Biological Behaviour of Craniopharyngiomas.

Jakob Erdheim (1874-1937) first described craniopharyn-giomas (CPs) as "hypophyseal duct tumours" and postulated the existence of two tumour types based on their histological features: (1) an aggressive type showing similarities to adamantinomas (tumours of the jaw) and (2) a more benign form characterised by the presence of papillary structures. More than a century later, these initial observations have been confirmed; based on their distinct genetic, epigenetic, and histological features, the WHO classifies CPs into two types: adamantinomatous CPs (ACPs) and papillary CPs (PCPs). Considerable knowledge has been generated on the biology of CPs in the last 20 years. Mutations in CTNNB1 (encoding ß-catenin) are prevalent in ACP, whilst PCPs frequently harbour mutations in BRAF (p.BRAF-V600E). The consequence of these mutations is the activation of either the WNT/ß-catenin (ACP) or the MAPK/ERK (PCP) pathway. Murine models support a critical role for these mutations in tumour formation and have provided important insights into tumour pathogenesis, mostly in ACP. A critical role for cellular senescence has been uncovered in murine models of ACP with relevance to human tumours. Several gene profiling studies of human and murine ACP tumours have identified potential targetable pathways, and novel therapeutic agents are being used in clinical and pre-clinical research, in some cases with excellent results. In this review, we will present the accumulated knowledge on the biological features of these tumours and summarise how these advances are being translated into potential novel treatments.

Visual Field Loss in a Case of Recurrent Cystic Craniopharyngioma During Concomitant Treatment With Pegylated Interferon α-2b.

A 13-year-old male with suprasellar cystic craniopharyngioma initially controlled with sequential subtotal resections and proton-beam irradiation was later treated with intracystic pegylated interferon α-2b due to progression and a lack of further surgical options. After initial successful control of recurrent cyst enlargement and stabilization of the ophthalmic examination, progressive and irreversible visual field loss ensued. Imaging revealed intracranial leakage from the intracystic catheter, and direct administration of interferon α-2b was discontinued. Given the recent interest in interferon α-2b, oncologists are advised to vigilantly monitor patients for signs of local toxicity that may result from unintended leakage during intracystic delivery.

Phase II study of peginterferon alpha-2b for patients with unresectable or recurrent craniopharyngiomas: a Pediatric Brain Tumor Consortium report.

BACKGROUND: Craniopharyngiomas account for approximately 1.2-4% of all CNS tumors. They are typically treated with a combination of surgical resection and focal radiotherapy. Unfortunately, treatment can lead to permanent deleterious effects on behavior, learning, and endocrine function. METHODS: The Pediatric Brain Tumor Consortium performed a multicenter phase 2 study in children and young adults with unresectable or recurrent craniopharyngioma (PBTC-039). Between December 2013 and November 2017, nineteen patients (median age at enrollment, 13.1 y; range, 2-25 y) were enrolled in one of 2 strata: patients previously treated with surgery alone (stratum 1) or who received radiation (stratum 2). RESULTS: Eighteen eligible patients (8 male, 10 female) were treated with weekly subcutaneous pegylated interferon alpha-2b for up to 18 courses (108 wk). Therapy was well tolerated with no grade 4 or 5 toxicities. 2 of the 7 eligible patients (28.6%) in stratum 1 had a partial response, but only one response was sustained for more than 3 months. None of the 11 stratum 2 patients had an objective radiographic response, although median progression-free survival was 19.5 months. CONCLUSIONS: Pegylated interferon alpha-2b treatment, in lieu of or following radiotherapy, was well tolerated in children and young adults with recurrent craniopharyngiomas. Although objective responses were limited, progression-free survival results are encouraging, warranting further studies.

Pegylated interferon-α-2b for children with recurrent craniopharyngioma.

OBJECT: Previous studies of systemic and intralesional administration of nonpegylated interferon have shown efficacy against craniopharyngioma. Pegylaion of interferon-α-2b (PI) prolongs the half-life, allowing sustained exposure of the drug over time, and enhances efficacy. The authors report the results of the use of PI in 5 children with recurrent craniopharyngiomas. METHODS: Five children, ranging in age from 9 to 15 years, with recurrent craniopharyngiomas were treated for up to 2 years with subcutaneous injections of PI at a dose of 1-3 µg/kg/week. Tumor response was assessed using MRI. RESULTS: All patients had stable disease or better in response to PI. One patient experienced a recurrence after gross-total resection (GTR). She initially showed an increase in the predominantly cystic tumor after 3 months of treatment, followed by a complete response. She required no further intervention and remains without evidence of disease 10 years after starting treatment. Another patient experienced recurrence 3.3 years after subtotal resection (STR) and radiation therapy. He had complete disappearance of the predominantly cystic component after 4 months of treatment, and a small residual calcified mass remains 5 years later. The third patient experienced recurrence after 3 GTRs. He had a complete response after 7 months of treatment and remains without evidence of disease 19 months after starting treatment. The fourth patient experienced recurrence after 2 STRs. He had a 30% decrease in tumor size after 4 months of treatment, which was maintained for 12 months at which point the cyst began to increase in size. The final patient experienced recurrence after GTR and has stable disease 6 months after starting treatment with PI. CONCLUSIONS: The use of PI in children with recurrent craniopharyngiomas can result in significant and durable responses and potentially delay or avoid the need for radiation therapy.