Individualized estimates of overall survival in radiation therapy plan optimization — A concept study

• Published in: Medical physics (Lancaster) 2018-11, Vol.45 (11), p.5332-5342
• Main Authors: Modiri, Arezoo, Stick, Line Bjerregaard, Rice, Stephanie Renee, Rechner, Laura Ann, Vogelius, Ivan Richter, Bentzen, Søren Møller, Sawant, Amit
• Format: Article
• Language: English
• Subjects: Adult; Breast Neoplasms - radiotherapy; Female; Hodgkin Disease - radiotherapy; Humans; Male; Middle Aged; optimization; radiotherapy outcomes; Radiotherapy Planning, Computer-Assisted - methods; Radiotherapy, Intensity-Modulated; Risk; secondary disease; Survival Analysis; treatment planning
• ISSN: 0094-2405; 2473-4209
• DOI: 10.1002/mp.13211

Purpose Current radiation therapy planning uses a set of defined dose–volume constraints to ensure a specified level of tumor coverage while constraining the dose distribution in the organs at risk. Such constraints are aggregated, population‐based quantities that do not adequately consider patient‐specific risk factors. Furthermore, these constraints are calculated for each organ independently and it is therefore not guaranteed that the optimal trade‐off between organs is achieved. We introduce a novel radiotherapy planning approach where a patient‐specific all‐cause mortality risk is minimized using inverse plan optimization. As illustration of concept, our outcome risk model incorporates patient age, sex, cardiac risk factor (CRF), and smoking. Methods and materials We retrospectively analyzed a left‐sided breast cancer case and a Hodgkin's lymphoma case, both clinically treated with three‐dimensional conformal radiotherapy (3D‐CRT). Our objective function for inverse plan optimization was an equally weighted summation of risk models for cancer recurrence and mortality from radiation‐induced coronary heart disease and secondary lung and breast cancers incorporating patient age, sex, CRF, and smoking. We allowed the optimization algorithm to choose from a large set of gantry angles. The optimization task was to choose beams and optimize monitor units (MUs) so that overall survival was maximized (and the total risk of cancer recurrence and mortality from radiation‐induced causes were minimized). The sensitivity analysis was performed in the lymphoma case by changing the tumor control probability model from using mean dose (Model 1) to using generalized equivalent uniform dose (Model 2). Results For the breast case in this study, the 3D‐CRT clinical plan used eight beams while the proposed 3D‐CRT outcome‐optimized plan used five beams, reducing the total risk — summation of the risks of recurrence and secondary disease mortality — from 3% to 2%. The mean doses to clinical target volume (CTV) and internal mammary nodes (IMN) were increased in the outcome‐optimized plan by 1.9 and 1.8 Gy, respectively. For the Hodgkin's lymphoma case, the clinical 3D‐CRT plan used two beams, while the proposed 3D‐CRT outcome‐optimized plan used three beams, reducing the total risk by 6% (from 16% to 10%). Using either of the two tumor control models for the lymphoma case resulted in outcome‐optimized plans where tumor control was compensated at the cost of saving organs at r