Endobronchial Ultrasonography to Assess and Evaluate Tracheobronchial Tree Invasion in cT4b Esophageal Cancer Patients Treated with Definitive Chemoradiotherapy: Assessment of Resectability.

BACKGROUND: In cT4b esophageal cancer, accurate assessment of tracheobronchial tree invasion after definitive chemoradiotherapy (dCRT) aids in the selection of patients for whom an oncologic radical esophagectomy can be achieved. The current report aimed to determine the accuracy of endobronchial ultrasound in assessing tumor invasion in the tracheobronchial tree after dCRT in patients with cT4b esophageal cancer. METHODS: Esophageal cancer patients with suspicion of tracheobronchial tree invasion on the diagnostic contrast-enhanced computed tomography (CT) who underwent a staging endobronchial ultrasonography (EBUS) were eligible for inclusion in this study. To assess the accuracy of the EBUS in assessing tumor ingrowth in the tracheobronchial tree after dCRT, patients who had an EBUS during restaging and underwent surgery were included in the final analysis. RESULTS: The final analysis included 26 patients. For 18 (90%) of 20 patients in whom the anatomy of the tracheobronchial tree was restored on the restaging EBUS and tumor invasion was considered to be absent, a radical esophagectomy was achieved. In six patients, persistent ingrowth was observed during the restaging EBUS. For these patients, the EBUS was repeated after a median of 9 weeks. Tumor invasion was considered to be absent in four patients, and a radical resection was achieved in three of these patients. CONCLUSION: The EBUS provides valuable information on the assessment of tracheobronchial tree invasion in cT4b esophageal cancer patients after dCRT. This information could aid in the proper selection of patients who benefit from a curative but highly invasive esophagectomy.

Salvage Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) for T4b Esophageal Cancer After Definitive Chemoradiotherapy.

BACKGROUND: Patients  with esophageal cancer  that invades adjacent structures (cT4b) are precluded from surgery and usually treated with definitive chemoradiotherapy (dCRT). dCRT might result in sufficient downstaging to enable a radical resection, possibly improving survival. This study aimed to assess the perioperative and oncologic outcomes of a salvage robot-assisted minimally invasive esophagectomy (RAMIE) in patients with cT4b esophageal cancer after dCRT. METHODS: Between June 2012 and November 2019, patients who underwent a RAMIE with a gastric conduit reconstruction after completion of dCRT for cT4b esophageal carcinoma were identified from a prospectively maintained surgical database at the University Medical Center Utrecht. RESULTS: In total, 24 patients with a histopathologically confirmed T4b adenocarcinoma or squamous cell carcinoma of the esophagus were included. The adjacent organs involved were the tracheobronchial tree (67%), aorta (21%) or both (13%). No conversions or major intraoperative complications were observed. A radical resection was achieved in 22 patients (92%), and a pathologic complete response was observed in 13 (54%) patients. Postoperative grade 2 or higher complications occurred in 20 patients (83%). The disease-free survival at 24 months was 68% for the patients in whom a radical resection was achieved. CONCLUSION: In patients with cT4b esophageal cancer treated with dCRT followed by a salvage RAMIE, a radical resection rate of 92% was achieved, with acceptable complications and promising survival rates. These results demonstrate the feasibility of a curative surgical treatment for patients with initially irresectable esophageal cancer but underscore the importance of a proper preoperative patient selection.

The treatment and survival of elderly patients with locally advanced pancreatic cancer: A post-hoc analysis of a multicenter registry.

BACKGROUND: The treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant. This study aims to clarify the association between increasing age, treatment and overall survival in patients with LAPC. METHODS: Post-hoc analysis of a multicenter registry including consecutive patients with LAPC, who were registered in 14 centers of the Dutch Pancreatic Cancer Group (April 2015-December 2017). Patients were divided in three groups according to age (<65, 65-74 and ≥75 years). Primary outcome was overall survival stratified by primary treatment strategy. Multivariable regression analyses were performed to adjust for possible confounders. RESULTS: Overall, 422 patients with LAPC were included; 162 patients (38%) aged <65 years, 182 patients (43%) aged 65-74 and 78 patients (19%) aged ≥75 years. Chemotherapy was administered in 86%, 81% and 50% of the patients in the different age groups (p<0.01). Median overall survival was 12, 11 and 7 months for the different age groups (p<0.01).Patients treated with chemotherapy showed comparable median overall survival of 13, 14 and 10 months for the different age groups (p=0.11). When adjusted for confounders, age was not associated with overall survival. CONCLUSION: Elderly patients are less likely to be treated with chemotherapy, but when treated with chemotherapy, their survival is comparable to younger patients.

Recurrence after preoperative chemotherapy and surgery for gastric adenocarcinoma: a multicenter study.

BACKGROUND: In most western European countries perioperative chemotherapy is a part of standard curative treatment for gastric cancer. Nevertheless, recurrence rates remain high after multimodality treatment. This study examines patterns of recurrence in patients receiving perioperative chemotherapy with surgery for gastric cancer in a real-world setting. METHODS: All patients diagnosed with gastric adenocarcinoma between 2010 and 2015 who underwent at least preoperative chemotherapy and a gastrectomy with curative intent (cT1N+/cT2-4a,X; any cN; cM0) in 18 Dutch hospitals were selected from the Netherlands Cancer Registry. Additional data on chemotherapy and recurrence were collected from medical records. Rates, patterns, and timing of recurrence were examined. Multivariable Cox proportional hazard analyses were used to determine prognostic factors for recurrence. RESULTS: 408 patients were identified. After a median follow-up of 27.8 months, 36.8% of the gastric cancer patients had a recurrence of which the majority (88.8%) had distant metastasis. The 1-year recurrence-free survival was 71.8%. The risk of recurrence was higher in patients with an ypN+ stage (HR 4.92, 95% CI 3.35-7.24), partial or no tumor regression (HR 2.63, 95% CI 1.22-5.64), 3 instead of ≥ 6 chemotherapy cycles (HR 3.04, 95% CI 1.99-4.63), R1 resection (HR 1.52, 95% CI 1.02-2.26), and < 15 resected lymph nodes (HR 1.64, 95% CI 1.14-2.37). CONCLUSION: A considerable amount of gastric cancer patients who were treated with curative intent developed a recurrence despite surgery and perioperative treatment. The majority developed distant metastases, therefore, multimodality treatment approaches should be focused on the prevention of distant rather than locoregional recurrences to improve survival.

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

BACKGROUND: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. METHODS: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. DISCUSSION: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. TRIAL REGISTRATION: NCT03208621 . This trial was registered prospectively on June 30, 2017.

Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013.

BACKGROUND: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival. METHODS: We included all patients diagnosed with synchronous metastatic esophageal cancer in the south of the Netherlands between 1 January 1994 and 31 December 2013. Proportions of patients treated with external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were described with respect to the period of diagnosis, patient and tumor characteristics. Independent risk factors for death were discriminated. RESULTS: A total of 1020 patients were included, 61.5% of these patients received palliative treatment with external beam radiotherapy, chemoradiotherapy, brachytherapy and/or chemotherapy. The use of external beam radiotherapy decreased from 44.5% in 1994 to 22.2% in 2013 (p = 0.0001), whereas the use of chemoradiotherapy increased from 2.9% in 1994 to 19.1% in 2013 (p < 0.0001). The prescription of systemic chemotherapy as single modality increased from 13.9% to 30.5% (p < 0.0001). The use of brachytherapy decreased from 20.9% in 1994 to 7.4% in 2013 (p = 0.0013). The odds of receiving external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were influenced by different tumor and patient characteristics, such as age, gender, histologic subtype and number of metastatic sites. The median overall survival in patients with metastatic esophageal cancer significantly improved over time from 18 weeks (one-year survival rate 14.4%) in 1994-1998 to 25 weeks (one-year survival rate 22.4%) in 2009-2013. Patients treated with chemoradiotherapy had the most favorable prognosis, followed by patients treated with chemotherapy as a single modality. CONCLUSION: The median overall survival of patients diagnosed with metastatic esophageal cancer improved from 18 weeks in 1994-1998 to 25 weeks in 2009-2013. Although this increase could be attributed to stage migration, our population-based study suggests that major changes in treatment strategies and appropriate patient selection might have played a role as well.

Burden of spousal caregivers of stage II and III esophageal cancer survivors 3 years after treatment with curative intent.

OBJECTIVES: The aim of this study is to examine caregiver burden of spousal caregivers of patients with esophageal cancer after curative treatment with neoadjuvant chemoradiation followed by resection and to assess factors associated with caregiver burden. METHODS: In this exploratory, cross-sectional study, spousal caregivers and patients were eligible if the caregiver was the patient's spouse and the patient had been treated with chemoradiation followed by surgery after esophageal carcinoma diagnosis. Forty-seven couples were included. Spousal caregivers completed a questionnaire, examining caregivers' burden (Self-Perceived Pressure from Informal Care (SPPIC, Dutch)), caregiver unmet needs (SCNS-P&S), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), and marital satisfaction (Maudsley Marital Questionnaire (MMQ)). Patients completed the latter two questionnaires and a cancer specific quality of life questionnaire (EORTC-QLQ C30 and OES18 (oesophageal module). Logistic regression analysis was performed to identify correlates for caregiver burden. RESULTS: The median time after esophagectomy was 38 months. Thirty-four percent of the spousal caregivers reported moderate or high burden. Spousal caregivers most frequently reported unmet needs were managing concerns about the cancer coming back (43%), dealing with others not acknowledging the impact on your life of caring for a person with cancer (38%), and balancing the needs of the person with cancer and one's own needs. A comparable proportion of spousal caregivers and patients showed symptoms of anxiety (23 vs 17%) and depression (17 vs 17%). Spousal caregivers reported significantly more dissatisfaction than patients on the marital scale (p < 0.01). Factors independently associated with higher caregiver burden were fatigue of the patient (OR = 1.66, 95% CI 1.12-2.47) and depression of the spousal caregiver (OR = 1.44, 95% CI 1.11-1.86). CONCLUSIONS: More than a third of the spousal caregivers of patients with esophageal cancer treated with curative intent report moderate or high burden 3 years after treatment. Fatigue of the patient and depression of the spousal caregiver are associated with caregiver burden. To improve clinical care, identification of spousal caregivers at risk for experiencing higher caregiver burden and implementation of specific interventions is needed.

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial.

BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma.

Gastroesophageal cancers are a major cause of death worldwide and treatment outcomes remain poor. Adequate predictive biomarkers have not been identified. Microsatellite instability (MSI) as a result of mismatch repair deficiency is present in four to twenty percent of gastroesophageal cancers and has been associated with favorable survival outcomes compared to microsatellite stable tumors. This prognostic advantage may be related to immunosurveillance, which may also explain the favorable response to immune checkpoint inhibition observed in MSI high (MSI-H) tumors. The value of conventional cytotoxic treatment in MSI-H tumors is unclear and results on its efficacy range from detrimental to beneficial effects. Here the recent data on MSI as a predictive factor for outcome of gastroesophageal cancer treatment is reviewed.

Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials.

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs).

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer-A Systematic Review.

Survival after potentially curative treatment of gastric cancer remains low, mostly due to peritoneal recurrence. This descriptive review gives an overview of available comparative studies concerning prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with neither clinically evident metastases nor positive peritoneal cytology who undergo potentially curative gastrectomy. After searching the PubMed, Embase, CDSR, CENTRAL and ASCO meeting library, a total of 11 studies were included comparing surgery plus prophylactic HIPEC versus surgery alone (SA): three randomised controlled trials and eight non-randomised comparative studies, involving 1145 patients. Risk of bias was high in most of the studies. Morbidity after prophylactic HIPEC was 17-60% compared to 25-43% after SA. Overall survival was 32-35 months after prophylactic HIPEC and 22-28 months after SA. The 5-year survival rates were 39-87% after prophylactic HIPEC and 17-61% after SA, which was statistically significant in three studies. Peritoneal recurrence occurred in 7-27% in the HIPEC group, compared to 14-45% after SA. This review tends to demonstrate that prophylactic HIPEC for gastric cancer can be performed safely, may prevent peritoneal recurrence and may prolong survival. However, studies were heterogeneous and outdated, which emphasizes the need for well-designed trials conducted according to current standards.

Management of resectable esophageal and gastric (mixed adeno)neuroendocrine carcinoma: A nationwide cohort study.

INTRODUCTION: The aim of this study is to provide insight in accuracy of diagnosing, current treatment and survival in patients with resectable esophageal and gastric neuroendocrine- and mixed adenoneuroendocrine carcinomas (NEC, MANEC). METHODS: All patients with esophageal or gastric (MA)NEC, who underwent surgical resection between 2006 and 2016, were identified from the Dutch national registry for histo- and cytopathology (PALGA). Patients with a neuroendocrine tumor lower than grade 3 were excluded. Data on patients, treatment and outcomes were retrieved from the patient records. Diagnosis by endoscopic biopsy was compared with diagnosis by resection specimen. Kaplan Meier survival analysis was performed. RESULTS: A total of 49 patients were identified in 25 hospitals, including 21 patients with esophageal (MA)NEC and 26 patients with gastric (MA)NEC on resection specimen. Biopsy diagnosis of (MA)NEC was correct in 23/27 patients. However, 20/47 patients with definitive diagnosis of (MA)NEC, were misdiagnosed on biopsy. Neoadjuvant therapy was administered in 13 (62%) esophageal (MA)NECs and 12 (46%) gastric (MA)NECs. Survival curves were similar with and without neoadjuvant therapy. One (4.8%) esophageal (MA)NEC and 4 (15%) gastric (MA)NECs died within 90 days postoperatively. For esophageal (MA)NEC the median overall survival (OS) after surgery was 37 months and 1-, 3- and 5-year OS were 71%, 50% and 35%, respectively. For gastric (MA)NEC, the median OS was 23 months and 1-, 3- and 5-year OS were 62%, 50% and 39%, respectively. CONCLUSION: Localized esophageal and gastric (MA)NEC are often misdiagnosed on endoscopic biopsies. After resection, long-term survival was achieved in respectively 35% and 39% of patients.

The effect of perioperative chemotherapy for patients with an adenocarcinoma of the gastroesophageal junction: A propensity score matched analysis.

BACKGROUND: The optimal neoadjuvant approach for patients with adenocarcinomas of the gastroesophageal junction (GEJ) remains unclear. Aim of this study was to evaluate the usefulness of perioperative chemotherapy in these patients. METHOD: Consecutive patients with GEJ adenocarcinoma, treated with surgery alone or chemotherapy plus surgery, were included from a prospective database (2003-2013). Propensity score matching was used to build comparable groups. Response to chemotherapy was assessed according to standardized regression grading. RESULTS: After propensity score matching, 196 patients were included. Chemotherapy was administered in 124 patients (63%). There was no difference between the chemotherapy plus surgery and surgery-alone group regarding overall and disease-free survival (p = 0.351 and p = 0.529). Pathological good response (i.e. tumor regression grading [TRG] 1-3) was achieved in 32 patients (34%), whereas 81 (66%) had poor response (TRG 4). Good responders had lower ypT-stage (p < 0.001), lower ypN-stage (p < 0.001) and more R0-resections (100% vs. 78%, p = 0.016) compared to surgery-alone patients, which improved the 5-year survival from 35% to 67% (p = 0.002). They also developed less recurrences (35% vs. 57%, p = 0.048). In poor responders, histopathology did not differ compared to surgery-alone and more recurrences were found (73% vs. 57%, p = 0.037). Overall survival in poor responders was 21% compared to 35% in surgery-alone patients (p = 0.551). CONCLUSION: Perioperative chemotherapy for GEJ adenocarcinoma leads to increased survival in good responders (34%) as compared to surgery alone. Poor responders had no survival benefit and developed more recurrences, which underlines the importance of the search for predictive biological or radiological markers to predict or assess chemotherapy sensitivity.

Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer.

INTRODUCTION: Palliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival. METHODS: Patients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival. RESULTS: Our data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19-21 weeks) and 16 weeks (95% CI 15-17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70-0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78-0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74-0.92) had a superior outcome. CONCLUSION: Improved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.

Volume matters in the systemic treatment of metastatic pancreatic cancer: a population-based study in the Netherlands.

PURPOSE: In pancreatic surgery, a relation between surgical volume and postoperative mortality and overall survival (OS) has been recognized, with high-volume centers reporting significantly better survival rates. We aimed to explore the influence of hospital volume on administration of palliative chemotherapy and OS in the Netherlands. METHODS: Patients diagnosed between 2007 and 2011 with metastatic pancreatic cancer were identified in the Netherlands Cancer Registry. Three types of high-volume centers were defined: high-volume (1) incidence center, based on the number of patients diagnosed with metastatic pancreatic cancer, (2) treatment center based on number of patients with metastatic pancreatic cancer who started treatment with palliative chemotherapy and (3) surgical center based on the number of resections with curative intent for pancreatic cancer. Independent predictors of administration of palliative chemotherapy were evaluated by means of logistic regression analysis. The multivariable Cox proportional hazard model was used to assess the impact of being diagnosed or treated in high-volume centers on survival. RESULTS: A total of 5385 patients presented with metastatic pancreatic cancer of which 24 % received palliative chemotherapy. Being treated with chemotherapy in a high-volume chemotherapy treatment center was associated with improved survival (HR 0.76, 95 % CI 0.67-0.87). Also, in all patients with metastatic pancreatic cancer, being diagnosed in a high-volume surgical center was associated with improved survival (HR 0.74, 95 % CI 0.66-0.83). CONCLUSIONS: Hospital volume of palliative chemotherapy for metastatic pancreatic cancer was associated with improved survival, demonstrating that a volume-outcome relationship, as described for pancreatic surgery, may also exist for pancreatic medical oncology.