Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study.

BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands. METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response. RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%. CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

Optimized whole-genome sequencing workflow for tumor diagnostics in routine pathology practice.

Two decades after the genomics revolution, oncology is rapidly transforming into a genome-driven discipline, yet routine cancer diagnostics is still mainly microscopy based, except for tumor type-specific predictive molecular tests. Pathology laboratories struggle to quickly validate and adopt biomarkers identified by genomics studies of new targeted therapies. Consequently, clinical implementation of newly approved biomarkers suffers substantial delays, leading to unequal patient access to these therapies. Whole-genome sequencing (WGS) can successfully address these challenges by providing a stable molecular diagnostic platform that allows detection of a multitude of genomic alterations in a single cost-efficient assay and facilitating rapid implementation, as well as by the development of new genomic biomarkers. Recently, the Whole-genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE) study demonstrated that WGS is a feasible and clinically valid technique in routine clinical practice with a turnaround time of 11 workdays. As a result, WGS was successfully implemented at the Netherlands Cancer Institute as part of routine diagnostics in January 2021. The success of implementing WGS has relied on adhering to a comprehensive protocol including recording patient information, sample collection, shipment and storage logistics, sequencing data interpretation and reporting, integration into clinical decision-making and data usage. This protocol describes the use of fresh-frozen samples that are necessary for WGS but can be challenging to implement in pathology laboratories accustomed to using formalin-fixed paraffin-embedded samples. In addition, the protocol outlines key considerations to guide uptake of WGS in routine clinical care in hospitals worldwide.

MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Imaging in interventional oncology, the better you see, the better you treat.

Imaging and image processing is the fundamental pillar of interventional oncology in which diagnostic, procedure planning, treatment and follow-up are sustained. Knowing all the possibilities that the different image modalities can offer is capital to select the most appropriate and accurate guidance for interventional procedures. Despite there is a wide variability in physicians preferences and availability of the different image modalities to guide interventional procedures, it is important to recognize the advantages and limitations for each of them. In this review, we aim to provide an overview of the most frequently used image guidance modalities for interventional procedures and its typical and future applications including angiography, computed tomography (CT) and spectral CT, magnetic resonance imaging, Ultrasound and the use of hybrid systems. Finally, we resume the possible role of artificial intelligence related to image in patient selection, treatment and follow-up.

Independent validation of CT radiomics models in colorectal liver metastases: predicting local tumour progression after ablation.

OBJECTIVES: Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM). MATERIALS AND METHODS: Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2-8 weeks post-ablation. Radiomics features were extracted from the AZ and a 10 mm peri-ablational rim (PAR) of liver parenchyma around the AZ. Three previously published prediction models (clinical, radiomics, combined) were tested without retraining. LTP was defined as new tumor foci appearing next to the AZ up to 24 months post-ablation. RESULTS: The internal cohort included 39 patients with 68 CRLM and the external cohort 52 patients with 78 CRLM. 34/146 CRLM developed LTP after a median follow-up of 24 months (range 5-139). The median time to LTP was 8 months (range 2-22). The combined clinical-radiomics model yielded a c-statistic of 0.47 (95%CI 0.30-0.64) in the internal cohort and 0.50 (95%CI 0.38-0.62) in the external cohort, compared to 0.78 (95%CI 0.65-0.87) in the previously published original cohort. The radiomics model yielded c-statistics of 0.46 (95%CI 0.29-0.63) and 0.39 (95%CI 0.28-0.52), and the clinical model 0.51 (95%CI 0.34-0.68) and 0.51 (95%CI 0.39-0.63) in the internal and external cohort, respectively. CONCLUSION: The previously published results for prediction of LTP after thermal ablation of CRLM using clinical and radiomics models were not reproducible in independent internal and external validation. CLINICAL RELEVANCE STATEMENT: Local tumour progression after thermal ablation of CRLM cannot yet be predicted with the use of CT radiomics of the ablation zone and peri-ablational rim. These results underline the importance of validation of radiomics results to test for reproducibility in independent cohorts. KEY POINTS: • Previous research suggests CT radiomics models have the potential to predict local tumour progression after thermal ablation in colorectal liver metastases, but independent validation is lacking. • In internal and external validation, the previously published models were not able to predict local tumour progression after ablation. • Radiomics prediction models should be investigated in independent validation cohorts to check for reproducibility.

Safety and efficacy of RFA versus MWA for T1a renal cell carcinoma: a propensity score analysis.

OBJECTIVES: Percutaneous radiofrequency ablation (RFA) is stated as a treatment option for renal cell carcinoma (RCC) smaller than 4 cm (T1a). Microwave ablation (MWA) is a newer technique and is still considered experimental in some guidelines. The objective of this study was to compare the safety and efficacy of RFA and MWA for the treatment of RCC. METHODS: Patients with T1a RCC treated by RFA or MWA in two referral centers were retrospectively analyzed. Patient records were evaluated to generate mRENAL nephrometry scores. Local tumor progression (LTP) was considered when new (recurrence) or residual tumor enhancement within/adjacent to the ablation zone was objectified. Differences in LTP-free interval (residual + recurrence) between ablation techniques were assessed with Cox proportional hazards models and propensity score (PS) methods. RESULTS: In 164 patients, 87 RFAs and 101 MWAs were performed for 188 RCCs. The primary efficacy rate was 92% (80/87) for RFA and 91% (92/101) for MWA. Sixteen patients had residual disease (RFA (n = 7), MWA (n = 9)) and 9 patients developed recurrence (RFA (n = 7), MWA (n = 2)). LTP-free interval was significantly worse for higher mRENAL nephrometry scores. No difference in LTP-free interval was found between RFA and MWA in a model with inverse probability weighting using PS (HR = 0.99, 95% CI 0.35-2.81, p = 0.98) and in a PS-matched dataset with 110 observations (HR = 0.82, 95% CI 0.16-4.31, p = 0.82). Twenty-eight (14.9%) complications (Clavien-Dindo grade I-IVa) occurred (RFA n = 14, MWA n = 14). CONCLUSION: Primary efficacy for ablation of RCC is high for both RFA and MWA. No differences in efficacy and safety were observed between RFA and MWA. KEY POINTS: • Both RFA and MWA are safe and effective ablation techniques in the treatment of T1a renal cell carcinomas. • High modified RENAL nephrometry scores are associated with shorter local tumor progression-free interval. • MWA can be used as heat-based ablation technique comparable to RFA for the treatment of T1a renal cell carcinomas.

Feasibility of whole-genome sequencing-based tumor diagnostics in routine pathology practice.

The current increase in number and diversity of targeted anticancer agents poses challenges to the logistics and timeliness of molecular diagnostics (MolDx), resulting in underdiagnosis and treatment. Whole-genome sequencing (WGS) may provide a sustainable solution for addressing current as well as future diagnostic challenges. The present study therefore aimed to prospectively assess feasibility, validity, and value of WGS in routine clinical practice. WGS was conducted independently of, and in parallel with, standard of care (SOC) diagnostics on routinely obtained tumor samples from 1,200 consecutive patients with metastatic cancer. Results from both tests were compared and discussed in a dedicated tumor board. From 1,200 patients, 1,302 samples were obtained, of which 1,216 contained tumor cells. WGS was successful in 70% (854/1,216) of samples with a median turnaround time of 11 days. Low tumor purity (<20%) was the main reason for not completing WGS. WGS identified 99.2% and SOC MolDx 99.7% of the total of 896 biomarkers found in genomic regions covered by both tests. Actionable biomarkers were found in 603/848 patients (71%). Of the 936 associated therapy options identified by WGS, 343 were identified with SOC MolDx (36.6%). Biomarker-based therapy was started in 147 patients. WGS revealed 49 not previously identified pathogenic germline variants. Fresh-frozen, instead of formalin-fixed and paraffin-embedded, sample logistics were easily adopted as experienced by the professionals involved. WGS for patients with metastatic cancer is well feasible in routine clinical practice, successfully yielding comprehensive genomic profiling for the vast majority of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Radiofrequency versus microwave ablation for intraoperative treatment of colorectal liver metastases.

INTRODUCTION: Intraoperative radiofrequency ablation (RFA) and the newer technique of microwave ablation (MWA) can both be of additional value in parenchyma preserving surgical treatment of colorectal liver metastases (CRLM). MWA is less influenced by the heat-sink effect of surrounding vessels and can generate more heat in less time but RFA is still widely used. True comparing studies are scarce. METHODS: This single centre retrospective cohort study analyzed patients who underwent ultrasound guided intraoperative ablation as a part of the surgical treatment of CRLM between 2013 and 2018. In September 2015, MWA was substituted for RFA. Outcomes included unsuccessful ablation rates at 1-year postoperative, 30-days major complication rates, progression free survival (PFS) and overall survival (OS). Logistic regression models were used for univariable and multivariable analyses to identify predictors of unsuccessful ablation. RESULTS: Forty-one patients underwent RFA of 98 lesions (median 2) and 79 patients underwent MWA of 193 lesions (median 2). The median diameter of the ablated lesions was 9 mm for both RFA and MWA. Unsuccessful ablation was observed in 7 metastases (7.1%) after RFA and 14 metastases (7.3%) after MWA (p = 1.000). Complications requiring re-intervention were observed after 8 procedures, 2 complications in the RFA group (4.9%) versus 6 complications in the MWA group (7.6%, p = 0.714), of which 6 were liver-related. Ninety-day mortality did not occur. Ablation technique was not associated with unsuccessful ablations. CRLM size was associated with unsuccessful ablation in the per lesion analysis (p < 0.001). CONCLUSION: Intraoperative RFA and MWA were equally effective for treatment of small CRLM.

Stage I non-small cell lung cancer: Treatment modalities, Dutch daily practice and future perspectives.

OBJECTIVES: Several treatment modalities are available for patients with stage I non-small cell lung cancer (NSCLC). Over the past decade, these treatment modalities have been further investigated and might have changed current treatment regimens. In this review we present an overview of the treatment options, developments and future perspectives for stage I NSCLC. Furthermore, we describe the current use of these treatment modalities in the Netherlands. MATERIALS AND METHODS: A bibliographical search was performed in PubMed and the Cochrane Library for publications concerning treatment modalities for stage I NSCLC. In addition, evidence-based guidelines of the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) were studied. RESULTS: The guideline-recommended treatment for operable stage I NSCLC patients is a lobectomy with systematic lymph node dissection. Inoperable patients or those refusing surgery are offered stereotactic ablative radiotherapy (SABR). Percutaneous ablation, such as radiofrequency ablation, is a non-surgical minimally invasive technique offered to those who are ineligible for surgery or SABR. The role of systemic therapy is currently limited. However, the efficacy of immunotherapy is being investigated in clinical trials. In the Netherlands, an increasing use of SABR and a relative decrease in resection rates have been observed. CONCLUSION: Surgery and SABR are currently the prevailing treatment modalities for stage I NSCLC patients. Despite optimization of treatment regimens, survival of patients with stage I NSCLC remains to be improved. Future studies are required to optimize treatment strategies, but also to investigate factors influencing treatment decision-making for patients with stage I NSCLC.

CBCT-based navigation system for open liver surgery: Accurate guidance toward mobile and deformable targets with a semi-rigid organ approximation and electromagnetic tracking of the liver.

PURPOSE: The surgical navigation system that provides guidance throughout the surgery can facilitate safer and more radical liver resections, but such a system should also be able to handle organ motion. This work investigates the accuracy of intraoperative surgical guidance during open liver resection, with a semi-rigid organ approximation and electromagnetic tracking of the target area. METHODS: The suggested navigation technique incorporates a preoperative 3D liver model based on diagnostic 4D MRI scan, intraoperative contrast-enhanced CBCT imaging and electromagnetic (EM) tracking of the liver surface, as well as surgical instruments, by means of six degrees-of-freedom micro-EM sensors. RESULTS: The system was evaluated during surgeries with 35 patients and resulted in an accurate and intuitive real-time visualization of liver anatomy and tumor's location, confirmed by intraoperative checks on visible anatomical landmarks. Based on accuracy measurements verified by intraoperative CBCT, the system's average accuracy was 4.0 ± 3.0 mm, while the total surgical delay due to navigation stayed below 20 min. CONCLUSIONS: The electromagnetic navigation system for open liver surgery developed in this work allows for accurate localization of liver lesions and critical anatomical structures surrounding the resection area, even when the liver was manipulated. However, further clinically integrating the method requires shortening the guidance-related surgical delay, which can be achieved by shifting to faster intraoperative imaging like ultrasound. Our approach is adaptable to navigation on other mobile and deformable organs, and therefore may benefit various clinical applications.

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

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.

[Experiences with axillary reverse mapping]. / Ervaring met 'axillary reverse mapping'.

Axillary reverse mapping (ARM) is a technique by which the lymphatic drainage system of the upper extremities is mapped, so that the lymph channels and glands can be preserved during axillary lymph node dissection (ALND). This can lead to less postoperative morbidity, such as lymphoedema. A randomised multicentre study showed that there are statistically significantly fewer post-operative symptoms if the lymph channels and glands of the upper extremities are spared with this technique. Despite the declining indication for an ALND, ARM can have added value for the patients who do have to undergo ALND.

A patient- and assessor-blinded randomized controlled trial of axillary reverse mapping (ARM) in patients with early breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) in breast cancer patients is infamous for its accompanying morbidity. Selective preservation of upper extremity lymphatic drainage and accompanying lymph nodes crossing the axillary basin - currently resected during a standard ALND - has been proposed as a valuable surgical refinement. METHODS: Peroperative Axillary Reversed Mapping (ARM) was used for selective preservation of upper extremity lymphatic drainage. A multicentre patient- and assessor-blinded randomized study was performed in clinical node negative, sentinel node positive early breast cancer patients. Patients were randomized to undergo either standard-ALND or ARM-ALND. Primary outcome was the presence of surgery-related lymphedema at six, 12 and 24 months post-operatively. Secondary outcomes included patient reported and objective signs and symptoms of lymphedema, pain, paraesthesia, numbness, loss of shoulder mobility, quality of life and axillary recurrence risk. RESULTS: No significant differences were found between both groups using the water displacement method with respect to measured lymphedema. ARM-ALND resulted in less reported complaints of lymphedema at six, 12 and 24 months postoperatively (p < 0.05). No axillary recurrence was found in both groups. CONCLUSIONS: In contrast to results of volumetric measurement, patient reported outcomes support selective sparing of the upper extremity lymphatic drainage using ARM as valuable surgical refinement in case of ALND in clinically node negative, sentinel node positive early breast cancer. If completion ALND in clinically node negative, sentinel node positive early breast cancer is considered, selective sparing of upper extremity axillary lymphatics by implementing ARM should be carried out in order to reduce morbidity.

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

Diffusion-weighted imaging of hepatocellular carcinoma before and after transarterial chemoembolization: role in survival prediction and response evaluation.

BACKGROUND: Survival outcomes of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) are heterogeneous. Measuring the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI) may improve overall survival prediction. AIM: To assess the value of measuring the ADC before and after TACE in predicting overall survival. METHODS: A retrospective analysis was performed in HCC patients treated with TACE at a tertiary referral center between 2008 and 2017. The ADC values and changes in ADC value (ΔADC) of HCC lesions (≥ 1 cm) and liver parenchyma were assessed by DWI ≤ 3 months before and after first TACE. Pre- and post-TACE ADC values were compared with tumor response according to mRECIST and correlated with overall survival (OS) in a univariable and multivariable Cox-regression analysis. RESULTS: A total of 89 patients were included, mostly Child-Pugh A (85%) and BCLC stage B (53%) with a median OS of 21.7 months (95% CI 17.6-25.9). Tumor ADC increased from 1081 mm2/s before (IQR 964-1225) to 1328 mm2/s (IQR 1197-1560) after TACE (p < 0.001). Responders according to mRECIST showed a higher ΔADC after first TACE than non-responders (26 vs. 14%, p = 0.048). Pre-TACE ADC and ΔADC were not significantly associated with OS in both univariable and multivariable analysis, whereas response according to mRECIST remained an independent predictor of OS. CONCLUSION: mRECIST was confirmed as an independent prognostic factor of OS, but pre- or post-TACE ADC measurements were not. Response according to mRECIST was associated with a higher increase in ADC than non-response.

Factors Affecting Oncologic Outcomes of 90Y Radioembolization of Heavily Pre-Treated Patients With Colon Cancer Liver Metastases.

INTRODUCTION: The purpose of this study was to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogram for OS. MATERIALS AND METHODS: Metabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure-related factors, as well as pre- and post-RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009 to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria In Solid Tumors 1.1 and European Organization for Research and Treatment of Cancer criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS), and subsequently tested in multivariate analysis (MVA). The nomogram was built using R statistical software and internally validated using bootstrap resampling. RESULTS: Patients received RAE at a median of 30.9 months (range, 3.4-161.7 months) after detection of CLM. The median OS and LPFS were 11.3 months (95% confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3-4.8 months), respectively. Of the 40 parameters tested, 6 were independently associated with OS in MVA. These baseline parameters included number of extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001), albumin (P = .005), alanine aminotransferase level (P < .001), tumor differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P < .001). The 1-year OS of patients with total points of < 25 versus > 80 was 90% and 10%, respectively. Bootstrap resampling showed good discrimination (optimism corrected c-index = 0.745) and calibration (mean absolute prediction error = 0.299) of the nomogram. Only baseline maximum standardized uptake value was significant in MVA for LPFS prediction (P < .001; SHR = 1.06). CONCLUSION: The developed nomogram included 6 pre-RAE parameters and provided good prediction of survival post-RAE in heavily pretreated patients. Baseline maximum standardized uptake value was the single significant predictor of LPFS.

Transarterial Radioembolization Following Chemoembolization for Unresectable Hepatocellular Carcinoma: Response Based on Apparent Diffusion Coefficient Change is an Independent Predictor for Survival.

PURPOSE: To evaluate whether response based on contrast-enhanced magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) change at diffusion-weighted MRI after transarterial radioembolization (TARE) can predict survival, in patients with prior transarterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). METHODS: We identified all patients who received DEB-TACE prior to TARE for HCC between 2007 and 2016. Response on MRI was determined by modified RECIST (mRECIST) and ADC change relative to pre-TARE imaging (ADCratio). Kaplan-Meier and log-rank tests were used to correlate the response/disease and treatment variables to overall survival. Multivariable Cox regression models were used to correct for confounders. RESULTS: A total of 29 consecutive patients were included. Univariable analysis showed that response determined by mRECIST was a nonsignificant predictor of survival (p = 0.057), and response determined by ADCratio was a significant predictor of survival (p = 0.011). Number of prior DEB-TACE procedures (p = 0.037), female gender (p < 0.001) and BCLC C (p = 0.03) were related to worse survival. The number of prior DEB-TACE procedure was significantly higher in non-responders determined by ADCratio (p = 0.028). Multivariable analyses showed that response based on ADCratio was an independent predictor of survival (p = 0.041). CONCLUSION: ADCratio following TARE is an independent predictor for survival in patients who previously underwent DEB-TACE for HCC.

Safety and Efficacy of Transarterial Radioembolisation in Patients with Intermediate or Advanced Stage Hepatocellular Carcinoma Refractory to Chemoembolisation.

INTRODUCTION: Transarterial chemoembolisation (TACE) is the most widely used locoregional treatment for patients with an unresectable hepatocellular carcinoma (HCC). Transarterial radioembolisation (TARE) with yttrium-90 containing microspheres is an emerging interventional treatment that could be complementary or an alternative to TACE. AIM: To evaluate the safety and efficacy of TARE in patients with HCC who are refractory to TACE with drug-eluting beads (DEB-TACE). METHODS: We identified all patients who received TARE for HCC following one or more sessions of DEB-TACE in the period 2007-2016. Grade ≥3 adverse events were graded according to Common Terminology Criteria for Adverse events. Response on MRI was determined on MRI by modified RECIST. Overall survival was estimated using the Kaplan-Meier method and was determined from the first TACE and from the TARE procedure. RESULTS: A total of 30 patients were included. Patients had a mean of 1.7 TACE procedures (range 1-4) prior to TARE. Grade 3 adverse events following TARE included: fatigue (20%), bilirubin increase (10%), cholecystitis (3.3%) and a gastric ulcer (3.3%). Response on MRI was achieved in 36.7%. Three patients (10%) were downstaged within the Milan criteria and received liver transplantation. The median overall survival after first TACE was 32.3 months (17.2-42.1 95% CI). The median overall survival after TARE was 14.8 months (8.33-26.5 95% CI). CONCLUSION: TARE is safe and can be effective in patients with an intermediate or advanced stage HCC who are refractory to TACE. This treatment strategy has the potential to downstage to liver transplantation.

Axillary reverse mapping in axillary surgery for breast cancer: an update of the current status.

Axillary reverse mapping (ARM) is a technique by which the lymphatic drainage of the upper extremity that traverses the axillary region can be differentiated from the lymphatic drainage of the breast during axillary lymph node dissection (ALND). Adding this procedure to ALND may reduce upper extremity lymphedema by preserving upper extremity drainage. This review of the current literature on the ARM procedure discusses the feasibility, safety and relevance of this technique. A PubMed literature search was performed until 12 August 2015. A total of 31 studies were included in this review. The studies indicated that the ARM procedure adequately identifies the upper extremity lymph nodes and lymphatics in the axillary basin using blue dye or fluorescence. Preservation of ARM lymph nodes and corresponding lymphatics was proven to be oncologically safe in clinically node-negative breast cancer patients with metastatic lymph node involvement in the sentinel lymph node (SLN) who are advised to undergo a completion ALND. The ARM procedure is technically feasible with a high visualisation rate using blue dye or fluorescence. ALND combined with ARM can be regarded as a promising surgical refinement in order to reduce the incidence of upper extremity lymphedema in selected groups of patients.

Type and Extent of Surgery for Screen-Detected and Interval Cancers at Blinded Versus Nonblinded Double-Reading in a Population-Based Screening Mammography Program.

BACKGROUND: This study aimed to compare the type and extent of surgery in patients with screen-detected and interval cancers after blinded or nonblinded double-reading of screening mammograms. METHODS: The study investigated a consecutive series of screens double-read in either a blinded (n = 44,491) or nonblinded (n = 42,996) fashion between 2009 and 2011. During a 2 year follow-up period, the radiology reports, surgical correspondence, and pathology reports of all the screen-detected and interval cancers were collected. RESULTS: Screen-detected breast cancer was diagnosed for 325 women at blinded and 284 women at nonblinded double-reading. The majority of the women were treated by breast-conserving surgery (BCS) at both reading strategies (78.2 vs. 81.7 %; p = 0.51). Larger total resection volumes were observed at BCS for ductal carcinoma in situ (DCIS) treatment for patients after blinded double-reading (p = 0.005). The proportions of positive resection margins after BCS were comparable for patients with DCIS (p = 0.81) or invasive screen-detected cancers (p = 0.38) for the two reading strategies. A total of 158 interval cancers were diagnosed. The proportions of patients treated with BCS were comparable for the two reading strategies (p = 0.42). The total resection volume (p = 0.13) and the proportion of positive resection margins after BCS (p = 0.32) for invasive interval cancer were comparable for the two cohorts. The BCS rate was higher for women after nonblinded double-reading (p = 0.04). CONCLUSIONS: Blinded and nonblinded double-reading yielded comparable surgical treatments for women with screen-detected or interval breast cancer except for larger total resection volumes at BCS for screen-detected DCIS and a higher BCS rate for interval cancers at nonblinded double-reading.