Nationwide Impact of Centralization, Neoadjuvant Therapy, Minimally Invasive Surgery, and Standardized Pathology Reporting on R0 Resection and Overall Survival in Pancreatoduodenectomy for Pancreatic Cancer.

BACKGROUND: Surgeons aim for R0 resection in patients with pancreatic cancer to improve overall survival. However, it is unclear whether recent changes in pancreatic cancer care such as centralization, increased use of neoadjuvant therapy, minimally invasive surgery, and standardized pathology reporting have influenced R0 resections and whether R0 resection remains associated with overall survival. METHODS: This nationwide retrospective cohort study included consecutive patients after pancreatoduodenectomy (PD) for pancreatic cancer from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database (2009-2019). R0 resection was defined as > 1 mm tumor clearance at the pancreatic, posterior, and vascular resection margins. Completeness of pathology reporting was scored on the basis of six elements: histological diagnosis, tumor origin, radicality, tumor size, extent of invasion, and lymph node examination. RESULTS: Among 2955 patients after PD for pancreatic cancer, the R0 resection rate was 49%. The R0 resection rate decreased from 68 to 43% (2009-2019, P < 0.001). The extent of resections in high-volume hospitals, minimally invasive surgery, neoadjuvant therapy, and complete pathology reports all significantly increased over time. Only complete pathology reporting was independently associated with lower R0 rates (OR 0.76, 95% CI 0.69-0.83, P < 0.001). Higher hospital volume, neoadjuvant therapy, and minimally invasive surgery were not associated with R0. R0 resection remained independently associated with improved overall survival (HR 0.72, 95% CI 0.66-0.79, P < 0.001), as well as in the 214 patients after neoadjuvant treatment (HR 0.61, 95% CI 0.42-0.87, P = 0.007). CONCLUSIONS: The nationwide rate of R0 resections after PD for pancreatic cancer decreased over time, mostly related to more complete pathology reporting. R0 resection remained associated with overall survival.

Population-based impact of COVID-19 on incidence, treatment, and survival of patients with pancreatic cancer.

BACKGROUND: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care. METHODS: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017-2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan-Meier and Log-rank tests. RESULTS: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017-2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017-2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). CONCLUSION: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer.

Age and prognosis in patients with pancreatic cancer: a population-based study.

BACKGROUND: The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged <60 years to older PDAC patients. METHOD: This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015-31 December 2018). Kaplan-Meier curves and Cox proportional hazards models were used to assess OS. RESULTS: Overall, 10,298 patients were included, of whom 1551 (15%) were <60 years. Patients <60 years were more often male, had better performance status, less comorbidities and less stage I disease, and more often received anticancer treatment (67 vs. 33%, p < 0.001) than older patients. Patients <60 years underwent resection of the tumour more often (22 vs. 14%p < 0.001), more often received chemotherapy, and had a better median OS (6.9 vs. 3.3 months, p < 0.001) compared to older patients. No differences in median OS were demonstrated between both age groups of patients who underwent resection (19.7 vs. 19.4 months, p = 0.123), received chemotherapy alone (7.8 vs. 8.5 months, p = 0.191), or received no anticancer treatment (1.8 vs. 1.9 months, p = 0.600). Patients <60 years with stage-IV disease receiving chemotherapy had a somewhat better OS (7.5 vs. 6.3 months, p = 0.026). CONCLUSION: Patients with PDAC <60 years more often underwent resection despite less stage I disease and had superior OS. Stratified for treatment, however, survival was largely similar.

Outcomes After Major Surgical Procedures in Octogenarians: A Nationwide Cohort Study.

INTRODUCTION: Aging of the worldwide population has been observed, and postoperative outcomes could be worse in elderly patients. This nationwide study assessed trends in number of surgical resections in octogenarians regarding various major surgical procedures and associated postoperative outcomes. METHODS: All patients who underwent surgery between 2014 and 2018 were included from Dutch nationwide quality registries regarding esophageal, stomach, pancreas, colorectal liver metastases, colorectal cancer, lung cancer and abdominal aortic aneurysms (AAA). For each quality registry, the number of patients who were 80 years or older (octogenarians) was calculated per year. Postoperative outcomes were length of stay (LOS), 30 day major morbidity and 30 day mortality between octogenarians and younger patients. RESULTS: No increase in absolute number and proportion of octogenarians that underwent surgery was observed. Median LOS was higher in octogenarians who underwent surgery for colorectal cancer, colorectal liver metastases, lung cancer, pancreatic disease and esophageal cancer. 30 day major morbidity was higher in octogenarians who underwent surgery for colon cancer, esophageal cancer and elective AAA-repair. 30 day mortality was higher in octogenarians who underwent surgery for colorectal cancer, lung cancer, stomach cancer, pancreatic disease, esophageal cancer and elective AAA-repair. Median LOS decreased between 2014 and 2018 in octogenarians who underwent surgery for stomach cancer and colorectal cancer. 30 day major morbidity decreased between 2014 and 2018 in octogenarians who underwent surgery for colon cancer. No trends were observed in octogenarians regarding 30 day mortality between 2014 and 2018. CONCLUSION: No increase over time in absolute number and proportion of octogenarians that underwent major surgery was observed in the Netherlands. Postoperative outcomes were worse in octogenarians.

SOURCE-PANC: A Prediction Model for Patients With Metastatic Pancreatic Ductal Adenocarcinoma Based on Nationwide Population-Based Data.

BACKGROUND: A prediction model for overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (PDAC) including patient and treatment characteristics is currently not available, but it could be valuable for supporting clinicians in patient communication about expectations and prognosis. We aimed to develop a prediction model for OS in metastatic PDAC, called SOURCE-PANC, based on nationwide population-based data. MATERIALS AND METHODS: Data on patients diagnosed with synchronous metastatic PDAC in 2015 through 2018 were retrieved from the Netherlands Cancer Registry. A multivariate Cox regression model was created to predict OS for various treatment strategies. Available patient, tumor, and treatment characteristics were used to compose the model. Treatment strategies were categorized as systemic treatment (subdivided into FOLFIRINOX, gemcitabine/nab-paclitaxel, and gemcitabine monotherapy), biliary drainage, and best supportive care only. Validation was performed according to a temporal internal-external cross-validation scheme. The predictive quality was assessed with the C-index and calibration. RESULTS: Data for 4,739 patients were included in the model. Sixteen predictors were included: age, sex, performance status, laboratory values (albumin, bilirubin, CA19-9, lactate dehydrogenase), clinical tumor and nodal stage, tumor sublocation, presence of distant lymph node metastases, liver or peritoneal metastases, number of metastatic sites, and treatment strategy. The model demonstrated a C-index of 0.72 in the internal-external cross-validation and showed good calibration, with the intercept and slope 95% confidence intervals including the ideal values of 0 and 1, respectively. CONCLUSIONS: A population-based prediction model for OS was developed for patients with metastatic PDAC and showed good performance. The predictors that were included in the model comprised both baseline patient and tumor characteristics and type of treatment. SOURCE-PANC will be incorporated in an electronic decision support tool to support shared decision-making in clinical practice.

Treatment and Survival of Elderly Patients with Stage I-II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium.

BACKGROUND: Elderly patients with pancreatic cancer are underrepresented in clinical trials, resulting in a lack of evidence. OBJECTIVE: The aim of this study was to compare treatment and overall survival (OS) of patients aged ≥ 70 years with stage I-II pancreatic cancer in the EURECCA Pancreas Consortium. METHODS: This was an observational cohort study of the Belgian (BE), Dutch (NL), and Norwegian (NOR) cancer registries. The primary outcome was OS, while secondary outcomes were resection, 90-day mortality after resection, and (neo)adjuvant and palliative chemotherapy. RESULTS: In total, 3624 patients were included. Resection (BE: 50.2%; NL: 36.2%; NOR: 41.3%; p < 0.001), use of (neo)adjuvant chemotherapy (BE: 55.9%; NL: 41.9%; NOR: 13.8%; p < 0.001), palliative chemotherapy (BE: 39.5%; NL: 6.0%; NOR: 15.7%; p < 0.001), and 90-day mortality differed (BE: 11.7%; NL: 8.0%; NOR: 5.2%; p < 0.001). Furthermore, median OS in patients with (BE: 17.4; NL: 15.9; NOR: 25.4 months; p < 0.001) and without resection (BE: 7.0; NL: 3.9; NOR: 6.5 months; p < 0.001) also differed. CONCLUSIONS: Differences were observed in treatment and OS in patients aged ≥ 70 years with stage I-II pancreatic cancer, between the population-based cancer registries. Future studies should focus on selection criteria for (non)surgical treatment in older patients so that clinicians can tailor treatment.

Conditional Survival After Resection for Pancreatic Cancer: A Population-Based Study and Prediction Model.

BACKGROUND: Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. METHODS: This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005-2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0-5 years after resection was calculated using the Kaplan-Meier method. A prediction model was constructed. RESULTS: Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17-18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. CONCLUSIONS: This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers.

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis.

Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival.Material and methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007-2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient, tumor, and hospital characteristics, were used to analyze variation of chemotherapy use.Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007-2011 to 37% in 2012-2016 (p < .001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007-2011: 12-67%, 2012-2016: 20-54%) whereas overall survival increased from 5.6 months to 6.4 months (p < .001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015-2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015-2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy.Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens.

Patient characteristics and treatment considerations in pancreatic cancer: a population based study in the Netherlands.

BACKGROUND: Pancreatic cancer carries a poor prognosis. To date, there has been little research devoted to decision-making regarding treatment options in pancreatic cancer, including the rationale for choosing to withhold tumor targeting treatment (TTT). This study aims to gain insight into the characteristics of patients receiving no TTT, the reasons for this decision and their survival. METHODS: All patients diagnosed in the Netherlands between 1 January 2014 and 30 June 2015 with a proven pancreatic adenocarcinoma or a pathologically unverified pancreatic tumor were identified in the Netherlands Cancer Registry. Information on initial management, patient characteristics, main reasons for no TTT (as reported in medical charts) and survival were analyzed. RESULTS: A total of 3090 patients was included. Of these patients, 1818 (59%) received no TTT. Median age of no TTT patients was 74 years (range 35-99) versus 66 years (30-87) for TTT patients. In the no TTT group 77% had a clinical stage III/IV versus 57% of patients who received TTT. Main reasons for not starting TTT were patient's choice (27%) and extensive disease (21%). Median survival of patients who did not receive TTT was 1.9 months, ranging from a median survival of 0.8 months (when main reason to withhold TTT was short life expectancy) to 4.4 months (main reason to withhold TTT: old age). In the latter group, a relatively large proportion of clinical stage I tumors was present (37%). CONCLUSION: The majority of patients with pancreatic cancer received no TTT and had a very poor median survival. In most patients, patient's choice not to start treatment was the main reason for withholding treatment, suggesting patient's involvement in decision-making.

Association of the location of pancreatic ductal adenocarcinoma (head, body, tail) with tumor stage, treatment, and survival: a population-based analysis.

BACKGROUND: The association between pancreatic ductal adenocarcinoma (PDAC) location (head, body, tail) and tumor stage, treatment and overall survival (OS) is unclear. METHODS: Patients with PDAC diagnosed between 2005 and 2015 were included from the population-based Netherlands Cancer Registry. Patient, tumor and treatment characteristics were compared with the tumor locations. Multivariable logistic and Cox regression analyses were used. RESULTS: Overall, 19,023 patients were included. PDAC locations were 13,451 (71%) head, 2429 (13%) body and 3143 (16%) tail. Differences were found regarding metastasized disease (head 42%, body 69%, tail 84%, p < .001), size (>4 cm: 21%, 40%, 51%, p < .001) and resection rate (17%, 4%, 7%, p < .001). For patients without metastases, median OS did not differ between head, body, tail (after resection: 16.8, 15.0, 17.3 months, without resection: 5.2, 6.1, 4.6 months, respectively). For patients with metastases, median OS differed slightly (2.6, 2.4, 1.9 months, respectively, adjusted HR body versus head 1.17 (95%CI 1.10-1.23), tail versus head 1.35 (95%CI 1.29-1.41)). CONCLUSIONS: PDAC locations in body and tail are larger, more often metastasized and less often resectable than in the pancreatic head. Whereas survival is similar after resection, survival in metastasized disease is somewhat less for PDAC in the pancreatic body and tail.

Elderly Patients Strongly Benefit from Centralization of Pancreatic Cancer Surgery: A Population-Based Study.

BACKGROUND: Series from expert centers suggest that pancreas cancer surgery is safe for elderly patients but nationwide data, taking hospital volume into account, are lacking. METHODS: From the Netherlands Cancer Registry, all 3420 patients who underwent pancreatoduodenectomy (PD) for primary pancreatic or periampullary carcinoma in 2005-2013 were selected. Associations between age (<75, ≥75 years), hospital volume (tertiles), and postoperative mortality (30, 90 day) were evaluated by χ (2) tests and logistic regression analyses. Overall survival was investigated by means of Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: The proportion of elderly patients (≥75 years) undergoing PD increased from 15 % in 2005-2007 to 20 % in 2011-2013 (p = 0.009). In low (<15 per year), medium (15-28 per year), and high (>28 per year) hospital volume tertiles, the proportion of elderly patients was 16, 20, and 17 %, respectively (p = 0.10). With increasing hospital volume, 30-day postoperative mortality was 6.0-4.5-2.9 % (p = 0.002) and 90-day mortality 9.3-8.0-5.3 % (p = 0.001), respectively. Within each volume tertile, adjusted 30- and 90-day mortality of elderly patients was 1.6-2.5 times higher compared to outcomes of younger patients. Adjusted 30-day mortality in elderly patients was higher in low-volume hospitals (odds ratio = 2.87, 95 % confidence interval 1.15-7.17) compared to high-volume hospitals. Similarly, elderly patients had a worse overall survival in low-volume hospitals (hazard ratio = 1.28, 95 % confidence interval 1.01-1.63). Postoperative mortality of elderly patients in high-volume hospitals was similar to mortality of younger patients in low- and medium-volume hospitals. CONCLUSIONS: Elderly patients benefit from centralization by undergoing PD in high-volume hospitals, both with respect to postoperative mortality and survival. It would seem reasonable to place elderly patients into a high-risk category; they should only undergo surgery in the highest-tertile-volume hospitals.

National compliance to an evidence-based multidisciplinary guideline on pancreatic and periampullary carcinoma.

BACKGROUND: We evaluated national compliance to selected quality indicators from the Dutch multidisciplinary evidence-based guideline on pancreatic and periampullary carcinoma and identified areas for improvement. METHODS: Compliance to 3 selected quality indicators from the guideline was evaluated before and after implementation of the guideline in 2011: 1) adjuvant chemotherapy after tumor resection for pancreatic carcinoma, 2) discussion of the patient within a multidisciplinary team (MDT) meeting and 3) a maximum 3-week interval between final MDT meeting and start of treatment. RESULTS: In total 5086 patients with pancreatic or periampullary carcinoma were included. In 2010, 2522 patients were included and in 2012, 2564 patients. 1) Use of adjuvant chemotherapy following resection for pancreatic carcinoma increased significantly from 45% (120 out of 268) in 2010 to 54% (182 out of 336) in 2012 which was mainly caused by an increase in patients aged <75 years. 2) In 2012, 64% (896 of 1396) of patients suspected of a pancreatic or periampullary carcinoma was discussed within a MDT meeting which was higher in patients aged <75 years and patients starting treatment with curative intent. 3) In 2012, the recommended 3 weeks between final MDT meeting and start of treatment was met in 39% (141 of 363) of patients which was not influenced by patient and tumor characteristics. CONCLUSION: Compliance to three selected quality indicators in pancreatic cancer care was low in 2012. Areas for improvement were identified. Future compliance will be investigated through structured audit and feedback from the Dutch Pancreatic Cancer Audit.

Pancreatic cancer surgery in elderly patients: Balancing between short-term harm and long-term benefit. A population-based study in the Netherlands.

BACKGROUND: At a national level, it is unknown to what degree elderly patients with pancreatic or periampullary carcinoma benefit from surgical treatment compared to their younger counterparts. We investigated resection rates and outcomes after surgical treatment among elderly patients. METHODS: From the Netherlands Cancer Registry, 20 005 patients diagnosed with primary pancreatic or periampullary cancer in 2005-2013 were selected. The associations between age (<70, 70-74, 75-79, ≥80 years) and resection rates were investigated using χ(2) tests, and surgical outcomes (30-, 90-day mortality) were evaluated using logistic regression analysis. Overall survival after resection was investigated by means of Kaplan-Meier and Cox proportional hazard regression analysis. RESULTS: During the study period, resection rates increased in all age groups (<70 years: 20-30%, p < 0.001; ≥80 years: 2-8%, p < 0.001). Of 3845 patients who underwent tumour resection for pancreatic or periampullary carcinoma, the proportion of octogenarians increased from 3.5% to 5.5% (p = 0.03), whereas postoperative mortality did not increase (30-day: 6-3%, p = 0.06; 90-day: 9-8%, p = 0.21). With rising age, 30-day postoperative mortality increased (4-5-7-8%, respectively, p < 0.001), while 90-day mortality was 6-10-13-12% (p < 0.001) and three-year overall survival rates after surgery were 35-33-28-31%, respectively (p < 0.001). After adjustment for confounding factors, octogenarians who survived 90 days postoperative exhibited an overall survival close to younger patients [hazard ratio (≥80 vs. <70 years) = 1.21, 95% confidence interval (0.99-1.47), p = 0.07]. CONCLUSION: Despite higher short-term mortality, octogenarians who underwent pancreatic resection showed long-term survival similar to younger patients. With careful patient screening and counselling of elderly patients, a further increase of resection rates may be combined with improved outcomes.

Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly.

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality.

Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly.

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality.

Differences between colon and rectal cancer in complications, short-term survival and recurrences.

PURPOSE: Many apparent differences exist in aetiology, genetics, anatomy and treatment response between colon cancer (CC) and rectal cancer (RC). This study examines the differences in patient characteristics, prevalence of complications and their effect on short-term survival, long-term survival and the rate of recurrence between RC and CC. METHODS: For all stage II-III CC and RC patients who underwent resection with curative intent (2006-2008) in five hospitals in the Netherlands, occurrence of complications, crude survival, relative survival and recurrence rates were compared. RESULTS: A total of 767 CC and 272 RC patients underwent resection. Significant differences were found for age, gender, emergency surgery, T-stage and grade. CC patients experienced fewer complications compared to RC (p = 0.019), but CC patients had worse short-term mortality rates (1.5 versus 6.7 % for 30-day mortality, p = 0.001 and 5.2 versus 9.5 % for 90-day mortality, p = 0.032). The adjusted HR (overall survival) for CC patients with complications was 1.57 (1.23-2.01; p < 0.001) as compared to patients without complications; for RC, the HR was 1.79 (1.12-2.87; p = 0.015). Relative survival analyses showed high excess mortality in the first months after surgery and a sustained, prolonged negative effect on both CC and RC. Complications were associated with a higher recurrence rate for both CC and RC; adjusted analyses showed a trend towards a significant association. CONCLUSION: Large differences exist in patient characteristics and clinical outcomes between CC and RC. CC patients have a significantly higher short-term mortality compared to RC patients due to a more severe effect of complications.

Volume-outcome relationships in pancreatoduodenectomy for cancer.

BACKGROUND: Volume-outcome relationships in pancreatic surgery are well established, but an optimal volume remains to be determined. Studies analyzing outcomes in volume categories exceeding 20 procedures annually are lacking. STUDY DESIGN: A consecutive 3420 patients underwent PD for primary pancreatic or periampullary carcinoma (2005-2013) and were registered in the Netherlands Cancer Registry. Relationships between hospital volume (< 5, 5-19, 20-39 and ≥ 40 PDs/year) and mortality and survival were explored. RESULTS: There was a non-significant decrease in 90-day mortality from 8.1 to 6.7% during the study period (p = 0.23). Ninety-day mortality was 9.7% in centers performing < 5 PDs/year (n = 185 patients), 8.9% for 5-19 PDs/year (n = 1432), 7.3% for 20-39 PDs/year (n = 240) and 4.3% for ≥ 40 PDs/year (n = 562, p = 0.004). Within volume categories, 90-day mortality did not change over time. After adjustment for confounding factors, significantly lower mortality was found in the ≥ 40 category compared to 20-39 PDs/year (OR = 1.72 (1.08-2.74)). Overall survival adjusted for confounding factors was better in the ≥ 40 category compared to categories under 20 PDs/year: HR (≥ 40 vs 5-19/year) = 1.24 (1.09-1.42). In the ≥ 40 category significantly more patients received adjuvant chemotherapy and had > 10 lymph nodes retrieved compared to lower volume categories. CONCLUSIONS: Volume-outcome relationships in pancreatic surgery persist in centers performing ≥ 40 PDs annually, regarding both mortality and survival. The volume plateau for pancreatic surgery has yet to be determined.

Centralization of esophagectomy: how far should we go?

BACKGROUND: This study was designed to define a statistically sound and clinically meaningful cutoff point for annual hospital volume for esophagectomy. Higher hospital volumes are associated with improved outcomes after esophagectomy. However, reported optimal volumes in literature vary, and minimal volume standards in different countries show considerable variation. So far, there has been no research on the noncategorical, nonlinear, volume-outcome relationship in esophagectomy. METHODS: Data were derived from the Netherlands Cancer Registry. Restricted cubic splines were used to investigate the nonlinear effects of annual hospital volume on 6 month and 2 year mortality rates. Outcomes were adjusted for year of diagnosis, case-mix, and (neo)adjuvant treatment. RESULTS: Between 1989 and 2009, 10,025 patients underwent esophagectomy for cancer in the Netherlands. Annual hospital volumes varied between 1 and 83 year, increasing over time. Increasing annual hospital volume showed a continuous, nonlinear decrease in hazard ratio (HR) for mortality along the curve. Increasing hospital volume from 20 year (baseline, HR = 1.00) to 40 and 60 year was associated with decreasing 6 month mortality, with a HR of 0.73 (95 % confidence interval (0.65-0.83) and 0.67 (0.58-0.77) respectively. Beyond 60 year, no further decrease was detected. Higher hospital volume also was associated with decreasing 2 year mortality until 50 esophagectomies year with a HR of 0.86 (0.79-0.93). CONCLUSIONS: Centralization of esophagectomy to a minimum of 20 resections/year has been effectively introduced in the Netherlands. Increasing annual hospital volume was associated with a nonlinear decrease in mortality up to 40-60 esophagectomies/year, after which a plateau was reached. This finding may guide quality improvement efforts worldwide.

Risk factors for excess mortality in the first year after curative surgery for colorectal cancer.

BACKGROUND: Thirty-day mortality after surgery for colorectal cancer may vastly underestimate 1-year mortality. This study aimed to quantify the excess mortality in the first postoperative year of stage I-III colorectal cancer patients and to identify risk factors for excess mortality. METHODS: All 2,131 patients who were operated with curative intent for stage I-III colorectal cancer in the western region of the Netherlands between January 1, 2006, and December 31, 2008, were analyzed. Thirty-day mortality and relative survival were calculated. In addition, relative excess risk (RER) of death was estimated by a multivariable model. RESULTS: Thirty-day mortality was 4.9%. One-year mortality was 12.4%. Risk factors for excess mortality in the first postoperative year for colon cancer patients were emergency surgery (excess mortality 29.7%, RER 2.5, 95% confidence interval 2.5-5.0), a Charlson score of >1 (excess mortality 12.6%, RER 2.3, 95% confidence interval 1.5-3.7), stage II or III disease (excess mortality 14.9%, RER 3.9, 95% confidence interval 1.9-8.1), and postoperative adverse events (excess mortality 22.6%, RER 2.1, 95% confidence interval 1.4-3.2). CONCLUSIONS: The 30-day mortality rate highly underestimates the risk of dying in the first year after surgery, with excess 1-year mortality rates varying from 15 to 30%. This excess mortality was especially prominent in patients with comorbidities, higher stages of disease, emergency surgery, and postoperative surgical complications.