A session at the World Conference on Interventional Oncology (WCIO; 8–11 June, Boston, USA), organised by the Society of Interventional Oncology (SIO), identified the most influential publications of 2016–17. The session was moderated by Muneeb Ahmed (Beth Israel Deaconess Medical Center, Boston, USA) and David C Madoff (Weill Cornell Medical Center, New York, USA).
The PREMIERE trial (chemoembolization vs. radioembolization for primary liver cancer); PANFIRE study (feasibility of irreversible electroporation to treat pancreatic neoplasms); and a study of ablation in combination with Tremelimumab for advanced hepatocellular carcinoma were among the top picks from research published in the last year.
Commencing, Riad Salem (Northwestern University, Chicago, USA) reported on the findings from the study PREMIERE (Prospective randomised study of chemoembolization vs. radioembolization for the treatment of hepatocellular carcinoma) trial. The study was published in December 2016 in Gastroenterology. The randomised, phase II study set out to compare the effects of conventional transarterial chemoembolization (cTACE) and Y-90 radioembolization in patients with hepatocellular carcinoma.
“In this study of patients classified as Barcelona clinic liver cancer (BCLC) stages A or B, we found Y-90 radioembolization provided significantly longer time to progression than cTACE. Y-90 radioembolization provides better tumour control and could reduce drop-out from transplant waitlists,” Salem said.
He told WCIO delegates: “Level one evidence shows that Y-90 treatment outperforms cTACE with regard to time to progression. This is a timely finding given the new mandatory six-month wait time prior to transplantation. Y-90 should be considered in the bridge-to-transplantation patient population using the segmentectomy technique. The findings of this study confirm our rationale for Y-90 as our institutional standard of care.”
Immune checkpoint inhibitors and ablation
Then, Tim Greten (National Cancer Institute, Bethesda, USA) spoke on the paper “Tremelimumab, an immune checkpoint inhibitor in combination with ablation in patients with advanced hepatocellular carcinoma” that was published in the Journal of Hepatology in March 2017.
The researchers set out to ascertain whether Tremelimumab could be combined safely and feasibly with ablation. As reported in the journal, Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Findings from the study led the authors to conclude that Tremelimumab in combination with tumour ablation is a potential new treatment for patients with advanced hepatocellular carcinoma, and leads to the accumulation of intratumoural CD8+ T cells.
Greten said: “The combination of tumour ablation and anti-CTLA-4 therapy is feasible and the treatment is safe. Immune correlates suggest an activation of tumour virus-specific immune responses. Anti-CTLA-4 therapy leads to infiltration of CD8+ T cells in the tumour of the responding patients.”
Next under the lens was a study that used ablation to treat pancreatic cancer, with Martijn R Meijerink (VU University Medical Center, Amsterdam, The Netherlands) presenting on a phase I/II study that treated patients with percutaneous irreversible electroporation. Published in Radiology in February 2017, this study investigated the safety of irreversible electroporation in the treatment of locally advanced pancreatic cancer. It also set out to evaluate the quality of life, pain perception, and efficacy in terms of time to local progression, event-free survival, and overall survival.
The investigators concluded that percutaneous irreversible electroporation for locally advanced pancreatic cancer is generally well tolerated, “although major adverse events can occur”. “Preliminary survival data are encouraging and support the set-up of larger phase II and III clinical trials to assess the efficacy of irreversible electroporation plus chemotherapy in the neoadjuvant and adjuvant or second-line setting compared with more widely adopted regimens such as chemotherapy and/or radiation therapy,” they write.
“There is promising survival, especially if neo-adjuvant folforinox can evoke a specific immune response,” said Meijerink. He also alluded to the fact that percutaneous irreversible electroporation is a difficult procedure with a long learning curve. “Further, there is no uniform protocol and there are no comparative studies as yet,” he added.
Local and systemic effects of irreversible electroporation vs. radiofrequency ablation
In the final presentation, Muneeb Ahmed reported on the periablational and systemic effects of two mechanistically different types of ablation: thermal radiofrequency ablation and electroporative ablation with irreversible electroporation in appropriately selected animal models. The study was published in August 2016 in Radiology.
Introducing the topic, Ahmed said: “Thermal ablation (radiofrequency and microwave) is used to treat solid tumours in the liver, lung, kidney and other organs. Complete ablation requires treating a rim of normal parenchyma in all cases, ie. an ablative margin. Recent experimental and clinical evidence suggests that thermal ablation may also [elicit] distant tumour growth. Potential secondary systemic effects from ablation are not completely understood.”
The study set out to compare radiofrequency ablation and irreversible electroporation on periablational changes after ablation; cytokine and growth factor production; and distant tumour growth in two animal models.
The results of the study found there were differences in tissue injury patterns between the two ablative modalities, with vascular patency persisting within the electroporation zone. The post-ablation inflammatory cell response was also different with more robust wound healing seen with irreversible electroporation. The latter modality also resulted in higher systemic release of IL-6. Compared to radiofrequency ablation, hepatic irreversible electroporation stimulated growth of tumours in one specific animal model and also led to growth reduction in distant tumours in another.
Ahmed and colleagues noted that persistent patency of vasculature within the coagulated zone from irreversible electroporation increases the area and accumulation of infiltrative cells that is associated with a higher serum IL-6 level than radiofrequency ablation. These local changes of irreversible electroporation induce stronger systemic effects, including both tumorigenic and immunogenic effects.