Biomarker-Guided Radiotherapy Dosing Shows Promise for High-Risk Liver Cancer Patients

08/16/17

By Marilynn Larkin

NEW YORK (Reuters Health) – Individualizing radiotherapy according to levels of a patient-specific biomarker of liver function safely achieves local control in cancer patients at high risk for liver damage, researchers say.

“Standard radiation therapy relies on population-based toxicity estimates, which limit the intensity of therapy for 95% of patients based on the risk of toxicity to the most sensitive 5%,” Dr. Theodore Lawrence of the University of Michigan, Ann Arbor, told Reuters Health by email.

“We designed a trial for patients with hepatocellular cancers to test the hypothesis that adapting treatment for the individual patient based on the change in liver function during the course of treatment could optimize the therapeutic index for each patient,” he explained.

Dr. Lawrence and colleagues recruited patients from 2010 to 2014 for the phase 2 study, which used indocyanine green retention at 15 minutes (ICGR15) as a direct biomarker of liver function. The planned course of stereotactic body radiation therapy (SBRT) was modified midway through the course, if needed, in an effort to maintain liver function after the complete course.

As reported online August 10 in JAMA Oncology, 90 patients (median age, 62; 70% male) were treated for 116 tumors: 77% of patients had hepatocellular carcinoma; 4%, intrahepatic cholangiocarcinoma; and 19%, metastatic. The median tumor size was 3 cm, and 18% of patients had portal-vein involvement.

More than two-thirds of patients had cirrhosis, and about one-quarter were Child-Pugh (CP) grade B.

Sixty-two patients (69%) received all five SBRT fractions (median delivered dose, 49 Gy): 47 received the full dose, and 15 had the final two doses reduced because of a rise in ICGR15 after the initial treatment phase.

Treatment was well tolerated, with a lower-than-expected complication rate even without adaptation: six patients experienced a 2-point decline in CP liver function six months after treatment.

Local control rates were 99% at one year post-SBRT and 95% at two years.

However, local control was not associated with improved survival, and overall survival at two years was only 36%. The authors attribute these outcomes to the late stage at which most patients were treated, with a median of two prior treatments, which they note “exacerbates the competing risk of progressive cirrhosis and the development of additional primary tumors...”

The study results serve “as proof of principle that radiation can safely control intrahepatic cancers,” the authors state, “and we would anticipate improved survival if radiation therapy were used earlier in the course of disease.”

Dr. Lawrence noted that the team “also used an adaptive approach in lung cancer with equally promising results.” (http://bit.ly/2wayPLy)

“Taken together,” he concluded, “our findings suggest that individualized adaptive radiotherapy may represent a new treatment paradigm for radiation oncology in which dose is based on individual, rather than population-based, response to treatment.”

Dr. Jessica Frakes of Moffitt Cancer Center, Tampa, Florida, told Reuters Health by email, “This study is an example of personalized radiation medicine entering the clinic for patients with varying degrees of liver dysfunction.”

“The findings are highly provocative and potentially practice changing,” she said, “suggesting that this innovative study has opened the door for optimizing the safest delivery of noninvasive ablative stereotactic radiation.”

SOURCE: http://bit.ly/2vZQvsW

JAMA Oncol 2017.

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