Medical Oncology in 2016: What the Interventional Oncology Clinician Should Know

Interventional oncologists are now firmly established as part of the multidisciplinary team at most cancer centers across the world. As the interventional oncology (IO) armamentarium continues to grow, it is becoming more challenging to decide when is the appropriate situation to apply a new device or modality. The multidisciplinary tumor board is of critical importance to guide decision-making in areas where limited data exist for application of a given modality. In this article, I will describe my framework for decision-making in challenging cases where an IO option exists.

Let me start by making some general comments about cancer. This is my “oncology 101” talk that I give to many patients when I first meet them. Although it is appealing to believe that cancer can be removed surgically, in many cases, relapses occur. Most patients with cancer don’t understand why we cannot just “cut it out.” Many patients ask “how many spots are affected” in the lungs or the liver for example, without understanding that visible metastases are usually the tip of the iceberg. William Halsted was the pioneer of the radical mastectomy – removal of the breast, pectoralis major muscle, axillary nodes, supraclavicular nodes and sometimes ribs and mediastinal (internal mammary) nodes. Less radical surgery was considered to be “mistaken kindness.” It was only after 15 years of performing radical mastectomies that Halsted started reporting his data in surgical conferences – the local recurrence rate was very low, but most patients still died. He eventually stopped reporting his data after showing that most patients with no nodal involvement survived and most with nodal involvement died, suggesting that it was the original stage that determined the outcome, not the radicality of the surgery. 

For patients with curative potential, for example early stage breast cancer, colon cancer, and even pancreatic cancer, surgery is usually combined with other modalities to sterilize margins and reduce the risk of distant relapse. This is still very challenging because our current understanding of metastases is limited. Even small tumors can release cancer cells into the blood. Most of these cells do not take root in distant sites, but some do. These can sometimes remain dormant for many years. Traditional cytotoxic chemotherapy does not kill slowly growing or dormant cells and this is why recurrences can occur years after the diagnosis. For patients with metastatic disease, although some metastatic tumors can be cured, the general rule is for palliative treatment aimed at prolonging survival while trying to improve symptoms and maintain quality of life. The concept of “oligometastatic disease” refers to cancers such as colorectal cancer that have a predilection for having 1 or 2 metastatic lesions in the liver or lung that may be amenable to potential cure by applying a local therapy at the metastatic site. However, the likely possibility of occult micrometastatic disease still needs to be considered in these cases.

Getting back now to decision making in IO, the overriding principle in deciding what to do for a particular patient is that patient’s unique tumor biology. Figure 1 shows the 5-year survival by stage for a few common cancers. Breast cancer has the longest natural history of those illustrated, with up to 22% of patients diagnosed with stage IV disease living beyond 5 years. Pancreatic cancer has the shortest natural history with only 1% of stage IV patients surviving for 5 years.  

In general, tumors with a long natural history or more indolent behavior may derive more benefit from local therapies. Cancers with a very short natural history and therefore a very aggressive behavior are unlikely to benefit from local therapy options. Tumor biology is of course very heterogeneous. Two patients with liver-limited metastatic colorectal cancer (mCRC) may have completely different disease courses and we are now learning about other factors that influence the prognosis. For example, mCRC patients with a BRAF mutation have very short life expectancies at this time, whereas patients without BRAF or RAS mutations have the best prognosis and can live for many years with metastatic disease.

Once we have a grasp of the patient’s tumor biology, the next point to consider is whether a patient would be better served by systemic therapy or locoregional therapy or a combination of both. The menu of modalities available is long (Table 1) and although there are many differences between locoregional therapies, the common denominator is that they all focus the therapy on one area. Systemic therapy, however, can potentially treat cancer in multiple locations.

As a medical oncologist, does it matter to me what local therapy is used if I have a patient who I think needs it? The answer is sometimes yes. For example, why not refer every patient with 1 or 2 small liver metastases for percutaneous ablation? Sometimes surgical resection gives me more information, such as the pathological response of the lesions to preoperative therapy (which can help plan postoperative therapy). More importantly, surgical exploration is diagnostic as well as therapeutic – many times occult peritoneal or other disease might be detected at the time of surgery that can completely change the way I approach that patient’s care in the future. However, in many cases, I do not need this information, or it may not be safe to do surgery and a minimally invasive approach may be preferred.

Fortunately, we are moving away in the tumor boards from “the strongest person wins” to now embracing emerging clinical trial data to guide our decisions. A good example of very important data in the IO field was the presentation of 2 pivotal randomized trials at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. I was present at that meeting when the SIRFLOX2 and CLOCC3 trials were presented. I am happy that the organizers of this meeting elected to present these two studies back to back in the same session because the contrast between these studies is very instructive. 

The SIRFLOX trial examined chemotherapy with or without selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres in the front-line treatment of patients with metastatic colorectal cancer. Most of the data with SIRT up to that point had been in chemotherapy-refractory patients, but the oncology community always wondered if it would be safe and effective to incorporate SIRT earlier in the disease course. The SIRFLOX investigators defined a new term which was progression-free survival in the liver (liver PFS) which was improved from 12.6 months in the chemotherapy-only arm to 20.5 months in the chemotherapy plus SIRT arm (P=.002). However, the primary endpoint of overall PFS was not different between the 2 arms because 40% of patients enrolled had extrahepatic disease. 

The EORTC 40004/CLOCC trial evaluated chemotherapy with or without radiofrequency ablation in patients with liver-only metastatic colorectal cancer. In contrast to the SIRFLOX trial, the CLOCC trial excluded patients with extrahepatic disease. This study demonstrated an improvement in PFS from 9.9 months with chemotherapy alone to 16.8 months with chemotherapy plus ablation (P=.005). This translated into a statistically significant 5-month improvement in overall survival.

For those of us who were at that session in Chicago in June 2015 listening to these presentations, the key difference between these two studies was very obvious. One study testing a liver-directed therapy included patients with extrahepatic disease and did not meet its primary endpoint, whereas the second study testing a different liver-directed therapy excluded patients with extrahepatic disease and surpassed all expectations. The lesson here is that systemic therapy can be successfully combined with local therapy in liver-limited mCRC, but the value is probably less in patients with extrahepatic disease. These studies have definitely impacted how we make decisions in the multidisciplinary tumor boards. I think the IO community will learn from the SIRFLOX trial in terms of future trial design and also in terms of what it takes to convince medical oncologists that a modality is valuable.  

My take-home message is that we need to respect the principles of cancer, understand the patient’s tumor biology, and continue to strive for high-quality data to inform decisions on applying interventional modalities to our patients.

References

  1. American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016.
  2. 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. 
  3. Ruers T, Punt C, Van Coevorden F, et al; EORTC Gastro-Intestinal Tract Cancer Group, Arbeitsgruppe Lebermetastasen und—tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) and the National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012;23(10):2619-2626. 

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. Hosein can be reached at phosein@miami.edu.

Suggested citation: Hosein PJ. Medical Oncology in 2016: What the Interventional Oncology Clinician Should Know. Articles from the official show daily for Synergy 2016. Intervent Oncol 360. 2017;6(1):E8-E11. 

Authors