Although uncommon, some people with cancer will develop granulomas, the clumps of immune cells that are a hallmark of sarcoidosis — and those who do are more likely to have better survival outcomes, a new study reports.
Sarcoidosis is caused by an over-active immune system and is characterized by the formation of granulomas in body tissues. Prior research has suggested that people with sarcoidosis are at an increased risk of developing cancer. However, there is little published data on sarcoidosis risk among patients with cancer.
Now, a research team analyzed data from 1,809 cancer patients from two institutions: the University of Miami Hospital, Miami Veterans Affairs Medical Center, in Florida, in the U.S., and Chiba University in Chiba, Japan. Of note, this clinical trial (NCT03844698) is still enrolling participants; the study is expected to run through February 2022.
Altogether, 133 of the patients analyzed (7.4%) were found to have sarcoidosis-like granulomas on biopsies done after their cancer diagnoses. A total of 61 patients were male and 72 were female; their mean age at granuloma identification was 64.5 years. The most common types of cancer among these patients were skin (22.5%) and breast (20.3%) cancers, followed by lymph node (12.8%) and prostate (10.5%) cancers.
Among the patients, 36.1% were white, 26.3% were Asian, and 23.3% were Latino.
Of note, statistical analyses indicated that Japanese patients were significantly less likely to develop granulomas within five years of cancer diagnosis, compared with American patients.
Next, the researchers assessed the relationship between granulomas and patient clinical outcomes, and evaluated two groups of patients. The first group included cancer patients who developed granulomas within three years of their cancer diagnosis; for each person in the first group, the researchers then selected a patient with the same type of cancer but without granulomas to serve as a control group.
The mean age at cancer diagnosis was 57.95 in the control group and 58.37 in the granuloma group. Follow-up was conducted for more than five years.
Statistical analyses indicated that, compared with controls, the individuals with granulomas were 4.6 times more likely to be alive two years after their diagnosis. Similar benefits to survival rates were seen at four, six, and 10 years after diagnosis. Notably, at 10 years, cancer patients with granulomas were 5.53 times more likely to be alive compared with those with cancer without sarcoid-like immune cell clumps.
Additionally, the individuals with such immune cell clumps were significantly less likely to experience metastasis, which occurs when a tumor spreads from one location and starts growing in other body parts. Since metastasis is associated with worse survival outcomes across cancer types, this finding complements the survival data found.
Similarly, fewer individuals with sarcoid-like granulomas were treated with chemotherapy or radiation — likely because fewer of them experienced metastasis or more advanced cancer stages to prompt such treatment.
“The frequency of metastatic cancer was significantly lower in patients with sarcoid-like granulomas than in controls. Moreover, [the data] showed a significant survival advantage in those with sarcoid-like granulomas,” the researchers wrote.
“Thus, finding sarcoid-like granulomas could serve as a prognostic biomarker,” they added.
Subsequent analyses looking at individual cancer types did not find a significant association between granulomas and survival, although researchers noted that these results were limited by the relatively small number of patients with any one type of cancer in the groups analyzed.
Since the immune system is able to kill cancer cells, the researchers speculated that granulomas might be associated with better outcomes because they are indicative of increased immune activity that might limit cancer growth.
“Further investigation of this speculation may lead to new therapeutic agents for cancer immunotherapy,” the team wrote. The researchers also noted a need for further research into how granulomas form in general, and in cancer patients specifically.
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