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PURPOSE/OBJECTIVE(S) Apparent diffusion coefficient (ADC) values extractable by diffusion-weighted imaging (DWI) are reported as useful in predicting the outcome of surgery and radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). However, their relationship with local tumor control (LC) after proton beam therapy (PBT) has not been fully evaluated. This study aimed to investigate interobserver variability in ADC histogram metrics and their usefulness in predicting LC in HCC patients who underwent PBT. MATERIALS/METHODS The ADC maps of the liver of HCC patients who underwent PBT between 2015 and 2020 were reviewed. The inclusion criteria were imaging DWI at 1.5T within 6 weeks before PBT and the largest tumor dimension between 2 and 10 cm. Twenty-nine patients and 32 tumors were eligible. Axial DWI was acquired using a single-shot spin-echo echo-planar sequence and the b values of 0 and 1000 s mm-2. The ADC maps generated were transferred to a workstation. Five board-certified radiation oncologists (ROs) contoured the whole tumor regions-of-interest (ROIs) on these maps, using anatomical images obtained together as reference. For each ROI, the minimum (ADCmin), mean (ADCmean), maximum (ADCmax), and the 5th (ADC5), 25th (ADC25), 50th (ADC50), 75th (ADC75), and 95th (ADC95) percentiles were extracted. The intraclass correlation coefficient (2,1) (ICC) was calculated to determine interobserver reproducibility: ICC of 0.75 - 0.90 was considered good and > 0.90 excellent. The ADC metrics were averaged among 5 ROs. The optimal cut-off values that determined LC, i.e., non-progressive disease (PD) based on the modified RECIST, were identified using receiver-operating characteristics (ROC) analysis. The LC rates were calculated using the Kaplan-Meier method, and statistical significance was assessed by log-rank test. RESULTS The median calculated biologically effective dose (α / β = 10) was 97 GyE. With a median follow-up of 39 months (5 - 62), 5 tumors had local PD. The ADCmin, ADCmean, ADCmax, ADC5, ADC25, ADC50, ADC75, and ADC95 of all tumors ranged between 0 - 1131, 748 - 1726, 1566 - 3149, 396 - 1430, 600 - 1566, 723 - 1719, 858 - 1874, and 1166 - 2426 (×10-6 mm 2 s-1), respectively. The ICC were 0.761, 0.969, 0.513, 0.864, 0.978, 0.983, 0.974, and 0.859, respectively. For ADCmean, ADC25, ADC50, and ADC75 which showed excellent reproducibility, the optimal cut-off values to determine LC were 1025, 1005, 1156, and 1132 (×10-6 mm 2 s-1), respectively. The tumors with higher ADC metrics had higher 2-year LC rates than their counterparts (100 % vs 40 %, P = 0.002; 100% vs 74%, P = 0.011; 100% vs 76%, P = 0.024; 100% vs 25%, P < 0.001, respectively). CONCLUSION ADCmean, ADC25, ADC50, and ADC75 showed excellent interobserver reproducibility. Pre-treatment ADC histogram metrics may be useful in predicting LC after PBT in HCC.

Purpose Hypofractionated irradiation is often used in precise radiotherapy instead of conventional multifractionated irradiation. We propose a novel mathematical method for selecting a hypofractionated or multifractionated irradiation regimen based on physical dose distribution adding to biologic consideration. Methods and Materials The linear–quadratic model was used for the radiation effects on tumor and normal tissues, especially organs at risk (OARs). On the basis of the assumption that the OAR receives a fraction of the dose intended for the tumor, the minimization problem for the damage effect on the OAR was treated under the constraint that the radiation effect on the tumor is fixed. Results For an N -time fractionated irradiation regimen, the constraint of tumor lethality was described by an N -dimensional hypersphere. The total dose of the fractionated irradiations was considered for minimizing the damage effect on the OAR under the hypersphere condition. It was found that the advantage of hypofractionated or multifractionated irradiation therapies depends on the magnitude of the ratio of α/β parameters for the OAR and tumor in the linear–quadratic model and the ratio of the dose for the OAR and tumor. Conclusions Our mathematical method shows that multifractionated irradiation with a constant dose is better if the ratio of α/β for the OAR and tumor is less than the ratio of the dose for the OAR and tumor, whereas hypofractionated irradiation is better otherwise.

Purpose To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. Methods and Materials Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. Results The average change in position of the treatment couch during the treatment time was 0.45 ± 2.23 mm (mean ± standard deviation), −1.65 ± 5.95 mm, and 1.50 ± 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. Conclusions Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers.

Purpose To evaluate the effectiveness of the stereotactic body frame (SBF), with or without a diaphragm press or a breathing cycle monitoring device (Abches), in controlling the range of lung tumor motion, by tracking the real-time position of fiducial markers. Methods and Materials The trajectories of gold markers in the lung were tracked with the real-time tumor-tracking radiotherapy system. The SBF was used for patient immobilization and the diaphragm press and Abches were used to actively control breathing and for self-controlled respiration, respectively. Tracking was performed in five setups, with and without immobilization and respiration control. The results were evaluated using the effective range, which was defined as the range that includes 95% of all the recorded marker positions in each setup. Results The SBF, with or without a diaphragm press or Abches, did not yield effective ranges of marker motion which were significantly different from setups that did not use these materials. The differences in the effective marker ranges in the upper lobes for all the patient setups were less than 1mm. Larger effective ranges were obtained for the markers in the middle or lower lobes. Conclusion The effectiveness of controlling respiratory-induced organ motion by using the SBF+diaphragm press or SBF + Abches patient setups were highly dependent on the individual patient reaction to the use of these materials and the location of the markers. They may be considered for lung tumors in the lower lobes, but are not necessary for tumors in the upper lobes.

Materials/Methods: Intra-fractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study. Prostate motion has been monitored with the Calypso System: systematic and random prostate motion was largest in the anterior-posterior direction (AP) with S = 2.3 mm and s = 2.9 mm for all trajectories. An industrial Mitsubishi robot moved a cylindrical prostate phantom on these 3D trajectories, this motion was detected via an infrared camera system (Polaris system, NDI) and the robotic HexaPOD (Medical Intelligence) treatment couch was used for real-time correction. Residual phantom motion with and without real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of step-and-shoot intensity-modulated radiotherapy (IMRT) for the three prostate trajectories with the largest random and systematic prostate motion. Results: Without motion compensation, the displacement of the prostate phantom was larger than 1 mm and 5 mm (3D error vector) in 83.3% ± 11.5% and 25% ± 19.8% during the 15 treatment fractions, respectively. No predictive algorithms were used and no post-processing of motion data was performed; measured phantom motion was intended to be fully compensated by couch countersteering. Real-time couch tracking reduced the proportion of the treatment fractions with displacements larger than 1 mm and 5 mm to 6.1% ± 4.6% and 0.3% ± 0.4%, respectively. Couch tracking reduced systematic and random phantom motion in AP direction to S = 0 mm and s = 0.55 mm. Maximum speed and acceleration of the couch during real-time tracking was 9.9 mm/s and 39.3 mm/s 2 (3D vector), respectively. Delay of the whole tracking system was 0.7s. If the moving average of the measured phantom motion (over 1s and 2s) was used as tracking command, residual phantom motion was slightly worse without resulting in smother couch motion. Compared to IMRT delivery to a static phantom, gamma values (2%/2 mm) of