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... Show moreSentinel 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 (R)) 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 CPGEP 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. Show less
Benign retroperitoneal tumors (BRT) represent a rare group of heterogeneous diseases. The literature lacks high-quality evidence about the optimal management of BRT, and most of the information... Show moreBenign retroperitoneal tumors (BRT) represent a rare group of heterogeneous diseases. The literature lacks high-quality evidence about the optimal management of BRT, and most of the information available takes the form of case reports or case series. The aim of this review is to provide an overview of current management strategies for adult patients with BRT.A literature search using PubMed indexed articles was conducted and BRT were classified into five different biological subgroups: 1) lipomatous tumors, 2) smooth muscle tumors, 3) peripheral nerve sheath tumors, 4) myofibroblastic tumors, and 5) others. Tumors that are primarily pelvic in origin were excluded.Despite the significant heterogeneity of the disease, several generic considerations have emerged and can be applied to the management of BRT. Specifically, the risk of misdiagnosing a BRT with another pathology such as retroperitoneal sarcoma is notable. When encountered, suspected BRT should therefore be referred to a specialized sarcoma center. Multidisciplinary tumor boards, present at these centers, have a pivotal role in managing BRT. The decision of whether to offer surgery, nonsurgical treatment or a "watch-and-wait" approach should be made after multidisciplinary discussion, depending on tumor histology. Moving forward, collaborative research efforts dedicated to BRT remain crucial in gathering evidence and knowledge to further optimize patient care. (c) 2022 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. 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
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
Rauwerdink, D.J.W.; Meerten, E.V. van; Hage, J. van der; Kapiteijn, E. 2022
Immunotherapy has revolutionized the treatment of metastatic melanoma. Response to therapy can be complex to evaluate, as Response Evaluation Criteria in Solid Tumor (RECIST) does not capture... Show moreImmunotherapy has revolutionized the treatment of metastatic melanoma. Response to therapy can be complex to evaluate, as Response Evaluation Criteria in Solid Tumor (RECIST) does not capture heterogeneous responses. In this retrospective single-institution analysis, we describe the management, clinicopathological characteristics, RECIST and disease course of metastatic melanoma patients with a heterogeneous response to first-line anti-CLTA-4 and/or anti-PD-1 between September 2011 and September 2020. In 196 patients, 37 had a heterogeneous response to immunotherapy (19%). Distinct identified responses included a mixed response (MR) (15%), pseudoprogressive disease (PP) (3%), and a sarcoid-like reaction (2%). Patients with a MR and possibly no response to therapy (MR-NR) had a higher median lactic acid dehydrogenase (LDH) (P = 0.01), were more often male (P = 0.04), had more involved disease sites (P = 0.01), and had brain metastasis more frequently (P = 0.02). MR patients with later response to therapy (MR-R) and PP patients had a longer overall survival of 1.7 [95% confidence interval (CI), 1.1-2.7] and 1.6 years (95% CI, 1.3-2.0) versus MR-NR 1.2 (0.7-1.7) (P < 0.01). In this cohort study, we identified prognostic clinical characteristics that can contribute to clinical decision-making for patients with a MR. Additionally, patients with pseudoprogression had benefited from therapy continuation, suggesting the importance of not halting therapy early in case of suspected PP. The male sex, more involved disease sites, brain metastasis and had a higher median LDH were associated with a poor survival for patients with a MR, suggesting that these clinical variables could be used to predict whether a mixed responder will possibly respond to therapy. Show less
Purpose Decision-making and dexterity, features that become increasingly relevant in (robot-assisted) minimally invasive surgery, are considered key components in improving the surgical accuracy.... Show morePurpose Decision-making and dexterity, features that become increasingly relevant in (robot-assisted) minimally invasive surgery, are considered key components in improving the surgical accuracy. Recently, DROP-IN gamma probes were introduced to facilitate radioguided robotic surgery. We now studied if robotic DROP-IN radioguidance can be further improved using tethered Click-On designs that integrate gamma detection onto the robotic instruments themselves. Methods Using computer-assisted drawing software, 3D printing and precision machining, we created a Click-On probe containing two press-fit connections and an additional grasping moiety for a ProGrasp instrument combined with fiducials that could be video tracked using the Firefly laparoscope. Using a dexterity phantom, the duration of the specific tasks and the path traveled could be compared between use of the Click-On or DROP-IN probe. To study the impact on surgical decision-making, we performed a blinded study, in porcine models, wherein surgeons had to identify a hidden Co-57-source using either palpation or Click-On radioguidance. Results When assembled onto a ProGrasp instrument, while preserving grasping function and rotational freedom, the fully functional prototype could be inserted through a 12-mm trocar. In dexterity assessments, the Click-On provided a 40% reduction in movements compared to the DROP-IN, which converted into a reduction in time, path length, and increase in straightness index. Radioguidance also improved decision-making; task-completion rate increased by 60%, procedural time was reduced, and movements became more focused. Conclusion The Click-On gamma probe provides a step toward full integration of radioguidance in minimal invasive surgery. The value of this concept was underlined by its impact on surgical dexterity and decision-making. Show less
Bagaria, S.P.; Swallow, C.; Suraweera, H.; Raut, C.P.; Fairweather, M.; Cananzi, F.; ... ; Gronchi, A. 2021
Background Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but... Show moreBackground Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. Methods In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo >= 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. Results Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). Conclusion Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection. Show less
Background Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures... Show moreBackground Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function.Objectives To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS.Methods The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019.Results Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery.Conclusion Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging. Show less
IJzerman, N.S.; Mohammadi, M.; Tzanis, D.; Gelderblom, H.; Fiore, M.; Fumagalli, E.; ... ; Smith, M. 2020
Background: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the managementmay influence outcome, but there is a lack of understanding regarding contemporary... Show moreBackground: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the managementmay influence outcome, but there is a lack of understanding regarding contemporary variancein care. A multicenter, international, retrospective cohort study was performed to elucidate characteristicsand outcomes of rectal GIST in European practice, with particular reference to surgical approach.Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five Europeandatabases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meiermethod. Possible confounders were identified using Cox regression analyses.Results: From 210 patients, 155 patients had surgery. The three main types of surgery were local tumourresection (LTR, n ¼ 46), low anterior resection (LAR, n ¼ 31) and abdomino-perineal resection (APR,n ¼ 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Localrecurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences werefound in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours weresmaller, while LAR and APR patients more often received perioperative imatinib. General hospitalstreated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for localrecurrence was higher age (HR 1.06, CI 1.00e1.12, p ¼ 0.048).Conclusions: In European clinical practice for rectal GIST, LTR, LAR and APR have comparable localcontrol. Multimodal approach is higher and tumour rupture less frequent in specialist centres comparedto general hospitals. Show less
IJzerman, N.S.; Mohammadi, M.; Tzanis, D.; Gelderblom, H.; Fiore, M.; Fumagalli, E.; ... ; Smith, M. 2020
Background: Rectal gastrointestinal stromal tumours (GISTS) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary... Show moreBackground: Rectal gastrointestinal stromal tumours (GISTS) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach.Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses.Results: From 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTS, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00-1.12, p = 0.048).Conclusions: In European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Rauwerdink, D.J.W.; Molina, G.; Frederick, D.T.; Sharova, T.; Hage, J. van der; Cohen, S.; Boland, G.M. 2020
Background Immunotherapy has improved overall survival in metastatic melanoma. Response to therapy can be difficult to evaluate as the traditionally used RECIST 1.1 criteria do not capture... Show moreBackground Immunotherapy has improved overall survival in metastatic melanoma. Response to therapy can be difficult to evaluate as the traditionally used RECIST 1.1 criteria do not capture heterogeneous responses. Here we describe the clinical characterization of melanoma patients with a clinically defined mixed response to immunotherapy. Methods This was a single institution, retrospective analysis of stage IV melanoma patients who received first-line anti-CTLA-4, anti-PD1, or combination anti-CTLA-4/anti-PD1. Therapy response was assessed via clinical definitions, which consisted of cross-sectional imaging combined with clinical exam. Course of disease, clinicopathological characteristics, and management in patients with a mixed clinical response were analyzed. Results In 292 patients (anti-CTLA4 = 63; anti-PD1 = 148, anti-CTLA4/anti-PD1 = 81), 103 were responders (35%), 64 mixed responders (22%), and 125 patients had progressive disease (43%). Of patients with a mixed response, 56% eventually had response to therapy (mixed response followed by response, MR-R), while 31% progressed on therapy (MR-NR). MR-NR patients had higher median LDH (p < 0.01), 3 or more organ sites with metastases (p < 0.01), and more frequently had M1d disease (p < 0.01). Mixed responders who underwent surgery (n = 20) had a significantly longer mean OS compared to patients who did not undergo surgery (6.9 years, 95% CI 6.2-7.6 vs. 6.0 years, 95% CI 4.6-7.3, p = 0.02). Discussion Mixed response to immunotherapy in metastatic melanoma was not uncommon in our cohort (22%). Clinical characteristics associated with progression of disease after initial mixed response included higher LDH, brain metastases, and >= 3 organ sites with metastases. Surgical treatment for highly selected patients with a mixed response was associated with improved outcomes. Show less
Haas, R.L.M.; Gelderblom, H.; Sleijfer, S.; H.H. van boven; Scholten, A.; Dewit, L.; ... ; Coevorden, F. van 2015
