UC is associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial. [ABSTRACT FROM AUTHOR]

Abstract: Aim: For an evaluation of the progress achieved in the field of kidney cancer care in the Netherlands in the last decades, we described trends in incidence, treatment, mortality and relative survival. Methods: All adult patients newly diagnosed with kidney cancer between 1989 and 2009 (N =32,545) were selected from the Netherlands Cancer Registry. Age-standardised incidence and mortality rates were calculated. Follow-up was completed until January 2010. In order to assess trends estimated annual percentages of change (EAPC) were estimated. Results: The incidence of kidney cancer has been fairly stable between 1989 and 2001 with a European Standardised Rate of approximately 11 per 100,000 person years (PY). Since 2001 the incidence increased to 13 per 100,000 PY in 2009 (EAPC: 2.4%; 95%confidence interval (CI): 1.5 to 3.4%). The mortality rate decreased slightly over time, from 6.2 per 100,000 PY in 1989 to 5.6 in 2010. No changes in treatment were observed, except for the introduction of targeted therapies for stage IV disease, since 2005. The 5-year relative survival improved from 51% in 1989–1994 to 58% in 2005–2009 (EAPC: 0.9%; 95%CI 0.7 to 1.2%). Improvement in survival was especially seen in males, younger age groups and low stages. Conclusions: The incidence of kidney cancer has increased slightly, and survival improved modestly, resulting in a decreasing mortality. A positive effect of the introduction of targeted therapies for metastatic kidney cancer was observed in 1-year relative survival. For progress in kidney cancer care, effective prevention strategies and new therapies remain warranted. [Copyright &y& Elsevier]

Objective The aim of the study was to evaluate the effect of positive surgical margins (PSM) on health-related quality of life and illness perception after radical prostatectomy in patients with prostate cancer. Methods Of all patients with prostate cancer diagnosed between 2006 and 2009 in 7 participating hospitals in the Eindhoven region of the Netherlands Cancer Registry, 197 patients who underwent radical prostatectomy were invited to fill in a questionnaire. Data from the Netherlands Cancer Registry were combined with questionnaire data (including European Organization for Research and Treatment of Cancer quality of life questionnaire-C30, quality of life questionnaire–Prostate Module 25, and the Brief Illness Perception Questionnaire). Mean scores per margin status group were compared in multivariate linear regression. Results Of the addressed patients, 166 (84%) responded to the questionnaire. At time of questioning, their surgery was 1.7 to 6.4 years ago. The prevalence of PSM was 34%. On most scales, patients with PSM reported more favorable scores than patients with negative surgical margins. However, differences were mostly trivial (<5 points on 100-point scales), or of small (5–10) to medium (10–20) clinical importance. Only differences on hormonal complaints and illness comprehensibility were statistically significant. Effect of PSM on scores did not vary between patients who were at different time points after surgery. Conclusion Although patients with PSM showed a trend toward more favorable scores, these differences were of little or no clinical importance. Additional research is needed to evaluate how patients value these differences with respect to oncological outcomes. [ABSTRACT FROM AUTHOR]