By Jemianne B Jia, MS4, University of California, Irvine

A cancer diagnosis can turn a patient’s emotional state into a pendulum, swinging back and forth amid uncertainty. In addition to the difficult physical and emotional effects that accompany the diagnosis, significant adverse effects often accompany the treatment options available.

There are a number of challenges in cancer therapy including adverse effects of systemic therapy, therapeutic radiation dose constraints for each organ, morbidity of surgical procedures, and the poor surgical candidacy of many patients inflicted with cancer. While the role of IO has historically been palliative, the field is making strides toward shaping future cancer care. This article reviews the current techniques used in IO, novel therapies in development, and ways to learn more and get involved.

Interventional oncology (IO) is the branch of IR devoted to the treatment and palliation of patients with cancer and is an emerging pillar in modern oncologic care. The benefits of IO stem from the minimally-invasive nature of the procedures, limiting systemic toxicities and complications. Avoiding systemic damage, a thin probe can be placed into a tumor delivering intense heat or cold to a predetermined spherical area. A catheter can directly deliver chemotherapy eluting beads to the arteries supplying a tumor. Patients often can leave same-day and with just a small incision at their groin or no incision at all. The role of IO in cancer treatment continues to grow as the minimally-invasive nature of endovascular treatments is especially valuable for patients who are poor surgical candidates or who have reached their threshold of therapeutic radiation.

With the advent of many novel techniques and innovations in IO, several clinical trials have been carried out to compare IO with the current standard of care. The SIRFLOX trial, a large prospective randomized trial, was recently performed comparing first-line chemotherapy treatment for metastatic colorectal carcinoma to first-line chemotherapy AND radioembolization treatment. This study found a significant difference between tumor growths of the two groups; the addition of radioembolization delayed tumor growth by up to 8 months (1). This study serves to help support the benefit of IO in cancer treatment and its enlarging role in the future of oncology.

Current Practice

Transarterial chemoembolization (TACE) and selective internal radiation therapy (SIRT)

TACE is a commonly used procedure for treatment of hepatocellular carcinoma (HCC) and metastases to the liver. Super-selective catheterization of the arteries feeding the tumor is achieved and either chemotherapy and embolic material (cTACE) or drug eluting beads (debTACE) are released. If there are multiple nodules, an entire lobe or multiple lobes may be treated. TACE is currently the treatment of choice for patients with multinodular, intermediate stage HCC according to AASLD guidelines.

SIRT or radioembolization is the release of glass or resin microspheres filled with the radioactive isotope, yttrium-90 (Y-90), into the liver for treatment of HCC or metastasis. Due to the precise delivery of the particles, a high dose of radiation is delivered to the cancerous cells while tissues outside the liver are largely unaffected.

Both TACE and SIRT take advantage of the dual supply of the liver – supplied by the hepatic arteries and the portal vein. Importantly, the vast majority of tumors receive their primary blood supply from the hepatic arteries while normal liver parenchyma receives the bulk of its blood supply from the portal vein. Therefore, when chemotherapy and radiation is delivered through the hepatic arteries, it preferentially affects the diseased tissue without severely jeopardizing the blood supply of the normal parenchyma. In addition, these techniques utilize embolization and chemotherapy or radiation for a multifaceted approach again cancer cells. Furthermore, TACE and SIRT are associated with low complication rates. Patients can usually be discharged on the same or next day.

Percutaneous Local Ablative Therapy (PLAT): radiofrequency ablation (RFA), microwave ablation, cryoablation, and irreversible electroporation

Radiofrequency ablation is the use of intensely high temperatures from an electrical conduction system to ablate tumor tissue. Microwave ablation is also a form of thermal ablation, however it uses electromagnetic waves in the microwave spectrum to produce its tissue damaging effects. Cryoablation works similarly to the other ablation techniques, however it utilizes extreme cold rather than heat to damage target tissue. Irreversible electroporation uses bursts of electrical pulses to create pores in cell membranes leading to cell death. These localized ablative techniques are most frequently used in renal, liver, lung, and spinal lesions. The unique characteristics of each organ make different types of ablation more suitable than others. For example, cryoablation is used in the kidney because the renal vascularity is extremely vulnerable to damage caused by extreme heat. RFA, on the other hand, is used in the liver because the large surface area reduces risk of damaging vessels or neighboring organs. In addition, cryotherapy in the liver has been associated with fracture. There is a low complication rate in patients receiving PLAT and it is standard for patients to be released the same day.

Future Therapies

High-intensity focused ultrasound (HIFU)

HIFU is an emerging treatment that uses high frequency sound waves to inflict tissue damage. Preliminary studies using HIFU for treatment of tumors have been performed with promising results in osteosarcoma, HCC, metastases to the liver, pancreatic cancer, breast cancer, renal cell carcinoma, uterine fibroids, and soft tissue sarcomas (2).

Immunotherapy

There is great interest in harnessing a patient’s own immune system to fight cancer. There is evidence that RFA may provoke an immune response towards cancer cells with non-treated tumor undergoing spontaneous regression following treatment of other areas. When necrotic cells release their contents, they trigger “danger signals” to the immune system inciting an antitumor specific immune response (3). There is ongoing research on engineering viruses that target tumor cells without damaging normal cells. SillaJen is currently on Phase 3 of clinical trials for Pexa-Vec, an immunotherapy composed of a virus mutated to target cancer cells and an immune stimulatory GM-CSF protein for immunomodulatory effects. Pexa-Vec selectively replicates in and ultimately lyses cancer cells (4).

Targeted therapy

There is also interest in developing cancer therapies for more selective and improved delivery. Heat shock protein 90 (Hsp90) is essential for cell survival following heat injury. There are new advances in combining a thermo-responsive elastin-like polypeptide conjugated to a potent Hsp 90 inhibitor, geldanamycin, with RFA to improve tumor destruction. By combining a heat sensitive polypeptide with geldanamycin, treatment is targeted to areas that are being treated with RFA (i.e. the tumor areas). Preliminary in vitro and in vivo results are promising (5). Another area of interest is synthesizing a targeted-doxorubicin prodrug for use in TACE by exploiting a protein that is upregulated in a number of tumors (6).

Targeted nanoparticles

There is also a foray into the creation of nanoparticles to better target and treat cancer. Johns Hopkins is currently doing work on nanoparticle mediated DNA delivery to HCC cells using poly(beta-amino ester)s (PBAEs). These nanoparticles have utility as a possible vehicle for future gene delivery treatments (7).

Learn More

If you are interested in IO, the World Conference of Interventional Oncology (WCIO) is an annual conference on the subject where experts discuss the latest advancements in the field. In 2016, it will be held in Boston, MA from June 9-12. As a medical student, I attended the conference this year and I was able to learn immensely about IO. I also met many people passionate about cancer research from around the world and learned about the cutting edge research and new technologies currently being developed. If you are interested in IO, I highly encourage you to submit abstracts for either poster or oral presentations.

The annual Society of Interventional Radiology Conference is also a valuable place to learn about IO. There is a significant amount of IO programming and it is a rare opportunity to learn about the field and research. It is also a place to meet experts in the field and find mentors. There is designated programming for medical students and residents. In 2016, the annual conference will be held in Vancouver from April 2-7.

The Journal of Vascular and Interventional Radiology and Cardiovascular and Interventional Radiology are the official journals of the Society of Interventional Radiology and the Cardiovascular and Interventional Radiological Society of Europe, respectively. These journals are worthwhile sources to keep up with new developments in IO.

IO Central at http://www.io-central.org/, is an online community for people with an interest in IO to communicate and interact. It is also a helpful resource for trainees interested in the field of IO.

Looking Forward

IO is a dynamic field that will continue to move forward, creating new alternatives for the treatment of cancer and palliative care. With its localized nature, low complication rate, quality outcomes, and short hospital stays, IO is sure to continue to grow as an important pillar in oncology.

References

  1. Gibbs, Peter, Heinemann, Volker, Sharma, Navesh K., Findlay, Michael P. N., Ricke, Jens, Gebski, Val, Van Buskirk, Mark, Van Hazel, Guy A., SIRFLOX Study Group, SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 {+/-} bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) {+/-} bev in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol (Meeting Abstracts)201533:3502
  2. Orsi F, Arnone P, Chen W, Zhang L. High intensity focused ultrasound ablation: a new therapeutic option for solid tumors. J Cancer Res Ther. 2010;6(4):414-20.
  3. Haen SP, Pereira PL, Salih HR, Rammensee HG, Gouttefangeas C. More than just tumor destruction: immunomodulation by thermal ablation of cancer. Clin Dev Immunol. 2011;2011:160250.
  4. Lichty BD, Breitbach CJ, Stojdl DF, Bell JC. Going viral with cancer immunotherapy. Nat Rev Cancer. 2014;14(8):559-67.
  5. Chen Y, Youn P, Pysher TJ, Scaife CL, Furgeson DY. Tumour eradication using synchronous thermal ablation and Hsp90 chemotherapy with protein engineered triblock biopolymer-geldanamycin conjugates. Int J Hyperthermia. 2014;30(8):550-64.
  6. Jemianne Jia, Minzhi Xing, Xiaoxi Ling, Mingfeng Bai, Hyun S. Kim. Novel mitochondria-targeted Doxorubicin Prodrug for colorectal cancer and hepatocellular carcinoma: In vitro studies.In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; 2015. Abstract nr 4407.
  7. C.G. Zamboni, L. J. Higgins, K. Kozielski, I. Nibb, M.G. Pomper, J. Green.8:00 AM, Abstract No. 21 – Cancer-specific nanoparticle mediated DNA delivery to human hepatocellular carcinoma using synthetic poly(BETA-amino ester) vectors. JVIR. 2015;6(2): S16