OS02.7 Dose constraint model to predict neuroendocrine dysfunction in young patients with brain tumours- Data from a prospective study of stereotactic conformal radiotherapy

Introduction: Dose threshold to hypothalamic pituitary axis (HPA) following radiotherapy to predict neuroendocrine dysfunction is poorly defined. We report a possible dose constraint model for HPA, based on a prospective study of low grade and benign residual/progressive brain tumours in children and young adults, treated with stereotactic conformal radiotherapy (SCRT). Materials and Methods: HPA was meticulously contoured in 51 such patients treated prospectively with SCRT. Dose volume histograms were studied in patients with at least 2 years and up to 5 years follow up, and correlated with subsequent neuroendocrine dysfunction using logistic regression model. Results: All patients received a prescribed dose of 54 Gy in 30 fractions to the planning target volume (PTV). The mean HPA volume in our patient cohort was 1.34 cc. Post RT endocrine dysfunction (either new deficit or worsening of pre-existing one) was seen in 27/51 patients. Of these, 66% had HPA located inside the PTV. Majority of these deficits (82%) got manifested within the first 3 years of clinical follow-up. Growth hormone axis was the most commonly impaired (66%), followed by steroid axis (48%), pubertal axis (40%) and thyroid axis (22%). Mean Dmax and Dmin (maximum and minimum dose received) to HPA were 46.6 Gy and 40.5 Gy respectively. For patients with no neuroendocrine dysfunction, mean Dmax and Dmin to HPA were 36.5 Gy and 29.6 Gy respectively. On comparing HPA doses between post RT neuroendocrine dysfunction and post RT stable groups, a possible correlation is observed between development of neuroendocrine dysfunction and corresponding mean Dmax (p=0.075) and Dmin values (p=0.089). Median Dmin to HPA in post RT stable group was 34 Gy, much lower than median Dmin in post RT worsening group i.e. 51.8 Gy. On correlating HPA dose with endocrine follow up using logistic regression, V50 (% volume of HPA receiving 50% of prescribed dose) parameter was statistically significant (p=0.038). This may imply a four times higher risk of developing neuroendocrine dysfunction if HPA receives more than 27 Gy (>50% of the prescribed dose here). The incidence of hormonal impairment increased significantly in patients in whom HPA received a dose exceeding 29 Gy. CONCLUSION: Our dose constraint model incorporates HPA dosimetric parameters such as Dmax, Dmin, and V50 to optimize planning of high precision RT for brain tumours. It may lead to earlier and more specific evaluation of endocrine effects in rout