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Contains fulltext : 292870.pdf (Publisher’s version ) (Open Access) Few clinical trials address efficacy of adjuvant systemic treatment in patients with in-transit melanoma (ITM). This study describes adjuvant systemic therapy of ITM patients beyond clinical trials. In this study, we included stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between July 2018 and December 2020. Patients were divided into three groups: nodal disease only, ITM only and ITM and nodal disease. Recurrence patterns, recurrence-free survival (RFS) and overall survival (OS) at 12-months were analyzed. In our study population of 1037 patients, 66.8% had nodal disease only, 16.7% had ITM only and 16.2% had ITM with nodal disease. RFS at 12-months was comparable in the nodal only and ITM only group (72.2% vs70.1%, P = .97) but lower in ITM and nodal disease patients (57.8%; P = .01, P

Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR 5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR 5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.

ObjectiveComplication rates after cytoreductive surgery are important quality indicators for hospitals that treat patients with advanced-stage ovarian cancer. Case-mix factors are patient and tumor characteristics that may influence hospital outcomes such as the complication rates. Currently, no case-mix adjustment model exists for complications after cytoreductive surgery; therefore, it is unclear whether hospitals are being compared correctly. This study aims to develop the first case-mix adjustment model for complications after surgery for advanced-stage ovarian cancer, enabling an accurate comparison between hospitals.MethodsThis population-based study included all patients undergoing cytoreductive surgery for advanced-stage ovarian cancer registered in the Netherlands in 2017–2019. Case-mix variables were identified and assessed using logistic regressions. The primary outcome was the composite outcome measure ‘complicated course’. Patients had a complicated course when at least one of the following criteria were met: (1) any complication combined with a prolonged length of hospital stay; (2) complication requiring reintervention; (3) any complication with a prolonged length of stay in the intensive care unit; or (4) 30-day mortality or in-hospital mortality during admission following surgery. Inter-hospital variation was analyzed using univariable and multivariable logistic regressions and visualized using funnel plots.ResultsA total of 1822 patients were included, of which 10.7% (n=195) had a complicated course. Comorbidity and tumor stage had a significant impact on complicated course rates in multivariable logistic regression. Inter-hospital variation was not significant for case-mix factors. Complicated course rates ranged between 2.2% and 29.1%, and case-mix adjusted observed/expected ratios ranged from 0.20 to 2.67 between hospitals. Three hospitals performed outside the confidence intervals for complicated course rates. These hospitals remained outliers after case-mix adjustment.ConclusionThere is variation between hospitals regarding complicated course rates after cytoreductive surgery for ovarian cancer in the Netherlands. While comorbidity and tumor stage significantly affected the complicated course rates, adjusting for case-mix factors did not significantly affect hospital outcomes. The limited impact of case-mix adjustment could be a result of the Dutch centralized healthcare model.

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1, intralesionally administered in patients with stage IIIB/C-IVM1a unresectable melanoma. When surgery is not a treatment option in the head and neck region, T-VEC can be an elegant alternative to systemic immunotherapy. Ten patients with metastatic melanoma in the head and neck region started treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events (AEs), and baseline characteristics. For response evaluation, we used clinical evaluation with photography, 3-monthly PET/computed tomography (PET/CT) using 18F-fluoro-2-D-deoxyglucose, and histological biopsies. Median age at baseline was 78.2 (35-97) years with a median follow-up of 11.6months. Of these 10 patients, 5 had a complete response (CR), 3 had a partial response, 1 had stable disease and 1 showed progressive disease (PD) as their best response. Best overall response rate (ORR) was 80%. Median progression-free survival was 10.8 months (95% confidence interval, 2.2-19.4). Grade 1 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms, and injection site pain. PET-CT and histological biopsies proved to be clinically useful tools to evaluate treatment response for T-VEC monotherapy, confirming pCR or PD to stage IV disease requiring systemic treatment. ORR for T-VEC monotherapy for melanoma in the head and neck region at our institute was 80% with 50% achieving a CR. This realworld data demonstrates promising results and suggests T-VEC can be an alternative to systemic therapy in this select, mostly elderly patient population.

Contains fulltext : 293454.pdf (Publisher’s version ) (Open Access) The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab-nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients' survival based on their baseline and disease characteristics.

Aim: To provide insight into healthcare resource utilization and hospital expenditure of patients treated for diabetes in Dutch hospitals. Materials and methods: We conducted an observational cohort study of 193 840 patients aged ≥18 years and treated for diabetes mellitus in 65 Dutch hospitals in 2019 to 2020, using real-world reimbursement data. Consultations, hospitalizations, technology use, total hospital and diabetes care costs (encompassing all care for diabetes itself) were assessed during 1-year follow-up. In addition, expenditure was compared with that in the general Dutch population. Results: Total hospital costs for all patients with diabetes were €1 352 690 257 (1.35 billion) per year, and 15.9% (€214 963 703) was associated with treatment of diabetes. Mean yearly costs per patient were €6978, with diabetes care costs of €1109. Mean hospital costs of patients exceeded that of the Dutch population three- to sixfold. Total hospital costs increased with age, whereas diabetes expenditure decreased with age (18-40 years, €1575; >70 years, €932). Of all patients with diabetes, 51.3% (n = 99 457) received care related to cardiovascular complications. Micro- and macrovascular complications, or a combination, increased hospital costs (1.4-5.3 times higher). Conclusions: The hospital resource use of Dutch diabetes patients is high, with a large burden of cardiovascular complications. Resource use is rooted mainly in hospital care of diabetes-related complications, not in the treatment of diabetes. Early treatment and prevention of complications remain imperative to taper future healthcare expenditure on patients with diabetes.

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus type 1, which can be administered intralesionally in patients with stage IIIB/C-IVM1a (American Joint Committee of Cancer; AJCC 7th edition) unresectable melanoma. In the case of disease recurrence, T-VEC can be re-introduced for the same category of patients. Five patients with recurrent disease after a prior achieved complete response (CR) recommenced treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We collected data on response, adverse events and baseline characteristics. All 5 patients that were re-treated with T-VEC presented with in-transit metastases on the lower limb. Median age at baseline was 72.1 years with a median follow-up time of 30.4 months. Histologically proven CR was achieved after a median of 8 T-VEC courses on the initial exposure. Duration of response (time between first CR and recurrence) varied between 3.8 and 14.2 months. All 5 patients achieved a histologically and/or positron emission tomography/computed tomography proven CR again after re-introduction of T-VEC with a median of 5 courses. One patient (20%) developed a second recurrence and is currently still on treatment with T-VEC. No patients developed distant metastases. Grade 1 adverse events occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site pain. Response to re-introduction of T-VEC monotherapy in this select patient population is promising. This real world data on re-introduction of T-VEC monotherapy in stage IIIB/C-IVM1a melanoma suggests T-VEC could be a treatment option for chronic disease control.

The COVID‐19 pandemic had a severe impact on medical care. Our study aims to investigate the impact of COVID‐19 on advanced melanoma care in the Netherlands. We selected patients diagnosed with irresectable stage IIIc and IV melanoma during the first and second COVID‐19 wave and compared them with patients diagnosed within the same time frame in 2018 and 2019. Patients were divided into three geographical regions. We investigated baseline characteristics, time from diagnosis until start of systemic therapy and postponement of anti‐PD‐1 courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P‐value, What's new? Little is known about the effects of COVID‐19 on advanced melanoma care. In this study, the authors examined several quality indicators of care. They observed a worsening in baseline characteristics, longer time between diagnosis and start of treatment and more postponed anti‐PD‐1 antibody courses with differences between the northern, middle and southern regions. Future studies are necessary to assess the long‐term consequences of our observed changes in advanced melanoma care.

Background: Oncological sigmoid and rectal resections are accompanied with substantial risk of anastomotic leakage. Preoperative risk assessment and patient selection remain difficult, highlighting the importance of finding easy-to-use parameters. This study evaluates the prognostic value of contrast-enhanced (CE) computed tomography (CT)-based muscle measurements for predicting anastomotic leakage. Methods: Patients that underwent oncological sigmoid and rectal resections in the LUMC between 2016 and 2020 were included. Preoperative CE-CT scans, were analyzed using Vitrea software to measure total abdominal muscle area (TAMA) and total psoas area (TPA). Muscle areas were standardized using patient's height into: psoas muscle index (PMI) and skeletal muscle index (SMI) (cm(2)/m(2)). Results: In total 46 patients were included, of which 13 (8.9%) suffered from anastomotic leakage. Patients with anastomotic leakage had a significantly lower PMI (22.1 vs. 25.1, p < 0.01) and SMI (41.8 vs. 46.6, p < 0.01). After adjusting for confounders (age and comorbidity), lower PMI (odds ratio [OR]: 0.85, 95% confidence interval [CI] 0.71-0.99, p = 0.03) and SMI (OR: 0.93, 95%CI 0.86-0.99, p = 0.02) were both associated with anastomotic leakage. Conclusion: This study showed that lower PMI and SMI were associated with anastomotic leakage. These results indicate that preoperative CT-based muscle measurements can be used as prognostic factor for risk stratification for anastomotic leakage.

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Simple Summary BRAF/MEK therapy and anti-PD-1 therapy have shown better recurrence-free survival of stage III melanoma in patients with BRAF V600 mutations in clinical trials. However, little is known about how these therapies compare to each other in everyday practice. The aim of our study was to describe the toxicity and survival of patients treated with BRAF/MEK therapy and anti-PD-1 therapy in daily practice. We demonstrated that grade >= 3 toxicity occurred in 11.5% of patients and was the most common cause of early treatment discontinuation (71.1%). We also show that at 12 months, patients treated with BRAF/MEK therapy have less progression than those treated with anti-PD-1 therapy. However, this is no longer the case at 18 months. Adjuvant BRAF/MEK- and anti-PD-1 inhibition have significantly improved recurrence-free survival (RFS) compared to placebo in resected stage III BRAF-mutant melanoma. However, data beyond the clinical trial setting are limited. This study describes the toxicity and survival of patients treated with adjuvant BRAF/MEK inhibitors and compares outcomes to adjuvant anti-PD-1. For this study, stage III BRAF V600 mutant cutaneous melanoma patients treated with adjuvant BRAF/MEK-inhibition or anti-PD-1 were identified from the Dutch Melanoma Treatment Registry. BRAF/MEK- and anti-PD-1-treated patients were matched based on propensity scores, and RFS at 12 and 18 months were estimated. Between 1 July 2018 and 31 December 2021, 717 patients were identified. Of these, 114 patients with complete records were treated with BRAF/MEK therapy and 532 with anti-PD-1. Comorbidities (p = 0.04) and geographical region (p < 0.01) were associated with treatment choice. In 45.6% of BRAF/MEK-treated patients, treatment was prematurely discontinued. Grade >= 3 toxicity occurred in 11.5% of patients and was the most common cause of early discontinuation (71.1%). At 12 and 18 months, RFS in BRAF/MEK-treated patients was 85% and 70%, compared to 68% and 68% in matched anti-PD-1-treated patients (p = 0.03). In conclusion, comorbidities and geographical region determine the choice of adjuvant treatment in patients with resected stage III BRAF-mutant melanoma. With the currently limited follow-up, BRAF/MEK-treated patients have better RFS at 12 months than matched anti-PD-1-treated patients, but this difference is no longer observed at 18 months. Therefore, longer follow-up data are necessary to estimate long-term effectiveness.

Background: Merkel cell carcinoma (MCC) is a cutaneous tumor with a high tendency to metastasize, and a significant proportion of patients have metastases at first presentation. This study aims to determine the value of baseline ultrasound (US) and (18)fluorodeoxyglucose-positron emission tomography/computed tomography ((18)FDG-PET/CT) imaging in both patients with clinically localized MCC (Stage I/II) and patients who present with palpable lymph nodes (Stage III). Methods: This retrospective cohort included 135 MCC patients who underwent baseline US (with fine needle aspiration cytology (FNAC)) and/or FDG-PET/CT imaging between 2015 and 2021. Results: Of the 104 patients with clinically localized disease, 48% were upstaged to Stage III and 3% to Stage IV by imaging or sentinel lymph node biopsy (SLNB). FDG-PET/CT imaging identified regional metastases in 23%, while US with FNAC identified regional metastases in 19%. SLNB was performed in 56 patients, of whom 57% were upstaged to Stage III. Of the 31 patients who presented with palpable lymph nodes, 16% were upstaged to Stage IV by FDG-PET/CT imaging. Conclusion: Baseline imaging frequently upstages Stage I/II MCC patients to Stage III, both by US and FDG-PET/CT, Stage IV disease is rarely identified. Patients who present with palpable nodes are frequently upstaged to Stage IV by FDG-PET/CT imaging.

Treatment with targeted therapy and immune checkpoint inhibitors has significantly improved survival of patients with advanced melanoma. Unfortunately, a large proportion of patients are either primary non-responders or will eventually develop secondary resistance. In 2017, Nosrati and colleagues published a prediction scale in the British Journal of Cancer, which included five clinical parameters that were associated with lower response to anti-PD-1 treatment; female sex (1 point), age 1]. This study used a derivation cohort of 228 patients treated in California, and a validation cohort of 87 patients treated in Switzerland. The primary outcome measure was best tumour response to treatment evaluated using computed tomography at 12 and 16 weeks after the first administration of anti-PD-1 monotherapy, and every 12 weeks thereafter. The aim of this correspondence is to validate the prediction scale, published by Nosrati and colleagues.

Simple Summary Nodular melanoma is associated with a higher locoregional recurrence rate and worse overall survival outcomes. Whether this histologic subtype affects the efficacy of immunotherapy or targeted therapy is unclear. The aim of our multi-center nationwide study is to identify the efficacy of immunotherapy and BRAF/MEKi therapy in metastatic nodular melanoma compared with the efficacy in metastatic superficial spreading melanoma. Our study results demonstrate no difference between the effectiveness of immunotherapy and BRAF/MEKi in metastatic nodular versus superficial melanoma patients. A shorter distant metastasis-free survival and reduced overall survival (measured as the time between primary melanoma up to death or last follow-up) was observed in the nodular melanoma patient group, suggesting worse overal survival of nodular melanoma is mainly driven by propensity of metastatic outgrowth of nodular melanoma after primary diagnosis. Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7-4.2) compared with SSM patients at 3.1 years (CI 95% 1.3-6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85-1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81-1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis.

Surgical resection is the mainstay of curative treatment for rectal cancer. Post-operative complications, low anterior resection syndrome (LARS), and the presence of a stoma may influence the quality of life after surgery. This study aimed to gain more insights into the long-term trade-off between stoma and anastomosis.All patients who underwent sphincter-sparing surgical resection for rectal cancer in the Leiden University Medical Center and the Reinier de Graaf Gasthuis between January 2012 and January 2016 were included. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, EQ-5D-5L, and the LARS score. A comparison was made between patients with a stoma and without a stoma after follow-up.Some 210 patients were included of which 149 returned the questionnaires (70.9%), after a mean follow-up of 3.69 years. Overall quality of life was not significantly different in patients with and without stoma after follow-up using the EORTC-QLQ-C30 (p = 0.15) or EQ-5D-5L (p = 0.28). However, after multivariate analysis, a significant difference was found for the presence of a stoma on global health status (p = 0.01) and physical functioning (p 0.01). Additionally, there was no difference detected in the quality of life between patients with major LARS or a stoma.This study shows that after correction for possible confounders, a stoma is associated with lower global health status and physical functioning. However, no differences were found in health-related quality of life between patients with major LARS and patients with a stoma. This suggests that the choice between stoma and anastomosis is mainly preferential and that shared decision-making is required.

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.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.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.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.

The use of Patient-Reported Outcome Measures (PROMs) for individual patient management within clinical practice is becoming increasingly important. New evidence about graphic visualization formats for PROMs scores has become available. This systematic literature review evaluated evidence for graphic visualization formats of PROMs data in clinical practice for patients and clinicians, for both individual and group level PROMs data.Studies published between 2000 and 2020 were extracted from CINAHL, PubMed, PsychInfo, and Medline. Studies included patients ≥ 18 years old in daily clinical practice. Papers not available in English, without full-text access, or that did not specifically describe visualization of PROMs data were excluded. Outcomes were: visualization preferences; interpretation accuracy; guidance for clinical interpretation.Twenty-five out of 789 papers were included for final analysis. Most frequently studied formats were: bar charts, line graphs, and pie charts. Patients preferred bar charts and line graphs as these were easy and quick for retrieving information about their PROMs scores over time. Clinicians' interpretation accuracy and preferences were similar among graphic visualization formats. Scores were most often compared with patients' own previous scores; to further guide clinical interpretation, scores were compared to norm population scores. Different 'add-ons' improved interpretability for patients and clinicians, e.g. using colors, descriptions of measurement scale directionality, descriptive labels, and brief definitions.There was no predominant graphical visualization format approach in terms of preferences or interpretation accuracy for both patients and clinicians. Detailed clarification of graph content is essential.Patient-Reported Outcome Measures (PROMs) capture patients' self-reported health through the use of questionnaires. PROMs measure health related quality of life, daily functioning, and symptom experience, which are becoming increasingly important to incorporate in clinical practice for individual patient management. To present PROMs within clinical practice, raw or summarized PROMs scores can be visualized in graphical formats. To be useful during clinical encounters, both patients and clinicians ought to interpret such formats correctly. New evidence about graphic visualization formats for PROMs scores has become available. Therefore, we systematically reviewed the literature to evaluate evidence for graphic visualization formats of PROMs data in clinical practice. In 25 included papers, most studies used graphical formats like bar charts, line graphs, and pie charts for presenting PROMs scores. There was no predominant graphical visualization format approach in terms of preferences or interpretation accuracy for both patients and clinicians. Patients preferred bar charts and line graphs as these were easy and quick for retrieving information about their PROMs scores over time. Clinicians’ interpretation accuracy and preferences were similar among graphic visualization formats. The graphical interpretation of PROMs data for patients and clinicians can be improved by using colors, descriptions of measurement scale directionality, descriptive labels, and brief definitions.

Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous and nodal melanoma lesions in stage IIIB-IVM1a patients. This study set out to identify prognostic factors for achieving a complete response that can be used to optimize patient selection for T-VEC monotherapy.Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2020-01 with a follow-up time 6 months, were included. Data were collected on baseline characteristics, responses and adverse events (AEs). Uni- and multivariable analyses were conducted, and a prediction model was developed to identify prognostic factors associated with CR.A total of 93 patients were included with a median age of 69 years, median follow-up time was 16.6 months. As best response, 58 patients (62%) had a CR, and the overall response rate was 79%. The durable response rate (objective response lasting 6 months) was 51%. Grade 1-2 AEs occurred in almost every patient. Tumor size, type of metastases, prior treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving CR. The prediction model includes the predictors tumor size, type of metastases and number of lesions.This study shows that intralesional T-VEC monotherapy is able to achieve high complete and durable responses. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting use earlier in the course of the disease.

Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAFWe selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAFBetween 2014 and 2017, a total of 330 and 254 advanced melanoma patients received BRAF/MEK inhibitors and anti-PD-1 monotherapy as first-line systemic therapy. In the matched cohort, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year overall survival compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months (95% CI: 37.3-NE) vs. 19.8 months (95% CI: 16.7-24.3) and 65.4% (95% CI: 58.1-73.6) vs. 41.7% (95% CI: 34.2-51.0).Our data suggest that in the matched BRAF

Wetenschappelijke verenigingen van medisch specialisten hebben de afgelopen jaren kwaliteitsregistraties geinitieerd die zijn opgezet volgens het clinical-auditing principe. Het primaire doel van deze landelijke audits is het verbeteren van zorguitkomsten, door behandelaars te voorzien van spiegelinformatie, waarmee zij de kwaliteit van hun zorgproces kunnen monitoren en verbeteren. Directe betrokkenheid van dokters bij de opzet en uitvoering van de audit, tijdige terugkoppeling van kwaliteitsaspecten die door henzelf belangrijk worden gevonden en het proactief volgen van ontwikkelingen in de zorg, zijn essentieel voor het succes van kwaliteitsregistraties. De mogelijkheid voor behandelaars om resultaten te monitoren, richtlijnnavolging en de introductie van de mogelijkheid om nieuwe technieken te evalueren en met kwaliteitsintiatieven hun uitkomsten te verbeteren, heeft tot substantiele vermindering van morbiditeit en mortaliteit geleid op diverse chirurgische terreinen. Registratie aan de bron, structurele financiering en goede afspraken over transparantie, zijn essentieel om clinical auditing te bestendigen als krachtig instrument in het kwaliteitsbeleid van wetenschappelijke verenigingen.

Textbook outcome (TO) studies have previously shown that a composite measure can provide additional information on the overall quality of surgical care. However, these were binominal outcomes which do not give individual hospitals the required information on how to improve their performance. The aim of this study is to create an ordered TO consisting of multiple outcome parameters for bariatric surgery to assess the extent of hospital variation.Patients who underwent a primary bariatric procedure in the Netherlands were included for analyses. The outcomes were ordered as mortality, severe postoperative complications, readmission, mild complications and prolonged length of stay (LOS) within 30 days after primary surgery with TO defined as none of these outcomes occurring. Hospitals were identified with a significantly higher or lower observed/expected ratio than expected based on case-mix and the extent of hospital variation was expressed as the median and interquartile range (IQR).From a total of 27,360 patients on average, 88.7% reached TO (range 35.5-96.9%). Two hospitals had less than expected TO due to more prolonged LOS (57.6%) in one hospital and more mild complications in another (17.1%). Hospital variation was much smaller for TO (median OR 0.91 IQR [0.62-1.06]) than for an ordered TO (median POR 0.66 IQR [0.55-0.96]).Using the ordered TO for bariatric surgery, more hospital variation was captured thereby enabling individual hospitals to identify which outcomes and specific groups need improvement. This could attribute to the ongoing effort to improve the quality of the outcome of bariatric surgery.

To evaluate treatment strategies and survival of patients with unresectable stage IIIc or IV melanoma since the 2012 introduction of new drugs in the Netherlands.Prospective cohort study.We analysed data from the Dutch Melanoma Treatment Registry (DMTR) regarding patients diagnosed with unresectable stage IIIc or IV melanoma in the period of 1 July 2012 to 31 December 2015. We estimated survival times using the Kaplan-Meier method. The relationship between year of diagnosis and survival was estimated using Cox regression analysis, adjusted for age, WHO performance status, lactate dehydrogenase values, stage, brain metastases and distant metastases.Out of 2,768 registered patients, approximately three-quarters received systemic therapy. This treatment was subject to change every year. Median survival was 10.7 months (95% CI: 9.6-13.2) in 2012 and 13.8 months (95% CI: 11.8-15.6) in 2015. Median survival for patients receiving systemic therapy was 17.1 months in 2015. 2-year survival in this period increased from 23% to 40%. Patients diagnosed in 2015 had better survival than patients of 2014 (hazard ratio (HR) 0.82; 95% CI: 0.73-0.93). This was also true for patients receiving systemic therapy (HR: 0.79; 95% CI: 0.69-0.91).Fast availability of new drugs, initiated by the then minister of VWS (health, welfare and sport) and the professional organisation, has thoroughly changed treatment of unresectable stage IIIc and IV melanoma. Data from the DMTR indicate safe use of these new drugs in daily practice and improved survival of advanced-melanoma patients in recent years.

In 2011, the NABON Breast Cancer Audit (NBCA) was instituted as a nation-wide audit to address quality of breast cancer care and guideline adherence in the Netherlands. The development of the NBCA and the results of 4 years of auditing are described.Clinical and pathological characteristics of patients diagnosed with invasive breast cancer or in situ carcinoma (DCIS) and information regarding diagnosis and treatment are collected in all hospitals (n = 92) in the Netherlands. Thirty-two quality indicators measuring care structure, processes and outcomes were evaluated over time and compared between hospitals.The NBCA contains data of 56,927 patients (7,649 DCIS and 49,073 invasive cancers). Patients being discussed in pre- and post-operative multidisciplinary team meetings improved (2011: 83% and 91%; 2014: 98% and 99%, respectively) over the years. Tumour margin positivity rates after breast-conserving surgery for invasive cancer requiring re-operation were consistently low (∼5%). Other indicators, for example, the use of an MRI-scan prior to surgery or immediate breast reconstruction following mastectomy showed considerable hospital variation.Results shown an overall high quality of breast cancer care in all hospitals in the Netherlands. For most quality indicators improvement was seen over time, while some indicators showed yet unexplained variation. J. Surg. Oncol. 2017;115:243-249. © 2016 Wiley Periodicals, Inc.

Precise nerve localization is of major importance in both surgery and regional anesthesia. Optically based techniques can identify tissue through differences in optical properties, like absorption and scattering. The aim of this study was to evaluate the potential of optical spectroscopy (diffuse reflectance spectroscopy) for clinical nerve identification in vivo. Eighteen patients (8 male, 10 female, age 53 ± 13 years) undergoing inguinal lymph node resection or resection or a soft tissue tumor in the groin were included to measure the femoral or sciatic nerve and the surrounding tissues. In vivo optical measurements were performed using Diffuse Reflectance Spectroscopy (400-1600 nm) on nerve, near nerve adipose tissue, muscle, and subcutaneous fat using a needle-shaped probe. Model-based analyses were used to derive verified quantitative parameters as concentrations of optical absorbers and several parameters describing scattering. A total of 628 optical spectra were recorded. Measured spectra reveal noticeable tissue specific characteristics. Optical absorption of water, fat, and oxy- and deoxyhemoglobin was manifested in the measured spectra. The parameters water and fat content showed significant differences (P 0.005) between nerve and all surrounding tissues. Classification using k-Nearest Neighbor based on the derived parameters revealed a sensitivity of 85% and a specificity of 79%, for identifying nerve from surrounding tissues. Diffuse Reflectance Spectroscopy identifies peripheral nerve bundles. The differences found between tissue groups are assignable to the tissue composition and structure.

Background Due to increasing healthcare costs, discussions regarding increased hospital costs when operating on high-risk patients is rising. Therefore, the aim of this study was to analyze if oldest-old colorectal cancer patients have a greater impact on hospital costs than their younger counterparts.All colorectal cancer procedures performed in 29 Dutch hospitals between 2010 and 2012 and listed in the Dutch Surgical Colorectal Audit were analyzed. Oldest-old patients (≥85 years) were compared to patients85 years. Ninety-day hospital costs were measured uniformly in all hospitals based on time-driven activity-based costs.Compared to85-year-old patients (n = 9130), the oldest old (n = 783) had longer hospital stays (LOS) (11.3 vs. 13.2, P 0.001), more severe complications (21.8% vs. 29.0%, P 0.001), more failure to rescue (13.9% vs. 37.0%, P 0.001) and higher mortality (3.0% vs. 10.7%, P 0.001). Deceased oldest-old patients had significantly less LOS and less LOS ICU. Total hospital costs were 3% lower for oldest-old patients (€13,168) than for85-year-old patients (€13,644, P 0.001). In cases of severe complications or death, hospital costs for the oldest old were 25% and 31% lower than those of85-year-old patients (both P 0.001).Although frequently assumed to be more expensive, operating on oldest-old patients with colorectal cancer does not increase hospital costs compared to younger patients. This was most likely due to faster deterioration or less aggressive treatment of oldest-old patients when (severe) complications occurred. J. Surg. Oncol. 2016;114:1009-1015. © 2016 Wiley Periodicals, Inc.

All Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5%. This study determined the value of IBTR as an indicator to compare quality of care between hospitals.Cohort studyAll patients with breast cancer (pT1-3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated using the Kaplan-Meier method. Hospital variation was presented in funnel plots . Multivariate analysis was used to assess hospital characteristics associated with IBTR rates.A total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85% (95%-CI 2.68-3.03) and was significantly lower for BCS than for mastectomy (2.38% vs 3.45%, p0.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70% between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5%. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates.Our population-based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value.

The objective of this study was to explore the association among adverse events, body mass index (BMI), and hospital costs after colorectal cancer surgery in a country with an intermediate BMI distribution.All colorectal cancer procedures in 29 Dutch hospitals listed in a 2010-2012 population-based database and with a BMI 18.5 were included (n = 8687). Hospital costs were measured uniformly and based on time-driven activity-based costing. The BMI classification of the World Health Organization was used.Patients in obesity classes 1 (23.6% [after risk-adjustment OR 1.245, CI 1.064-1.479, P = 0.007]) and ≥2 (28.1% [after risk-adjustment OR 1.816, CI 1.382-2.388, P 0.001]) were associated with more severe complications and higher hospital costs (€14,294, +9.6%, after risk-adjustment +7.9%, P 0.001; and €15,913 +22.0%, after risk-adjustment +21.2%, P 0.001, respectively) than normal weight patients (20.8% and €13,040, respectively). Pre-obese patients had significantly lower mortality rates (2.7%, after risk-adjustment, OR 0.756, CI 0.577-0.991, P = 0.042) than normal-weight patients (3.9%).Obese surgical colorectal cancer patients in a country with an intermediate BMI distribution are associated with a significant increase in hospital costs because these patients suffer from more severe complications. This is the first study to provide evidence for the "obesity-paradox" for mortality in colorectal cancer surgery. J. Surg. Oncol. 2016;113:489-495. © 2016 Wiley Periodicals, Inc.

Mortality following severe complications (failure-to-rescue, FTR) is targeted in surgical quality improvement projects. Rates may differ between colon- and rectal cancer resections.Analysis of patients undergoing elective colon and rectal cancer resections registered in the Dutch Surgical Colorectal Audit in 2011-2012. Severe complication- and FTR rates were compared between the groups in univariate and multivariate analysis.Colon cancer (CC) patients (n = 10,184) were older and had more comorbidity. Rectal cancer (RC) patients (n = 4,906) less often received an anastomosis and had more diverting stomas. Complication rates were higher in RC patients (24.8% vs. 18.3%, P 0.001). However, FTR rates were higher in CC patients (18.6% vs. 9.4%, P 0.001). Particularly, FTR associated with anastomotic leakage, postoperative bleeding, and infections was higher in CC patients. Adjusted for casemix, CC patients had a twofold risk of FTR compared to RC patients (OR 1.89, 95% CI 1.06-3.37).Severe complication rates were lower in CC patients than in RC patients; however, the risk of dying following a severe complication was twice as high in CC patients, regardless of differences in characteristics between the groups. Efforts should be made to improve recognition and management of postoperative (non-)surgical complications, especially in colon cancer surgery.

Quality indicators (QI) have been developed to measure quality of colorectal cancer care in the Netherlands. The aim of this study is to evaluate if these QI consistently assess the quality of colorectal cancer care in a hospital (internal consistency) and if these QI correlate with each other (construct validity).The performance of 85 hospitals participating in the Dutch Surgical Colorectal Audit between the 1st of January 2010 and 31st of December 2010, were evaluated on nine QI: three process indicators for colon cancer, three process indicators for rectal cancer and three outcome indicators. Consistency between all process indicators was assessed, and correlations between all process and outcome indicators were evaluated for colon and rectal cancer care separately.Hospital performance on the nine QI ranged widely. There was little consistency between the process indicators in assessing hospital performance. Most evaluated process indicators for colorectal cancer care did not correlate with each other, but were associated with better hospital specific patient outcomes.QI on colorectal cancer care do provide complementary information. Individual QI are not suitable as a surrogate measure for the quality of colorectal cancer care. More comprehensive measures are needed for true assessment of hospital performance.

The aim of this study was to describe the epidemiology and treatment of skin adnexal carcinoma (SAC) in the Netherlands and to identify prognostic factors for survival in patients with SAC.We used population-based nationwide data from the Netherlands Cancer Registry with cases diagnosed during 1989-2010 and followed up to February 1st, 2012.A total of 2,220 SACs were diagnosed during 1989-2010 (age-standardized incidence rate 5.3 per million). Incidence increased by 2.7% and 1.7% annually in males and females, respectively. Fifteen different morphological types were registered. The 5-year relative survival rate increased from 80% in 1989-1994 to 91% in 2006-2010. The majority of all patients (91%) received surgery. Adjuvant radiotherapy and/or lymph node dissection was performed in only a minority of cases. The risk of death was significantly higher in patients who did not receive surgery.The rising incidence of SAC together with the predilection for the head and neck region suggests a role for UV radiation in the carcinogenesis of SAC. Furthermore, we found an improved survival of SAC in the Netherlands between 1989 and 2010. In view of the low proportion of patients receiving adjuvant therapy there may be further room for improving survival.

To determine whether systematic audit and feedback of information about the process and outcomes improve the quality of surgical care.Systematic literature review.Embase, PubMed, and Web of Science databases were searched for publications on 'quality assessment' and 'surgery'. The references of the publications found were examined as well. Publications were included in the review if the effect of auditing on the quality of surgical care had been investigated.In the databases 2415 publications were found. After selection, 28 publications describing the effect of auditing, whether or not combined with a quality improvement project, on guideline adherence or indications of outcomes of care were included. In 21 studies, a statistically significant positive effect of auditing was reported. In 5 studies a positive effect was found, but this was either not significant or statistical significance was not determined. In 2 studies no effect was observed. 5 studies compared the combination of auditing with a quality improvement project with auditing alone; 4 of these reported an additional effect of the quality improvement project.Audit and feedback of quality information seem to have a positive effect on the quality of surgical care. The use of quality information from audits for the purpose of a quality improvement project can enhance the positive effect of the audit.

The aims of the study were to determine the percentage of false-negative sentinel node procedures in melanoma patients, to investigate the time cohort of these recurrences, whether a learning phase was involved and to search for causes of the failures.Between December 1993 and December 2008, 708 melanoma patients underwent a sentinel node biopsy. The procedure was considered false-negative if a recurrence developed in the basin from which a tumor-free sentinel node had been removed. Of all false-negative cases, the pre-operative images, operative report and pathology slides were reviewed.Sentinel node biopsy was positive in 164 (23%) of the patients and false-negative in 10 (1.4%), which results in a false-negative rate of 5.7%. Five of the 10 failures occurred in the first year after the sentinel node biopsy was introduced. Causes for these false-negative procedures could be attributed once to the nuclear medicine physician, once to the surgeon and twice to the pathologist.The sentinel node procedure failed to identify involvement in 5.7% of the patients with lymph node metastases. Half of the false-negative biopsies took place in the first year after the procedure was introduced, illustrating the existence of a learning period.

To determine whether the quality indicator 'tumour positive surgical margin following breast-conserving surgery, consistently measured the quality of breast-cancer surgery independently of the different definitions used and differences in case mix, taking statistical random variation into account.Descriptive study.Data was collected from 762 patients who underwent breast-conserving surgery for invasive or in situ carcinoma of the breast, in the period 1 July 2007 - 30 June 2008 in 1 of the 9 hospitals in the region of the Comprehensive Cancer Centre West in the Netherlands. We compared 3 definitions for 'tumour positive surgical margin': the one used by the Health Care Inspectorate, the one used by the organisation 'Zichtbare Zorg' ('transparent care') and the percentage of re-resection. For case mix correction we identified risk factors for tumour margin positivity with logistic regression. The results were presented in a funnel plot, using 95% confidence interval (CI) around the national standard of 20%.Depending on the definition used, the tumour positive surgical margin rate of the total group varied from 11 to 21%. Individual hospital rates varied by up to 19%. In situ carcinoma was associated with higher tumour positive surgical margin rates. Results differed significantly between hospitals for all 3 definitions. However, the funnel plot showed that results for most hospitals fell within the 95% CI of the standard. Whether a hospital fell within the 95% CI of the standard depended upon on the definition used and case mix correction.The lack of a single definition for the quality indicator 'tumour positive surgical margin following breast-conserving surgery' and the lack of case-mix correction undermine the validity of the indicator. Standardisation of definitions, uniform registration and the use of funnel plots can provide a more transparent insight into the quality of care.

In recent years there have been significant improvements in rectal cancer treatment. New surgical techniques as well as effective neoadjuvant treatment regimens have contributed to these improvements. Key is to spread these advances towards every rectal cancer patient and to ensure that not only patients who are treated within the framework of clinical trials may benefit from these advancements. Throughout Europe there have been interesting quality programmes that have proved to facilitate the spread of up to date knowledge and skills among medical professionals resulting in improved treatment outcome. Despite these laudable efforts there is still a wide variation in treatment outcome between countries, regions and institutions, which calls for a European audit on cancer treatment outcome.