Single-fraction radiation therapy showed promise in metastatic Merkel cell carcinoma

ALBUQUERQUE – Single-fraction radiotherapy of distant metastatic Merkel cell carcinomas led to complete response rates ranging from 52% to 81%, and caused no adverse effects except rare transient pain flares, according to a single-center, single-arm study of 26 patients.

The rate of initial response was 94%, and three-quarters of responders never progressed during the study period, Dr. Paul Nghiem said at the annual meeting of the Society for Investigative Dermatology.

Merkel cell carcinoma (MCC) creates a "terribly frustrating situation" when it metastasizes because although two-thirds of patients initially respond to chemotherapy, the effect is short-lived, with a median progression-free survival of only 94 days, said Dr. Nghiem, professor of dermatology at the University of Washington, Seattle.

Radiation therapy is often used as an adjuvant or palliative treatment in MCC, but it is almost always fractionated, requiring multiple visits and potentially killing T cells that function in tumor immunity, Dr. Nghiem said. In light of evidence that single-fraction radiotherapy (SFRT) enhanced tumor immunity in mice, he and his colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle decided to "think outside the box and do something different."

Therefore, in 2010, the researchers began using 8-Gy SFRT on distant MCC metastases. In all, they targeted 93 tumors in 26 patients (median age, 68 years). Survivors were followed for a median of 252 days (range, 76-699 days). The median tumor size was 4 cm (range, 1-19 cm), and patients had 1-28 tumors, with an average of 3.5 tumors per patient.

The investigators classified half of patients (n = 13) as high risk because they were immunosuppressed and/or had prior chemotherapy. Other patients were categorized as low risk. High-risk patients had 60 tumors and a 3.5-month median interval from chemotherapy to start of SFRT. The low-risk group had 33 tumors.

A complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (P = .008), Dr. Nghiem reported. No tumor that completely responded ever recurred, regardless of risk, he said. In one case, a patient with a 5-cm metastasis compressing the trachea reported greater ease of breathing several days after SFRT, and subsequent imaging studies showed complete response with no recurrence at 20 months, he said, adding that the patient remained on an immunostimulant.

The rate of recurrence also was significantly lower in low-risk (9%) versus high-risk patients (30%; P = .02), Dr. Nghiem said. The P value "was statistically significant in this midsize trial, suggesting that the immune system really matters in controlling these lesions," he said, adding that Merkel cell carcinoma, "maybe more than most other cancers, is extremely linked to immune function. As we increase radiation dose, we see more cancer killing [activity], and more immune cell activation at lower doses."

The investigators did not perform post-treatment biopsies to quantify abscopal effects, Dr. Nghiem noted.

The National Cancer Institute, the American Cancer Society, and the National Institutes of Health funded the research. Dr. Nghiem reported no relevant conflicts of interest.

ALBUQUERQUE – Single-fraction radiotherapy of distant metastatic Merkel cell carcinomas led to complete response rates ranging from 52% to 81%, and caused no adverse effects except rare transient pain flares, according to a single-center, single-arm study of 26 patients.

The rate of initial response was 94%, and three-quarters of responders never progressed during the study period, Dr. Paul Nghiem said at the annual meeting of the Society for Investigative Dermatology.

Merkel cell carcinoma (MCC) creates a "terribly frustrating situation" when it metastasizes because although two-thirds of patients initially respond to chemotherapy, the effect is short-lived, with a median progression-free survival of only 94 days, said Dr. Nghiem, professor of dermatology at the University of Washington, Seattle.

Radiation therapy is often used as an adjuvant or palliative treatment in MCC, but it is almost always fractionated, requiring multiple visits and potentially killing T cells that function in tumor immunity, Dr. Nghiem said. In light of evidence that single-fraction radiotherapy (SFRT) enhanced tumor immunity in mice, he and his colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle decided to "think outside the box and do something different."

Therefore, in 2010, the researchers began using 8-Gy SFRT on distant MCC metastases. In all, they targeted 93 tumors in 26 patients (median age, 68 years). Survivors were followed for a median of 252 days (range, 76-699 days). The median tumor size was 4 cm (range, 1-19 cm), and patients had 1-28 tumors, with an average of 3.5 tumors per patient.

The investigators classified half of patients (n = 13) as high risk because they were immunosuppressed and/or had prior chemotherapy. Other patients were categorized as low risk. High-risk patients had 60 tumors and a 3.5-month median interval from chemotherapy to start of SFRT. The low-risk group had 33 tumors.

A complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (P = .008), Dr. Nghiem reported. No tumor that completely responded ever recurred, regardless of risk, he said. In one case, a patient with a 5-cm metastasis compressing the trachea reported greater ease of breathing several days after SFRT, and subsequent imaging studies showed complete response with no recurrence at 20 months, he said, adding that the patient remained on an immunostimulant.

The rate of recurrence also was significantly lower in low-risk (9%) versus high-risk patients (30%; P = .02), Dr. Nghiem said. The P value "was statistically significant in this midsize trial, suggesting that the immune system really matters in controlling these lesions," he said, adding that Merkel cell carcinoma, "maybe more than most other cancers, is extremely linked to immune function. As we increase radiation dose, we see more cancer killing [activity], and more immune cell activation at lower doses."

The investigators did not perform post-treatment biopsies to quantify abscopal effects, Dr. Nghiem noted.

The National Cancer Institute, the American Cancer Society, and the National Institutes of Health funded the research. Dr. Nghiem reported no relevant conflicts of interest.

ALBUQUERQUE – Single-fraction radiotherapy of distant metastatic Merkel cell carcinomas led to complete response rates ranging from 52% to 81%, and caused no adverse effects except rare transient pain flares, according to a single-center, single-arm study of 26 patients.

The rate of initial response was 94%, and three-quarters of responders never progressed during the study period, Dr. Paul Nghiem said at the annual meeting of the Society for Investigative Dermatology.

Merkel cell carcinoma (MCC) creates a "terribly frustrating situation" when it metastasizes because although two-thirds of patients initially respond to chemotherapy, the effect is short-lived, with a median progression-free survival of only 94 days, said Dr. Nghiem, professor of dermatology at the University of Washington, Seattle.

Radiation therapy is often used as an adjuvant or palliative treatment in MCC, but it is almost always fractionated, requiring multiple visits and potentially killing T cells that function in tumor immunity, Dr. Nghiem said. In light of evidence that single-fraction radiotherapy (SFRT) enhanced tumor immunity in mice, he and his colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle decided to "think outside the box and do something different."

Therefore, in 2010, the researchers began using 8-Gy SFRT on distant MCC metastases. In all, they targeted 93 tumors in 26 patients (median age, 68 years). Survivors were followed for a median of 252 days (range, 76-699 days). The median tumor size was 4 cm (range, 1-19 cm), and patients had 1-28 tumors, with an average of 3.5 tumors per patient.

The investigators classified half of patients (n = 13) as high risk because they were immunosuppressed and/or had prior chemotherapy. Other patients were categorized as low risk. High-risk patients had 60 tumors and a 3.5-month median interval from chemotherapy to start of SFRT. The low-risk group had 33 tumors.

A complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (P = .008), Dr. Nghiem reported. No tumor that completely responded ever recurred, regardless of risk, he said. In one case, a patient with a 5-cm metastasis compressing the trachea reported greater ease of breathing several days after SFRT, and subsequent imaging studies showed complete response with no recurrence at 20 months, he said, adding that the patient remained on an immunostimulant.

The rate of recurrence also was significantly lower in low-risk (9%) versus high-risk patients (30%; P = .02), Dr. Nghiem said. The P value "was statistically significant in this midsize trial, suggesting that the immune system really matters in controlling these lesions," he said, adding that Merkel cell carcinoma, "maybe more than most other cancers, is extremely linked to immune function. As we increase radiation dose, we see more cancer killing [activity], and more immune cell activation at lower doses."

The investigators did not perform post-treatment biopsies to quantify abscopal effects, Dr. Nghiem noted.

The National Cancer Institute, the American Cancer Society, and the National Institutes of Health funded the research. Dr. Nghiem reported no relevant conflicts of interest.