Methods
From the years 2007 to 2016 we retrieved all records of patients with MBL and FAP, adopting the following main inclusion criteria:
1. documented germline APC mutations
2. centrally-reviewed histopathological diagnosis of MBL;
3. no age limit;
4. one or more conventional brain MRI studies, reviewed by the authors (LC; AE);
5. genetic counseling for FAP, and documentation and assessment of family history.
For two patients, who were probands, APC germline analysis was performed on genomic DNA extracted from blood samples by Sanger direct sequencing. Moreover, large deletions or duplications were investigated by Multiplex Ligation Dependent Probe Amplification (MLPA). Four patients, who were not probands, were submitted to predictive genetic test, in order to find the mutation present in the family;
MRI studies were reviewed according to Patay criteria14. Briefly, on the basis of anatomic lesion patterns, Patay distinguished 4 location-based subtypes: 1) midline-intraventricular as subtype A, 2) midline-extraventricular as subtype B, 3) off-midline–intraventricular as subtype C, and 4) off-midline– extraventricular as subtype D, which represent a continuum. WNT-sub-group MBLs are in fact close to the midline yet there are also lateralized tumors originating from structures around the foramen of Luschka .
By examining these patients’ diagnostic and treatment data, we aimed to: i) describe their progression-free survival and overall survival; ii) confirm the favorable prognosis reported in the recent literature15, and describe the potential (clinical, therapeutic, pathological and molecular) prognostic factors associated with successful treatment; and iii) examine in depth the complex hereditary genetic mechanism behind the onset and course of MBL in these patients.
We also considered acute, i.e. craniospinal irradiation duration, chemotherapy courses received, total drug doses administered, and long-term toxicities, i.e. endocrine and neurocognitive deficits, of the treatments administered. All survivors’ current state of health and social status was reported with a view (if possible and judged necessary) to reducing the post-surgical treatment of this particular group of MBL in the light of patients’ prognosis and the toxicity they experienced.
Oncological disease-free survival after the diagnosis of MBL was calculated with Kaplan Meier methods.
The study was approved by our institution’s independent ethical committee (prot. 166/20). Patients or parents gave their consent to this analysis.