Early PET/CT Response Assessment for Selective FDG PET-Guided Dose Escalation in Locally Advanced NSCLC Patients Enrolled on the FLARE-RT Protocol

Abstract

Dose escalation in unselected patients with locally advanced (LA) non-small cell lung cancer (NSCLC) was detrimental to survival in RTOG 0617, yet local failures persist. The phase II Functional Lung Avoidance & Response-adaptive Escalation (FLARE-RT) trial selects a resistant subset of LA-NSCLC patients for dose-escalation to FDG PET-avid regions at high failure risk, while simultaneously mitigating pneumonitis risk with functional lung avoidance in all patients. We report the ongoing trial results. Stage IIB-IIIB NSCLC patients receiving definitive chemoradiation underwent an early on-treatment PET/CT after 24Gy in 12 fractions. Patients were classified as responders (PET-R) and non-responders (PET-NR) based on early-RT changes in tumor glycolytic metabolism (SUVpeak and metabolic tumor volume MTV) and nuclear medicine diagnostic reads. PET-R received 60Gy in 30 fractions over 6 weeks while PET-NR received a concomitant 14Gy boost over the final 15 fractions (74Gy total) with heterogeneous escalation to FDG-avid regions. Patients were treated with a mix of IMRT/VMAT/Protons. Primary trial endpoint is 2-yr overall survival (superiority) relative to historical controls. Fisher’s Exact and Mann-Whitney tests of differences between PET-R and PET-NR subgroups were performed. FLARE-RT has recruited 22 patients to date. Due to a protocol-required PET/CT <30 days prior to RT, Stage IV progression was detected on short-interval repeat pre-treatment PET/CT in 2/22 patients (9%), while 1/22 withdrew. On early-RT PET/CT scans, Stage IV progression was detected in 2/19 patients (11%). We categorized 7/19 PET-NR (37%) and 12/19 PET-R (63%). SUVpeak decreased by 13% (8-23%) in PET-NR compared to 40% (32-48%) in PET-R (p<0.01). MTV decreased by 9% ([-5]-21%) in PET-NR compared to 40% (32-62%) in PET-R (p<0.01). 17 patients completed treatment per protocol, of whom 6 PET-NR received 74Gy to PTVmidtx and 89Gy (80-93Gy) to SUVpeak volumes. Esophageal, Lung-CTV, and heart doses were similar between PET-NR and PET-R (Table 1, all p>0.05). Grade 3 acute toxicity (CTCAE v4.0) was observed in 2/17 patients (12%) with no difference between PET-R and PET-NR (p=0.9). Tracking of sub-acute / chronic toxicities and outcomes are ongoing. FLARE-RT leverages a precision medicine trial design to escalate dose to FDG-avid regions in select LA-NSCLC patients without increasing toxicity risk. Short-interval FDG-PET/CT scans prior to and during the third week of RT significantly altered management in 18% of patients. Reports on safety and efficacy will be forthcoming.Abstract TU_32_3642; Table 1Dosimetry comparison of early-RT PET responders vs. PET non-responders on FLARE-RT trial.MedianEarly-RT PET category(n)PTV, vol. ccEso., Mean (Gy)Eso., V60 (%)Heart, V5 (%)Heart, Dmean (Gy)Lung- CTV, Dmean (Gy)Lung - CTV, V20 (%)PET-R(12)629.630.821.429.89.814.830.2PET-NR(6)417.215.29.033.54.28.622.9 Open table in a new tab