A new study published by Jaoude et al in Clinical Cancer Research demonstrates that a specialized high-dose type of radiation delivery may significantly improve outcomes for patients with large bile duct tumors in the liver, known as intrahepatic cholangiocarcinoma.
The retrospective study was led by two researchers from The University of Texas MD Anderson Cancer Center—Ethan Ludmir, MD, Associate Professor, and Eugene Koay, MD, PhD, Professor, both of the Department of Gastrointestinal Radiation Oncology. According to the results, patients treated with ablative radiotherapy plus chemotherapy had a median survival more than twice that of the patients treated with chemotherapy alone.
“Traditionally, patients with very large tumors were not treated with radiation due to safety concerns,” Dr. Ludmir explained. “But our ability to more precisely deliver higher doses of radiation has dramatically improved over the last 10 to 15 years to the point that we can now treat these tumors safely. This study makes a compelling case that there is a very significant benefit from this approach.”
Study Background
Intrahepatic cholangiocarcinoma forms tumors in the bile ducts of the liver, and some can grow larger than 10 cm. These larger cases are known as supermassive tumors. Up until about a decade ago, delivering a large enough radiation dose to impact a supermassive tumor would require a dose higher than the remaining healthy liver tissue could tolerate. Additionally, these tumors are often near other critical organs and structures, such as the stomach or bowels, which could be damaged by large doses of radiation.
Historically, there also was a widespread belief that supermassive tumors were biologically different from smaller ones and that, even if radiation could achieve local control, it might not prolong survival.
However, advanced radiation centers now have the ability to deliver an ablative dose of radiation—high enough to eradicate tumors completely—to even these difficult-to-treat locations, and deliver it accurately enough to minimize damage to the surrounding healthy tissue.
Over the last 15 years, some patients at MD Anderson have been treated using this ablative radiation technique, but this study is the first to analyze outcomes for the approach. The relative rarity of these particular supermassive tumors means this trial likely represents the best possible evidence for this treatment strategy, the authors explained.
Key Findings
At a median follow-up of 17.9 months, 34 patients treated with ablative radiation in combination with chemotherapy had a median overall survival of 28.7 months compared to 11.9 months for 29 patients who received chemotherapy alone. The combination group also had lower rates of tumor-related liver failure, at 12.1%, compared to 47.1%.
The researchers compared this data to qualifying patients in the National Cancer Database who received chemotherapy alone, which had an overall survival of 11.6 months.
Ablative radiation therapy also was well tolerated by patients, with no grade 4 or 5 adverse effects. Nine patients (26.5%) had manageable grade 3 radiation-induced liver disease and two patients had late-onset grade 3 gastrointestinal hemorrhage, which was manageable. There were no other adverse effects above grade 3.
The researchers also did comparisons on several biological aspects of these tumors and found they were not biologically different from smaller tumors. According to Dr. Koay, this led to their hypothesis that tumor size should not be a limiting factor in the use of radiation therapy.
“Molecular and histological analyses showed that these very large tumors are not fundamentally different from smaller ones,” Dr. Koay said. “As a result, it shouldn’t come as a surprise that they responded well to ablative radiation like their smaller counterparts. This study has some limitations, but this is very compelling evidence that this approach is effective and safe in a patient population that has a need for better treatment options.”
DISCLOSURE: This study was funded by the National Institutes of Health. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
