Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma

Sydney Grob, David M Mirsky, Andrew M Donson, Nathan Dahl, Nicholas K Foreman, Lindsey M Hoffman, Todd C Hankinson, Jean M Mulcahy Levy, Sydney Grob, David M Mirsky, Andrew M Donson, Nathan Dahl, Nicholas K Foreman, Lindsey M Hoffman, Todd C Hankinson, Jean M Mulcahy Levy

Abstract

Adamantinomatous craniopharyngioma (ACP) makes up between 6 and 8% of pediatric brain tumors and is the most common pediatric tumor arising in the sellar/suprasellar region of the brain. The 10-year survival for patients diagnosed with craniopharyngioma ranges between 64 and 92%, but complicating factors such as location, common cyst formation, and potential hypothalamic infiltration cause significant morbidity in this population. There are a number of therapeutic options for children with ACP, including surgery, radiation, and cyst directed therapies such as interferon and bleomycin. Research has raised concerns regarding the efficacy and side effects associated with these conventional therapies, as well as with the difficulty in treating recurrent cystic ACP. Evidence from our group and others has shown that the cystic and solid tumor components of craniopharyngioma have high levels of IL-6R and IL-6, providing a potential target for therapy. Tocilizumab, a humanized monoclonal antibody, acts against soluble and membrane bound IL-6R, and has been widely utilized in pediatric patients. Two patients with recurrent cystic ACP were offered systemically administered tocilizumab or a combination of tocilizumab and bevacizumab on a compassionate use basis. Both patients' tumors had a significant response, with decreased cyst burden, supporting the assertion that tocilizumab with or without bevacizumab may be an option for patients suffering from cystic ACP.

Keywords: IL-6; bevacizumab; craniopharyngioma; pediatric; tocilizumab.

Figures

Figure 1
Figure 1
Cyst volume (cm3) in response to treatment course for patient 1. (A) Diagnostic MRis. (B) Early response to interferon. (C) Response at end of bleomycin. (D) Best response to tocilizumab alone. (E) Best response to tocilizumab and bevacizumab. (F) Six months off all therapy. (G) Most recent scan. (H) Cyst volume (cm3) in response to treatment course.
Figure 2
Figure 2
Cyst volume (cm3) in response to treatment course for patient 2. (A) Diagnostic MRis. (B) Scan immediately before ommaya reservoir replacement. (C) Scan immediately stopping bleomycin for right frontal lobe edema. (D) Scan while on Tocilizumab. (E) Patient two cyst volume (cm3) in response to treatment course.
Figure 3
Figure 3
IL-6 Levels at diagnosis for patient 1, patient 2, a group of ACP Patients, and a group of pilocytic astrocytoma. The IL-6 levels (pg/mL) found in the cystic fluid of patient 1 and patient 2 at diagnosis as well as a group of 6 craniopharyngioma patients and a group of 5 patients with pilocytic astrocytoma.

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