Quantitative Analysis of Inter-fractional Setup Errors and Anisotropic Margin Adaptation Using Daily Cone-beam Computed Tomography in Head-and-neck Radiotherapy.

Purpose: To quantify inter-fractional translational and rotational setup errors in head-and-neck cancer patients undergoing radiotherapy with daily cone-beam computed tomography (CBCT) and to derive anisotropic clinical-to-planning target volume (CTV-PTV) margins for improved precision and organ-at-risk (OAR) sparing. Materials and Methods: A retrospective analysis of 1160 daily CBCT scans from 40 patients treated with curative-intent head-and-neck radiotherapy was conducted. Translational (X, Y, and Z) and rotational (pitch, roll, and yaw) displacements were determined by rigid registration of daily CBCT to planning CT. Systematic (Σ) and random (σ) errors were computed, and CTV-PTV margins were derived using the ICRU 62, Stroom, and van Herk margin recipes. The frequency of positional deviations exceeding 3 mm and 5 mm and correlations with clinical factors such as weight loss were analyzed. Results: Mean systematic errors were 1.5 mm (X), 1.6 mm (Y), and 1.7 mm (Z), while random errors were 0.5 mm, 1.2 mm, and 1.1 mm, respectively. Mean rotational displacements were 0.6° (pitch), 0.5° (roll), and 0.7° (yaw). Margins derived using van Herk's formula ranged from 4.10 to 5.02 mm. Weight loss showed a moderate correlation with cranio-caudal setup variability ( Conclusion: Daily CBCT allows the precise quantification of inter-fractional setup errors and supports direction-specific margin adaptation. Incorporating clinical parameters such as weight loss and rotational deviation into adaptive workflows can enhance treatment precision, OAR sparing, and overall treatment safety in head-and-neck radiotherapy.