Faculty Bibliography

OPINION STATEMENT: In the setting of liver metastases from colorectal cancer (CRC), radioembolization with yttrium-90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. SIRFLOX is an ongoing, multi-center, phase 3 randomized trial comparing first-line chemotherapy alone or in combination with yttrium-90 radioembolization in patients with CRC who have isolated liver metastases or liver-dominant metastases. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall progression-free survival (PFS) between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 versus 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 versus 12.6 months; p = 0.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Since radioembolization targets liver disease, it is plausible that the trial failed to achieve an improvement in PFS given that 40 % of the SIRFLOX population had extra-hepatic disease. It is also possible that the overall median PFS may be a poor surrogate endpoint, and other endpoints like overall survival still needs to be delineated in this setting. In addition, it is crucial to document improvement or delay in time to deterioration in quality of life symptom endpoints in this population. SIRFLOX is the first of three prospective studies that assess the efficacy of adding radioembolization to first-line chemotherapy, and the combined data from these trials will provide the necessary power for an overall survival analysis. The final results of SIRFLOX will be eagerly awaited to determine if the increased hepatic PFS in preliminary data will translate to increased overall survival benefit.

Portal vein thrombosis (PVT) is common in cirrhotic patients and presents a challenge at the time of transplant. Owing to the increased posttransplant morbidity and mortality associated with complete PVT, the presence of PVT is a relative contraindication to liver transplantation at many centers. Our group began performing portal vein (PV) recanalization and transjugular intrahepatic portostystemic shunt placement (PVR-TIPS) several years ago to optimize the transplant candidacy of patients with PVT. The procedure has evolved to include transsplenic access to assist with recanalization, which is now our preferred method due to its technical success without significant added morbidity. Here, we describe in detail our approach to PVR-TIPS with a focus on the transsplenic method. The procedure was attempted in 61 patients and was technically successful in 60 patients (98%). After transitioning to transsplenic access to assist with recanalization, the technical success rate has improved to 100%. The recanalized portal vein and TIPS have maintained patency during follow-up, or to the time of transplant, in 55 patients (92%) with a mean follow-up of 16.7 months. In total, 23 patients (38%) have undergone transplant, all of whom received a physiologic anastomosis (end-to-end anastomosis in 22 of 23 patients, 96%). PVR-TIPS placement should be considered as an option for patients with chronic PVT in need of transplantation. Transsplenic access makes the procedure technically straightforward and should be considered as the primary method for recanalization.

Recurrent deep venous thrombosis and inferior vena cava (IVC) thrombosis are well-described complications following IVC filter placement. IVC thrombosis ranges in severity of clinical presentation, but can lead to significant morbidity and mortality with incidence rates depending on patient population and type of filter used. Endovascular therapies such as catheter-directed thrombolysis, mechanical thrombectomy, balloon venoplasty, and stenting are safe and effective in restoration of venous patency.

PURPOSE: To assess the feasibility of conducting pretreatment mesenteric angiography, coil embolization, 99mTc macroaggregated albumin (99mTc-MAA) scintigraphy, and 90Y radioembolization treatment in a single, same-day, combined outpatient encounter. METHODS: This was a retrospective study of 78 patients treated during the period 2008 - 2015 who were managed in a single outpatient encounter under the guidance of the Interventional Radiology Department and The Nuclear Medicine Department. Pretreatment planning was performed by reviewing baseline imaging and estimated perfused liver volume bearing the tumor. The region of interest was estimated using 3-D software; this value was used for dosimetry planning. Maximum lung shunting fractions of 10 % for hepatocellular carcinoma and 5 % for liver metastases were assumed. Subsequently, hepatic angiography and 99mTc-MAA scintigraphy were performed followed by 90Y treatment in one outpatient encounter. Total in-room procedure time was recorded. RESULTS: All patients underwent same-day angiography, 99mTc-MAA scintigraphy and 90Y radioembolization. Of the 78 patients, 16 received multiple segmental treatments to both lobes, 44 received treatment to the right lobe, and 18 received treatment to the left lobe. The median dose was 106 Gy. The median number of 90Y vials needed was two (range one to six). The median in-room time was 160 min (75 - 250 min). The residential status of the patients was as follows, 18 % (14/78) were local residents, 55 % (43/78) traveled from outside the city limits, 18 % (14/78) were from out-of-state, and 9 % (7/78) were resident abroad. Of the 78 patients, 61 (77 %) had hepatocellular carcinoma, and 17 (22 %) had liver metastases. The median lung dose was 3.5 Gy. CONCLUSION: This study demonstrated the feasibility of same-day 90Y evaluation and treatment while maintaining the principles of safe and effective 90Y infusion including tumoricidal dosimetry (lobar, segmentectomy), minimization of nontarget flow, and minimization of lung dose. This paradigm translates into expeditious cancer care and significant cost savings.

PURPOSE: To determine the efficacy of single- versus triple-drug chemoembolization for the treatment of hepatocellular carcinoma, as measured by toxicity, tumor response, time to progression (TTP), and overall survival (OS). MATERIALS AND METHODS: A single-center retrospective review was performed on 337 patients who underwent chemoembolization over a 14-year period; 172 patients underwent triple-drug conventional transarterial chemoembolization, and 165 patients underwent single-agent doxorubicin chemoembolization. Imaging characteristics and clinical follow-up after conventional transarterial chemoembolization were evaluated to determine TTP. Imaging response was determined per World Health Organization and European Association for the Study of Liver criteria. OS from time of first chemoembolization was calculated. RESULTS: Median TTP was similar between groups: 7.9 months (95% confidence interval [CI], 7.1-9.4) and 6.8 months (95% CI, 4.6-8.6) for triple- and single-drug regimens, respectively (P > .05). For single-agent conventional transarterial chemoembolization, median OS varied significantly by Barcelona Clinic for Liver Cancer (BCLC) stage: A, 40.8 months; B, 36.4 months; C, 10.9 months (P < .01). Median OS for triple-drug therapy also varied significantly by BCLC: A, 28.9 months; B, 18.1 months; C, 9.0 months (P < .01). Single-drug conventional transarterial chemoembolization demonstrated longer median OS compared with triple-drug therapy (P < .05) for BCLC A/B patients. CONCLUSIONS: Single-agent chemoembolization with doxorubicin and ethiodized oil demonstrates acceptable efficacy as measured by TTP and OS. Results compare favorably with traditional triple-drug therapy.

BACKGROUND & AIMS: Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. METHODS: From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. RESULTS: Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99). CONCLUSIONS: In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.

PURPOSE: Radioembolization with (90)Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of (90)Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe (90)Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma +/- tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. METHODS: Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with (90)Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. RESULTS: Ninety-seven patients successfully underwent left hepatic lobe (90)Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 +/- 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 +/- 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 +/- 41 Gy. There were no reportable or recordable medical events. Of the patients, 34% reported abdominal pain that was grade 1-2; 65% of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. CONCLUSION: Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass microspheres.

Hepatocellular carcinoma can be treated using minimally invasive, image-guided, catheter-based or percutaneous techniques. Such procedures offer compelling clinical outcomes with a favorable side-effect profile in a population of patients who are poor candidates for surgical or systemic treatment. This article discusses key data regarding the effectiveness of locoregional therapies in treating these patients. Disease-specific treatment is discussed in the context of hepatocellular carcinoma, with additional data discussed in the context of transplantation. As rapid innovation occurs in the realm of oncology, interventional oncology represents a safe, effective alternative that continues to generate impressive data that could potentially change treatment paradigms.