Publications by authors named "Cornelis Verhoef"

295 Publications

Unraveling Desmoid-Type Fibromatosis-Specific Health-Related Quality of Life: Who Is at Risk for Poor Outcomes.

Cancers (Basel) 2022 Jun 16;14(12). Epub 2022 Jun 16.

Department of Surgical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.

Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, but their local aggressive tumour growth and unpredictable behaviour can have a significant impact on health-related quality of life (HRQoL). Little is known about which DTF patients are particularly affected by an impaired HRQoL. The objectives of this study were to assess HRQoL among different groups of DTF patients and to investigate which socio-demographic and clinical characteristics were associated with DTF-specific HRQoL. A cross-sectional study was conducted among DTF patients from the United Kingdom and the Netherlands. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), accompanied by the DTF-QoL to assess DTF-specific HRQoL. The scores were compared amongst subgroups, based on the socio-demographic and clinical characteristics of DTF patients. Multiple linear regression analyses with a backward elimination were conducted to identify the factors associated with DTF-specific HRQoL. A total of 235 DTF patients completed the questionnaires. Female patients, patients with more than two comorbidities, or patients who received treatment other than only active surveillance (AS) or surgery scored significantly worse on the subscales of both the EORTC QLQ-C30 and DTF-QoL. Patients that were ≥ 40 years scored significantly worse on the physical functioning scale of the EORTC QLQ-C30, while younger patients (18-39 years) scored significantly worse on several DTF-QoL subscales. Differences in the DTF-QoL subscales were found for tumour location, time since diagnosis and the presence of recurrent disease. Furthermore, treatments other than AS or surgery only, female sex, younger age and the presence of comorbidities were most frequently associated with worse scores on the DTF-QoL subscales. This study showed that (DTF-specific) HRQoL differs between groups of DTF patients. Awareness of these HRQoL differences could help to provide better, personalised care that is tailored to the needs of a specific subgroup.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14122979DOI Listing
June 2022

Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I-II Melanoma Patients at Risk of Disease Relapse.

Cancers (Basel) 2022 Jun 9;14(12). Epub 2022 Jun 9.

Departments of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.

Background: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I-II melanoma) is watchful waiting, while >40% of patients with stage IB-IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I-II melanoma at risk of disease relapse.

Methods: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (the Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only.

Results: In total, 535 patients (stage I-II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4-96.4) in CP-GEP low-risk patients ( = 122) versus 80.7% (95%CI: 76.3-84.3) in CP-GEP high-risk patients ( = 413; hazard ratio 2.93 (95%CI: 1.41-6.09), < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a 'low risk' of recurrence (96.8% 5-year RFS (95%CI 91.6-98.8), 130), 49% as 'intermediate risk' (88.4% 5-year RFS (95%CI 83.6-91.8), 261), and 26% as 'high risk' (61.1% 5-year RFS (95%CI 51.9-69.1), 137).

Conclusion: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I-II melanoma into two groups differentiated by RFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14122854DOI Listing
June 2022

Intraperitoneal paclitaxel for patients with primary malignant peritoneal mesothelioma: a phase I/II dose escalation and safety study-INTERACT MESO.

BMJ Open 2022 Jun 22;12(6):e062907. Epub 2022 Jun 22.

Department of Surgical Oncology, Erasmus MC Kanker Instituut, Rotterdam, The Netherlands.

Introduction: Malignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment. The benefit of systemic treatment for these patients is limited at the cost of considerable morbidity. Hence, there is a need for appropriate palliative treatment options for patients with MPM. As MPM rarely disseminates outside the abdominal cavity, these patients might benefit from local treatment. A higher, more effective dose of chemotherapy can directly be delivered at the site of the disease. Systemic uptake will be limited, likely resulting in less toxicity. The aim of the INTERACT MESO trial is to determine the maximum tolerable dose of intraperitoneal paclitaxel monotherapy in patients with MPM. Secondary endpoints are to assess safety and toxicity, feasibility and the pharmacokinetic profile of this treatment.

Methods And Analysis: The INTERACT MESO trial is a prospective, open-label, single-centre, phase I study with a classic three-plus-three dose escalation design. The study population consists of adult patients with primary MPM, without extra-abdominal disease, who are not eligible to undergo CRS-HIPEC. According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of CRS-HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8-16 weekly cycles of intraperitoneal chemotherapy will be administered.

Ethics And Dissemination: The Central Committee on Research Involving Human Subjects (CCMO, The Hague, The Netherlands) and the Medical Research Ethics Committee (METC, Rotterdam, The Netherlands) have granted permission to carry out this study protocol. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.

Trial Registration Number: NL9718. EudraCT: 2021-003637-11.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2022-062907DOI Listing
June 2022

The Impact of Low Skeletal Muscle Mass on Short- and Long-Term Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Ann Surg Oncol 2022 Jun 1. Epub 2022 Jun 1.

Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal metastases from colorectal cancer (CRC) or pseudomyxoma peritonei (PMP). Because of the considerable morbidity of this treatment, optimal patient selection is key. This study aimed to assess the impact of low skeletal muscle mass (SMM) on outcomes after CRS-HIPEC.

Methods: Patients who underwent CRS-HIPEC between 2014 and 2020 at a tertiary center were included. SMM was measured on computed tomography by means of the L3 muscle index. Postoperative complications and survival outcomes were compared between groups by use of logistic regression and Kaplan-Meier survival analyses.

Results: Of 284 included patients, 149 had low SMM. Occurrence of severe postoperative complications did not differ between groups (28.9% for patients with low vs. 34.1% for patients with normal SMM). Low SMM was not associated with postoperative complications (p = 0.344). For CRC patients, no significant differences were observed in disease-free (DFS) or overall survival (OS) between patients with low (median DFS 7 months [IQR 4-14], median OS 33 months [IQR 14-NR]) and patients with normal SMM (median DFS 8 months [IQR 5-20], median OS 35 months [IQR 18-NR]). Regarding PMP, survival outcomes did not significantly differ between groups (3-year DFS 47.3% for patients with low SMM vs. 54.5% for patients with normal SMM, p = 0.676; 3-year OS 70.8% vs. 90.9% respectively, p = 0.172).

Conclusions: Low SMM could not be identified as a predictor of severe complications or survival outcomes after CRS-HIPEC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-022-11941-2DOI Listing
June 2022

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights.

Br J Cancer 2022 Jun 1. Epub 2022 Jun 1.

Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-022-01859-7DOI Listing
June 2022

Hospital costs and cosmetic outcome of benign and high-risk breast lesions managed by vacuum-assisted excision versus surgical excision.

Br J Radiol 2022 Jun 9:20220117. Epub 2022 Jun 9.

Department of Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands.

Objectives: Although vacuum-assisted excision (VAE) is a safe and effective alternative to surgical excision (SE), the latter is most commonly used for the management of benign and high-risk breast lesions. To evaluate the healthcare benefit of VAE, hospital costs and cosmetic outcome after VAE were compared to SE. Additionally, the impact of VAE implementation on hospital costs was investigated.

Methods: This was a single-centre retrospective cohort study with two cohorts: "VAE" and "SE". All patients with a benign or high-risk lesion excised by VAE or SE from January 2016 up to December 2019 were included. Cosmetic outcome was measured with the BCTOS-cosmetic subscale, and hospital costs were presented as mean (SD) and median (IQR).

Results: During the study period, 258 patients with 295 excised lesions were included. The initial procedure was VAE in 102 patients and SE in 156 patients. Hospital costs after (median € 2324) were significantly lower than before (median € 3,144) implementation of VAE (mean difference € 1,004, < 0.001), most likely attributable to the lower costs for patients treated with VAE (mean difference € 1,979, < 0.001). Mean cosmetic outcome was comparable between VAE (median 1.35) and SE (median 1.44, = 0.802).

Conclusions: Implementing VAE as an alternative treatment option for benign and high-risk breast lesions resulted in a large decrease in hospital costs but a cosmetic benefit of VAE could not be demonstrated in this retrospective study.

Advances In Knowledge: Costs associated with the complete patient pathway were included and not only VAE was compared to SE but also the before cohort was compared to the after cohort to demonstrate the benefit of VAE implementation in clinical practice. Additionally, cosmetic outcome was compared between VAE and SE using patient reported outcome measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20220117DOI Listing
June 2022

Absence of association between CT-assessed skeletal muscle mass and long-term oncological outcomes after curative therapy for colorectal liver metastasis.

HPB (Oxford) 2022 Apr 26. Epub 2022 Apr 26.

Department of Surgical Oncology and Gastro-intestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2022.04.009DOI Listing
April 2022

Optimizing discharge after major surgery using an artificial intelligence-based decision support tool (DESIRE): An external validation study.

Surgery 2022 May 4. Epub 2022 May 4.

Department of Surgical Oncology, Erasmus MC Cancer Institute University Medical Center, Rotterdam, The Netherlands.

Background: In the DESIRE study (Discharge aftEr Surgery usIng aRtificial intElligence), we have previously developed and validated a machine learning concept in 1,677 gastrointestinal and oncology surgery patients that can predict safe hospital discharge after the second postoperative day. Despite strong model performance (area under the receiver operating characteristics curve of 0.88) in an academic surgical population, it remains unknown whether these findings can be translated to other hospitals and surgical populations. We therefore aimed to determine the generalizability of the previously developed machine learning concept.

Methods: We externally validated the machine learning concept in gastrointestinal and oncology surgery patients admitted to 3 nonacademic hospitals in The Netherlands between January 2017 and June 2021, who remained admitted 2 days after surgery. Primary outcome was the ability to predict hospital interventions after the second postoperative day, which were defined as unplanned reoperations, radiological interventions, and/or intravenous antibiotics administration. Four forest models were locally trained and evaluated with respect to area under the receiver operating characteristics curve, sensitivity, specificity, positive predictive value, and negative predictive value.

Results: All models were trained on 1,693 epsiodes, of which 731 (29.9%) required a hospital intervention and demonstrated strong performance (area under the receiver operating characteristics curve only varied 4%). The best model achieved an area under the receiver operating characteristics curve of 0.83 (95% confidence interval [0.81-0.85]), sensitivity of 77.9% (0.67-0.87), specificity of 79.2% (0.72-0.85), positive predictive value of 61.6% (0.54-0.69), and negative predictive value of 89.3% (0.85-0.93).

Conclusion: This study showed that a previously developed machine learning concept can predict safe discharge in different surgical populations and hospital settings (academic versus nonacademic) by training a model on local patient data. Given its high accuracy, integration of the machine learning concept into the clinical workflow could expedite surgical discharge and aid hospitals in addressing capacity challenges by reducing avoidable bed-days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2022.03.031DOI Listing
May 2022

Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases.

Radiol Imaging Cancer 2022 May;4(3):e210105

From the Department of Surgery (N.J.W., R.K., G.K.) and Department of Radiology and Nuclear Medicine (J.H.T.M.v.W., I.M.G.C.N., F.S., I.O.A., S.S.K.S.P., M.R.W.E., J.S.), Cancer Center Amsterdam, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Department of Medical Oncology (K.B., C.J.A.P.) and Department of Surgery (S.v.D., T.M.v.G., R.J.S.), Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Medical Imaging, Radboud University Medical Center, Radboud University Nijmegen, Nijmegen, the Netherlands (M.J.v.A., J.J.H.); Department of Hepatobiliary, Transplantation, and Endocrine Surgery, Antwerp University Hospital, Antwerp, Belgium (T.C.); Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands (C.H.C.D.); Department of Surgery, Universitätsklinikum Aachen, Aachen, Germany (C.H.C.D.); Department of Surgery, Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, the Netherlands (M.F.G.); Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands (D.G., C.V.); Department of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, Groningen, the Netherlands (K.P.d.J., J.M.K.); Department of Surgery, Medical Spectrum Twente, Enschede, the Netherlands (M.S.L.L.); Department of Interventional Radiology, St Antonius Hospital, Nieuwegein, the Netherlands (K.P.v.L.); Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St Antonius Hospital, Nieuwegein, the Netherlands (I.Q.M.); Department of Surgery, Isala Hospital, Zwolle, the Netherlands (G.A.P.); Department of Surgery, Amphia Hospital, Breda, the Netherlands (A.M.R.); Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands (T.M.R.); Department of Surgery, Radboud University Medical Center, Radboud University Nijmegen, Nijmegen, the Netherlands (J.H.W.d.W.); Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands (C.J.A.P.); and Department of Health, SAS Institute, Huizen, the Netherlands (J.H.).

Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morphologic response with gene mutation status, targeted therapy, and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 measurements. Materials and Methods Participants with initially unresectable CRLM receiving different systemic therapy regimens from the randomized, controlled CAIRO5 trial (NCT02162563) were included in this prospective imaging study. Three radiologists independently assessed morphologic tumor response on baseline and first follow-up CT scans according to previously published criteria. Two additional radiologists evaluated disagreement cases. Interobserver agreement was calculated by using Fleiss κ. On the basis of the majority of individual radiologic assessments, the final morphologic tumor response was determined. Finally, the relation of morphologic tumor response and clinical prognostic parameters was assessed. Results In total, 153 participants (median age, 63 years [IQR, 56-71]; 101 men) with 306 CT scans comprising 2192 CRLM were included. Morphologic assessment performed by the three radiologists yielded 86 (56%) agreement cases and 67 (44%) disagreement cases (including four major disagreement cases). Overall interobserver agreement between the panel radiologists on morphology groups and morphologic response categories was moderate (κ = 0.53, 95% CI: 0.48, 0.58 and κ = 0.54, 95% CI: 0.47, 0.60). Optimal morphologic response was particularly observed in patients treated with bevacizumab ( = .001) and in patients with mutation ( = .04). No evidence of a relationship between RECIST 1.1 and morphologic response was found ( = .61). Conclusion Morphologic tumor response assessment following systemic therapy in participants with CRLM demonstrated considerable interobserver variability. Tumor Response, Observer Performance, CT, Liver, Metastases, Oncology, Abdomen/Gastrointestinal Clinical trial registration no. NCT02162563 © RSNA, 2022.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/rycan.210105DOI Listing
May 2022

Survival Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Patients with Synchronous Versus Metachronous Onset of Peritoneal Metastases of Colorectal Carcinoma.

Ann Surg Oncol 2022 May 5. Epub 2022 May 5.

Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases (PM) from colorectal carcinoma (CRC). Because of considerable morbidity, optimal patient selection is essential. This study was designed to determine the impact of the onset of PM (synchronous vs. metachronous) on survival outcomes after CRS-HIPEC.

Methods: Patients undergoing CRS-HIPEC for colorectal PM in two academic centers in the Netherlands between 2010 and 2020 were eligible for inclusion. Patients were classified as synchronous (s-PM, i.e., diagnosis at time of presentation, staging, or primary surgery) or metachronous onset (m-PM, i.e., diagnosis during follow-up) of colorectal PM. Survival outcomes were compared between groups by Kaplan-Meier survival and Cox regression analyses.

Results: Of 390 included patients, 179 (45.9%) had synchronous onset of colorectal PM. These patients more often presented with higher TN-stage and poor differentiation/signet cell histology. Treatment with perioperative chemotherapy was more common in s-PM patients. m-PM patients experienced more serious postoperative complications (Clavien-Dindo ≥ III). There was no significant difference in disease-free survival (DFS) between s-PM (median 9 months, interquartile range [IQR] 5-15) and m-PM patients (median 8 months, IQR 5-17). Overall survival (OS) was significantly shorter for s-PM (median 28 months, IQR 11-48) versus m-PM patients (median 33 months, IQR 18-66, p = 0.049). Synchronous onset of PM was not independently associated with OS in a multivariable analysis.

Conclusions: Synchronous onset of colorectal PM was associated with poor tumor characteristics and more advanced disease, but was not an independent predictor of survival outcomes after CRS-HIPEC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-022-11805-9DOI Listing
May 2022

Interregional practice variations in the use of local therapy for synchronous colorectal liver metastases in the Netherlands.

HPB (Oxford) 2022 Apr 19. Epub 2022 Apr 19.

Erasmus MC Cancer Institute, Department of Surgical Oncology and Gastrointestinal Surgery, Rotterdam, the Netherlands. Electronic address:

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. Te 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2022.04.006DOI Listing
April 2022

Histopathological and immunological spectrum in response evaluation of talimogene laherparepvec treatment and correlation with durable response in patients with cutaneous melanoma.

Melanoma Res 2022 Apr 21. Epub 2022 Apr 21.

Department of Pathology.

Objective: Talimogene laherparepvec (T-VEC) is an intralesional oncolytic virotherapy for patients with irresectable stage III-IVM1a cutaneous melanoma. Although this treatment is considered to mainly act through T cell-mediated mechanisms, prominent numbers of plasma cells after T-VEC treatment have been described. The aim was to investigate how often these plasma cells were present, whether they were relevant in the response to treatment, and if these or other histopathological features were associated with durable response to treatment.

Methods: Histopathological (granulomas, perineural inflammation, etc.) and immunological features [e.g. B cells/plasma cells (CD20/CD138) and T cells (CD3,CD4,CD8)] were scored and correlated with durable tumor response [i.e. complete response (CR) persisting beyond 6 months after treatment]. Plasmacellular infiltrate was examined with next-generation sequencing and immunohistochemistry (IgG, IgM, IgA, and IgD).

Results: Plasma cells were present in all T-VEC injected biopsies from 25 patients with melanoma taken at 3-5 months after starting treatment. In patients with a durable response (n = 12), angiocentric features and granulomas were more frequently identified compared with patients without a (durable) response (n = 13); 75% versus 29% for angiocentric features (P = 0.015) and 58% versus 15% for granulomas (P = 0.041). There was a class switch of IgM to IgG with skewing to certain dominant Ig heavy chain clonotypes.

Conclusion: An angiocentric granulomatous pattern in T-VEC injected melanoma lesions was associated with a durable CR (>6 months). Plasma cells are probably a relevant feature in the mechanism of response but were not associated with durable response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CMR.0000000000000824DOI Listing
April 2022

Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment.

Eur J Cancer 2022 06 14;168:25-33. Epub 2022 Apr 14.

Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands. Electronic address:

Background: The aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics.

Methods: Consecutive patients after complete resection of CRLM were included from two centres (1992-2019). A prediction model providing 10-year OS probabilities was developed using Cox regression analysis, including KRAS, BRAF and histopathological growth patterns. Discrimination and calibration were assessed using cross-validation. A web-based calculator was built to predict individual 10-year OS probabilities.

Results: A total of 4112 patients were included. The estimated 10-year OS was 30% (95% CI 29-32). Fifteen patient, tumour and treatment characteristics were independent prognostic factors for 10-year OS; age, gender, location and nodal status of the primary tumour, disease-free interval, number and diameter of CRLM, preoperative CEA, resection margin, extrahepatic disease, KRAS and BRAF mutation status, histopathological growth patterns, perioperative systemic chemotherapy and hepatic arterial infusion pump chemotherapy. The discrimination at 10-years was 0.73 for both centres. A simplified risk score identified four risk groups with a 10-year OS of 57%, 38%, 24%, and 12%.

Conclusions: Ten-year OS after resection of CRLM is best predicted with a model including 15 patient, tumour, and treatment characteristics. The web-based calculator can be used to inform patients. This model serves as a benchmark to determine the prognostic value of novel biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2022.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117473PMC
June 2022

The added value of chest imaging after neoadjuvant radiotherapy for soft tissue sarcoma of the extremities and trunk wall: A retrospective cohort study.

Eur J Surg Oncol 2022 Jul 31;48(7):1543-1549. Epub 2022 Mar 31.

Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.

Introduction: There is no clear evidence regarding the benefit of restaging for distant metastases after neoadjuvant radiotherapy (RTX) in patients with soft tissue sarcoma (STS) of the extremities and trunk wall. This study aimed to determine how often restaging of the chest identified metastatic disease that altered management in these patients.

Methods: We performed a single-centre retrospective study from 2010 to 2020. All patients with non-metastatic STS of the extremities and trunk wall who were treated with neoadjuvant RTX and received a staging and restaging chest CT scan or X-ray for distant metastasis were included. The outcome of interest was change in treatment strategy due to restaging after neoadjuvant RTX.

Results: Within the 144 patients who were staged and treated with neoadjuvant RTX, a restaging chest CT or X-ray was performed in 134 patients (93%). A change in treatment strategy due to new findings at restaging after RTX was observed in 26 out of 134 patients (19%). In 24 patients the scheduled resection of the primary STS was cancelled at restaging (24/134, 18%), given the findings at restaging. The other two patients did receive the intended local resection, but either with palliative intent, or as a part of a previously unplanned multimodality treatment.

Conclusion: In approximately one in five patients restaging results in a change in treatment strategy. This underlines the added value of routine restaging for distant metastases with chest CT or X-ray after neoadjuvant RTX in patients with STS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejso.2022.03.231DOI Listing
July 2022

Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study.

Cancers (Basel) 2022 Mar 18;14(6). Epub 2022 Mar 18.

Department of Surgical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Background: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification.

Methods: Ten GIST patients, planned to undergo resection, were included. During surgery, 10 mg of ICG was intravenously administered, and NIRF imaging was performed at 5, 10, and 15 min after the injection. The tumor fluorescence intensity was visually assessed, and tumor-to-background ratios (TBRs) were calculated for exophytic lesions.

Results: Eleven GIST lesions were imaged. The fluorescence intensity of the tumor was visually synchronous and similar to the background in five lesions. In one lesion, the tumor fluorescence was more intense than in the surrounding tissue. Almost no fluorescence was observed in both the tumor and healthy peritoneal tissue in two patients with GIST lesions adjacent to the liver. In three GISTs without exophytic growth, no fluorescence of the tumor was observed. The median TBRs at 5, 10, and 15 min were 1.0 (0.4-1.2), 1.0 (0.5-1.9), and 0.9 (0.7-1.2), respectively.

Conclusion: GISTs typically show similar fluorescence intensity to the surrounding tissue in NIRF imaging after intraoperative ICG administration. Therefore, intraoperatively administered ICG is currently not applicable for adequate tumor identification, and further research should focus on the development of tumor-specific fluorescent tracers for GISTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14061572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946640PMC
March 2022

In desmoid-type fibromatosis cells sorafenib induces ferroptosis and apoptosis, which are enhanced by autophagy inhibition.

Eur J Surg Oncol 2022 Jul 19;48(7):1527-1535. Epub 2022 Feb 19.

Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands. Electronic address:

Introduction: Desmoid-type fibromatosis (DTF) is a rare, soft tissue tumour. Sorafenib, a multikinase inhibitor, has demonstrated antitumour efficacy in DTF patients. Little is known about the underlying molecular mechanisms, which are crucial to know to further optimize systemic treatments. Here we investigated the molecular effects of sorafenib exposure on DTF and stromal cells, with an emphasis on cell death mechanisms.

Material And Methods: DTF primary cell cultures, with known CTNNB1 status, and primary stromal cell cultures, derived from DTF tissue, were exposed to clinically relevant concentrations of sorafenib in the presence or absence of inhibitors of ferroptosis, apoptosis and autophagy. Cell viability was determined after 24 and 48 h using MTT assays. Annexin V/PI staining, lipid peroxidation analysis and immunoblotting were performed to assess apoptosis, ferroptosis and autophagy.

Results: Exposure to sorafenib caused a significant, concentration- and time-dependent decrease in cell viability in all primary DTF and stromal cell cultures. Inhibitors of ferroptosis and apoptosis protected against sorafenib-mediated cytotoxicity implicating that both cell death mechanisms are activated. Annexin V/PI stainings and lipid peroxidation analyses confirmed induction of apoptosis and ferroptosis, respectively. Autophagy inhibition enhanced the cytotoxic effect of sorafenib and led to a stronger induction of apoptosis and ferroptosis.

Conclusion: This study identified ferroptosis and apoptosis as mechanisms for the sorafenib induced cell death in DTF cells as well as stromal cells. Furthermore, autophagy inhibition enhanced the cytotoxic effects of sorafenib. Knowledge of the mechanisms by which sorafenib affects DTF at a cellular level may help to optimize its clinical efficacy and mitigate toxic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejso.2022.02.020DOI Listing
July 2022

The role of perioperative chemotherapy in primary high-grade extremity soft tissue sarcoma: a risk-stratified analysis using PERSARC.

Eur J Cancer 2022 04 24;165:71-80. Epub 2022 Feb 24.

Department of Orthopaedic Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.

Objective: The aim of the study is to assess the effect of perioperative chemotherapy (CTX) in patients with grade II-III extremity soft tissue sarcoma (eSTS) on overall survival (OS) and evaluate whether the PERSARC prediction tool could identify patients with eSTS more likely to benefit from CTX.

Methods: Patients (18-70 years) with primary high-grade eSTS surgically treated with curative intent were included in the retrospective cohort study. The effect of any perioperative CTX and anthracycline + ifosfamide (AI)-based CTX on OS was investigated in three PERSARC-risk groups (high/intermediate/low). The PERSARC-risk groups were defined by the 33% and 66% quantile of the predicted 5-year OS of the study population equal to a 5-year OS of 65.8% and 79.8%, respectively. The effect of CTX on OS was investigated with weighted Kaplan-Meier curves and multivariable Cox models with an interaction between risk group and CTX.

Results: This study included 5683 patients. The weighted Kaplan-Meier curves did not demonstrate a beneficial effect of any CTX and AI-based CTX on OS in the overall population. However, in the high PERSARC-risk group the 5-year OS of AI-based CTX was significantly better than no CTX (69.8% vs 59.0%, respectively, p = 0.004) (HR 0.66, 95%CI 0.53-0.83).

Conclusions: This study demonstrated a beneficial effect of AI-based CTX on OS in a selected group of high-risk patients with an absolute survival benefit of 11% as stratified by the PERSARC prediction tool. However, no beneficial effect of CTX on OS was found in the overall population of patients with primary high-grade eSTS younger than 70 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2022.01.013DOI Listing
April 2022

Quality of life of caregivers of breast cancer patients: a cross-sectional evaluation.

Health Qual Life Outcomes 2022 Feb 19;20(1):29. Epub 2022 Feb 19.

Academic Breast Cancer Center, Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Room NA-2117, 3000 WB, Rotterdam, The Netherlands.

Background: The aim of this study was to evaluate the care-related quality of life in caregivers of breast cancer patients, to assess its association with breast cancer patients' health-related quality of life (HRQoL), and to identify its potential predictors.

Methods: Caregivers of breast cancer patients at six and twelve months follow up were identified through the institutes electronic patient reported outcome measurement collection tool. The Care-related Quality of Life Instrument (CarerQoL) was used to obtain CarerQoL utility scores by applying a pre-existent set of Dutch tariffs and the CarerQoL VAS score, which represented the overall happiness of caregivers. The associations between breast cancer patients' EQ-5D-5L and EORTC QLQ-C30 scores and caregivers' CarerQoL scores was determined with Spearman's correlation coefficients. Associations between log transformed CarerQol scores and patient and caregiver characteristics were analyzed with multivariable linear regression analyses.

Results: A total of 116 completed CarerQoL questionnaires were analyzed. Most caregivers were male spouses or partners (81.4%) with a mean age of 55.7 ± 16.4. The median CarerQoL utility score was 92.4/100 and median CarerQoL VAS was 8.0/10. We found weak correlations between CarerQoL VAS scores and patients' EQ-5D-5L utility score (0.301, p = 0.002) and EQ VAS score (0.251, p = 0.009), and between EORTC QLQ-C30 scores and CarerQol VAS (0.339, p < 0.001) and utility score (0.236, p = 0.015). There was a negative association between chemotherapy and log-transformed CarerQoL utility score (B =  - 0.063, p = 0.001) and VAS score (B =  - 0.044, p = 0.038) at six months follow-up.

Conclusions: This study provides the first evaluation of the CarerQoL in caregivers of Dutch breast cancer patients. Caregivers' happiness was associated with breast cancer patients' HRQoL. Our results can be used as reference values for future care-related quality of life evaluations. Breast cancer patients face many difficulties during their cancer journey and often need the support of their caregivers. Despite the fact that successfully providing informal care can have positive effects on caregivers' wellbeing, it may also have a negative impact on their quality of life. Monitoring the quality of life using a standardized questionnaire, such as the CarerQoL questionnaire, may result in early detection of possible quality of life issues. In this study, we evaluated 116 caregivers and found overall high CarerQoL scores. The scores showed a positive relation to the patients' quality of life. Lower CarerQoL scores at six months after surgery were found in caregivers of patients who received chemotherapy. Our research underlines the importance to include caregivers of breast cancer patients in clinical practice, provides reference values for future research, and the results can be used to manage the caregivers' expectations prior to treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12955-022-01930-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858558PMC
February 2022

A Nationwide Prospective Clinical Trial on Active Surveillance in Patients with Non-Intra-Abdominal Desmoid-Type Fibromatosis: The GRAFITI Trial.

Ann Surg 2022 Feb 15. Epub 2022 Feb 15.

Department of Surgical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands Department of Orthopaedics and Sports Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Surgical Oncology, University Medical Center Utrecht, the Netherlands; Department of Surgical Oncology, Diakonessenhuis Utrecht, The Netherlands Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands Department of Surgical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

Objective: To assess tumour behaviour and the efficacy of active surveillance (AS) in patients with desmoid-type fibromatosis (DTF).

Summary Background Data: AS is recommended as initial management for DTF patients. Prospective data regarding the results of AS are lacking.

Methods: In this multicentre prospective cohort study (NTR4714), adult patients with non-intra-abdominal DTF were followed during an initial AS approach for 3 years. Tumour behaviour was evaluated according to RECIST. Cumulative incidence of the start of an active treatment and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Factors predictive for start of active treatment were assessed by Cox regression analyses.

Results: A total of 105 patients started with AS. Median tumour size at baseline was 4.1 cm (IQR 3.0-6.6). Fifty-seven patients had a T41A CTNNB1 mutation; 14 patients a S45F CTNNB1 mutation. At 3 years, cumulative incidence of the start of active treatment was 30% (95% CI 21-39) and PFS was 58% (95% CI 49-69). Median time to start active treatment and PFS were not reached at a median follow-up of 33.7 months. During AS, 32% of patients had stable disease, 28% regressed and 40% demonstrated initial progression. Larger tumour size (≥5 cm; hazard ratio (HR) = 2.38 [95% CI 1.15-4.90]) and S45F mutation (HR = 6.24 [95% CI 1.92-20.30]) were associated with the start of active treatment.

Conclusions: The majority DTF patients undergoing AS do not need an active treatment and experience stable or regressive disease, even after initial progression. Knowledge about the natural behaviour of DTF will help to tailor the follow-up schedule to the individual patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005415DOI Listing
February 2022

Development of a Disease-Specific Health-Related Quality of Life Questionnaire (DTF-QoL) for Patients with Desmoid-Type Fibromatosis.

Cancers (Basel) 2022 Jan 29;14(3). Epub 2022 Jan 29.

Department of Surgical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.

Sporadic desmoid-type fibromatosis (DTF) is a rare, non-metastasising soft-tissue tumour. Patients can experience a variety of disease-specific issues related to the unpredictable clinical course and aggressiveness of DTF, which negatively impacts health-related quality of life (HRQoL). These DTF-specific issues are not captured by generic HRQoL tools. A 102-item provisional DTF-specific HRQoL tool, the DTF-QoL, was previously developed. The aim of this study was to pre-test the psychometric properties of the DTF-QoL by administering it together with the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) to 236 DTF patients from the United Kingdom and the Netherlands. Construct validity and reliability were determined based on factor analysis, multi-trait scaling analysis, Cronbach's alpha, and correlations with the EORTC QLQ-C30 scales. Ninety-six items were selected, conceptualised into three symptom scales, eleven disease-impact scales and six single items, together forming the final DTF-QoL. Scaling assumptions were fully or moderately met for ten out of fourteen scales. Cronbach's alpha ranged from 0.551-0.908. Most scales of the DTF-QoL were weakly or moderately correlated with the EORTC QLQ-C30. The DTF-QoL is a promising tool capturing the whole spectrum of DTF-specific issues. Implementation of the DTF-QoL in research and clinical practice will help to personalise HRQoL measurement and clinical care for DTF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14030709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833407PMC
January 2022

Mesenchymal-epithelial transition factor (MET) immunoreactivity in positive sentinel nodes from patients with melanoma.

Ann Diagn Pathol 2022 Jun 7;58:151909. Epub 2022 Feb 7.

Department of Pathology, Erasmus MC, Rotterdam, the Netherlands. Electronic address:

Objective: Patients with cutaneous melanoma and a positive sentinel node (SN) are currently eligible for adjuvant treatment with targeted therapy and immune checkpoint inhibitors. Near-infrared (NIR) fluorescence imaging could be an alternative and less invasive tool for SN biopsy to select patients for adjuvant treatment. One potential target for NIR is the mesenchymal-epithelial transition factor (MET). This study aimed to assess MET immunoreactivity in positive SNs and to evaluate its potential diagnostic, prognostic and therapeutic value.

Methods: In this retrospective study, positive SN samples from patients with primary cutaneous melanoma were collected to assess MET immunoreactivity. To this end, paraffin-embedded SNs were stained for MET (monoclonal antibody D1C2). A 4-point Histoscore was used to determine cytoplasmic and membranous immunoreactivity (0 negative/1 weak/2 moderate/3 strong). Samples were considered positive when ≥10% of the cancer cells showed MET expression (staining intensity ≥1). Patient and clinicopathological characteristics were used for descriptive statistics, binary logistic regression, and survival analyses.

Results: Positive MET immunohistochemistry was observed in 24 out of 37 samples (65%). No statistically significant associations were found between MET positivity and the following prognostic factors: Breslow thickness (P = 0.961), ulceration (P = 1.000), and SN tumor burden (P = 0.792). According to MET positivity, Kaplan-Meier curves showed no significant differences in survival.

Conclusion: This exploratory study found no evidence to support MET immunoreactivity in positive SNs as a possible diagnostic or prognostic indicator in patients with melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anndiagpath.2022.151909DOI Listing
June 2022

Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.

Thorax 2022 Feb 11. Epub 2022 Feb 11.

Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Kanker Instituut, Rotterdam, The Netherlands

Introduction: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993.

Materials And Methods: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed.

Results: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001).

Conclusion: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2021-217709DOI Listing
February 2022

A Colon Resection and Pump Implantation in the Same Surgical Procedure: Is it Safe?

Ann Surg Oncol 2022 05 11;29(5):2754-2755. Epub 2022 Feb 11.

Department of Surgery, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-022-11423-5DOI Listing
May 2022

Local tumour control after radiofrequency or microwave ablation for colorectal liver metastases in relation to histopathological growth patterns.

HPB (Oxford) 2022 Jan 24. Epub 2022 Jan 24.

Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address:

Background: Regrowth after ablation is common, but predictive factors for local control are scarce. This study investigates whether histopathological growth patterns (HGP) can be used as a predictive biomarker for local control after ablation of colorectal liver metastases (CRLM).

Methods: Patients who received simultaneous resection and ablation as first treatment for CRLM between 2000 and 2019 were considered eligible. HGPs were determined on resected CRLM according to international guidelines and were classified as desmoplastic or non-desmoplastic. As minimal inter-tumoural heterogeneity has been demonstrated, the HGP of resected and ablated CRLM were presumed to be identical. Local tumour progression (LTP) was assessed on postoperative surveillance imaging. Uni- and multivariable competing risk methods were used to compare LTP.

Results: In total 221 patients with 443 ablated tumours were analysed. A desmoplastic HGP was found in 60 (27.1%) patients who had a total of 159 (34.7%) ablated lesions. Five-year LTP [95%CI] was significantly higher for ablated CRLM with a presumed non-desmoplastic HGP (37% [30-43] vs 24% [17-32], Gray's-test p = 0.014). On multivariable analysis, a non-desmoplastic HGP (adjusted HR [95%CI]; 1.55 [1.03-2.35]) was independently associated with higher LTP rates after ablation.

Conclusion: HGP is an independent predictor of local tumour progression following ablation of CRLM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2022.01.010DOI Listing
January 2022

Assessment of Radiofrequency Ablation for Papillary Microcarcinoma of the Thyroid: A Systematic Review and Meta-analysis.

JAMA Otolaryngol Head Neck Surg 2022 04;148(4):317-325

Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Importance: Papillary microcarcinomas of the thyroid (mPTCs) account for an increasing proportion of thyroid cancers in past decades. The use of radiofrequency ablation (RFA) has been investigated as an alternative to surgery. The effectiveness and safety of RFA has yet to be determined.

Objective: To evaluate the effectiveness and safety of RFA for low-risk mPTC.

Data Sources: Embase, MEDLINE via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched from inception to May 28, 2021.

Study Selection: Articles reporting on adult patients with mPTC treated with RFA were included. Studies that involved patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension were excluded. Final article selection was conducted by multiple reviewers based on consensus. The proportion of eligible articles was 1%.

Data Extraction And Synthesis: This meta-analysis was conducted in accordance with the MOOSE guidelines. Random and fixed-effect models were applied to obtain pooled proportions and 95% CIs.

Main Outcomes And Measures: The primary outcome was the complete disappearance rate of mPTC. Secondary outcomes were tumor progression and complications.

Results: Fifteen studies were included in this meta-analysis. A total of 1770 patients (1379 women [77.9%]; mean [SD] age, 45.4 [11.4] years; age range, 42.5-66.0 years) with 1822 tumors were treated with RFA; 49 tumors underwent 1 additional RFA session and 1 tumor underwent 2 additional RFA sessions. Mean (SD) follow-up time was 33.0 (11.4) months (range, 6-131 months). The pooled complete disappearance rate at the end of follow-up was 79% (95% CI, 65%-94%). The overall tumor progression rate was 1.5% (n = 26 patients), local residual mPTC in the ablation area was found in 7 tumors (0.4%), new mPTC in the thyroid was found in 15 patients (0.9%), and 4 patients (0.2%) developed lymph node metastases during follow-up. No distant metastases were detected. Three major complications occurred (2 voice changes lasting >2 months and 1 cardiac arrhythmia). Minor complications were described in 45 patients.

Conclusions And Relevance: The findings of this systematic review and meta-analysis suggest that RFA is a safe and efficient method to treat selected low-risk mPTCs. Radiofrequency ablation could be envisioned as step-up treatment after local tumor growth under active surveillance for an mPTC or initial treatment in patients with mPTCs with anxiety about active surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2021.4381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832309PMC
April 2022

Histopathological growth patterns of resected non-colorectal, non-neuroendocrine liver metastases: a retrospective multicenter study.

Clin Exp Metastasis 2022 06 6;39(3):433-442. Epub 2022 Feb 6.

Department of Surgical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.

Background: Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods: A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan-Meier and multivariable Cox regression analysis.

Results: In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36-78%) versus 40% (30-53%), and 33% (19-61%) versus 15% (9-27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p = 0.031 & p = 0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25-0.86]) and RFS (0.38 [0.21-0.69]).

Conclusions: This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10585-022-10153-yDOI Listing
June 2022

Differential Diagnosis and Molecular Stratification of Gastrointestinal Stromal Tumors on CT Images Using a Radiomics Approach.

J Digit Imaging 2022 04 27;35(2):127-136. Epub 2022 Jan 27.

Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

Treatment planning of gastrointestinal stromal tumors (GISTs) includes distinguishing GISTs from other intra-abdominal tumors and GISTs' molecular analysis. The aim of this study was to evaluate radiomics for distinguishing GISTs from other intra-abdominal tumors, and in GISTs, predict the c-KIT, PDGFRA, BRAF mutational status, and mitotic index (MI). Patients diagnosed at the Erasmus MC between 2004 and 2017, with GIST or non-GIST intra-abdominal tumors and a contrast-enhanced venous-phase CT, were retrospectively included. Tumors were segmented, from which 564 image features were extracted. Prediction models were constructed using a combination of machine learning approaches. The evaluation was performed in a 100 × random-split cross-validation. Model performance was compared to that of three radiologists. One hundred twenty-five GISTs and 122 non-GISTs were included. The GIST vs. non-GIST radiomics model had a mean area under the curve (AUC) of 0.77. Three radiologists had an AUC of 0.69, 0.76, and 0.84, respectively. The radiomics model had an AUC of 0.52 for c-KIT, 0.56 for c-KIT exon 11, and 0.52 for the MI. The numbers of PDGFRA, BRAF, and other c-KIT mutations were too low for analysis. Our radiomics model was able to distinguish GISTs from non-GISTs with a performance similar to three radiologists, but less observer dependent. Therefore, it may aid in the early diagnosis of GIST, facilitating rapid referral to specialized treatment centers. As the model was not able to predict any genetic or molecular features, it cannot aid in treatment planning yet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10278-022-00590-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921463PMC
April 2022

Diagnostic value of F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients.

J Neurooncol 2022 Feb 13;156(3):559-567. Epub 2022 Jan 13.

Department of Neurology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.

Purpose: Detecting malignant peripheral nerve sheath tumors (MPNSTs) remains difficult. F-FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated.

Methods: A retrospective cohort study was performed including patients from two hospitals with a clinical or radiological suspicion of MPNST between 2013 and 2019. Several markers were studied for ideal threshold values and differences among adults and children. A diagnostic algorithm was subsequently developed.

Results: Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved.

Conclusion: F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-021-03936-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860956PMC
February 2022

Outcome after treatment for sebaceous carcinoma: A multicenter study.

J Surg Oncol 2022 Mar 6;125(4):730-735. Epub 2022 Jan 6.

Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: Sebaceous carcinoma (SC) is a rare malignant tumour whereby, comprehensive long-term data are scarce. This study aimed to assess the outcome of patients treated with resection for SC.

Methods: Patients treated at four tertiary centres were included. Cumulative incidence curves were calculated for recurrences.

Results: A total of 100 patients (57 males, 57%) were included with 103 SCs. The median age was 72 (range, 15-95) years with a median follow-up of 52 (interquartile range [IQR], 24-93) months. Most SCs were located (peri)ocular (49.5%). Of all SCs, 17 locally recurred (16.5%) with a median time to recurrence of 19 (IQR, 8-29) months. The cumulative incidence probability for recurrence was statistically higher for (peri)ocular tumours (p = 0.005), and for positive resection margins (p = 0.001). Two patients presented with lymph node metastases and additional seven patients (8.7%) developed lymph node metastases during follow-up with a median time to metastases of 8 (IQR, 0.5-28) months. Three patients had concurrent in-transit metastases and one patient also developed liver and bone metastases during follow-up.

Conclusion: SC is a rare, yet locally aggressive tumour. Positive resection margins and (peri)ocular SCs are more frequently associated with local recurrence. SC infrequently presents with locoregional or distant metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26774DOI Listing
March 2022

Corrigendum to 'Age-related differences of oncological outcomes in primary extremity soft tissue sarcoma: a multistate model including 6260 patients' [Eur J Cancer 141 (2020) 128-136].

Eur J Cancer 2022 Feb 31;162:247-249. Epub 2021 Dec 31.

The Netherlands Department of Orthopedic Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2021.12.002DOI Listing
February 2022
-->