Widening the Therapeutic Window for Central and Ultra-Central Thoracic Oligometastatic Disease with Stereotactic MR-Guided Adaptive Radiation Therapy (SMART)

Abstract

<h3>Purpose/Objective(s)</h3> Central ©/ultra-central (UC) thoracic tumors are challenging to treat with stereotactic radiotherapy due to the narrow therapeutic window. Stereotactic MR guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath hold gating and real-time MR imaging as well as the option for daily online adaptive replanning (ARP) to account for changes in target and/or organ-at-risk (OAR) location. Iso-toxic (OAR constraints-driven plan adaptation) SMART may provide an optimal balance of safety and local control (LC) for C/UC thoracic oligo-metastases (OM) or oligo-progression (OP). Here we report our institutional experience. <h3>Materials/Methods</h3> In this IRB-approved retrospective study, we reviewed the records of patients with C/UC thoracic OM/OP tumors treated with 5-fraction isotoxic SMART in 10/2019-8/2021. Tumor was considered UC if the planning target volume (PTV) abutted/overlapped the proximal tracheobronchial tree (PBT), great vessels, or esophagus. Data collection included dose to targets/OARS, frequency/clinical necessity for ARP, toxicity (CTCAE v5.0), and outcomes. Typical OAR constraints observed were PBT V40, great vessel V52.5, and esophagus V35 <0.03 cc. Local failures were defined as recurrences overlapping the PTV. <h3>Results</h3> 5 C/17 UC thoracic tumors were treated with SMART in 20 patients. Median age was 66 yrs (range 35-77). 73% had OP on systemic therapy and 27% were OM. Histology included non-small cell lung cancer (32%), and 9% each of mesothelioma, colorectal, prostate/bladder, and cervical/uterine. 55% of tumors were located in lung/pleura and 45% in hilum/mediastinum. All PTVs were <2 cm from any mediastinal organ and 59% <2 cm from the PBT. PTV abutted/overlapped the PBT in 32%, great vessel in 36%, heart in 36%, and esophagus in 41%. Median target volume was 10 cc for GTV and 18 cc for PTV (margin 3-5 mm). Median dose prescribed was 50 Gy in 5 fractions (range 35-60 Gy). 104/109 (95%) fractions required ARP, necessary to meet OAR constraints in 79% and target coverage in 21%. Median PTV V95 was 94% (range 53-100). Median follow up was 9 months. 1-yr LC rate was 94% (1/22 local failure for NUT-midline paraesophageal metastasis receiving 40 Gy/5 fx). 1-yr distant failure rate was 83% (n=16). 1-yr OS rate was 64%. 14% had acute G2 toxicities (esophagitis, dysphagia, or anorexia). There were no G3+ acute or late toxicities, and no G2+ pneumonitis. 8 (40%) patients had patient reported outcome measures available pre- and post-SMART with EORTC QLQ-C30 (symptom: median Δ -5 [-15, 15]; functional: median Δ 2 [-36, 13]; global health: median Δ -4 [-42, 17]) and QLQ-LC13 (median Δ 0 [-8, 3]) showing most had minimal negative change. <h3>Conclusion</h3> Iso-toxic 5-fraction SMART, with ARP 95% of the time to ensure OAR sparing and target coverage, resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk OM/OP thoracic tumors; further study in larger cohorts is needed.