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.

Somatostatin Analogs in Acromegaly

Somatostatin Analogs in Acromegaly

In vitro, native somatostatin retains its inhibitory effect on GH secretion in many GH-secreting tumors, and this led to the development of analogs of somatostatin for clinical use in the treatment of acromegaly 1).

The two analogs of somatostatin available for clinical use are the cyclic octapeptides octreotide (Dphe-cys-phe-Dtrp-lys-thr-cys-thr-ol) and lanreotide (Dnal-cys-tyr-Dtrp-lys-val-cys-thr) (1, 5–7). Octreotide is the only analog currently available for clinical use in the treatment of acromegaly in the United States.


Clinically available somatostatin analogs control GH or IGF-I excess in about 50–60% of patients whether used as primary or secondary therapy. Signs and symptoms of the disease improve in most patients. Tumor shrinkage occurs with somatostatin analogs used as adjunctive therapy in about 30% of patients and with their use as primary therapy in about 48% of patients. The shrinkage in most patients is greater than 20%, but less than 50% of tumor size 2).


Current data suggest that response to these drugs is better analyzed by taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA 3).


Somatostatin analogues may be used when complete recovery cannot be achieved by surgical excision of GH-secreting pituitary adenomas or the patient declines surgery. This position statement is established based on the consensus of opinion among experts and evidence from published data regarding the use of somatostatin analogs in patients with acromegaly. However, this position statement cannot be considered as complete, given the clinical characteristics of acromegaly and the absence of large-scale clinical data in Korea; at this time, the clinical judgment of the physician should take precedence over this statement. This position statement will be revised as needed when additional data for Korean patients become available 4).


Shao et al. retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After Somatostatin Analogs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, the study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly 5).

Lanreotide for Acromegaly.

Octreotide for Acromegaly.


1)

Lamberts SW. The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. Endocr Rev. 1988 Nov;9(4):417-36. doi: 10.1210/edrv-9-4-417. PMID: 2905987.
2)

Freda PU. Somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2002 Jul;87(7):3013-8. doi: 10.1210/jcem.87.7.8665. PMID: 12107192.
3)

Colao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev. 2011 Apr;32(2):247-71. doi: 10.1210/er.2010-0002. Epub 2010 Dec 1. PMID: 21123741.
4)

Chin SO, Ku CR, Kim BJ, Kim SW, Park KH, Song KH, Oh S, Yoon HK, Lee EJ, Lee JM, Lim JS, Kim JH, Kim KJ, Jin HY, Kim DJ, Lee KA, Moon SS, Lim DJ, Shin DY, Kim SH, Kwon MJ, Kim HY, Kim JH, Kim DS, Kim CH. Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement. Endocrinol Metab (Seoul). 2019 Mar;34(1):53-62. doi: 10.3803/EnM.2019.34.1.53. PMID: 30912339; PMCID: PMC6435847.
5)

Shao XQ, Chen ZY, Wang M, Yang YP, Yu YF, Liu WJ, Wang Y, Zeng FF, Gong W, Ye HY, Wang YF, Zhao Y, Zhang L, Zhang ZY, He M, Li YM. Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases. Horm Metab Res. 2022 Jan;54(1):25-32. doi: 10.1055/a-1717-9332. Epub 2022 Jan 5. PMID: 34986497.
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