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Melanoma of unknown primary (MUP) may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. We therefore evaluated the overall survival (OS) among patients with MUP in the era of novel therapy. Data for stage III or IV MUP were extracted from a nationwide database for the period 2003–2016, with classification based on the eighth edition of the American Joint Committee on Cancer criteria. The population was divided into pre‐ (2003–2010) and post‐ (2011–2016) novel therapy eras. Also, OS in the post‐novel era was compared between patients with stage IV MUP by whether they received novel therapy. In total, 2028 of 65,110 patients (3.1%) were diagnosed with MUP. Metastatic sites were known in 1919 of 2028 patients, and most had stage IV disease (53.8%). For patients with stage III MUP, the 5‐year OS rates were 48.5% and 50.2% in the pre‐ and post‐novel eras, respectively (p = 0.948). For those with stage IV MUP, the median OS durations were unchanged in the pre‐novel era and post‐novel era when novel therapy was not used (both 4 months); however, OS improved to 11 months when novel therapy was used in the post‐novel era (p < 0.001). In conclusion, more than half of the patients with MUP are diagnosed with stage IV and the introduction of novel therapy appears to have significantly improved the OS of these patients. What's new? Melanoma of unknown primary (MUP) site may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. Knowledge about outcomes could however aid clinical management of patients with MUP. In this nationwide study from 2003 to 2016, the authors show that the introduction of novel therapy has significantly improved the overall survival for patients with stage IV melanoma of unknown primary, who represented more than half of the patients diagnosed with MUP in the Netherlands. [ABSTRACT FROM AUTHOR]

The aim of the study is to assess whether indocyanine green (ICG) fluorescence can replace technetium in the preoperative detection of sentinel lymph nodes (SLN) from cutaneous melanoma. The current golden standard for SLN detection is the radioisotope technetium. A promising alternative is fluorescence imaging (FLI) using ICG. In this study, we enrolled patients undergoing sentinel lymph node biopsy (SLNB) for skin melanoma at the Erasmus Medical Center between November 2022 and July 2023. The SLNB procedure was performed as a standard of care. After general anesthesia, ICG was injected intradermally around the primary tumor site. Both the patient and the surgeon were not blinded for the location of the SLN. FLI was performed before incision, in vivo after incision, and ex vivo. Fluorescent SLNs were confirmed using the gamma probe in all cases. Thirty-two patients were included in this study, and a total of 39 SLNs were harvested. The transcutaneous detection rate of ICG was 21.9%. The combined ex vivo ICG fluorescence and technetium uptake was 94.9%. One SLN contained only ICG (2.6%) and one SLN contained only technetium-uptake (2.6%). FLI using ICG resulted in a relatively low transcutaneous detection, which means that exclusive use of this technique in its present form is not feasible. However, we did find a high accumulation of ICG in the SLN, indicating the potential of ICG in combination with other imaging techniques., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection., Methods: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference., Results: The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use., Conclusion: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Introduction: Amidst the rising number of cancer survivors and personnel shortages, optimisation of follow-up strategies is imperative, especially since intensive follow-up does not lead to survival benefits. Understanding patient preferences and identifying the associated patient profiles is crucial. Coping style may be a key determinant in achieving this. Our study aims to evaluate preferences, identify coping styles and their associated factors, and explore the association between coping style and patients' preferences in colorectal cancer (CRC) follow-up., Methods: In a prospective multicentre implementation study, patients completed the Threatening Medical Situations Inventory (TMSI) to determine their coping style. Simultaneously patients choose their follow-up preferences for the CRC trajectory regarding frequency of tumour marker determination, location of blood sampling, and manner of contact., Results: A total of 188 patients completed the TMSI questionnaire after inclusion. A more intensive follow-up was preferred by 71.5% of patients. Of all patients, 52.0% had a coping style classified as 'blunting' and 34.0% as 'monitoring'. Variables such as a younger age, female gender, higher educational level, and lower ASA scores were associated with having higher monitoring scores. However, there were no significant associations between follow-up preferences and patients' coping styles., Conclusion: This study suggests that none of the provided options in a patient-led follow-up are unsuitable for patients who underwent curative surgery for primary CRC, based on coping style determined at baseline. Low-intensity surveillance after curative resection of CRC may, therefore, be suitable for a wide range of patients independent of coping styles., (© 2024. The Author(s).)

Introduction: 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., Methods: 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 ( 99m Tc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump., Results: 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%., Conclusion: 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS)., Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model., Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions., Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making., Competing Interests: No author has any form of disclosure., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Phase 1-2 trials involving patients with resectable, macroscopic stage III melanoma have shown that neoadjuvant immunotherapy is more efficacious than adjuvant immunotherapy., Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma, in a 1:1 ratio, to receive two cycles of neoadjuvant ipilimumab plus nivolumab and then undergo surgery or to undergo surgery and then receive 12 cycles of adjuvant nivolumab. Only the patients in the neoadjuvant group who had a partial response or nonresponse received subsequent adjuvant treatment. The primary end point was event-free survival., Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of the patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% among patients in the neoadjuvant group who had a major pathological response, 76.1% among those who had a partial response, and 57.0% among those who had a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of the patients in the neoadjuvant group and in 14.7% in the adjuvant group., Conclusions: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.)., (Copyright © 2024 Massachusetts Medical Society.)

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.)

Objective: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM)., Methods: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP. The primary endpoint was complete response (CR) rate at three months, and safety in terms of incidence and severity of adverse events (AEs)., Results: A total of 20 patients were included. AEs of any grade occurred in 90% of patients in the nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 3 AEs were reported in 40% and 30% respectively, most commonly related to wound infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in the placebo arm. The 1-year OS was 100% in both arms., Conclusion: For patients with melanoma ITM, the addition of a single systemic dose of nivolumab the day before ILP is considered safe and feasible with promising efficacy. Accrual will continue in a phase 2 trial., Competing Interests: Declaration of competing interest ACJvA is a member of the Advisory Board for, and received consultancy honoraria from, Amgen, Bristol-Myers Squibb, Neracare, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC. WvH has received institutional honoraria, speakers honorarium, or institutional research grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Belpharma, Sanofi and Sirius Medical. ROB has received institutional research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honorarium from Roche and Pfizer and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme. Remaining authors have no conflicts of interest to declare., (© 2024 Published by Elsevier Ltd.)

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: 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: The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage., Methods: Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve [AUC]) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia)., Findings: The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3-7·8) in the development cohort and 5·0 years (2·2-8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0-75·1) and 5-year melanoma-specific survival was 86·5% (85·3-87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6-67·7) and 83·3% (82·0-84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78-0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79-0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71-0·75) and 0·76 (0·74-0·78), respectively., Interpretation: Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas., Funding: Erasmus Medical Centre Cancer Institute., Competing Interests: Declaration of interests RCS reports honoraria (paid to their institution) from Amgen. AAMvdV reports consultancy fees (paid to their institution) from Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Pierre Fabre, Ipsen, Eisai, Merck, Pfizer, Novartis, and Roche. RPMS has received honoraria for advisory board participation from Merck Sharp & Dohme, Novartis, and Qbiotics, and speaker fees from Bristol Myers Squibb and Novartis. AHRV has received honoraria from Novartis. RAS has received fees for professional services from MetaOptima Technology, F Hoffmann-La Roche, Evaxion, Provectus, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol Myers Squibb, Myriad Genetics, and GlaxoSmithKline. GVL reports consultancy or advisory fees from Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal, Highlight Therapeutics, Innovent Biologics, Novartis, OncoSec, PHMR, Pierre Fabre, Provectus, Qbiotics, and Regeneron. JFT has received honoraria for advisory board participation from Bristol Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline, and Provectus, and travel and conference support from GlaxoSmithKline, Provectus, and Novartis. PR reports research funding (paid to their institution) from Merck Sharp & Dohme and Pfizer, and has received honoraria for lectures and advisory board participation from Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, Pierre Fabre, Sanofi, Merck, Philogen, and Blueprint Medicines. UK has received consulting fees from Merck Sharp & Dohme, travel support from Merck Serono and Pfizer, and grants for educational activities from Merck Serono, Bristol Myers Squibb, and Pierre-Fabre. ACJvA reports honoraria for consultancy and serving on advisory boards (all paid to their institution) from Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Merck, Pfizer, Neracare, Novartis, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC, and research grants (paid to their institution) from Amgen, Merck, and Pfizer. DvK has participated on the data and safety monitoring boards of the FAST CABG and Multivessel Talent trials. DJG has served on data and safety monitoring boards for Amgen and Novartis (funds paid to their institution). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Malignant peripheral nerve sheath tumours (MPNSTs) have high local recurrence (LR) rates. Literature varies on LR risk factors and treatment. This study aimed to elucidate treatment options and risk factors for first and second LRs (LR1 and LR2) in a large multicentre cohort., Method: Surgically treated primary MPNSTs between 1988 and 2019 in the MONACO multicentre cohort were included. Cox regression analysed LR1 and LR2 risk factors and overall survival (OS) after LR1. Treatment of LR1 and LR2 was evaluated., Results: Among 507 patients, 28% developed LR1. Median follow-up was 66.9 months, and for survivors 111.1 months. Independent LR1 risk factors included high-grade tumours (HR 2.63; 95% c.i. 1.15 to 5.99), microscopically positive margins (HR 2.19; 95% c.i. 1.51 to 3.16) and large tumour size (HR 2.14; 95% c.i. 1.21 to 3.78). Perioperative radiotherapy (HR 0.62; 95% c.i. 0.43 to 0.89) reduced the risk. LR1 patients had poorer OS. Synchronous metastasis worsened OS (HR 1.79; 95% c.i. 1.02 to 3.14) post-LR1, while surgically treated LR was associated with better OS (HR 0.38; 95% c.i. 0.22 to 0.64) compared to non-surgical cases. Two-year survival after surgical treatment was 71% (95% c.i. 63 to 82%) versus 28% (95% c.i. 18 to 44%) for non-surgical LR1 patients. Most LR1 (75.4%) and LR2 (73.7%) patients received curative-intent treatment, often surgery alone (64.9% versus 47.4%). Radiotherapy combined with surgery was given to 11.3% of LR1 and 7.9% of LR2 patients., Conclusion: Large, high-grade MPNSTs with R1 resections are at higher LR1 risk, potentially reduced by radiotherapy. Surgically treated recurrences may provide improved survival in highly selected cases., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: Textbook outcome (TO) represents a multidimensional quality measurement, encompassing the desirable short-term outcomes following surgery. This study aimed to investigate whether achieving TO after resection of colorectal liver metastases (CRLM) surgery is related to better overall survival (OS) in a national cohort., Method: Data was retrieved from the Dutch Hepato Biliary Audit. A modified definition of TO (mTO) was used because readmissions were only recorded from 2019. mTO was achieved when no severe postoperative complications, mortality, prolonged length of hospital stay, occurred and when adequate surgical resection margins were obtained. To compare outcomes of patients with and without mTO and reduce baseline differences between both groups propensity score matching (PSM) was used for patients operated on between 2014 and 2018., Results: Out of 6525 eligible patients, 81 % achieved mTO. For the cohort between 2014 and 2018, those achieving mTO had a 5-year OS of 46.7 % (CI 44.8-48.6) while non-mTO patients had a 5-year OS of 33.7 % (CI 29.8-38.2), p < 0.001. Not achieving mTO was associated with a worse OS (aHR 1.34 (95 % CI 1.17-1.53), p < 0.001. Median follow-up was 76 months., PSM assigned 519 patients to each group. In the PSM cohort patients achieving mTO, 5-year OS was 43.6 % (95 % CI 39.2-48.5) compared to 36.4 % (95 % CI 31.9-41.2) in patients who did not achieve mTO, p = 0.006., Conclusion: Achieving mTO is associated with improved long-term survival. This emphasizes the importance of optimising perioperative care and reducing postoperative complications in surgical treatment of CRLM., 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.)

Purpose: The accessibility of cancer care faces challenges due to the rising prevalence of colorectal cancer (CRC) coupled with a shrinkage of healthcare professionals-known as the double aging phenomenon. To ensure sustainable and patient-centred care, innovative solutions are needed. This study aims to assess the needs of CRC patients regarding their follow-up care., Methods: This study uses a mixed-method approach divided in three phases. The initial phase involved focus group sessions, followed by semi-structured interviews to identify patients' needs during follow-up. Open analysis was done to define main themes and needs for patients. In the subsequent quantitative phase, a CRC follow-up needs questionnaire was distributed to patients in the follow-up., Results: After two focus groups (n = 14) and interviews (n = 5), this study identified six main themes. Findings underscore the importance of providing assistance in managing both physical and mental challenges associated with cancer. Participants emphasised the need of a designated contact person and an increased focus on addressing psychological distress. Furthermore, patients desire individualised feedback on quality of life questionnaires, and obtaining tailored information. The subsequent questionnaire (n = 96) revealed the priority of different needs, with the highest priority being the need for simplified radiology results. A possible approach to address a part of the diverse needs could be the implementation of a platform; nearly 70% of patients expressed interest in the proposed platform., Conclusions: CRC patients perceive substantial room for improvement of their follow-up care. Findings can help to develop a platform fulfilling the distinct demands of CRC patients during follow-up., (© 2024. The Author(s).)

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88-1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73-2.38; p = 0.44). Grade 3-4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p < 0.001). In conclusion, while adjuvant nDC treatment in stage IIIB/C melanoma patients generated specific immune responses and was well tolerated, no benefit in RFS was observed., (© 2024. The Author(s).)

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.

Background: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT., Methods: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039., Findings: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0])., Interpretation: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging., Funding: The Dutch Cancer Society and Bayer AG - Pharmaceuticals., Competing Interests: Declaration of interests BE received honoraria from Medtronic for lectures. KH has a leadership role in the Dutch Colorectal Cancer group. DJL received honoraria from Intuitive surgical. MMa received support for travel to attend the following courses where she gave lectures: ECIO 2023, ESGAR Liver Imaging workshop, and Alimentary tract cancer course New York 2023. MMe received grants from Medtronic–Covidien, Johnson & Johnson, Immunophotonics, and Angiodynamics. MMe also received consulting fees from Angiodynamics and Medtronic–Covidien; honoraria from Medtronic–Covidien, Johnson & Johnson, and Angiodynamics; and support for attending meetings from Angiodynamics. MMe is participating in the Data Safety and Monitoring Board of the Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma trial and had leadership or fiduciary roles in the Society of Interventional Oncology, CIRSE & ECIO, and CVIR. ÅAF received honoraria from Bayer AG, Olympus Healthcare, and Siemens Healthineers. JS received funding from the Dutch Cancer Society (grant number 11916) and is president-elect of the European Society of Gastrointestinal and Abdominal Radiology. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS)., Methods: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2-3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes., Results: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9-53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145)., Conclusion: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest This study was partially funded by SkylineDx. All other authors declare that they have no potential or competing interests., (© 2023 Published by Elsevier Ltd.)

Background: Histopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM., Methods: Patients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan-Meier and Cox regression methods, respectively., Results: We included 1233 patients. In the dHGP group (n = 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (n = 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32-0.73, p < 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45-0.82, p < 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72-2.32, p = 0.40)., Conclusions: There is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM., (© 2023. The Author(s).)

Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27-4.28, p < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53-10.04, p < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13-19.17, p < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients.

Objective: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study., Materials and Methods: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded., Results: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001)., Conclusion: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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., Conclusion: In patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study., Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons., Results: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0-12% and 27-62%, and for permanently unresectable CRLM between 3-40% and 6-47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients., Conclusion: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice., (© 2023. The Author(s).)

Introduction: In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM)., Methods: This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan-Meier analysis on patients operated until 2018., Results: Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50-0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50-0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99-0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10-0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50-0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94-0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21., Conclusion: Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery., (© 2023. The Author(s).)

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., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine., Methods: Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed., Results: 265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL [IQR: 0.472-0.747] for cycle 1 day 7, 0.579 ng/mL [IQR: 0.470-0.693] for cycle 1 day 15, 0.646 ng/mL [IQR: 0.463-0.8546] for cycle 2 day 7, and 0.534 ng/mL [IQR: 0.4257-0.7075] for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation. The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %-37.8 %) over a period of 15 days (n = 18)., Conclusion: Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time., Competing Interests: Conflict of Interest Statement 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 © 2023. Published by Elsevier Masson SAS.)

Aim: Follow-up after colorectal cancer requires frequent surveillance of the tumour marker carcinoembryonic antigen (CEA). Home-based blood sampling could be beneficial in terms of patients' well-being and societal cost-effectiveness. Blood sampling by venepuncture is unsuitable for home-based sampling. The aim of this feasibility study is to evaluate the long-term whole-blood stability of CEA., Method: In this prospective feasibility study capillary blood withdrawal was collected in a Hem-Col ® microtube containing a patented stabilization buffer using an internal lithium standard to correct for dilution. Long-term whole-blood stability was considered adequate if the relative bias in CEA concentration between delayed analysis of capillary samples and directly processed venepuncture is within the total error margin of CEA., Results: Twenty two colorectal cancer patients were included to determine the stability of CEA in capillary sampling compared with directly processed (i.e. within 2 h) venepuncture sampling. The median time between venous sampling and CEA analysis and capillary sampling and CEA analysis was 2 h (interquartile range 1-4 h) and 76 h (interquartile range 74-95 h), respectively. A Bland-Altman difference plot excluding outliers showed an overall relative bias of -1.23%. The two capillary samples in our outlier analysis also showed the highest lithium concentrations., Conclusion: Home-based capillary sampling with the use of the Hem-Col ® buffer is a feasible method for CEA determination when analysed within 4 days after blood withdrawal, allowing monitoring for colorectal cancer patients from home. High lithium concentrations due to insufficient filling of the Hem-Col ® tube suggest less reliable CEA measurements., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: To examine the impact of an active surveillance (AS) approach on the health-related quality of life (HRQoL) of patients with desmoid-type fibromatosis (DTF)., Background Data: AS is recommended as initial approach in DTF patients. AS might however negatively affect HRQoL due to physical symptoms or stress and anxiety., Methods: In a prospective observational study, the GRAFITI trial (NTR4714), DTF patients were followed during an initial AS approach for 3 years. HRQoL was assessed by the EORTC QLQ-C30 at baseline, 6, 12 and 24-month follow-up. Patients who completed questionnaires at≥1-time point were included in this analysis of the secondary endpoint. A multivariable linear mixed-effects model with random intercept was conducted to assess trends of HRQoL scores over time and to explore the effect of treatment strategy on HRQoL., Results: All 105 patients enrolled in the GRAFITI trial were eligible for the HRQoL analyses. During 24-month follow-up, 75 patients (71%) continued AS and 30 patients (29%) started an active treatment (AT). DTF patients who continued AS demonstrated relatively stable HRQoL scores during follow-up. HRQoL scores of patients who started AT worsened compared to patients who continued AS, although no significant changes in HRQoL score over time were found in the mixed-model analyses. Overall, DTF patients who started AT scored significantly worse on pain (β=10.08, P =0.039) compared to patients who continued AS., Conclusions: An initial AS approach did not impair HRQoL of DTF patients who continued AS over time, therefore providing further support for AS as the frontline approach in DTF patients. Longitudinal assessment of HRQoL should be part of clinical follow-up to identify patients who may need a change in treatment strategy., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Previous trials found that more intensive postoperative surveillance schedules did not improve survival. Oncological follow-up also provides an opportunity to address psychological issues (for example anxiety, depression, and fear of recurrence). This systematic review assessed the impact of a less intensive surveillance strategy on health-related quality of life (HRQoL), emotional well-being, and patient satisfaction., Methods: A systematic search was conducted in PubMed/MEDLINE, Embase, Web of Science, Cochrane database, PsycINFO, and Google Scholar to identify studies comparing different follow-up strategies after oncological surgery and their effect on HRQoL and patient satisfaction, published before 4 May 2022. A meta-analysis was conducted on the most relevant European Organisation for Research and Treatment of Cancer QLQ-C30 and Hospital Anxiety and Depression Scale subscales., Results: Thirty-five studies were identified, focusing on melanoma (4), colorectal (10), breast (7), prostate (4), upper gastrointestinal (4), gynaecological (3), lung (2), and head and neck (1) cancers. Twenty-two studies were considered to have a low risk of bias, of which 14 showed no significant difference in HRQoL between follow-up approaches. Five studies with a low risk of bias showed improved HRQoL or emotional well-being with a less intensive follow-up approach and three with an intensive approach. Meta-analysis of HRQoL outcomes revealed no negative effects for patients receiving less intensive follow-up., Conclusion: Low-intensity follow-up does not diminish HRQoL, emotional well-being, or patient satisfaction., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM., Methods: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel. If no consensus existed among panel surgeons (i.e. same vote for (un)resectability of CRLM), conclusion was based on majority. The association of tumour biological (sidedness, synchronous CRLM, carcinoembryonic antigen and RAS/BRAF V600E mutation status) and technical anatomical factors with consensus among panel surgeons, secondary resectability and early recurrence (<6 months) without curative-intent repeat local treatment was analysed by uni- and pre-specified multivariable logistic regression., Results: After systemic treatment, 240 (50%) patients received complete local treatment of CRLM of which 75 (31%) patients experienced early recurrence without repeat local treatment. Higher number of CRLM (odds ratio 1.09 [95% confidence interval 1.03-1.15]) and age (odds ratio 1.03 [95% confidence interval 1.00-1.07]) were independently associated with early recurrence without repeat local treatment. In 138 (52%) patients, no consensus among panel surgeons was present prior to local treatment. Postoperative outcomes in patients with and without consensus were comparable., Conclusions: Almost a third of patients selected by an expert panel for secondary CRLM surgery following induction systemic treatment experience an early recurrence only amenable to palliative treatment. Number of CRLM and age, but no tumour biological factors are predictive, suggesting that until there are better biomarkers; resectability assessment remains primarily a technical anatomical decision., Competing Interests: Conflict of interest statement C.J.A.P. has an advisory role for Nordic Pharma. This funding is not related to the current research. The remaining authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The aim of this pilot study was to assess whether an electronic nose can detect patients with soft tissue sarcoma (STS) based on volatile organic compound profiles in exhaled breath. Patients & methods: In this cross-sectional pilot study, patients with primary STS and healthy controls, matched on sex and age, were included for breath analysis. Machine learning techniques were used to develop the best-fitting model. Results: Fifty-nine breath samples were collected (29 STS and 30 control) from March 2018 to March 2022. The final model yielded a c-statistic of 0.85 with a sensitivity of 83% and specificity of 60%. Conclusion: This study suggests that exhaled volatile organic compound analysis could serve as a noninvasive diagnostic biomarker for the detection of STS with a good performance.

Histopathological Growth Patterns (HGPs) have prognostic and predictive value in patients with Colorectal Liver Metastases (CRLM). This study examined whether preoperative measurement of Circulating Tumour Cells (CTCs) is associated with HGP. CTCs were prospectively enumerated in 7.5 ml of blood using the FDA-approved CellSearch system in patients who underwent local treatment of CRLM with curative intent between 2008 and 2021. All CTC samples were collected on the day of local treatment. Patients treated with neoadjuvant chemotherapy for CRLM or with extrahepatic disease at the time of CTC sampling were excluded. HGP was scored retrospectively following the current consensus guidelines. The association between CTCs and HGP was investigated through multivariable logistic regression. Data were available for 177 patients, desmoplastic HGP (dHGP) was observed in 34 patients (19%). There were no statistically significant differences in patient and tumour characteristics between dHGP and non-dHGP at baseline. Patients with dHGP had longer overall - and disease-free survival (logrank p = 0.003 and 0.003, respectively) compared to patients with non-dHGP. CTCs were not detected in 25(74%) of dHGP patients and in 68(48%) of non-dHGP patients (chi-squared p = 0.006). Preoperative absence of CTCs was the only significant predictor for dHGP in multivariable logistic regression (Odds Ratio 2.7, 95%CI 1.1-6.8, p = 0.028), Table 3. Preoperative absence of CTCs is associated with dHGP in chemo naive CRLM patients without extrahepatic disease. Based on our results, CTC count alone is not sufficient to preoperatively identify HGPs, but integration of CTC count in multivariable prediction models may aid the preoperative identification of HGPs of CRLM., (© 2022. The Author(s).)

Background & Aims: In contrast to mismatch repair deficient colorectal carcinoma (CRC), MMR proficient (pMMR) CRC does not respond to immune checkpoint blockade. We studied immune checkpoint stimulation via glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) on ex vivo functionality of human tumor-infiltrating lymphocytes (TIL) isolated from pMMR primary CRC and liver metastases (CRLM)., Methods: Using lymphocytes from resected tumor, adjacent tissues, and peripheral blood mononuclear cells (PBMC) of 132 pMMR primary CRC or CRLM patients, we determined GITR expression and the in vitro T-cell agonistic activity of recombinant GITR ligation., Results: Here, we show that GITR was overexpressed on TIL when compared with other stimulatory immune checkpoints (4-1BB, OX40). Its expression was enhanced in TIL compared with PBMC and adjacent tissues. Among CD4 + TIL, GITR expression was primarily expressed by CD45RA - FoxP3 hi activated regulatory T cells. Within CD8 + TIL, GITR was predominantly expressed on functionally exhausted and putative tumor-reactive CD103 + CD39 + TIL. Strikingly, recombinant GITRL reinvigorated ex vivo TIL responses by significantly enhancing CD4 + and CD8 + TIL numbers. Dual treatment with GITRL and nivolumab (anti-PD1) enhanced CD8 + TIL expansion compared with GITRL monotherapy. Moreover, GITRL/anti-PD1 dual therapy further improved anti-PD1-mediated reinvigoration of interferon gamma secretion by exhausted CD8 TIL from primary CRC., Conclusions: GITR is overexpressed on CD4 + and CD8 + TIL from pMMR CRC and CRLM. Agonistic targeting of GITR enhances ex vivo human TIL functionality and may therefore be a promising approach for novel monotherapy or combined immunotherapies in primary pMRR CRC and CRLM., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The etiology of cutaneous angiosarcoma (cAS) may be idiopathic (I-cAS), or arise secondary to radiotherapy (RT-cAS), in chronic lymphedema (ST-cAS), or related to UV exposure (UV-cAS). The aim of this study was to evaluate oncological outcomes of different cAS subtypes., Patients and Methods: Non-metastatic cAS patients, treated with surgery for primary disease with curative intent, were retrospectively analyzed for oncological outcome, including local recurrence (LR), distant metastases (DM), and overall survival (OS)., Results: A total of 234 patients were identified; 60 I-cAS, 122 RT-cAS, 9 ST-cAS, and 43 UV-cAS. The majority was female (78%), the median age was 66 years (IQR 57-76 years), the median tumor size was 4.4 cm (IQR 2.5-7.0 cm), and most common site of disease was the breast (59%). Recurrence was identified in 66% (44% LR and/or 41% DM), with a median follow up of 26.5 months (IQR 12-60 months). The 5-year OS was estimated at 50%, LRFS at 47%, and DMFS at 50%. There was no significant difference in LR, DM, or OS between the subtypes. Age < 65 years and administration of radiotherapy (RT) were significantly associated with lower LR rates (HR 0.560, 95% CI 0.3373-0.840, p = 0.005 and HR 0.421, 95% CI 0.225-0.790, p = 0.007, respectively), however no prognostic factors were identified for development of DM. Development of DM, but not LR (p = 0.052), was significantly associated with decreased OS (HR 6.486, 95% CI 2.939-14.318 p < 0.001)., Conclusion: We found no significant difference in oncological outcome between the different cAS subtypes. OS remains relatively poor, and RT is associated with lower LR rates., (© 2022. Society of Surgical Oncology.)

Fear of cancer recurrence (FCR) is often reported as an unmet concern by cancer patients. The aim of our study was to investigate (1) the prevalence of FCR in sarcoma survivors; (2) the factors associated with a higher level of FCR; the relationship between (3) FCR and global health status and (4) FCR and use of follow-up care., Methods: A cross-sectional study was conducted among sarcoma survivors 2 to 10 years after diagnosis. Patients completed the Cancer Worry Scale (CWS), the global health status subscale of the EORTC QLQ-C30 and a custom-made questionnaire on follow-up care., Results: In total, 1047 patients were included (response rate 55%). The prevalence of high FCR was 45%. Factors associated with high FCR were female sex with 1.6 higher odds (95% CI 1.22-2.25; p = 0.001); having ≥1 comorbidities and receiving any treatment other than surgery alone with 1.5 (95% CI 1.07-2.05; p = 0.017) and 1.4 (95% CI 1.06-1.98; p = 0.020) higher odds, respectively. Patients on active follow-up had 1.7 higher odds (95% CI 1.20-2.61; p = 0.004) and patients with higher levels of FCR scored lower on the global health status scale (72 vs. 83 p ≤ 0.001)., Conclusions: Severe FCR is common in sarcoma survivors and high levels are related to a decreased global health status. FCR deserves more attention in sarcoma survivorship, and structured support programs should be developed to deliver interventions in a correct and time adequate environment.

Background: Sex differences in cancer have gained attention in recent years. The role of sex as a prognostic factor in gastrointestinal stromal tumours (GIST) has not been well established. The aim of this research was to elucidate potential sex differences in GIST patients and the influence of sex on disease-specific survival (DSS)., Methods: A review of the literature was carried out to obtain an overview of all literature with sex as a covariate on GIST survival analyses. Furthermore, in the Dutch GIST Registry, GIST characteristics between males and females were compared and the influence of sex on DSS was analysed., Results: A total of 118 articles from the review of the literature met our selection criteria; 58% of the articles found no sex difference in survival and 42% did find a sex difference. All differences favoured female patients, although there was substantial overlap of individual patients in the various reported groups. The Dutch GIST Registry cohort consisted of 1425 patients (46% female). Compared with female patients, male patients had larger tumours (mean 9.0 cm versus 7.9 cm) and higher mitotic rates (34.4% versus 28.0% >5 mitoses/5 mm 2 ). GIST in males was more often metastasized at diagnosis (21.3% versus 13.7%) and incurable (38.5% versus 31.0%). Male patients less often received surgery of the primary tumour (71.7% versus 78.9%), but did experience more tumour ruptures (18.2% versus 13.3%). Male patients had a worse DSS than females. This was not statistically significant when corrected for differences in GIST characteristics., Conclusions: In case of sex differences in GIST in the literature, male patients have a worse outcome. In our Dutch GIST cohort a similar finding was made, but sex was shown not to be an independent factor. Male patients more often had aggressive GISTs, with larger tumours, higher mitotic rates, more tumour ruptures, and metastases, which could explain the sex differences in DSS., Competing Interests: Disclosure RM received research grants from Astellas, Bayer, Cristal Therapeutics, PamGene, Pfizer, Roche, Sanofi, Servier. NS provided consultation or attended advisory boards for Boehringer Ingelheim, Ellipses Pharma, Hengrui Europe Therapeutics; NS received research grants for the institute from AB Science, AbbVie, Actuate Therapeutics, ADC Therapeutics, Amgen, Array, Ascendis Pharma, Astex, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio, Bristol-Myers Squibb, Cantargia, Celgene, CellCentric, Crescendo, Cytovation, Deciphera, Eli Lilly, Exelixis, Genentech, Genmab, Gilead, GlaxoSmithKline, Incyte, InteRNA, Janssen/Johnson & Johnson, Kinate, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Novartis, Numab, Pfizer, Pierre Fabre, Regeneron, Roche, Sanofi, Seattle Genetics, Servier, Taiho, Takeda (outside the submitted work). WTAvdG received a research grant from Eli Lilly (to the institute); WTAvdG was on advisory boards from SpringWorks, Bayer and PTC Therapeutics (all to the institute); WTAvdG other non-financial interests: president EORTC, board member ECO, Chair Dutch Sarcoma Group, Chair Dutch AYA ‘Young and Cancer’ Care Network, board member (CTOS). All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The incidence of melanoma is increasing and 37% of patients with metastatic melanoma eventually have brain metastasis (BM). Currently, there is no consensus on screening for BM in patients with resected stage III melanoma. However, given the high incidence of BM, routine screening magnetic resonance imaging (MRI) of the brain is considered in patients with completely resected stage III melanoma before the start of adjuvant treatment. The aim of this study was to assess the yield of screening for BM in these patients., Materials and Methods: A single-center cohort study was carried out in the Erasmus MC, Rotterdam, The Netherlands, a large tertiary referral center for patients with melanoma. Eligible patients with complete resection of stage III melanoma and a screening MRI of the brain, made within 12 weeks after resection and before adjuvant treatment (programmed cell death protein 1 inhibitors, dabrafenib-trametinib), available between 1 August 2018 and 1 January 2021, were included., Results: A total of 202 patients were included. Eighteen (8.9%) of 202 patients had extracranial metastasis at screening. Two (1.1%) of the remaining 184 patients had BM at screening, resulting in a switch from adjuvant treatment to ipilimumab-nivolumab. At a median follow-up of 21.2 months, BM was detected in another 4 (2.4%) of 166 patients who started with adjuvant treatment., Conclusions: The yield of screening MRI of the brain is low after complete resection of stage III melanoma, before the start of adjuvant treatment. Therefore, routine screening MRI is not recommended in this setting., Competing Interests: Disclosure AAMvdV: consultancy boards (fees paid to the institution) for BMS, MSD, Merck, Sanofi, Pierre Fabre, Roche, Novartis, Pfizer, Eisai, Ipsen. MS: speaker fee (paid to the institution) from AuntMinnie. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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., Conclusion: TO differs between indications for liver resection and can be used to assess between hospital and network differences., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This meta-analysis aimed to evaluate the effectiveness of intensive follow-up after curative intent treatment for five common solid tumours, in terms of survival and treatment of recurrences., Methods: A systematic literature search was conducted, identifying comparative studies on follow-up for colorectal, lung, breast, upper gastro-intestinal and prostate cancer. Outcomes of interest were overall survival (OS), cancer specific survival (CSS), and treatment of recurrences. Random effects meta-analyses were conducted, with particular focus on studies at low risk of bias., Results: Fourteen out of 63 studies were considered to be at low risk of bias (8 colorectal, 4 breast, 0 lung, 1 upper gastro-intestinal, 1 prostate). These studies showed no significant impact of intensive follow-up on OS (hazard ratio, 95% confidence interval) for colorectal (0.99; 0.92-1.06), breast 1.06 (0.92-1.23), upper gastro-intestinal (0.78; 0.51-1.19) and prostate cancer (1.00; 0.86-1.16). No impact on CSS (hazard ratio, 95% confidence interval) was found for colorectal cancer (0.94; 0.77-1.16). CSS was not reported for other cancer types. Intensive follow-up increased the rate of curative treatment (relative risk; 95% confidence interval) for colorectal cancer recurrences (1.30; 1.05-1.61), but not for upper gastro-intestinal cancer recurrences (0.92; 0.47-1.81). For the other cancer types, no data on treatment of recurrences was available in low risk studies., Conclusion: For colorectal and breast cancer, high quality studies do not suggest an impact of intensive follow-up strategies on survival. Colorectal cancer recurrences are more often treated locally after intensive follow-up. For other cancer types evaluated, limited high quality research on follow-up is available., Competing Interests: Conflict of Interest statement 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 © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Sarcopenia is associated with impaired short- and long-term outcomes in gastrointestinal cancers. Whether sarcopenia is associated with impaired survival after local therapy of Colorectal Cancer Liver Metastases (CRLM) remains controversial. This study aimed to determine the influence of sarcopenia on long-term outcomes after curative-intent therapy for CRLM., Methods: Patients undergoing local therapy for CRLM between 2003 and 2019 were retrospectively analyzed using the skeletal muscle index at the level of the third lumbar vertebra as an indicator of sarcopenia. Factors associated with overall (OS) and disease-free (DFS) survival were analyzed using univariable and multivariable cox regression., Results: In total 213/465 patients (46%) were considered sarcopenic. Sarcopenic patients had no impaired 5-year OS or DFS compared to non-sarcopenic patients, 38% vs 44% (p = 0.153) and 19 vs 23% (p = 0.339) respectively. Sarcopenia was not associated with impaired OS (HR = 1.11, 95%CI = 0.85-1.46, p = 0.43) or DFS (HR = 0.99, 95%CI = 0.77-1.28, p = 0.96) in multivariable analysis. There were no significant differences in postoperative complications (p = 0.47), the incidence (p = 0.65) and treatment (p = 0.37) of recurrent metastases. Five-year OS after resection for recurrences was 14% (sarcopenic) and 22% (non-sarcopenic) p 0.716., Conclusion: Sarcopenia assessed by computed tomography was not associated with impaired survival outcomes in the group of CRLM patients overall., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022. The Author(s).)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)