title: HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival.
abstract: Following standard treatment, the prognosis remains poor in patients with high-grade glioma and new therapies are urgently required. Herpes simplex virus 1716 (HSV1716) is an ICP34.5 null mutant that is selectively replication competent and shown to be safe and to replicate following injection into high-grade glioma. We demonstrate that following surgical resection, HSV1716 is safe when injected into the brain adjacent to excised tumour. In all, 12 patients with recurrent or newly diagnosed high-grade glioma underwent maximal resection of the tumour. HSV1716 was injected into eight to 10 sites around the resulting tumour cavity with the intent of infecting residual tumour cells. As clinically indicated, patients proceeded to further radiotherapy or chemotherapy. There has been no clinical evidence of toxicity associated with the administration of HSV1716. Longitudinal follow-up has allowed the assessment of overall survival compared to that of similar patients not treated with HSV1716. Three patients remain alive and clinically stable at 15, 18 and 22 months postsurgery and HSV1716 injection. Remarkably, the first patient in the trial, who had extensive recurrent disease preprocedure, is alive at 22 months since injection of HSV1716 and 29 months since first diagnosis. Imaging has demonstrated a reduction of residual tumour over the 22-month period despite no further medical intervention since the surgery and HSV1716 injection. In this study, we demonstrate that on the basis of clinical observations, there has been no toxicity following the administration of HSV1716 into the resection cavity rim in patients with high-grade glioma. The survival and imaging data, in addition to the lack of toxicity, give us confidence to proceed to a clinical trial to demonstrate efficacy of HSV1716 in glioma patients.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, University of Glasgow, Southern General Hospital, Glasgow, UK.
authors.forename: S
authors.initials: S
authors.lastname: Harrow
authors.forename: V
authors.initials: V
authors.lastname: Papanastassiou
authors.forename: J
authors.initials: J
authors.lastname: Harland
authors.forename: R
authors.initials: R
authors.lastname: Mabbs
authors.forename: R
authors.initials: R
authors.lastname: Petty
authors.forename: M
authors.initials: M
authors.lastname: Fraser
authors.forename: D
authors.initials: D
authors.lastname: Hadley
authors.forename: J
authors.initials: J
authors.lastname: Patterson
authors.forename: S M
authors.initials: SM
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Rampling
mesh_terms: D000328:Adult; D000368:Aged; D001691:Biological Therapy; D001921:Brain / Q000821:virology; D001932:Brain Neoplasms / Q000601:surgery / Q000628:therapy* / Q000821:virology; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000601:surgery / Q000628:therapy* / Q000821:virology; D006561:Herpes Simplex / Q000150:complications* / Q000821:virology; D018259:Herpesvirus 1, Human; D006801:Humans; D016867:Immunocompromised Host; D007276:Injections, Intraventricular; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000601:surgery / Q000628:therapy* / Q000821:virology; D012449:Safety; D015996:Survival Rate; D014779:Virus Replication