by Vera Martinella
a very rare and benign brain tumor, difficult to treat. Therapies often leave significant side effects, but a study with new drugs opens a window of opportunity
Papillary craniopharyngioma is a very rare form of brain tumor which, although benign, has important consequences for patients. It is, in fact, treated with surgery, but it is often not possible to completely remove the lesion, and with radiotherapy, the toxicity of which can cause permanent damage. Patients often have to deal with neuroendocrine dysfunction, partial loss of vision and memory problems. A study conducted by American experts from the Mass General Cancer Center and published in New England Journal of Medicine opens up a glimmer of hope with the use of a new drug which managed, in all 15 patients involved in the trial, to significantly reduce the tumor mass.
Delicate area
When we talk about brain tumors we must keep in mind that we are actually referring to many different diseases (around 150 different types have been catalogued). There are 6 thousand new cases in Italy every year and 4 thousand deaths: in fact, they remain difficult to treat diseases also because they affect a delicate and complex organ that can be touched with a scalpel or other therapies without leaving long-term consequences. Specifically, craniopharyngioma is a rare tumor of the hypothalamic-pituitary region, affecting approximately one person in a million per year and affecting two age groups: children and adolescents between 5 and 15 years old and adults between 40 and 60 years old. . Although it is histologically considered a benign neoplasm (WHO grade I), it can reach considerable dimensions and often shows a marked tendency to infiltrate adjacent cerebral (hypothalamus, pituitary and optic chiasm) and neurovascular structures.
Two variations
The histological classification of craniopharyngiomas distinguishes two variants, the adamantinomatous craniopharyngioma, which is the most frequent, found in both children and adults, and the papillary craniopharyngioma, even rarer and prevalent in the adult population with an average age of onset between 40 and 60 years old – explains Enrico Franceschi, director of Oncology of the nervous system at the IRCCS Institute of Neurological Sciences in Bologna –. The two subtypes differ from each other in terms of frequency, age distribution, morphological and molecular biology aspects and also show different prognosis and clinical life expectancy.
Symptoms
What are the symptoms
and how do you get to the diagnosis? For the most part, the first signs are nonspecific, generally related to the effect created by the mass of the tumor growing in the region of the brain where it develops. The most frequent are headache (75 percent of cases) and vision problems (60-80 percent) – replies Franceschi -. Other symptoms can be caused by pituitary hormone deficiencies, observed in more than 50% of patients. The radiological tests to have a certain diagnosis are magnetic resonance imaging, with specific sequences aimed at the sellar region (an anatomically complex part of the brain, which includes the pituitary gland) and computerized tomography. These assessments can then be completed by further preparatory tests for surgery such as CT angiography, MRI angiography and angiographies.
The therapies
The main therapeutic approach is surgery. Craniopharyngioma often shows a marked tendency to infiltrate nearby brain structures, therefore complete surgical resection, although constituting the first therapeutic choice, is however rather difficult to obtain. To avoid neurological or hormonal complications, subtotal surgery on the tumor is often performed, followed by radiotherapy on the tumor residue. However, the post-operative recurrence rate is 20-25 percent. The new research fits into this scenario. Medical oncological therapy of craniopharyngioma has made important progress in recent years, drawing great benefits from discoveries regarding the molecular mechanisms underlying the development and growth of these rare tumors – clarifies Franceschi -. The alterations of the oncological pathways are specific depending on the histological subtype of the craniopharyngioma, in particular the papillary one characterized, in approximately 90% of cases, by the BRAF-V600E mutation, which is an ideal target for personalized therapy.
I study
Nello study published in the New England Journal of Medicine, of phase II on a few patients (phase two is the one in which the safety and efficacy of a new medicine are tested), 16 patients suffering from papillary craniopharyngioma, with an average age of 50 years, were treated with a molecularly targeted therapy against the BRAF-V600E mutation which involved the use of vemurafenib (which blocks the activity of BRAF V600E) and cobimetinib (which blocks the activity of an enzyme known as MEK). 15 patients (94 percent) had a response to treatment with a median tumor volume reduction of 91 percent. Progression-free survival was 87 percent at 12 months from the start of therapy and 58 percent at 24 months. Overall, the treatment was well tolerated by the patients and the toxicities were easy to manage. The finding of the BRAF mutation in papillary craniopharyngiomas has therefore opened the way to new therapeutic possibilities, absent in the past, similarly to what happened in other tumors more frequent in the population but carriers of the same mutation, such as melanoma, thyroid carcinoma and colorectal cancer.
September 29, 2023 (modified September 29, 2023 | 11:59)
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