Multi-institutional experimental validation of online adaptive proton therapy workflows.

Objective. To experimentally validate two online adaptive proton therapy (APT) workflows using Gafchromic EBT3 films and optically stimulated luminescent dosimeters (OSLDs) in an anthropomorphic head-and-neck phantom. Approach. A three-field proton plan was optimized on the planning CT of the head-and-neck phantom with 2.0 Gy(RBE) per fraction prescribed to the clinical target volume. Four fractions were simulated by varying the internal anatomy of the phantom. Three distinct methods were delivered: daily APT researched by the Paul Scherrer Institute (DAPT PSI ), online adaptation researched by the Massachusetts General Hospital (OA MGH ), and a non-adaptive (NA) workflow. All methods were implemented and measured at PSI. DAPT PSI performed full online replanning based on analytical dose calculation, optimizing to the same objectives as the initial treatment plan. OA MGH performed Monte-Carlo-based online plan adaptation by only changing the fluences of a subset of proton beamlets, mimicking the planned dose distribution. NA delivered the initial plan with a couch-shift correction based on in-room imaging. For all 12 deliveries, two films and two sets of OSLDs were placed at different locations in the phantom. Main results. Both adaptive methods showed improved dosimetric results compared to NA. For film measurements in the presence of anatomical variations, the [min-max] gamma pass rates (3%/3 mm) between measured and clinically approved doses were [91.5%-96.1%], [94.0%-95.8%], and [67.2%-93.1%] for DAPT PSI , OA MGH , and NA, respectively. The OSLDs confirmed the dose calculations in terms of absolute dosimetry. Between the two adaptive workflows, OA MGH showed improved target coverage, while DAPT PSI showed improved normal tissue sparing, particularly relevant for the brainstem. Significance. This is the first multi-institutional study to experimentally validate two different concepts with respect to online APT workflows. It highlights their respective dosimetric advantages, particularly in managing interfractional variations in patient anatomy that cannot be addressed by non-adaptive methods, such as internal anatomy changes.