Lay Summary: Autologous stem cell transplantation is an investigational modality for Ewing and PNET.
Initial chemotehrapy is recommended, although there is no one superior regimen. The INT-0091 study from the COG reported no benefit with the addition of IE to a standard backbone of vincristine, actinomycin-D, cyclophosphamide, and doxorubicin (VACD) . In the second Intergroup Ewing Sarcoma Study (IESS-2), the addition of 5-fluorouracil (5-FU) failed to improve outcome in this subset of patients. In a phase II trial from the Pediatric Oncology Group, high-dose alkylator therapy with topotecan or topotecan plus cyclophosphamide did not improve patient outcomes; however, the latter combination did show activity against metastatic disease (response rate of 57%).
Primitive neuroepithelial tumors include medulloblastoma, neuroblastoma arising in the central nervous system, ependymoblastoma, or pineoblastoma. All show a similar histology and are principally distinguished by their site of origin. Essentially, medulloblastoma may be considered a cerebellar or posterior fossa PNET while pineoblastoma may be considered a PNET arising in the pineal gland, and neuroblastomas may be considered a central PNET. PNETs have been referred to by different terms depending on their location and extent of neural differentiation: peripheral neuroepithelioma, Askin tumor, adult neuroblastoma, peripheral neuroblastoma, and primitive neuroectodermal tumors. The collective term is primitive neuroectodermal tumors. Ewing’s sarcoma and PNET represent a biological spectrum of the same tumor. Since these tumors exhibit only neuroectodermal markers of differentiation, it has been suggested that they arise from neural crest cells. Because treatment is the same for these tumors, they are also referred to as Ewing’s sarcoma/PNET. With this classification, data from all these tumor types can be pooled for anlaysis. Many patients with metastatic disease at diagnosis respond well to the therapy given to patients with localized disease; however, in most cases the disease is only partially controlled or recurs. Currently there are trials using more intensive therapy with or without stem cell transplant although it is not known if this strategy improves outcome.
- Dose-intensive chemotherapy with growth factor support is not recommended in the first-line treatment of patients with inoperable locally advanced or metastatic soft tissue sarcoma.
- There is insufficient data to support the use of high-dose chemotherapy with autologous bone marrow/stem cell transplantation as first-line treatment in this group of patients.
A January 2008 search of the National Cancer Institute (NCI) PDQ database on ongoing clinical trials identified the following open Phase III randomized studies on PNETs: Phase III study of radiotherapy, high-dose cisplatin, vincristine, and cyclophosphamide, and autologous stem-cell rescue in patients with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor (SJCRH-SJMB03) Phase III pilot study of induction chemotherapy followed by consolidation myeloablative chemotherapy comprising thiotepa and carboplatin with or without etoposide and autologous hematopoietic stem cell rescue in pediatric patients with previously untreated malignant brain tumors. (NCT00392886) The 2006 National Comprehensive Cancer Care Network Guidelines on Central Nervous System Cancers do not address high-dose chemotherapy with stem-cell support for PNET of the CNS.
- Eligible patients should be encouraged to enter clinical trials assessing novel approaches or compounds.
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