Key topics related to intrahepatic cholangiocarcinoma (CCA) were presented at the 2021 Society of Interventional Oncology (SIO) and the Society of Interventional Radiology (SIR) meetings and were discussed during the CCA Summit. Bruno C. Odisio, MD, FSIR, Interventional Radiologist and Co-Director of Research, Department of Interventional Radiology, M.D. Anderson Cancer Center, Houston, TX, reviewed the significance of these findings.
“One common theme that we can see between those 2 meetings is that there is an increased number of research topics on CCA,” Dr Odisio said. “I believe these are reflections of our challenges and demands in clinical practice and the current need to further understand the role of interventional radiology in the management of patients with cholangiocarcinoma.”
The overarching theme of the 6 topics discussed here is the fundamental and growing role that interventional radiology plays in the multidisciplinary care of patients with intrahepatic CCA.
Transperitoneal biopsy for pathological diagnosis can help optimize treatment selection but remains controversial because of the risk for peritoneal metastasis. At the 2021 SIO meeting, Matthew T. Quirk, MD, Assistant Professor of Radiology, University of California, Los Angeles, Calabasas, reviewed the study titled “Transperitoneal Biopsy for Cholangiocarcinoma Is Not Associated with Increased Risk of Peritoneal Metastasis.”
This single-center retrospective analysis included 90 patients with intrahepatic or hilar CCA diagnosed between 2001 and 2017. Among these 90 patients, 57 patients had transperitoneal liver biopsy and 37 did not. Those who had transperitoneal biopsy were more likely to be women and had a significantly larger tumor than those who did not have such biopsy (mean, 6.7 cm vs 3.2 cm; P = .0001).
The incidence of peritoneal metastasis was 21.1% after a transperitoneal biopsy versus 33.3% in patients who did not have a transperitoneal biopsy, a nonsignificant difference (odds ratio, 0.56). Similarly, the incidence of peritoneal metastasis in patients who received percutaneous needle biopsy was 22.7% versus 33.3% in those who did not (odds ratio, 0.59).
Based on these findings, neither preoperative percutaneous needle biopsy nor any form of transperitoneal biopsy increased the risk for peritoneal metastases, Dr Quirk noted.
“This is important information for our clinical practice, because we know that more and more, we need to biopsy patients with CCA, since genetic alterations understanding increasingly are necessary for further management of those patients,” Dr Odisio observed.
Percutaneous microwave ablation is a minimally invasive procedure used in the treatment of metastasis to the liver in patients with hepatocellular carcinoma or colorectal cancer.
At the 2021 SIO meeting, Gaby E. Gabriel, MD, Assistant Professor of Radiology and Surgery, University of Kentucky College of Medicine, Lexington, discussed the results of “Microwave Ablation of Intrahepatic Cholangiocarcinoma: A Single Institutional Cohort,” which was conducted at the University of Kentucky College of Medicine.
This retrospective analysis was based on safety and efficacy data for 11 patients with intrahepatic CCA who had hepatic microwave ablation of 30 tumors over 6 years. All the procedures were performed with the guidance of computed tomography.
Overall, 9% of the 11 patients had well-differentiated tumors, 27% moderately differentiated, 9% poorly differentiated, and 55% were unknown. Almost half (45%) of the patients had stage T1a CCA, 18% had stage 1b disease, and 36% had stage T2b disease. In all, 73% of the patients received neoadjuvant or adjuvant chemotherapy.
The completed tumor ablation rate was 89.9% (N = 26) versus 12.9% (N = 4) of tumors that were not completely ablated with this technology. All patients were discharged the next day.
“The investigators demonstrated the ability to provide local tumor control in approximately 90% of the tumors that were ablated, [which is] further evidence that doing thermal ablation is safe and effective in properly selected patients,” Dr Odisio said. “I think this should be part of the armamentarium on the multidisciplinary care on the measurement of patients who have intrahepatic CCA.”
These results show that this procedure is feasible and safe in early-stage intrahepatic CCA, Dr Gabriel noted, adding that a larger, long-term study is warranted.
Transarterial radioembolization (TARE) is one of the treatment options used in patients with intrahepatic CCA. At the 2021 SIO meeting, experts from the Department of Radiology, Neuroradiology and Minimal-Invasive Therapy, Klinikum Bogenhausen, München, Germany, reviewed real-world outcomes from the Cardiovascular and Interventional Radiological Society of Europe Registry for SIR-Spheres Therapy (CIRT) study, titled “Real-World Outcomes of Patients with Intrahepatic Cholangiocarcinoma Treated with Trans-Arterial Radioembolization: Results from CIRT, a Large European Prospective Multi-Centre Observational Study.”
CIRT is the first European prospective multicenter observational study that evaluated the outcomes of 120 patients from 18 European sites who received TARE using yttrium-90 (Y-90) resin microspheres. Overall, 39.1% of the patients received first-line Y-90 therapy and 27.4% received second-line Y-90 therapy. In 69.2% of patients, the treatment intention was palliative, and tumor downstaging was the intention in 20.8% of the patients.
At the time of the analysis, the median overall survival (OS) was 14.7 months, the median progression-free survival (PFS) was 5.7 months, and the median hepatic PFS was 6.2 months. The mean global health status using the Quality of Life Questionnaire-30 was 59.3 at baseline, which decreased to 56 by 6 months. After 12 months, the mean global health status improved to 63.
“Notably, radiation induced liver disease was only recorded in 1.7% of those patients,” said Dr Odisio. “Radiation induced liver disease is a common concern when we do Y-90 radioembolization for those patients. Based on this prospective registry, we see that such incidents are relatively low.”
Grade 3 or 4 adverse events occurred in 10.8% of the patients. The investigators noted that in the real-world setting, TARE with Y-90 resin that is used early is a safe treatment, with no meaningful deterioration of quality of life.
“This is relevant information for our clinical practice, since many times patients with intrahepatic CCA are candidates for transarterial radioembolization,” Dr Odisio said. “A common concern is that the potential additive effects of systemic chemotherapy and radiation therapy could create worsening of overall health status. Based on these data, we can see that applying Y-90 for those patients seems to be relatively safe,” he concluded.
Recent studies of molecular profiling reveal a clear pattern of somatic mutations in patients with intrahepatic CCA. Dr Odisio reviewed a study titled “A Multi-Institutional Investigation of Image-Guided Percutaneous Ablation for Intrahepatic Cholangiocarcinoma: Outcomes Analysis and Impact of Molecular Profiling.”
The results of the study were presented at the 2021 SIR meeting; Dr Odisio participated in this study, together with Milind M. Javle, MD, and other experts from M.D. Anderson Cancer Center, Houston, TX, in conjunction with researchers at the University of Turin in Italy.
“Our motivation to evaluate the role of liver ablation is the limited data on efficacy and safety of percutaneous ablation in this patient population, given the unfortunately advanced tumor burden at the diagnosis of this disease,” Dr Odisio said. “We’d like to see if there is any interplay between local therapy outcomes, specifically liver ablation, and genetic alterations,” he added.
The study included 46 patients with intrahepatic CCA who had a total of 69 percutaneous ablation events between 2007 and 2019, including 25 radiofrequency ablations; 39 microwave ablations; and 5 irreversible electroporation procedures. The median tumor size of the cohort was 1.7 cm. Of the 46 patients, 29 patients had recurrence post–liver resection.
At a mean follow-up of 26 months, local tumor progression (local recurrence at the site of ablation) was 18.5%. The mean OS from the time of ablation was 34.4 months, and the median intrahepatic PFS was 6 months.
“The 3-year local tumor PFS was 71.5%, which means that most of those patients who undergo liver ablation tend to recur with new tumors on their liver, not necessarily with recurrence at the tumors that we ablated,” said Dr Odisio.
The mean OS was 47.1 months for the entire cohort, and 28.8 months for those with poor prognosis. Major adverse events occurred in 1 patient, Dr Odisio said, “who had a liver abscess after percutaneous liver ablation,” which was successfully treated. No deaths were reported with liver ablation.
Of the 18 patients who had next-generation sequencing (NGS), or molecular profiling, 13 (72%) had molecular mutations, including 6 (33%) patients with poor-prognosis mutations; of these, 3 had FGFR alterations. A subanalysis of patients who had NGS did not reveal differences in the median OS and local tumor PFS between those with and without poor-prognosis mutations, he noted.
“Our conclusion is that ablation is a safe and effective local therapy for patients with intrahepatic CCA,” Dr Odisio said. “We still need further understanding of the interplay between genetic alterations and ablation outcomes. Based on these limited analyses we have done so far, ablation seems to be a very effective local therapy for patients with CCA, especially among patients who present with post–resection recurrence. It slows local recurrence rates.”
“Our ability to provide ablation and rescue those patients at a time of tumor recurrence is a relevant piece of information for clinical practice,” Dr Odisio concluded.
Finally, Dr Odisio discussed 2 studies that were presented at the 2021 SIR meeting concerning the use of Y-90 resin radioembolization in patients with intrahepatic CCA.
The first study was titled “Post-Surgical Outcomes for Patients with Intrahepatic Cholangiocarcinoma Treated with Neoadjuvant Resin Yttrium-90 Radioembolization Using MIRD Dosimetry,” and was presented by Michael W. Subrize, MD, Interventional Radiology Resident, Beth Israel Deaconess Medical Center, Boston, MA.
This single-center retrospective analysis included 20 years of data, identifying 36 patients who underwent intrahepatic CCA resection, with a median follow-up of 17 months. There was a significant difference in baseline median tumor size between patients who had received Y-90 before resection and those who did not (8 cm vs 4 cm). Y-90 radioembolization was performed in a segmental fashion on 58% of patients and in a lobar fashion on 42% of patients.
“An interesting point of this study is that the MIRD method was applied in 11 of the 12 patients submitted to Y-90,” said Dr Odisio. “The body surface area model, which is more like the classic model for Y-90, was applied in just 1 patient.” The median absorbed dose to target tumors was 139 Gy (range, 122-164 Gy).
The tumor recurrence rate after resection was significantly lower in patients who received neoadjuvant Y-90 therapy versus those who had resection without neoadjuvant Y-90 (33% vs 75%, respectively). Although not a significant difference, negative margins (R0) were more common in patients who had neoadjuvant Y-90 therapy than in patients who had surgery alone (75% vs 46%), and the median time to recurrence was 22 months versus 16 months, respectively.
The median OS was 52 months in patients who received Y-90 versus 39 months in those who did not receive Y-90, and the 2-year OS rate was 75% versus 54%, respectively. These trends are worthwhile to investigate further, said Dr Odisio.
“The clinical relevance of this study is that Y-90 seems, at least based on these retrospective data, to provide a long term benefit, if it’s applied in a neoadjuvant setting before resection on patients with intrahepatic CCA,” he concluded.
The second study was “Yttrium-90 Radioembolization in Unresectable Intrahepatic Cholangiocarcinoma: A 17-Year Single-Institution Study.” The results were presented at the SIR meeting by Aakash N. Gupta, BS, Medical Student, Northwestern University, Chicago, IL, and then reviewed by Dr Odisio.
More than 50% of patients with intrahepatic CCA undergo resection by the time of their diagnosis, Dr Odisio said. The median OS in patients who do not receive systemic treatment is usually as low as 6 months compared with approximately 15 months in patients who receive chemotherapy with the standard gemcitabine plus cisplatin regimen.
In this single-center study, the investigators evaluated the safety, efficacy, and survival with Y-90 therapy in 136 patients with advanced, unresectable intrahepatic CCA. Overall, 36% of the patients had extrahepatic CCA, and 40% of the patients had vascular involvement. In all, 56 (40.6%) received previous systemic chemotherapy.
A complete or partial radiologic response was achieved in 37% of the patients, and 8% of the patients were downstaged to resection after receiving Y-90 treatment, which resulted in a postresection OS rate of 41.8 months.
The median OS after Y-90 therapy for the entire cohort was 14.2 months. On multivariate analysis, variables that had a positive impact on survival were a solitary tumor, a lack of vascular involvement, and an increased baseline serum albumin. The use of previous systemic chemotherapy was not a variable that altered survival.
The safety profile was acceptable. Grade 3 or 4 adverse events within 3 months were recorded in 12% of patients.
We must learn more about the optimal timing between Y-90 therapy and systemic chemotherapy in this patient population, and how contemporary Y-90 dosimetry methods, such as the partition method, would potentially affect outcomes, Dr Odisio observed.
“We hope that further refinement and synergies between our local and systemic therapies, combined with the understanding of the genetic alterations of patients with intrahepatic CCAs, will improve even more the prospects of the patients with this challenging disease,” Dr Odisio concluded.
