Historically, surgery has been the mainstay of locoregional treatment for small volume liver metastases. Over the years, as surgical techniques have evolved, long term cure rates have improved. In fact, a recent series of patients with solitary colorectal liver metastases from Aloia et al from MD Anderson Cancer Center has reported 5 year survival outcomes of over 70%. Surgery still remains the gold standard with the best long term outcomes.
However, many patients with limited liver metastases cannot undergo surgery. With our aging population in Florida, many patients have comorbidities that preclude resection. Moreover, patients often have disease adjacent to a major blood vessel that contraindicates a margin negative (R0) resection.
In this setting, more locoregional treatment options have emerged. At MoffittCancerCenter, we have a weekly multidisciplinary tumor board with GI surgeons, radiation oncologists, medical oncologists, pathologists, and interventional radiologists who all specialize in the management of gastrointestinal cancers. Patients with liver metastases have their films and cases presented so that all of their options for treatment can be discussed. We discuss the role of systemic therapy vs. locoregional therapy and whether the individual patient may be a candidate for both. If so, we then discuss how such therapies should be sequenced. We often will re-present the patient’s case after treatment to determine whether their disease has been downstaged enough for curative resection.
Patients with disease not amenable to surgery have many non-surgical options. First, we consider the role of radiofrequency ablation, RFA. This involves placement of a probe directly into the tumor, either percutaneously with CT guidance or by an open surgical approach, to use heat for ablation. Long term data shows excellent control rates with RFA with excellent rates of patient toleration. The highest control rates with RFA are for small tumors, generally 3cm or less.
Location is also an important consideration for RFA. Tumors that are adjacent to major blood vessels are not eligible for this approach due to the creation of a heat sink. A new technique, called IRE or irreversible electroporation, has been developed which allows tumors adjacent to blood vessels to be treated since the mechanism of action does not depend on thermal ablation. Rather, IRE (also known as Nanoknife) works by sending electrical pulses to the cancer cell creating channels or pores in the cell membrane and subsequently leading to cell death. This option has limited clinical data at the present time but appears very promising.
If neither RFA nor IRE are options, we can consider the role of radiation. In the last ten years, advances have been piloted with both external as well as internal techniques. The capacity to image the liver as a patient breathes has led to the development of SABR, stereotactic ablative body radiotherapy. With this technique, a dose of radiation up to 10 times the standard dose can be delivered in 5 or less fractions with high precision. One method of delivery is to use respiratory gating, such that the beam is only “on” when the patient exhales. Experience to date demonstrates high efficacy rates with small tumors, with the University of Colorado group reporting 100% local control rates at 2 years with tumors 3 cm or less. Our interventional radiology group often implants radio-opaque markers called fiducials adjacent to the tumor. Our radiation oncology colleagues then measure the location of the fiducials in maximum exhale, allowing treatment to be delivered with tight margins to avoid high doses to the surrounding normal tissue. For medial tumors, if a CT guided fiducial approach is not technically feasible, then we consider endoscopic placement of fiducial markers. Finally, for tumors that are at the dome of the liver, our IR group will often deliver Lipiodol (iodinated poppyseed oil) intravascularly to the tumor for target volume delineation purposes.
These options are appropriate in the setting of oligometastatic disease. For patients with bilobar or bulky disease, we consider embolization options. Although bland embolization or chemoembolization have been accepted techniques for the past few decades, a newer technique termed radioembolization incorporating millions of radioactive spheres has been reported as effective for patients with minimal extrahepatic disease. The procedure involves placement of a catheter through the femoral artery up into the hepatic artery, taking advantage of the liver’s dual blood supply and the fact that malignant tumors preferentially derive the majority of their blood supply from the hepatic artery. At our institution we have open clinical trials utilizing radioembolization in the setting of intrahepatic cholangiocarcinoma or colorectal metastases to liver progressive after first line chemotherapy.
Management of metastatic liver disease is truly a multidisciplinary challenge. By evaluating patients with a multi-specialty team when patients first present with liver disease, we are able to carefully consider all therapeutic options and how best to sequence them. Often, combination treatments are recommended in order to maximize downstaging. With new modalities developing at an increasingly fast pace in the modern oncology era, collaboration with a liver specific team will become more important than ever to optimize a potentially curative treatment approach.
By Junsung Choi, MD
Junsung Choi, MD is the Director of Interventional Radiology at Moffitt Cancer Center. He is a Senior Member and has been on faculty over 14 years. Dr Choi has extensive experience in radioembolization, chemoembolization, bland embolization, and percutaneous liver treatments such as radiofrequency ablation. He received his undergraduate training at Rensselaer Polytechnic Institute and then his medical degree from SUNY in Syracuse, NY. Dr. Choi has been on staff at Moffitt Cancer Center ever since completing his fellowship at the University of South Florida. He is accepting new patients for consultation which can be scheduled at 813-745-3980.