COLLISION Course
By Lauren Swisher
Radiology Today
Vol. 25 No. 7 P. 22

The COLLISION trial sets a new standard for colorectal liver metastases treatment.

Thermal ablation has been in use for decades but is only recently being considered as a standard treatment for certain cancers. “Thermal ablation treatments are actually being performed quite a lot across the globe at present via the skin (percutaneous), laparoscopic, or via open surgery,” says Brad Wood, MD, director of the National Institutes of Health Center for Interventional Oncology.

“Thermal ablation involves radiofrequency ablation, although it’s come to be incorporated with cryonic ablation, microwave ablation, irreversible electroporation, pulsed electrical fields, focused ultrasound, histotripsy, and [high-intensity focused ultrasound],” he adds.

Focused ultrasound was first studied in the 1940s as a noninvasive way to apply ultrasound. Soon after, radiofrequency ablation began to be used to treat trigeminal neuralgia through the application of radio waves and electricity at an alternating current. It was introduced as a tumor ablation method in the 1990s. Within a short time, radiofrequency ablation evolved into microwave ablation.

Wood describes these procedures as image-guided, minimally invasive applications of probes or needles to locally destroy cancerous tissues with the goal of preventing local recurrence. Ablation procedures may also be used for pain control, debulking, or in combination with other treatments. It is important to note that treatment decisions are best made as part of a multidisciplinary cancer team, and ablation can be applied to various tumor types and clinical stages.

“The 2024 National Comprehensive Cancer Network includes thermal ablation as a treatment option for select surgical candidates that can be treated with adequate margins, provided that all visible disease is treated by either ablation alone or in combination with resection,” says Robert J. Lewandowski, MD, FSIR, president of the Society of Interventional Radiology.

Biological Modulation
Notably, the complementary effects of ablation are now being studied, such as the effect of ablation when combined with immunotherapy, chemoembolization, or checkpoint inhibitors. There are many ways to apply energy locally with minimally invasive, image-guided therapy. Several recent trials and studies have suggested that thermal ablation can induce a therapeutically effective systemic antitumor response, also known as the abscopal effect.

Wood says biology is modulated whenever minimally invasive, image-guided therapy is applied. “You have the opportunity to potentially augment or modulate the immune response with some local therapies. It’s one of the real advances in cancer therapy in the last number of decades,” Wood says on the topic of immunomodulation studies. For example, checkpoint inhibitors are a type of immunomodulator. They are one of the first in their category to receive clinical approval for primary liver cancers.

Colorectal cancer is the second most common cause of cancer-related death and the third most common malignancy worldwide. Half of patients with colorectal cancer will develop colorectal liver metastases. Radiofrequency ablation and microwave ablation have quickly demonstrated high-level evidence promoting them into clinical guidelines for the treatment of unresectable liver tumors.

However, radiofrequency ablation has significant drawbacks when treating cancerous tumors in the liver or in other highly perfused organs. It can cause heat injury in the surrounding ablated area, or heat can be lost due to flowing blood, also known as the heatsink effect. Microwave ablation has a lower incidence of the heat-sink effect due to its broader power density and zone of distribution. It is known to be effective when used on organs or tissues with high percentages of water and has improved performance near blood vessels.

COLLISION Trial
The COLLISION trial is a Phase 3, noninferiority, randomized controlled trial comparing traditional surgery with thermal ablation. It is the first trial to address a growing need previously suggested by various professionals. According to the study, patients with colorectal liver metastases could only be cured of their cancer through surgical resection. However, what is considered resectable varies from center to center and lacks a clear definition.

The trial was conducted by a team at Amsterdam University Medical Center, led by Martijn Ruben Meijerink, MD, PhD, in collaboration with the Dutch Colorectal Cancer Group. It has also been endorsed by Dutch national societies for IR, radiology, surgery, and the liver surgery working group. The trial specifically examined patients aged 18 and older with untreated colorectal cancer, metastases up to 3 cm in size confined to the liver, and who were eligible for either surgical resection or ablation across 14 centers in the Netherlands, Belgium, and Italy. Patients were put into low, intermediate, and high disease burden subgroups and then randomly assigned to undergo either surgical resection or thermal ablation. The trial stopped at halftime after meeting predefined goals.

One of the more recent challenges with thermal ablation comes with the standardization of the process. It needs to be reproduced in different settings while managing variability. “There may be variabilities in how things are done. Especially if you’re doing composite ablations with multiple needles and you have to place them manually,” Wood notes. Without standardization or technological advances in minimally invasive care, cases with complexity, anatomical challenges, or high-risk profiles and a high number of targets would require an expert. Standardization lowers the experience threshold for the treatment team and allows more practitioners who have the necessary technology and training to deliver viable treatments.

Promising Results
The traditional method of treating colorectal liver metastases, surgical resection, removes tumors with a scalpel or a laparoscopic approach. Surgical resection of metastases has long been considered the standard treatment for these patients. However, surgical tumor removal is invasive and subjects patients to high hospitalization rates, lengthy recoveries, cost complications, and the associated morbidity and/or mortality of surgery.

The COLLISION trial is of significant importance because the results may change the gold standard for tumor removal. The trial demonstrated that thermal ablation offers comparable overall survival rates but with fewer complications, shorter hospital stays, and lower recurrence rates than the traditional surgical approach.

“What this study beautifully does is it separates out the approaches in a randomized fashion across a wide range of operators, centers, and health care systems. Health care systems let you try to answer the question, ‘What are the pros and cons of two different approaches in a controlled fashion?’” Wood says. “This trial arms the physician, surgeon, and most importantly, the patient with valuable, high-level evidence.”

The COLLISION trial is currently under peer review. “We hope the full data are published soon so we can operationalize this treatment in the field, move the standard of care forward, and give patients new hope for not just treatment but recovery,” Lewandowski says.

— Lauren Swisher is an editorial intern and freelance writer at Great Valley Publishing.