Craniospinal irradiation with concomitant and adjuvant temozolomide--a feasibility assessment of toxicity in patients with glioblastoma with a PNET component

J Neurooncol. 2016 Apr;127(2):295-302. doi: 10.1007/s11060-015-2033-5. Epub 2016 Feb 2.

Abstract

There is no standard treatment for glioblastoma with elements of PNET (GBM-PNET). Conventional treatment for glioblastoma is surgery followed by focal radiotherapy with concurrent temozolomide. Given the increased propensity for neuroaxial metastases seen with GBM-PNETs, craniospinal irradiation (CSI) with temozolomide (TMZ) could be a feasible treatment option but little is known regarding its toxicity. The clinical records of all patients treated at two UK neuro-oncology centres with concurrent CSI and TMZ were examined for details of surgery, radiotherapy, chemotherapy and toxicities related to the CSI-TMZ component of their treatment. Eight patients were treated with CSI-TMZ, the majority (6/8) for GBM-PNET. All patients completed radiotherapy to the craniospinal axis 35-40 Gy in 20-24 daily fractions with a focal boost to the tumour of 14-23.4 Gy in 8-13 daily fractions. Concurrent TMZ was administered at 75 mg/m(2) for seven of the cohort, with the other patient receiving 50 mg/m(2). The most commonly observed non-haematological toxicities were nausea and vomiting, with all patients experiencing at least grade 2 symptoms of either or both. All patients had at least grade 3 lymphopaenia. Two patients experience grade 4 neutropaenia and grade 3 thrombocytopaenia. Three of the eight patients required omission of TMZ for part of their chemoradiotherapy and 3/8 required hospital admission at some point during chemoradiotherapy. The addition of TMZ to CSI did not interrupt radiotherapy. Principal toxicities were neutropaenia, lymphopaenia, thrombocytopaenia, nausea and vomiting. Treatment with CSI-TMZ merits further investigation and may be suitable for patients with tumours at high-risk of metastatic spread throughout the CNS who have TMZ-sensitive pathologies.

Keywords: Craniospinal irradiation; GBM-PNET; Glioblastoma; PNET; Temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Alkylating / adverse effects
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Chemoradiotherapy / adverse effects*
  • Chemotherapy, Adjuvant
  • Child
  • Craniospinal Irradiation / adverse effects*
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Dose Fractionation, Radiation
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Lymphopenia / diagnosis*
  • Lymphopenia / etiology
  • Male
  • Neoplasm Staging
  • Neuroectodermal Tumors, Primitive / pathology
  • Neuroectodermal Tumors, Primitive / therapy*
  • Neutropenia / diagnosis*
  • Neutropenia / etiology
  • Prognosis
  • Survival Rate
  • Temozolomide
  • Thrombocytopenia / diagnosis*
  • Thrombocytopenia / etiology
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide