Failure to “blind” a study effectively Proteases inhibitor becomes particularly relevant and, possibly, very difficult, if the side effects of the treatment under study are marked and if the primary measure of outcome is “soft,” such as patients with PBC who want very much to have their fatigue or pruritus reduced. Only with close examination of the “strange” results of our crossover trial-design to evaluate the effect of ondansetron on fatigue in PBC did we “figure out” that the results were invalidated both by patient anticipation

of benefit and the near-universal side effects of odansetron! In a more recently published trial in patients with autoimmune hepatitis (AIH), one outcome marker was the combined biochemical response and the change in sense of “well-being,” the latter of which may have been compromised by different dosing regimens for the two arms of the study.10 Patients with PBC tend to be more “informed” than most. My failure to take this into account taught Opaganib datasheet me that before designing, writing, submitting, and securing funding, one should, first of all, solicit the patient’s interest! My RCT of hormone replacement therapy (HRT) for osteoporosis failed because

the patients were either dead set against, or were already taking, HRT and few sat “on the fence.” In a more recent study of the effect of antiviral therapy for chronic hepatitis C (CHC) on central nervous system integrity,11 I learned that if measures of outcome take time to conduct or collect, it is particularly hard to encourage untreated controls to return for repeat evaluation 1 year later. These examples highlight MCE公司 that small omissions in planning can ruin even the best-intentioned RCT. Sadly, we are familiar with some of the past mistakes in judgement

when subjects were not fully informed and/or may have been coerced to participate in clinical trials.12 The process of informed consent needs to be written in a clear style and appropriate language for the average adult. But, “informed consent” in 2011 seems to me to “go overboard.” Patients must read consent forms running to so many pages, it is hard to imagine that any patient reads them in their entirety. The process could indeed be perceived as coercion, particularly if participation may be that individual’s only way to gain access to treatment. Meanwhile, the need to mention every “potential” side effect may deter others from entering the trial, thereby missing the benefits from the “experimental” therapy. Blame for this should not be laid just at the feet of “industry.” These aspects of informed consent are the downside of what is basically very important: equipoise in the recruitment and conduct of clinical trials.13 This argument can be taken further if we take language, culture, and circumstance into account. We need a reevaluation of the consent process to ensure that patients not only have “access” to information, but that they are able to “consume and digest” that information.

Failure to “blind” a study effectively Inhibitor Library high throughput becomes particularly relevant and, possibly, very difficult, if the side effects of the treatment under study are marked and if the primary measure of outcome is “soft,” such as patients with PBC who want very much to have their fatigue or pruritus reduced. Only with close examination of the “strange” results of our crossover trial-design to evaluate the effect of ondansetron on fatigue in PBC did we “figure out” that the results were invalidated both by patient anticipation

of benefit and the near-universal side effects of odansetron! In a more recently published trial in patients with autoimmune hepatitis (AIH), one outcome marker was the combined biochemical response and the change in sense of “well-being,” the latter of which may have been compromised by different dosing regimens for the two arms of the study.10 Patients with PBC tend to be more “informed” than most. My failure to take this into account taught Cytoskeletal Signaling inhibitor me that before designing, writing, submitting, and securing funding, one should, first of all, solicit the patient’s interest! My RCT of hormone replacement therapy (HRT) for osteoporosis failed because

the patients were either dead set against, or were already taking, HRT and few sat “on the fence.” In a more recent study of the effect of antiviral therapy for chronic hepatitis C (CHC) on central nervous system integrity,11 I learned that if measures of outcome take time to conduct or collect, it is particularly hard to encourage untreated controls to return for repeat evaluation 1 year later. These examples highlight 上海皓元 that small omissions in planning can ruin even the best-intentioned RCT. Sadly, we are familiar with some of the past mistakes in judgement

when subjects were not fully informed and/or may have been coerced to participate in clinical trials.12 The process of informed consent needs to be written in a clear style and appropriate language for the average adult. But, “informed consent” in 2011 seems to me to “go overboard.” Patients must read consent forms running to so many pages, it is hard to imagine that any patient reads them in their entirety. The process could indeed be perceived as coercion, particularly if participation may be that individual’s only way to gain access to treatment. Meanwhile, the need to mention every “potential” side effect may deter others from entering the trial, thereby missing the benefits from the “experimental” therapy. Blame for this should not be laid just at the feet of “industry.” These aspects of informed consent are the downside of what is basically very important: equipoise in the recruitment and conduct of clinical trials.13 This argument can be taken further if we take language, culture, and circumstance into account. We need a reevaluation of the consent process to ensure that patients not only have “access” to information, but that they are able to “consume and digest” that information.

The

study was a prospective investigation of the changes in immunoregulatory markers in the blood, bone marrow, and liver allograft in recipients converted from TAC monotherapy to SRL monotherapy for clinical indications (e.g., TAC toxicity). Inclusion criteria were as follows: age ≥18 years; ≥6 months post-LT; TAC monotherapy ≥1 month before SRL monotherapy conversion for nephrotoxicity (glomular filtration rate [GFR] 30-60 cc/min by modified diet in renal disease [MDRD]) or other indication; ≥6 months without a rejection episode; this website no lymphocyte depletion therapy for ≥1 year; normal liver-function tests; and no rejection or fibrosis on preconversion liver biopsy. Exclusion criteria were as follows: previous liver or multiorgan transplant; previous immune or viral liver disease unless hepatitis C virus (HCV) RNA was undetectable; proteinuria (≥0.5 g/day); estimated glomerular filtration rate (eGFR) ≤30 cc/min; ≥2 rejections

post-LT; history of hepatic artery thrombosis; hematological abnormalities or severe hypertriglyceridemia; active infection or malignancy; and inadequacy for follow-up. All patients signed informed consent and were followed for 7 months after SRL conversion. The protocol conformed to the Declaration of Helsinki guidelines and was approved by the Northwestern Institutional selleck products Review Board (Northwestern University Feinberg School of Medicine, Chicago, IL). History and physical exams, complete blood counts, comprehensive metabolic panels, fasting lipids, hemoglobin A1C tests (HgA1C), and spot urine protein:creatinine ratios were performed before and 3 and 6 months after conversion. Bone marrow aspirations and percutaneous liver biopsies were performed once before and 6 months after conversion. For conversion, SRL at 2 or 3 mg (< or ≥100 kg body weight) daily was initiated with subsequent weekly SRL trough-level monitoring. When these reached ≥5 ng/mL, TAC was discontinued followed by weekly laboratory tests and SRL trough levels (goal, 5-8 ng/mL) for 1 month,

then monthly. Prospective liver- and renal-function tests, lipid levels, urine protein:creatinine MCE ratios, and any new SRL toxicities were recorded. Treg immunophenotyping (twice before conversion and 3, 4, 6, and 7 months after conversion): Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized samples on Ficoll-Hypaque gradients. Tregs were enumerated utilizing extracellular immunofluorescent staining with CD3-FITC (fluorescein isothiocyanate), CD4-PerCP (peridinin-chlorophyll protein complex), CD8-PerCP, CD25-APC, and CD127-FITC (BD Biosciences, San Diego, CA). After fixation and permeabilization, the cells were washed and incubated with anti-human FOXP3-PE (phycoerythrin) or rat immunoglobulin G2a-PE isotype control (eBioscience, San Diego, CA) (21, 22).

Additional Supporting Information may be found in the online version of this article. “
“Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor. In all, 290 noncirrhotic HCV genotype (GT)-1 patients with prior null (<1 log10 viral load [VL] drop at any time on treatment) or partial response (≥1 log10 VL drop but never undetectable on treatment) were randomized 2:1:1 to receive 48 weeks of peginterferon alfa-2a and ribavirin

(PegIFN/RBV) in combination with faldaprevir 240 mg once daily (QD) with 3 days PegIFN/RBV lead-in (LI), 240 mg QD without LI, or 240 mg twice daily (BID) with LI. Patients in the 240 mg QD/LI group achieving maintained rapid virologic response (mRVR; VL <25 IU/mL [Roche TaqMan] at week 4 and undetectable at Apitolisib clinical trial BAY 73-4506 weeks 8 to 20) were rerandomized to cease all treatment at week 24 or continue PegIFN/RBV up to week 48. Sustained virologic response (SVR) rates were 32%, 50%, and 42% in prior partial responders, and 21%, 35%, and 29% in prior null responders in the faldaprevir 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively.

In the 240 mg QD/LI group, a significantly higher proportion of mRVR patients rerandomized to 48 weeks’ treatment achieved SVR compared with those assigned to 24 weeks treatment (72% versus 43%; P = 0.035). Rates of gastrointestinal disorders, jaundice, dry skin, and photosensitivity

were increased at 240 mg BID compared with the 240 mg QD dose. Faldaprevir discontinuations owing to adverse events occurred in 6%, 4%, and 23% of patients in the 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. Conclusion: Faldaprevir 240 mg QD with PegIFN/RBV was safe and tolerable and produced substantial SVR rates in prior null and partial MCE responders. The 240 mg QD dose is currently undergoing phase 3 evaluation. (Hepatology 2013;57:2155–2163) Hepatitis C represents one of the most common chronic infectious diseases, affecting 150 to 170 million people worldwide. Of the described hepatitis C virus (HCV) genotypes (GT), GT-1 is most common in many parts of the world. Historically, GT-1 has been less responsive to peginterferon alfa (PegIFN) and ribavirin (RBV) treatment, with around 50% to 60% of treatment-naïve patients failing to achieve a sustained virologic response (SVR). Treatment options for these patients were previously limited to a repeated course of PegIFN/RBV, with a low chance of cure (□15% SVR).1, 2 Recent approval of the HCV NS3/4A protease inhibitors (PIs) boceprevir and telaprevir has resulted in significantly improved SVR rates in GT-1-infected patients including those who failed to respond to prior PegIFN/RBV treatment.

Additional Supporting Information may be found in the online version of this article. “
“Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor. In all, 290 noncirrhotic HCV genotype (GT)-1 patients with prior null (<1 log10 viral load [VL] drop at any time on treatment) or partial response (≥1 log10 VL drop but never undetectable on treatment) were randomized 2:1:1 to receive 48 weeks of peginterferon alfa-2a and ribavirin

(PegIFN/RBV) in combination with faldaprevir 240 mg once daily (QD) with 3 days PegIFN/RBV lead-in (LI), 240 mg QD without LI, or 240 mg twice daily (BID) with LI. Patients in the 240 mg QD/LI group achieving maintained rapid virologic response (mRVR; VL <25 IU/mL [Roche TaqMan] at week 4 and undetectable at AZD2281 supplier selleck chemical weeks 8 to 20) were rerandomized to cease all treatment at week 24 or continue PegIFN/RBV up to week 48. Sustained virologic response (SVR) rates were 32%, 50%, and 42% in prior partial responders, and 21%, 35%, and 29% in prior null responders in the faldaprevir 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively.

In the 240 mg QD/LI group, a significantly higher proportion of mRVR patients rerandomized to 48 weeks’ treatment achieved SVR compared with those assigned to 24 weeks treatment (72% versus 43%; P = 0.035). Rates of gastrointestinal disorders, jaundice, dry skin, and photosensitivity

were increased at 240 mg BID compared with the 240 mg QD dose. Faldaprevir discontinuations owing to adverse events occurred in 6%, 4%, and 23% of patients in the 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. Conclusion: Faldaprevir 240 mg QD with PegIFN/RBV was safe and tolerable and produced substantial SVR rates in prior null and partial 上海皓元 responders. The 240 mg QD dose is currently undergoing phase 3 evaluation. (Hepatology 2013;57:2155–2163) Hepatitis C represents one of the most common chronic infectious diseases, affecting 150 to 170 million people worldwide. Of the described hepatitis C virus (HCV) genotypes (GT), GT-1 is most common in many parts of the world. Historically, GT-1 has been less responsive to peginterferon alfa (PegIFN) and ribavirin (RBV) treatment, with around 50% to 60% of treatment-naïve patients failing to achieve a sustained virologic response (SVR). Treatment options for these patients were previously limited to a repeated course of PegIFN/RBV, with a low chance of cure (□15% SVR).1, 2 Recent approval of the HCV NS3/4A protease inhibitors (PIs) boceprevir and telaprevir has resulted in significantly improved SVR rates in GT-1-infected patients including those who failed to respond to prior PegIFN/RBV treatment.

Quality of life improvements are similar compared to lung, kidney and heart transplantation. Heterogeneity between studies precluded quantitative analysis. Conclusions: Liver transplantation confers specific long-term quality of life and functional benefits when compared to pre-operative status. This information can assist in providing a more complete estimate of the overall health of liver transplant recipients and the effectiveness of surgery. Guidelines for future studies are provided.

M ZUBAIR, C CONNELLY, L AYRES, C WELMAN, S GALHENAGE, KOYA AYONRINDE, J OLYNYK, L MANNING, L MOLLISON Departments of Medicine, Gastroenterology, Infectious Diseases and Radiology, Fremantle Hospital, Fremantle, WA, 6160 Background and Aims: Assessment of liver fibrosis is integral to the work up for patients with chronic viral U0126 research buy hepatitis. Liver biopsy remains the gold standard for assessing this but is invasive and costly. Non-invasive methods for assessing the same are becoming increasingly

popular. Typically, transient elastography/Fibroscan™ (FS) and liver ultrasonography are performed separately. Recently short/shear wave elastography (SWE) has become available and has been shown Stem Cell Compound Library screening to correlate well with liver biopsy in chronic hepatitis B and C. We aimed to audit the correlation of between SWE and FS in a cohort of patients with viral hepatitis. Methods: A retrospective analysis of 40 patients with hepatitis B or C who were assessed with FS and routine ultrasound including SWE were examined retrospectively. SWE was performed using a Philips EPIQ Ultrasound™ system to a set protocol. Statistical comparison of kPa values obtained from the two methods was performed using Spearman-rank and Pearson correlation tests. Results: 10 patients had hepatitis B; 30 patients had hepatitis C. For hepatitis B correlation between FS and SWE was high (Spearman r = 0.62, P = 0.06; Pearson r = 0.88, P = 0.009). For hepatitis C, similarly a good correlation

was observed (Spearman r = 0.45, P = 0.01). Conclusions: There is at least a moderate correlation between FS and SWE in this 上海皓元医药股份有限公司 group of patients. Agreement is better for hepatitis B than hepatitis C. Further exploration of correlation between the tests including comparison of fibrosis stages obtained by the two methods is required. K LIU,1,2 R WANG,1 M WELLS,3 S STRASSER,1,3 G MCCAUGHAN,1,3 C CORTE,1,2 RWL LEONG1,2 1Faculty of Medicine, The University of Sydney, Sydney, 2Gastroenterology and Liver Services, Concord Hospital, Sydney, 3AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia Introduction: Primary sclerosing cholangitis (PSC) is an uncommon but often progressive inflammatory fibrotic stricturing disease of the biliary tree that may lead to cirrhosis and liver failure requiring orthotopic liver transplantation (OLT). The 2012 Australian prevalence of PSC was estimated to be 872 cases (1).

Quality of life improvements are similar compared to lung, kidney and heart transplantation. Heterogeneity between studies precluded quantitative analysis. Conclusions: Liver transplantation confers specific long-term quality of life and functional benefits when compared to pre-operative status. This information can assist in providing a more complete estimate of the overall health of liver transplant recipients and the effectiveness of surgery. Guidelines for future studies are provided.

M ZUBAIR, C CONNELLY, L AYRES, C WELMAN, S GALHENAGE, KOYA AYONRINDE, J OLYNYK, L MANNING, L MOLLISON Departments of Medicine, Gastroenterology, Infectious Diseases and Radiology, Fremantle Hospital, Fremantle, WA, 6160 Background and Aims: Assessment of liver fibrosis is integral to the work up for patients with chronic viral learn more hepatitis. Liver biopsy remains the gold standard for assessing this but is invasive and costly. Non-invasive methods for assessing the same are becoming increasingly

popular. Typically, transient elastography/Fibroscan™ (FS) and liver ultrasonography are performed separately. Recently short/shear wave elastography (SWE) has become available and has been shown check details to correlate well with liver biopsy in chronic hepatitis B and C. We aimed to audit the correlation of between SWE and FS in a cohort of patients with viral hepatitis. Methods: A retrospective analysis of 40 patients with hepatitis B or C who were assessed with FS and routine ultrasound including SWE were examined retrospectively. SWE was performed using a Philips EPIQ Ultrasound™ system to a set protocol. Statistical comparison of kPa values obtained from the two methods was performed using Spearman-rank and Pearson correlation tests. Results: 10 patients had hepatitis B; 30 patients had hepatitis C. For hepatitis B correlation between FS and SWE was high (Spearman r = 0.62, P = 0.06; Pearson r = 0.88, P = 0.009). For hepatitis C, similarly a good correlation

was observed (Spearman r = 0.45, P = 0.01). Conclusions: There is at least a moderate correlation between FS and SWE in this MCE group of patients. Agreement is better for hepatitis B than hepatitis C. Further exploration of correlation between the tests including comparison of fibrosis stages obtained by the two methods is required. K LIU,1,2 R WANG,1 M WELLS,3 S STRASSER,1,3 G MCCAUGHAN,1,3 C CORTE,1,2 RWL LEONG1,2 1Faculty of Medicine, The University of Sydney, Sydney, 2Gastroenterology and Liver Services, Concord Hospital, Sydney, 3AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia Introduction: Primary sclerosing cholangitis (PSC) is an uncommon but often progressive inflammatory fibrotic stricturing disease of the biliary tree that may lead to cirrhosis and liver failure requiring orthotopic liver transplantation (OLT). The 2012 Australian prevalence of PSC was estimated to be 872 cases (1).

1D,E). We also assessed predictive performance of 3-year OS of three prognosis models by calculating AUCs from ROC analysis. Not surprisingly, the AUC of the 65-gene risk score (0.68; 95% CI, 0.604-0.761) is highly similar to those from original prognosis models (Supporting Fig. 1). This result strongly suggests that the expression patterns of the 65 genes are sufficient to predict the prognosis of HCC patients, although this dataset represents only 5.8% of genes in the NCI proliferation signature and 10.3% of genes in the SNU recurrence signature. To test whether genes not shared by two prognostic signatures have similar discriminatory

power, two additional risk scores were generated from 65 genes that were randomly selected from nonoverlapped gene lists in each prognostic signature and applied to NCI and SNU cohorts. As expected, the NCI proliferation signature risk score showed

www.selleckchem.com/products/lee011.html significant predictive performance on patients in NCI cohorts (Supporting Fig. 2B). However, it failed to show significant predictive performance on patients in SNU cohorts (Supporting Fig. 2C). The SNU recurrence signature risk score also showed opposite predictive performance on patients from two different cohorts (Supporting Fig. 2B,C). However, common gene risk scores showed consistent Neratinib clinical trial predictive performance on patients from both cohorts. These data suggest that genes shared in two independent prognostic signatures might be more robust than those only present in one signature. We next sought to validate the risk score using expression data of the 65 genes from the independent HCC cohort. Gene expression data for 100 tumors from Korean patients with HCC were collected and used as an independent test set. The coefficient and threshold value (8.36) MCE derived from the NCI cohort were directly applied. When patients

in the Korean cohort were stratified according to their risk score, the patient group with a low risk score had a significantly better prognosis (P = 5.6 × 10−5 for OS, log-rank test) (Fig. 2A) than patients with a high risk score. The risk score was further validated in another independent cohort (LCI cohort, P = 5.0 × 10−4 for OS, log-rank test) (Fig. 2B). Taken together, these results demonstrate that it is possible to determine a risk score on the basis of the expression of a small number of genes. We next combined clinical data from two test cohorts and assessed the prognostic association between our newly developed 65-gene risk score and other known clinical risk factors using univariate Cox regression analyses. In addition to the alpha-fetoprotein (AFP) level, tumor size, grade, and vasculature invasion, which are already well-known risk factors, the risk score was a significant indicator for OS (Table 3).

27 BI 6727 cell line CT or MR are more effective for follow-up monitoring beyond 1 month: They will confirm CR and detect tumor recurrence. This is as frequent as after surgical resection (>70% at 5 years), and how to register it is discussed below. Assessment of chemoembolization is also challenging.

Necrosis is also estimated by the absence of contrast uptake, but the rate of CR is lower. Residual disease is frequent, and this has led to the proposing of a system to measure the amount of tumor necrosis according to the extent of residual viable tissue by summing the length of the remnant viable parts.23, 28 This parallels the definitions of conventional RECIST and is presented as modified RECIST (Table 1).28 Extensive necrosis by chemoembolization correlates with outcome,29, 30 but several aspects need validation. There is risk of overestimation of the necrosis extent, as also happens with ablation. Some patients classified as CR have residual disease at the time of explant, if resected or transplanted.31-33 This risk may vary according to the agent used AZD6738 price for vessel obstruction. Thus, comparison of the response rate (RR) between different technologies may be not be reliable.

Evaluation of radioembolization is more controversial. Tumor necrosis is achieved after several months, and the optimal timing for assessment needs to be ascertained.30, 34 Lipiodol uptake and retention has been used as a surrogate of necrosis, but studies in transplanted patients show that there is risk of major response overestimation.33 Two of the critical issues in chemoembolization are (1) when treatment should be repeated (until achieving CR, at regular intervals or on demand) and (2) when it should be cancelled. CR is not achieved in a large proportion of cases. In addition, whatever degree of necrosis is obtained,

the tumor will regain vascularization during follow-up and/or show an increase in the remnant viable area. In our positive trial,29 we performed two treatment sessions at baseline, then repeated chemoembolization every 6 months. Other investigators apply a more intense schedule, but the absence of survival benefit, in some studies, may be caused 上海皓元 by the fact that the antitumoral efficacy of intensive retreatment is counterbalanced by a negative effect in liver function. This stresses the need to define when treatment is no longer to be repeated. In oncology, progression is seen as treatment failure, and a common parameter to describe treatment efficacy is time to progression (TTP). This is not the case in locoregional treatment. Progression (i.e., either regrowth of initially treated tumor sites or appearance of a new intrahepatic nodule) may be successfully treated and the disease may be again kept under control. If progression is major (e.g., extrahepatic spread and vascular invasion), retreatment may be of no benefit and survival may be impaired.

27 Erlotinib chemical structure CT or MR are more effective for follow-up monitoring beyond 1 month: They will confirm CR and detect tumor recurrence. This is as frequent as after surgical resection (>70% at 5 years), and how to register it is discussed below. Assessment of chemoembolization is also challenging.

Necrosis is also estimated by the absence of contrast uptake, but the rate of CR is lower. Residual disease is frequent, and this has led to the proposing of a system to measure the amount of tumor necrosis according to the extent of residual viable tissue by summing the length of the remnant viable parts.23, 28 This parallels the definitions of conventional RECIST and is presented as modified RECIST (Table 1).28 Extensive necrosis by chemoembolization correlates with outcome,29, 30 but several aspects need validation. There is risk of overestimation of the necrosis extent, as also happens with ablation. Some patients classified as CR have residual disease at the time of explant, if resected or transplanted.31-33 This risk may vary according to the agent used U0126 solubility dmso for vessel obstruction. Thus, comparison of the response rate (RR) between different technologies may be not be reliable.

Evaluation of radioembolization is more controversial. Tumor necrosis is achieved after several months, and the optimal timing for assessment needs to be ascertained.30, 34 Lipiodol uptake and retention has been used as a surrogate of necrosis, but studies in transplanted patients show that there is risk of major response overestimation.33 Two of the critical issues in chemoembolization are (1) when treatment should be repeated (until achieving CR, at regular intervals or on demand) and (2) when it should be cancelled. CR is not achieved in a large proportion of cases. In addition, whatever degree of necrosis is obtained,

the tumor will regain vascularization during follow-up and/or show an increase in the remnant viable area. In our positive trial,29 we performed two treatment sessions at baseline, then repeated chemoembolization every 6 months. Other investigators apply a more intense schedule, but the absence of survival benefit, in some studies, may be caused 上海皓元 by the fact that the antitumoral efficacy of intensive retreatment is counterbalanced by a negative effect in liver function. This stresses the need to define when treatment is no longer to be repeated. In oncology, progression is seen as treatment failure, and a common parameter to describe treatment efficacy is time to progression (TTP). This is not the case in locoregional treatment. Progression (i.e., either regrowth of initially treated tumor sites or appearance of a new intrahepatic nodule) may be successfully treated and the disease may be again kept under control. If progression is major (e.g., extrahepatic spread and vascular invasion), retreatment may be of no benefit and survival may be impaired.