Interventional Oncology 2016: The State of the Union Is Good!

Interventional Radiology (IR) has had an historic year, receiving the first new primary specialty designation awarded by the American Board of Medical Specialties in over 25 years. In parallel, the University of Miami took the extraordinary step of establishing a formal IR department. Interventional Oncology (IO) represents the first subspecialty of IR and is flourishing. IO content dominates the Society of Interventional Radiology Annual Scientific Meeting and has led to a number of successful standalone meetings, including the annual Synergy conference in Miami, Florida. 

The relative role of IO as an additional pillar of cancer care to medical, surgical, and radiation oncology is a topic of increasing discussion.^1,2 Interventional oncology physicians view this acceptance as crucial to validate the accomplishments of the subspecialty. My viewpoint is that IO is already firmly established as a crucial component of cancer care. The reliance of oncology practitioners on serial large-gauge image-guided core biopsies to direct therapies proves this point. Beyond this point, the most exciting part of IO remains the growth of ablative and intra-arterial locoregional therapies with increasing utilization in multidisciplinary guidelines for management of hepatocellular cancer, neuroendocrine tumors, and renal cell carcinoma.^3-5

Recent Developments

In the past year, there have been several important IO contributions to the oncology literature highlighted by three prospective randomized trials in high impact factor journals.^6-8 Additionally, a deeper dive into existing conventional chemoembolization literature resulted in fruitful data mining of this modality.⁹ These studies and their approaches have tremendous value and also provide insight regarding where the research focus of IO needs to be directed moving forward. 

Randomized, prospective studies are the idealized goal of medical research. The SIRFLOX study represents the largest randomized prospective trial published to date in IO.⁸ This study demonstrated that the addition of yttrium-90 (Y90) to first-line chemotherapy for liver-dominant metastases from colorectal cancer substantially delayed time to progression of liver metastases compared to chemotherapy alone. However, overall time to progression was no different between groups. SIRFLOX faced a significant challenge to meet the endpoint of time to progression given the effectiveness of first-line therapy. Oxaliplatin-based first-line therapy has response rates up to 81%.¹⁰ However, the effectiveness in delaying progession of liver metastases (20.5 vs 12.6 months) has increased interest within the medical oncology community, and earlier referral for Y90 prior to salvage therapy seems to be occurring. 

The other randomized prospective trials compared IO therapies against each other. Karen Brown, MD, from Memorial Sloan Kettering Cancer Center and Riad Salem, MD, from Northwestern University are to be commended for their work on prospective trials published in the Journal of Clinical Oncology and Gastroenterology, respectively.^6,7 These projects show the level of research that IO clinicians can generate from investigator-initiated trials. These papers also reveal how far the majority of IO research has to go to increase acceptance within the greater oncology community. A disproportionate quantity of IO research focuses on comparison of one embolization therapy to another to find a “best” modality. The majority of these projects are retrospective and poorly powered. While this approach is useful for novel therapies, we need to recognize that our IO treatments are mature enough to break through to the next level of study construction. As an example, several years ago, chemoembolization and radioembolization of HCC were shown to have similar overall survival.¹¹ Authors of this study found that a prospective trial to find a survival difference would require approximately 1000 patients to be appropriately powered.¹¹ Given that SIRFLOX had 530 patients enrolled over many years, such a study is unlikely to occur. It also represents a zero-sum outcome for IO. Moving forward, the largest wins for the subspecialty of IO will come from combining our treatments with systemic therapies to find novel avenues for therapy in different pathologic entities rather than focusing on the minor technical differences of various embolic devices. 

The systematic review by Lencioni et al of lipiodol chemoembolization of HCC is an excellent example of using large data sets to maximize the value of a publication.⁹ Large data sets are also increasingly being prospectively collected using registries. Commonplace in specialties such as thoracic surgery,^12,13 this method of data collection is rapidly gaining ground in IO. The Tracking Renal tumors After renal Cryoablation Evaluation (TRACE) (NCT01117779) study is a 150-patient prospective registry that completed enrollment during 2016. The Radiation Emitting Selective Internal Radiation Spheres in non-resectable liver tumor (RESIN) registry opened this year (disclosure: I am principal investigator). As of the beginning of September 2016, 17 sites are open and more than 130 patients have been recruited (NCT02685631). Most sites have opened since June of this year and recruitment is rapidly increasing. The goal of this registry is to gather information on less common tumors and find high signal/noise ratio areas where chemotherapy is combined with Y90 with the goal of focused prospective trials in the future.

What’s on the Horizon

Future goals for IO should be to increase multicenter collaborative research for larger wins as a subspecialty over single-center retrospective data reviews. The evolution of our research mindset as a subspecialty will be the best way to advance clinical practice. These networks could form collaborative groups, similar to the Southwest Oncology Group (SWOG) or Eastern Cooperative Oncology Group (ECOG). These long-standing groups have not yet generated significant collaborative data in IO. New networks should focus on including both private practice and academic groups. 

The majority of first and second-line chemotherapy for colorectal carcinoma is given in the community setting. Recruitment in these centers may improve our ability to generate larger data sets. Compared to SIRFLOX, second-line therapy for colorectal cancer may be a better target for a major win. The response rate for second-line therapy has a much lower response rate (15%-25%) than first-line treatment with time to progression of 6-8 months.¹⁴ The IO community is in dire need of a trial combining Y90 with second-line chemotherapy for colorectal carcinoma liver metastases. The good news is that there is an existing prospective randomized trial in this space, the Efficacy Evaluation of TheraSphere Following Failed First-line Chemotherapy (EPOCH) study (NCT01483027). Unfortunately, this study has struggled to accrue even in light of the tremendous opportunity for IO. Practitioners able to treat these patients need to get involved. 

Opportunities Await

The development of multicenter research collaborative networks will result in more powerful research and drive future innovation in IO. Novel platforms will allow better research to initiate ways to integrate IO therapies into the treatment of other disease processes, improving patient options and outcomes. Opportunities to grow IO are available but the work in doing so is challenging. I believe IR is up to this task. 

References

1. Brown DB. Interventional oncology: adding options to the care of patients with cancer. J Natl Compr Canc Netw. 2015;13(6):825-826.
2. van den Bosch MA, Prevoo W, van der Linden EM, et al. The radiologist as the treating physician for cancer: interventional oncology [article in Dutch]. Ned Tijdschr Geneeskd. 2009;153:A532.
3. Benson AB 3rd, Abrams TA, Ben-Josef E, et al. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw. 2009;7(4):350-391.
4. Clark OH, Benson AB 3rd, Berlin JD, et al. NCCN clinical practice guidelines in oncology: neuroendocrine tumors. J Natl Compr Canc Netw. 2009;7(7):712-747.
5. Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 3.2015. J Natl Compr Canc Netw. 2015;13(2):151-159.
6. Brown KT, Do RK, Gonen M, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol. 2016;34(17):2046-2053.
7. Salem R, Gordon AC, Mouli S, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016; pii: S0016-5085(16)34971-X. doi: 10.1053/j.gastro.2016.08.029. 
8. van Hazel GA, Heinemann V, Sharma NK, et al. SIRFLOX: randomized phase iii trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2016;34(15):1723-1731.
9. Lencioni R, de Baere 2, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 2016;64(1):106-116.
10. Gruenberger T, Bridgewater J, Chau I, et al. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015;26(4):702-708.
11. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140(2):497-507.
12. Beckmann A, Funkat AK, Lewandowski J, et al. German heart surgery report 2015: The annual updated registry of the German society for thoracic and cardiovascular surgery. Thorac Cardiovasc Surg. 2016;64(6):462-474.
13. Cao C, Zhu ZH, Yan TD, et al. Video-assisted thoracic surgery versus open thoracotomy for non-small-cell lung cancer: a propensity score analysis based on a multi-institutional registry. Eur J Cardiothorac Surg. 2013;44(5):849-854.
14. Nakayama G, Uehara K, Ishigure K, et al. The efficacy and safety of bevacizumab beyond first progression in patients treated with first-line mFOLFOX6 followed by second-line FOLFIRI in advanced colorectal cancer: a multicenter, single-arm, phase II trial (CCOG-0801). Cancer Chemother Pharmacol. 2012;70(4):575-581.

Editor’s note: This article first appeared in the Synergy Daily conference newspaper, available to attendees of the Synergy Miami interventional oncology meeting in November 2016. This article did not undergo peer review. Dr. Brown reports that he is a principal investigator for The Radiation Emitting Selective Internal Radiation Spheres in nonresectable liver tumor (RESIN) registry, mentioned in this article.

Suggested citation: Brown DB. Interventional oncology 2016: The state of the union is good! Articles from the official show daily for Synergy 2016. Intervent Oncol 360. 2017;6(1):E4-E7.