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.

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: Case report and review of the literature

“…For recurrent GBM different therapeutic approaches are provided such as resurgery, reirradiation and systemic chemotherapy based on alkylating agents, bevacizumab, carboplatin, etoposide and their combination (21). On the other hand PNETs of the brain show a high tendency of leptomeningeal dissemination and extracranial metastasization (22), so the standard therapy consists of surgery followed by CSI combined with concurrent platinum-based chemotherapy, particularly carboplatin, or other concomitant chemotherapeutic agents, such as etoposide and TMZ (11).…”

“…Extracranial metastasis in PNET are rare but more frequent than in GBM. PNET is generally treated with surgery followed by craniospinal irradiation (CSI) combined with platinum-based chemotherapy in order to prevent CSF dissemination (11). In May 2016 the latest WHO Classification of Tumors of the Central Nervous System was published.…”

“…In magnetic resonance imaging (MRI) the PNET areas of hypercellularity are seen as reduced apparent diffusion coefficient (ADC) (14). Regarding genetic alterations it's possible to observe 'glioma-like' characteristics, such as 10q deletion, EGFR amplification or 1p/19q deletions and 'PNET-like' characteristics, such as high Ki-67 index, N-myc or C-myc amplifications (7,11). The role of mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 remains controversial.…”

“…Since most of the data concerning the management of GBM/PNETs are based on single case reports or case series (2,(7)(8)(9)11,12,15,(18)(19)(20) and despite therapeutic strategies have been identified for GMBs and PNETs, a common therapeutic protocol for GBM/PNETs has not yet been defined. In addition no evidence on treatment survival outcomes are published (11).…”

“…In addition no evidence on treatment survival outcomes are published (11). Therefore GBM/PNETs constitute a challenging diagnostic and therapeutic dilemma, since GBM is typically treated with alkylating agents while PNETs respond to platinum-based chemotherapy.…”