Ablative Dose Prescribed to Oligometastases Near Gastrointestinal Luminal Structures is Well Tolerated Using Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (SMART)

Abstract

Randomized data demonstrate that chemotherapy (CTX) plus stereotactic body radiation therapy (SBRT) improve progression-free survival (PFS) and also potentially overall survival (OS) compared to CTX alone for patients with oligometastases (OM). While SBRT is ideally delivered with ablative dose (biologically effective dose: BED10 at least 100 Gy), non-ablative dose may be prescribed when computerized tomography (CT) guidance is used for targets near gastrointestinal (GI) luminal structures; this may compromise long-term local control (LC) and PFS. Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) may facilitate safe delivery of ablative dose to all OM targets by utilizing on-table adaptive replanning based on daily changes in normal organ and/or tumor anatomy, and markedly improve long-term tumor control. A single institution retrospective analysis was performed of 28 OM lesions in 19 consecutive patients treated on an MR Linac, each specifically treated using SMART because ablative dose was planned for a lesion in proximity to the stomach and/or bowel. Definitive management of the primary tumor was performed in 89.5% and all OM were metachronous. The most common primary tumors were colorectal (31.6%) or cervical/ovarian (21.1%). Median interval between OM diagnosis and SMART was 28.3 months. Patients had either 1 (47.4%), 2 (42.1%), or 3 (10.5%) OM, typically involving a para-aortic node (39.3%), pelvic node (21.4%), adrenal gland (14.3%), or mesenteric node (14.3%). No patient had fiducial markers placed. Moving targets were typically treated in mid-inspiration breath hold. No concurrent CTX was given. Toxicity was evaluated using CTCAE version 5 and radiographic response according to RECIST 1.1. Median prescribed dose was 50 Gy in 5 fractions (range: 30-50 Gy in 5-10 fractions) and median prescribed BED10 was 100 Gy (range: 48-100 Gy). Median gross tumor volume (GTV) volume was 7.9 cc (range: 1.2-224.6 cc), median mean dose was 57.8 Gy (range: 32.3-63.8 Gy), and median maximum dose was 65.8 Gy (range: 37.7-79.4 Gy). Median planning target volume (PTV) volume was 27.6 cc (range: 3.3-332.2 cc), median mean dose was 53.3 Gy (range: 28.6-63.8 Gy), and median maximum dose was 66.3 Gy (range: 37.7-79.4 Gy). With median follow-up of 6.0 months (range: 1.0-14.6 months) LC, PFS, and OS were 96.4%, 68.4%, and 89.5%, respectively. Acute grade 2 toxicity was 5.3% (fatigue; n = 1). No patient experienced late grade 2 or any grade 3+ toxicity. Our initial outcomes suggest that SMART permits a BED10 of at least 100 Gy to be safely prescribed to lesions near stomach and/or bowel. We plan to prospectively evaluate whether dose escalation for OM near GI luminal structures using SMART achieves a clinically meaningful improvement in long-term outcomes compared to doses prescribed using CT guidance.