Toward Optimizing Risk Adjustment in the Dutch Surgical Aneurysm Audit

Background: To compare hospital outcomes of aortic aneurysm surgery, casemix correction for preoperative variables is essential. Most of these variables can be deduced from mortality risk prediction models. Our aim was to identify the optimal set of preoperative variables associated with mortality to establish a relevant and efficient casemix model.Methods: All patients prospectively registered between 2013 and 2016 in the Dutch Surgical Aneurysm Audit (DSAA) were included for the analysis. After multiple imputation for missing variables, predictors for mortality following univariable logistic regression were analyzed in a manual backward multivariable logistic regression model and compared with three standard mortality risk prediction models: Glasgow Aneurysm Score (GAS, mainly clinical parameters), Vascular Biochemical and Haematological Outcome Model (VBHOM, mainly laboratory parameters), and Dutch Aneurysm Score (DAS, both clinical and laboratory parameters). Discrimination and calibration were tested and considered good with a C-statistic &gt; 0.8 and Hosmer-Lemeshow (H-L) P &gt; 0.05. Results: There were 12,401 patients: 9,537 (76.9%) elective patients (EAAA), 913 (7.4%) acute symptomatic patients (SAAA), and 1,951 (15.7%) patients with acute rupture (RAAA). Overall postoperative mortality was 6.5%; 1.8% after EAAA surgery, 6.6% after SAAA, and 29.6% after RAAA surgery. The optimal set of independent variables associated with mortality was a mix of clinical and laboratory parameters: gender, age, pulmonary comorbidity, operative setting, creatinine, aneurysm size, hemoglobin, Glasgow coma scale, electrocardiography, and systolic blood pressure (C-statistic 0.871). External validation overall of VBHOM, DAS, and GAS revealed C-statistics of 0.836, 0.782, and 0.761, with an H-L of 0.028, 0.00, and 0.128, respectively.Conclusions: The optimal set of variables for casemix correction in the DSAA comprises both clinical and laboratory parameters, which can be collected easily from electronic patient files and will lead to an efficient casemix model.</p

Quality Improvement of Pancreatic Surgery by Centralization in the Western Part of the Netherlands

BACKGROUND: Centralization of pancreatic surgery in high-volume hospitals is under debate in many countries. In the western part of the Netherlands, the professional network of surgical oncologists agreed to centralize all pancreatic surgery from 2006 in two high-volume hospitals. Our aim is to evaluate whether centralization of pancreatic surgery has improved clinical outcomes and has changed referral patterns. MATERIALS AND METHODS: Data of the Comprehensive Cancer Centre West (CCCW) of all 249 patients who had a resection for suspected pancreatic cancer between 1996 and 2008 in the western part of the Netherlands were analyzed. Multivariable modeling was used to evaluate survival for 3 time periods; 1996–2000, 2001–2005 (introduction of quality standards), and 2006–2008 (after centralization). In addition, the differences in referral pattern were analyzed. RESULTS: From 2006, all pancreatic surgery was centralized in 2 hospitals. The 2-year survival rate increased after centralization from 39% to 55% (P = .09) for all patients who had a pancreatic resection for pancreatic cancer. After adjustment for age, tumor location, stage, histology, and adjuvant treatment, the latter period was significantly associated with improved survival (hazard ratio [HR] 0.50; 95% confidence interval [95% CI] 0.34–0.73). CONCLUSIONS: Centralization of pancreatic surgery was successful and has resulted in improved clinical outcomes in the western part of the Netherlands, demonstrating the effectiveness of centralization

Laparoscopic conversion in colorectal cancer surgery; is there any improvement over time at a population level?

Conversion of laparoscopic colorectal cancer resection has been associated with worse outcome, but this might have been related to a learning curve effect. This study aimed to evaluate incidence, predictive factors and outcomes of laparoscopic conversion after the implementation phase of laparoscopic surgery at a population level. Patients undergoing elective resection of non-locally advanced, non-metastatic colorectal cancer between 2011 and 2015 were included. Data were extracted from the Dutch Surgical Colorectal Audit. Patients were grouped as laparoscopic completed (LR), laparoscopic converted (CONV) with further specification of timing (within or after 30 min) as registered in the DSCA, and open resection (OR). Uni- and multi-variate analyses were used to determine predictors of conversion and outcome (complicated course and mortality), with evaluation of trends over time. A total of 23,044 patients with colon cancer and 11,324 with rectal cancer were included. Between 2011 and 2015, use of laparoscopy increased from 55 to 84% in colon cancer, and from 49 to 89% in rectal cancer. Conversion rates decreased from 11.8 to 8.6% and from 13 to 8.0%, respectively. Laparoscopic hospital volume was independently associated with conversion rate. Only for colon cancer, the rate of complicated course was significantly higher after CONV compared to OR (adjusted odds ratio 1.486; 95% CI 1.298-1.702), and significantly higher after late (> 30 min) compared to early conversion (adjusted odds ratio 1.341; 1.046-1.719). There was no impact of CONV on mortality in both colon and rectal cancer. The use of laparoscopic colorectal cancer surgery increased to more than 80% at a national level, accompanied by a decrease in conversion which is significantly related to the laparoscopic hospital volume. Conversion was only associated with complicated course in colon cancer, especially when the reason for conversion consisted of an intra-operative complication, without affecting mortalit

Discontinuation of anti-PD-1 monotherapy in advanced melanoma:Outcomes of daily clinical practice

There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma:A Nationwide Cohort Study

SIMPLE SUMMARY: Melanoma is a malignant form of skin cancer. The overall survival of patients with advanced stages of disease were initially low. Fortunately, in recent years systemic treatment with immunotherapy has prolonged survival. We set out to answer the question whether men and women with advanced melanoma differ in prognostic factors, tumor-response to immunotherapy, and treatment-related adverse events. All patients in the Netherlands were registered between July 2013 and July 2018. We showed that although clinical and tumor characteristics differ, the safety profile of immunotherapy is comparable. Furthermore, overall, a 10% survival advantage for women was seen. Following immunotherapy there was no survival difference. ABSTRACT: Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013–July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3–4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients ≥60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference

Hospital Variation in Cancer Treatments and Survival OutComes of Advanced Melanoma Patients:Nationwide Quality Assurance in The Netherlands

Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hospital variation in treatment patterns and outcomes is evaluated in the Dutch Melanoma Treatment Registry. The aim of this study was to assess center variation in treatments and 2-year survival probabilities of patients diagnosed between 2013 and 2017 in the Netherlands.Methods: We selected patients diagnosed between 2013 and 2017 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. Centers' performance on 2-year survival was evaluated using Empirical Bayes estimates calculated in a random effects model. Treatment patterns of the centers with the lowest and highest estimates for 2-year survival were compared.Results: For patients diagnosed between 2014 and 2015, significant center variation in 2-year survival probabilities was observed even after correcting for case-mix and treatment with new systemic therapies. The different use of new systemic therapies partially explained the observed variation. From 2016 onwards, no significant difference in 2-year survival was observed between centers.Conclusion: Our data suggest that between 2014 and 2015, after correcting for patient case-mix, significant variation in 2-year survival probabilities between Dutch melanoma centers existed. The use of new systemic therapies could partially explain this variation. In 2013 and between 2016 and 2017, no significant variation between centers existed.</p

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

BACKGROUND: Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. METHODS: Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. RESULTS: 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). CONCLUSION: Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12072-021-10151-4

Chest Wall Resection for Adult Soft Tissue Sarcomas and Chondrosarcomas: Analysis of Prognostic Factors

Background: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. Methods: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. Results: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. Conclusions: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis

Survival outcomes of patients with advanced mucosal melanoma diagnosed from 2013 to 2017 in the Netherlands - A nationwide population-based study

Background: Mucosal melanoma (MM) is rare and has a poor prognosis. Since 2011, new effective treatments are available for advanced melanoma. It is unclear whether patients with mucosal melanoma equally benefit from these new treatments compared with patients with cutaneous melanoma (CM). Methods: Patients with advanced MM and CM diagnosed between 2013 and 2017 were included from a nationwide population-based registry – the Dutch Melanoma Treatment Registry. Overall survival (OS) was estimated with the Kaplan-Meier method (also for a propensity score-matched cohort). A Cox model was used to analyse the association of possible prognostic factors with OS. Results: In total, 120 patients with MM and 2960 patients with CM were included. Median OS was 8.7 months and 14.5 months, respectively. Patients with MM were older (median age 70 versus 65 years) and more often female (60% versus 41%), compared with CM. In total, 77% and 2% of the MM patients were treated with first-line immunotherapy and targeted therapy, respectively, compared with 49% and 33% of the CM patients. In contrast to CM, OS for MM did not improve for patients diagnosed in 2015–2017, compared with 2013–2014. ECOG performance score ≥1 (HR = 1.99 [1.26–3.15; p = 0.003]) and elevated LDH level (HR = 1.63 [0.96–2.76]; p = 0.069) in MM were associated with worse survival. Conclusions: Within the era of immune and targeted therapies, prognosis for patients with advanced MM has not improved as much as for CM. Collaboration is necessary to enlarge sample size for research to improve immunotherapeutic strategies and identify targetable mutations