Thierry de Baere

EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma

EASL–EORTC Clinical Practice Guidelines (CPG) on the management of hepatocellular carcinoma (HCC) define the use of surveillance, diagnosis, and therapeutic strategies recommended for patients with this type of cancer. This is the first European joint effort by the European Association for the Study of the Liver (EASL) and the European Organization for Research and Treatment of Cancer (EORTC) to provide common guidelines for the management of hepatocellular carcinoma. These guidelines update the recommendations reported by the EASL panel of experts in HCC published in 2001 [1]. Several clinical and scientific advances have occurred during the past decade and, thus, a modern version of the document is urgently needed. The purpose of this document is to assist physicians, patients, health-care providers, and health-policy makers from Europe and worldwide in the decision-making process according to evidencebased data. Users of these guidelines should be aware that the recommendations are intended to guide clinical practice in circumstances where all possible resources and therapies are available. Thus, they should adapt the recommendations to their local regulations and/or team capacities, infrastructure, and cost– benefit strategies. Finally, this document sets out some recommendations that should be instrumental in advancing the research and knowledge of this disease and ultimately contribute to improve patient care. The EASL–EORTC CPG on the management of hepatocellular carcinoma provide recommendations based on the level of evidence and the strength of the data (the classification of evidence is adapted from National Cancer Institute [2]) (Table 1A) and the strength of recommendations following previously reported systems (GRADE systems) (Table 1B).

Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria—A 10-Year Update

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Guidelines for Patient Radiation Dose Management

Michael S. Stecker, MD, Stephen Balter, PhD, Richard B. Towbin, MD, Donald L. Miller, MD, Eliseo Vano, PhD,Gabriel Bartal, MD, J. Fritz Angle, MD, Christine P. Chao, MD, Alan M. Cohen, MD, Robert G. Dixon, MD,Kathleen Gross, MSN, RN-BC, CRN, George G. Hartnell, MD, Beth Schueler, PhD, John D. Statler, MD,Thierry de Baere, MD, and John F. Cardella, MD, for the SIR Safety and Health Committee and the CIRSEStandards of Practice Committee

Antitumor electrochemotherapy: New advances in the clinical protocol

Electrochemotherapy (ECT) is a new antitumor approach that combines systemic bleomycin (BLM) with electric pulses (EP) delivered locally at the tumor site. These EP permeabilize the cells in the tissue, allow BLM delivery inside the cells, and increase BLM cytotoxicity. As an extension of our initial Phase I trial on patients with head and neck squamous cell carcinoma (HNSCC) permeation nodules, we tested variations of ECT protocol to determine how to improve it.

Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC) : Results of a phase II study

New systemic therapies are needed to improve the prognosis of patients with advanced‐stage hepatocellular carcinoma (HCC). In a Phase II trial involving previously untreated patients with advanced HCC, the more favorable schedule from a previous pilot study was evaluated.

Quality Improvement Guidelines for Radiofrequency Ablation of Liver Tumours

The development of image-guided percutaneous techniques for local tumour ablation has been one of the major advances in the treatment of liver malignancies. Among these methods, radiofrequency ablation (RFA) is currently established as the primary ablative modality at most institutions. RFA is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when liver transplantation or surgical resection are not suitable options [1, 2]. In addition, RFA is considered a viable alternate to surgery (1) for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer, and (2) for patients deemed ineligible for surgical resection because of extent and location of the disease or concurrent medical conditions [3]. These guidelines were written to be used in quality-improvement programs to assess RFA of HCC and liver metastases. The most important processes of care are (1) patient selection, (2) performing the procedure, and (3) monitoring the patient. The outcome measures or indicators for these processes are indications, success rates, and complication rates.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Transcatheter treatment of hepatocellular carcinoma with doxorubicin-loaded dc bead (DEBDOX): Technical recommendations

Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

BackgroundWe have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown.MethodsPatients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m2 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen).ResultsForty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively.ConclusionsHAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.

Evaluation of contrast-enhanced color Doppler ultrasound for the quantification of angiogenesis in vivo.

Lassau N, Koscielny S, Opolon P, et al. Evaluation of contrast-enhanced color Doppler ultrasound for the quantification of angiogenesis in vivo. Invest Radiol 2001;36:50–55. rationale and objectives.To evaluate contrast-enhanced color Doppler ultrasonography (CDUS) aimed at quantifying angiogenesis in vivo. methods.Eight colon tumors xenografted into mice were studied with CDUS both without and after injection of SHU 508A. The number of intratumor vessels and pedicles visualized with CDUS and the value of the acoustic intensity quantified by computer were compared with the evaluation of angiogenesis by study of digitized histological slides. results.SHU 508A increased the number of intratumor vessels and pedicles depicted by CDUS, which could also be quantified by acoustic intensity. The comparison of CDUS and digitized histological slide studies showed that the detection threshold after SHU 508A administration allowed visualization of small vessels (40 &mgr;m in diameter). The “hot spots” seen on histology were superimposable onto vessels seen with CDUS. Regions in which no vessels were detected by CDUS corresponded to regions in which vascularization was absent by histological analysis. conclusion.Injection of SHU 508A significantly increased vessel detection with CDUS.