MR-guided SBRT of infra-diaphragmatic soft tissue metastases – early toxicity and dosimetric results

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Conference Proceeding

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Radiother Oncol


Purpose or Objective The recommended biologically effective dose (BED10) of at least 100 Gy in stereotactic body radiotherapy (SBRT) is challenging to achieve for metastases close to radiosensitive organs at risk (OAR) without risking unacceptable toxicity. The MR linac may help overcome this challenge by offering online adaption and real-time imaging during treatment. We present early toxicity and dosimetric results from a prospective multicenter phase-2 study (SOFT), where the safety and efficacy of risk-adapted MR-guided SBRT of infra-diaphragmatic soft tissue metastases in patients with OMD were investigated ( ID NCT04407897). Materials and Methods A risk-adapted strategy was applied, and prespecified OAR constraints were prioritized over target coverage. Fractionation schemes were 45 Gy/3 fractions (f), 50 Gy/5 f, and 60 Gy/8 f, depending on proximity to OAR. PTV margins followed institutional practice. Inhomogeneous dose prescription aimed at gross tumor volume (GTV) D99% >95%, mean GTV dose ≥ 100% and planning target volume (PTV) D99% >67%. All dose plans were exported for central dosimetric analysis. To account for the different dose levels prescribed, the achieved dose to the target (GTV D99%) was recalculated into BED10. Early toxicity was assessed according to the Common Terminology Criteria for Adverse Events v.5.0 at baseline and 2, 6, and 12 weeks after the end of treatment. Results The study closed in February 2022 after the inclusion of 121 patients with 147 metastatic targets. Most patients had prostate, colorectal, lung, or kidney cancer. Targets were mainly located in the liver (41%), lymph nodes (35%), or adrenal glands (14%). Almost half of the targets (48%) were located less than 10 mm from radiosensitive OARs. Normal tissue constraints to visceral organs were respected in all plans. Figure 1 shows the achieved GTV coverage. The prescription, GTV D99% >95% was achieved for 63% of the targets (median = 96% isodose, range 45.8%-108.0%). Mean GTV dose > 100% was achieved for 91% of the targets (median=105.4% isodose, range 76.8%-124.2%). The prescription, PTV D99% > 67% was achieved for 67 % of the targets (median=70.2% isodose, range 20.4%-94.8 %). The closer the target was to the OAR, the harder it was to reach the desired BED10 > 100 Gy for GTV D99%, but it was still achievable in some cases, as illustrated in Figure 2. Overall, the most common treatment-related adverse events (TRAE) were fatigue (n=70), nausea (n=35), and pain from the irradiated site (n=34). No patients experienced early grade (G) 4-5 TRAE. Only two patients had G3 TRAE, and both were fatigue. Forty-eight patients (40%) had G2, and 68 (56%) had G1 TRAE. Conclusion With MR-guided risk-adapted SBRT, ablative doses can be achieved for high-risk infra-diaphragmatic targets with an acceptable early toxicity rate. [Figure presented]



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