Adrenocorticotropic Hormone-producing Pituitary Tumors: 12- to 22-year Follow-up after Treatment with Stereotactic Radiosurgery

Abstract OBJECTIVE To study retrospectively long-term outcomes of patients with adrenocorticotropic hormone-producing pituitary tumors that were treated with stereotactic Leksell gamma knife unit radiosurgery. METHODS Eighty-nine patients aged 5 to 67 years were treated between 1976 and 1985. Eighteen patients aged 18 to 68 years (mean age, 41 yr) were followed in detail. Fifteen patients were women. None had previously received conventional radiotherapy, but pituitary microsurgery had been performed in two patients, and one patient had had an adrenalectomy. In the remaining 15 patients, radiosurgery was the primary therapy. RESULTS Sixty-four patients had one stereotactic treatment, and 25 patients had two or more treatments. No complications were observed during treatment and the immediate follow-up period. At follow-up, 17 patients had died 1 to 20 years after the first treatment. No deaths were related to the treatment. In our 18 patients, the follow-up time after the first radiosurgical treatment was 12 to 22 years (mean follow-up period, 17 yr). Urinary cortisol levels gradually normalized in 83% of the patients. No recurrences were observed. Pituitary hormone insufficiencies developed in about two of every three patients and occurred even more than 10 years after treatment. Eight patients had transient hyperprolactinemia. The patients' vision and visual fields were unaffected, and none of them had signs of radiation-induced side effects such as brain tumors or brain necrosis. CONCLUSION Stereotactic radiosurgery is a safe and effective method in the treatment of patients with adrenocorticotropic hormone-producing pituitary tumors, and the effect of treatment is long-lasting. Stereotactic radiosurgery is mainly a complement to microsurgery because of its gradually appearing effect and the occurrence of pituitary insufficiency. New pituitary deficiencies may be found more than 10 years after treatment.

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Adrenocorticotropic Hormone-producing Pituitary Tumors: 12- to 22-year Follow-up after Treatment with Stereotactic Radiosurgery

Neurosurgery ◽

10.1227/00006123-200108000-00008 ◽

2001 ◽

Vol 49 (2) ◽

pp. 284-292 ◽

Cited By ~ 63

Author(s):

Charlotte Höybye ◽

Eva Grenbäck ◽

Tiit Rähn ◽

Marie Degerblad ◽

Marja Thorén ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Adrenocorticotropic Hormone ◽

Pituitary Tumors

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Efficacy and Safety of CyberKnife Stereotactic Radiosurgery in Acromegaly

Neuro-Oncology ◽

10.1093/neuonc/noab195.035 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv14-iv14

Author(s):

Desiree Seguna ◽

Scott Akker ◽

James Ahlquist ◽

Aparna Pal ◽

Antonia Brooke ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumour Size ◽

External Beam Radiotherapy ◽

Visual Fields ◽

Somatostatin Analogue ◽

Pituitary Hormone ◽

Blurred Vision ◽

Cranial Nerve Palsies ◽

Secondary Hypothyroidism

Abstract Aims Objective: Active acromegaly is associated with increased mortality. While surgery is the mainstay of treatment, it is not always curative. In selected cases, CyberKnife stereotactic radiosurgery (CK SRS) can be used as adjuvant treatment in patients with persistent disease. Method Methodology: Biochemical response was measured using serum IGF-1 levels, calculated as a percentage of the upper limit of normal (% ULN). Levels were recorded prior to treatment, at 6-12 months post-treatment and at the most recent follow-up. Anterior pituitary hormone deficits were assessed before and after treatment. Tumour size was followed-up using MRI. Results 10 patients (7 male, mean age 36 yrs [+/- 12.6, SD]) with acromegaly were treated with CK SRS. 9 were treated following failure to attain biochemical remission with TSS. 1 had primary CK SRS. 2 had previous conventional fractionated external beam radiotherapy. Median tumour diameter was 6 mm (IQR 5.2-10.5 mm), with cavernous sinus invasion in 2 cases. The dose was 20-24Gy/1#. 4 patients were on dopamine agonist, 4 on somatostatin analogue and 2 on pegvisomant. Mean follow-up 31.6 months (+/- 13.5 months, SD). Median IGF-1 % ULN was 146% pre-treatment (IQR 126.5-208.5), 109% at 6-12 months (IQR 76.5-131%) and 71% (IQR 59-91%) at last follow-up. Mean radiological follow-up 16.6 months (+/- 15.9 months, SD). No cases showed tumour enlargement. One patient developed secondary hypothyroidism. Side-effects: headache (7 patients), blurred vision (1 patient), fatigue/nausea (1 patient). No new visual fields defects, cranial nerve palsies, cerebrovascular events or secondary tumours. Conclusion Conclusions: CK SRS appears safe and effective in selected patients with acromegaly, when there is failure to attain biochemical cure with surgery and in patients intolerant or resistant to medical treatment.

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RADI-24. VENTRICULOMEGALY AFTER STEREOTACTIC RADIOSURGERY (SRS) FOR BRAIN METASTASES (BM): A PILOT ANALYSIS OF TWO INSTITUTIONAL EXPERIENCES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.116 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i26-i26

Author(s):

Ali Alattar ◽

Jiri Bartek ◽

Brian HIrshman ◽

Clark Chen

Keyword(s):

Stereotactic Radiosurgery ◽

Cerebral Atrophy ◽

White Matter Injury ◽

Whole Brain Radiation ◽

History Of ◽

Radiation Induced ◽

A Prospective Study ◽

The University ◽

Brain Radiation

Abstract INTRODUCTION: Ventriculomegaly, or dilatation of the cerebrospinal fluid (CSF) space, occurs after whole-brain radiation (WBRT) of brain metastasis (BM) patients due to either 1) hydrocephalus or 2) cerebral atrophy from radiation-induced white matter injury. In this study, we examined whether cumulative radiation from repeat stereotactic radiosurgery (SRS) increases the risk of ventriculomegaly. METHODS: Patients were included if they underwent SRS of BM from 2007–2017 and had imaging follow-up. We examined a cohort of 214 patients treated at the University of California San Diego (1,106 BM) and a second cohort of 148 patients (1,760 BM) treated at Karolinska Institutet. Ventriculomegaly was defined according to established morphometric criteria. Patients were grouped according to the development of new ventriculomegaly at last follow-up. Demographic, clinical, and dosimetric factors were compared between groups using univariable and multivariable logistic regressions. RESULTS: In the UCSD cohort, 63 patients (29%) presented with ventriculomegaly before SRS. Of 151 remaining patients with normal ventricular size before first SRS, 30 (20%) developed new ventriculomegaly. The odds of developing ventriculomegaly increased with history of WBRT (OR 5.247, p< 0.001) and trended toward significance with a greater number of SRS treatments (OR 1.296, p=0.075). In the Karolinska cohort, the odds of developing new ventriculomegaly trended towards significance with a greater number of SRS treatments (OR 1.605, p=0.26). To test whether this trend would achieve significance in a larger sample, we repeated the analysis in the combined cohort of 362 patients. The association between number of SRS treatments and developing ventriculomegaly reached significance (OR 1.254, p=0.049). CONCLUSIONS: These pilot findings suggest that cumulative radiation from repeat stereotactic radiosurgery (SRS) potentially increases the risk of ventriculomegaly. Based on our study, a prospective study of >350 patients will be needed to further test this hypothesis.

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104 Stereotactic Radiosurgery for Spetzler-Martin Grade IV and V Arteriovenous Malformations: An International Multicenter Study

Neurosurgery ◽

10.1093/neuros/nyx417.104 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 220-221

Author(s):

Jason P Sheehan ◽

Mohana Rao Patibandla ◽

Dale Ding ◽

Hideyuki Kano ◽

Zhiyuan Xu ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

Independent Predictor ◽

Multivariate Logistic Regression Analysis ◽

Favorable Outcome ◽

Single Session ◽

Radiation Induced ◽

International Multicenter Study ◽

Induced Changes

Abstract INTRODUCTION Due to the complexity of Spetzler-Martin (SM) grade IV-V arteriovenous malformations (AVM), the management of these lesions remains controversial. The aims of this multicenter, retrospective study are to evaluate outcomes after single-session stereotactic radiosurgery (SRS) for SM grade IV-V AVMs and determine predictive factors. METHODS We pooled data from 233 patients (mean age 33 years) with SM grade IV (94.4%) or V AVMs (5.6%) treated with single-session SRS at eight participating centers in the International Gamma Knife Research Foundation. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cc, 17.3 Gy, and 84.5 months, respectively. RESULTS >At a mean follow-up interval of 84.5 months, favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC) and was achieved in 26.2% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37% and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0%. Symptomatic and permanent RIC occurred in 10.7% and 4% of the patients, respectively. Only larger AVM diameter (P = 0.04) found to be an independent predictor of unfavorable outcome in the multivariate logistic regression analysis. The rate of favorable outcome was significantly lower for unruptured SM grade IV-V AVMs compared to ruptured ones (P = 0.042). Prior embolization was a negative independent predictor of AVM obliteration (P = 0.024) and radiologically evident RIC (P = 0.05) in multivariate analyses. CONCLUSION In this multi-institutional study, single session SRS had limited efficacy in the management of SM grade IV-V AVMs Favorable outcome was only achieved in a minority of unruptured SM grade IV-V AVMs, which supports less frequent utilization of SRS for the management of these lesions. A volume staged SRS approach for large AVMs represents an alternative approach for high grade AVM’s, but it requires further investigation.

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More II It than Meets the Eye: Outcomes After Single-Fraction Stereotactic Radiosurgery in a Case Series of Low-Grade Arteriovenous Malformations

Operative Neurosurgery ◽

10.1093/ons/opz153 ◽

2019 ◽

Cited By ~ 1

Author(s):

Christopher S Graffeo ◽

Michael J Link ◽

Scott L Stafford ◽

Yolanda I Garces ◽

Robert L Foote ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Proportional Hazards ◽

Case Series ◽

Cox Proportional Hazards ◽

Low Grade ◽

Single Fraction ◽

Kaplan Meier ◽

Radiation Induced ◽

Martin Grade

Abstract BACKGROUND Surgical resection is typically cited as the optimal treatment of patients with Spetzler-Martin Grade I-II arteriovenous malformation (AVM). OBJECTIVE To report our experience with single-fraction stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I-II AVM. METHODS A prospectively maintained registry was reviewed for patients with nonsyndromic Spetzler-Martin Grade I-II AVM having SRS from 1990 to 2011. Patients with <24 mo of follow-up or prior radiotherapy/SRS were excluded, resulting in a study population of 173 patients. Actuarial analysis was performed using the Kaplan-Meier method, and Cox proportional hazards modeling was performed with excellent outcomes (obliteration without new deficits) as the dependent variable. RESULTS Median post-SRS follow-up was 68 mo (range, 24-275). AVM obliteration was achieved in 132 (76%) after initial SRS. Eleven additional patients achieved obliteration after repeat SRS for an overall obliteration rate of 83%. The rate of obliteration was 60% at 4 yr and 78% at 8 yr. Post-SRS hemorrhage occurred in 7 patients (4%), resulting in 3 minor deficits (2%) and 1 death (<1%). Radiation-induced complications occurred in 5 patients (3%), resulting in minor deficits only. One hundred and thirty-seven patients (79%) had excellent outcomes at last follow-up. CONCLUSION SRS is a safe and effective treatment for patients with Spetzler-Martin Grade I-II AVM. Selection bias is likely a contributing factor to explain the superior outcomes generally noted in reported series of microsurgery for patients with low grade AVM.

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STEREOTACTIC RADIOSURGERY FOR RADIATION-INDUCED MENINGIOMAS

Neurosurgery ◽

10.1227/01.neu.0000336765.85922.d9 ◽

2009 ◽

Vol 64 (3) ◽

pp. 463-470 ◽

Cited By ~ 30

Author(s):

Douglas Kondziolka ◽

Hideyuki Kano ◽

Hilal Kanaan ◽

Ricky Madhok ◽

David Mathieu ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Gamma Knife Radiosurgery ◽

World Health ◽

Morbidity Rate ◽

Induced Tumors ◽

Radiation Induced ◽

Grade Ii ◽

Health Organization ◽

The Brain

Abstract OBJECTIVE Radiation-induced meningiomas of the brain are typically managed with surgical resection. Stereotactic radiosurgery (SRS) has become an important primary or adjuvant management for patients with intracranial meningiomas, but the value of this approach for radiation-induced tumors is unclear. METHODS This series consisted of 19 patients (mean age, 40 years) with 24 tumors. The patients met criteria for a radiation-induced meningioma and underwent gamma knife radiosurgery. Seven patients had undergone a previous resection. The World Health Organization tumor grades for those with prior histology were Grade I (n = 5) and Grade II (n = 2). The median tumor volume was 4.4 cm3. Radiosurgery was performed using a median margin dose of 13 Gy. RESULTS Serial imaging was evaluated in all patients at a median follow-up of 44 months. The control rate was 75% after primary radiosurgery. Delayed resection after radiosurgery was performed in 5 patients (26%) at an average of 39 months. The median latency between radiation therapy for original disease and SRS for radiation-induced meningiomas was 29.7 years (range, 7.3–59.0 years). The overall survival after SRS was 94.1% and 80.7% at 3 and 5 years, respectively. No patient developed a subsequent radiation-induced tumor. The overall morbidity rate was 5.3% (1 optic neuropathy). Asymptomatic peritumoral imaging changes compatible with an adverse radiation effect developed in 1 patient. CONCLUSION SRS provides satisfactory control rates either after resection or as an alternative to resection. Its role is most valuable for patients whose tumors affect critical neurological regions and who are poor candidates for resection.

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Stereotactic Radiosurgery with the Cobalt-60 Gamma Unit in the Treatment of Growth Hormone-Producing Pituitary Tumors

Neurosurgery ◽

10.1227/00006123-199111000-00004 ◽

1991 ◽

Vol 29 (5) ◽

pp. 663-668 ◽

Cited By ~ 64

Author(s):

Marja Thorén ◽

Tiit Rähn ◽

Guo Wan-Yuo ◽

Werner Sigbritt

Keyword(s):

Growth Hormone ◽

Stereotactic Radiosurgery ◽

Clinical Signs ◽

Young Patients ◽

Pituitary Tumors ◽

Normal Serum ◽

External Irradiation ◽

Clinical Activity ◽

Radiation Doses ◽

Pituitary Insufficiency

Abstract Stereotactic radiosurgery on the pituitary given with the cobalt-60 gamma unit was used in the treatment of 21 patients with growth hormone (GH)-producing pituitary adenomas and acromegaly. All but one patient had locally invasive macroadenomas, and in the majority of cases, there was parasellar growth. Radiosurgery was the initial treatment for seven patients. Fourteen patients were previously treated by pituitary surgery, eight of whom had undergone conventional external pituitary irradiation as well. All patients had clinical signs of active acromegaly before radiosurgery. The radiation doses given to the previously untreated patients or those who only underwent surgery were 40 to 70 Gy in each of one to three irradiations. The patients with previous external irradiation received a lower dose of 30 to 50 Gy in each of one or two irradiations. The patients were observed during a period of 1 to 21 years from the first radiosurgical session. Two young patients had a clinical remission with a substantial decline of GH levels to near normal serum profiles. Another eight patients obtained reduction of GH levels and clinical activity. More than half of the patients (11 of 21) had minor or no effects from the treatment. There were no complications from the radiosurgery except the development of pituitary insufficiency in 2 of 13 patients who did not undergo previous conventional external irradiation. The remission rates were lower than the results previously reported by us for radiosurgery for Cushing's disease. This may be a result of the predominance in the present study of invasive macroadenomas and single treatments and to the lower radiation doses used in the patients who underwent conventional irradiation previously. In the future, the effect of higher radiation doses will be evaluated. The presently available stereotactic magnetic resonance imaging with contrast enhancement, which improves the visualization of the target volume, may aid in improving future radiosurgical results in the treatment of GH-producing pituitary tumors.

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Management of incidental pituitary tumors

Oncology Reviews ◽

10.4081/oncol.2011.232 ◽

2011 ◽

Vol 5 (4) ◽

pp. 232

Author(s):

Nicholas F. Marko ◽

Robert J. Weil

Keyword(s):

Clinical Symptoms ◽

Visual Fields ◽

Pituitary Tumors ◽

Field Testing ◽

Serum Levels ◽

Thyroid Stimulating Hormone ◽

Mri Imaging ◽

Asymptomatic Patients ◽

Stimulating Hormone

Pituitary incidentalomas are common lesions for which neurosurgical referrals may become progressively more frequent, given the increasing application of neuroimaging. The initial evaluation of a patient with radiographic evidence of an incidentaloma should focus on addressing two questions: (1) is the lesion causing neurological symptoms, and (2) is the lesion hormonally active? The answers to these two questions provide a framework for subsequent clinical management. The initial patient assessment should include a detailed history and physical examination, including the bedside assessment of visual fields. High-quality MRI imaging is essential, and formal visual field testing should be obtained in patients where the lesion abuts or compresses the optic apparatus. The initial biochemical workup is intended to assess potential pituitary hypo- or hyperfunction and should include measurement of serum levels of prolactin, insulin-like growth factor type-1, free thyroxine, testosterone, and an assessment of axis hypothalamic–pituitary–adrenal axis function. Additional testing may include serum thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone levels. Neurologically-asymptomatic patients without endocrine dysfunction can be managed with observation at regular intervals, including MRI imaging at 6 months and 1 year and then annually for a period of 3 years. Follow-up biochemical assessment is not necessary in the absence of clinical symptoms or radiographic enlargement of the lesion. After 3 years the follow-up interval may be prolonged, although closer follow-up may be indicated for patients with lesions C1 cm. Most patients who either present with or who subsequently develop neurologic or endocrinologic symptoms should be considered for surgery as the first-line therapy.

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Stereotactic Radiosurgery for Brainstem Arteriovenous Malformations: A Multicenter Study

Neurosurgery ◽

10.1093/neuros/nyx189 ◽

2017 ◽

Vol 81 (6) ◽

pp. 910-920 ◽

Cited By ~ 13

Author(s):

Or Cohen-Inbar ◽

Robert M Starke ◽

Cheng-Chia Lee ◽

Hideyuki Kano ◽

Paul Huang ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Multicenter Study ◽

Cranial Nerve ◽

Arteriovenous Malformations ◽

Maximum Dose ◽

Latency Period ◽

Medical Centers ◽

Formidable Challenge ◽

Radiation Induced

Abstract BACKGROUND The management of brainstem arteriovenous malformations (bAVMs) is a formidable challenge. bAVMs harbor higher morbidity and mortality compared to other locations. OBJECTIVE To review the outcomes following stereotactic radiosurgery (SRS) of bAVMs in a multicenter study. METHODS Six medical centers contributed data from 205 patients through the International Gamma Knife Research Foundation. Median age was 32 yr (6-81). Median nidus volume was 1.4 mL (0.1-69 mL). Favorable outcome (FO) was defined as AVM obliteration and no post-treatment hemorrhage or permanent symptomatic radiation-induced complications. RESULTS Overall obliteration was reported in 65.4% (n = 134) at a mean follow-up of 69 mo. Obliteration was angiographically proven in 53.2% (n = 109) and on MRA in 12.2% (n = 25). Actuarial rate of obliteration at 2, 3, 5, 7, and 10 yr after SRS was 24.5%, 43.3%, 62.3%, 73%, and 81.8% respectively. Patients treated with a margin dose >20 Gy were more likely to achieve obliteration (P = .001). Obliteration occurred earlier in patients who received a higher prescribed margin dose (P = .05) and maximum dose (P = .041). Post-SRS hemorrhage occurred in 8.8% (n = 18). Annual postgamma knife latency period hemorrhage was 1.5%. Radiation-induced complications were radiologically evident in 35.6% (n = 73), symptomatic in 14.6% (n = 30), and permanent in 14.6% (n = 30, which included long-tract signs and new cranial nerve deficits). FO was achieved in 64.4% (n = 132). Predictors of an FO were a higher Virginia radiosurgery AVM scale score (P = .003), prior hemorrhage (P = .045), and a lower prescribed maximum dose (P = .006). CONCLUSION SRS for bAVMs results in obliteration and avoids permanent complications in the majority of patients.

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Stereotactic radiosurgery for Spetzler-Martin Grade IV and V arteriovenous malformations: an international multicenter study

Journal of Neurosurgery ◽

10.3171/2017.3.jns162635 ◽

2018 ◽

Vol 129 (2) ◽

pp. 498-507 ◽

Cited By ~ 9

Author(s):

Mohana Rao Patibandla ◽

Dale Ding ◽

Hideyuki Kano ◽

Zhiyuan Xu ◽

John Y. K. Lee ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Arteriovenous Malformations ◽

Independent Predictor ◽

Multivariate Logistic Regression Analysis ◽

Favorable Outcome ◽

Single Session ◽

Radiation Induced ◽

International Multicenter Study ◽

Induced Changes

OBJECTIVEDue to the complexity of Spetzler-Martin (SM) Grade IV–V arteriovenous malformations (AVMs), the management of these lesions remains controversial. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for SM Grade IV–V AVMs and determine predictive factors.METHODSThe authors retrospectively pooled data from 233 patients (mean age 33 years) with SM Grade IV (94.4%) or V AVMs (5.6%) treated with single-session SRS at 8 participating centers in the International Gamma Knife Research Foundation. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cm3, 17.3 Gy, and 84.5 months, respectively. Statistical analyses were performed to identify factors associated with post-SRS outcomes.RESULTSAt a mean follow-up interval of 84.5 months, favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC) and was achieved in 26.2% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0%. Symptomatic and permanent RIC occurred in 10.7% and 4% of the patients, respectively. Only larger AVM diameter (p = 0.04) was found to be an independent predictor of unfavorable outcome in the multivariate logistic regression analysis. The rate of favorable outcome was significantly lower for unruptured SM Grade IV–V AVMs compared with ruptured ones (p = 0.042). Prior embolization was a negative independent predictor of AVM obliteration (p = 0.024) and radiologically evident RIC (p = 0.05) in the respective multivariate analyses.CONCLUSIONSIn this multi-institutional study, single-session SRS had limited efficacy in the management of SM Grade IV–V AVMs. Favorable outcome was only achieved in a minority of unruptured SM Grade IV–V AVMs, which supports less frequent utilization of SRS for the management of these lesions. A volume-staged SRS approach for large AVMs represents an alternative approach for high-grade AVMs, but it requires further investigation.

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