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Background: Desmoid‐type fibromatosis (DTF) has a highly variable clinical course with varying intensity of symptoms. The objectives of this study were to identify subgroups of DTF patients based on physical symptom burden and to compare symptom burden subgroups on health‐related quality of life (HRQoL) and healthcare use (univariate and multivariate). Methods: Desmoid‐type fibromatosis patients from the United Kingdom and the Netherlands received cross‐sectional questionnaires on HRQoL (EORTC QLQ‐C30), DTF‐specific HRQoL (DTF‐QoL) and healthcare utilisation. Latent class cluster analysis was performed to identify subgroups based on patients' symptom burden using EORTC QLQ‐C30 and DTF‐QoL physical symptom items. Multivariate linear and logistic regression analyses were conducted to examine associations of symptom burden with HRQoL and healthcare utilisation, respectively. Results: Among 235 DTF patients, four symptom burden clusters were identified, with low symptom burden (24%), intermediate symptom burden‐low pain (20%), intermediate symptom burden‐high pain (25%) and high symptom burden (31%). DTF patients with high symptom burden had clinically relevant lower HRQoL scores compared to patients with low and intermediate symptom burden (p < 0.001) and reported more general and DTF‐related visits to their general practitioner compared to the low symptom burden cluster (p < 0.01). In the multivariate analyses, symptom burden was independently associated with both HRQoL and healthcare utilisation. Conclusions: This study identified four distinct subgroups of DTF patients based on their level of symptom burden, with a considerable number of patients being highly symptomatic. Knowledge of the level of symptom burden DTF patients experience can help to identify patients at risk of poorer outcomes and tailor supportive care to the individual needs of DTF patients. [ABSTRACT FROM AUTHOR]

Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery. This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment. 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score ≥3 (aOR 0.70, CI 0.51–0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44–0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34–0.94, p = 0.02), Charlson Comorbidity Index ≥2 (aOR 0.73, CI 0.54–0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36–0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed. TO differs between indications for liver resection and can be used to assess between hospital and network differences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Timely recognition of soft tissue sarcomas (STS) remains challenging, potentially leading to unplanned excisions (also known as 'whoops procedures'). This population-based study charted the occurrence of unplanned excisions and identified associated patient, tumour, and treatment-related characteristics. Furthermore, it presents an overview of the outcomes and clinical management following an unplanned excision. From the Netherlands Cancer Registry (NCR) database, information was obtained on 2187 adult patients diagnosed with STS in 2016–2019 who underwent surgery. Tumours located in the mediastinum, heart or retroperitoneum were excluded, as well as incidental findings. Differences between patients with planned and unplanned excisions were assessed with chi-square tests and a multivariable logistic regression model. Overall, unplanned excisions comprise 18.2% of all first operations for STS, with a quarter of them occurring outside a hospital. Within hospitals, the unplanned excision rate was 14.4%. Unplanned excisions were more often performed on younger patients, and tumours unsuspected of being STS prior to surgery were generally smaller (≤5 cm) and superficially located. Preoperative imaging was omitted more frequently in these cases. An unplanned excision more often resulted in positive margins, requiring re-excision. Patients who had an unplanned excision outside of a sarcoma centre were more often discussed at or referred to a sarcoma centre, particularly in case of residual tumour. Potential improvement in preventing unplanned excisions may be achieved by better compliance to preoperative imaging and referral guidelines, and stimulating continuous awareness of STS among general surgeons, general practitioners and private practices. [ABSTRACT FROM AUTHOR]

Histopathological growth patterns (HGPs) are a reliable, reproducible, and strong prognostic biomarker that can be assessed on haematoxylin and eosin‐stained sections of resected colorectal liver metastases (CRLM). Assessment estimates the relative fraction of the tumour–liver interface for each of the three growth patterns; the desmoplastic HGP reflects good prognosis. Whether preoperative chemotherapy affects the HGP is currently unclear. The present international multicentre study evaluates this in an original cohort of 877 consecutive patients treated in the Netherlands, an external validation cohort of 1,203 consecutive patients treated in the USA, and a post hoc analysis from the phase III randomised controlled European Organization for Research and Treatment of Cancer (EORTC) 40983 trial (n = 70). All patients underwent resection of CRLM with or without preoperative systemic chemotherapy. Trial patients were randomised between perioperative chemotherapy and resection or resection alone. HGPs were determined according to consensus guidelines and compared for preoperative treatment status. Data from three separate tumour regression grading systems were available for the trial cohort. These were correlated with HGP stratified for treatment arm. In the original cohort, the average presence of desmoplastic HGP was 43% for chemo‐naïve versus 67% for preoperatively treated patients (p < 0.001). A significant association between chemotherapy and desmoplastic HGP was found on multivariable analysis (β [95% confidence interval, CI]: 24.57 [18.28–30.87], p < 0.001). In the validation cohort, the average presence of desmoplastic HGP was 40% for chemo‐naïve versus 63% for preoperatively treated patients (p < 0.001). This association remained on multivariable analysis (β [95% CI]: 24.18 [18.70–29.66], p < 0.001). In the EORTC 40983 trial, the average desmoplastic HGP presence was 33% in the resection arm versus 61% in the chemotherapy arm (p = 0.005). Chemotherapy was independently associated with an increase in desmoplastic HGP (β [95% CI]: 23.29 [1.78–44.79], p = 0.022). All three tumour regression gradings were significantly associated with the desmoplastic HGP in the chemotherapy arm (all p < 0.04). None were associated in the resection arm (all p > 0.11). Preoperative chemotherapy induces histopathological changes that alter the HGP of CRLM. [ABSTRACT FROM AUTHOR]

Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found. Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found. [ABSTRACT FROM AUTHOR]

Purpose. Desmoid-type fibromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of definitive treatments, and the chronic character of the disease can significantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a specific HRQoL questionnaire for this patient group. Methods. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. Results. The most highly ranked issues by patients (n = 29) were issues concerning "tumour growth," "feeling that there is something in the body that does not belong there," and "fear of tumour growth into adjacent tissues or organs" with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1–4). British patients scored higher on most issues compared to Dutch patients (M 2.2 vs. M 1.5). HCPs (n = 31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8). Conclusion. This study identified the most relevant issues for DTF patients, which should be included in a DTF-specific HRQoL questionnaire. Additionally, we identified differences in priority scores between British and Dutch participating patients. Field testing in a large, international cohort is needed to confirm these findings and to devise a comprehensive and specific HRQoL questionnaire for DTF patients. [ABSTRACT FROM AUTHOR]

Skin cancer is the most common type of cancer and its incidence is increasing. The objective of this study was to describe the trends in reimbursed drug and hospital costs of benign and (pre)malignant skin tumours, and to present future projections. Therefore, nationwide hospital and drug reimbursement data (for the period 2007-17) were used. In 2017, malignant skin tumours were the 4th most costly cancer in the Netherlands (after breast, colorectal, and lung cancer). The total costs for skin tumours increased from €278 million for 384,390 patients (in 2007) to €465 million for 578,355 patients (in 2017). Drug costs increased from €0.7 million to €121 million (over the period 2007-17), resulting in a 26% share of overall costs in 2017. Future costs are projected to reach €1.35 billion in 2030. In conclusion, the increasing costs of skin cancer are strongly affected by the increasing incidence and introduction of expensive drugs, and future projections are for an alarming increase. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy (SLNB) is recommended for patients with >pT1b cutaneous melanoma, and should be considered and discussed with patients diagnosed with pT1b cutaneous melanoma for the purpose of staging, prognostication and determining eligibility for adjuvant therapy. Previously, the clinicopathologic and gene expression profile (CP-GEP, Merlin Assay®) model was developed to identify patients who can forgo SLNB because of a low risk for sentinel node metastasis. The aim of this study was to evaluate the clinical use and implementation of the CP-GEP model in a prospective multicenter study in the Netherlands. Both test performance and feasibility for clinical implementation were assessed in 260 patients with T1-T4 melanoma. The CP-GEP model demonstrated an overall negative predictive value of 96.7% and positive predictive value of 23.7%, with a potential SLNB reduction rate of 42.2% in patients with T1-T3 melanoma. With a median time of 16 days from initiation to return of test results, there was sufficient time left before the SLNB was performed. Based on these outcomes, the model may support clinical decision-making to identify patients who can forgo SLNB in clinical practice. [ABSTRACT FROM AUTHOR]

Routine treatment with preoperative systemic chemotherapy (CTx) in patients with colorectal liver metastases (CRLM) remains controversial due to lack of consistent evidence demonstrating associated survival benefits. This study aimed to determine the effect of preoperative CTx on overall survival (OS) compared to surgery alone and to assess hospital and oncological network variation in 5-year OS. This was a population-based study of all patients who underwent liver resection for CRLM between 2014 and 2017 in the Netherlands. After 1:1 propensity score matching (PSM), OS was compared between patients treated with and without preoperative CTx. Hospital and oncological network variation in 5-year OS corrected for case-mix factors was calculated using an observed/expected ratio. Of 2820 patients included, 852 (30.2%) and 1968 (69.8%) patients were treated with preoperative CTx and surgery alone, respectively. After PSM, 537 patients remained in each group, median number of CRLM; 3 [IQR 2–4], median size of CRLM; 28 mm [IQR 18–44], synchronous CLRM (71.1%). Median follow-up was 80.8 months. Five-year OS rates after PSM for patients treated with and without preoperative chemotherapy were 40.2% versus 38.3% (log-rank P = 0.734). After stratification for low, medium, and high tumour burden based on the tumour burden score (TBS) OS was similar for preoperative chemotherapy vs. surgery alone (log-rank P = 0.486, P = 0.914, and P = 0.744, respectively). After correction for non-modifiable patient and tumour characteristics, no relevant hospital or oncological network variation in five-year OS was observed. In patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone. [ABSTRACT FROM AUTHOR]

Introduction. Nonsurgical management of patients with desmoid-type fibromatosis (DF) is increasing. This study tries to provide insight on type, usage, and outcome of first-line nonsurgical management strategies. Patients and Methods. From the Dutch Pathology Registry (PALGA), patients with extra-abdominal or trunk/abdominal wall DF, diagnosed between 1993 and 2013, were identified. First-line treatment was analyzed. Best response (BR) using RECIST criteria from start of treatment/surveillance until change of treatment or last follow-up was analyzed. Results. Ninety-one of the 1141 identified patients had first-line nonsurgical management. The percentage of patients treated nonsurgically increased from 0.6% in 1993–1998 to 12.8% in 2009–2013. Thirty-seven patients had surveillance (41%), 35 radiotherapy (38%), and 19 systemic treatment (21%). BR for surveillance was complete response (CR) in 2/37, partial response (PR) in 4/37, stable disease (SD) in 21/37, progressive disease (PD) in 5/37, and unknown in 5/37 patients. BR for radiotherapy was CR in 4/35, PR in 11/35, SD in 16/35, and unknown in 4/35. BR for systemic treatment was CR in 1/19, PR in 1/19, SD in 10/19, PD in 2/19, and unknown in 5/19. Totally, 91% of patients did not progress. Discussion. Given the low percentage (9%) of PD of nonsurgical management, these data can be used in shared decision making with the patient regarding optimal treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 40% of patients with MPNSTs develop distant metastasis (DM) within five years. Identification of MPNST patients more likely to develop DM and the identification of prognostic factors after DM diagnosis may guide clinical decision-making and may result in a better balance between quantity and quality of life. This study aimed to identify clinicopathologic and treatment-related factors associated with the development of DM and with overall survival (OS) after DM diagnosis. NF1, high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. This is the first study that reveals that NF1 status is also independently associated with worse survival after DM diagnosis with a median survival difference of more than 6 months between NF1 and no-NF1 patients. Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). Methods: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. Results: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with worse OS after DM diagnosis. Metastasectomy, chemotherapy and the metastatic site category 'other' were associated with prolonged survival after DM diagnosis. Conclusions: This analysis provides important insights into clinicopathologic and treatment factors associated with outcomes in metastatic MPNST. Moreover, NF1-status is associated with a higher risk of DM; it is also independently associated with worse survival in metastatic MPNST. [ABSTRACT FROM AUTHOR]

B Background: b The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy was 61% in clinical trials from Memorial Sloan Kettering Cancer Center (MSKCC). After a median of 43 days (IQR 29-52) following surgery all patients received the first dose of HAIP chemotherapy, which was completed uneventfully in all patients. B Conclusions: b Pump implantation is safe and administration of HAIP chemotherapy is feasible in patients with resectable CRLM after training of a dedicated multidisciplinary team. [Extracted from the article]

The aim of this study was to evaluate the Dutch regional practice variation in treatment of synchronous colorectal liver metastases (CRLM) over time and assess their impact on patients survival. Two cohorts of patients with synchronous CRLM were selected from the Netherlands Cancer Registry (NCR). All patients diagnosed between 2014 and 2018 were selected to analyze interregional practice variations in local therapy (LT) with multivariable logistic regression. Overall survival (OS) was assessed for patients diagnosed from 2008 to 2013 using Kaplan Meier method and Cox regression analyses. The proportion of patients who underwent LT increased from 15.5% to 21.9%. Interregional use of LT varied from 19.1% to 25.0%. Multivariable logistic regression showed significant differences between regions in the use of LT (p = 0.001) in 2014–2018. There was no association between OS and region of diagnosis for patients who underwent LT after correction for confounders.The use of LT for CRLM increased from 15.5% in 2008–2013 to 21.9% in 2014–2018. Three-year OS increased from 16% to 19% respectively. Interregional practice variations have decreased. The remaining differences are not associated with OS. The use of local therapy and 3-year overall survival have increased over time. Local practice should be monitored to prevent undesirable variation in outcomes. [ABSTRACT FROM AUTHOR]

This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0–2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with rare cancers face obstacles including delays in diagnosis, inadequate treatments and limited scientific evidence to guide decision making. These obstacles may have a unique impact on their experience with the healthcare system and might be different at various ages. Some aspects of care that shape the experience with the healthcare system include information needs, satisfaction with care and supportive care. Very little is known about these aspects of care, specifically for rare cancer patients. Sarcomas are prime examples of rare cancers and are diagnosed at all ages. In this study, we explored the experience of sarcoma patients (N = 1099) with the healthcare system and looked into detail at whether differences in experience existed between age groups. The results of this nationwide study showed that healthcare experiences differ per age group and we identified needs related to the rarity of these tumors, such as improvements concerning (non-)medical guidance and diagnostic intervals. The aim of this study was to explore the experience of rare cancer patients with the healthcare system and examine differences between age groups (adolescents and young adults (AYA, 18–39 years), older adults (OA, 40–69 years) and elderly (≥70 years)). Dutch sarcoma patients, 2–10 years after diagnosis, completed a questionnaire on their experience with the healthcare system, satisfaction with care, information needs, patient and diagnostic intervals (first symptom to first doctor's visit and first doctor's visit to diagnosis, respectively) and received supportive care. In total, 1099 patients completed the questionnaire (response rate 58%): 186 AYAs, 748 OAs and 165 elderly. Many survivors experienced insufficient medical and non-medical guidance (32% and 38%), although satisfaction with care was rated good to excellent by 94%. Both patient and diagnostic intervals were >1 month for over half of the participants and information needs were largely met (97%). AYAs had the longest patient and diagnostic intervals, experienced the greatest lack of (non-)medical guidance, had more desire for patient support groups and used supportive care most often. This nationwide study among sarcoma survivors showed that healthcare experiences differ per age group and identified needs related to the rarity of these tumors, such as improvements concerning (non-)medical guidance and diagnostic intervals. [ABSTRACT FROM AUTHOR]

B Background: b Diagnosis and treatment of bone- and soft tissue sarcomas (STS) and gastro-intestinal stromal tumours (GIST) are challenging. B Results: b Annually, approximately 1400 patients are diagnosed with sarcoma in the Netherlands (STS: 800, GIST: 400, bone sarcoma: 200). Centralisation and involvement of the experience of the sarcoma reference centres is essential in improving care for sarcoma patients. [Extracted from the article]

Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by KIT/PDGFR mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks KIT/PDGFR mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown. We therefore aimed to describe the clinical, pathological and molecular characteristics of GIST in in YA. YA GIST patients registered in the Dutch GIST Registry (DGR) were included, and data were compared to those of older adults (OA). From 1010 patients in the DGR, 52 patients were YA (54% male). Main tumour locations were stomach (46%) and small intestine (46%). GIST genetic profiles were mutations in KIT (69%), PDGFRA (6%), SDH deficient (8%), NF1 associated (4%), ETV6-NTRK3 gene fusion (2%) or wildtype (10%). Statistically significant differences were found between the OA and YA patients (localisation, syndromic and mutational status). YA presented more often than OA in an emergency setting (18% vs. 9%). The overall five-year survival rate was 85%. In conclusion, YA GISTs are not similar to typical adult GISTs and also differ from paediatric GISTs, as described in the literature. In this series, we found a relatively high percentage of small intestine GIST, emergency presentation, 25% non-KIT/PDGFRA mutations and a relatively good survival. [ABSTRACT FROM AUTHOR]

• PORT is associated with less recurrences in stage III MCC. • PORT does not improve MCC-related survival. • OS benefit of PORT in MCC patients is likely associated with selection bias. Postoperative radiotherapy (PORT) is currently recommended for the treatment of Merkel cell carcinoma. Nevertheless, deviations occur frequently due to the generally elderly and frail patient population. We aimed to evaluate the influence of PORT on survival in stage I-III MCC patients treated in the Netherlands. Patients were included retrospectively between 2013 and 2018. Fine-Gray method was used for cumulative incidence of recurrence and MCC-related death, cox regression was performed for overall mortality. Analyses were performed in patients with clinical (sentinel node biopsy [SN] not performed) stage I/II (c-I/II-MCC), pathologic (SN negative) stage I/II (p-I/II-MCC) and stage III MCC (III-MCC), separately. Propensity score matching (PSM) was performed to assess confounding by indication. In total 182 patients were included, 35 had p-I/II-MCC, 69 had c-I/II-MCC and 78 had III-MCC. Median follow up time was 53.5 (IQR 33.4–67.4), 30.5 (13.0–43.6) and 29.3 (19.3–51.0) months, respectively. Multivariable analysis showed PORT to be associated with less recurrences and reduced overall mortality, but not with MCC-related mortality. In stage III-MCC, extracapsular extension (sub-distribution hazard [SDH] 4.09, p = 0.012) and PORT (SDH 0.45, p = 0.044) were associated with recurrence, and ≥ 4 positive lymph nodes (SDH 3.24, p = 0.024) were associated with MCC-related mortality. PORT was associated with less recurrences and reduced overall mortality in patients with stage I-III MCC, but not with MCC-related mortality. Trends in overall survival benefit are likely to be caused by selection bias suggesting further refinement of criteria for PORT is warranted, for instance by taking life expectancy into account. [ABSTRACT FROM AUTHOR]

The optimal treatment sequence for patients with synchronous colorectal liver metastases (CRLM) remains uncertain. This study aimed to assess factors associated with the use of simultaneous resections and impact on hospital variation. This population-based study included all patients who underwent liver surgery for synchronous colorectal liver metastases between 2014 and 2019 in the Netherlands. Factors associated with simultaneous resection were identified. Short-term surgical outcomes of simultaneous resections and factors associated with 30-day major morbidity were evaluated. Of 2146 patients included, 589 (27%) underwent simultaneous resection in 28 hospitals. Simultaneous resection was associated with age, sex, BMI, number, size and bilobar distribution of CRLM, and administration of preoperative chemotherapy. More minimally invasive and minor resections were performed in the simultaneous group. Hospital variation was present (range 2.4%–83.3%) with several hospitals performing simultaneous procedures more and less frequently than expected. Simultaneous resection resulted in 13% 30-day major morbidity, and 1% mortality. ASA classification ≥3 was independently associated with higher 30-day major morbidity after simultaneous resection (aOR 1.97, CI 1.10–3.42, p = 0.018). Distinctive patient and tumour characteristics influence the choice for simultaneous resection. Remarkable hospital variation is present in the Netherlands. [ABSTRACT FROM AUTHOR]

Failure to rescue (FTR) is defined as postoperative complications leading to mortality. This nationwide study aimed to assess factors associated with FTR and hospital variation in FTR after liver surgery. All patients who underwent liver resection between 2014 and 2017 in the Netherlands were included. FTR was defined as in-hospital or 30-day mortality after complications Dindo grade ≥3a. Variables associated with FTR and nationwide hospital variation were assessed using multivariable logistic regression. Of 4961 patients included, 3707 (74.4%) underwent liver resection for colorectal liver metastases, 379 (7.6%) for other metastases, 526 (10.6%) for hepatocellular carcinoma and 349 (7.0%) for biliary cancer. Thirty-day major morbidity was 11.5%. Overall mortality was 2.3%. FTR was 19.1%. Age 65–80 (aOR: 2.86, CI:1.01–12.0, p = 0.049), ASA 3+ (aOR:2.59, CI: 1.66–4.02, p < 0.001), liver cirrhosis (aOR:4.15, CI:1.81–9.22, p < 0.001), biliary cancer (aOR:3.47, CI: 1.73–6.96, p < 0.001), and major resection (aOR:6.46, CI: 3.91–10.9, p < 0.001) were associated with FTR. Postoperative liver failure (aOR: 26.9, CI: 14.6–51.2, p < 0.001), cardiac (aOR: 2.62, CI: 1.27–5.29, p = 0.008) and thromboembolic complications (aOR: 2.49, CI: 1.16–5.22, p = 0.017) were associated with FTR. After case-mix correction, no hospital variation in FTR was observed. FTR is influenced by patient demographics, disease and procedural burden. Prevention of postoperative liver failure, cardiac and thromboembolic complications could decrease FTR. [ABSTRACT FROM AUTHOR]

Liver resection is high-risk surgery in particular in elderly patients. The aim of this study was to explore postoperative outcomes after liver resection in elderly patients. In this nationwide study, all patients who underwent liver resection for primary and secondary liver tumours in the Netherlands between 2014 and 2019 were included. Age groups were composed as younger than 70 (70-), between 70 and 80 (septuagenarians), and 80 years or older (octogenarians). Proportion of liver resections per age group and 30-day major morbidity and 30-day mortality were assessed. In total, 6587 patients were included of whom 4023 (58.9%) were younger than 70, 2135 (32.4%) were septuagenarians and 429 (6.5%) were octogenarians. The proportion of septuagenarians increased during the study period (aOR:1.06, CI:1.02–1.09, p < 0.001). Thirty-day major morbidity was higher in septuagenarians (11%) and octogenarians (12%) compared to younger patients (9%, p = 0.049). Thirty-day mortality was higher in septuagenarians (4%) and octogenarians (4%) compared to younger patients (2%, p < 0.001). Cardiopulmonary complications occurred more frequently with higher age, liver-specific complications did not. Higher age was associated with higher 30-day morbidity and 30-day mortality in multivariable logistic regression. Thirty-day major morbidity and 30-day mortality are higher after liver resection in elderly patients, attributed mainly to non-surgical cardiopulmonary complications. [ABSTRACT FROM AUTHOR]

Data on surgical outcomes of laparoscopic liver resection (LLR) versus open liver resection (OLR) of benign liver tumour (BLT) are scarce. This study aimed to provide a nationwide overview of postoperative outcomes after LLR and OLR of BLT. This was a nationwide retrospective study including all patients who underwent liver resection for hepatocellular adenoma, haemangioma and focal nodular hyperplasia in the Netherlands from 2014 to 2019. Propensity score matching (PSM) was applied to compare 30-day overall and major morbidity and 30-day mortality after OLR and LLR. In total, 415 patients underwent BLT resection of whom 230 (55.4%) underwent LLR. PSM for OLR and LLR resulted in 250 matched patients. Median (IQR) length of stay was shorter after LLR than OLR (4 versus 6 days, 5.0–8.0, p < 0.001). Postoperative 30-day overall morbidity was lower after LLR than OLR (12.0% vs. 22.4%, p = 0.043). LLR was associated with reduced 30-day overall morbidity in multivariable analysis (aOR:0.46, CI:0.22–0.95, p = 0.043). Both 30-day major morbidity and 30-day mortality were not different. LLR for BLT is associated with shorter hospital stay and reduced overall morbidity and is preferred if technically feasible. [ABSTRACT FROM AUTHOR]

Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation. In this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery. Of 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy. Significant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy. [ABSTRACT FROM AUTHOR]

Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands. Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age ≤18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs. A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival. In localized MPNSTs, risk stratification for survival can be done using several patient- and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear. • Resectability is the most prognostic factor for survival in localized MPNSTs. • In MPNSTs, NF1, older age, tumour size, and depth are associated with poorer survival. • Retroperitoneal MPNST is a small subgroup with a worse prognosis. • R0 and R1 resections have similar survival in MPNSTs of any location. • The added value of radiotherapy and chemotherapy is unclear for survival in MPNSTs. [ABSTRACT FROM AUTHOR]

Abstract Background Diagnosing and treating soft tissue sarcomas (STSs) remains challenging, stressing the urgency for centralisation. This nationwide survey aimed to evaluate the centralisation of STS surgery and its effect on survival. Methods Patients operated for primary STS from 2006 to 2015 were queried from the Netherlands Cancer Registry. Hospitals in which STS surgery was performed were allocated into three categories: low-volume (1–9 resections per year), medium-volume (10–19 resections) or high-volume (≥20 resections). Differences in tumour characteristics and outcome were calculated. A multivariable regression analysis was performed to adjust for case-mix. Results Of the 5282 identified patients, 42% was treated in low-volume hospitals, 7.7% in medium-volume hospitals and 51% in high-volume hospitals, with a significant trend over time towards treatment in a high-volume hospital (p < 0.01). In high-volume hospitals, more often patients with non low-grade, large and deep-seated tumours were treated than in low-volume hospitals. For the whole group, there was no survival benefit for patients treated in high-volume hospitals, with 10-year net survival rates of 76% (low-volume), 68% (medium-volume) and 68% (high-volume). However, subgroup analysis for patients with non low-grade and deep-seated tumours did reveal a benefit from treatment in a high-volume hospitals with 10-year survival rates of 54% (high-volume), 49% (low-volume) and 42% (medium-volume) and a relative risk of 1.3 (high-volume versus low-volume, p = 0.03). Conclusion Centralisation of STS surgery has increased in the past decade. Surgery in a high-volume hospital improved survival of patients with non low-grade and deep-seated tumours, and therefore these patients should be referred to such a hospital. Highlights • Centralisation of soft tissue sarcoma (STS) surgery has increased over time. • Patients with deep and large STS are more often referred to high-volume hospitals. • Treatment in high-volume hospitals reduced surgery-related morbidities. • Centralisation improved survival for patients with non low-grade and deep-seated STS. [ABSTRACT FROM AUTHOR]

Background: In 2013, the nationwide Dutch Hepato Biliary Audit (DHBA) was initiated. The aim of this study was to evaluate changes in indications for and outcomes of liver surgery in the last decade., Methods: This nationwide study included all patients who underwent liver surgery for four indications, including colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), and intrahepatic- and perihilar cholangiocarcinoma (iCCA - pCCA) between 2014 and 2022. Trends in postoperative outcomes were evaluated separately for each indication using multilevel multivariable logistic regression analyses., Results: This study included 8057 procedures for CRLM, 838 for HCC, 290 for iCCA, and 300 for pCCA. Over time, these patients had higher risk profiles (more ASA-III patients and more comorbidities). Adjusted mortality decreased over time for CRLM, HCC and iCCA, respectively aOR 0.83, 95%CI 0.75-0.92, P < 0.001; aOR 0.86, 95%CI 0.75-0.99, P = 0.045; aOR 0.40, 95%CI 0.20-0.73, P < 0.001. Failure to rescue (FTR) also decreased for these groups, respectively aOR 0.84, 95%CI 0.76-0.93, P = 0.001; aOR 0.81, 95%CI 0.68-0.97, P = 0.024; aOR 0.29, 95%CI 0.08-0.84, P = 0.021). For iCCA severe complications (aOR 0.65 95%CI 0.43-0.99, P = 0.043) also decreased. No significant outcome differences were observed in pCCA. The number of centres performing liver resections decreased from 26 to 22 between 2014 and 2022, while median annual volumes did not change (40-49, P = 0.66)., Conclusion: Over time, postoperative mortality and FTR decreased after liver surgery, despite treating higher-risk patients. The DHBA continues its focus on providing feedback and benchmark results to further enhance outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Approximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR)., Methods: This population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database., Results: Data of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM >5 cm (aHR 1.58, 95% CI: 1.07-2.34, P = 0.023), >3 CRLM (aHR 1.33, 95% CI: 1.00-1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25-2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09-1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%)., Conclusion: Significant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified., Methods: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020-2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP)., Results: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 -3.2%) and 3.3% (0-16.7%) for minor and major LR, and 2.7% (0-7.0%) and 0.6% (0-4.2%) for PD and DP respectively. FTR rates were 5.4% (0-33.3%), 14.2% (0-100%), 7.5% (1.6%-28.5%) and 3.1% (0-14.9%). For major morbidity rate, corresponding rates were 9.8% (0-20.5%), 28.1% (0-47.1%), 36% (15.8%-58.3%) and 22.3% (5.2%-46.1%). For TO, corresponding rates were 73.6% (61.3%-94.4%), 54.1% (35.3-100), 46.8% (25.3%-59.4%) and 63.3% (30.7%-84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers., Conclusion: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: This study compares the characteristics, referral and treatment patterns and overall survival (OS) of gastrointestinal stromal tumor (GIST) patients treated in reference and non-reference centers in the Netherlands., Patients and Methods: This retrospective cohort study on patients diagnosed between 2016 and 2019, utilises data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database. Patients were categorized into two groups: patients diagnosed in or referred to reference centers and patients diagnosed in non-reference centers without referral., Results: This study included 1,550 GIST patients with a median age of 67.0 in reference and 68.0 years in non-reference centers. Eighty-seven per cent of patients were diagnosed in non-reference centers, of which 36.5% (493/1,352) were referred to a reference center. Referral rates were higher for high-risk (62.2% [74/119]) and metastatic patients (67.2% [90/134]). Mutation analysis was performed in 96.9% and 87.6% of these cases in reference and in non-reference centers (p < 0.01), respectively. Systemic therapy was given in reference centers versus non-reference in 89.5% versus 82.0% (p < 0.01) of high-risk and in 94.1% versus 65.9% (p < 0.01) of metastatic patients, respectively. The proportion of positive resection margins and tumor rupture did not differ between reference and non-reference centers. Median OS was not reached., Conclusion: A substantial amount of metastatic GIST patients in non-reference centers did not receive systemic treatment. This might be due to valid reasons. However, optimisation of the referral strategy of GIST patients in the Netherlands could benefit patients. Further research is needed to explore reasons for not starting systemic treatment in metastatic GIST patients.

Introduction: Colorectal cancer (CRC) is the third most common type of cancer in the Netherlands. Approximately 90% of patients can be treated with surgery, which is considered potentially curative. Postoperative surveillance during the first 5 years after surgery pursues to detect metastases in an early, asymptomatic and treatable stage. Multiple large randomised controlled trials have failed to show any (cancer-specific) survival benefit of intensive postoperative surveillance compared with a minimalistic approach in patients with CRC. This raises the question whether an (intensive) in-hospital postoperative surveillance strategy is still warranted from both a patient well-being and societal perspective. A more modern, home-based surveillance strategy could be beneficial in terms of patients' quality of life and healthcare costs., Methods and Analysis: The multicentre, prospective FUTURE-primary study implements a patient-led home-based surveillance after curative CRC treatment. Here, patients are involved in the choice regarding three fundamental aspects of their postoperative surveillance. First regarding frequency, patients can opt for additional follow-up moments to the minimal requirement as outlined by the current Dutch national guidelines. Second regarding the setting, both in-hospital or predominantly home-based options are available. And third, concerning patient-doctor communication choices ranging from in-person to video chat, and even silent check-ups. The aim of the FUTURE-primary study is to evaluate if such a patient-led home-based follow-up approach is successful in terms of quality of life, satisfaction and anxiety compared with historic data. A successful implementation of the patient-led aspect will be assessed by the degree in which the additional, optional follow-up moments are actually utilised. Secondary objectives are to evaluate quality of life, anxiety, fear of cancer recurrence and cost-effectiveness., Ethics and Dissemination: Ethical approval was given by the Medical Ethics Review Committee of Erasmus Medical Centre, The Netherlands (2021-0499). Results will be presented in peer-reviewed journals., Trial Registration Number: NCT05656326., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks., Methods: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed., Results: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction., Conclusion: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: After resection of colorectal cancer liver metastases (CRLM), 2 main histopathological growth patterns can be observed: a desmoplastic and a nondesmoplastic subtype. The desmoplastic subtype has been associated with superior survival. These findings require external validation., Methods: An international multicenter retrospective cohort study was conducted in patients treated surgically for CRLM at 3 tertiary hospitals in the United States and the Netherlands. Determination of histopathological growth patterns was performed on hematoxylin and eosin-stained sections of resected CRLM according to international guidelines. Patients displaying a desmoplastic histopathological phenotype (only desmoplastic growth observed) were compared with patients with a nondesmoplastic phenotype (any nondesmoplastic growth observed). Cutoff analyses on the extent of nondesmoplastic growth were performed. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier and multivariable Cox analysis. All statistical tests were 2-sided., Results: In total 780 patients were eligible. A desmoplastic phenotype was observed in 19.1% and was associated with microsatellite instability (14.6% vs 3.6%, P  = .01). Desmoplastic patients had superior 5-year OS (73.4%, 95% confidence interval [CI] = 64.1% to 84.0% vs 44.2%, 95% CI = 38.9% to 50.2%, P  < .001) and DFS (32.0%, 95% CI = 22.9% to 44.7% vs 14.7%, 95% CI = 11.7% to 18.6%, P  < .001) compared with their nondesmoplastic counterparts. A desmoplastic phenotype was associated with an adjusted hazard ratio for death of 0.36 (95% CI = 0.23 to 0.58) and 0.50 (95% CI = 0.37 to 0.66) for cancer recurrence. Prognosis was independent of KRAS and BRAF status. The cutoff analyses found no prognostic relationship between either OS or DFS and the extent of nondesmoplastic growth observed (all P  > .1)., Conclusions: This external validation study confirms the remarkably good prognosis after surgery for CRLM in patients with a desmoplastic phenotype. The extent of nondesmoplastic growth does not affect prognosis., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Differences in patient demographics and disease burden can influence comparison of hospital performances. This study aimed to provide a case-mix model to compare short-term postoperative outcomes for patients undergoing liver resection for colorectal liver metastases (CRLM)., Methods: This retrospective, population-based study included all patients who underwent liver resection for CRLM between 2014 and 2018 in the Netherlands. Variation in case-mix variables between hospitals and influence on postoperative outcomes was assessed using multivariable logistic regression. Primary outcomes were 30-day major morbidity and 30-day mortality. Validation of results was performed on the data from 2019., Results: In total, 4639 patients were included in 28 hospitals. Major morbidity was 6.2% and mortality was 1.4%. Uncorrected major morbidity ranged from 3.3% to 13.7% and mortality ranged from 0.0% to 5.0%. between hospitals. Significant differences between hospitals were observed for age higher than 80 (0.0%-17.1%, p < 0.001), ASA 3 or higher (3.3%-36.3%, p < 0.001), histopathological parenchymal liver disease (0.0%-47.1%, p < 0.001), history of liver resection (8.1%-36.3%, p < 0.001), major liver resection (6.7%-38.0%, p < 0.001) and synchronous metastases (35.5%-62.1%, p < 0.001). Expected 30-day major morbidity between hospitals ranged from 6.4% to 11.9% and expected 30-day mortality ranged from 0.6% to 2.9%. After case-mix correction no significant outliers concerning major morbidity and mortality remained. Validation on patients who underwent liver resection for CRLM in 2019 affirmed these outcomes., Conclusion: Case-mix adjustment is a prerequisite to allow for institutional comparison of short-term postoperative outcomes after liver resection for CRLM., Competing Interests: Declaration of conpeting interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 University Medical Center Groningen. Published by Elsevier Ltd.. All rights reserved.)

Background: Merkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported., Methods: Patients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity., Results: Fifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5-35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3-22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6-15.5) months, and the median OS was 25.8 (95% CI 9.1-42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4-5 toxicity was seen., Conclusions: In this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC., Competing Interests: Competing interests: MJBA, FALME, KBMIK, LBB, DG, AvA, MJ and METT report to hold a position on an advisory board for Merck., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Malignant peripheral nerve sheath tumors (MPNST) are rare and aggressive non-rhabdomyoblastic soft-tissue sarcomas (NRSTS) in children. This study set out to investigate clinical presentation, treatment modalities, and factors associated with survival in pediatric MPNST using Dutch nationwide databases., Methods: Data were obtained from the Netherlands Cancer Registry (NCR) and the Dutch Pathology Database (PALGA) from 1989 to 2017. All primary MPNSTs were collected. Demographic differences were analyzed between adult and pediatric (age ≤18 years) MPNST. In children, demographic and treatment differences between neurofibromatosis type 1 (NF1) and non-NF1 were analyzed. A Cox proportional hazard model was constructed for localized pediatric MPNSTs., Results: A total of 70/784 MPNST patients were children (37.1% NF1). Children did not present differently from adults. In NF1 children, tumor size was more commonly large (> 5 cm, 92.3% vs 59.1%). Localized disease was primarily resected in 90.6%, and radiotherapy was administered in 37.5%. Non-NF1 children tended to receive chemotherapy more commonly (39.5% vs 26.9%). Overall, estimated five-year survival rates of localized NF1-MPNST was 52.4% (SE: 10.1%) compared with 75.8% (SE: 7.1%) in non-NF1 patients. The multivariate model showed worse survival in NF1 patients (HR: 2.98; 95% CI, 1.17-7.60, P = 0.02) and increased survival in patients diagnosed after 2005 (HR: 0.20; 95% CI, 0.06-0.69, P = 0.01). No treatment factors were independently associated with survival., Conclusion: Pediatric MPNSTs have presentations similar to adult MPNSTs. In children, NF1 patients present with larger tumors, but are treated similarly to non-NF1 MPNSTs. In localized pediatric MPNST, NF1 is associated with worse survival. Promisingly, survival has increased for pediatric MPNSTs after 2005., (© 2019 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Background: The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs., Study Design: A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien-Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy., Results: A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51-64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29-52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed uneventfully in all patients., Conclusion: Pump implantation is safe, and administration of HAIP chemotherapy is feasible, in patients with resectable CRLMs, after training of a dedicated multidisciplinary team.

Background: The Dutch Hepato Biliary Audit (DHBA) was initiated in 2013 to assess the national quality of liver surgery. This study aimed to describe the initiation and implementation of this audit along with an overview of the results and future perspectives., Methods: Registry of patients undergoing liver surgery for all primary and secondary liver tumors in the DHBA is mandatory. Weekly, benchmarked information on process and outcome measures is reported to surgical teams. In this study, the first results of patients with colorectal liver metastases were presented, including results of data verification., Results: Between 2014 and 2017, 6241 procedures were registered, including 4261 (68%) resections for colorectal liver metastases. For minor- and major liver resections for colorectal liver metastases, the median [interquartile range] hospital stay was 6 [4-8] and 8 [6-12] days, respectively. A postoperative complicated course (complication leading to >14 days of hospital stay, reintervention or death) occurred in 26% and 43% and the 30-day/in-hospital mortality was 1% and 4%, respectively. The completeness of data was 97%. In 3.6% of patients, a complicated postoperative course was erroneously omitted., Conclusion: Nationwide implementation of the DHBA has been successful. This was the first step in creating a complete evaluation of the quality of liver surgery., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: The disease-free interval (DFI) between resection of primary colorectal cancer (CRC) and diagnosis of liver metastases is considered an important prognostic indicator; however, recent analyses in metastatic CRC found limited evidence to support this notion., Objective: The current study aims to determine the prognostic value of the DFI in patients with resectable colorectal liver metastases (CRLM)., Methods: Patients undergoing first surgical treatment of CRLM at three academic centers in The Netherlands were eligible for inclusion. The DFI was defined as the time between resection of CRC and detection of CRLM. Baseline characteristics and Kaplan-Meier survival estimates were stratified by DFI. Cox regression analyses were performed for overall (OS) and disease-free survival (DFS), with the DFI entered as a continuous measure using a restricted cubic spline function with three knots., Results: In total, 1374 patients were included. Patients with a shorter DFI more often had lymph node involvement of the primary, more frequently received neoadjuvant chemotherapy for CRLM, and had higher number of CRLM at diagnosis. The DFI significantly contributed to DFS prediction (p =0.002), but not for predicting OS (p =0.169). Point estimates of the hazard ratio (95% confidence interval) for a DFI of 0 versus 12 months and 0 versus 24 months were 1.284 (1.114-1.480) and 1.444 (1.180-1.766), respectively, for DFS, and 1.111 (0.928-1.330) and 1.202 (0.933-1.550), respectively, for OS., Conclusion: The DFI is of prognostic value for predicting disease recurrence following surgical treatment of CRLM, but not for predicting OS outcomes.

In the 7 th edition of the AJCC staging system, the mitotic rate criterion replaced Clark level to increase correct classification of high-risk thin melanoma patients (pT1B). Additionally, sentinel node biopsy (SNB) was recommended for nodal staging of pT1B melanomas. The aim of this article was to evaluate the effects on pT1 substaging and clinical implications in the national pT1 melanoma population. All pT1 melanomas diagnosed in the Netherlands between 2003 and 2014 were selected from the Netherlands Cancer Registry (IKNL). Patients were stratified by cohort according to AJCC edition: (1) 2003-2009 (6 th ) and (2) 2010-2014 (7 th ). Relative survival was calculated to estimate melanoma-specific survival. A total of 29.546 pT1 melanoma patients were included. The pT1b proportion increased from 10.1% in Cohort 1 to 21.5% in Cohort 2. The proportion of performed SNBs per cohort increased: for pT1b melanomas alone from 4.5% to 13.0%. SNB positivity rate decreased from 10.5% to 8.8% for the entire pT1 population, and for pT1b melanomas from 11.3% to 8.6%. At 5 years, the relative survival rate was similar for pT1a and pT1b in both cohorts, namely, pT1a 100% vs pT1b 97% (Cohort 1), and pT1a 100% vs pT1b 98% (Cohort 2). The 7 th edition of the AJCC staging system has caused an increased number of patients to undergo SNB, without an increase in SNB positivity rate. Survival between pT1 subgroups remains similar. The mitotic rate criterion for pT1b classification and the recommendation to perform SNB for pT1b melanomas should be reconsidered., (© 2017 UICC.)

Background: Aggressive fibromatosis (AF) is a locally infiltrating soft-tissue tumor. In a population-based study in the Netherlands, we evaluated time trends for the incidence and treatment of AF., Methods: In PALGA: Dutch Pathology Registry, all patients diagnosed between 1993 and 2013 as having extra-abdominal or abdominal wall aggressive fibromatosis were identified and available pathology data of the patients were evaluated. Epidemiological and treatment-related factors were analyzed with χ (2)and regression analysis., Results: During the study period, 1134 patients were identified. The incidence increased from 2.10 to 5.36 per million people per year. Median age at the time of diagnosis increased annually by B 0.285 (P = 0.001). Female gender prevailed and increased over time [annual odds ratio (OR) 1.022; P = 0.058]. All anatomic localizations, but in particular truncal tumors, became more frequent. During the study period diagnostic histological biopsies were performed more often (annual OR 1.096; P < 0.001). The proportion of patients who underwent surgical treatment decreased (annual OR 0.928; P < 0.001). When resection was preceded by biopsy, 49.8 % of the patients had R0-resection versus 30.7 % in patients without biopsy (P < 0.001)., Conclusions: In this population-based study, an increasing incidence of extra-abdominal and abdominal-wall aggressive fibromatosis was observed. The workup of patients improved and a trend towards a nonsurgical treatment policy was observed.