Delivered dose-effect analysis of radiation induced rib fractures after thoracic SBRT

Anatomical changes during the stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC) may cause the delivered dose to deviate from the planned dose. We investigate if normal tissue complication probability (NTCP) models based on the delivered dose predict radiation-induced rib fractures better than models based on the planned dose.

437 NSCLC patients treated to a median dose of 3x18 Gy were included. Delivered dose was estimated by accumulating EQD2-corrected fraction doses after being deformed with daily CBCT-to-planning CT deformable image registration. Dosimetric parameters D_x (dose to a relative volume x) were extracted for each rib included in the CBCTs field-of-view. An NTCP model was constructed for both planned and delivered dose, optimizing the parameters TD₅₀ (dose with 50% toxicity risk), m (steepness of the curve) and x, using maximum likelihood estimation. Best NTCP model was determined using Akaike weights (Aw). Differences between the models were tested for significance using the Vuong's test.

Median time to fracture of 110 fractured ribs was 22.5 months. The maximum rib dose, D₀, best predicted fractures for both planned and delivered dose. The average delivered D₀ was significantly lower than planned (p < 0.001). NTCP model based on the delivered D₀ was the best, with Aw = 0.95. The models were not significantly different.

Delivered maximum dose to the ribs was significantly lower than planned. The NTCP model based on delivered dose improved predictions of radiation-induced rib fractures but did not reach statistical significance.