Publications by authors named "Warner Prevoo"

32 Publications

Hospital variation in combined liver resection and thermal ablation for colorectal liver metastases and impact on short-term postoperative outcomes: a nationwide population-based study.

HPB (Oxford) 2021 06 18;23(6):827-839. Epub 2020 Nov 18.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands.

Background: Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation.

Methods: In this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery.

Results: Of 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy.

Conclusion: Significant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy.
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http://dx.doi.org/10.1016/j.hpb.2020.10.003DOI Listing
June 2021

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases: Multidisciplinary Consensus Document from the COLLISION Trial Group.

Cancers (Basel) 2020 Jul 3;12(7). Epub 2020 Jul 3.

Department of Radiology, Isala Ziekenhuis, 8025 AB Zwolle, The Netherlands.

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.
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http://dx.doi.org/10.3390/cancers12071779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407587PMC
July 2020

Renal biopsies performed before versus during ablation of T1 renal tumors: implications for prevention of overtreatment and follow-up.

Abdom Radiol (NY) 2021 01 20;46(1):373-379. Epub 2020 Jun 20.

Department of Urology, OLVG, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands.

Purpose: To assess the difference between renal mass biopsy (RMB) performed either before or during the ablation procedure.

Methods: A retrospective multicenter study was performed in patients with a cT1 renal mass treated with ablation between January 2007 and July 2019, including a search in the national pathology database for patients with a RMB planned for ablation. Patient and tumor characteristics and information on malignant, benign, and non-diagnostic biopsy results were collected to establish rates of overtreatment and number of ablations avoided in case of benign or non-diagnostic histology.

Results: RMB was performed in 714 patients, of which 231 patients received biopsy before planned ablation, and 483 patients at the time of ablation. Pathology results before ablation were malignant in 63% (145/231), benign in 20% (46/231) and non-diagnostic in 17% (40/231). Pathology results at the time of ablation were malignant in 67.5% (326/483), benign in 16.8% (81/483) and non-diagnostic in 15.7% (76/483), leading to a total of 32.5% of ablation of benign or non-diagnostic lesions. Of the patients with a benign biopsy obtained before ablation, 80.4% (37/46) chose not to undergo ablation. Patients with inconclusive biopsy before planned ablation chose an informed individualized approach including ablation, repeated biopsy, or no intervention in 56%, 34% and 10%.

Conclusion: This study emphasizes the importance of obtaining a biopsy prior to the ablation procedure in a separate session to lower the rate of potentially unnecessary ablations.
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http://dx.doi.org/10.1007/s00261-020-02613-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864836PMC
January 2021

Phase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM).

Melanoma Res 2020 06;30(3):252-260

Departments of Medical Oncology.

Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit. Preclinical experiments demonstrated that radiofrequency ablation (RFA) induced durable responses in combination with anti-CTLA-4. The aim of this phase Ib/II study was to assess safety and efficacy of RFA plus ipilimumab in uveal melanoma. Patients underwent RFA of one liver lesion and subsequently received four courses ipilimumab 0.3, 3 or 10 mg/kg every 3 weeks in a 3 + 3 design. Primary endpoints were safety in terms of dose limiting toxicities per cohort to define the recommended phase II dose (RP2D) in the phase Ib part and confirmed the objective response rate and disease control rate (DCR) of non-RFA lesions in the phase II part. Secondary endpoints were progression-free survival (PFS) and OS. Ipilimumab 10 mg/kg + RFA was initially defined as the RP2D. However, after 19 patients, the study was amended to adjust the RP2D to ipilimumab 3 mg/kg + RFA, because 47% of patients treated with 10 mg/kg had developed grade 3 colitis. In the 3 mg/kg cohort, also 19 patients have been treated. Immunotherapy-related grade ≥3 adverse events were observed in 53% of patients in the 10 mg/kg cohort versus 32% in the 3 mg/kg cohort. No confirmed objective responses were observed; the confirmed DCR was 5% in the 10 mg/kg cohort and 11% in the 3 mg/kg cohort. Median PFS was 3 months and comparable for both cohorts, median OS was 14.2 months for the 10 mg/kg cohort versus 9.7 months for the 3 mg/kg cohort. Combining RFA with ipilimumab 3 mg/kg was well tolerated, but showed very limited clinical activity in uveal melanoma.
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http://dx.doi.org/10.1097/CMR.0000000000000653DOI Listing
June 2020

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy After Resection of Colorectal Liver Metastases: Results of a Safety and Feasibility Study in The Netherlands.

Ann Surg Oncol 2019 Dec 22;26(13):4599-4607. Epub 2019 Oct 22.

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

Background: The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs.

Study Design: A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien-Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy.

Results: A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51-64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29-52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed uneventfully in all patients.

Conclusion: Pump implantation is safe, and administration of HAIP chemotherapy is feasible, in patients with resectable CRLMs, after training of a dedicated multidisciplinary team.
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http://dx.doi.org/10.1245/s10434-019-07973-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863781PMC
December 2019

Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients.

Sci Transl Med 2019 10;11(513)

Department of Molecular Oncology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.

There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.
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http://dx.doi.org/10.1126/scitranslmed.aay2574DOI Listing
October 2019

Outcome of sentinel lymph node biopsy in patients with clinically non-metastatic renal cell carcinoma.

Scand J Urol 2018 Oct - Dec;52(5-6):411-418. Epub 2018 Dec 11.

a Department of Urology, The Netherlands Cancer Institute , Amsterdam , The Netherlands.

Objective: To investigate the rate of occult SN metastases, oncological outcome, and association of recurrence with the pattern of lymphatic tumour drainage in RCC.

Materials And Methods: A pooled RCC sub-group analysis was conducted of secondary endpoints from a published feasibility and a phase II prospective single-arm SN study to investigate oncological outcome. Patients with cT1-3 (<10 cm) cN0M0 RCC of any sub-type were enrolled. After intratumoural injection of Tc nanocolloid, pre-operative imaging of SNs with SPECT/CT was followed by (partial) nephrectomy with SN and regional lymph node dissection using a γ-probe. The patients were followed with a risk-adapted surveillance programme. Endpoints of the studies were analysed using Cox proportional hazard models.

Results: Sixty-six RCC patients were included. Two patients (3%, 95% CI =0.5-11%) had occult SN metastases and remained free of disease at 57 and 72 months. Ten patients (15%, 95% CI =7-26%) developed recurrences, and four (6%, 95% CI =2.3-14.5%) had died of disease at a median follow-up of 57 months (IQR =18-72 months). Occurrence of distant metachronous metastases were associated with tumour size (HR =1.39, p = 0.02), pT stage (HR =6.83, p < 0.01 for comparison T1 vs T3/4), Grade 3/4 (HR =8.38, p = 0.05 for comparison 1/2 vs 3/4) and interaortocaval sentinel lymph node location (HR =10.52, p = 0.03 for comparison yes vs no).

Conclusions: The rate of occult metastatic SN is low, but long disease-free survival (DFS) was observed in two patients with occult SN metastases. We hypothesize an interaortocaval lymphatic route in thoracic recurrences. Evaluation of the prognostic and therapeutic role of sentinel lymph node biopsy (SLNB) requires a clinical trial in high-risk RCC.
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http://dx.doi.org/10.1080/21681805.2018.1531057DOI Listing
August 2019

An analysis of SPECT/CT non-visualization of sentinel lymph nodes in renal tumors.

EJNMMI Res 2018 Dec 3;8(1):105. Epub 2018 Dec 3.

Department of Urology, The Netherlands Cancer Institute, Postbus 90203, 1006 BE, Amsterdam, The Netherlands.

Background: Sentinel lymph node biopsy (SLNB) after intratumoral injection of Tc labeled nanocolloid and imaging with scintigraphy and SPECT/CT in renal tumors is feasible. However, sentinel lymph node (SN) non-detection rate with scintigraphy and SPECT/CT is high. The aim of the study was to determine factors affecting non-visualization (NV) of SN imaging in renal tumors. Seventy-eight patients with cT1-3 renal tumors received intratumoral injection of 225 MBq Tc-labeled nanocolloid 1 day before (partial) nephrectomy. Radiotracer injection was followed by anterioposterior and lateral scintigraphy in combination with SPECT/CT 20 min and 2-4 h after. Surgical treatment of the tumor with sentinel lymph node biopsy by aid of γ-probe and-camera was performed the next day. Scintigraphy and SPECT/CT images were evaluated and patient, tumor, and procedure characteristics were collected for 73 eligible patients used in uni- and multivariable analysis of a potential association with NV.

Results: A total of 80 (mean 1.1, IQR 0-2, max 6) sentinel lymph nodes in 46 patients were detected with scintigraphy and SPECT/CT. Preoperative visualization rate and intraoperative detection rate was 63% [95% CI 50-73%] and 61% [95% CI 49-72%], respectively. In uni- and multivariable analysis, the only factor associated with non-visualization was age, showing higher odds of non-visualization with higher age.

Conclusion: Our study demonstrated that non-visualization of SNs in renal tumors is relatively high and is associated with patient age. Furthermore, kidneys and also its tumors are highly vascularized which may cause a wash-out effect that could be identified with decreased kidney-liver ratios. However, in our data, the effect was statistically inconclusive. Further studies are needed to improve visualization and standardize the procedure of SLNB in renal tumors. The percentage of NV limits the use of SLNB for research and clinical purposes in renal cancer.
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http://dx.doi.org/10.1186/s13550-018-0460-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277398PMC
December 2018

Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival.

Eur Radiol 2019 Apr 25;29(4):1882-1892. Epub 2018 Sep 25.

Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Objectives: Cholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA).

Patients And Methods: We retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated.

Results: Fifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures.

Discussion: PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease.

Key Points: • Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies. • PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease. • Side effects seem to be tolerable and comparable to other systemic or local treatment strategies.
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http://dx.doi.org/10.1007/s00330-018-5729-zDOI Listing
April 2019

Radiofrequency and Microwave Ablation Compared to Systemic Chemotherapy and to Partial Hepatectomy in the Treatment of Colorectal Liver Metastases: A Systematic Review and Meta-Analysis.

Cardiovasc Intervent Radiol 2018 Aug 17;41(8):1189-1204. Epub 2018 Apr 17.

Medical Evaluation and Technology Assessment (ME-TA), Rotselaar, Belgium.

Purpose: To assess safety and outcome of radiofrequency ablation (RFA) and microwave ablation (MWA) as compared to systemic chemotherapy and partial hepatectomy (PH) in the treatment of colorectal liver metastases (CRLM).

Methods: MEDLINE, Embase and the Cochrane Library were searched. Randomized trials and comparative observational studies with multivariate analysis and/or matching were included. Guidelines from National Guideline Clearinghouse and Guidelines International Network were assessed using the AGREE II instrument.

Results: The search revealed 3530 records; 328 were selected for full-text review; 48 were included: 8 systematic reviews, 2 randomized studies, 26 comparative observational studies, 2 guideline-articles and 10 case series; in addition 13 guidelines were evaluated. Literature to assess the effectiveness of ablation was limited. RFA + systemic chemotherapy was superior to chemotherapy alone. PH was superior to RFA alone but not to RFA + PH or to MWA. Compared to PH, RFA showed fewer complications, MWA did not. Outcomes were subject to residual confounding since ablation was only employed for unresectable disease.

Conclusion: The results from the EORTC-CLOCC trial, the comparable survival for ablation + PH versus PH alone, the potential to induce long-term disease control and the low complication rate argue in favour of ablation over chemotherapy alone. Further randomized comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical. Hence, the highest achievable level of evidence for unresectable CRLM seems reached. The apparent selection bias from previous studies and the superior safety profile mandate the setup of randomized controlled trials comparing ablation to surgery.
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http://dx.doi.org/10.1007/s00270-018-1959-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021475PMC
August 2018

Sensitivity and Reproducibility of Automated Feeding Artery Detection Software during Transarterial Chemoembolization of Hepatocellular Carcinoma.

J Vasc Interv Radiol 2018 03 3;29(3):425-431. Epub 2018 Feb 3.

Department of Radiology and Medical Imaging, Henri Mondor University Hospital, 51 Avenue du maréchal de Lattre de Tassigny, 94010 Creteil, France; Medical School, Université Paris Est Créteil, Créteil, France; Unité INSERM U 955, Equipe 18, Créteil, France. Electronic address:

Purpose: To evaluate the performance of automated feeder detection (AFD) software (EmboGuide; Philips Healthcare, Best, The Netherlands) on hepatocellular carcinoma (HCC) tumors during transarterial chemoembolization.

Materials And Methods: Forty-four first-time transarterial chemoembolization patients (37 men; mean age, 62 ± 11 years) were enrolled between May 2012 and July 2013. A total of 86 HCC lesions were treated (2.0 ± 1.4 lesions per patient; 27.6 ± 15.9 mm maximum diameter). One hundred forty-seven feeding arteries were found with digital subtraction angiography (DSA), cone-beam computed tomography (CT), and AFD software with the option of manual adjustment (MA). Three independent interventional radiologists analyzed the cone-beam CT images retrospectively with and without AFD and MA. Compared with the number of treated vessels, the number of true positives, false positives, false negatives, sensitivity, and interreader agreement were determined using clustered binary data analysis.

Results: Cone-beam CT enabled detection of 100 ± 3.5 feeding arteries (70% sensitivity) with 68.6% agreement among readers. AFD software significantly improved detection to 127±0.6 feeding arteries (86% sensitivity, P = .008) with 99.7% reader agreement and reduced the number of false negatives from an average of 47 ± 3.5 to 20 ± 0.6 (P = .008). MA of the AFD results produced similar feeding artery detection rates (127 ± 5.1, 86% sensitivity, P = .8), with lower interreader agreement (91.6%) and slightly fewer false positives (16 ± 0.0 to 14 ± 2.5, P = .4).

Conclusions: AFD software significantly improved feeding artery detection rates during transarterial chemoembolization of HCC lesions with better user reproducibility compared with cone-beam CT alone. In conjunction with DSA, AFD enables maximum feeding artery detection in this setting.
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http://dx.doi.org/10.1016/j.jvir.2017.10.025DOI Listing
March 2018

Lymphatic Drainage from Renal Tumors In Vivo: A Prospective Sentinel Node Study Using SPECT/CT Imaging.

J Urol 2018 06 6;199(6):1426-1432. Epub 2017 Dec 6.

Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

Purpose: Lymphatic drainage from renal tumors is unpredictable. In vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern of renal tumors in vivo with single photon emission/computerized tomography after intratumor radiotracer injection.

Materials And Methods: We performed a phase II, prospective, single arm study to investigate the distribution of sentinel nodes from renal tumors on single photon emission/computerized tomography. Patients with cT1-3 (less than 10 cm) cN0M0 renal tumors of any subtype were enrolled in analysis. After intratumor ultrasound guided injection of 0.4 ml Tc-nanocolloid we performed preoperative imaging of sentinel nodes with lymphoscintigraphy and single photon emission/computerized tomography. Sentinel and locoregional nonsentinel nodes were resected with a γ probe combined with a mobile γ camera. The primary study end point was the location of sentinel nodes outside the locoregional retroperitoneal templates on single photon emission/computerized tomography. Using a Simon minimax 2-stage design to detect a 25% extralocoregional retroperitoneal template location of sentinel nodes on imaging at α = 0.05 and 80% power at least 40 patients with sentinel node imaging on single photon emission/computerized tomography were needed.

Results: Of the 68 patients 40 underwent preoperative single photon emission/computerized tomography of sentinel nodes and were included in primary end point analysis. Lymphatic drainage outside the locoregional retroperitoneal templates was observed in 14 patients (35%). Eight patients (20%) had supradiaphragmatic sentinel nodes.

Conclusions: Sentinel nodes from renal tumors were mainly located in the respective locoregional retroperitoneal templates. Simultaneous sentinel nodes were located outside the suggested lymph node dissection templates, including supradiaphragmatic sentinel nodes in more than a third of the patients.
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http://dx.doi.org/10.1016/j.juro.2017.11.112DOI Listing
June 2018

Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma.

BMC Med 2016 11 14;14(1):185. Epub 2016 Nov 14.

Centre for Evolution and Cancer, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.

Background: Molecular intratumour heterogeneity (ITH) is common in clear cell renal carcinomas (ccRCCs). However, it remains unknown whether this is mirrored by heterogeneity of drug responses between metastases in the same patient.

Methods: We performed a retrospective central radiological analysis of patients with treatment-naïve metastatic ccRCC receiving anti-angiogenic tyrosine kinase inhibitors (TKIs) (sunitinib or pazopanib) within three similar phase II trials. Treatment was briefly interrupted for cytoreductive nephrectomy. All patients had multiple metastases that were measured by regular computed tomography scans from baseline until Response Evaluation Criteria In Solid Tumours (RECIST)-defined progression. Each metastasis was categorised as responding, stable or progressing. Patients were classed as having a homogeneous response if all lesions were of the same response category and a heterogeneous response if they differed.

Results: A total of 115 metastases were assessed longitudinally in 27 patients. Of these patients, 56% had a heterogeneous response. Progression occurred through the appearance of new metastases in 67%, through progression of existing lesions in 11% and by both in 22% of patients. Despite RECIST-defined progression, 57% of existing metastases remained controlled. The sum of controlled lesions was greater than that of uncontrolled lesions in 47% of patients who progressed only with measurable new lesions.

Conclusions: We identified frequent ITH of anti-angiogenic TKI responses, with subsets of metastases responding and progressing within individual patients. This mirrors molecular ITH and may indicate that anti-angiogenic drug resistance is confined to subclones and not encoded on the trunk of the tumours' phylogenetic trees. This is clinically important, as patients with small-volume progression may benefit from drug continuation. Predominant progression with new rather than in existing metastases supports a change in disease biology through anti-angiogenics. The results highlight limitations of RECIST in heterogeneous cancers, which may influence clinical trial data validity. This analysis requires prospective confirmation.

Trial Registration: European Clinical Trials Database(EudraCT): 2009-016675-29 , registered 17 March 2010; EudraCT: 2006-004511-21 , registered 09 March 2007; EudraCT: 2006-006491-38 , registered 22 December 2006.
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http://dx.doi.org/10.1186/s12916-016-0729-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108081PMC
November 2016

In vivo tumor identification of colorectal liver metastases with diffuse reflectance and fluorescence spectroscopy.

Lasers Surg Med 2016 11 8;48(9):820-827. Epub 2016 Sep 8.

Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background And Objective: Over the last decade, an increasing effort has been put towards the implementation of optical guidance techniques to aid surgeons during cancer surgery. Diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) are two of these new techniques. The objective of this study is to investigate whether in vivo optical spectroscopy is able to accurately discriminate colorectal liver metastases (CRLM) from normal liver tissue in vivo.

Materials And Methods: DRS and FS were incorporated at the tip of a needle and were used for in vivo tissue differentiation during resection of CRLM. Measurements were taken in and around the tumor lesions and measurement sites were marked and correlated to histology (i.e., normal liver tissue or tumor tissue). Patients with and without neoadjuvant systemic chemotherapy were included into the study.

Results: Four hundred and eighty-four measurements were taken in and near 19 liver lesions prior to resection. Overall sensitivity and specificity for DRS was 95% and 92%, respectively. Bile was the most discriminative parameter. The addition of FS did not improve the overall accuracy. Sensitivity and specificity was not hampered by neo-adjuvant chemotherapy; sensitivity and specificity after neo-adjuvant chemotherapy were 92% and 100%, respectively.

Conclusion: We have successfully integrated spectroscopy technology into a disposable 15 Gauge optical needle and we have shown that DRS and FS can accurately discriminate CRLM from normal liver tissue in the in vivo setting regardless of whether the patient was pre-treated with systemic therapy. This technique makes in vivo guidance accessible for common surgical practice. Lasers Surg. Med. 48:820-827, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.22581DOI Listing
November 2016

In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures.

J Biomed Opt 2016 09;21(9):97004

Netherlands Cancer Institute, Department of Surgery, Plesmanlaan 121, 1066CX Amsterdam, The NetherlandsfUniversity of Twente, MIRA Institute, Drienerlolaan 5, Zuidhorst ZH116, 7522 NB Enschede, The Netherlands.

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle. Interventional imaging was coregistered with the DR spectra. Pathology results were compared with the DR spectroscopy data at the final measurement position. Bile was the primary discriminator between normal liver tissue and tumor tissue. Relative differences in bile content matched with the tissue diagnosis based on histopathological analysis in all 24 clinical cases. Continuous DR measurements during needle insertion in three patients showed that the method can also be applied for biopsy guidance or tumor recognition during surgery. This study provides an important validation step for DR spectroscopy-based tissue characterization in the liver. Given the feasibility of the outlined approach, it is also conceivable to make integrated fiber-optic tools for other clinical procedures that rely on accurate instrument positioning.
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http://dx.doi.org/10.1117/1.JBO.21.9.097004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357329PMC
September 2016

Spectral sensing for tissue diagnosis during lung biopsy procedures: The importance of an adequate internal reference and real-time feedback.

Lung Cancer 2016 08 26;98:62-68. Epub 2016 May 26.

Department of Surgery, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, Netherlands; MIRA Institute, University of Twente, Building Zuidhorst, Room ZH 116, Enschede, Netherlands.

Objectives: Difficulties in obtaining a representative tissue sample are a major obstacle in timely selecting the optimal treatment for patients with lung cancer or other malignancies. Having a modality to provide needle guidance and confirm the biopsy site selection could be of great clinical benefit, especially when small masses are targeted. The objective of this study was to evaluate whether diffuse reflectance spectroscopy (DRS) at the tip of a core biopsy needle can be used for biopsy site confirmation in real time, thereby enabling optimized biopsy acquisition and improving diagnostic capability.

Materials And Methods: We included a total of 23 patients undergoing a routine computed tomography (CT) guided transthoracic needle biopsy of a lesion suspected for lung cancer or metastatic disease. DRS measurements were acquired during needle insertion and clinically relevant parameters were extracted from the spectral data along the needle paths. Histopathology results were compared with the DRS data at the final measurement position.

Results: Analysis of the collective data acquired from all enrolled subjects showed significant differences (p<0.01) for blood content, stO2, water content, and scattering amplitude. The identified spectral contrast matched the final pathology in 20 out of 22 clinical cases that could be used for analysis, which corresponds with an overall diagnostic performance of 91%. Three cases underlined the importance of adequate reference measurements and the need for real time diagnostic feedback. Continuous real time DRS measurements performed during a biopsy procedure in one patient provided clear information with respect to the variation in tissue and allowed identification of the tumour boundary.

Conclusions: The presented technology creates a basis for the design and clinical implementation of integrated fibre-optic tools for a variety of minimal invasive applications.
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http://dx.doi.org/10.1016/j.lungcan.2016.05.019DOI Listing
August 2016

Baseline tumor volume in assessing prognosis of patients with intermediate-risk synchronous metastatic renal cell carcinoma.

Urol Oncol 2016 06 25;34(6):258.e7-258.e13. Epub 2016 Jan 25.

Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Objective: To analyze if prediction of survival for patients with synchronous metastatic renal cell cancer (mRCC) could be further refined by baseline volume of the primary tumor, the metastases, or the remaining volume after surgery; this study was performed because survival expectancies of patients with intermediate-risk mRCC vary substantially.

Material And Methods: The predictive value of the different volumes on overall survival (OS) was analyzed retrospectively in patients with intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk profile and ≤3 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) factors, who received sunitinib in our institute. Tumor volumes were calculated on segmented computed tomography using in-house developed software. A multivariate analysis was performed including number of metastatic sites and baseline tumor burden (TB).

Results: A total of 68 patients were included. Median OS for patients without cytoreductive nephrectomy (CN) was 6 months (95% CI: 3.0-8.9mo) vs. 31 months (95% CI: 23.1-38.8mo) for those with CN, respectively. More second-line treatment was given after CN (49% vs. 17%, P = 0.125). There was no correlation between tumor volume and TB measured by Response Evaluation Criteria in Solid Tumors. Of all included clinical and volumetric parameters, remaining volume after CN, CN status and 2 vs. 3 IMDC factors were significantly correlated with OS. In the Cox regression analysis, CN was the only remaining significant parameter (P = 0.003).

Conclusions: None of the baseline volumetric parameters is an independent prognostic factor in patients with intermediate MSKCC risk mRCC with≤3 IMDC factors receiving sunitinib. Only CN status correlated significantly with prognosis. None of the baseline volumes nor TB by Response Evaluation Criteria in Solid Tumors was associated with CN status, suggesting that extent of disease had no significant influence on the decision to perform surgery.
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http://dx.doi.org/10.1016/j.urolonc.2015.12.007DOI Listing
June 2016

Real-time In Vivo Tissue Characterization with Diffuse Reflectance Spectroscopy during Transthoracic Lung Biopsy: A Clinical Feasibility Study.

Clin Cancer Res 2016 Jan 31;22(2):357-65. Epub 2015 Aug 31.

Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands. MIRA Institute, University of Twente, Enschede, the Netherlands.

Purpose: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers.

Experimental Design: Tissues from 21 consented patients undergoing lung cancer surgery were measured intraoperatively using the fiber-optic platform capable of assessing various physical tissue properties highly correlated to tissue architecture and composition. In addition, the method was tested for clinical use by performing DRS tissue sensing during 11 routine biopsy procedures in patients with suspected lung cancer.

Results: We found that water content and scattering amplitude are the primary discriminators for the transition from healthy lung tissue to tumor tissue and that the reliability of these parameters is not affected by the amount of blood at the needle tip. In the 21 patients measured intraoperatively, the water-to-scattering ratio yielded a 56% to 81% contrast difference between tumor and surrounding tissue. Analysis of the 11 image-guided lung biopsy procedures showed that the tissue diagnosis derived from DRS was diagnostically discriminant in each clinical case.

Conclusions: DRS tissue sensing integrated into a biopsy needle may be a powerful new tool for biopsy guidance that can be readily used in routine diagnostic lung biopsy procedures. This approach may not only help to increase the successful biopsy yield for histopathologic analysis, but may also allow specific sampling of vital tumor tissue for genetic profiling.
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http://dx.doi.org/10.1158/1078-0432.CCR-15-0807DOI Listing
January 2016

[18F]Fluorodeoxyglucose PET for Interventional Oncology in Liver Malignancy.

PET Clin 2014 Oct 12;9(4):469-95, vi. Epub 2014 Aug 12.

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands. Electronic address:

[(18)F]Fluorodeoxyglucose (FDG) PET is a functional imaging tool that provides metabolic information, which has the potential to detect a lesion before it becomes anatomically apparent. This ability constitutes a strong argument for using FDG-PET/computed tomography (CT) in the management of oncology patients. Many studies have investigated the accuracy of FDG-PET or FDG-PET/CT for these purposes, but with small sample sizes based on retrospective cohorts. This article provides an overview of the role of FDG-PET or FDG-PET/CT in patients with liver malignancies treated by means of surgical resection, ablative therapy, chemoembolization, radioembolization, and brachytherapy, all being liver-directed oncologic interventions.
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http://dx.doi.org/10.1016/j.cpet.2014.07.004DOI Listing
October 2014

Diffuse reflectance spectroscopy: toward real-time quantification of steatosis in liver.

Transpl Int 2015 Apr 21;28(4):465-74. Epub 2015 Jan 21.

Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real-time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy-eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients. Liver steatosis was quantified from the collected optical spectra and compared with the histology analysis from the measurement location by three independent pathologists. Twenty two patients were diagnosed with <5% steatosis, 15 patients had mild steatosis, and four had moderate steatosis. Severe steatosis was not identified. Intraclass correlation between the pathologists analysis was 0.949. A correlation of 0.854 was found between the histology and DRS analyses of liver steatosis ex vivo. For the same liver tissue, a correlation of 0.925 was demonstrated between in vivo and ex vivo DRS analysis for steatosis quantification. DRS can quantify steatosis in liver tissue both in vivo and ex vivo with good agreement compared to histopathology analysis. This analysis can be performed real time and may therefore be useful for fast objective assessment of liver steatosis in liver surgery.
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http://dx.doi.org/10.1111/tri.12517DOI Listing
April 2015

Monitoring of tumor radio frequency ablation using derivative spectroscopy.

J Biomed Opt 2014 Sep;19(9):97004

The Netherlands Cancer Institute, Department of Surgery, Plesmanlaan 121, Amsterdam 1066CX, The NetherlandsdUniversity of Twente, MIRA Institute, Building Zuidhorst P.O. Box 217, Enschede 7500 AE, The Netherlands.

Despite the widespread use of radio frequency (RF) ablation, an effective way to assess thermal tissue damage during and after the procedure is still lacking. We present a method for monitoring RF ablation efficacy based on thermally induced methemoglobin as a marker for full tissue ablation. Diffuse reflectance (DR) spectra were measured from human blood samples during gradual heating of the samples from 37 to 60, 70, and 85°C. Additionally, reflectance spectra were recorded real-time during RF ablation of human liver tissue ex vivo and in vivo. Specific spectral characteristics of methemoglobin were extracted from the spectral slopes using a custom optical ablation ratio. Thermal coagulation of blood caused significant changes in the spectral slopes, which is thought to be caused by the formation of methemoglobin. The time course of these changes was clearly dependent on the heating temperature. RF ablation of liver tissue essentially led to similar spectral alterations. In vivo DR measurements confirmed that the method could be used to assess the degree of thermal damage during RF ablation and long after the tissue cooled.
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http://dx.doi.org/10.1117/1.JBO.19.9.097004DOI Listing
September 2014

Can previous diagnostic examinations prevent preoperative angiographic assessment of the internal mammary perforators for (micro)surgical use?

Ann Plast Surg 2014 May;72(5):560-5

From the *Department of Plastic and Reconstructive Surgery and Handsurgery at the University Medical Center Utrecht; and †Departments of Nuclear Medicine, ‡Plastic and Reconstructive Surgery, and §Radiology at the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background And Aim: Preoperative assessment of the internal mammary artery perforating (IMAP) branches enhances IMAP-based reconstructive procedures. Conventionally, color-flow Doppler, selective catheter arteriography, or CT angiography is used for such assessment. We studied how often these examinations may be rendered superfluous by assessment of previously performed diagnostic examinations.

Methods: A radiologist and a plastic surgeon jointly assessed whether information on the dominant IMAP could sufficiently be obtained from the thoracic CT scans of 12 head and neck cancer patients and 12 breast cancer patients, and from the mammary MRI of 12 breast cancer patients. Secondly, we retrospectively assessed in how many of the 10 patients who underwent an IMAP-flap head and neck reconstruction, and in how many of the 10 women who consecutively underwent a deep inferior epigastric perforator (DIEP) flap mammary reconstruction such previous diagnostic examinations were available and informative regarding the level of the dominant perforator.

Results: All 24 CT scans and 11 of the 12 MRI scans sufficiently allowed assessment of the level of the dominant IMAP. Previous information had already been available in all 10 DIEP flap patients and 6 of the 10 IMAP-flap patients. The distribution of IMAP dominance over the intercostal levels on the scans differed from that found by cadaveric or intraoperative assessment.

Conclusions: Previously performed diagnostic CT scans and MRI scans that included the parasternal region usually allow sufficient preoperative assessment of the internal mammary perforators for reconstructive procedures. We advocate re-assessment of such previous examinations before ordering additional angiography. Additionally, we suggest to include the parasternal region in diagnostic scans.
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http://dx.doi.org/10.1097/SAP.0b013e318268a896DOI Listing
May 2014

Probability of downsizing primary tumors of renal cell carcinoma by targeted therapies is related to size at presentation.

Urology 2013 Jan 13;81(1):111-5. Epub 2012 Nov 13.

Department of Urology at the Netherlands Cancer Institute, Amsterdam, The Netherlands.

Objective: To evaluate the probability of downsizing primary renal tumors by targeted therapy in correlation to size.

Methods: A literature search was conducted and our own data were pooled with data of retrospective series and prospective trials in which patients were treated with tyrosine kinase inhibitors (TKIs) and in which tumor sizes before and after treatment were reported. Included were 89 primary clear cell renal tumors, including 34 from our institutes. The longest diameter of the primary tumors before and after treatment was obtained. Primary tumor size at presentation was divided in 4 categories: <5 cm (n=10), 5 to 7 cm (n=21), 7 to 10 cm (n=31), and >10 cm (n=27). Pearson correlation and t test were used for statistical analysis.

Results: The TKI was sorafenib in 21 tumors and sunitinib in the remaining 68. Smaller tumor size was related to more effective downsizing (P=0.01). Median downsizing was 32% (-46% to 11%) in the first group (<5 cm) and 11% (-55% to 16%) in the second group (5-7 cm); however, 8 of 21 (38%) in this group reduced to a range of 2.3 to 4.7 cm in which ablative techniques are feasible and nephron-sparing surgery may benefit from the reduced size. Median downsizing was 18% (-39% to 2%) in tumors of 7 to 10 cm and 10% (-31% to 0%) in those>10 cm.

Conclusion: The smaller the primary tumor, the greater the likelihood and the more effective the downsizing. A potential benefit of neoadjuvant treatment to downsize the primary tumor for ablative techniques or nephron-sparing surgery may exist, particularly in tumors sized 5 to 7 cm.
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http://dx.doi.org/10.1016/j.urology.2012.09.014DOI Listing
January 2013

Local treatment of pulmonary metastases: from open resection to minimally invasive approach? Less morbidity, comparable local control.

Surg Endosc 2012 Aug 21;26(8):2312-21. Epub 2012 Feb 21.

Department of Surgery, Netherlands Cancer Institute-Antoni van Leeuwenhoekziekenhuis, PO Box 90203, 1006, BE, Amsterdam, The Netherlands.

Background: The level of evidence for efficacy of local treatment of pulmonary metastases is low; therefore, complication rates should be minimized. Minimally invasive techniques may have the potential to reduce morbidity but potentially lead to more local and/or ipsilateral recurrences. The objective of this study was to evaluate the introduction of a new treatment strategy incorporating the increased use of video-assisted thoracic surgery (VATS) and radiofrequency ablation (RFA), weighing complications against recurrence rates.

Methods: We retrospectively reviewed results of all local treatment of pulmonary metastases in the Netherlands Cancer Institute from 2002 to 2007. Each of 158 identified interventions was analyzed separately to retrieve procedure-related data. Overall survival data were analyzed per patient. To evaluate the introduction of a strategy incorporating minimally invasive techniques, the study period was split in two (before and after the introduction of this strategy in July 2004).

Results: In Strategy I, 47 interventions (2 VATS, no RFA) were performed in 37 patients; in Strategy II 111 interventions (51 VATS and RFA) in 86 patients. Metastases of a variety of primary tumors were treated. Median hospital stay was shorter (5 vs. 7 days) and procedure-related morbidity was less with Strategy II (p < 0.01). Time-to-recurrence rates were comparable (p = 0.18), as were local and ipsilateral recurrence rates within 3 years (p = 0.72). Estimated overall 3-year survival was 59% for patients treated with Strategy I and 54% with Strategy II.

Conclusions: Increased use of minimally invasive techniques for local treatment of pulmonary metastatic disease is associated with low morbidity, without apparent reduction in (local) disease control.
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http://dx.doi.org/10.1007/s00464-012-2181-zDOI Listing
August 2012

Percutaneous radiofrequency ablation of a small renal mass complicated by appendiceal perforation.

Cardiovasc Intervent Radiol 2012 Jun 20;35(3):695-9. Epub 2011 Oct 20.

Department of Radiology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam, The Netherlands.

Percutaneous radiofrequency ablation (RFA) has gained wide acceptance as nephron-sparing therapy for small renal masses in select patients. Generally, it is a safe procedure with minor morbidity and acceptable short-term oncologic outcome. However, as a result of the close proximity of vital structures, such as the bowel, ureter, and large vessels, to the ablative field, complications regarding these structures may occur. This is the first article describing appendiceal perforation as a complication of computed tomography-guided RFA despite hydrodissection. When performing this innovative and promising procedure one should be aware of the possibility of particular minor and even major complications.
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http://dx.doi.org/10.1007/s00270-011-0281-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353108PMC
June 2012

Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours.

Tumour Biol 2011 Aug 5;32(4):647-52. Epub 2011 Mar 5.

Department of Clinical Chemistry, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.

In the event of diffuse hepatic metastases, hepatic artery embolization (HAE) can be a successful treatment option in patients with well-differentiated neuroendocrine tumours (NET). However, embolization causes hypoxia which stimulates angiogenesis and therefore tumour growth. This study investigates angiogenesis activity following HAE by measuring vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and C-terminal proendothelin-1 (proET-1) in blood. Twelve patients with well-differentiated NET and liver metastases underwent HAE. VEGF, ET-1 and proET-1 were measured before embolization and the days following treatment during hospitalization. Mean levels during treatment were compared with those at baseline. From 12 patients, 90 blood samples were obtained before and daily for 8 days following HAE. Mean (± SE) VEGF level at baseline was 116 (± 33)ng/l which increased after HAE to 313 (± 46)ng/l at day 6, followed by a gradual decrease. ProET-1 showed a similar pattern, with a mean baseline level of 9.2 (± 2.0)pmol/l and the highest level of 40.8 (± 5.7)pmol/l at day 6. Some fluctuations were observed for ET-1, with maximum levels at day 3 compared to baseline levels. In patients with well-differentiated NET who underwent hepatic arterial embolization, angiogenic growth factors increase temporarily. This implies a need to investigate the effect of anti-angiogenic drugs as an adjuvant therapy to embolization.
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http://dx.doi.org/10.1007/s13277-011-0164-7DOI Listing
August 2011

Local progression after radiofrequency ablation for pulmonary metastases.

Cancer 2011 Aug 11;117(16):3781-7. Epub 2011 Feb 11.

Department of Surgery, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: Local treatment for pulmonary metastases is considered to be a reasonable treatment option in patients with oligometastatic disease. Percutaneous radio frequency ablation (RFA) has been reported as an alternative to surgery. Results of RFA for local control of pulmonary metastases were evaluated.

Methods: All consecutive patients treated with RFA for pulmonary metastases (2004-2009) were included. RFA was performed percutaneously under computed tomographic guidance. Follow-up was scheduled at 1, 3, and 6 months after treatment and every 6 months thereafter. Major outcome parameters were local and any-site progression, complications, and survival.

Results: Ninety pulmonary metastases were treated, in 46 patients at 65 sessions. Many patients had recurrent metastases after previous surgery (n = 36 of 46). Pneumothorax occurred in 34% (chest drain in 25%) and major complications in 6%. After median follow-up of 22 months (range, 2-65 months), 25 local progressions occurred after RFA; the 2-year local progression rate per lesion was 35%. Overall survival at 3 years was 69%.

Conclusions: Notwithstanding its relatively low morbidity, follow-up after RFA for pulmonary metastases shows a considerable rate of local progression. The role of local ablation techniques for long-term disease control in oligometastatic disease is discussed.
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http://dx.doi.org/10.1002/cncr.25958DOI Listing
August 2011

Feasibility of sentinel node detection in renal cell carcinoma: a pilot study.

Eur J Nucl Med Mol Imaging 2010 Jun 29;37(6):1117-23. Epub 2010 Jan 29.

Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Purpose: Lymphatic drainage from renal cell carcinoma is unpredictable and the therapeutic benefit and extent of lymph node dissection are controversial. We evaluated the feasibility of intratumoural injection of a radiolabelled tracer to image and sample draining lymph nodes in clinically non-metastatic renal cell carcinoma.

Methods: Eight patients with cT1-2 cN0 cM0 (<6 cm) renal cell carcinoma prospectively received percutaneous intratumoural injections of (99m)Tc-nanocolloid under ultrasound guidance (0.4 ml, 225 MBq at one to four intratumoural locations depending on tumour size). Lymphoscintigraphy was performed 20 min, 2 h and 4 h after injection. After the delayed images a hybrid SPECT/CT was performed. SPECT was fused with CT to determine the anatomical localization of the sentinel node. Surgery with sampling was performed the following day using a gamma probe and a portable mini gamma camera.

Results: Eight patients, seven with right-sided renal cell carcinoma, were included with a mean age of 55 years (range: 45-77). The mean tumour size was 4 cm (range: 3.5-6 cm). Six patients had sentinel nodes on scintigraphy (two retrocaval, four interaortocaval, including one hilar) with one extraretroperitoneal location along the internal mammary chain. All nodes could be mapped and sampled. In two patients no drainage was visualized. Renal cell carcinomas were of clear cell subtype with no lymph node metastases.

Conclusion: Sentinel node identification using preoperative and intraoperative imaging to locate and sample the sentinel node at surgery in renal cell carcinoma is feasible. Sentinel node biopsy may clarify the pattern of lymphatic drainage and extent of lymphatic spread which may have diagnostic and therapeutic implications.
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http://dx.doi.org/10.1007/s00259-009-1359-7DOI Listing
June 2010

[The radiologist as the treating physician for cancer: interventional oncology].

Ned Tijdschr Geneeskd 2009 ;153:A532

Universitair Medisch Centrum Utrecht, afd. Radiologie, Utrecht, The Netherlands.

Interventional oncology is a new specialism which focuses on image-guided minimal-invasive treatment of cancer patients. Interventional oncology has joined the traditional treatments of surgery, chemotherapy and radiotherapy as the fourth pillar of cancer care. Oncological interventions can be divided into three categories: intra-arterial techniques, tumour ablation techniques, and palliative procedures. Two examples of such interventions in Dutch hospitals are the intra-arterial Yttrium-90 microsphere radioembolisation of colorectal liver metastases and the CT-guided radiofrequency ablation of tumours such as renal cell carcinoma. In interventional oncology all procedures are performed under image guidance. Imaging is used to guide the instruments and for real-time monitoring of the procedure.
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November 2009
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