2812 - Randomized Controlled Trial to Analyze Technical Feasibility of Dosimetric Hippocampal Sparing Radiotherapy in Head and Neck Cancers Involving Base of Skull or with Target Volume in Proximity to Hippocampus: An Interim Analysis

Purpose/Objective(s): Primary objective was to determine the dosimetric differences that can be achieved with and without hippocampal optimization. Secondary objective was to assess whether HSRT preserves neurocognitive function, assessed by Addenbrooke’s Cognitive Examination (ACE)- III, at 3- and 6-months post- radiotherapy.

Materials/Methods: This was a prospective, open labelled randomized controlled trial. The study recruited 56 non-metastatic Head and Neck cancer patients of age 18-74 years with curative radiotherapy treatment volumes reaching ITF and skull base were prospectively recruited and randomized to HS (Hippocampal sparing) and NHS (Non-Hippocampal sparing) groups equally in both adjuvant and radical strata. The primary hypothesis was that the dosimetric differences between Hippocampal sparing and non-Hippocampal sparing Radiotherapy in patients of head and neck cancers can be technically achieved. This endpoint was measured using the mean. The sample size needed after inclusion of stratification factor was 56 considering 15% dropout rate. Treatment planning via VMAT technique was done with and without hippocampal optimization of hippocampal doses in HS and NHS arms respectively with hippocampal dose constraints based on RTOG 0933. All participants underwent neurocognitive assessment using ACE- III before treatment and at 3- and 6-months post-treatment.

Statistical analysis: In univariable analysis, a two-sided two-sample t-test was used to assess baseline and outcome differences between HS group and NHS group. Statistical analysis was performed using R software (version 4.2.2). Treatment plan metrics were compared using t test with an upper bound of p < 0.05. Descriptive analysis used to summarize data. Continuous variables have been presented as mean ± standard deviation (SD) or Median (IQR). Categorical data has been presented as numbers (percentages). Normality of data was assessed using Shapiro Wilk test. The scores were plotted for all visits separately for both the arms and tested using p < 0.05.

Results: The dosimetric evaluation demonstrated that hippocampal doses were significantly reduced in HSRT arm. The accrued cases are still being followed up for the secondary objectives. In ipsilateral hippocampus, Median Dmax, Dmean, D40% were 13.94Gy vs 32.26Gy (p= 0.00), 6.42Gy vs 15.07Gy (p=0.00), 6.88Gy vs 16.44Gy (p=0.00) respectively in HS and NHS arms. Similar statistically significant reductions were observed in contralateral hippocampus. These reductions in hippocampal doses were achieved without significant differences in doses in planning target volume. The median D98% of HR- PTV was 94.54% vs 93.87% (p=0.36) in HS vs NHS arms.

Conclusion: This study concludes that HSRT is feasible in Head and Neck cancer patients with VMAT technique and can achieve a significant reduction in hippocampal doses without compromising target volume coverage. Hence, hippocampus can be considered an Organ-at-risk in head and neck cancer radiotherapy.