PC3 - 142 Gamma Knife Radiosurgery in Patients with Persistent Acromegaly or Cushing’s Disease: Long-Term Risk of Hypopituitarism

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.

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Radiosurgery for Cushing's disease after failed transsphenoidal surgery

Journal of Neurosurgery ◽

10.3171/jns.2000.93.5.0738 ◽

2000 ◽

Vol 93 (5) ◽

pp. 738-742 ◽

Cited By ~ 175

Author(s):

Jonas M. Sheehan ◽

Mary L. Vance ◽

Jason P. Sheehan ◽

Dilantha B. Ellegala ◽

Edward R. Laws

Keyword(s):

Gamma Knife ◽

Cushing’S Disease ◽

Tumor Size ◽

Transsphenoidal Surgery ◽

Gamma Knife Radiosurgery ◽

Magnetic Resonance Images ◽

Cushing's Disease ◽

Content Type ◽

Fine Print

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

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Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients

Journal of Neurosurgery ◽

10.3171/2018.2.jns172361 ◽

2019 ◽

Vol 130 (6) ◽

pp. 1799-1808 ◽

Cited By ~ 4

Author(s):

Kyung-Jae Park ◽

Hideyuki Kano ◽

Aditya Iyer ◽

Xiaomin Liu ◽

Daniel A. Tonetti ◽

...

Keyword(s):

Tumor Progression ◽

Stereotactic Radiosurgery ◽

Gamma Knife ◽

Cavernous Sinus ◽

Gamma Knife Radiosurgery ◽

Tumor Control ◽

Cavernous Sinus Meningioma ◽

Long Term Study

OBJECTIVEThe authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).METHODSThe authors retrospectively assessed treatment outcomes 5–18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22–83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1–37.3 cm3), and the median margin dose was 13.0 Gy (range 10–20 Gy).RESULTSTumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year follow-ups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8–120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438–12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041–0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3–85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026–12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS.CONCLUSIONSThis long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

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Evaluation of Fractionated Radiotherapy and Gamma Knife Radiosurgery in Cavernous Sinus Meningiomas: Treatment Strategy

Neurosurgery ◽

10.1227/01.neu.0000179924.76551.cd ◽

2005 ◽

Vol 57 (5) ◽

pp. 873-886 ◽

Cited By ~ 84

Author(s):

Philipe Metellus ◽

Jean Regis ◽

Xavier Muracciole ◽

Stephane Fuentes ◽

Henry Dufour ◽

...

Keyword(s):

Gamma Knife ◽

Cavernous Sinus ◽

Treatment Strategy ◽

Gamma Knife Radiosurgery ◽

Tumor Control ◽

Fractionated Radiotherapy ◽

Group I ◽

Group Ii

Abstract OBJECTIVE: To investigate the respective role of fractionated radiotherapy (FR) and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma (CSM) treatment. METHODS: The authors report the long-term follow-up of two populations of patients harboring CSMs treated either by FR (Group I, 38 patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I) and in 23 patients (Group II), FR and GKS radiosurgery were performed as first line treatment. In our early experience with GKS radiosurgery (1992, date of gamma knife availability in the department), patients with tumors greater than 3 cm, showing close relationship with the optic apparatus (<3 mm) or skull base dural spreading, were treated by FR. Secondarily, with the advent of new devices and our growing experience, these criteria have evolved. RESULTS: The median follow-up period was 88.6 months (range, 42–168 mo) for Group I and 63.6 months (range, 48–92 mo) for Group II. According to Sekhar's classification, 26 (68.4%) patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P < 0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%) patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm3 in Group I and 5.2 cm3 in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and 94.4% in Group I and II, respectively. Clinically, improvement was seen for 24 (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05). Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and 2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II. CONCLUSION: FR and GKS radiosurgery are safe and efficient techniques in treatment of CSMs, affording comparable satisfactory long-term tumor control. However, GKS radiosurgery provides better radiological response, is far more convenient, and fits into most patients lives much better than FR. Therefore, in the authors' opinion, GKS radiosurgery should be advocated in first intention for patients with CSMs, whereas conventional radiotherapy should be reserved for cases that are not amenable to this technique, thus making these two therapeutic modalities not alternative but complementary tools in CS meningioma treatment strategy.

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Results of Gamma Knife surgery for Cushing's disease

Journal of Neurosurgery ◽

10.3171/2013.7.jns13217 ◽

2013 ◽

Vol 119 (6) ◽

pp. 1486-1492 ◽

Cited By ~ 55

Author(s):

Jason P. Sheehan ◽

Zhiyuan Xu ◽

David J. Salvetti ◽

Paul J. Schmitt ◽

Mary Lee Vance

Keyword(s):

Median Time ◽

Gamma Knife ◽

Cushing’S Disease ◽

Cranial Nerves ◽

Gamma Knife Surgery ◽

High Rate ◽

Cushing's Disease ◽

Tumor Control

Object Cushing's disease is a challenging neuroendocrine disorder. Although resection remains the primary treatment option for most patients, the disease persists if there is residual or recurrent tumor. Stereotactic radiosurgery has been used to treat patients with persistent Cushing's disease after a prior resection. The authors report on the long-term risks and benefits of radiosurgery for Cushing's disease. Methods A retrospective review of a prospectively collected database of radiosurgery patients was undertaken at the University of Virginia. All patients with Cushing's disease treated with Gamma Knife surgery (GKS) were identified. Those without at least 12 months of clinical and radiological follow-up were excluded from this analysis. Rates of endocrine remission, tumor control, and adverse events were assessed. Statistical methods were used to identify favorable and unfavorable prognostic factors. Results Ninety-six patients with the required follow-up data were identified. The mean tumor margin dose was 22 Gy. The median follow-up was 48 months (range 12–209.8 months). At the last follow-up, remission of Cushing's disease occurred in 70% of patients. The median time to remission among all patients was 16.6 months (range 1–165.7 months). The median time to remission in those who had temporarily stopped taking ketoconazole at the time of GKS was 12.6 months, whereas it was 21.8 months in those who continued to receive ketoconazole (p < 0.012). Tumor control was achieved in 98% of patients. New loss of pituitary function occurred in 36% of patients. New or worsening cranial neuropathies developed in 5 patients after GKS, with the most common involving cranial nerves II and III. Conclusions Gamma Knife surgery offers a high rate of tumor control and a reasonable rate of endocrine remission in patients with Cushing's disease. The cessation of cortisol-lowering medications around the time of GKS appears to result in a more rapid rate of remission. Delayed hypopituitarism and endocrine recurrence develop in a minority of patients and underscore the need for long-term multidisciplinary follow-up.

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Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas

Acta Endocrinologica ◽

10.1530/eje.0.1490195 ◽

2003 ◽

pp. 195-200 ◽

Cited By ~ 56

Author(s):

S Cannavo ◽

B Almoto ◽

C Dall'Asta ◽

S Corsello ◽

RM Lovicu ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Long Term Results ◽

Cushing's Disease ◽

Tumor Diameter ◽

Pituitary Macroadenoma ◽

Second Surgery ◽

Acth Secreting

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.

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Gamma knife radiosurgery in patients with persistent acromegaly or Cushing's disease: long-term risk of hypopituitarism

Clinical Endocrinology ◽

10.1111/cen.12938 ◽

2015 ◽

Vol 84 (4) ◽

pp. 524-531 ◽

Cited By ~ 23

Author(s):

Or Cohen-Inbar ◽

Arjun Ramesh ◽

Zhiyuan Xu ◽

Mary Lee Vance ◽

David Schlesinger ◽

...

Keyword(s):

Gamma Knife ◽

Cushing’S Disease ◽

Gamma Knife Radiosurgery ◽

Cushing's Disease

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Gamma knife radiosurgery is a successful adjunctive treatment in Cushing’s disease

Acta Endocrinologica ◽

10.1530/eje.1.02323 ◽

2007 ◽

Vol 156 (1) ◽

pp. 91-98 ◽

Cited By ~ 122

Author(s):

F Castinetti ◽

M Nagai ◽

H Dufour ◽

J-M Kuhn ◽

I Morange ◽

...

Keyword(s):

Adverse Effects ◽

Stereotactic Radiosurgery ◽

Gamma Knife ◽

Cushing’S Disease ◽

Gamma Knife Radiosurgery ◽

Disease Recurrence ◽

Cushing's Disease ◽

Adjunctive Treatment ◽

Significant Difference

Objective: Though transsphenoidal surgery remains the first-line treatment of Cushing’s disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely. The aim of this study was to determine long-term hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing’s disease. Design: Forty patients with Cushing’s disease treated by GK were prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven of them were treated with GK as a primary treatment. Methods: Radiosurgery was performed at the Department of Functional Neurosurgery of Marseille, France, using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy. Patients were considered in remission if they had normalized 24-h free urinary cortisol and suppression of plasma cortisol after low-dose dexamethasone suppression test. Results: Seventeen patients (42.5%) were in remission after a mean of 22 months (range 12–48 months). The two groups did not differ in terms of initial hormonal levels. Target volume was significantly higher in uncured than in remission group (909.8 vs 443 mm3, P = 0.038). We found a significant difference between patients who were on or off anticortisolic drugs at the time of GK (20 vs 48% patients in remission respectively, P = 0.02). Conclusion: With 42% of patients in remission after a median follow-up of 54 months, GK stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may represent an alternative to other therapeutic options in view of their adverse effects.

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Gamma knife radiosurgery in patients with Cushing's Disease: Is it a curative option?

Egyptian Journal of Neurosurgery ◽

10.1186/s41984-021-00131-z ◽

2021 ◽

Vol 36 (1) ◽

Author(s):

Ignatius N. Esene ◽

Tarek Elserry ◽

Hesham Radwan ◽

Ahmad Mohammed Elsabaa

Keyword(s):

Gamma Knife ◽

Cushing’S Disease ◽

Tumor Volume ◽

De Novo ◽

Gamma Knife Radiosurgery ◽

Cushing's Disease ◽

Volume Control ◽

First Line ◽

Number Of Patients

Abstract Background The first line of treatment of Cushing’s disease (CD) is surgery. However, surgical resection is not amenable in all cases and the role of radiosurgical management of residual tumors or upfront treatment has been reported. Our study highlights the effectiveness and safety of Gamma Knife Radiosurgery for the treatment of Cushing’s disease. Methods This was an ambidirectional descriptive cohort study on 16 consecutive patients with a confirmed Cushing’s disease that underwent Gamma Knife Radiosurgery (GKR) before July 2014 and assessed for outcome during the study period between January 2014 and June 2016 (30 Months). We included patients with a minimum of two years follow up. The main outcomes were biochemical remission and tumor volume control. Secondary outcomes were visual field changes and morbidity. Results Sixteen cases with CD were included into the study. The Mean age ± SD was 34.81 ± 10.10 years. The male to female sex ratio was 1:3. Six cases (37.5%) were de novo. Normalization of hypersecretion at 2 years was achieved in 13 cases (81.3%).The median hormone normalization time was 23 months. Tumor volume control was achieved in all the cases, whereas tumor shrinkage was achieved in (10 cases) 62.5%. The median shrinkage time was 13 months. Of the 12 eyes with pre-Gamma Knife visual affection, 8 (75%) normalized, 4 (25%) improved, and none deteriorated. No patient developed new hypopituitarism after GK radiosurgery. One case developed diplopia at 24 months follow up from abducens palsy. No mortality occurred in our series. Conclusion Gamma Knife Stereotactic Radiosurgery is an effective and safe treatment option for Cushing’s disease. It can be used as a complementary therapeutic procedure to classic surgery or as a first line treatment in selected number of patients.

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