Dosimetric Implications of Weekly On-Line MR-Guided Adaptive Radiotherapy (RT) for Glioblastomas (GBM) Growing during RT

Abstract

The UNITED trial (NCT04726397) involves once-weekly on-line adaptive RT for patients with GBM on a 1.5T MRI-Linac (MRL). For tumors that continue to enlarge during the course of RT, we hypothesize that the adaptive strategy improves the dosimetric coverage of the target relative to a non-adaptive strategy. As per the trial protocol, T1+contrast (T1c) and FLAIR MRI sequences were acquired once per week during RT to re-define and adapt the gross tumor volume (GTV) as the contrast enhanced volume, the clinical target volume (CTV) as a 5mm expansion around the GTV plus adjacent FLAIR hyperintense regions considered at-risk by the radiation oncologist, and a 3 mm PTV around the CTV. Nine UNITED patients with tumors that grew throughout RT (GTV and/or CTV) were identified. 5/9 patients were treated with 60 Gy in 30 fractions (6 weekly adaptions) and 4/9 with 40 Gy in 15 fractions (3 weekly adaptions). For the final week's GTV and CTV (GTVfinal and CTVfinal), the dosimetric outcomes of the delivered and adaptive summative plans (Dsum) were compared to dose of the baseline plan (Dbaseline) generated on Fraction 1 of treatment, the latter being indicative of the theoretical situation where no further adaption was taken. We measured the dose to 99% of the GTVfinal and CTVfinal: Dsum99 and Dbaseline99. For each adaptive fraction, the plan was optimized to achieve an objective of D99 greater than 95% of the prescription (D99>95%) for both the GTV and CTV. The relative increase in GTVfinal and CTVfinal from baseline was on average 119% (range: 98% to 144.7%) and 128% (range: 109% to 176%), respectively. The proportion of CTVfinal that was outside the baseline plan's PTV was on average 11.5% (range: 0% to 32%). The GTVfinal did not extend beyond the baseline PTV for any of the 9 cases. GTVfinal Dsum99 was >95% for all cases while CTVfinal Dsum99 was < 95% in 2 of 9 cases (74%, and 87%). By contrast, the baseline plan, if given for all fractions with no further adaptation, yielded a D99 for CTVfinal of <95% in 5 of 9 cases (28%, 52%, 75%, 84%, and 87%). In general, coverage of the CTVfinal decreased with increasing levels of CTVfinal outside of the baseline PTV. For all 5 cases where CTVfinal D99<95% on the baseline plan, more than 10% of CTVfinal was outside of the baseline PTV. Small margin, weekly adaptive RT on an MRL for GBM maintains coverage of the GTV in the presence of tumor growth while minimizing the degree of normal brain tissue irradiated. Dosimetric impact on non-GTV/CTV brain is outside the scope of the present study. Preliminary results indicate that a once weekly adaptive approach for small margin MR-guided RT improves tumor coverage for progressive tumors compared to a static (baseline) plan without adaptation.