...A safe alternative for treatment of ACTH-producing pituitary adenomas?
For the next few posts, I'm going to examine the latest research about the use of Gamma Knife (GK) radiosurgery in the treatment of pituitary adenomas, especially ACTH-producing adenomas.
Although GK is called radiosurgery, there is no cutting involved. 201 "beams" of cobalt-60 gamma radiation are focused on the region to be treated. The beams go through the skull in different spots, with each beam too weak to hurt normal tissue. However, when they all come together in the area to be treated, they are then strong enough to destroy the tumor. It is a type of single-fraction radiosurgery.
Another method often used is fractionated stereotactic radiotherapy. The Johns Hopkins' site explains FSR this way:
[With FSR] multiple fractionated doses or fractionated stereotactic radiation can be delivered. The main advantage of fractionation is that it allows higher doses to be delivered to the tumor because of increased tolerance of the surrounding normal tissues to these smaller fractionated doses. In other words, while single-dose stereotactic radiation takes advantage of differences in the pattern of radiation given, fractionated stereotactic radiation takes advantage of not only the pattern, but more importantly of the differing radiosensitivities of normal and surrounding tissues. Another advantage is so-called ”iterative” treatment, meaning the shape and intensity of the treatment plan can be modified during the course of therapy.
Dr. Molitch and Professor Grossman1, in the March 2009 issue of Pituitary which focuses on radiotherapy for pituitary tumors, introduce the issue as guest editors. In their introduction, they say:
As of yet, there are no adequate studies to conclude whether there is one mode of single-dose radiotherapy that has superior efficacy or safety, and indeed direct comparisons of single-dose vs. fractionated stereotactic radiotherapy (FSR) are all but non-existent.
GK radiosurgery is done in one session. FSR takes multiple sessions spread over a period of time. The head must be in the exact position during each session. For many reasons, including ease, GK has become the preferred method.
In the same issue of Pituitary, Dr. Mary Vance at the University of Virginia2 discusses the use of radiation therapy in the treatment of Cushing's disease. According to Dr. Vance, radiation therapy is used "most commonly as adjunctive therapy after unsuccessful pituitary surgery."
Dr. Vance reiterates the fact that GK is "not suitable for a large lesion close to the optic nerves or optic chiasm" and that all radiation therapies do cause loss of pituitary function eventually. She also emphasizes "There are no prospective studies comparing the results among different methods of radiation delivery regarding efficacy, development of new pituitary hormone deficiency or complications."
Points that Dr. Vance makes about any type of radiation therapy:
- Basically used when transsphenoidal surgery doesn't work
- Takes time (months to years) before it works
- Medical therapy (ketoconazole or metyrapone) to lower cortisol may be needed in conjunction with radiation treatment until it works
- Patient needs to be monitored closely for liver problems due to drug therapy and for lower natural production of cortisol
Dr. Vance has a nice summary of the various types of radiation therapy which include gamma knife (GK).
The Gamma knife series of 90 patients treated at the University
of Virginia found that a normal 24 h UFC level occurred in 49 patients (54%) at an average time of 13 months (range 2–67 months). Ten patients (20%) had relapse of Cushing’s with the mean time to relapse of 27 months (range 6–60 months). Seven of these patients underwent a second Gamma knife treatment, three achieved remission. Five of the seven patients (71%) who had a second Gamma knife treatment developed a new visual or 3rd, 4th or 6th cranial nerve deficit. These cranial nerve deficits either resolved (two patients), improved (two patients) or persist(one patient) (New pituitary hormone deficiency developed in 20 patients (22%)
This research also indicates there is no known safe radiation value for second attempts with GK.
The development of cranial nerve deficits and visual loss after a second Gamma knife treatment, in this study and in an another report , suggests that the presumed safe radiation dose to the cavernous sinus and optic chiasm and optic nerves is not known. For this reason, and until more definitive information is obtained, a second Gamma knife treatment should probably be avoided.
Dr. Vance points out that although radiation therapy is not perfect, there really is no perfect treatment for Cushing's disease at this time.
More posts on GK as a treatment coming this week.
1. Mark E. Molitch, Ashley B. Grossman (2008). Pituitary radiotherapy Pituitary, 12 (1), 1-2 DOI: 10.1007/s11102-008-0148-9
2. Mary Lee Vance (2008). Cushing’s disease: radiation therapy Pituitary, 12 (1), 11-14 DOI: 10.1007/s11102-008-0117-3