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... Show moreBackground: 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. Show less
Kooij, M.K. van der; Joosse, A.; Suijkerbuijk, K.P.M.; Aarts, M.J.B.; Berkmortel, F.W.P.J. van den; Blank, C.U.; ... ; Kapiteijn, E. 2022
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... Show moreTreatment 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 <65 years (1 point), history of ipilimumab (anti-CTLA-4) treatment (2 points), elevated lactate dehydrogenase (LDH) (1 point), and the presence of liver metastasis (2 points) [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. Show less
Introduction: The NABON Breast Cancer Audit showed that more than 70% of the Dutch women undergoing surgery for breast cancer (BC) maintained their breast contour by breast conserving surgery (BCS)... Show moreIntroduction: The NABON Breast Cancer Audit showed that more than 70% of the Dutch women undergoing surgery for breast cancer (BC) maintained their breast contour by breast conserving surgery (BCS) or by immediate reconstruction after ablative surgery. The proportion of oncoplastic surgery applied in patients undergoing breast conserving treatment (BCT) remains unknown. The aim of our study was to assess the need for standardization of oncoplastic breast conserving surgery (OPBCS) in an attempt to enable measurement of the quality of OPBCS. Methods: To gain a better understanding of current practice in OPBCS we sent a questionnaire to all breast surgeons in the Netherlands who are member of the breast surgery working group (n=134). Results: A total of 60 breast surgeons, representing different hospitals in the Netherlands, responded. 61.7% of the breast surgeons performed BCS in 60%-100% of their patients. 68.3% responded that BCS was performed using OPS techniques in up to 40% of their patients. OPBCS was defined as level I volume displacement by 45.2% of the breast surgeons and as BCS performed by a breast surgeon and plastic surgeon together by 32.3% of the breast surgeons. 94.5% indicated that there is a need for standardization of the definition of OPBCS in the Netherlands. Conclusion: This study demonstrates that OPBCS is a major part of daily clinical practice of Dutch breast surgeons treating BC patients. Despite of this, there is no clear definition of OPS in BCT in the Netherlands. Only after standardization, a classification code and quality indicator can be initiated for OPBCS. Ultimately, this will facilitate improvement in quality of BC care. Show less
Introduction: The NABON Breast Cancer Audit showed that more than 70% of the Dutch women undergoing surgery for breast cancer maintained their breast contour by breast-conserving surgery (BCS) or... Show moreIntroduction: The NABON Breast Cancer Audit showed that more than 70% of the Dutch women undergoing surgery for breast cancer maintained their breast contour by breast-conserving surgery (BCS) or by immediate reconstruction after ablative surgery. The proportion of oncoplastic surgery applied in patients undergoing breast-conserving treatment remains unknown. The aim of our study was to assess the need for standardization of oncoplastic breast-conserving surgery (OPBCS) in an attempt to enable measurement of the quality of OPBCS. Methods: To gain a better understanding of current practice in OPBCS, we sent a questionnaire to all breast surgeons in The Netherlands who are members of the breast surgery working group (n = 134). Results: A total of 60 breast surgeons, representing different hospitals in The Netherlands, responded. 61.7% of the breast surgeons performed BCS on 60–100% of their patients. 68.3% responded that BCS was performed using OPS techniques in up to 40% of their patients. OPBCS was defined as level I volume displacement by 45.2% of the breast surgeons and as BCS performed by a breast surgeon and plastic surgeon together by 32.3% of the breast surgeons. 94.5% indicated that there is a need for standardization of the definition of OPBCS in The Netherlands. Conclusion: This study demonstrates that OPBCS is a major part of daily clinical practice of Dutch breast surgeons treating BC patients. Despite this, there is no clear definition of OPS in breast-conserving treatment in The Netherlands. Only after standardization can a classification code and quality indicator be initiated for OPBCS. Ultimately, this will facilitate improvement in quality of BC care. Show less
BACKGROUND Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable... Show moreBACKGROUND Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5x10(9) TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P < 0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. CONCLUSIONS In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab. Show less
Introduction: This study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with... Show moreIntroduction: This study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with the power of a large prospective nation-wide population-based study cohort. Materials and methods: A development cohort was formed by using the DCRA (Dutch ColoRectal Audit), a mandatory population-based repository of all patients who undergo colorectal cancer resection in the Netherlands. Patients aged 18 years or older were included who underwent surgical resection for rectal cancer with primary anastomosis (with or without deviating ileostomy) between 2011 and 2019. Anastomotic leakage was defined as clinically relevant leakage requiring reintervention. Multivariable logistic regression was used to build a prediction model and cross-validation was used to validate the model. Results: A total of 13.175 patients were included for analysis. AL was diagnosed in 1319 patients (10%). A deviating stoma was constructed in 6853 patients (52%). The following variables were identified as significant risk factors and included in the prediction model: gender, age, BMI, ASA classification, neo-adjuvant (chemo)radiotherapy, cT stage, distance of the tumor from anal verge, and deviating ileos-tomy. The model had a concordance-index of 0.664, which remained 0.658 after cross-validation. In addition, a nomogram was developed. Conclusion: The present study generated a discriminative prediction model based on preoperatively available variables. The proposed score can be used for patient counselling and risk-stratification before undergoing rectal resection for cancer. (c) 2022 Published by Elsevier Ltd. Show less
Ismail, R.K.; Suijkerbuijk, K.P.M.; Boer, A. de; Dartel, M. van; Hilarius, D.L.; Pasmooij, A.M.G.; ... ; Wouters, M.W.J.M. 2022
Recent results of patients with advanced melanoma treated with first-line BRAF-MEK inhibitors in clinical trials showed 5-year survival in one-third of patients with a median overall survival (OS)... Show moreRecent results of patients with advanced melanoma treated with first-line BRAF-MEK inhibitors in clinical trials showed 5-year survival in one-third of patients with a median overall survival (OS) of more than 2 years. This study aimed to investigate these patients' real-world survival and identify the characteristics of long-term survivors. The study population consisted of patients with advanced cutaneous melanoma with a BRAF-V600 mutated tumor who were treated with first-line BRAF-MEK inhibitors between 2013 and 2017. Long-term survival was defined as a minimum OS of 2 years from start therapy. The median progression-free survival (mPFS) and median OS (mOS) of real-world patients (n = 435) were respectively 8.0 (95% CI, 6.8-9.4) and 11.7 (95% CI, 10.3-13.5) months. Two-year survival was reached by 28% of the patients, 22% reached 3-year survival and 19% reached 4-year survival. Real-world patients often had brain metastases (41%), stage IV M1c disease (87%), ECOG PS >= 2 (21%), >= 3 organ sites (62%) and elevated LDH of >= 250 U/I (49%). Trial-eligible real-world patients had an mOS of 17.9 months. Patients surviving more than 2 years (n = 116) more often had an ECOG PS <= 1 (83%), normal LDH (60%), no brain metastases (60%), no liver metastases (63%) and <3 organ sites (60%). Long-term survival of real-world patients treated with first-line BRAF-MEK inhibitors is significantly lower than that of trial patients, which is probably explained by poorer baseline characteristics of patients treated in daily practice. Long-term survivors generally had more favorable characteristics with regard to age, LDH level and metastatic sites, compared to patients not reaching long-term survival. Show less
This study focuses on the impact of complications after rectal cancer surgery on the short-and long-term Health-related Quality of Life (HRQoL). The results show that. short-term HRQoL was affected... Show moreThis study focuses on the impact of complications after rectal cancer surgery on the short-and long-term Health-related Quality of Life (HRQoL). The results show that. short-term HRQoL was affected by complications. Twelve months postoperative HRQoL had returned to the preoperative level regardless of complications. In patients that survived 14-years, there was no effect of complications on HRQoL detected.Background: Survival for rectal cancer patients has improved over the past decades. In parallel, long-term health -related quality of life (HRQoL) is gaining interest. This study focuses on the effect of complications following rectal cancer surgery on HRQoL and survival. Methods: The TME-trial (1996-1999) randomized patients with operable rectal cancer between surgery with preoperative short-course radiotherapy and surgery. Questionnaires including the Rotter-dam Symptom Checklist were sent at 6 time points within the first 24 months and after 14 years the EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. Differences in HRQoL and survival between patients with and without compli-cations were analyzed. Results: A total of 1207 patients were included, of which 482 (39.9%) patients experienced complications, surgical complications occurred in 177 (14.6%) patients, non-surgical complications in 197 (16.3%) and 108 patients (8.9%) had a combination of both types of complications. Three months after surgery, patients with a combination of surgical-and non-surgical complications, especially patients with anastomotic leakage, had the worst HRQoL. Twelve months postoperative HRQoL returned to a similar level as before surgery, regardless of complications. In patients who survived 14 years, no significant differences in HRQoL were seen between patients with and without complications. However, patients with complications did have lower overall survival. Conclusion: This study shows that survival and short-term HRQoL are negatively affected by complications. Twelve months after surgery HRQoL had returned to the preoperative level regardless, of complications. Also, in patients that survived 14 years, there was no effect of complications on HRQoL detected. Show less
Blankenstein, S.A.; Bonenkamp, J.J.; Aarts, M.J.B.; Berkmortel, F.W.P.J. van den; Blank, C.U.; Blokx, W.A.M.; ... ; Akkooi, A.C.J. van 2022
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... Show moreSimple 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. Show less
Rauwerdink, D.J.W.; Doorn, R. van; Hage, J. van der; Eertwegh, A.J.M. van den; Haanen, J.B.A.G.; Aarts, M.; ... ; Kapiteijn, E. 2022
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... Show moreNodular 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. Show less
Blankenstein, S.A.; Bonenkamp, J.J.; Aarts, M.J.B.; Berkmortel, F.W.P.J. van den; Blank, C.U.; Blokx, W.A.M.; ... ; Akkooi, A.C.J. van 2022
Introduction: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they... Show moreIntroduction: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they have progressed to metastatic melanoma in the era prior to adjuvant therapy? Methods: Data were retrieved from the Dutch Melanoma Treatment Registry, a prospectively collected, nationwide database of patients with unresectable stage IIIC or IV (advanced) melanoma between 2012 and 2018. Melanoma-specific survival (MSS) was compared between patients with advanced cutaneous melanoma, previously treated with a wide local excision (WLE) or WLE combined with SLNB as initial treatment of their primary tumor. Cox regression analyses were used to analyze the influence of different variables on MSS. Results: In total, 2581 patients were included, of whom 1412 were treated with a WLE of the primary tumor alone and 1169 in whom this was combined with SLNB. At a median follow-up of 44 months from diagnosis of advanced melanoma, MSS was significantly longer in patients who had previously undergone SLNB {median 23 months (95% confidence interval [CI] 19-29) vs. 18 months (95% CI 15-20) for patients treated with WLE alone; p = 0.002}. However, multivariate Cox regression did not identify SLNB as an independent favorable prognostic factor for MSS after diagnosis of advanced melanoma. Conclusion: Prior to the availability of adjuvant systemic therapy, once patients have unresectable stage IIIC or IV (advanced) melanoma, there was no difference in disease outcome for patients who were or were not previously staged with SLNB. Show less
Background 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... Show moreBackground 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. Methods 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. Results 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. Conclusion 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. Show less
Breeschoten, J. van; Ismail, R.K.; Wouters, M.W.J.M.; Hilarius, D.L.; Wreede, L.C. de; Haanen, J.B.; ... ; Eertwegh, A.J.M. van den 2022
During the COVID-19 pandemic, a 13.6 per cent reduction in the number of surgical procedures performed was observed in 2020. Despite great pressure on healthcare, the COVID-19 pandemic did not... Show moreDuring the COVID-19 pandemic, a 13.6 per cent reduction in the number of surgical procedures performed was observed in 2020. Despite great pressure on healthcare, the COVID-19 pandemic did not cause an increase in adverse surgical outcomes, and oncological surgery-related duration of hospital and ICU stay were significantly shorter.Background The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. Methods A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. Results Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). Conclusion The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.Lay Summary COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018-2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations. Show less
Elfrink, A.K.E.; Alberga, A.J.; Henegouwen, M.I.V.; Scheurs, W.H.; Geest, L.G.M. van der; Verhagen, H.J.M.; ... ; DICA Study Grp 2022
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... Show moreIntroduction 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. Show less
Background: The Dutch Surgical Aneurysm Audit (DSAA) is a nationwide mandatory quality registry that evaluates the perioperative outcomes of abdominal aortic aneurysms (AAAs). The DSAA includes... Show moreBackground: The Dutch Surgical Aneurysm Audit (DSAA) is a nationwide mandatory quality registry that evaluates the perioperative outcomes of abdominal aortic aneurysms (AAAs). The DSAA includes perioperative outcomes that occur up to 30 days, but various complications following AAA repair occur after this period. Administrative healthcare data yield the possibility to evaluate later occuring outcomes such as reinterventions, without increasing the registration burden. The aim of this study is to assess the feasibility and the potential benefit of administrative healthcare data to evaluate mid-term reinterventions following intact AAA repair. Method: All patients that underwent primary endovascular aneurysm repair (EVAR) or open surgical repair (OSR) for an intact infrarenal AAA between January 2017 and December 2018 were selected from the DSAA. Subsequently, these patients were identified in a database containing reimbursement data. Healthcare activity codes that refer to reinterventions following AAA repair were examined to assess reinterventions within 12 and 15 months following EVAR and OSR. Results: We selected 4043 patients from the DSAA, and 2059 (51%) patients could be identified in the administrative healthcare database. Reintervention rates of 10.4% following EVAR and 9.5% following OSR within 12 months (p = 0.719), and 11.5% following EVAR and 10.8% following OSR within 15 months (p = 0.785) were reported. Conclusion: Administrative healthcare data as an addition to the DSAA is potentially beneficial to evaluate midterm reinterventions following intact AAA repair without increasing the registration burden for clinicians. Further validation is necessary before reliable implementation of this tool is warranted. Show less
Single-agent Talimogene Laherparepvec (T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying... Show moreSingle-agent Talimogene Laherparepvec (T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying response rates. The purpose of this systematic review and meta-analysis was to investigate the efficacy and safety of T-VEC. Of 341 publications that were identified, eight studies with a total of 642 patients were included. In patients with stage IIIB-IVM1a, the pooled complete-and overall response rate (CRR and ORR) were 41% and 64%, respectively. In patients with stage IIIB-IVM1c, the pooled CRR and ORR were 30% and 44%, respectively. In patients with stage IVM1b and IVM1c, the pooled CRR and ORR were 4% and 9%, respectively. Adverse events (AEs) were seen in 41-100% of all patients and 0-11% of AEs were severe. In conclusion, single agent T-VEC achieves the highest response rates in patients with early metastatic melanoma and is well-tolerated with generally only mild toxicities. Show less
PURPOSE: Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma. MATERIALS AND METHODS: All patients with... Show morePURPOSE: Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma. MATERIALS AND METHODS: All patients with advanced melanoma treated with first-line anti-PD-1 or ipilimumab-nivolumab between 2012 and 2021 in the nationwide Dutch Melanoma Treatment Registry were included in this cohort study. Objective response rate, progression-free survival (PFS), and overall survival (OS) were analyzed according to BRAF and NRAS status. A multivariable Cox model was used to analyze prognostic factors associated with PFS and OS. RESULTS: In total, 1764 patients received anti-PD-1 and 759 received ipilimumab-nivolumab. No significant differences in PFS were found in the anti-PD-1 cohort. In the ipilimumab-nivolumab cohort, median PFS was significantly higher for BRAF-mutant melanoma (9.9 months; 95% CI, 6.8 to 17.2) compared with NRAS-mutant (4.8 months; 95% CI, 3.0 to 7.5) and double wild-type (5.3 months; 95% CI, 3.6 to 7.1). In multivariable analysis, BRAF-mutant melanoma was significantly associated with a lower risk of progression or death in the ipilimumab-nivolumab cohort. Median OS was significantly higher for BRAF-mutant melanoma compared with NRAS-mutant and double wild-type melanoma for both immune checkpoint inhibitor regimens. CONCLUSION: Ipilimumab-nivolumab-treated patients with BRAF-mutant melanoma display improved PFS and OS compared with patients with NRAS-mutant and double wild-type melanoma. BRAF mutation status is a factor to consider while choosing between mono and dual checkpoint inhibition in advanced melanoma. Show less
Oratie uitgesproken door Prof. Dr. Michel W.J.M. Wouters bij de aanvaarding van het ambt van bijzonder hoogleraar Kwaliteit van de oncologische zorg, in het bijzonder data-gedreven verbetering van... Show moreOratie uitgesproken door Prof. Dr. Michel W.J.M. Wouters bij de aanvaarding van het ambt van bijzonder hoogleraar Kwaliteit van de oncologische zorg, in het bijzonder data-gedreven verbetering van patiëntuitkomsten aan de Universiteit Leiden op maandag 16 mei 2022. Show less