Abstract PR05: Adaptive chemo-radiotherapy for head and neck cancer based on multiparametric MRI: Interim results of a prospective randomized trial
Authors: Eisbruch Avraham , Cao Yue , Hawkins Peter , Lee Jae , Lee Choonik , Aryal Madhava , Mierzwa Michelle , Spector Matthew , Worden Frank , Swiecicki Paul , Wolf Gregory 
Published: December 2017

Abstract
Purpose/Objective(s): Tumor regions characterized by hypo-perfusion (HP) with dynamic contrast-enhanced (DCE)-MRI and restricted diffusion (RD) with diffusion-weighted (DW)-MRI have been reported to harbor aggressive disease. We report interim results of a randomized trial assessing boosting the doses to HP and RD sub-volumes in poor-prognosis head and neck cancer (HNC).
Materials/Methods: Prospective randomized trial: Patients with either T4/N3 HPV(+) and heavy smoking history or T3-4/N3 HPV(-) HNC undergo PET-FDG and multiparametric MRI at baseline and at 2 weeks mid-treatment. HP is defined as DCE-MRI-measured fractional plasma volume &lt;0.042. RD is defined as DW-MRI-measured apparent diffusion coefficient &lt;1.2 x 10-3 mm2/sec. We characterize the HP and RD regions within the tumor pretreatment and after 2 weeks of chemoradiation. Patients with spatially stable HP or RD sub-volumes at both baseline and 2 weeks are randomized to boost to these sub-volumes to biologically equivalent 86 Gy, or to standard dose (70 Gy). Paired two-tailed t-tests were used to compare changes in sub-volumes, and univariate Cox-regression to correlate clinical and imaging variables to locoregional failure (LRF).
Results: Of the planned 80, 36 patients were accrued to date: 15 randomized to receive boost and 15 to standard therapy. In addition, 6 patients did not retain high- risk sub-volumes at 2 weeks and were treated like the standard dose arm.
HP sub-volume comprised a mean of 23% of the primary tumor at baseline and 15% at 2 weeks (p=0.042). The RD sub-volume comprised a mean of 41% of the primary tumor at baseline and 21% at 2 weeks (p&lt;0.001). The average volume of overlap between the HP and RD sub-volumes comprised 8% of the primary tumor at baseline and 3% at 2 weeks (p=0.036). The sub-volumes planned for boost, comprising both stable HP and RD, averaged 22% (SD 11%) of the gross tumor volumes.
At median follow-up 8.9 months, 31 patients were evaluable for clinical outcome: 13 on the boost arm and 18 on the standard dose arm. Of these, 2 (15%) and 4 (22%) patients experienced LRF in the boost and standard arms, respectively. All failures in the boost arm were HPV (-), while in the standard arm, failures occurred in both HPV (+) and (-) patients. No difference in grade &gt; 3 acute or late toxicities was observed between arms. Mean RD subvolume at 2 weeks emerged as a near-statistically significant factor for LRF. updated clinical and radiological results will be presented.
Conclusion: HP and RD sub-volumes are spatially distinct and only slightly overlap in advanced HNC, suggesting they represent different biological features of aggressive cancer and provide rationale to using both for radiation boost, as has been done in the current study. As this study continues, we will assess whether LRF arise preferentially in regions of HP or RD, and whether boosting these regions improves locoregional control.
This abstract is also being presented as Poster 01.
Citation Format: Avraham Eisbruch, Yue Cao, Peter Hawkins, Jae Lee, Choonik Lee, Madhava Aryal, Michelle Mierzwa, Matthew Spector, Frank Worden, Paul Swiecicki, Gregory Wolf. Adaptive chemo-radiotherapy for head and neck cancer based on multiparametric MRI: Interim results of a prospective randomized trial [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr PR05.