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

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/m2 for seven of the cohort, with the other patient receiving 50 mg/m2. 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.

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Acknowledgments

Shobadevi Marudamuthi for initial data-search of the Royal Marsden electronic patient record. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR.

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Correspondence to Frank Saran.

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The authors declare no conflicts of interest.

Funding

Ben O’Leary is funded by a National Institute for Health Research (NIHR) academic clinical fellowship.

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O’Leary, B., Mandeville, H.C., Fersht, N. et al. Craniospinal irradiation with concomitant and adjuvant temozolomide—a feasibility assessment of toxicity in patients with glioblastoma with a PNET component. J Neurooncol 127, 295–302 (2016). https://doi.org/10.1007/s11060-015-2033-5

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Keywords

  • Craniospinal irradiation
  • Temozolomide
  • Glioblastoma
  • PNET
  • GBM-PNET