Precise radiotherapy may be safe second-line option for Cushing’s
Intensity-modulated radiation therapy found effective with few side effects
A form of precise radiation therapy, called intensity-modulated radiation therapy (IMRT), may be safe and effective for Cushing’s disease when a tumor in the brain’s pituitary gland has not been completely removed or has returned after surgery, a study suggests.
The study, “Intensity-modulated radiotherapy for cushing’s disease: single-center experience in 70 patients,” was published in Frontiers in Endocrinology.
The stress hormone cortisol is produced by the adrenal glands located atop the kidneys in response to the adrenocorticotropic hormone, which is released by the brain’s pituitary gland.
In Cushing’s, there is too much cortisol in the body because of a pituitary adenoma, a usually benign (non-cancerous) tumor that forms in the pituitary gland. This causes a wide range of symptoms, including weight gain, muscle weakness, and extreme fatigue.
Standard radiation therapy associated with high risk of toxicity
Usually, the first-line treatment for Cushing’s is surgery to remove the pituitary tumor. Radiation therapy, also called radiotherapy, may be used to help destroy tumor cells and shrink the tumor in patients who are not eligible for surgery, when the tumor comes back after surgery, and in cases of tumors invading nearby tissues.
Standard radiotherapy for Cushing’s shows high efficacy, but is associated with a “high risk of toxicity, mainly attributed to the harm to healthy surrounding structures,” the researchers wrote.
IMRT delivers beams of radiation that are shaped to match the shape of the tumor, and the intensity of each beam can be modulated. As such, this approach “can spare the surrounding normal structure better by a more conformal and precise dose distribution,” the researchers wrote.
However, no study has evaluated IMRT’s long-term safety and efficacy in a large group of Cushing’s patients.
To address this knowledge gap, a team of researchers in China looked at data from 70 people, ages 11 to 66 years, with Cushing’s disease who underwent IMRT at their center from April 2012 to August 2021 and were followed for at least three months.
Most (85.7%) were female, with a median age of 32 years, and they were followed for a median of 36.8 months (about three years).
Most patients (97.1%) underwent IMRT because the tumor was not removed completely or came back after surgery, or because cortisol levels did not return to normal (disease remission). The remaining two patients (2.9%) underwent the precise radiation therapy because they were not eligible for surgery.
Besides surgery, eight patients received medical treatment before undergoing IMRT. More than a third of the patients (38.8%) showed hypopituitarism, which occurs when the pituitary gland fails to produce enough of certain hormones.
Endocrine remission was defined as normal cortisol levels in urine or a normal decrease in cortisol levels after treatment with dexamethasone, a lab-made steroid similar to cortisol.
The proportion of patients who achieved endocrine remission was 28.5% at one year after IMRT, 50.2% at two years, 62.5% at three years, and 74% at five years. The median time to endocrine remission was 24 months, or two years.
Among demographic, clinical, and molecular factors, a higher Ki-67 proliferation index, indicating a higher % of tumor cells that may be dividing or multiplicating, was the only factor found to significantly predict endocrine remission.
At last follow-up, five patients (13.5%) showed endocrine recurrence, defined as having higher-than-normal cortisol levels after achieving remission. This occurred nearly two years after endocrine remission.
The proportion of recurrence-free patients dropped slightly over time, from 98.2% at one year to 88.7% at years three and five.
Tumor control rate was 98% during follow-up
A total of 51 patients had repeated magnetic resonance imaging before and after IMRT. During follow-up, the tumor control rate was 98%: in 20 patients, the tumor shrank, whereas in 30, it did not grow larger. In the remaining patient, the tumor was larger one year after radiation therapy.
“Endocrine remission, tumor control and recurrence rates were comparable” to other forms of radiation therapy, the researchers wrote.
Also, IMRT-induced hypopituitarism was reported in 16 patients (22.9%). “New onset hypopituitarism was less prevalent after IMRT than after conventional [radiation therapy],” the team wrote.
The only other complication was worsening of visual problems in one patient (1.3%) who also had an autoimmune disease called lupus. There were no reports of cerebrovascular accidents (strokes) or secondary brain tumors, but the short median follow-up time may have limited the detection of these late complications, the researchers noted.
Overall, these findings suggest that IMRT is “a highly effective second-line therapy with low side effect profile for [Cushing’s disease] patients,” the team wrote.