Background: The utility of adaptive radiotherapy (ART) for head and neck squamous cell carcinoma (HNSCC) remains poorly defined. Daily ART (DART) promises both anatomic adaptation and planning target volume (PTV) reduction. In this prospective trial using cone-beam computed tomography-based ART, patients with HNSCC undergoing definitive radiotherapy (RT) or chemoradiotherapy (CRT) were randomly assigned to DART with reduced PTV margins or no ART with standard margins (image-guided RT [IGRT]). Methods: Eligibility criteria included a diagnosis of oropharynx, larynx, or hypopharynx HNSCC receiving definitive radiotherapy. All individuals received involved nodal radiotherapy per previous institutional study. The PTV margins were 1 mm (2 mm craniocaudal) vs 5 mm in the DART and IGRT arms, respectively. The primary endpoint was patient-reported xerostomia at 1 year, assessed with the Xerostomia Questionnaire (XQ). Results: Fifty patients were enrolled (26 IGRT, 24 DART) between March 2022 and June 2023. The cohort consisted of 38 oropharynx and 12 larynx/hypopharynx patients. The mean ipsilateral parotid gland, ipsilateral and contralateral submandibular gland doses were significantly lower with DART. There was significantly less acute dermatitis in the DART arm (Grade 0/1/2 0%/69%/31% vs 17%/75%/8% DART, P = .01) but no significant difference in any patient-reported outcome at 1 year. The adjusted difference in XQ score at 1 year was 10.0 (95% CI = −4.7 to 24.7, P = .58). Conclusion: Online DART for HNSCC is oncologically sound and improved acute toxicity profiles, but it did not reduce patient-reported xerostomia, the primary endpoint. Additional evidence is needed to understand the potential benefits and limitations of this paradigm, including its cost-effectiveness. Trial registration: clinicaltrials.gov identifier, NCT04883281

Purpose: To develop a model of the internal vasculature of the adult liver and demonstrate its application to the differentiation of radiopharmaceutical decay sites within liver parenchyma from those within organ blood. Method: Computer-generated models of hepatic arterial (HA), hepatic venous (HV), and hepatic portal venous (HPV) vascular trees were algorithmically created within individual lobes of the ICRP adult female and male livers (AFL/AML). For each iteration of the algorithm, pressure, blood flow, and vessel radii within each tree were updated as each new vessel was created and connected to a viable bifurcation site. The vascular networks created inside the AFL/AML were then tetrahedralized for coupling to the PHITS radiation transport code. Specific absorbed fractions (SAF) were computed for monoenergetic alpha particles, electrons, positrons, and photons. Dual-region liver models of the AFL/AML were proposed, and particle-specific SAF values were computed assuming radionuclide decays in blood within two locations: (1) sites within explicitly modeled hepatic vessels, and (2) sites within the hepatic blood pool residing outside these vessels to include the capillaries and blood sinuses. S values for 22 and 10 radionuclides commonly used in radiopharmaceutical therapy and imaging, respectively, were computed using the dual-region liver models and compared to those obtained in the existing single-region liver model. Results: Liver models with virtual vasculatures of ~ 6000 non-intersecting straight cylinders representing the HA, HPV, and HV circulations were created for the ICRP reference. For alpha emitters and for beta and auger-electron emitters, S values using the single-region models were approximately 11% (AML) to 14% (AFL) and 11% (AML) to 13% (AFL) higher than the S values obtained using the dual-region models, respectively. Conclusions: The methodology employed in this study has shown improvements in organ parenchymal dosimetry through explicit consideration of blood self-dose for alpha particles (all energies) and for electrons at energies below ~ 100 keV.

Objective . Phantoms of the International Commission on Radiological Protection provide a framework for standardized dosimetry. The modeling of internal blood vessels—essential to tracking circulating blood cells exposed during external beam radiotherapy and to account for radiopharmaceutical decays while still in blood circulation—is, however, limited to the major inter-organ arteries and veins. Intra-organ blood is accounted for only through the assignment of a homogeneous mixture of parenchyma and blood [single-region (SR) organs]. Our goal was to develop explicit dual-region (DR) models of intra-organ blood vasculature of the adult male brain (AMB) and adult female brain (AFB). Approach . A total of 4000 vessels were created amongst 26 vascular trees. The AMB and AFB models were then tetrahedralized for coupling to the PHITS radiation transport code. Absorbed fractions were computed for monoenergetic alpha particles, electrons, positrons, and photons for both decay sites within the blood vessels and for tissues outside these vessels. Radionuclide S -values were computed for 22 and 10 radionuclides commonly employed in radiopharmaceutical therapy and nuclear medicine diagnostic imaging, respectively. Main results . For radionuclide decays, values of S (brain tissue ← brain blood) assessed in the traditional manner (SR) were higher than those computed using our DR models by factors of 1.92, 1.49, and 1.57 for therapeutic alpha-emitters, beta-emitters, and Auger electron-emitters, respectively in the AFB and by factors of 1.65, 1.37, and 1.42 for these same radionuclide categories in the AMB. Corresponding ratios of SR and DR values of S (brain tissue ← brain blood) were 1.34 (AFB) and 1.26 (AMB) for four SPECT radionuclides, and were 1.32 (AFB) and 1.24 (AMB) for six common PET radionuclides. Significance . The methodology employed in this study can be explored in other organs of the body for proper accounting of blood self-dose for that fraction of the radiopharmaceutical still in general circulation.

Purpose: Balancing quality and efficiency has been a challenge for online adaptive therapy. Most systems start the online re‐optimization with the original planning goals. While some systems allow planners to modify the planning goals, achieving a high‐quality plan within time constraints remains a common barrier. This study aims to bolster plan quality by leveraging a deep‐learning dose prediction model to predict new planning goals that account for inter‐fractional anatomical changes.Methods: Fine‐tuned patient‐specific (FT‐PS) models were clinically evaluated to accurately predict dose for 23 adaptive fractions of 15 head‐and‐neck (H&N) patients treated with Ethos ART. The original adapted plan from the adaptive treatment session was used as the quality baseline. Based on physician‐approved adaptive treatment contours, the FT‐PS model predicted subsequent planning goals for high‐impact organs at risk (OARs). These goals were retrospectively re‐optimized in Ethos to compare the original adapted plan (IOE‐Auto Plan) with the newly re‐optimized plan (AI‐guided IOE Plan). A physician blindly selected the preferred plan.Results: Dose savings were observed for nine high impact OAR's including the constrictor, ipsilateral/contralateral parotid, ipsilateral/contralateral submandibular gland, oral cavity, and esophagus, mandible and larynx with a maximum value of 5.47 Gy. Of the 23 plans reviewed in the blind observer study, 19 re‐optimized plans were chosen over the original adapted session plan.Conclusions: Our preliminary results demonstrate the feasibility of utilizing an AI dose predictor to predict optimal planning goals with anatomical changes, thereby improving adaptive plan quality. This method is feasible for both online and offline adaptive radiotherapy (ART) and has the potential to significantly enhance treatment outcomes for head‐and‐neck (H&N) cancer patients.

Objective. To develop a comprehensive mesh-based computational human phantom library of adult males and females that span current US body-size distributions. The phantom library was developed jointly between the University of Florida and Memorial Sloan-Kettering Cancer Center and termed the UF/MSK Phantom Library. Approach. Adult phantoms were modeled by rescaling and systematically deforming the International Commission on Radiological Protection Publication 145 mesh-type reference computational phantoms to match heights, body mass, and CDC National Health and Nutrition Examination Survey-derived secondary anthropometric parameters. Low body-mass phantoms underwent uniform two-dimensional scaling of abdominal organs to avoid collision with subcutaneous fat. To accommodate larger body circumferences, a rigging procedure was developed to smoothly deform the limbs while maintaining anatomical realism and preserving tissue. A companion ‘arms-up’ version of the library appropriate for computed tomography (CT) dosimetry simulation was also constructed. A validated CT source term was developed for the Canon Aquilion ONE/GENESIS considering technique factors such as tube voltage, bowtie filter size, and beam collimation, and was used to compute slice-specific organ doses for a subset of library phantoms. Main results. A large library of 186 male and 171 female (357 total) phantoms was created. Standing height ranged from 150–200 cm for males and 150–195 cm for females, and total body mass ranged from 40–150 kg for males and 40–155 kg for females. Simulated CT organ doses varied smoothly with BMI for a fixed phantom height. Significance. The UF/MSK adult phantom library has been constructed with body morphometries representative of the US population. Organ doses computed for phantoms of varying body sizes demonstrate the importance having a morphometrically robust selection of computational phantoms for patient matching. While the immediate application of this library is to expand phantom selection options in MIRDct software ( www.mirdsoft.org ), the library can be further utilized in other applications including radiopharmaceutical, radiography, fluoroscopy, and radiotherapy organ dose reconstructions.

Purpose or Objective: To evaluate the feasibility and clinical utility of integrating sequential PSMA-PET imaging into an offline–online adaptive workflow for response-based dominant intraprostatic lesion (DIL)-boosting high-risk prostate cancer treated with stereotactic ablative radiotherapy (SABR). Materials and Methods: As part of a prospective trial, patients were treated on MR- or CBCT-guided adaptive radiotherapy (ART) systems with prostate/pelvic node 5-fraction SABR (36.25 Gy/25 Gy) with DIL boost (50 Gy). Whereas traditional DIL boost volumes delineate full pre-therapy imaging-defined disease (GTVinitial), this study serially refined DIL boost volumes based on treatment response defined by PSMA-PET scans after neoadjuvant androgen deprivation therapy (nADT, GTVmb1) and fraction 3 SABR (GTVmb2). DIL delineation employed PET-PSMA fusion to CT/MR simulation and was guided by a rule-based %SUVmax threshold approach. Comparisons of GTV volumes and OAR dosimetry were performed between plans using GTVinitial versus GTVmb1/GTVmb2 for DIL boost, for each of the initial cohorts of five patients from the initially treated cohorts. Results: Five patients treated on MR-Linac (n = 3) or CBCT-based ART (n = 2) were analyzed. Three patients exhibited complete imaging response after nADT, omitting GTVmb boosts. Offline GTVmb refinements based on PSMA-PET were seamlessly integrated into ART workflows without introducing additional treatment time. DIL GTV volumes significantly decreased (p = 0.03) from an initial mean of 11.4 cc (GTVinitial) to 4.1 cc (GTVmb1) and 3.0 cc (GTVmb2). Dosimetric analysis showed meaningful reductions in OAR doses: rectal wall D0.035 cc decreased by up to 12 Gy, while bladder wall D0.035 cc and V18.3 Gy reduced from 52.3 Gy and 52.3 cc (Plan_initial) to 42.9 Gy and 24.9 cc (Plan_mb2), respectively. Urethra doses remained stable, with minor reductions. Sigmoid and femoral head doses remained within acceptable limits. Online adaptation efficiently addressed daily anatomical variations, enabling simulation-free plan re-optimization. Conclusion: PSMA-PET-guided adaptive microboosting for HRPCa SABR is feasible and effective. Standard MR-Linac and CBCT systems offer practical alternatives to BgRT platforms, enabling biology-driven dose personalization and potentially reducing toxicity.