New imaging method helps pinpoint tumors in Cushing’s disease
CXCR4-targeting PET/MRI may help identify patients at higher recurrence risk
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In Cushing’s disease, an imaging technique that uses a radioactive tracer targeting the CXCR4 protein may help locate the tumor responsible for the condition, according to a Chinese study. The researchers also found that tumors with lower levels of CXCR4 were linked to higher recurrence rates.
This technique combines positron emission tomography (PET) and magnetic resonance imaging (MRI) to more accurately locate tumors in the brain’s pituitary gland, including both small and large growths. Tumors with lower levels of CXCR4, a protein found on tumor cell surfaces, tended to be larger and were linked to poorer progression-free survival.
These findings could help inform “personalized management strategies” for people with Cushing’s disease, researchers wrote in the study, “The value of targeting CXCR4 with 68Ga-Pentixafor PET/MRI for Cushing’s disease: a retrospective cohort study,” published in the European Journal of Nuclear Medicine and Molecular Imaging.
Understanding Cushing’s disease and how tumors are located
Cushing’s syndrome occurs when the body produces too much cortisol. High levels of this hormone can cause symptoms such as high blood pressure and high blood sugar. In Cushing’s disease, excess cortisol is caused by a tumor in the pituitary gland that releases adrenocorticotropic hormone (ACTH), which tells the body to produce cortisol.
Pinpointing the exact location of the tumor is critical so surgeons can remove it while minimizing damage to surrounding structures. A newer imaging technique called 68Ga-pentixafor PET/MRI combines PET, which shows how tissues are functioning, with MRI, which provides detailed images of the body’s structures. The radioactive tracer targets CXCR4, a protein believed to help tumor cells grow and survive.
However, some pituitary tumors appear to have low levels of CXCR4. To examine whether CXCR4 levels were linked to tumor behavior and the risk of recurrence, the researchers divided 138 patients (median age 37) into two groups based on their CXCR4 levels. All patients had a confirmed diagnosis of Cushing’s disease.
The imaging results were highly accurate. When PET/MRI was combined with standard contrast-enhanced MRI, which uses a dye to make internal structures easier to see, tumors were correctly located with very high sensitivity (98.7%) and diagnostic accuracy (96.3%). Sensitivity refers to how well a test detects a disease when it is actually present.
Using receiver operating characteristic analysis — a statistical method used to determine the best cutoff for a biological marker — the researchers divided patients into two groups based on CXCR4 levels. Most patients (95) had high CXCR4 levels, while the remaining 43 patients had low levels of the protein.
CXCR4 levels may help predict recurrence risk
Patients with low CXCR4 levels had higher rates of relapse than those with high levels of the protein (34.9% vs. 12.6%). Tumors in the low-CXCR4 group were also significantly larger, with a median diameter of 10 millimeters compared with 7 millimeters (about 0.39 vs. 0.28 inches) and were more than twice as large in volume. These tumors also produced lower levels of ACTH (median score 122.6 vs. 231.2).
Among patients who achieved remission, meaning their cortisol levels returned to normal after treatment, tumors were more likely to recur in those with low CXCR4 levels (17.6% vs. 3.7%). After about 2.5 years, patients with low CXCR4 levels had significantly worse progression-free survival, defined as the length of time a person lives without the disease worsening.
Because tumors with low CXCR4 levels tended to be larger, the researchers also examined outcomes in patients with macroadenomas (large tumors) and microadenomas (smaller tumors). Among patients with macroadenomas, recurrence tended to be more common in those with low CXCR4 levels (25% vs. 3.2%). Among those with microadenomas, remission and recurrence rates were similar regardless of CXCR4 levels.
Measuring CXCR4 levels may help classify patients into different risk groups and could support future treatment decisions. Although it may seem unexpected that lower CXCR4 levels were linked to larger tumors, the researchers suggested that tumors with higher CXCR4 levels may produce more ACTH. This could lead to symptoms appearing earlier, allowing tumors to be detected while they are still smaller and less advanced.
“Further multicenter prospective studies [in which patients are followed forward in time] are warranted to validate the reliability of this approach,” the researchers wrote.
