Download - High – dose chemotherapy for medulloblastoma treatment in children older than 3 years old
High – dose chemotherapy for medulloblastoma treatment in children older than 3 years old
Medulloblastoma is the most common malignant brain tumor in childhood
During last two decades survival rate have been improved in average risk patients
However survival in high risk patients is still poor and remains near 50%
In our study we used multiple high – dose chemotherapy with autologous peripheral blood stem cells rescue after risk adapted craniospinal radiotherapy with boos to posterior fossa
Risk group stratification
Average risk High risk
Residual tumor < 1.5 cm2 > 1.5 cm2
Extent of metastases
M0 M+ (M1, M2, M3)
Histological type
Large cell/anaplastic
Risk – adapted radiotherapy
Average Risk High Risk
23,4 Gy CSI 36 Gy CSI
+ boost to posterior fossa
(total dose 54 Gy)
After 6 weeks of radiotherapy completion all patients receive 4 cycles of cyclophosphamide – based high dose
chemotherapy
Day – 4: vincristine 1 mg/m2
День – 4: cisplatin 75 mg/m2
День – 3: cyclophosphamide 2000 mg/m2
День – 2: cyclophosphamide 2000 mg/m2
День – 1: Hydration
День 0: Infusion of peripheral blood stem cells
День + 1: GCSF – 5 μg/kg until ANC> 2*109/L
День + 6: vincristine 1 mg/m2
Between 2008 and 2012 we have enrolled 30 patients in our trial
Surgical excision of tumor was performed in Burdenko Neurosurgery Institute
Radiotherapy course patients received in our clinic and in Institute of rentgenoradiology
Courses of high dose chemotherapy performed in our clinic
Clinical characteristics of enrolled patients
Characteristic Number of patients
Characteristic Number of patients
Sex: Male Female
17 (56,7%)13 (43,3%)
Histological characteristics: Classic
Nodular desmoplastic
Large cell/anaplastic
26 (86,7%)
1 (3,3%)
3 (10%)
Age (years) Median (range) 10,7 (3 – 18)
Extent of resection R0 R1
19 (56,7%)11 (43,3%)
Extent of metastases M0 M+ (M1 – M3)
20 (66,7%)10 (23,3%)
Toxicity of chemotherapy regimen All patients had hematopoietic toxicity and requires blood and
platelet transfusion Other main type of toxicity was infection, almost all patients had
febrile neutropenia. Hepatic toxicity (grade II – III) was observed in 5 patients
(16,7%) Two patients receiving chemotherapy have died of sepsis and
organ failure. 25% of enrolled patients required parenteral nutrition.
Peripheral blood stem cell rescue The number of PBSCs infused per cycle ranged from
0,2*106/kg to 2,8*106/kg Median CD 34+ cells number – 1,27*106/kg Median bone marrow recovery time ranged from 8 to 29 days There was significant correlation between bone marrow
recovery and CD 34+ number. (p = 0,001) Duration of neutropenia in patient group who received CD
34+ cells less than 1*106/kg was longer compared with those who received more than 1*106/kg CD 34+ cells. Neutropenia duration was 10,2 days in first group and 14,3 days in second group.
Results
3 – year PFS in all patients was 72,2%±9,0%
Median follow up was 57,9±4 months (5 – 68)
3 – year PFS for High risk and Average risk patients
3 – year PFS for High risk patients was – 66,1±11,4% (median follow up - 39,4±4,7 months)
3 – year PFS for Average risk patients was - 77,4±11,5% (median follow up - 56,8±5,6 months)
3 – year PFS based on extent of resection
3 – year PFS in group with residual tumor was 63,5±16,9% (median follow up 38,1±5,3 months)
3 - year PFS in group without residual tumor was 77,5±9,0% (median follow up 56,5±5)
3 – year PFS based on extent of metastases
3 – year PFS in patient with M+ stage (M1, M2 and M3) was 62,2±17,8% (median follow up 38,6±6,6 months)
3 – year PFS in patients with M0 stage was 77,2±10,1% (median follow up – 54,9±4,9 months)
Conclusion Our study demonstrates that an intensive chemotherapy
regimen is feasible and effective after tumor resection and craniospinal radiotherapy in treatment of newly diagnosed medulloblastoma
Main type of toxicity was hematopoietic toxicity and requires blood and platelet transfusion.
Treatment mortality was 6,7%, caused by sepsis (multiresistant Pseudomonas aeruginosa)
As a result we have reached better survival in high group risk patients (3 – year PFS - 77,4%)
However, recent studies have shown that medulloblastoma is biologically heterogeneous tumor and requires new approaches in diagnostic and treatment.
Thank you for your attention!