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Internal Radiation Therapy Slows Liver-Disease Progression in mCRC

Chase Doyle
Published Online:7:33 PM, Fri June 12, 2015
Peter Gibbs, MD

Peter Gibbs, MD

The combination of selective internal radiation therapy (SIRT) with first-line chemotherapy showed a 31% reduction in the risk of disease progression within the liver of patients with metastatic colorectal cancer (mCRC) compared with chemotherapy alone. According to data presented at a press conference of the 2015ASCO Annual Meeting, SIRT improves control of liver metastases and may benefit overall survival (OS).

“SIRFLOX has shown us, in an unbiased manner, that we can not only deliver high doses of radiation to the liver safely with this approach, but we can do so using concurrent chemotherapy,” said principal US investigator of the trial, Navesh K. Sharma DO, PhD, assistant professor at the University of Maryland Medical Center. “Concurrent chemo-radiation has been one of the most effective ways to treat cancer in general, especially those of gastrointestinal origin.”

As lead author, Peter Gibbs, MD, associate professor, medical oncology at The Royal Melbourne and Western Hospitals in Melbourne, Australia, explained, SIRT employs Yttrium-90 (Y-90)–labeled resin microspheres as a liver-directed therapy. These tiny microspheres, which contain a radiation dose, are administered by a radiologist via catheter in the groin artery, which travels through the major arterial system and ends up in the liver artery. Tens of millions of radioactive Y-90–coated particles are then injected through the catheter, delivering a high dose of radiation directly to the liver tumors, according to Gibbs.

“It’s the single dose which is important,” emphasized Gibbs. “Most of the other treatments that we use in medical oncology are repeat dosing every 2 to 3 weeks—often for many months at a time. SIRT is important, because it’s a one-off treatment that has an ongoing impact over long period of time.”
According to Gibbs, with over 500 patients recruited, SIRFLOX is the largest study to investigate the effect of chemo-radiotherapy as a first-line treatment for colorectal cancer that has spread to the liver.
Patients were stratified according to presence or absence of extrahepatic metastases, degree of liver involvement, whether or not the physician intended to use bevacizumab in the patient, and by institution. Ultimately, 530 patients were randomized 1:1 to receive systemic chemotherapy alone (mFOLFOX6  ± bevacizumab) or same treatment plus SIRT. The primary endpoint of the study was overall progression-free survival (PFS) in the intent-to-treat population.
Although analysis showed no difference in overall PFS between the two arms, changes in PFS were observed within the liver. Median PFS in the systemic-therapy–alone arm was 12.6 months. With the addition of SIRT, however, median PFS increased to 20.5 months, a difference of 7.9 months (HR, 0.69; P  = .002).

“Another way of saying this is that patients treated with SIRT experienced a 31% reduction in the risk of disease progression within the liver,” said Gibbs.
Gibbs also noted that the rate of complete responses in the liver of patients receiving SIRT plus chemotherapy (6.0%) was more than triple that of patients treated with chemotherapy alone at 1.9% (P = .02).

Acceptable Toxicity
Radiation oncologists have been traditionally cautious of irradiating large liver volumes because of the adverse events (AEs) associated with such treatments, Sharma reported. While patients treated with SIRT plus chemotherapy did experience additional toxicity—AEs were significantly increased in the SIRT arm for neutropenia (40.7%) and thrombocytopenia (9.8%) compared with the control arm (28.5% and 2.6%, respectively)—investigators insisted that these events had no impact on duration of systemic therapy.

“It’s a prolonged benefit, it’s safe to administer, and it’s a one-off treatment,” said Gibbs. “All of these things are benefits of SIRT, particularly if you’re trying to choose from a range of treatments.”

Future Studies Planned
SIRFLOX is the first of three randomized controlled trials in a preplanned combined analysis of SIRT’s impact on OS. SIRFLOX, FOXFIRE, and FOXFIRE Global have accrued a total of 1103 patients. Combined analysis of OS data from these three trials will be looked at first in 2017.

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