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

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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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Authors and Affiliations

  1. The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK

    Ben O’Leary, Henry C. Mandeville, Julie Mycroft, Stergios Zacharoulis, Sucheta Vaidya & Frank Saran

  2. The Institute of Cancer Research, 237 Fulham Rd, London, SW3 6JB, UK

    Ben O’Leary

  3. Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK

    Naomi Fersht & Francesca Solda

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  1. Ben O’Leary
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Correspondence to Frank Saran.

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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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  • DOI: https://doi.org/10.1007/s11060-015-2033-5

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