Chemotherapy plays an important role in the treatment of supratentorial PNETs.
- Chemotherapy is recommended as adjunctive therapy for newly diagnosed supratentorial PNETs.
- Intensive chemotherapy with autologous stem cell rescue is beneficial in younger children to delay or avoid radiation therapy (RT) 17.
German studies highlighted the difficulty of finding a chemotherapy protocol to delay RT in infants and young children. The HIT-SKK87 and HIT-SKK 92 trials examined 29 pediatric patients under the age of 3.
HIT-SKK87 trial:
Children were divided into:
- Low risk (complete resection, no dissemination)
- Maintenance therapy until RT administered after age 3
- High risk (subtotal resection or metastases)24
- Induction chemotherapy post surgery followed by maintenance chemotherapy until age 3
Overall survival rate after 3 years was 17%
HIT-SKK92 trial:
Three cycles of methotrexate based chemotherapy was given after surgery
Overall survival rate after 3 years 15%
Conclusion: RT is important therapy in supratentorial PNET. If possible, delay of RT should be limited to a maximum of 6 months during initial therapy24
Link: Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91 J Neurooncol 2007 Jan;81(2):217-23. Epub 2006 Aug 29
There is however evidence to support the use of chemotherapy to delay RT in young patients:
Head Start (HS) I and II:
Intensive induction chemotherapy followed by consolidation chemotherapy and autologous hematopoietic cell rescue (AuHCR) in children with a new diagnosis of supratentorial PNET.
- 43 patients studied in this study
- Upper age limit of 6 years old (HS I trial), 10 years old (HS II trial)
Patients given induction chemotherapy, 5 cycles every 3 weeks (vincristine, cisplatin, cyclophosphamide and etoposide) post surgery8
HS II with CSA metastatic disease:
If there was CSA metastatic disease in HS II: High dose methotrexate and leucovorin rescue used and then if there was evidence of disease response (defined as tumor remission on MRI and clearance of malignant cells in CSF) patients received a single cycle of high dose consolidation chemotherapy (carboplatin, thiotepa and etopside) followed by AuHCR.
Post chemotherapy, patients were then offered RT per recommended dosage, if they were 6 years old at the time of diagnosis
Results: Estimated 5-year outcome survival and event free survival for the entire study for HS I was 39% and HS II was 49% respectively
Head Start study shows possibility of successful deferral or even avoidance of RT in some patients with supratentorial PNET
Link: Myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for childhood central nervous system tumors. Bone Marrow Transplantation (2008) 41, 167–172; doi:10.1038/sj.bmt.1705953; published online 7 January 2008
Additional recent studies supporting the role of chemotherapy in treating supratentorial PNETs:
North American study by Strother21:
All patients had initial surgery to resect the maximal amount of tumor possible.
HDCT (high dose chemotherapy with stem cell rescue) as first line therapy post surgery and CSA RT (craniospinal radiation therapy).
High-risk disease = presence of metastasis or >1.5cm2 residual tumor
- Treated with topotecan for six weeks followed by standard CSA RT.
Average risk disease = absence of metastatic disease and gross total resection of tumor or < 1.5cm2 residual tumor
All patients were then started on four, 4 week cycles of high dose cyclophosphamide, cisplatin and vincristine, each followed by stem cell or bone marrow rescue
Results:
- 2-year progression free survival for average risk patients to be 93.6% (+/- 4.7%)
- 2-year progression free survival for high risk was found to be 73.7% (+/- 10.5%)22
Study shows the role as well as the effectiveness of HDCT in pediatric patients post CSA RT, however the results of longer follow up from this study are awaited.
CCG 99701 protocol:
Aim: to determine dose and duration of caboplatin to be used during RT in children aged 3-21 with PNET brain tumors
Eligible patients: high risk (M1-M3 or >1.5cc residual tumor remaining) PNET (supra/infra tentorial)
Patients received carboplatin in a dose escalation format
Given with daily CSA RT and local boost RT
Patients then treated with vincristine and cyclophosphamide or vincristine, cyclophosphamide and cisplatin for maintenance chemotherapy
Results: Event free survival and overall survival for supratentorial PNETs currently unavailable
CCG 99703 protocol:
A Pilot Study of Intensive Chemotherapy with Peripheral Stem Cell Support for
Infants with Malignant Brain Tumors
Aim: to determine the dose limited toxicity of the drug thiotepa and viability of giving cycles of high dose chemotherapy followed by peripheral blood stem cell rescue in infants with malignant brain tumors (6-35 months old)
Patients underwent 6 cycles of chemotherapy post surgery
Induction regimen of cisplatin, etoposide, cyclophosphamide, and vincristine followed by three cycles of consolidation with carboplatin, thiotepa and PBSC rescue
Results awaited
COG-ACNS0332: This is a COG phase III trial for children older than 3 years with high risk medulloblastoma or supratentorial PNET. The trial is currently ongoing and evaluating the efficacy of adding carboplatin to radiation therapy with vincristine, followed by maintenance chemotherapy with conventional adjuvant chemotherapy and isotretinoin.
Key points:
- Improving the efficacy and reducing the toxicity of chemotherapy is a major area of focus for studies on supratentorial PNET.
- Latest research evaluates combination and intensity of chemotherapy for best response.
- Exemplified in the CCG protocols 99701 and 99703 studies discussed above.
