Somatostatin analogs in meningioma

Somatostatin analogs in meningioma

Meningiomas are associated with several sex hormones-related risk factors and demonstrate a predominance in females. These associations led to investigations of the role that hormones may have on meningioma growth and development. While it is now accepted that most meningiomas express progesterone and somatostatin receptors, the conclusion for other receptors has been less definitive.

Miyagishima et al. performed a review of what is known regarding the relationship between hormones and meningiomas in the published literature. Furthermore, they reviewed clinical trials related to hormonal agents in meningiomas using MEDLINE PubMedScopus, and the NIH clinical trials database.

They identified that all steroid-hormone trials lacked receptor identification or positive receptor status in the majority of patients. In contrast, four out of five studies involving somatostatin analogs used positive receptor status as part of the inclusion criteria.

Several clinical trials have recently been completed or are now underway using somatostatin analogs in combination with other therapies that appear promising, but a reevaluation of hormone-based monotherapy is warranted. Synthesizing this evidence, they clarified the remaining questions and present future directions for the study of the biological role and therapeutic potential of hormones in meningioma and discuss how the stratification of patients using features such as grade, receptor status, and somatic mutations, might be used for future trials to select patients most likely to benefit from specific therapies 1)


Jensen et al. performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. They applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. They included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked “very low.” Stable disease was reported in 58% of patients as best radiological response. Per 100 mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistency in study designs is warranted to assess somatostatin analog therapy for well-defined meningioma subgroups 2).

Between January 1996 and December 2010, 13 patients harboring a progressive residual meningioma (as indicated by MR imaging criteria) following operative therapy were treated with a monthly injection of the SST analog octreotide (Sandostatin LAR [long-acting repeatable] 30 mg, Novartis). Eight of 13 patients had a meningioma of the skull base and were analyzed in the present study. Postoperative tumor enlargement was documented in all patients on MR images obtained before the initiation of SST therapy. All tumors were benign. No patient received radiation or chemotherapy before treatment with SST. The growth of residual tumor was monitored by MR imaging every 12 months.

Results: Three of the 8 patients had undergone surgical treatment once; 3, 2 times; and 2, 3 times. The mean time after the last meningioma operation (before starting SST treatment) and tumor enlargement as indicated by MR imaging criteria was 24 months. A total of 643 monthly cycles of Sandostatin LAR were administered. Five of the 8 patients were on SST continuously and stabilized disease was documented on MR images obtained in these patients during treatment (median 115 months, range 48-180 months). Three of the 8 patients interrupted treatment: after 60 months in 1 case because of tumor progression, after 36 months in 1 case because of side effects, and after 36 months in 1 case because the health insurance company denied cost absorption.

Conclusions: Although no case of tumor regression was detected on MR imaging, the study results indicated that SST analogs can arrest the progression of unresectable or recurrent benign meningiomas of the skull base in some patients. It remains to be determined whether a controlled prospective clinical trial would be useful 3).


1)

Miyagishima DF, Moliterno J, Claus E, Günel M. Hormone therapies in meningioma-where are we? J Neurooncol. 2022 Nov 23. doi: 10.1007/s11060-022-04187-1. Epub ahead of print. PMID: 36418843.
2)

Jensen LR, Maier AD, Lomstein A, Graillon T, Hrachova M, Bota D, Ruiz-Patiño A, Arrieta O, Cardona AF, Rudà R, Furtner J, Roeckle U, Clement P, Preusser M, Scheie D, Broholm H, Kristensen BW, Skjøth-Rasmussen J, Ziebell M, Munch TN, Fugleholm K, Walter MA, Mathiesen T, Mirian C. Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data. Neurosurg Rev. 2022 Oct;45(5):3067-3081. doi: 10.1007/s10143-022-01849-6. Epub 2022 Aug 19. PMID: 35984552.
3)

Schulz C, Mathieu R, Kunz U, Mauer UM. Treatment of unresectable skull base meningiomas with somatostatin analogs. Neurosurg Focus. 2011 May;30(5):E11. doi: 10.3171/2011.1.FOCUS111. PMID: 21529167.

Foramen magnum meningioma

Foramen magnum meningioma

Foramen magnum meningiomas (FMMs) are slow growing, posterior fossa meningiomas most often intradural and extramedullar. They are those arising anteriorly from the inferior third of the clivus to the superior edge of the C2 body, laterally from the jugular tubercle to the C2 laminae, and posteriorly from the anterior border of the occipital squama to the spinous process of C2 1) 2) 3).

They represent 2% of all meningioma4).

The mean age of the patients with these lesions at the time of diagnosis is approximately 55 years old, but these tumors have been reported in patients of almost every age 5) 6) 7) 8) 9).

They have traditionally been said to involve the lower third of the clivus and the C1 C2 area. However, the last categorizations are arbitrary.

There are some tumors that involve the entire clivus, and others that involve the mid and lower third of the clivus. (The upper clivus is the area above the trigeminal root, the mid-clivus extends to the level of the glossopharyngeal nerve, and the lower clivus is the region below the glossopharyngeal nerve).

The indolent clinical course of FMMs and their insidious onset of symptoms are important factors that contribute to delayed diagnosis and relative large size at the time of presentation. Symptoms are often produced by compression of surrounding structures (such as the medulla oblongata, upper cervical spinal cord, lower cranial nerves, and vertebral artery) within a critically confined space

Matsoukas S, Oemke H, Lopez LS, Gilligan J, Tabani H, Bederson JB. Suboccipital Craniectomy for an Anterior Foramen Magnum Meningioma-Optimization of Resection Using Intraoperative Augmented Reality: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2022 Nov 1;23(5):e321. doi: 10.1227/ons.0000000000000373. Epub 2022 Aug 8. PMID: 36103323.


Emerson SN, Toczylowski M, Al-Mefty O. Dejerine Syndrome Variant Due to Medullary Perforating Artery Ischemia During Foramen Magnum Meningioma Resection: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2022 Jul 1;23(1):e52-e53. doi: 10.1227/ons.0000000000000211. Epub 2022 Apr 20. PMID: 35726936. Danish B, Costello MC, Patel NV, Higgins DMO, Komotar RJ, Ivan ME. Commentary: Dejerine Syndrome Variant Due to Medullary Perforating Artery Ischemia During Foramen Magnum Meningioma Resection: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2022 Sep 1;23(3):e205-e206. doi: 10.1227/ons.0000000000000336. Epub 2022 Jul 11. PMID: 35972118.


Danish B, Costello MC, Patel NV, Higgins DMO, Komotar RJ, Ivan ME. Commentary: Dejerine Syndrome Variant Due to Medullary Perforating Artery Ischemia During Foramen Magnum Meningioma Resection: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2022 Sep 1;23(3):e205-e206. doi: 10.1227/ons.0000000000000336. Epub 2022 Jul 11. PMID: 35972118.


Medina EJ, Revuelta Barbero JM, Porto E, Garzon-Muvdi T, Henriquez O, Solares CA, Pradilla G. Exoscopic and Microscopic Combined Far Lateral Retrocondylar Approach for Resection of a Ventral Foramen Magnum Lesion: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2022 Aug 1;23(2):e126. doi: 10.1227/ons.0000000000000250. Epub 2022 May 9. PMID: 35838470.


Jeelani Y, Ibn Essayed W, Al-Mefty O. Extended Transcondylar Approach With C-1 Lateral Mass Resection for the Removal of a Calcified Ventral “Spinocranial” Meningioma: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2022 Aug 1;23(2):e117-e118. doi: 10.1227/ons.0000000000000278. Epub 2022 May 9. PMID: 35838463.


Essayed W, Aboud E, Al-Mefty O. Foramen Magnum Meningioma-The Attainment of the Intra-Arachnoidal Dissection: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2021 Nov 15;21(6):E518-E519. doi: 10.1093/ons/opab317. PMID: 34498699.


Campero A, Baldoncini M, Villalonga JF, Paíz M, Giotta Lucifero A, Luzzi S. Transcondylar Fossa Approach for Resection of Anterolateral Foramen Magnum Meningioma: 2-Dimensional Operative Video. World Neurosurg. 2021 Oct;154:91-92. doi: 10.1016/j.wneu.2021.07.058. Epub 2021 Jul 21. PMID: 34303002.


1)

öçmez C, Göya C, Hamidi C, Kamaşak K, Yilmaz T, Turan Y, et al. Three-dimensional analysis of foramen magnum and its adjacent structures. J Craniofac Surg. 2014;25(1):93–97.
2)

George B, Lot G, Boissonnet H. Meningioma of the foramen magnum: a series of 40 cases. Surg Neurol. 1997;47(4):371–9.
3) , 4)

Bruneau M, George B. Foramen magnum meningiomas: detailed surgical approaches and technical aspects at Lariboisière Hospital and review of the literature. Neurosurg Rev. 2008 Jan;31(1):19-32; discussion 32-3. doi: 10.1007/s10143-007-0097-1. Epub 2007 Sep 20. PMID: 17882459; PMCID: PMC2077911.
5)

Colli BO, Carlotti-Junior CG, Assirati-Junior JA, Borba LA, Coelho-Junior Vde P, Neder L. Foramen magnum meningiomas: surgical treatment in a single public institution in a developing country. Arq Neuropsiquiatr. 2014;72(7):528–37.
6)

Pirotte BJ, Brotchi J, DeWitte O. Management of anterolateral foramen magnum meningiomas: surgical vs conservative decision making. Neurosurgery. 2010;67(3):58–70.
7)

Flores BC, Boudreaux BP, Klinger DR, Mickey BE, Barnett SL. The far-lateral approach for foramen magnum meningiomas. Neurosurg Focus. 2013;35(6):E12. doi:10.3171/2013.10.FOCUS13332.
8)

Borba LA, de Oliveira JG, Giudicissi-Filho M, Colli BO. Surgical management of foramen magnum meningiomas. Neurosurg Rev. 2009;32(1):49–60.
9)

Goel A, Desai K, Muzumdar D. Surgery on anterior foramen magnum meningiomas using a conventional posterior suboccipital approach: a report on an experience with 17 cases. Neurosurgery. 2001;49(1):102–7.
10)

Suisa H, Soustiel JF, Grober Y. IgG4-related pachymeningitis masquerading as foramen magnum meningioma: illustrative case. J Neurosurg Case Lessons. 2021 Dec 6;2(23):CASE21398. doi: 10.3171/CASE21398. PMID: 36061082; PMCID: PMC9435580.
11)

Uramaru K, Sakata K, Shimohigoshi W, Kawasaki T, Manaka H. Primary Meningeal Melanocytoma Located in the Craniovertebral Junction: A Case Report and Literature Review. NMC Case Rep J. 2021 Jun 25;8(1):349-354. doi: 10.2176/nmccrj.cr.2020-0191. PMID: 35079487; PMCID: PMC8769411.

Brain metastases treatment guidelines

Brain metastases treatment guidelines

Please see the full-text version of this guideline https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-treatment-of-adults-with-metastatic-bra-2 for the target population of each recommendation listed below.

SURGERY FOR METASTATIC BRAIN TUMORS AT NEW DIAGNOSIS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo Brain metastases surgeryStereotactic radiosurgery for brain metastases (SRS), or whole brain radiotherapy (WBRT)?

RECOMMENDATIONS:

Level of Evidence 1: Surgery + WBRT is recommended as first-line treatment in patients with single brain metastases with favorable performance status and limited extracranial disease to extend overall survivalmedian survival, and local control.

Level of Evidence 3: Surgery plus SRS is recommended to provide survival benefit in patients with metastatic brain tumors

Level of Evidence 3: Multimodal treatments including either surgery + WBRT + SRS boost or surgery + WBRT are recommended as alternatives to WBRT + SRS in terms of providing overall survival and local control benefits.

SURGERY AND RADIATION FOR METASTATIC BRAIN TUMORS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgical resection followed by WBRT, SRS, or another combination of these modalities?

RECOMMENDATIONS:

Level 1: Surgery + WBRT is recommended as superior treatment to WBRT alone in patients with single brain metastases.

Level 3: Surgery + SRS is recommended as an alternative to treatment with SRS alone to benefit overall survival.

Level 3: It is recommended that SRS alone be considered equivalent to surgery + WBRT.

SURGERY FOR RECURRENT METASTATIC BRAIN TUMORS QUESTION: Should patients with recurrent metastatic brain tumors undergo surgical resection?

RECOMMENDATIONS:

Level 3: Craniotomy is recommended as a treatment for intracranial recurrence after initial surgery or SRS.   SURGICAL TECHNIQUE AND RECURRENCE QUESTION A: Does the surgical technique (en bloc resection or piecemeal resection) affect recurrence?

RECOMMENDATION:

Level 3: En bloc resection of the tumor, as opposed to piecemeal resection, is recommended to decrease the risk of postoperative leptomeningeal disease when resecting single brain metastases.

QUESTION B:

Does the extent of surgical resection (gross total resection or subtotal resection) affect recurrence?

RECOMMENDATION:

Level 3: Gross total resection is recommended over subtotal resection in Recursive partitioning analysis class 1 class I patients to improve overall survival and prolong time to recurrence1)


1)

Nahed BV, Alvarez-Breckenridge C, Brastianos PK, Shih H, Sloan A, Ammirati M, Kuo JS, Ryken TC, Kalkanis SN, Olson JJ. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors. Neurosurgery. 2019 Mar 1;84(3):E152-E155. doi: 10.1093/neuros/nyy542. PubMed PMID: 30629227.
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