High-dose Radiation Spaced Over Week Safe Option for Cushing’s Patients with Difficult Tumors, Study Says

High doses of radiation therapy delivered over two-to-five sessions offer results similar to that of radiation given in a single high-dose session for Cushing’s disease patients whose cortisol levels remain high after surgery, a retrospective study found.

Unlike the single-dose approach, this multi-session therapy may also be a safe and convenient option for people with larger tumors or tumors near the optic nerves, who are often treated with courses of radiotherapy lasting five to six weeks.

The study, “Outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for refractory Cushing’s disease,” was published in the journal Pituitary.

Radiation therapy is commonly given to people with Cushing’s disease who are not eligible for surgery or who have some tumor remaining after surgery. A course of radiotherapy usually takes five to six weeks, and it can take several years to fully restore cortisol levels.

Stereotactic radiation therapy (SRS) is a variation of radiation therapy that targets the tumor more precisely and applies large doses of radiation in a single session. A one-time session is more convenient and associated with lesser time to regaining normal cortisol levels.

Hypofractionated stereotactic radiotherapy (HSRT) is a variation of SRS that targets the tumor as precisely, but applies two-to-five fractions of the full dose over one week. This treatment is also easier on patients than traditional radiation therapy, because it takes less time to finish and to restore cortisol levels. It is also less toxic to adjacent tissues than SRS, because it applies lower radiation doses each time.

HSRT is an alternative for patients whose risk of side effects associated with SRS is high, such as those whose tumors are near important nerves like the optic nerve. However, no studies to date have compared the outcomes of HSRT and SRS in people with Cushing’s disease.

Researchers at Vanderbilt University did a retrospective study comparing the toxicity and effectiveness of HSRT and SRS in Cushing’s disease patients who did not achieve cortisol balance after surgery.

They looked at whether these patients achieved normal cortisol levels with or without extra medication, the time to achieve normal cortisol levels, if the tumor continued to grow after the treatment, and complications.

Overall, 18 patients treated at their institution post-surgery with either SRS or HSRT (1996 to 2018) took part in the study, nine patients for each type of radiotherapy. Participants were mostly Caucasian women, with a median age of 42, and a median follow-up time of 3.4 years.

None of the tumors continued to grow after the treatment. On average, the patients achieved normal cortisol levels with complementary medication after nine months, and after 41 months (around 3.5 years) they achieved normal levels without medication. Five achieved normal cortisol levels during the follow-up, four did not need any complementary medication.

Whether or not patients achieved cortisol balance and the time to cortisol balance did not differ between the groups.

“HSRT is a feasible and appropriate treatment approach in the radiosurgical management of Cushing’s disease. Patients treated by HSRT appear to have comparable rates of biochemical control [cortisol balance] and time to biochemical control compared to SRS,” the researchers wrote.

Neither group of patients showed any significant long-term complications after the treatment, but two people in the SRS group developed hypothyroidism — low levels of the thyroid hormone — and two in the HSRT group developed adrenal insufficiency — when the adrenal glands do not produce enough steroid hormones.

However, “HSRT may offer patients with large tumors or tumors with chiasmatic involvement [near optic nerves] a safe treatment comparable with IMRT [traditional radiotherapy] with the convenience of a single week of treatment,” the investigators said.

Since this was a retrospective, or backwards looking, study with few participants, the scientists noted that “[p]rospective studies of HRST are needed to validate the findings of this work.”