Michael Vouche

Radiation lobectomy: Time-dependent analysis of future liver remnant volume in unresectable liver cancer as a bridge to resection

BACKGROUND & AIMS Portal vein embolization (PVE) is a standard technique for patients not amenable to liver resection due to small future liver remnant ratio (FLR). Radiation lobectomy (RL) with (90)Y-loaded microspheres (Y90) is hypothesized to induce comparable volumetric changes in liver lobes, while potentially controlling the liver tumor and limiting tumor progression in the untreated lobe. We aimed at testing this concept by performing a comprehensive time-dependent analysis of liver volumes following radioembolization. METHODS 83 patients with right unilobar disease with hepatocellular carcinoma (HCC; N=67), cholangiocarcinoma (CC; N=8) or colorectal cancer (CRC; N=8) were treated by Y90 RL. The total liver volume, lobar (parenchymal) and tumor volumes, FLR and percentage of FLR hypertrophy from baseline (%FLR hypertrophy) were assessed on pre- and post-Y90 CT/MRI scans in a dynamic fashion. RESULTS Right lobe atrophy (p=0.003), left lobe hypertrophy (p<0.001), and FLR hypertrophy (p<0.001) were observed 1 month after Y90 and this was consistent at all follow-up time points. Median %FLR hypertrophy reached 45% (5-186) after 9 months (p<0.001). The median maximal %FLR hypertrophy was 26% (-14 → 86). Portal vein thrombosis was correlated to %FLR hypertrophy (p=0.02). Median Child-Pugh score worsening (6 → 7) was seen at 1 to 3 months (p=0.03) and 3 to 6 months (p=0.05) after treatment. Five patients underwent successful right lobectomy (HCC N=3, CRC N=1, CC N=1) and 6 HCCs were transplanted. CONCLUSIONS Radiation lobectomy by Y90 is a safe and effective technique to hypertrophy the FLR. Volumetric changes are comparable (albeit slightly slower) to PVE while the right lobe tumor is treated synchronously. This novel technique is of particular interest in the bridge-to-resection setting.

Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology-pathology correlation and survival of radiation segmentectomy

Resection and radiofrequency ablation (RFA) are treatment options for hepatocellular carcinoma (HCC) <3 cm; there is interest in expanding the role of ablation to 3‐5 cm. RFA is considered high‐risk when the lesion is in close proximity to critical structures. Combining microcatheter technology and the localized emission properties of Y90, highly selective radioembolization is a possible alternative to RFA in such cases. We assessed the efficacy (response, radiology‐pathology correlation, survival) of radiation segmentectomy in solitary HCC not amenable to RFA or resection. Patients with treatment‐naïve, unresectable, solitary HCC ≤5 cm not amenable to RFA were included in this multicenter study. Administered dose, response rate, time‐to‐progression (modified Response Evaluation Criteria in Solid Tumors [mRECIST]), radiology‐pathology correlation and long‐term survival were assessed. In all, 102 patients were included in this study. mRECIST complete response (CR), partial response (PR), and stable disease (SD) were 47/99 (47%), 39/99 (39%), and 12/99 (12%), respectively. Median time‐to‐disease‐progression was 33.1 months. In all, 33/102 (32%) patients were transplanted with a median (interquartile range [IQR]) time‐to‐transplantation of 6.3 months (3.6‐9.7). Pathology revealed 100% and 50‐99% necrosis in 17/33 (52%) and 16/33 (48%), respectively. Median overall survival was 53.4 months. Univariate analysis demonstrated a survival benefit for Eastern Cooperative Oncology Group (ECOG) 0 patients. In the multivariate model, age <65, ECOG 0, and Child‐Pugh A were characteristics associated with longer survival. Conclusion: Radiation segmentectomy is an effective technique with a favorable risk profile and radiology‐pathology outcomes for solitary HCC ≤5 cm. This approach may allow for treatment of HCC in difficult locations. Since RFA and resection are not options given tumor location, there appears to be a strong rationale for this technique as second choice. (Hepatology 2014;60:192–201)

Radioembolization for hepatocellular carcinoma with portal vein thrombosis: Impact of liver function on systemic treatment options at disease progression

BACKGROUND & AIMS Yttrium-90 ((90)Y) radioembolization is a microembolic procedure. Hence, it is commonly used in hepatocellular carcinoma (HCC) patients with portal venous thrombosis (PVT). We analyzed liver function, imaging findings, and treatment options (local/systemic) at disease progression following (90)Y treatment in HCC patients with PVT. METHODS We treated 291 HCC patients with (90)Y radioembolization. From this cohort, we included patients with liver-only disease, PVT and Child-Pugh (CP) score ≤ 7; this identified 63 patients with HCC and PVT (CP-A:35, CP-B7:27). Liver function, CP status, and imaging findings at progression were determined in order to assess potential candidacy for systemic treatment/clinical trials. Survival, time-to-progression (TTP), and time-to-hepatic decompensation analyses were performed using Kaplan-Meier methodology. RESULTS Of 35 CP-A and 28 CP-B7 patients, 29 and 15 progressed, respectively. Median survival and TTP were 13.8 and 5.6 months in CP-A and 6.5 and 4.9 months in CP-B7 patients, respectively. Of the 29 CP-A patients who progressed, 45% maintained their CP status at progression (55% decompensated to CP-B). Of the 15 CP-B7 patients who progressed, 20% improved to CP-A, 20% maintained their CP score and 60% decompensated. CONCLUSIONS Knowledge of liver function and CP score of HCC with PVT progressing after (90)Y is critically relevant information, as these patients may be considered for systemic therapy/clinical trials. If a strict CP-A status is mandated, our study demonstrated that 64% of cases exhibited inadequate liver function and were ineligible for systemic therapy/clinical trials. An adjuvant approach using local therapy and systemic agents prior to progression should be investigated.

Radiological-pathological analysis of WHO, RECIST, EASL, mRECIST and DWI: Imaging analysis from a prospective randomized trial of Y90 ± sorafenib

The aim of this study was to compare radiological and pathological changes and test the adjunct efficacy of Sorafenib to Y90 as a bridge to transplantation in hepatocellular carcinoma (HCC). 15 patients with 16 HCC lesions were randomized to Y90 without (Group A, n = 9) or with Sorafenib (Group B, n = 7). Size (WHO, RECIST), enhancement (EASL, mRECIST) and diffusion‐weighted imaging criteria (apparent diffusion coefficient, ADC) measurements were obtained at baseline, then at 1 and every 3 months after treatment until transplantation. Percentage necrosis in explanted tumors was correlated with imaging findings. 100%, 50%‐99% and <50% pathological necrosis was observed in 6 (67%), 1 (11%), and 2 (22%) tumors in Group A and 3 (42%), 2 (28%), and 2 (28%) in Group B, respectively (P = 0.81). While ADC (P = 0.46) did not change after treatment, WHO (P = 0.06) and RECIST (P = 0.08) response at 1 month failed to reach significance, but significant responses by EASL (P < 0.01/0.03) and mRECIST (P < 0.01/0.03) at 1 and 3 months were observed. Response was equivalent by EASL or mRECIST. No difference in response rates was observed between groups A and B at 1 and 3 months by WHO, RECIST, EASL, mRECIST or ADC measurements. Despite failing to reach significance, smaller baseline size was associated with complete pathological necrosis (CPN) (RECIST: P = 0.07; WHO: P = 0.05). However, a cut‐off size of 35 mm was predictive of CPN (P = 0.005). CPN could not be predicted by WHO (P = 0.25 and 0.62), RECIST (P = 0.35 and 0.54), EASL (P = 0.49 and 0.46), mRECIST (P = 0.49 and 0.60) or ADC (P = 0.86 and 0.93). Conclusion: The adjunct of Sorafenib did not augment radiological or pathological response to Y90 therapy for HCC. Equivalent significant reduction in enhancement at 1 and 3 months by EASL/mRECIST was noted. Neither EASL nor mRECIST could reliably predict CPN. (HEPATOLOGY 2013;58:1655–1666)

Prospective randomized pilot study of Y90 +/− sorafenib as bridge to transplantation in hepatocellular carcinoma

BACKGROUND & AIMS To investigate the safety and adverse event profile of sorafenib plus radioembolization (Y90) compared to Y90 alone in patients awaiting liver transplantation. METHODS 20 patients with HCC were randomized to Y90 alone (Group A) or Y90+sorafenib (Group B). Adverse events, dose reductions, and peri-transplant complications were assessed. RESULTS All patients in the sorafenib group necessitated dose reductions. Seventeen of 20 patients underwent liver transplantation; median time-to-transplant was 7.8 months (range: 4.2-20.3) and similar between groups (p = 0.35). In the sorafenib group, there were 4/8 peri-transplant (<30 days) biliary complications (p = 0.029) and 3/8 acute rejections (p = 0.082); there were none in the Y90-only group. Survival rates were 70% (Group A) and 72% (Group B) at 3 years (p = 0.57). CONCLUSIONS The addition of sorafenib to Y90 necessitated dose reductions in all patients awaiting transplantation. Preliminary data suggest that the combination was associated with more peri-transplant biliary complications and potentially trended towards more acute rejections. Caution should be exercised when considering sorafenib in the transplant setting. Further investigation is warranted.

Pretransplant Portal Vein Recanalization-Transjugular Intrahepatic Portosystemic Shunt in Patients With Complete Obliterative Portal Vein Thrombosis.

Background Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. Methods Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. Results The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. Conclusions The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.

Portal Vein Recanalization–Transjugular Intrahepatic Portosystemic Shunt Using the Transsplenic Approach to Achieve Transplant Candidacy in Patients with Chronic Portal Vein Thrombosis

PURPOSE To present the transsplenic route as an alternative approach for portal vein recanalization-transjugular portosystemic shunt (PVR-TIPS) for chronic main portal vein thrombosis (PVT) in potential transplant candidates. MATERIALS AND METHODS In 2013-2014, 11 consecutive patients with cirrhosis-induced chronic main PVT underwent transsplenic PVR-TIPS. All patients had been denied listing for transplant because of the presence of main PVT, a relative contraindication in this center. The patients were followed for adverse events. Portal vein patency was assessed at 1 month by splenoportography and every 3 months subsequently by ultrasound or magnetic resonance imaging. After PVR-TIPS, patients were reviewed (and subsequently listed for transplant) at a weekly multidisciplinary conference. RESULTS PVR-TIPS using the transsplenic approach was successful in all 11 patients with no major complications. Median age was 61 years (range, 33-67 y) and 9 of 11 patients (82%) were men. Nonalcoholic steatohepatitis was the leading cause of liver disease in 4 of 11 patients (36%), and hepatitis C was present in 4 of 11 patients (36%). Complete main PVT was found in 8 of 11 patients (73%). Of 11 patients, 4 (36%) had a Model for End-Stage Liver Disease score > 18, and 8 (73%) had a baseline Child-Pugh score of 7-10. Minor adverse events occurred in 2 of 11 patients (fever, encephalopathy). At the end of the procedure, 5 of 11 patients (45%) exhibited some minor remaining thrombus in the portal vein; 3 of the 5 patients (60%) had complete thrombus resolution at 1 month, with the remaining 2 patients having resolution at 3 months (no anticoagulation was needed). Three patients underwent successful liver transplant with end-to-end anastomoses. CONCLUSIONS Transsplenic PVR-TIPS is a potentially safe and effective method to treat PVT and improve transplant candidacy.

Chemoradiation of hepatic malignancies: Prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization

PURPOSE Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ((90)Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of (90)Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. METHODS AND MATERIALS Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver (90)Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after (90)Y infusion. If a DLT was not observed, the (90)Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of (90)Y with full-dose capecitabine. RESULTS Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing (90)Y MTD were not met, indicating an MTD of >170 Gy. CONCLUSION The MTD of (90)Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest (90)Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.

Cancer concepts and principles: Primer for the interventional oncologist - Part i

A sophisticated understanding of the rapidly changing field of oncology, including a broad knowledge of oncologic disease and the therapies available to treat them, is fundamental to the interventional radiologist providing oncologic therapies, and is necessary to affirm interventional oncology as one of the four pillars of cancer care alongside medical, surgical, and radiation oncology. The first part of this review intends to provide a concise overview of the fundamentals of oncologic clinical trials, including trial design, methods to assess therapeutic response, common statistical analyses, and the levels of evidence provided by clinical trials.

Ethanol Embolotherapy of Vascular Malformations: Clinical Outcomes at a Single Center

PURPOSE To retrospectively evaluate the results of endovascular therapy of vascular malformations principally treated with ethanol embolization at a single center. MATERIALS AND METHODS From May 1999 to December 2012, 46 patients (28 female, 18 male) with vascular malformations (31 venous malformations, 15 arteriovenous malformations [AVMs]) throughout the body (nine upper extremity, 31 lower extremity, and six truncal) who underwent ethanol embolization were studied and followed up. Demographic factors, clinical findings, imaging data, and patient-reported changes in symptoms were collected and analyzed. Follow-up data were obtained by office visits, repeat imaging, and telephone contact. RESULTS Twenty-four patients (52.2%) were considered cured, 12 (26.1%) showed improvement, and 10 (21.7%) had no change or showed worsening. Similar rates of cure or improvement were seen for AVMs and venous malformations (P = 0.67). Lesion location, depth, and size were not associated with differences in outcomes (P = .87, P = .37, and P = .61, respectively). Type 1 and type 2 AVMs were cured more often than other AVM types. The overall complication rate was 24% (11 of 46 patients). Minor complications were seen in six individuals (13%), and major complications developed in five patients (11%). CONCLUSIONS Ethanol embolization of vascular malformations produces good outcomes, with control or relief of symptoms in a majority of patients.