Update: Prolactinoma Radiosurgery

Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy 1).

GKRS plays a significant role in the treatment of non-functioning [NFA] and hormonal-active [HAA] pituitary adenoma. It affords high rate of tumor control and offers low risk of collateral neurological or endocrine axis injury. A study showed that control of tumor growth was achieved in 90% patients, shrinkage of tumor in 54% and arrest of progression in 36% cases after GKRS treatment. The biochemical remission rate in GH secreting adenoma was 57%, ACTH adenoma was 67% and prolactinoma was 40%. Age less than 50 years and tumor volume less than 5cm3 were associated with a favourable radiosurgical outcome 2).

Case series

2015

Radiotherapy as an alternative and adjuvant treatment for prolactinomas has been performed at the Department of Radiation Oncology, Prince of Wales Cancer Centre, Sydney, New South Wales, Australia, with the linear accelerator since 1990.

In a retrospective review of 13 patients managed with stereotactic radiosurgery (SRS) and 5 managed with fractionated stereotactic radiotherapy (FSRT), as well as 5 managed with conventional radiotherapy, at the Prince of Wales Hospital. Patients with a histopathologically diagnosed prolactinoma were eligible. Those patients who had a confirmed pathological diagnosis of prolactinoma following surgical intervention, a prolactin level elevated above 500 μg/L, or a prolactin level persistently elevated above 200 μg/L with exclusion of other causes were represented in this review.

At the end of documented follow-up (SRS median 6 years, FSRT median 2 years), no SRS patients showed an increase in tumour volume. After FSRT, 1 patient showed an increase in size, 2 showed a decrease in size and 2 patients showed no change. Prolactin levels trended towards improvement after SRS and FSRT, but no patients achieved the remission level of <20 μg/L. Seven of 13 patients in the SRS group achieved a level of <500 μg/L, whereas no patients reached this target after FSRT.

A reduction in prolactin level is frequent after SRS and FSRT for prolactinomas; however, true biochemical remission is uncommon. Tumour volume control in this series was excellent, but this may be related to the natural history of the disease. Morbidity and mortality after stereotactic radiation were very low in this series 3).


Cohen-Inbar et al., reviewed the outcome of patients with medically and surgically refractory prolactinomas treated with Gamma Knife radiosurgery (GKRS) during a 22 years follow-up period.

They reviewed the patient database at the University of Virginia Gamma Knife center during a 25-year period (1989-2014), identifying 38 patients having neurosurgical, radiological and endocrine follow-up.

Median age at GKRS treatment was 43 years. Median follow-up was 42.3 months (range 6-207.9). 55.3 % (n = 21) were taking a dopamine agonist at time of GKRS. 63.2 % (n = 24) had cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off of a dopamine agonist) was achieved in 50 % (n = 19). GKRS induced hypopituitarism occurred in 30.3 % (n = 10). Cavernous sinus involvement was shown to be a significant negative prognosticator of endocrine remission. Taking a dopamine agonist drug at the time of GKRS showed a tendency to decrease the probability for endocrine remission.

GKRS for refractory prolactinomas can lead to endocrine remission in many patients. Hypopituitarism is the most common side effect of GKRS 4).

2013

evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3–11.6). The marginal tumor dose (median= 15 Gy, range 12–25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12–185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy 5).

2006

Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%).

Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most 6).

2000

Twenty patients with prolactinomas were followed after GKS. Five patients were treated successfully; their prolactin (PRL) levels dropped into the normal range and dopaminergic drugs could be discontinued. Two spontaneous pregnancies were observed and 11 patients experienced improvement. Improvement was defined as normal PRL levels with the continued possibility of reduced medical treatment or a substantially reduced medical treatment dose with some degree of hyperprolactinemia maintained. The treatment failed in three patients who experienced no improvement. Patients treated with dopaminergic drugs during GKS did significantly less well in comparison with the untreated group when a cumulative distribution function (Kaplan-Meier estimate) was used. CONCLUSIONS:

The results of GKS for prolactinomas in this investigation are better than the results published by others. This may be an effect of case selection because there were no “salvage cases” in our group of patients. Because a dopamine agonist seemed to induce radioprotection in this series, it is suggested that GKS be performed during an intermission in drug therapy when the dopamine agonist is discontinued 7).

1)

Wong A, Eloy JA, Couldwell WT, Liu JK. Update on prolactinomas. Part 2: Treatment and management strategies. J Clin Neurosci. 2015 Oct;22(10):1568-74. doi: 10.1016/j.jocn.2015.03.059. Epub 2015 Aug 1. Review. PubMed PMID: 26243714.

2)

Narayan V, Mohammed N, Bir SC, Savardekar AR, Patra DP, Bollam P, Nanda A. Long term Outcome of Non-functioning and Hormonal-active Pituitary Adenoma after Gamma Knife Radio Surgery. World Neurosurg. 2018 Mar 21. pii: S1878-8750(18)30576-X. doi: 10.1016/j.wneu.2018.03.094. [Epub ahead of print] PubMed PMID: 29574220.

3)

Wilson PJ, Williams JR, Smee RI. Single-centre experience of stereotactic radiosurgery and fractionated stereotactic radiotherapy for prolactinomas with the linear accelerator. J Med Imaging Radiat Oncol. 2015 Jun;59(3):371-8. doi: 10.1111/1754-9485.12257. Epub 2014 Nov 20. PubMed PMID: 25410143.

4)

Cohen-Inbar O, Xu Z, Schlesinger D, Vance ML, Sheehan JP. Gamma Knife radiosurgery for medically and surgically refractory prolactinomas: long-term results. Pituitary. 2015 Dec;18(6):820-30. doi: 10.1007/s11102-015-0658-1. PubMed PMID: 25962347.

5)

Liu X, Kano H, Kondziolka D, Park KJ, Iyer A, Shin S, Niranjan A, Flickinger JC, Lunsford LD. Gamma knife stereotactic radiosurgery for drug resistant or intolerant invasive prolactinomas. Pituitary. 2013 Mar;16(1):68-75. PubMed PMID: 22302560.

6)

Pouratian N, Sheehan J, Jagannathan J, Laws ER Jr, Steiner L, Vance ML. Gamma knife radiosurgery for medically and surgically refractory prolactinomas. Neurosurgery. 2006 Aug;59(2):255-66; discussion 255-66. PubMed PMID: 16883166.

7)

Landolt AM, Lomax N. Gamma knife radiosurgery for prolactinomas. J Neurosurg. 2000 Dec;93 Suppl 3:14-8. PubMed PMID: 11143231.

Update: Cystic metastases

Cystic metastases

Epidemiology

The development of cystic brain metastases remains a relatively rare occurrence.

Etiology

Metastatic brain tumors are normally composed of cystic components, however, the reasons for the cyst formation have not been clearly investigated 1). Stem 2) reported that the brain cyst fluid protein always presents in the inflammatory exudates. Cumings 3) also reported that the cyst fluid formation may be correlated with the tumor degeneration. Gardner et al 4) found that fluid accumulating in brain tumors runs in the normal drainage route, since there are no lymphatic vessels in the tumors.

Gamma knife radiosurgery (GKRS) is occasionally a useful tool for maintaining good brain status in patients with brain metastases (METs). Conversely, Ishikawa et al. experienced patients with delayed cyst formation (DCF) several years after GKRS, a complication not previously reported 5).

Differential diagnosis

The main challenge in discrimination between intracranial cystic lesions is to differentiate benign inflammatory cystic lesions (as cerebral abscess) from malignant cystic lesions (as cystic metastases and cystic glioma) which have totally different management.

Cerebral abscess.

Hydatid cyst.

Other intra-axial cysts, e.g. intracranial arachnoid cyst, neuroglial cyst, porencephalic cyst.

The most common tumors are, hemangioblastoma, pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, tanycytic ependymoma, intraparenchymal schwannoma, desmoplastic infantile ganglioglioma.

Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma 6).

Treatment

In a review, Kim et al. describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes 7).

Case series

2017

Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively.

The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p=0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction.

For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst 8).

2016

Lee et al. retrospectively reviewed the clinical, radiological, and dosimetry data of 37 cystic brain metastases of 28 patients who were treated with GKRS. Cyst drainage was performed in 8 large lesions before GKRS to decrease the target volume. The mean target volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean prescription dose was 16.6 (range, 13-22) Gy.

The actuarial median survival time was 17.7 ± 10.2 months, and the primary tumor status was a significant prognostic factor for survival. The actuarial local tumor control rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various factors, only prescription dose (>15 Gy) was a significant factor related to local tumor control after multivariate analysis (p = 0.049). Cyst volume or cyst/total tumor volume ratio did not influence local control after GKRS, when the target volume was reduced to about 15 cc after cyst drainage.

According to this results, they suggest that stereotactic radiosurgery should be considered as one of the treatment options for cystic brain metastases, when large tumor volume can be reduced by surgical drainage before radiosurgery, especially for patients with a controlled primary tumor 9).


A study involved 48 patients who were diagnosed with cystic metastatic brain tumors between January 2008 and December 2012 in the Department of Neurosurgery of Nanfang Hospital Southern Medical University (Guangzhou, China). Every patient underwent Leksell stereotactic frame, 1.5T magnetic resonance imaging (MRI)-guided stereotactic cyst aspiration and Leksell GKRS. Subsequent to the therapy, MRI was performed every 3 months. The results indicated that 48 cases were followed up for 24-72 months, with a mean follow-up duration of 36.2 months. Following treatment, 44 patients (91.7%) exhibited tumor control and 4 patients (8.3%) experienced progression of the local tumor. During this period, 35 patients (72.9%) succumbed, but only 2 (4.2%) of these succumbed to the brain metastases. The total local control rate was 91.7% and the median overall survival time of all patients was 19.5 months. The 1-year overall survival rate was 70.8% and the 2-year overall survival rate was 26.2%. In conclusion, these results indicated that the method of stereotactic cyst aspiration combined with GKRS was safe and effective for patients with large cystic brain metastases. This method is effective for patients whose condition is too weak for general anesthesia and in whom the tumors are positioned at eloquent areas. This method enables patients to avoid a craniotomy, and provides a good tumor control rate, survival time and quality of life 10).

2014

Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).

Before aspiration, the mean total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6 cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0 cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (±1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (±0.42) and 6.8 (±0.38) months.

Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time 11).

2013

Ebinu et al. reviewed a prospectively maintained database of brain metastases patients treated between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response.

A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component.

This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates 12).

2012

Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined.

Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement.

The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases 13).

2009

Hydrofiber dressing is a sodium carboxymethylcellulose hydrocolloid polymer with high fluid-absorptive capacity. This material was originally used as a dressing for exudative wounds. Hydrofiber dressing was used for 8 patients with cystic-type metastatic brain tumor. Tumor removal was performed after hydrofiber dressing was inserted into the cyst cavity to transform the tumor into a solid-type tumor.

Transformation of cystic-type metastatic brain tumors into smaller solid-type tumors using hydrofiber dressing facilitated en bloc resection of tumor. The dressing also absorbed residual cyst fluid and was thus also effective in preventing intraoperative dissemination of tumor cells. This approach enabled ideal en bloc resection in all patients. There were no adverse events.

These findings suggest hydrofiber dressing may be useful in surgery for cystic-type metastatic brain tumors 14).

2008

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 +/- 11 years, range 38-75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score >or= 70; and 5) histological diagnosis of a malignant tumor.

Non-small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8-68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2-32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12-25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3-64.1%) and 34.2% (95% confidence interval 23.1-45.3%). Local tumor control was achieved in 91.3% of the patients.

The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis 15).

Case reports

2015

A study describes the first case of histopathologically-confirmed brainstem metastasis originating from lung adenosquamous carcinoma, and discusses the outcomes of treatment by stereotactic aspiration combined with gamma knife radiosurgery (GKRS). A 59-year-old female presented with a cystic mass (15×12×13 mm; volume, 1.3 cm3) located in the pons, two years following surgical treatment for adenosquamous carcinoma of the lung. The patient received initial GKRS for the lesion in the pons with a total dose of 54.0 Gy, however, the volume of the mass subsequently increased to 3.9 cm3 over a period of three months. Computed tomography-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 2.0 cm3 of yellow-white fluid. Histology confirmed the diagnosis of adenosquamous carcinoma. Aspiration provided immediate symptomatic relief, and was followed one week later by repeat GKRS with a dose of 12.0 Gy. The patient survived for 12 months following the repeat GKRS; however, later succumbed to the disease after lapsing into a two-week coma. The findings of this case suggest that stereotactic aspiration of cysts may improve the effects of GKRS for the treatment of cystic brainstem metastasis; the decrease in tumor volume allowed a higher radiation dose to be administered with a lower risk of radiation-induced side effects. Therefore, stereotactic aspiration combined with GKRS may be an effective treatment for brainstem metastasis originating from adenosquamous carcinoma 16).

2009

A 71-year-old man who was admitted to the emergency department after an episode of loss of consciousness. On neurological examination a left hemiparesis was observed. The patient’s previous history entailed a total cystectomy and radical prostatectomy 7 months ago because of a transitional cell carcinoma (TCC) of the urinary bladder. Brain imaging work-up revealed a cystic lesion with perifocal edema in the right frontal lobe. The patient was operated and the histological diagnosis was consistent with a metastatic carcinoma, with morphological, histochemical and immunohistochemical features comparable to those of the primary tumor. Postoperative the patient was in excellent neurological state and received complementary chemotherapy and total brain irradiation. Additional imaging and laboratory examinations excluded other metastatic lesion. The patient died 18 months later due to systemic disease. Although intracranial metastases from TCC of urinary bladder have a low incidence, in follow-up examinations any alterations in neurological status in these patients should be thoroughly evaluated 17).


Cystic brain metastases from small-cell lung carcinomas are exceedingly rare and neurosurgical operations are not suitable for those cases considering invisible micrometastases. A 34-year-old female patient presented with small-cell lung carcinoma that metastasized to the brain as a solitary cyst with a thin wall 24 months after a good partial response to initial chemoradiotherapy. The brain mass volume and the main symptom of left hemiplegia, which made the Karnofsky performance status (KPS) fall to 30%, did not respond to whole brain irradiation. Therefore, an Ommaya reservoir was inserted, which dramatically improved the KPS to 70%. This minimally invasive surgical strategy is suitable even for patients with a poorer KPS bearing cystic brain metastases 18).

References

1)

Kim MS, Lee SI, Sim SH. Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated? Stereotact Funct Neurosurg. 1999;72 Suppl 1:38-44. PubMed PMID: 10681689.
2)

Stem K. Chemical study of fluids obtained from cerebral cysts: Report on 56 cases. Brain. 1939;62:88. doi: 10.1093/brain/62.1.88.
3)

CUMINGS JN. The chemistry of cerebral cysts. Brain. 1950 Jun;73(2):244-50. PubMed PMID: 14791790.
4)

GARDNER WJ, COLLIS JS Jr, LEWIS LA. Cystic brain tumors and the blood-brain barrier. Comparison of protein fractions in cyst fluids and sera. Arch Neurol. 1963 Mar;8:291-8. PubMed PMID: 13946556.
5)

Ishikawa E, Yamamoto M, Saito A, Kujiraoka Y, Iijima T, Akutsu H, Matsumura A. Delayed cyst formation after gamma knife radiosurgery for brain metastases. Neurosurgery. 2009 Oct;65(4):689-94; discussion 694-5. doi: 10.1227/01.NEU.0000351771.46273.22. PubMed PMID: 19834373.
6)

Ramanathan N, Kamaruddin KA, Othman A, Mustafa F, Awang MS. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report. Malays J Med Sci. 2016 May;23(3):92-4. PubMed PMID: 27418876; PubMed Central PMCID: PMC4934725.
7)

Kim M, Cheok S, Chung LK, Ung N, Thill K, Voth B, Kwon DH, Kim JH, Kim CJ, Tenn S, Lee P, Yang I. Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration. Brain Tumor Res Treat. 2015 Apr;3(1):1-7. doi: 10.14791/btrt.2015.3.1.1. Epub 2015 Apr 29. Review. PubMed PMID: 25977901; PubMed Central PMCID: PMC4426272.
8)

Oshima A, Kimura T, Akabane A, Kawai K. Optimal implantation of Ommaya reservoirs for cystic metastatic brain tumors preceding Gamma Knife radiosurgery. J Clin Neurosci. 2017 May;39:199-202. doi: 10.1016/j.jocn.2016.12.042. Epub 2017 Jan 20. PubMed PMID: 28117259.
9)

Lee SR, Oh JY, Kim SH. Gamma Knife radiosurgery for cystic brain metastases. Br J Neurosurg. 2016;30(1):43-8. doi: 10.3109/02688697.2015.1039489. Epub 2015 May 11. PubMed PMID: 25958957.
10)

Wang H, Qi S, Dou C, Ju H, He Z, Ma Q. Gamma Knife radiosurgery combined with stereotactic aspiration as an effective treatment method for large cystic brain metastases. Oncol Lett. 2016 Jul;12(1):343-347. Epub 2016 May 18. PubMed PMID: 27347148; PubMed Central PMCID: PMC4907086.
11)

Jung TY, Kim IY, Jung S, Jang WY, Moon KS, Park SJ, Lim SH. Alternative treatment of stereotactic cyst aspiration and radiosurgery for cystic brain metastases. Stereotact Funct Neurosurg. 2014;92(4):234-41. doi: 10.1159/000362935. Epub 2014 Aug 19. PubMed PMID: 25138737.
12)

Ebinu JO, Lwu S, Monsalves E, Arayee M, Chung C, Laperriere NJ, Kulkarni AV, Goetz P, Zadeh G. Gamma knife radiosurgery for the treatment of cystic cerebral metastases. Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):667-71. doi: 10.1016/j.ijrobp.2012.06.043. Epub 2012 Aug 9. PubMed PMID: 22885145.
13)

Higuchi F, Kawamoto S, Abe Y, Kim P, Ueki K. Effectiveness of a 1-day aspiration plus Gamma Knife surgery procedure for metastatic brain tumor with a cystic component. J Neurosurg. 2012 Dec;117 Suppl:17-22. doi: 10.3171/2012.7.GKS121001. PubMed PMID: 23205784.
14)

Okuda T, Teramoto Y, Yugami H, Kataoka K, Kato A. Surgical technique for a cystic-type metastatic brain tumor: transformation to a solid-type tumor using hydrofiber dressing. Surg Neurol. 2009 Dec;72(6):703-6; discussion 706. doi: 10.1016/j.surneu.2009.07.045. Epub 2009 Oct 15. PubMed PMID: 19836065.
15)

Franzin A, Vimercati A, Picozzi P, Serra C, Snider S, Gioia L, Ferrari da Passano C, Bolognesi A, Giovanelli M. Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis. J Neurosurg. 2008 Aug;109(2):259-67. doi: 10.3171/JNS/2008/109/8/0259. PubMed PMID: 18671638.
16)

DU C, Li Z, Wang Z, Wang L, Tian YU. Stereotactic aspiration combined with gamma knife radiosurgery for the treatment of cystic brainstem metastasis originating from lung adenosquamous carcinoma: A case report. Oncol Lett. 2015 Apr;9(4):1607-1613. Epub 2015 Feb 16. PubMed PMID: 25789009; PubMed Central PMCID: PMC4356421.
17)

Zigouris A, Pahatouridis D, Mihos E, Alexiou GA, Nesseris J, Zikou AK, Argyropoulou MI, Goussia A, Voulgaris S. Solitary cystic cerebral metastasis from transitional cell carcinoma of the bladder. Acta Neurol Belg. 2009 Dec;109(4):322-5. PubMed PMID: 20120215.
18)

Takeda T, Saitoh M, Takeda S. Solitary cystic brain metastasis of small-cell lung carcinoma controlled by a stereotactically inserted Ommaya reservoir. Am J Med Sci. 2009 Mar;337(3):215-7. doi: 10.1097/MAJ.0b013e3181833847. PubMed PMID: 19204557.

Update: Trigeminal schwannoma radiosurgery

Stereotactic radiosurgery (SRS) is an effective and minimally invasive management option for patients with residual or newly diagnosed trigeminal schwannomas. The use resulted in good tumor control and functional improvement 1).

Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment 2).

Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required 3).

Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas 4).

It is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision 5).

Case series

2013

The records of 52 patients who underwent stereotactic radiosurgery (SRS) for trigeminal schwannoma were reviewed using a retrospective study. The median patient age was 47.1 years (range, 18-77); 20 patients (38.5%) had undergone prior tumor resection and 32 (61.5%) underwent radiosurgery on the basis of imaging diagnosis only. The most frequent presenting symptoms were facial numbness (29 patients), jaw weakness (11 patients), facial pain (10 patients) and diplopia (4 patients). Fifty-two cases with solid tumors were mainly solid in 44 cases (84.6%), mostly cystic in 2 cases (3.8%), and cystic and solid mixed in 6 cases (11.5%). Two cases of mostly cystic tumor first underwent stereotactic cystic fluid aspiration and intracavitary irradiation, and then had MRI localization scan again for gamma knife treatment. The mean tumor volume was 7.2 ml (range, 0.5-38.2). The mean prescription radiation dose was 13.9 Gy (range, 11-17), and the mean prescription isodose configuration was 47.9%.

At a mean follow-up of 61 months (range, 12-156), neurological symptoms or signs improved in 35 patients (67.3%), 14 patients (26.9%) had a stable lesion, and worsening of the disease occurred in 2 patients (3.8%). On imaging, the schwannomas almost disappeared in 8 (15.4%), shrank in 32 (61.5%), remained stable in 5 (9.6%), and increased in size in 7 patients (13.5%). Tumor growth control was achieved in 45 (86.5%) of the 52 patients.

SRS is an effective and minimally invasive management option for patients with residual or newly diagnosed trigeminal schwannomas. The use of SRS to treat trigeminal schwannomas resulted in good tumor control and functional improvement 6).

2009

The records of 33 consecutive patients with trigeminal schwannoma treated via Gamma Knife surgery were retrospectively reviewed. The median patient age was 49.5 years (range 15.1-82.5 years). Eleven patients had undergone prior tumor resection. Two patients had neurofibromatosis Type 2. Lesions were classified as root type (6 tumors), ganglion type (17 tumors), and dumbbell type (10 tumors) based on their location. The median radiosurgery target volume was 4.2 cm3 (range 0.5-18.0 cm3), and the median dose to the tumor margin was 15.0 Gy (range 12-20 Gy).

At an average of 6 years (range 7.2-147.9 months), the rate of progression-free survival (PFS) at 1, 5, and 10 years after SRS was 97.0, 82.0, and 82.0%, respectively. Factors associated with improved PFS included female sex, smaller tumor volume, and a root or ganglion tumor type. Neurological symptoms or signs improved in 11 (33.3%) of 33 patients and were unchanged in 19 (57.6%). Three patients (9.1%) had symptomatic disease progression. Patients who had not undergone a prior tumor resection were significantly more likely to show improvement in neurological symptoms or signs.

Stereotactic radiosurgery is an effective and minimally invasive management option in patients with residual or newly diagnosed trigeminal schwannomas. Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment 7).

2007

Phi et al. reviewed the clinical records and radiological data in 22 consecutive patients who received GKS for a trigeminal schwannoma. The median tumor volume was 4.1 ml (0.2-12.0 ml), and the mean tumor margin dose was 13.3 +/- 1.3 Gy at an isodose line of 49.9 +/- 0.6% (mean +/- standard deviation). The median clinical follow-up period was 46 months (range 24-89 months), and the median length of imaging follow-up was 37 months (range 24-79 months).

Tumor growth control was achieved in 21 (95%) of the 22 patients. Facial pain responded best to radiosurgery, with two thirds of patients showing improvement. However, only one third of patients with facial hypesthesia improved. Six patients (27%) experienced new or worsening cranial neuropathies after GKS. Ten patients (46%) showed tumor expansion after radiosurgery, and nine of these also showed central enhancement loss. Loss of central enhancement, tumor expansion, and a tumor in a cavernous sinus were found to be significantly related to the emergence of cranial neuropathies.

The use of GKS to treat trigeminal schwannoma resulted in a high rate of tumor control and functional improvement. Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required 8).


Twenty-six patients with trigeminal schwannomas underwent GKS at the University of Virginia Lars Leksell Gamma Knife Center between 1989 and 2005. Five of these patients had neurofibromatosis and one patient was lost to follow up. The median tumor volume was 3.96 cm(3), and the mean follow-up period was 48.5 months. The median prescription radiation dose was 15 Gy, and the median prescription isodose configuration was 50%. There was clinical improvement in 18 patients (72%), a stable lesion in four patients (16%), and worsening of the disease in three patients (12%). On imaging, the schwannomas shrank in 12 patients (48%), remained stable in 10 patients (40%), and increased in size in three patients (12%). These results were comparable for primary and adjuvant GKSs. No tumor growth following GKS was observed in the patients with neurofibromatosis.

Gamma Knife surgery affords a favorable risk-to-benefit profile for patients harboring trigeminal schwannomas. Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas 9).

2001

A patient developed severe corneal neovascularization within four weeks and the contact lens had to be removed. Three months later an MRI scan was performed, which showed an intracranial tumor originating from the first branch of the trigeminal nerve. Neurinoma of the trigeminal nerve was suspected, and this presumed diagnosis was confirmed by fine needle biopsy. The patient underwent radiosurgery seven weeks later. The epithelium closed, the cornea recovered and stayed stable until the last examination 18 months after radiosurgery.

Radiosurgery is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision 10).

References

1) , 6)

Sun J, Zhang J, Yu X, Qi S, Du Y, Ni W, Hu Y, Tian Z. Stereotactic radiosurgery for trigeminal schwannoma: a clinical retrospective study in 52 cases. Stereotact Funct Neurosurg. 2013;91(4):236-42. doi: 10.1159/000345258. Epub 2013 Mar 26. PubMed PMID: 23548989.
2) , 7)

Kano H, Niranjan A, Kondziolka D, Flickinger JC, Dade Lunsford L. Stereotactic radiosurgery for trigeminal schwannoma: tumor control and functional preservation Clinical article. J Neurosurg. 2009 Mar;110(3):553-8. PubMed PMID: 19301456.
3) , 8)

Phi JH, Paek SH, Chung HT, Jeong SS, Park CK, Jung HW, Kim DG. Gamma Knife surgery and trigeminal schwannoma: is it possible to preserve cranial nerve function? J Neurosurg. 2007 Oct;107(4):727-32. PubMed PMID: 17937215.
4) , 9)

Sheehan J, Yen CP, Arkha Y, Schlesinger D, Steiner L. Gamma knife surgery for trigeminal schwannoma. J Neurosurg. 2007 May;106(5):839-45. PubMed PMID: 17542528.
5) , 10)

Ardjomand N, Can B, Schaffler G, Eustacchio S, Scarpatetti M, Pendl G. [Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery]. Wien Klin Wochenschr. 2001 Aug 16;113(15-16):605-9. German. PubMed PMID: 11571839.

MÁSTER INTERNACIONAL EN TÉCNICAS DE RADIOCIRUGÍA DEL SISTEMA NERVIOSO CENTRAL

La Universidad Complutense de Madrid en colaboracion con la Sociedad Española de la Radiocirugía SER, esta organizando un Máster Internacional en Técnicas de Radiocirugía del Sistema Nervioso Central.

El Máster Internacional en Técnicas de Radiocirugía del Sistema Nervioso Central pretende proporcionar los conocimientos teóricos y prácticos en las técnicas básicas de radiocirugía, Gamma Knife, CyberKnifey Linac. Así como las indicaciones, criterios y requerimientos, conceptos radiobiológicos y radiofísicos de la radiocirugía.

El máster está dividido en dos módulos: el primero es íntegramente online y se aborda la parte teórica básica: la radiobiología, los conceptos de radiofísica, los sistemas de planificación, las indicaciones generales, la protección a la irradiación, los sistemas de radiocirugía, etc. El segundo módulo es presencial y combina la teoría y la práctica, donde se dedica un mes a cada una de las tecnologías que se emplean habitualmente y en el último mes se ofrece al alumno la posibilidad de elegir la tecnología que va a utilizar en el futuro.

Contacto Prof. Kita Sallabanda Díaz:

kitasall@ucm.es

International Stereotactic Radiosurgery Society

Dear Colleagues,

Our new Webinar Programme continues to bring you fortnightly webinars from expert speakers from around the world. The list of webinars is being added to all the time, so please check on our new website (http://www.isrsy.org/en/courses/webinars) for updates to this exciting new initiative. Members of the ISRS will be able to access recordings of previous webinars at the same webpage.
Best regards,

Ian Paddick
Consultant Physicist
Vice-President of the ISRS

Upcoming webinars

Radiosurgery for Trigeminal Neuralgia by Alessandra GORGULHO

1:00 pm (Dublin, Edinburgh, Lisbon, London) – 2:00 pm CET (Amsterdam, Berlin, Bern, Paris, Rome, Stockholm, Vienna) – 8:00 am (Eastern time – New York, Canada) – 9:00 am (Brasilia) – 9:00 pm (Tokyo) – 5:00 am (Pacific time – Los Angeles) – 10:00pm (Brisbane)

Radiosurgery for Trigeminal Neuralgia (TN) was the birth of radiosurgery. The popularization of this technique was only possible upon improvement of imaging techniques, which allowed proper targeting of the trigeminal pathway. Radiosurgery is a very attractive surgical modality, especially to the elderly. Radiosurgery centers offering Functional Radiosurgery need to be aware of extra scrutiny during protocol implementation and treatment execution. This webinar will place radiosurgery in the context of other surgical modalities options for TN, discuss indications, results, complications and nuances of different radiosurgery protocols, including frameless.

International Stereotactic Radiosurgery Society – www.isrsy.org

 

ISRS Secretariat – MCO Congrès
Villa Gaby 285, Corniche Kennedy – 13007 Marseille – France
T.: +33(0)4 95 09 38 00 | F.: +33(0)4 95 09 38 01 | isrs@myeventonline.net

Gamma Knife Radiosurgery of Brainstem Cavernous Malformations

Case series

2016

All patients who underwent GKS for the treatment of a hemorrhagic brainstem CM(s) in the Department of Neurosurgery, Lille University Hospital, CHU Lille, Université de Lille, Lille, France. between January 2007 and December 2012. The GKS was privileged when the surgical procedure was evaluated as very risky. The mean dose of radiation was 14.8 Gy, and the mean target volume was 0.282 cm3. All patients participated in a scheduled clinical follow-up. The posttreatment MRI was performed after 6 months and after 1 year, and then all patients had an annual MRI follow-up.

There were 19 patients with a mean age of 36.7 years. The mean follow-up period was 51.2 months. The annual hemorrhage rate (AHR) was 27.31% before GKS, 2.46% during the first 2 years following the GKS, and 2.46% after the first 2 years following the GKS. The decrease in AHR after GKS was significant (p < 0.001).

GKS should be suggested when the surgical procedure harbors a high risk of neurological morbidity in patients with brainstem CM. Compared to prior literature results, a lower dose than applied in this study could be discussed 1).


Between January of 2009 and December of 2014, 43 patients (20 males and 23 females) with brainstem cavernous malformations were treated at the West China Hospital, Sichuan University, Gamma Knife Center. The mean age of these patients was 41.7 years. All of the patients experienced 1 or more episodes of symptomatic bleeding (range 1-4) before undergoing GKS. The mean volume of the malformations at the time of GKS was 442.1mm3, and the mean prescribed marginal radiation dose was 11.9Gy. The mean follow-up period after radiosurgery was 36 months (range 12-120 months).

Before GKS, 50 hemorrhages (1.2 per patient) were observed (25.0% annual hemorrhage rate). Three hemorrhages following GKS were observed within the first 2 years (3.92% annual hemorrhage rate), and 1 hemorrhage was observed in the period after the first 2 years (1.85% annual hemorrhage rate). In this study of 43 patients, new neurological deficits developed in only 1 patient (2.32%; permanent paresthesia on the left side of the face and the right lower limb of the patient). There were no deaths in this study.

GKS is a favorable alternative treatment for brainstem CMs. Using a low marginal dose treatment might reduce the rate of hemorrhage and radiation-induced complications2).

2014

From 1992 to 2011, 49 patients with brainstem CMs were treated with Gamma Knife radiosurgery (GKS). Lee et al., classified patients into two groups: Group A (n = 31), patients who underwent GKS for a CM following a single symptomatic bleed, and group B (n = 18), patients who underwent GKS for a CM following two or more symptomatic bleeds. The mean marginal dose of radiation was 13.1 Gy (range 9.0-16.8 Gy): 12.8 Gy in group A and 13.7 Gy in group B. The mean follow-up period was 64.0 months (range 1-171 months).

In group A, the annual hemorrhage rate (AHR) following GKS was 7.06 % within the first 2 years and 2.03 % after 2 years. In group B, four patients (22.2 %) developed new or worsening neurologic deterioration as a result of repeat hemorrhages. In group B, the AHR was 38.36 % prior to GKS, 9.84 % within the first two years, and 1.50 % after two years. There was no statistically significant difference in the AHRs at each follow-up period after GKS between the two groups. Adverse radiation effects (AREs) developed in a total of four patients (8.2 %); among them, one patient (2.0 %) developed a permanent case of diplopia. No mortality occurred in this series.

In this study, GKS was demonstrated to be a safe and effective alternative treatment for brain stem CMs that resulted in a reduction in the AHR. Consequently, we suggest that even CM patients who have suffered only a single bleed should not be contraindicated for SRS 3).


39 patients (16 males, 23 females) were treated with GKS for BSCA from January 1997 to September 2012. Clinical data were analyzed retrospectively. The mean age was 41.5 years. All patients had a history of symptomatic bleeding once or more before performing GKS. Mean volume of BSCA was 1095.3mm(3) and median prescribed marginal dose was 13 Gy.

Mean follow-up period since diagnosis was 4.1 years. The number of hemorrhagic events between initial diagnosis and GKS was 5 over a total of 14.9 patients-years with annual hemorrhagic rate of 33.6%. Following GKS, there were five hemorrhagic events within the first 2 years (8.1%/year) and two after the first 2 years (2.4%/year). The difference was not statistically significant. Neurologic status improved in 24 patients (61.5%), and stationary in eleven (28.2%). 4 patients (10.3%) experienced the exacerbation of symptoms at the last follow-up and none of them were related to the radiation injury. Significant volume reduction after GKS was observed in 24 patients (61.5%). Surgical excision was performed in one patient due to swelling and rebleeding after GKS. Age at presentation, sex, mass size of BSCA, and location, GKS dose did not affect post-GKS hemorrhage.

GKS for BSCA using relatively low marginal dose is safe and effective. Long-term prospective study is needed to confirm the optimal dose for BSCA 4).


1) Aboukais R, Estrade L, Devos P, Blond S, Lejeune JP, Reyns N. Gamma Knife Radiosurgery of Brainstem Cavernous Malformations. Stereotact Funct Neurosurg.2016 Dec 20;94(6):397403. [Epub ahead of print] PubMed PMID: 27992870.
2) Liu HB, Wang Y, Yang S, Gong FL, Xu YY, Wang W. Gamma knife radiosurgery for brainstem cavernous malformations. Clin Neurol Neurosurg. 2016 Oct 11;151:55-60. doi: 10.1016/j.clineuro.2016.09.018. [Epub ahead of print] PubMed PMID: 27794267.
3) Lee SH, Choi HJ, Shin HS, Choi SK, Oh IH, Lim YJ. Gamma Knife radiosurgery for brainstem cavernous malformations: should a patient wait for the rebleed? Acta Neurochir (Wien). 2014 Oct;156(10):1937-46. doi: 10.1007/s00701-014-2155-0. PubMed PMID: 24965071.
4) Kim BS, Yeon JY, Kim JS, Hong SC, Lee JI. Gamma knife radiosurgery of the symptomatic brain stem cavernous angioma with low marginal dose. Clin Neurol Neurosurg. 2014 Nov;126:110-4. doi: 10.1016/j.clineuro.2014.08.028. PubMed PMID: 25238102.

New Book: Image-Guided Stereotactic Radiosurgery

Image-Guided Stereotactic Radiosurgery: High-Precision, Non-invasive Treatment of Solid Tumors
By Harun Badakhshi

Image-Guided Stereotactic Radiosurgery: High-Precision, Non-invasive Treatment of Solid Tumors

List Price:$109.00

ADD TO SHOPPING CART

This book provides the reader with a detailed update on the use of stereotactic radiosurgery (SRS) in patients with lesions of the brain and other parts of the body. The aim is not simply to explain the application of SRS and document its value with reference to the author’s own clinical experiences and other published evidence, but also to contextualize the technology within a new strategic concept of cancer care. When embedded within an appropriate conceptual framework, technology becomes pivotal in changing therapeutic strategies. A new paradigm that is increasingly impacting on clinical practice is the oligometastatic state, on the basis that long-term survival might be achieved in patients with a low volume and number of metastatic lesions. This book accordingly addresses the value of SRS in patients with oligometastases of solid tumors to the brain, lung, spine, and liver. In addition, it examines the use of SRS in patients with diverse brain lesions, early-stage stage lung cancer, liver cancer, and early-stage prostate cancer. Readers will be persuaded that SRS, using cutting-edge imaging technologies to deliver precisely targeted radiation therapy, represents an exciting non-invasive procedure that holds great promise for the present and the future of cancer care.


Dr Harun Badakhshi is Chief Physician and chairman of clinical radiation oncology at Ernst von Bergmann Medical Center, an academic teaching hospital of Humboldt University Berlin. He also serves as senior lecturer / assoc. professor at Charité School of Medicine Humboldt University Berlin, and is holding various functions in regional and European organizations and societies that are related to cancer research and education. He has previously worked as vice chairman of radiation oncology at University Hospital Charité.

His research interest is primarily in neurooncology, lung and breast cancer, and metastases research. A focus of his research lies, especially, in studying effects of image-guided high precision radiotherapy for benign and malignant tumors, as well in investigations about curative potentials for cancer with oligometastases.

He has published about 50 original peer-reviewed research papers to date and many reviews on different aspects of medicine, including prevention, education, health economics. He serves as a reviewer for more than 10 specialized journals, and as an appraiser for regional medical organizations and physician chamber.

Product Details

  • Published on: 2016-07-27
  • Original language: English
  • Number of items: 1
  • Dimensions: .0″ h x .0″ w x .0″ l, .0 pounds
  • Binding: Hardcover
  • 271 pages