Embracing Hepatic Artery Infusion Therapy for My Patients with Colorectal Cancer Liver Metastases

We recently incorporated Hepatic Artery Infusion (HAI) therapy into our oncology practice at Ochsner MD Anderson Cancer Center. Although HAI has been utilized since the early 90s, treatment protocols and patient selection have improved markedly since the therapy’s introduction. Those refinements, along with consistent data demonstrating a positive impact on patient outcomes, have spurred renewed enthusiasm for the therapy and increasing adoption by leading cancer centers around the country. Yet, despite compelling data and more widespread availability, many eligible patients are still not presented with the option.

A review of the clinical literature convinced me that HAI was well worth incorporating into our practice. I have since seen the impact of this therapy on my own patients. My hope is that by sharing my experience setting up an HAI program I can help encourage other oncologists to consider this therapy for appropriate patients who otherwise have limited options.

A Data-Driven Decision

Until recently, as I trained at a program that did not offer HAI, I was only vaguely familiar with HAI therapy and lacked a detailed understanding of the specifics. When one of our surgical oncologists who had long been interested in HAI therapy broached the idea of establishing our own HAI practice, my colleagues and I reviewed the literature to determine whether this would be a valuable offering at our cancer center.

HAI therapy uses an implantable pump that is activated by body heat to administer a continuous flow of floxuridine directly to tumors in the liver through the hepatic artery. As a result, this liver-directed therapy can achieve intratumor drug concentration up to 400 times higher than systemic chemotherapy. In addition, the 97% first-pass metabolism of floxuridine by the liver translates into negligible systemic exposure and side effects.

A review of the clinical literature for HAI revealed an impressive and consistently positive impact on patient outcomes in the treatment of colorectal cancer liver metastases (CRLM). Studies have shown that the application of HAI in combination with systemic chemotherapy significantly downsized initially unresectable tumors compared with systemic chemotherapy alone, enabling many previously unresectable CRLM to be resected. Notably, patients who converted to surgical resection with HAI therapy had long-term survival rates on par with patients who presented with initially resectable disease. This was very appealing since many of our patients remain unresectable even after maximal response to systemic chemotherapy. Furthermore, studies showed that median overall survival was doubled in patients with unresectable CRLM who were treated with HAI, regardless if they were able to achieve conversion to resection.

Data also strongly support use of HAI in the adjuvant setting – to delay or reduce the rate of recurrence after successful CRLM resection. Because HAI treats the entire liver, it addresses remaining microscopic disease before it can develop into macroscopic tumors that impact survival. Studies have documented that median overall survival among patients treated with HAI plus systemic chemotherapy following CRLM resection averages around two years longer than comparable surgical patients who received adjuvant systemic chemotherapy alone.

Multidisciplinary Commitment

While Ochsner had already established a strong program for treating metastatic colorectal cancer, we wanted to offer every option that could improve patients’ chances of survival all at one center, especially for those patients whose options were limited. The clinical data on HAI convinced us, and we were ready to move forward with implementing HAI to fill this gap.

We built a core HAI therapy team consisting of medical oncologists and advanced practice providers to oversee treatment, surgical oncologists to implant the pump, pharmacists to build out the dosing plan and verify dose adjustments, infusion nurses to manage the refill process, and a nurse navigator to assist with external referrals and education. To learn more about implementing the therapy, we consulted experts at established HAI centers for advice, clinical shadowing, and hands-on training. In addition, Intera Oncology, the manufacturer of the HAI pump, provided training and educational resources that were an integral part of the onboarding process. Once our core team was fully trained, we worked to educate our center staff and ensure all were aware of our program through informal lectures and department presentations.

Our First Patient

The first patient we selected to treat with HAI had high-burden unresectable disease confined to the liver that achieved the best response of stable disease on first-line multi-agent systemic chemotherapy. Treatment options for this patient were limited beyond lifelong chemotherapy given her lack of actionable mutations. When presented the option of HAI pump therapy, the patient understood the need to come in every two weeks for pump refills during active treatment and the importance of adhering to treatment guidelines. We implanted our first HAI pump in February 2024 and the patient began floxuridine through her pump 2 weeks thereafter. The patient tolerated the HAI therapy well and achieved radiographic shrinkage of her intrahepatic tumor burden and a precipitous and sustained decline in her CEA level. While receiving treatment via her HAI pump, we were able to lower the dose of her systemic chemotherapy, thereby reducing her overall side effect burden.This successful experience confirmed that we were on the right path and our eyes were open to other patients who might be a good fit for HAI therapy. We have observed similar biochemical and radiographic responses with HAI in many of our other patients with CRLM who had otherwise maximized their responses to systemic chemotherapy.

Embracing HAI

Nine months after starting our HAI program, we now have 12 patients receiving HAI under our care and receive patient referrals from community oncologists. In these cases, we work closely with the referring physicians to keep them updated while we temporarily manage the patients during active HAI treatment. After the treatment concludes, patients return to their referring physicians for ongoing care.

All the patients we treated were very amenable and eager to receive HAI, with many finding its liver-directed approach intuitive. In some cases, we discussed HAI around the time of diagnosis; in others, we kept it in mind as a potential option for later in their treatment journey.

For those reading this article and considering including HAI among their treatment options, my recommendation would be to:

1. Start with getting buy-in from the multidisciplinary team that will be involved in the therapy – partnership between surgical and medical oncologists in identifying patients and managing them through their HAI therapy is key.
2. Establish comfort with your team of infusion nurses in management of HAI pump refills. Intera Oncology offers invaluable support in this training. Clinical pharmacists are also a vital component of the treatment team.
3. Get required training and additional guidance from HAI experts from experienced centers. Maintaining communication with experts for guidance on individual patient scenarios that arise will improve your comfort with HAI therapy.
4. Identify patients who have liver confined CRLM who are failing to respond adequately to systemic treatment. This includes patients who are progressing on systemic treatment and those with stable disease where addition of HAI offers the possibility of downstaging for resection. Patients must also be healthy enough to undergo surgery and willing to commit to the treatment protocol.
5. Ensure these patients meet with the surgeon to evaluate whether they could be candidates for this therapy - the earlier this consultation occurs, the better.
6. Educate medical oncology colleagues at your center and community about your positive experience to make therapy accessible to patients who may benefit.

It took a concerted effort, but our multidisciplinary team really came together to make this important treatment option available, which was critical to the program’s success. I see our experience at Ochsner MD Anderson Cancer Center as a good example of how a new therapy can be integrated seamlessly, and I hope to continue seeing more patients benefit as adoption of HAI grows. When I think about the patients that we were able to help, who otherwise had limited treatment options, I am compelled to encourage others to take advantage of this therapy as a viable addition to the treatment armamentarium.