Radiation dose to neuroanatomical structures of pituitary adenomas and the effect of Gamma Knife radiosurgery on pituitary function

2020 ◽  
Vol 132 (5) ◽  
pp. 1499-1506
Author(s):  
I. Jonathan Pomeraniec ◽  
Davis G. Taylor ◽  
Or Cohen-Inbar ◽  
Zhiyuan Xu ◽  
Mary Lee Vance ◽  
...  

OBJECTIVEGamma Knife radiosurgery (GKRS) provides a safe and effective management option for patients with all types of pituitary adenomas. The long-term adverse effects of targeted radiation to the hypothalamic-pituitary axis in relationship to radiation dose remain unclear. In this retrospective review, the authors investigated the role of differential radiation doses in predicting long-term clinical outcomes and pituitary function after GKRS for pituitary adenomas.METHODSA cohort of 236 patients with pituitary tumors (41.5% nonfunctioning, 58.5% functioning adenomas) was treated with GKRS between 1998 and 2015. Point dosimetric measurements, with no minimum volume, to 14 consistent points along the hypothalamus bilaterally, pituitary stalk, and normal pituitary were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiological, and endocrine outcomes.RESULTSWith a median follow-up duration of 42.9 months, 18.6% of patients developed new loss of pituitary function. The median time to endocrinopathy was 21 months (range 2–157 months). The median dose was 2.1 Gy to the hypothalamus, 9.1 Gy to the pituitary stalk, and 15.3 Gy to the normal pituitary. Increasing age (p = 0.015, HR 0.98) and ratio of maximum dose to the pituitary stalk over the normal pituitary gland (p = 0.013, HR 0.22) were independent predictors of new or worsening hypopituitarism in the multivariate analysis. Sex, margin dose, treatment volume, nonfunctioning adenoma status, or ratio between doses to the pituitary stalk and hypothalamus were not significant predictors.CONCLUSIONSGKRS offers a low rate of delayed pituitary insufficiency for pituitary adenomas. Doses to the hypothalamus are low and generally do not portend endocrine deficits. Patients who are treated with a high dose to the pituitary stalk relative to the normal gland are at higher risk of post-GKRS endocrinopathy. Point dosimetry to specific neuroanatomical structures revealed that a ratio of stalk-to-gland radiation dose of 0.8 or more significantly increased the risk of endocrinopathy following GKRS. Improvement in the gradient index toward the stalk and normal gland may help preserve endocrine function.

2002 ◽  
Vol 97 ◽  
pp. 415-421 ◽  
Author(s):  
Günther Christian Feigl ◽  
Christine Maria Bonelli ◽  
Andrea Berghold ◽  
Michael Mokry

Object. The authors undertook a retrospective analysis of the incidence and time course of pituitary insufficiency following gamma knife radiosurgery (GKS) for pituitary adenomas. Methods. Pituitary adenomas in 92 patients were analyzed. There were 61 hormonally inactive tumors, 18 prolactinomas, and nine somatotropic and four adrenocorticotropic adenomas. The mean tumor volume was 3.8 cm3 (range 0.2–14.6 cm3). The mean prescription dose was 15 Gy. The mean prescription isodose was 50.7%. The mean follow-up time was 4.6 years (range 1.2–10 years). The following new or deteriorating insufficiencies that did not require treatment were recorded for the different pituitary axes: follicle-stimulating hormone (FSH)/luteinizing hormone (LH) 19 (20.6%), thyroid-stimulating hormone (TSH) 32 (34.8%), adenocorticotropic hormone (ACTH) 10 (10.9%), and growth hormone (GH) 26 (28.3%). For new insufficiencies or deterioration requiring replacement therapy, the figures were as follows: FSH/LH 20 (21.7%), TSH 22 (23.9%), ACTH eight (8.7%), and GH 12 (13%). Spot dosimetry was performed in 59 patients in the hypothalamic region, the pituitary gland, and pituitary stalk. The pituitary stalks in patients with deterioration of pituitary function received a statistically higher dosage of radiation, 7.7 ± 3.7 Gy compared with 5.5 ± 3 Gy (p = 0.03). Conclusions. The function of the residual normal pituitary gland is less affected following GKS of pituitary adenomas than after fractionated radiotherapy. Nonetheless, increased attention needs to be exercised to reduce the dose to the stalk and pituitary gland to minimize the incidence of these complications.


2011 ◽  
Vol 98 ◽  
pp. S38
Author(s):  
G. Sicignano ◽  
M. Losa ◽  
G.M. Cattaneo ◽  
A. Del Vecchio ◽  
R. Picozzi ◽  
...  

2011 ◽  
Vol 81 (2) ◽  
pp. S639-S640
Author(s):  
M.W. Tee ◽  
R. Weil ◽  
J. Valerio-Pascua ◽  
A. Hamrahian ◽  
J.H. Suh ◽  
...  

Neurosurgery ◽  
2003 ◽  
Vol 53 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Zbigniew Petrovich ◽  
Cheng Yu ◽  
Steven L. Giannotta ◽  
Chi-Shing Zee ◽  
Michael L.J. Apuzzo

Abstract OBJECTIVE In recent years, gamma knife radiosurgery (GKRS) has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing GKRS and the complications of this procedure are reviewed. METHODS Between 1994 and 2002, a total of 78 patients with pituitary adenomas underwent a total of 84 GKRS procedures in our medical center. This patient group comprised 46 men (59%) and 32 women (41%). All patients were treated for recurrent or residual disease after surgery or radiotherapy, with 83% presenting with extensive tumor involvement. The cavernous sinus was involved in 75 patients (96%), and 22 patients (28%) had hormone-secreting adenomas. This latter subset of patients included 12 prolactinomas (15%), 6 growth-hormone secreting tumors (8%), and 4 adrenocorticotropic hormone-secreting tumors (5%). The median tumor volume was 2.3 cm3, and the median radiation dose was 15 Gy defined to the 50% isodose line. The mean and median follow-up periods were 41 and 36 months, respectively. RESULTS GKRS was tolerated well in these patients; acute toxicity was uncommon and of no clinical significance. Late toxicity was noted in three patients (4%) and consisted of VIth cranial nerve palsy. In two patients, there was spontaneous resolution of this palsy, and in one patient, it persisted for the entire 3-year duration of follow-up. Of the 15 patients who presented with cranial nerve dysfunction, 8 (53%) experienced complete recovery and 3 (20%) showed major improvement within 12 months of therapy. Tumor volume reduction was slow, with 30% of patients showing decreased tumor volume more than 3 years after undergoing GKRS. None of the 56 patients with nonfunctioning tumors showed progression in the treated volume, and 4 (18%) of the 22 hormone-secreting tumors relapsed (P = 0.008). Of the four patients with adrenocorticotropic hormone-secreting adenomas, therapy failed in two of them. All six patients with growth hormone-producing tumors responded well to therapy. Of the 12 patients with prolactinomas 10 (83%) had normalization of hormone level and 2 patients experienced increasing prolactin level. Two patients with prolactinomas had three normal pregnancies after undergoing GKRS. CONCLUSION GKRS is a safe and effective therapy in selected patients with pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus. A radiation dose higher than 15 Gy is probably needed to improve control of hormone-secreting adenomas. Longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.


2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 153-159 ◽  
Author(s):  
Guenther Christian Feigl ◽  
Karin Pistracher ◽  
Andrea Berghold ◽  
Michael Mokry

Object Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. Methods A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. Results Complete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1–81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus (p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5 Gy to the pituitary gland (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients (77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time in patients with no new insufficiencies was 78.4 months (6.5 years, SD 4 years). Conclusions Gamma Knife surgery is a safe and effective treatment for patients with residual and recurrent pituitary adenomas. The rate of pituitary insufficiencies after GKS is still lower than that after conventional radiotherapy. Very low radiation doses are directed to the hypothalamus, and thus this structure does not play a major role in the development of pituitary insufficiencies after GKS. The results of this study show that patients in whom the pituitary stalk and pituitary gland receive a high mean point dose are more likely to develop pituitary insufficiencies after GKS than those who receive a lower dose.


2014 ◽  
Vol 120 (3) ◽  
pp. 647-654 ◽  
Author(s):  
Cheng-Chia Lee ◽  
Hideyuki Kano ◽  
Huai-Che Yang ◽  
Zhiyuan Xu ◽  
Chun-Po Yen ◽  
...  

Object Nonfunctioning pituitary adenomas (NFAs) are the most common type of pituitary adenoma and, when symptomatic, typically require surgical removal as an initial means of management. Gamma Knife radiosurgery (GKRS) is an alternative therapeutic strategy for patients whose comorbidities substantially increase the risks of resection. In this report, the authors evaluated the efficacy and safety of initial GKRS for NFAs. Methods An international group of three academic Gamma Knife centers retrospectively reviewed outcome data in 569 patients with NFAs. Results Forty-one patients (7.2%) underwent GKRS as primary management for their NFAs because of an advanced age, multiple comorbidities, or patient preference. The median age at the time of radiosurgery was 69 years. Thirty-seven percent of the patients had hypopituitarism before GKRS. Patients received a median tumor margin dose of 12 Gy (range 6.2–25.0 Gy) at a median isodose of 50%. The overall tumor control rate was 92.7%, and the actuarial tumor control rate was 94% and 85% at 5 and 10 years postradiosurgery, respectively. Three patients with tumor growth or symptom progression underwent resection at 3, 3, and 96 months after GKRS, respectively. New or worsened hypopituitarism developed in 10 patients (24%) at a median interval of 37 months after GKRS. One patient suffered new-onset cranial nerve palsy. No other radiosurgical complications were noted. Delayed hypopituitarism was observed more often in patients who had received a tumor margin dose > 18 Gy (p = 0.038) and a maximum dose > 36 Gy (p = 0.025). Conclusions In this study, GKRS resulted in long-term control of NFAs in 85% of patients at 10 years. This experience suggests that GKRS provides long-term tumor control with an acceptable risk profile. This approach may be especially valuable in older patients, those with multiple comorbidities, and those who have endocrine-inactive tumors without visual compromise due to mass effect of the adenoma.


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