Constantino Peña, MD, FSIR
Ripal Gandhi, MD, FSIR, FSVM
At the recent 2019 Symposium on Clinical Interventional Oncology (CIO) in Miami, course directors Constantino Peña, MD, FSIR, and Ripal Gandhi, MD, FSIR, FSVM, had a lot to say about this burgeoning field of oncology. In particular, interventional oncology is making inroads in therapeutic areas, and evidence is mounting for the use of these technologies in the treatment of a variety of solid tumors. Interventional oncology techniques are also being studied in combination with targeted therapies and immunotherapies in the hope of improving outcomes in patients with cancer.
Drs. Peña and Gandhi are interventional radiologists who work at the Miami Cancer Institute, which has devoted considerable resources to building the division of interventional oncology as one of the pillars of a multidisciplinary approach to the treatment of cancer. The ASCO Post interviewed both doctors at the CIO meeting in Miami about the current and future directions for this relatively new specialty.
Backward Glance at Specialty’s Growth
How long has interventional oncology been around?
Dr. Peña: Interventional oncology has been part of interventional radiology for many years. Over the past decade, there has been a proliferation of therapeutic options. Because of the complexity in management of patients with cancer, we have seen more interventional radiologists specializing in oncology. Learning about different types of imaging modalities and different disease states is important when we work as part of a multidisciplinary team. New technologies and applications of those technologies are driving the growth of the specialty, for example, image-guided catheter-based techniques.
Dr. Gandhi: Interventional oncology is a subspecialization within interventional radiology that utilizes imaging guidance to perform minimally invasive procedures to diagnose, treat, and manage the symptoms of cancer. Several minimally invasive options for therapeutic applications have been around for more than 20 years, and options for diagnosis as well as palliation have been around since the inception of interventional radiology over 50 years ago. Technologic advances are fostering significant growth of this field.
From Cardiology to Oncology
Interventional oncology was first introduced for cardiovascular applications. What generated interest in using interventional radiology techniques in oncology?
Dr. Peña: During my training at Mass General, we were doing early work with percutaneous interventions in oncology, using radiofrequency ablation to treat tumors. This was being used for inoperable cancers, and we analyzed tumor specimens to see how these therapies worked. Radiofrequency ablation was then considered an alternative therapy in the United States. Initially, these procedures were done with alcohol, but we moved on to thermal energies. The growth of image-guided procedures has spread interest in the field of interventional oncology.
Dr. Gandhi: Although many of the early procedures in interventional radiology were for cardiovascular applications, pioneers in this field looked for additional areas where these procedures would be valuable. It was the natural evolution of the field to apply similar techniques to treat cancer, given that many malignancies can be approached in a similar fashion.
Because of the complexity in management of patients with cancer, we have seen more interventional radiologists specializing in oncology.— Constantino Peña, MD, FSIR
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One of the goals of interventional oncology is to provide minimally invasive treatment options as a potential alternative to surgery or sometimes as a bridge to surgery. Compared with surgery, minimally invasive techniques are usually safer and less painful than surgery, result in fewer complications and hospital stays, and perhaps are less costly. In the modern era with newer techniques, we can offer less-invasive endovascular and percutaneous procedures as an alternative to surgery and achieve similar clinical outcomes for some malignancies.
Minimally invasive techniques can also be used as a bridge to surgery. For example, for patients with primary liver cancer who are beyond the Milan criteria for transplantation, interventional oncology techniques can be used to downstage the cancer, so patients can successfully receive a liver transplant. Per the United Network for Organ Sharing, there is a minimum 6-month waiting period for a liver transplant, even for patients who meet the Milan criteria, and the therapies we can offer prevent tumors from growing during that waiting period, serving as a bridge to transplantation. Therapies that would downsize the tumor include liver-directed therapies such as chemoembolization, radioembolization, or bland embolization, as well as ablation procedures.
Interventional oncologic procedures can also be used in conjunction with systemic therapy and may be synergistic. For example, yttrium-90 radioembolization can be used in the management of primary and metastatic liver cancers. In some cases, patients who are intolerant to chemotherapy or want a “chemoholiday” can be managed with such procedures. Finally, our therapies can be extremely helpful in the management of symptoms.
A Fourth Pillar of Cancer Care
What are some of the more established major applications of interventional oncology?
Dr. Peña: Interventional oncology is now at every major cancer center and is considered the fourth pillar of care along with surgical oncology, radiation oncology, and medical oncology. The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) include recommendations for liver-based therapies for primary hepatocellular carcinoma and for liver metastases. This depends on a multidisciplinary approach with tumor boards at major cancer centers where cases are discussed. The collaboration among specialties is aimed at identifying the best approach for each patient and personalizing care. I would say that liver-directed therapies for patients who are not surgical candidates is a major application. Also, these techniques are being used for small kidney lesions in patients with renal cell carcinoma who are not ideal surgical candidates. Treatment of pulmonary, adrenal, and painful osteolytic lesions is another area of much interest.
There is evidence for these techniques from registries, some of them large, but evidence from randomized controlled trials is mainly lacking. And it is difficult to perform those trials. Patients who benefit from these techniques are not standardized, and many have exhausted other therapeutic options. Evidence is building for these techniques in the treatment of osteolytic lesions and vertebral fractures related to metastases.
Dr Gandhi: Interventional oncology techniques are well established; they are supported by strong clinical data and NCCN Guidelines in the treatment of primary liver cancer as well as liver metastases, including those originating from colorectal cancer and neuroendocrine tumors. There is level 1 data supporting the use of locoregional therapies, including ablation and embolization, for treatment of hepatocellular carcinoma.
There are also robust data to support the use of these techniques in primary renal cell carcinoma—predominantly for smaller T1A lesions. Outcomes are similar to those with surgery, with a slightly higher recurrence rate. Patients who experience recurrence can be re-treated with ablation. The good news is that ablation does not decrease renal function, and it is a big plus that we can achieve similar outcomes without compromising renal function.
There are many studies supporting the role of ablation in the management of primary and metastatic lung cancers. There are growing data for the management of cancer-related pain due to the involvement of the musculoskeletal system.
How widespread is the adoption of interventional oncology as part of multidisciplinary care in the United States?
Dr. Peña: It is now an established specialty, with diagnostic, therapeutic, and palliative applications. The uptake is similar in the United States and Europe.
Dr. Gandhi: A lot of supportive data have been generated both here and abroad. At many centers in the United States, interventional oncology joins surgery, radiation, and chemotherapy in the treatment of patients with cancer, as previously mentioned. Our center in Miami has a dedicated division for interventional oncology that is about 2 years old. A lot of thought went into this, and it is considered an essential part of multidisciplinary treatment.
What are some growth areas for and future applications of interventional oncology?
Dr. Peña: Future applications of interventional radiology will include continued growth in liver-based therapies and combination therapies with medical oncology and radiation oncology to improve outcomes for our patients. For example, interventional oncology techniques are being studied in combination with chemotherapy, immunotherapy, targeted therapy, and also with radiation techniques. We will begin to see more combinations of therapies with better medications, more advanced imaging techniques, and other techniques.
Just because a patient is treated with radiofrequency ablation does not mean that he or she cannot also be on chemotherapy. There are synergies with combination approaches, and many of these combinations are currently under study. As results with immunotherapies improve, and medical imaging improves, we will see better outcomes. Even incremental differences in survival will add up to better outcomes.
Many of these potential combinations are unproven but may turn out to be advances in treatment. For example, irreversible electroporation along with immune checkpoint inhibitors may serve to increase responses and survival in solid tumors.
Dr. Gandhi: One area of growth is increased utilization of techniques to treat patients with cancer-related, musculoskeletal pain. At our institution, we are involved in a clinical trial comparing radiation therapy with radiation plus vertebral augmentation (vertebroplasty).
We are also involved in clinical trials for treatment of locally advanced pancreatic cancer. I am excited about this, because pancreatic cancer is a deadly disease, and current treatments have not moved the bar very far. At our center, a randomized phase III trial is evaluating chemotherapy versus intra-arterial chemotherapy in locally advanced pancreatic cancer. This approach allows the local delivery of high-dose chemotherapy directly to the tumor site. The goal is to improve outcomes, and early results are promising. Furthermore, we are evaluating irreversible electroporation, sometimes called the NanoKnife, for the treatment of locally advanced pancreatic cancer. This approach delivers ablation that disrupts cell membranes through electrical currents. Our center will be leading a randomized clinical trial as well as a registry utilizing irreversible electroporation for pancreatic cancer.
My hunch is that [interventional oncology] therapies will turn out to be less expensive than many traditional approaches.— Ripal Gandhi, MD, FSIR, FSVM
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Thyroid cancer is another potential area of growth. The current standard of care is surgery. We and other cancer centers are evaluating alcohol and thermal ablation techniques for the treatment of primary thyroid cancer.
These techniques are also being studied in breast cancer, including cryoablation for localized disease in patients who are not surgical candidates. At our center, we treat patients with breast cancer who have liver metastases using liver-directed therapies in patients who fail to respond to chemotherapy or who want a break from chemotherapy.
It is still early days, but interventional techniques are being applied in prostate cancer. Results are still preliminary in this tumor type.
In the future, we will see combination studies with immunotherapies, but this is still in its infancy. The hope is to achieve better outcomes through abscopal effects.
Another exciting area is the combination of targeted therapies with interventional techniques delivered directly to the tumor. In the future, a multidisciplinary approach that exploits the synergy of different approaches—whether it is adding immune or targeted therapies with or without radiation or surgery—may turn out to be combinations that achieve the best results for our patients.
Cost of Interventions
Will the cost of these interventions be prohibitive?
Dr. Peña: We always need to be concerned about cost. I think the cost of these interventions will come down with more widespread experience, as we have seen with next-generation genomic sequencing. We need to be mindful of value-based care and be sure we are delivering the right treatment to the right patient, in other words, individualizing patient care.
Dr. Gandhi: We always have to look at cost in the context of benefit, including survival benefit, and compare cost with other therapies used for the same indication. My hunch is that our therapies will turn out to be less expensive than many traditional approaches. ■
DISCLOSURE: Dr. Peña reported financial relationships with Boston Scientific, Bard BD, Sirtex Medical, Cook Medical, and Penumbra. Dr. Gandhi reported financial relationships with Boston Scientific, Bard BD, Sirtex Medical, and Medtronic.