Minimization of Geometric Uncertainties and Setup Errors Improves Tumor Control for Intracranial Stereotactic Radiosurgery

Purpose: To assess the lesion-level effect of 1-2-mm geometric uncertainty on tumor control probability (TCP) in brain-metastasis stereotactic radiosurgery (SRS), assuming a uniform 2-mm PTV margin. Methods:We retrospectively analyzed 75 brain metastases in 50 patients who underwent linear accelerator-based SRS.Geometric uncertainty was simulated by applying positional shifts to the treatment plan, and the resulting reduction in TCP was quantified.The resulting dosimetric and radiobiological characteristics were compared between tumors 20 mm and those > 20 mm. Results:Tumor size modulated the impact of geometric uncertainty.Small lesions ( 20 mm) exhibited steeper dose gradients (GI 3.6 vs 2.6; P = 0.001) and therefore larger reductions in GTV D100% under a 2-mm shift (median 4.5 Gy vs 3.3 Gy; P < 0.001).Yet, because their initial TCP was high (median 96.6%), the TCP decrement remained modest (median 3.4%).In contrast, large lesions (> 20 mm) began with a lower TCP (median 82.1%) and lay on the steep portion of the dose-response curve, so similar or smaller dose losses produced a substantially greater TCP decline (median 10.9% at 2 mm; P < 0.001).The same pattern was observed with 1-mm shifts (TCP 3.5% vs 1.0%). Conclusion:Patients with larger tumors (> 20 mm) may be most vulnerable to a significant loss of tumor control from geometric uncertainties in SRS.This analysis shows promise for personalizing treatment delivery, supporting a shift from applying fixed PTV margins towards strategies such as fractionated radiotherapy tailored to individual tumor size and radiobiological characteristics.This 3 hypothesis-generating study requires external validation, with fractionated SRT being a subject for future investigation.