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Intrathecal thiotepa: reappraisal of an established therapy
Paul G Fisher1, Nina S Kadan-Lottick, David N Korones
1Department of Neurology, Stanford University School of Medicine, Palo Alto, California 94305-5235, USA. pfisher@stanford.edu
Insights
Intrathecal thiotepa showed limited efficacy for pediatric leptomeningeal metastases (LM). The treatment resulted in poor outcomes and did not significantly improve survival rates in children with LM.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Cancer Treatment
Background:
- Leptomeningeal metastases (LM) in children is a serious complication of primary brain tumors.
- Intrathecal thiotepa is a recommended treatment for pediatric LM, but evidence is limited.
Purpose of the Study:
- To evaluate the efficacy of intrathecal thiotepa in treating pediatric leptomeningeal metastases.
- To assess the impact of intrathecal thiotepa on cerebrospinal fluid cytology, neuroimaging, neurologic status, and survival.
Main Methods:
- Retrospective review of 15 children with LM treated with intrathecal thiotepa at two tertiary children's hospitals.
- Outcomes assessed via cerebrospinal fluid cytology, neuroimaging, neurologic examination, and overall survival.
Main Results:
- Four of 15 children achieved cytologic clearance of malignant cells, sustained in only two.
- No neuroimaging response was observed; only one child showed neurologic improvement.
- Median survival was 15.1 weeks, with a 1-year overall survival rate of 26.7%.
Conclusions:
- Intrathecal thiotepa demonstrated limited benefit as a treatment for pediatric leptomeningeal metastases.
- The observed unfavorable outcomes suggest it adds little to combination therapy for pediatric LM.
Purpose:
Intrathecal thiotepa is recommended as a treatment of leptomeningeal metastases (LM) in children, although published data to support this approach are limited. The authors sought to determine the efficacy of intrathecal thiotepa for pediatric LM.
Patients And Methods:
The authors reviewed all children treated with intrathecal thiotepa for LM at two tertiary children's hospitals, assessing outcome by cerebrospinal fluid cytology, neuroimaging, neurologic examination, and overall survival rate.
Results:
Fifteen children with LM evidenced by malignant cells in the cerebrospinal fluid (mean age 7.3 years; five medulloblastoma, one anaplastic astrocytoma, one glioblastoma, one retinoblastoma, one neuroblastoma, two rhabdomyosarcoma, one non-Hodgkin lymphoma, two acute lymphoblastic leukemia, and one acute myelogenous leukemia) were treated with intrathecal thiotepa at 5 to 11.5 mg/m2 per dose for two to seven doses. Five children received concomitant craniospinal irradiation; 12 received simultaneous systemic or other intrathecal chemotherapy, or both. Four children experienced clearance of malignant cells from the spinal fluid, but this response was sustained in only two. All four children with cytologic response received concurrent radiotherapy, chemotherapy, or both. No patients showed partial or complete response on neuroimaging. Only one child had improvement on the neurologic examination; six were unchanged and eight had worsening neurologic signs. Median survival was 15.1 weeks, with a 1-year overall survival rate of 26.7% (standard error 11.4%).
Conclusions:
The unfavorable outcomes observed suggest that intrathecal thiotepa adds little to combination therapy for pediatric LM.