title: 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/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.
authors: The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK.|The Institute of Cancer Research, 237 Fulham Rd, London, SW3 6JB, UK.
authors: Ben
authors: B
authors: O'Leary
authors: The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK.
authors: Henry C
authors: HC
authors: Mandeville
authors: Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK.
authors: Naomi
authors: N
authors: Fersht
authors: Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK.
authors: Francesca
authors: F
authors: Solda
authors: The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK.
authors: Julie
authors: J
authors: Mycroft
authors: The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK.
authors: Stergios
authors: S
authors: Zacharoulis
authors: The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK.
authors: Sucheta
authors: S
authors: Vaidya
authors: The Royal Marsden Hospital NHS Trust, The Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK. frank.saran@rmh.nhs.uk.
authors: Frank
authors: F
authors: Saran
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D002648:Child; D061888:Craniospinal Irradiation / Q000009:adverse effects*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008231:Lymphopenia / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D009367:Neoplasm Staging; D018242:Neuroectodermal Tumors, Primitive / Q000473:pathology / Q000628:therapy*; D009503:Neutropenia / Q000175:diagnosis* / Q000209:etiology; D011379:Prognosis; D015996:Survival Rate; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000209:etiology; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Craniospinal irradiation; GBM-PNET; Glioblastoma; PNET; Temozolomide