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Background: Primary malignant brain tumours (PMBT) constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment options at relapse are limited. First-in-human solid tumour studies have historically excluded patients with PMBT due to the poor prognosis, concomitant drug interactions and concerns regarding toxicities., Methods: Retrospective data were collected on clinical and tumour characteristics of patients referred for consideration of Ph1 trials in the Royal Marsden Hospital between June 2004 and August 2016. Survival analyses were performed using the Kaplan-Meier method, Cox proportional hazards model. Chi squared test was used to measure bivariate associations between categorical variables., Results: 100pts with advanced PMBT were referred. At initial consultation, patients had a median ECOG PS 1, median age 48 years (range 18-70); 69% were men, 76% had glioblastoma; 68% were on AEDs, 63% required steroid therapy; median number of prior treatments was two. Median OS for patients treated on a Ph1 trials was 9.3 months (95% CI 5.9-12.9) versus 5.3 months (95% CI 4.1-6.1) for patients that did not proceed with a Ph1 trial, p = 0.0094. Steroid use, poor PS, neutrophil-to-lymphocyte ratio and treatment on a Ph1 trial were shown to independently influence OS., Conclusions: We report a survival benefit for patients with PMBT treated on Ph1 trials. Toxicity and efficacy outcomes were comparable to the general Ph1 population. In the absence of an internationally recognized standard second line treatment for patients with recurrent PMBT, more Ph1 trials should allow enrolment of patients with refractory PMBT and Ph1 trial participation should be considered at an earlier stage.

Tumors of the CNS are among the commonest malignancies occurring in teenage/young adult patients (i.e., those aged between 15 and 24 years). The treatment of this patient population is challenging. Adolescence and young adulthood are a turbulent period of life, with physical, emotional, social and cognitive changes. Best practice advocates their treatment in dedicated teenage/young adult units, with multidisciplinary team input and access to clinical trials. Treatment of CNS malignancies is dependent upon histological subtype and staging, with varying combinations of surgery, radiotherapy and chemotherapy used. Clinical trials directly targeted at this patient population are rare; treatments are based on pediatric protocols as studies have demonstrated improved outcomes in patients (with other malignancies) treated as such. Scope for improvement lies in minimizing patient risk of recurrence and long-term sequelae of treatment. Molecular characterization of tumors may provide further information.