Jean-Nicolas Vauthey

Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome

This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection.

Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer

AbstractBackground: The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases. Methods: Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded. Results: Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months’ median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease. Conclusions:RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.

Development of a Research Agenda for the Management of Metastatic Colorectal Cancer: Proceedings from a Multidisciplinary Research Consensus Panel

Colorectal cancer (CRC), the second leading cause of cancer death in the United States, occurs in an estimated more than 145,000 patients annually, with almost 50,000 deaths each year. Metastatic liver disease is the cause of death in the majority of them (1,2). Liver-only metastases affect up to one half of patients with CRC (1,2), with approximately 15% (range, 8%–26%) presenting synchronously (3,4) and an additional 15% found metachronously during the next 5 years (3). Colorectal liver metastases (CLMs) are resectable in 20%–25% of patients only; some of the remaining 75%–80% may benefit from “downsizing” therapy, which can result in 10%–20% more patients becoming resectable. Overall survival rates in patients with either primarily or secondarily resectable CLMs can be as high as 58% at 5 years and 15% at 10 years (5,6). Current front-line treatments available to improve downsizing and resectability include systemic therapies (chemotherapy with or without bevacizumab or cetuximab) and pre-operative portal vein embolization (PVE). Other approaches include local ablation therapies, regional intraarterial therapies with embolization (transcatheter arterial chemoembolization, or radio-embolization by selective internal radiation therapy with Yttrium 90-loaded microspheres) or infusion (ie, hepatic arterial infusion [HAI] pump chemotherapy), and external beam radiation therapy (RT). The role of these liver-targeted therapies to promote conversion from unresectable to resectable liver disease remains an evaluation in progress. For the majority of patients with unresectable CRC liver metastases, standard of care is first- and second-line triplet chemotherapy, which is associated with a median survival of 18–24 months (7–10). Multiple single-institution retrospective reports suggest the potential for improvement in survival time by the addition of liver-directed therapies such as chemoembolization, HAI, or radioembolization. This has not been prospectively evaluated in controlled trials, but could potentially represent a major development in Interventional Oncology (IO). The Society of Interventional Radiology (SIR) Foundation has identified the management of metastatic CRC (mCRC) as an emerging inter-ventional radiologic research priority and convened a Research Consensus Panel (RCP) Meeting on October 3, 2011 to establish a prioritized research agenda. This article reports the proceedings from this meeting.

The Prognostic Impact of KRAS Mutation in Patients Having Curative Resection of Synchronous Colorectal Liver Metastases

Backgroundm-KRAS has been recently reported to be a significant prognostic factor in patients undergoing resection of colorectal liver metastases. This is due to the lack of response to monoclonal epithelial growth factor receptor antibodies, and potentially as a result of a more aggressive tumor biology.MethodsThe National Cancer Database was queried to identify patients with known KRAS status presenting with colorectal cancer and liver metastases who underwent resection of the primary tumor and metastatic disease between 2010 and 2015.ResultsA total of 2655 patients were identified of which 1116 (42%) had m-KRAS. Tumor size, lymph node involvement rates, and margin status of the primary tumor were similar between patients with m-KRAS and wild-type KRAS (wt-KRAS). In the multivariable analysis, African-American race and right-sided colon cancers were independently associated with m-KRAS (both p < 0.001). m-KRAS patients had a significantly lower overall survival (OS) than those with wt-KRAS, with a 3- and 5-year OS of 51 vs. 64% and 31 vs. 42%, respectively (p < 0.001). After adjustment for available prognostic confounders, factors independently associated with worse OS were increasing age, receipt of monoagent chemotherapy, tumor size, positive lymph node, and resection margin status of the primary tumor, right-sided cancers, and m-KRAS.Conclusionsm-KRAS is associated with worse OS in patients presenting with colorectal cancer and liver metastases undergoing resection of the primary tumor and metastatic disease. Right-sided lesions and African-American race were associated with m-KRAS. However, while right-sided remained an independent prognostic factor for OS, race did not.