July 17, 2006 Combining thermal ablation with radiation therapy extends average life expectancy and decreases recurrences of tumors in patients who have early stages of inoperable lung cancer, according to researchers at Rhode Island Hospital.
In a retrospective study looking at patients over seven years, the median survival rate at three years increased from 20 months after radiation alone to 42 months when thermal ablation was followed by radiation for treatment of non-small-cell lung cancer. The results are published in the July issue of the Journal of Vascular and Interventional Radiology.
"This study shows us that even patients who are not eligible for surgery can still get very good results," says senior author Damian Dupuy, MD, director of ultrasound at Rhode Island Hospital and professor of diagnostic imaging at Brown Medical School, both in Providence, RI. "By combining thermal ablation and radiation, you have a better chance of survival than with either treatment alone."
With radiation alone, overall survival rates were as follows:
one year – 57 percent
two years – 36 percent
three years – 21 percent
With thermal ablation and radiation, they were significantly higher:
one year – 87 percent
two years – 70 percent
three years – 57 percent
Surgery is the standard treatment for lung cancer. However, only one-third of patients with early stage lung cancer qualify for surgery because of other underlying medical conditions. Radiation therapy has long been used for inoperable lung cancer, and more recently, doctors have used radiofrequency ablation (RFA) and microwave ablation, processes that heat tumors to destroy them. For patients who cannot have surgery or radiation, the median survival is about one year.
In this study, researchers looked retrospectively at 41 patients treated over seven years with thermal ablation (RFA or microwave ablation) and either standard radiation therapy or brachytherapy, a procedure in which a "seed" of radioactive material is implanted into the cancer or near it. Patients were diagnosed with Stage I or II lung cancer, meaning the lung cancer in most cases had not spread and was usually smaller than 3 centimeters, though not in all cases. While this study did not address the timing of combined treatment, brachytherapy radiation was typically administered within two hours of thermal ablation while external beam radiation was given within three to four weeks. Rhode Island Hospital may be the only hospital in the world to administer this combined treatment.
The recurrence rate was much lower with the combined treatment. With radiation therapy alone, about 50 percent of tumors recur within six to 12 months. By the end of this study, 24 percent of patients treated with ablation and radiation had recurrences at an average of 44 months. While there was an increased recurrence rate in larger tumors – 33 percent recurred at an average of 34 months – the overall survival rate was the same for patients with large and small tumors.
"We found that just because the tumor returns, that doesn't mean the patient lives less long," Dupuy says.
The combined treatments work because they create a "synergy," the authors write. When tumors are targeted with radiation therapy, oxygen is vital to help the radiation damage DNA and kill cancerous cells. While radiation is most effective in destroying cells around the edges of the tumor, it is less effective at targeting the center of the tumor, which tends to be a low-oxygen environment.
Thermal ablation, on the other hand, heats the tumor to kill cancerous cells – reaching the center of the tumor, but not necessarily killing all the cells at the edges. This can lead to a recurrence of the tumor, and the cancer may spread. Thermal ablation is delivered directly to cancerous cells with the guidance of a diagnostic image showing the tumor's location. However, if some cancerous cells have spread into small channels of the lung around the tumor, they tend to be small and not visible on a radiology scan. Thermal ablation, which sends electrical current into the tumor, may not penetrate far enough into the lung to kill these areas of cancer.
When the two therapies are combined, they complement each other. Thermal ablation kills the central tumor. In exchange, radiation kills the cells on the periphery of the tumor and elsewhere in the lung that are missed by thermal ablation.
While this study looked only at lung cancer, Dupuy also has pioneered the use of RFA in thyroid, kidney, adrenal and bone cancer. The combined treatment may have far-reaching effects, Dupuy says.
"You might be able to treat tumors elsewhere in the body with similar results," Dupuy says. "There are a lot of opportunities for exploring the synergy of thermal ablation and radiation."
Other authors on the paper are: C. Alexander Grieco, MD; Caroline J. Simon, MD, William W. Mayo-Smith, MD, Thomas A. DiPetrillo, MD; and Neal E. Ready, MD, all of Rhode Island Hospital and Brown Medical School.
This study was supported in part by grants from ValleyLab and Vivant Medical.
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