Radiotherapy helps prevent further tumor growth in Cushing’s disease
Study shows precise method also aids in hormonal control
Using precise, image-guided techniques for the delivery of radiotherapy can help control Cushing’s disease in cases where surgery to remove disease-causing tumors proves impossible or ineffective, a study reports.
This type of stereotactic radiotherapy prevented further tumor growth in nearly 95% of participants and helped several reach normal levels of cortisol. Using modern techniques and equipment, including a linear accelerator (LINAC) to deliver radiation, also helped avoid some off-target effects associated with radiotherapy, including the development of new hormonal issues.
“Hormonal deficits can be kept low with stereotactic technology,” the researchers wrote.
Results were similar regardless of whether participants received one larger dose of radiation or several smaller doses.
The study, “Results for LINAC-based radiosurgery or fractionated stereotactic radiotherapy for corticotropic pituitary tumors: a single-center retrospective cohort,” was published in the Journal of Endocrinological Investigation.
Most participants showed no growth in tumor size after radiotherapy
In Cushing’s disease, high production of the hormone cortisol leads to symptoms such as emotional changes, fatigue, and skin abnormalities. Tumors in the pituitary gland, an area at the base of the brain, cause this hormonal imbalance. Because of these tumors, the pituitary may release excess amounts of the signaling molecule adrenocorticotropic hormone (ACTH). High ACTH then prompts elevated cortisol production.
Surgery to remove the disease-causing tumor is usually the first-line treatment for Cushing’s. However, this procedure isn’t always possible and doesn’t always fully remove the tumor. In these cases, clinicians may rely on radiotherapy to destroy tumor cells and control Cushing’s symptoms.
Modern radiotherapy methods, including stereotactic and LINAC-based methods, generally produce good results in terms of disease control. However, even with precise targeting, radiation may have off-target effects on the body’s hormonal, visual, and nervous systems. For Cushing’s, “the main issue that remains is new hormonal deficits caused by [radiotherapy],” the researchers noted.
To investigate these effects, the researchers examined medical records from 59 patients with Cushing’s who received stereotactic radiotherapy. Their average age was 41.9, and nearly 80% were female. All but one participant previously had at least one surgery, and most (64.4%) had two or more.
Although local control is desirable, the main goal when treating [Cushing’s disease] is to control ACTH secretion.
Depending on clinical circumstances, participants either received a single dose of radiation or several smaller doses.
The team examined the time period between receiving treatment and experiencing disease progression. Nearly all participants (94.9%) showed local disease control in the tumor area after radiotherapy, with no growth in tumor size.
Three individuals saw local disease progression, or an increase in tumor size. Using statistical methods, the researchers estimated a mean of 78.5 months, or about 6.5 years, passed between radiotherapy and progression. No deaths were reported.
“Although local control is desirable, the main goal when treating [Cushing’s disease] is to control ACTH secretion,” the researchers noted.
All but one Cushing’s disease patient had at least a single surgery
Hormonal disease control was defined by the researchers as having normal levels of cortisol in a urine test without additional cortisol-suppressing treatment. Symptoms also needed to be under control.
At two years post-therapy, 37.7% of participants met these criteria for hormonal control. On average, cortisol levels decreased over time after radiotherapy. A mean of 38.3 months, or just over three years, passed before participants reached hormonal control.
There were no significant differences in local disease or hormonal control between participants who received single-dose radiation versus those who received multiple doses.
Prior treatment with cabergoline or ketoconazole — medicines sometimes used for Cushing’s disease — also didn’t significantly impact outcomes. However, the researchers didn’t include anyone still receiving those treatments as in full hormonal remission, potentially limiting results.
“Our data did not show any visual toxicities and limited neurological complications,” the team noted. Relatively few participants (5.1%) developed new hormonal deficits during the follow-up period.
As this is a retrospective study, meaning analyses were based on existing medical records after treatment, this work has several limitations, the team noted. Future studies with prospective designs, in which researchers enroll participants before treatment, could examine variables such as at what point during disease progression is radiotherapy most effective.
“Prospective data for timing and [radiotherapy] regimen are warranted,” the team wrote.
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