Patients’ medulloblastoma-related features
Six patients (5 of them females) were diagnosed between 2007 and 2016 and met our inclusion criteria. They were a median 10 years old (range 6-26 years) at medulloblastoma diagnosis. All patients presented at diagnosis with a clinical picture correlating with the tumor site (i.e. cerebellar deficits, endocranial hypertension, strabismus). None of them had had MRI before the suspect of brain tumor diagnosis for surveillance purposes .
The original MRI findings could be retrieved for review in 5/6 cases. Tumors were classified on the grounds of site, T2-weighted and DWI signal intensity, and contrast enhancement in accordance with the classification of WNT medulloblastoma proposed by Patay et al and already above summarized12. All tumors were located in the IV ventricle and characterized by uneven T2 hyperintensity, patchy contrast enhancement, and low ADC levels on DWI. All. Two were subtype A, and 3 were subtype B. Hydrocephalus was absent in 3 and present in 2 cases (Figure 1, case 5 not shown).
All patients underwent complete surgical excision of their tumors, which were all attributed to classic histotype and WNT subtype since WNT is deregulated where there is a germline APC pathogenetic mutation For all patients Beta-catenin immunostaining was assessed in tumoral tissue. Nuclear positivity at immunohistochemistry was found in 2/6 patients’ samples.
All patients were homogeneously treated irrespective of age under or over 18 years, as already reported16. Importantly, all patients received craniospinal irradiation (CSI) up to a total dose of 23.4 Gy, and a boost to the posterior fossa (in 3 patients) or tumor bed (in the other 3) up to a total dose of 54 Gy, delivered in fractions of 1.8 Gy, without any interruption due to acute side-effects of hematological toxicity (table 1).
In one patient (who was 26 years old at diagnosis), the post-operative schedule including cisplatin, vincristine and lomustine was changed - replacing cisplatin with carboplatin and omitting vincristine - due to ototoxicity after the second course and severe peripheral neurotoxicity with gait impairment .
All patients were in complete remission at 44-142 months after diagnosis (median 65 months) and were in active follow-up at the time of this report.
Late effects - Three patients had hypoacusia for acute tones, three had hypothyroidism (accompanied by thyroid nodules in 2 cases), two had growth hormone deficits, and five had vitamin D deficiency. One patient was married and having fertility treatment.
Three patients were still in main stream school, with special education program and extra-help teacher in one case each (at MBL diagnosis 6 and 10 years old, respectively), while the third one did not need education tailored program or help (6 years old at diagnosis).
One patient, 13 years old at diagnosis, was attending university; one, 12 years old at diagnosis, was working after completing a professional course and one, 26 years old at diagnosis, had a university degree, was married and stayed at home, fully independent. Full Intelligence Quotients (FIQ) were available for 5 patients after 2-7 years from diagnosis (table 1).
Table 1 shows also each patient’s oncological history after treatment for MBL. One patient developed a melanocytic tumor of uncertain malignant potential (MELTUMP), one a melanoma, another a thyroid nodule (classified as TIR3, i.e. uncertain malignancy, after needle biopsy) and a pancreatoblastoma a mean 6 years after MBL.
Figure 2 shows patients subsequent oncological disease-free survival, which was 50% at 5 years.