Clinical Outcomes of Biliary Drainage in Patients with Malignant Biliary Obstruction Caused by Colorectal Cancer Metastases

BACKGROUND AND AIM: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC) that is challenging to solve. Biliary drainage can be performed to relieve symptoms of jaundice, treat cholangitis, or enable palliative systemic therapy. The aim of this study is to evaluate clinical outcomes of biliary drainage of malignant biliary obstruction in mCRC patients. METHODS: Consecutive patients with malignant biliary obstruction due to mCRC who underwent endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography were included. Patient, disease, and procedural characteristics and outcomes were retrospectively collected from electronic medical records. Radiological data were prospectively reassessed. Main outcome was functional success, i.e. achievement of the intended goal of biliary drainage. Prognostic factors for functional success and survival were assessed. RESULTS: Thirty-seven patients were included. Functional success was achieved in 18 (50%) patients. Seventeen (46%) patients experienced adverse events (suspected to be) related to the procedure. Median overall survival after biliary drainage was 61 days (IQR 31-113). No prognostic factors of functional success were identified. Performance status, presence of the primary tumor, ascites, ≥ 5 intrahepatic metastases, estimated hepatic invasion of > 50% and above-median levels of bilirubin and lactate dehydrogenase were significantly associated with poorer survival. Improved survival was seen in patients with technical, functional, or biochemical success, and with subsequent oncologic treatment. CONCLUSIONS: Functional successful biliary drainage was achieved in half of the patients. Adverse events also occurred in nearly half of the patients. We observed a significantly longer survival in whom biliary drainage allowed palliative oncologic therapy

Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [ 166Ho]-Scout Over [ 99mTc]MAA in a Prospective Cohort Study

Purpose: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. Materials and Methods: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman’s rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. Results: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09–21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00–1.20 Gy; p 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). Conclusion: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. Trail registration: NCT01031784, registered December 2009. NCT01612325, registered June 2012. Graphical Abstract: (Figure presented.

Quality of life in patients with liver tumors treated with holmium-166 radioembolization

Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life

Surefire infusion system versus standard microcatheter use during holmium-166 radioembolization : study protocol for a randomized controlled trial

BACKGROUND: An anti-reflux catheter (ARC) may increase the tumor absorbed dose during radioembolization (RE) by elimination of particle reflux and its effects on hemodynamics. Since the catheter is fixed in a centro-luminal position, it may also increase the predictive accuracy of a scout dose administration before treatment. The purpose of the SIM trial is to compare the effects of ARC use during RE with holmium-166 ((166)Ho) microspheres in patients with colorectal liver metastases (CRLM), with the use of a standard end-hole microcatheter. METHODS/DESIGN: A within-patient randomized controlled trial (RCT) will be conducted in 25 patients with unresectable chemorefractory liver-dominant CRLM. Study participants will undergo a (166)Ho scout dose procedure in the morning and a therapeutic procedure in the afternoon. The ARC will be randomly allocated to the left/right hepatic artery, and a standard microcatheter will be used in the contralateral artery. SPECT/CT imaging will be performed for quantitative analyses of the microsphere distribution directly after the scout and treatment procedure. Baseline and follow-up investigations include (18)F-FDG-PET + liver CT, clinical and laboratory examinations. The primary endpoint is the comparison of tumor to non-tumor (T/N) activity ratio in both groups. Secondary endpoints include comparisons of mean absorbed dose in tumors and healthy liver tissue, infusion efficiency, the predictive value of (166)Ho scout dose for tumor response. In the entire cohort, a dose-response relationship, clinical toxicity, and overall survival will be assessed. The sample was determined for the expectation that the ARC will increase the T/N ratio by 25 % (mean T/N ratio 2.0 vs. 1.6). DISCUSSION: The SIM trial is a within-patient RCT that will assess whether (166)Ho RE treatment can be optimized by using an ARC. TRIAL REGISTRATION: The SIM trial is registered at clinicaltrials.gov ( NCT02208804 ). Registered on 31 July 2014

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres

UNLABELLED: Before (166)Ho radioembolization, a small batch of the same type of microspheres is administered as a scout dose instead of the conventional (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). The (166)Ho scout dose provides a more accurate and precise lung shunt assessment. However, in contrast to (99m)Tc-MAA, an unintended extrahepatic deposition of this β-emitting scout dose could inflict radiation damage, the extent of which we aimed to quantify in this study. METHODS: All patients eligible for radioembolization in our institute between January 2011 and March 2014 were reviewed. Of the extrahepatic depositions of (99m)Tc-MAA on SPECT, the amount and volume were measured. These were used to calculate the theoretic absorbed dose in the case a (166)Ho scout dose had been used. The extrahepatic activity was measured as the sum of all voxels of the deposition. Volumes were measured using a threshold technique including all voxels from the maximum voxel intensity up to a certain percentage. The threshold needed to obtain the true volume was studied in a phantom study. RESULTS: In the phantom study, a threshold of 40% was found to overestimate the volume, with the consequence of underestimating the absorbed dose. Of 160 patients, 32 patients (34 cases) of extrahepatic deposition were identified. The depositions contained a median of 1.3% (range, 0.1%-19.5%) of the administered activity in a median volume of 6.8 mL (range, 1.1-42 mL). The use of a scout dose of 250 MBq of (166)Ho microspheres in these cases would theoretically have resulted in a median absorbed dose of 6.0 Gy (range, 0.9-374 Gy). The dose exceeded a limit of 49 Gy (reported in 2013) in 2 of 34 cases (5.9%; 95% confidence interval, 0.7%-20.1%) or 2 of 160 (1.3%; 95% confidence interval, 0.1%-4.7%) of all patients. In these 2 patients with a large absorbed dose (112 and 374 Gy), the culprit vessel was identified in 1 case. CONCLUSION: Extrahepatic deposition of a (166)Ho scout dose seems to be theoretically safe in most patients. Its safety in clinical practice is being evaluated in ongoing clinical trials

Lung Shunting : An Indicator of Survival, But Not Necessarily a Tool for Selecting Patients for Radioembolization

UNC - CONICETEste artículo se concentra en la llamada objeción “democrática”, que cuestiona la legitimidad de las atribuciones judiciales para invalidar decisiones de los otros poderes. Revisa los límites y supuestos de esta postura, para luego presentar razones que justifican la intervención de los tribunales, en un modelo deliberativo de democracia. Finalmente, repasa los aportes de la objeción “democrática”, y a partir de ellos, propone modalidades graduales de actuación para ciertos casos