Material and Methods:
Forty-nine children operated for a central nervous system ependymoma between 2002 and 2018: 33 were located in the cerebral posterior fossa. Among these patients, seven were recurrences (five patients were operated on in another center for the first surgery). The mean time for diagnosis was 1 month. The clinical picture was dominated by an aspecific intracranial hypertension in 18 patients (54.5%), a torticollis in six patients (18.18%) and cerebellar troubles in four patients (12.1%). All children had a cranio-spinal MRI scan before removal of the tumor. All patients had a anatomopathological study of cerebrospinal fluid (CSF) after an endoscopic third ventriculocisternostomy (ETV) for 42.4% of cases or by a lumbar puncture at 15 days after surgery for the remaining 57.6%. Fourteen patients (42.4%) had an ETV before surgery. The mean time between VCS and surgery was 3 days. Surgery was performed in sitting position in 32 patients and in prone position in 1 patient for an in interventricular cardiac shunt defect. The removal was assessed by a post-operative MRI performed within 24/48 hours (Figure 1). A residue was reported in seven patients on the post-operative MRI (78.12% total resection) while the resection has been judged macroscopically complete in all but three by the surgeon. In five patients the complete resection was obtained after a second-look surgery before further treatments. Sixty-five surgeries were performed for 33 patients (33 initial + 32 for recurrence). Two patients were operated on for a spinal metastasis. All patients had a complementary treatment: chemotherapy alone for children younger than 3 years of age and/or combined with local radiotherapy even for infants. Eleven patients received postoperative chemotherapy (6 neoadjuvant and 5 relapse) and 35 radiotherapy (24 neoadjuvant and 11 cases at relapse) including neoadjuvant proton therapy (4 neoadjuvant cases and 2 at the relapse). The dose varied from 54 to 59.4 Gy according the SFOP protocols. Concerning chemotherapy: 2 protocols were used the ”BB-SFOP” with 3 cycles alternating every 21 days with 7 cycles in total and the SIOP EPENDYMOMA II.
All patients, except one who died in the 1st year of surgery, benefited during the follow-up of a cerebrospinal MRI every 3 months in the first year, every 6 months for two consecutive years and every year until the fifth year. Endocrine sequels after radiotherapy were observed in 3 patients (9.09%). A neuropsychological assessment was performed in all children at 1 and 3 years of surgery by a pediatric neuropsychologist with an age-appropriate IQ evaluation and the Vineland Adaptive Behaviour Scales (VABS). Quality of life was analyzed in all 21 alive patients. Survival curves (OS), were calculated according to Kaplan-Meier curves for overall survival, 5-year survival, progression-free survival (PFS). Differences with a p < 0.05 were considered statistically significant. Quality of life and overall motor function were scored with the Barthel Index and the Euro Qol 5 Dimensions (EQ-5D) scale. Educational outcomes were classified as normal and assisted schooling or specialized institution. No patient was lost to follow-up. The study was accepted by the local ethical committee
Results :
The mean age at diagnosis was 5.8 years old (median 4.7 years old, range: 9 months to 18 years). The most represented age range was between 3 and 6 years old with 12 cases (36.4%). There was a predominance of males, with 23 males for 10 females. The lesions were located in the fourth ventricle in 28 patients (84.8%), in the cerebellum and the cerebellopontine angle in 3 (9.1%) and 2 cases (6.1%) respectively. At the time of diagnosis, tumor cells were found in one patient’s CSF. Twenty patients had a Grade II and 13 had a Grade III, and we noted a Grade II to Grade III mutation at recurrence in 2 patients. The majority of the EpPCF were of the PFA group (90%). The main complications in the early postoperative period were cranial nerve palsy in 14 patients. A patient could have several nerves affected at the same time; facial nerve damage in 4 patients, abducens nerve damage in 5 cases, and oculomotor nerve damage in 2 patients. Six had mixed nerve damage, 2 of which required tracheotomies. A cerebellar mutism was observed in 2 patients. The overall survival rate of our series was of 63,6% and the mortality was of 36,3 % (n=12). The median survival was of 122 months and the median was of 104,7 months. The 10-year survival was 42,4 % (n=14) and the five years’ survival was of 63,6 % (n=21). The progression-free survival rate at 5 years was 57.69%. Male’s and female’s OS (65.2% and 66.7% respectively) did not differ significantly(p> 0.05) (Figure 2). OS was of 73.7% and 53.8% for WHO grade II and III (p> 0.05) (Figure 3). Sixteen patients (48%) had a recurrence (10 patients Grade II and 6 patients Grade III). Eight were children (47%) aged 0 to 3 years. Six patients (20%) were submitted to a second-look surgery to obtain a complete removal that was possible in four patients after the control MRI. In two patients, histology revealed an inflammatory granuloma. One patient refused surgery after a first recurrence and 2 others after a 4th recurrence. The metastasis rate after the initial surgery was 18.2% (6 patients) (Figure 4).
Twelve patients died: 10 for a progression (despite an initial complete removal) after relapse surgery and additional treatment. One patient died after a recurrence and the family refused a new operation and another after post-operative bulbar respiratory complications.
Morbidity was represented by: facial nerve palsy in 4 cases and swallowing troubles in 3 cases. Four patients had transient cerebellar syndrome. Five patients needed a ventriculo-peritonea shunt. Fifteen patients had a normal school program; six patients have had special schooling (Auxiliary for School Life). All had been assessed by the Service Mobile d’Accompagnement d’Evaluation and de Coordination (SMAEC). Among the 9 adult patients, 6 completed their studies and 3 are still students. Eight adults have normal full-time employment. We could identify 3 groups of patients: patients with a complete removal and alive (18 patients), patients with a complete removal and dead (8 patients) and patients with an incomplete removal (7 patients).
In the first group, four patients presented a recurrence (in the cerebello-pontine angle one case, two in the midline, at level of the floor of the fourth ventricle one case. All 18 patients are alive with a mean survival of 12 years (range: 6 to 19 years).
In the second group, one patient presented an extension at level of the floor of the fourth ventricle, three patients an extension in the cerebello-pontine angle of the left side and two of the right side and one in the cerebellar hemisphere.
All received a complementary treatment: only radiotherapy (5 cases), chemotherapy associated with radiotherapy (two cases) and only chemotherapy (one patient aged two years old).
Five patients presented an ependymoma of grade III with PFA signature in 3. All patients presented a recurrence and all were operated with a new complete removal and the survival varied from two months to 109 months with a median survival of three years and one months.
In the third group, only two patients are alive and 5 died. In this group, four patients had radiotherapy and three were treated with a radiotherapy associated with chemotherapy.
Two patients were operated three times and one patient was operated five times.
In this group, patient who presented a recurrence died after four years, twenty-two years, one year and two years.
Five patients were treated with radiotherapy and two patients with chemotherapy.