Impact of molecular biology and high precision radiotherapy in the management of brain tumours

Brain tumours comprise 1-2% of all cancers. They are however the commonest solid cancers in childhood and comprise a significant burden to overall cancer patient population. These tumours affect all ages and are quite diverse with some being extremely indolent and some associated with considerable morbidity and relatively poor survival. Modern management strategies of anatomical and detailed biological imaging for characterisation of tumours, meticulous surgical resections, highly precise radiation delivery, medical and biological therapies as well as greater emphasis on comprehensive rehabilitation has improved the outcomes of these tumours considerably. Up to 70% of childhood brain tumours are expected to be totally cured currently. Malignant gliomas in adults however, remain possibly the most challenging cancers anywhere in the body because of their extreme heterogeneous nature, deeply infiltrative nature limiting the efficacy of local management strategies of surgery and radiation and a relative lack of effective and robust systemic agents. Systemic anti-neoplastic therapies have traditionally been disappointing in view of their primary and acquired resistance, complex intracellular pathways regulating proliferation and survival, restricted delivery into the CNS and the tumour microenvironment. Recent improvement in understanding their molecular biology is set to change the landscape of understanding and management practice. Tremendous gains of knowledge and practice of highly precise and conformal dose delivery of radiation (3DCRT, IMRT, Protons/heavy ions) has made a huge impact in the minimisation of treatment related morbidity. Recognition of dose constraint models in sparing eloquent areas of brain including hippocampus and dominant temporal lobes have resulted in preservation of neurocognition in childhood brain tumours. Apart from traditional endpoints of local control and survival, issues of quality of life affected by both the tumour and its treatment are increasingly being recognized as important outcome endpoints, as well.