Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study

2021 ◽  
pp. 1-9
Author(s):  
I. Jonathan Pomeraniec ◽  
Zhiyuan Xu ◽  
Cheng-Chia Lee ◽  
Huai-Che Yang ◽  
Tomas Chytka ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Stereotactic Radiosurgery ◽  
Multicenter Study ◽  
Pituitary Adenomas ◽  
Pituitary Stalk ◽  
Tumor Control ◽  
Single Fraction ◽  
Neuroendocrine Function ◽  
Normal Pituitary Gland ◽  
The Impact

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Endocrinological outcome after pituitary transposition (hypophysopexy) and adjuvant radiotherapy for tumors involving the cavernous sinus

2011 ◽  
Vol 115 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Philipp Taussky ◽  
Ricky Kalra ◽  
Jeroen Coppens ◽  
Jahan Mohebali ◽  
Randy Jensen ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Stereotactic Radiosurgery ◽  
Cavernous Sinus ◽  
Stereotactic Radiotherapy ◽  
Pituitary Adenomas ◽  
Residual Tumor ◽  
Fractionated Stereotactic Radiotherapy ◽  
Normal Pituitary Gland ◽  
Radiotherapy Treatment

Object Stereotactic radiosurgery and fractionated stereotactic radiotherapy are commonly used in the treatment of residual or recurrent benign tumors of the skull base and cavernous sinus. A major risk associated with radiosurgical or radiotherapy treatment of residual or recurrent tumors adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors have used a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual tumor within the cavernous sinus. Here, the authors analyze the long-term endocrinological outcomes in patients with residual and recurrent tumors who undergo hypophysopexy and adjuvant radiosurgical or conformal fractionated radiotherapy treatment. Methods Pituitary transposition involves placement of a fat graft between the normal pituitary gland and residual tumor in the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and the graft is interposed between the pituitary gland and the residual tumor. The residual tumor may then be treated with stereotactic radiosurgery or conformal fractionated radiation therapy. The authors evaluated endocrinological outcome, safety of the procedure, and postoperative complications in patients who underwent this procedure during a 7-year period. Results Hypophysopexy has been used in 34 patients with nonfunctioning pituitary adenomas (19), functional pituitary adenomas (8), chordomas (2), meningiomas (2), chondrosarcoma (1), hemangiopericytoma (1), or hemangioma (1) involving the sella and cavernous sinus. Follow-up (radiographic and endocrinological) has been performed yearly in all patients. Two patients experienced postoperative endocrine deficits before radiosurgery (1 transient), but none of the patients developed new hypopituitarism during the median 4-year follow-up (range 1–8 years) after radiosurgery or fractionated stereotactic radiotherapy. Conclusions The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery or radiotherapy and effectively reduces the incidence of radiation injury to the normal pituitary gland when compared with historical controls.

Pituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 153-159 ◽  
Author(s):  
Guenther Christian Feigl ◽  
Karin Pistracher ◽  
Andrea Berghold ◽  
Michael Mokry
Keyword(s):  
Pituitary Gland ◽  
Gamma Knife ◽  
Side Effect ◽  
Pituitary Adenomas ◽  
Gamma Knife Surgery ◽  
Pituitary Stalk ◽  
Tumor Control ◽  
Pituitary Insufficiency ◽  
Endocrine Insufficiency

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.

MRI of pituitary adenomas: the position of the normal pituitary gland

1994 ◽  
Vol 36 (4) ◽  
pp. 295-297 ◽  
Author(s):  
M. Sumida ◽  
T. Uozumi ◽  
K. Mukada ◽  
K. Arita ◽  
K. Kurisu ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Pituitary Adenomas ◽  
Normal Pituitary Gland

Stereotactic Radiosurgery as an Alternative to Fractionated Radiotherapy for Patients with Recurrent or Residual Nonfunctioning Pituitary Adenomas

Neurosurgery ◽  
2003 ◽  
Vol 53 (5) ◽  
pp. 1086-1094 ◽  
Author(s):  
Bruce E. Pollock ◽  
Paul C. Carpenter
Keyword(s):  
Stereotactic Radiosurgery ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Growth Control ◽  
Tumor Control ◽  
Fractionated Radiotherapy ◽  
Nonfunctioning Pituitary Adenomas ◽  
Early Results ◽  
Anterior Pituitary Function ◽  
Radiation Induced

Abstract OBJECTIVE To evaluate tumor control rates and complications after stereotactic radiosurgery for patients with nonfunctioning pituitary adenomas. METHODS Between 1992 and 2000, 33 patients underwent radiosurgery for treatment of nonfunctioning pituitary adenomas. Thirty-two patients (97%) had undergone one or more previous tumor resections. Twenty-two patients (67%) had enlarging tumors before radiosurgery. The median tumor margin dose was 16 Gy (range, 12–20 Gy). The median follow-up period after radiosurgery was 43 months (range, 16–106 mo). RESULTS Tumor size decreased for 16 patients, remained unchanged for 16 patients, and increased for 1 patient. The actuarial tumor growth control rates at 2 and 5 years after radiosurgery were 97%. No patient demonstrated any decline in visual function. Five of 18 patients (28%) with anterior pituitary function before radiosurgery developed new deficits, at a median of 24 months after radiosurgery. The actuarial risks of developing new anterior pituitary deficits were 18 and 41% at 2 and 5 years, respectively. No patient developed diabetes insipidus. CONCLUSION Stereotactic radiosurgery safely provides a high tumor control rate for patients with recurrent or residual nonfunctioning pituitary adenomas. However, despite encouraging early results, more long-term information is needed to determine whether radiosurgery is associated with lower risks of new endocrine deficits and radiation-induced neoplasms, compared with fractionated radiotherapy.

scholarly journals Angiogenesis in Pituitary Adenomas and the Normal Pituitary Gland

2000 ◽  
Vol 85 (3) ◽  
pp. 1159-1162 ◽  
Author(s):  
Helen E. Turner ◽  
Zsusha Nagy ◽  
Kevin C. Gatter ◽  
Margaret M. Esiri ◽  
Adrian L. Harris ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Pituitary Adenomas ◽  
Anterior Pituitary ◽  
Pituitary Tumors ◽  
Anterior Pituitary Gland ◽  
Ulex Europaeus ◽  
Normal Pituitary Gland ◽  
Ulex Europaeus Agglutinin I ◽  
Acth Secreting ◽  
Tumor Types

Abstract Angiogenesis is essential for tumor growth beyond a few millimeters in diameter, and the intratumoral microvessel count that represents a measure of angiogenesis has been correlated with tumor behavior in a variety of different tumor types. To date no systematic study has assessed pituitary tumors of different secretory types, correlating vascular count with tumor size. The vascular densities of pituitary tumors and normal anterior pituitary were therefore assessed by counting vessels labeled using the vascular markers CD31 and ulex europaeus agglutinin I. One hundred and twelve surgically removed pituitary adenomas (30 GH-secreting, 25 prolactinomas, 15 ACTH-secreting, and 42 nonfunctioning tumors) were compared with 13 specimens of normal anterior pituitary gland. The vascular counts in the normal anterior pituitary gland were significantly higher (P < 0.05) than those in the tumors using both CD31 and ulex europaeus agglutinin I. In addition, microprolactinomas were significantly less vascular (P < 0.05) than macroprolactinomas, although there was no such difference between vascular densities of microadenomas and macroadenomas producing GH. ACTH-secreting tumors were, like microprolactinomas, of much lower vascular density than the normal pituitary and other secreting and nonsecreting tumor types. In marked contrast to other tumors, pituitary adenomas are less vascular than the normal pituitary gland, suggesting that there may be inhibitors of angiogenesis that play an important role in the behavior of these tumors.

scholarly journals PC3 - 138 Stereotactic Radiosurgery for Intracranial Hemangiopericytomas – A Multicenter Study

2016 ◽  
Vol 43 (S4) ◽  
pp. S21-S21
Author(s):  
O. Cohen-Inbar
Keyword(s):  
Stereotactic Radiosurgery ◽  
Multicenter Study ◽  
Radiation Effects ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Tumor ◽  
Who Grade ◽  
Fractionated Radiotherapy ◽  
Local Progression

Hemangiopericytomas (HPC) are widely recognized for their aggressive clinical behavior. We report a large multicenter study, through the International Gamma Knife Research Foundation reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly-discovered HPC’s. Methods: Eight centers participated, reviewing a total of 90 patients harboring 133 tumors. Prior treatments included embolization (n = 8), chemotherapy (n=2), and fractionated radiotherapy (n=34). The median tumor volume at the time of SRS was 4.9 ml (range 0.2-42.4 ml). WHO-grade II (typical) HPC’s formed 78.9% (n=71) of the cohort. The median margin and maximal doses delivered were 15 Gy (2.8-24) and 32 Gy (8-51), respectively. The median clinical and radiographic follow-up period was 59 months (6-190) and 59 months (6-183), respectively. Results: At last follow-up, 55% of tumors and 62.2% of patients demonstrated local tumor control. New remote intracranial tumors were found in 27.8%. 24.4% of patients developed extra-cranial metastases. Adverse radiation effects were noted in 6.7%. The overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression free survival was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Margin dose greater than 16 Gy (p=0.037) and tumor histology (p=0.006) were shown to influence PFS. Conclusions: SRS provides a reasonable rate of local tumor control and a low risk of adverse effects

The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases

2013 ◽  
Vol 119 (5) ◽  
pp. 1131-1138 ◽  
Author(s):  
Eric K. Oermann ◽  
Marie-Adele S. Kress ◽  
Jonathan V. Todd ◽  
Brian T. Collins ◽  
Riane Hoffman ◽  
...  
Keyword(s):  
Local Control ◽  
Local Tumor Control ◽  
Dose Fractionation ◽  
Tumor Control ◽  
Metastatic Tumors ◽  
Single Fraction ◽  
Frameless Radiosurgery ◽  
Whole Brain Radiation ◽  
The Impact ◽  
The Brain

Object Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2–5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. Methods The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2–5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. Results There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83–6.91, p = 0.032). Conclusions Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.

scholarly journals The Clinical Outcome of Hypofractionated Stereotactic Radiotherapy With CyberKnife Robotic Radiosurgery for Perioptic Pituitary Adenoma

2016 ◽  
Vol 15 (6) ◽  
pp. NP10-NP15 ◽  
Author(s):  
Putipun Puataweepong ◽  
Mantana Dhanachai ◽  
Ake Hansasuta ◽  
Somjai Dangprasert ◽  
Thiti Swangsilpa ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Stereotactic Radiotherapy ◽  
Pituitary Adenomas ◽  
Fractionated Stereotactic Radiotherapy ◽  
Tumor Control ◽  
Optic Pathway ◽  
Hypofractionated Stereotactic Radiotherapy ◽  
Single Fraction ◽  
Robotic Radiosurgery ◽  
Cyberknife Robotic Radiosurgery

Stereotactic radiation technique including single fraction radiosurgery and conventional fractionated stereotactic radiotherapy is widely reported as an effective treatment of pituitary adenomas. Because of the restricted radiation tolerance dose of the optic pathway, single fraction radiosurgery has been accepted for small tumor located far away from the optic apparatus, while fractionated stereotactic radiotherapy may be suitable for larger tumor located close to the optic pathway. More recently, hypofractionated stereotactic radiotherapy has become an alternative treatment option that provides high rate of tumor control and visual preservation for the perioptic lesions within 2 to 3 mm of the optic pathway. The objective of the study was to analyze the clinical outcomes of perioptic pituitary adenomas treated with hypofractionated stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median tumor volume was 3.35 cm3 (range, 0.82-25.86 cm3). The median prescribed dose was 25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were smaller in size. No patient’s vision deteriorated after hypofractionated stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13 patients. No newly developed hypopituitarism was detected in our study. These data confirmed that hypofractionated stereotactic radiotherapy achieved high rates of tumor control and visual preservation. Because of the shorter duration of treatment, it may be preferable to use hypofractionated stereotactic radiotherapy over fractionated stereotactic radiotherapy for selected pituitary adenomas immediately adjacent to the optic apparatus.

The Effect of Prescription Isodose Variation on Tumor Control and Toxicities in Stereotactic Radiosurgery for Sporadic Vestibular Schwannoma: Propensity Score-Matched Case–Control Study

2021 ◽  
Author(s):  
Achiraya Teyateeti ◽  
Christopher S. Graffeo ◽  
Avital Perry ◽  
Eric J. Tryggestad ◽  
Paul D. Brown ◽  
...  
Keyword(s):  
Propensity Score ◽  
Stereotactic Radiosurgery ◽  
Vestibular Schwannoma ◽  
Hearing Preservation ◽  
Tumor Control ◽  
Gamma Knife Stereotactic Radiosurgery ◽  
The Impact ◽  
Prescription Isodose

Abstract Objective Vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (SRS) was typically performed at 50% isodose line (IDL50); however, the impact of IDL variation on outcomes is poorly understood. This study aimed to compare tumor control (TC) and toxicities between treatment at 40% (IDL40) and 50% (IDL50). Methods and Materials Sporadic/unilateral VS patients treated with SRS dose 12 to 14 Gy and prescription isodose volume ≤10cm3 were included. Propensity score matching was applied to IDL40 cohort to generate an IDL50 companion cohort, adjusting for age and prescription isodose volume. After exclusion of patients with follow-up <24 months, there were 30 and 28 patients in IDL40 and IDL50 cohorts, respectively. Results Median follow-up time was 96 months (24–225 months). Actuarial and radiographic TC rates were 91.8% and clinical TC was 96.2% both at 5 and 10 years. TC was higher in IDL40 cohort but not significant (96.4 vs. 86.7%; p = 0.243). Hearing preservation (HP) rates were 71.9 and 39.2% at 5- and 10-year intervals, with significantly higher rates of HP noted in IDL40 cohort (83.3 vs. 57.1% at 5-year interval; 62.5 vs. 11.4% at 10-year interval; p = 0.017). Permanent facial neuropathy occurred in two patients, both from the IDL50 cohort (3.5%). Rates of post-SRS steroid treatment or shunt placement for hydrocephalus were slightly higher in IDL50 patients (6.9 vs. 17.9%; p = 0.208 and 3.3 vs. 7.1%; p = 0.532). Conclusion For treatment of VS with SRS, dose prescription at IDL40 or IDL50 provides excellent long-term TC and toxicity profiles. IDL40 may be associated with improved long-term HP.

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