News | Radiation Therapy | September 29, 2017

Radiation-Immunotherapy Combination Can Slow Tumor Growth in Some Metastatic Late-Stage Cancer

Phase II trial finds at least 30 percent of patients experienced favorable response after treatment

Radiation-Immunotherapy Combination Can Slow Tumor Growth in Some Metastatic Late-Stage Cancer

September 29, 2017 — A new study involving patients with stage IV cancer finds treatment with radiation therapy and immunotherapy can halt the growth of tumors by stimulating the body’s immune system to attack the cancer. In the phase II trial, patients with end-stage cancer that had spread to the lungs or liver demonstrated a favorable response to the combined treatment. Between 30 and 60 percent of the patients, depending on the treatment arm, found that their cancer stopped spreading. Findings were presented at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO), Sept. 24-27 in San Diego.

“This combination of immunotherapy and radiation therapy was safe and well-tolerated by patients with late-stage cancers. We were surprised that a large percentage of patients achieved stable disease several months after treatment — meaning that while their tumors didn’t shrink, they did stop growing,” said James Welsh, M.D., lead author of the study and an associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston.

“It appears that the radiation helped turn the tumor into a vaccine to stimulate an immune response. This heightened immune response was able to keep the tumors stable. Longer follow-up is needed to determine if this benefit of stable disease will endure over time.”

One hundred patients were enrolled in a phase II trial examining a combination of high-dose radiation therapy plus immunotherapy for patients with various types of stage IV cancers. Eligible patients included those with metastatic disease that was resistant to standard therapies, with one or more lesions in the liver or lung that was/were amenable to stereotactic radiation, and one or more additional metastases not touching the lung or liver lesion. The majority of patients (55 percent) had adenocarcinomas, while 13 percent had squamous cell carcinomas and the remaining 32 percent had various other histologies.

All patients received four cycles of ipilimumab (3 mg/kg every three weeks) and stereotactic body radiation therapy (SBRT) to the site(s) of metastasis in either the liver or the lungs. Radiation therapy was given either concurrently with or sequentially to immunotherapy. Concurrent radiation began on day two of the first immunotherapy cycle, to a total dose of 50 Gray (Gy) delivered in four fractions. Sequential radiation was given one week after the second immunotherapy cycle to a total radiation dose of 50 Gy delivered in four fractions, or 60 Gy in 10 fractions for larger lung or liver metastases — typically, those larger than 4 cm. Patients were enrolled in a nonrandomized fashion into one of the five treatment cohorts: concurrent lung, sequential 50-Gy lung, concurrent liver, sequential 50-Gy liver, and sequential 60-Gy liver or lung. There were 20 patients in each treatment arm.

Stable disease was achieved for half of the patients in the sequential 50-Gy lung cohort, 45 percent of the concurrent-lung group, 35 percent of the concurrent liver group and 30 percent of the sequential 50-Gy liver group. Sixty percent of patients in the larger-lesion, higher-dose radiation group demonstrated a favorable response to treatment.

The median progression-free survival (PFS) for all patients following radiation therapy combined with immunotherapy was five months (95 percent CI = 2.7-7.2 months). Median overall survival (OS) was 12 months (95 percent CI = 9.3-14.6 months). Patients who received sequential radiation to lung metastases rather than to liver metastases had better PFS (p = 0.055, 95 percent CI = 3.7-6.4) and OS (p = 0.059, CI = 7.9-20.0). No differences were found between the concurrent lung or liver groups for progression-free (p = 0.2) or overall (p = 0.3) survival.

There were no complete responses to treatment, but a partial response was found for three patients who received SBRT concurrently with ipilimumab, including two patients (10 percent) on the concurrent lung arm and one patient (5 percent) on the concurrent liver arm. No patients in the sequential radiation groups experienced a partial response.

“A small percentage of patients experienced a potential abscopal effect, where tumors that were not irradiated became smaller after we treated different sites with radiation,” explained Welsh. “For example, one patient with anaplastic thyroid cancer — one of the deadliest types of cancer — experienced a reduction in the primary tumor after we irradiated a lung metastasis. This patient had controlled disease for more than 13 months.”

Lesions from non-small cell lung cancer (NSCLC) were most responsive to the combined treatment; two thirds of these patients had a favorable response (partial response or stable disease) following SBRT plus immunotherapy. Response to treatment was scored using immune-related criteria (irRC). Partial response represented a 50 percent or greater decrease in tumor size. Progressive disease represented a 25 percent increase in tumor size. Stable disease responses included those that did not fall into complete, partial or progressive response categories.

No patients experienced Grade 4 or 5 treatment-related side effects. Twenty-seven patients experienced Grade 3 toxicities related to immunotherapy, including colitis (8 patients), diarrhea (7 patients), rash (4 patients), elevation of liver enzymes (3 patients), hypophysitis (3 patients), elevation of bilirubin (1 patient) and intestinal obstruction (1 patient). Two patients experienced Grade 3 toxicities related to combination therapy, including one patient with an increase in liver enzymes and one patient with pneumonitis. Side effects were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0.

“We found that the addition of SBRT for patients who are on immunotherapy to be safe and well-tolerated, meaning that radiation oncologists can feel confident continuing immunotherapy for most patients when adding SBRT to lung or liver metastases. In fact, there may be additional benefit from combining the therapies in terms of improved disease control. Follow-up research in larger clinical trials is needed to determine which types of tumors and patients will respond best to this immunotherapy-radiation approach,” said Welsh.

For more information: www.astro.org

Related Content

Clinical Trials and Cutting-Edge Radiation Oncology Research to Be Featured at ASTRO 2017

Related Content

Sponsored Content | Videos | Radiation Therapy | January 18, 2019
Join Chris Toth, president of Varian’s Oncology Systems business, for a look at product introductions for 2018 plus
Novel Technique May Significantly Reduce Breast Biopsies
News | Breast Biopsy Systems | January 17, 2019
A novel technique that uses mammography to determine the biological tissue composition of a tumor could help reduce...
Digital Mammography Increases Breast Cancer Detection
News | Mammography | January 16, 2019
The shift from film to digital mammography increased the detection of breast cancer by 14 percent overall in the United...
MIM Software Inc. Receives FDA 510(k) Clearance for Molecular Radiotherapy Dosimetry
Technology | Nuclear Imaging | January 16, 2019
MIM Software Inc. received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for molecular radiotherapy...
Artificial Intelligence Used in Clinical Practice to Measure Breast Density
News | Artificial Intelligence | January 15, 2019
An artificial intelligence (AI) algorithm measures breast density at the level of an experienced mammographer,...
Machine Learning Uncovers New Insights Into Human Brain Through fMRI
News | Neuro Imaging | January 11, 2019
An interdisciplinary research team led by scientists from the National University of Singapore (NUS) has successfully...
Mobile App Data Collection Shows Promise for Population Health Surveys
News | Population Health | January 10, 2019
Mobile app data collection can bring access to more potential clinical study participants, reduce clinical study...
Hypertension With Progressive Cerebral Small Vessel Disease Increases Cognitive Impairment Risk
News | Magnetic Resonance Imaging (MRI) | January 08, 2019
Patients with high blood pressure and progression of periventricular white matter hyperintensities showed signs of...
Artificial Intelligence Pinpoints Nine Different Abnormalities in Head Scans

A brain scan (left) showing an intraparenchymal hemorrhage in left frontal region and a scan (right) of a subarachnoid hemorrhage in the left parietal region. Both conditions were accurately detected by the Qure.ai tool. Image courtesy of Nature Medicine.

News | Artificial Intelligence | January 07, 2019
The rise in the use of computed tomography (CT) scans in U.S. emergency rooms has been a well-documented trend1 in...
Electronic Brachytherapy Effective in Long-Term Study of 1,000 Early-Stage Breast Cancers
News | Brachytherapy Systems, Women's Healthcare | January 07, 2019
Breast cancer recurrence rates of patients treated with intraoperative radiation therapy (IORT) using the Xoft Axxent...