Early clinical outcomes of helical tomotherapy/intensity-modulated proton therapy combination in nasopharynx cancer.

This study aimed to evaluate the feasibility of combining helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT) in treating patients with nasopharynx cancer (NPC). From January 2016 to March 2018, 98 patients received definitive radiation therapy (RT) with concurrent chemotherapy (CCRT). Using simultaneous integrated boost and adaptive re-plan, 3 different dose levels were prescribed: 68.4 Gy in 30 parts to gross tumor volume (GTV), 60 Gy in 30 parts to high-risk clinical target volume (CTV), and 36 Gy in 18 parts to low-risk CTV. In all patients, the initial 18 fractions were delivered by HT, and, after rival plan evaluation on the adaptive re-plan, the later 12 fractions were delivered either by HT in 63 patients (64.3%, HT only) or IMPT in 35 patients (35.7%, HT/IMPT combination), respectively. Propensity-score matching was conducted to control differences in patient characteristics. In all patients, grade ≥ 2 mucositis (69.8% vs 45.7%, P = .019) and grade ≥ 2 analgesic usage (54% vs 37.1%, P = .110) were found to be less frequent in HT/IMPT group. In matched patients, grade ≥ 2 mucositis were still less frequent numerically in HT/IMPT group (62.9% vs 45.7%, P = .150). In univariate analysis, stage IV disease and larger GTV volume were associated with increased grade ≥ 2 mucositis. There was no significant factor in multivariate analysis. With the median 14 month follow-up, locoregional and distant failures occurred in 9 (9.2%) and 12 (12.2%) patients without difference by RT modality. In conclusion, comparable early oncologic outcomes with more favorable acute toxicity profiles were achievable by HT/IMPT combination in treating NPC patients.

Compensation method for respiratory motion in proton treatment planning for mobile liver cancer.

We evaluated the dosimetric effect of a respiration motion, and sought an effective planning strategy to compensate the motion using four-dimensional computed tomography (4D CT) dataset of seven selected liver patients. For each patient, we constructed four different proton plans based on: (1) average (AVG) CT, (2) maximum-intensity projection (MIP) CT, (3) AVG CT with density override of tumor volume (OVR), and (4) AVG CT with field-specific proton margin which was determined by the range difference between AVG and MIP plans (mAVG). The overall effectiveness of each planning strategy was evaluated by calculating the cumulative dose distribution over an entire breathing cycle. We observed clear differences between AVG and MIP CT-based plans, with significant underdosages at expiratory and inspiratory phases, respectively. Only the mAVG planning strategy was fully successful as the field-specific proton margin applied in the planning strategy complemented both the limitations of AVG and MIP CT-based strategies. These results demonstrated that respiration motion induced significant changes in dose distribution of 3D proton plans for mobile liver cancer and the changes can be effectively compensated by applying field-specific proton margin to each proton field.

Dosimetric comparison of robust angles in carbon-ion radiation therapy for prostate cancer.

The objective of this study is to compare the plan robustness at various beam angles. Hence, the influence of the beam angles on robustness and linear energy transfer (LET) was evaluated in gantry-based carbon-ion radiation therapy (CIRT) for prostate cancer. 10 patients with prostate cancer were considered, and a total dose of 51.6 Gy (Relative biological effectiveness (RBE) was prescribed for the target volume in 12 fractions. Five beam field plans comprising two opposed fields with different angle pairs were characterized. Further, dose parameters were extracted, and the RBE-weighted dose and LET values for all angle pairs were compared. All plans considering the setup uncertainty satisfied the dose regimen. When a parallel beam pair was used for perturbed scenarios to take into account set-up uncertainty in the anterior direction, the LET clinical treatment volume (CTV) D 95% standard deviation was 1.5 times higher, and the standard deviation of RBE-weighted CTV D 95% was 7.9 times higher compared to an oblique pair. The oblique beam fields were superior in terms of dose sparing for the rectum compared to the dose distribution using two conventional lateral opposed fields for prostate cancer.

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients.

PURPOSE: To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. MATERIALS AND METHODS: The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks' RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. RESULTS: With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). CONCLUSIONS: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

Comparison of clinical outcomes between passive scattering versus pencil-beam scanning proton beam therapy for hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Our study aimed to compare the oncologic outcomes and toxicities between passive scattering (PS) proton beam therapy (PBT) and pencil-beam scanning (PBS) PBT for primary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The multidisciplinary team for liver cancer identified the PBT candidates who were ineligible for resection or radiofrequency ablation. We retrospectively analyzed 172 patients who received PBT for primary HCC from January 2016 to December 2017. The PS with wobbling method was applied with both breath-hold and regular breathing techniques, while the PBS method was utilized only for regular breathing techniques covering the full amplitude of respiration. To maintain the balance of the variables between the PS and PBS groups, we performed propensity score matching. RESULTS: The median follow-up duration for the total cohort was 14 months (range, 1-31 months). After propensity score matching, a total of 103 patients (70 in the PS group and 33 in the PBS group) were included in analysis. There were no significant differences in the rates of overall survival (OS), in-field local control (IFLC), out-field intrahepatic control (OFIHC), extrahepatic progression-free survival (EHPFS), and complete response (CR) between the matched groups. In the subgroup analyses, no subgroup showed a significant difference in IFLC between the PS and PBS groups. There was also no significant difference in the toxicity profiles between the groups. CONCLUSION: There are no differences in oncologic outcomes, including OS, IFLC, OFIHC, EHPFS, and CR rates, or in the toxicity profiles between PS and PBS PBT for primary HCC.

Investigations of line scanning proton therapy with dynamic multi-leaf collimator.

PURPOSE: Scanning proton therapy has dosimetric advantage over passive treatment, but has a large penumbra in low-energy region. This study investigates the penumbra reduction when multi-leaf collimators (MLCs) are used for line scanning proton beams and secondary neutron production from MLCs. METHODS: Scanning beam plans with and without MLC shaping were devised. Line scanning proton plan of 36 energy layers between 71.2 and 155.2 MeV was generated. The MLCs were shaped according to the cross-sectional target shape for each energy layer. The two-dimensional doses were measured through an ion-chamber array, depending on the presence of MLC field, and Monte Carlo (MC) simulations were performed. The plan, measurement, and MC data, with and without MLC, were compared at each depth. The secondary neutron dose was simulated with MC. Ambient neutron dose equivalents were computed for the line scanning with 10 × 10 × 5 cm3 volume and maximum proton energy of 150 MeV, with and without MLCs, at lateral distances of 25-200 cm from the isocenter. The neutron dose for a wobbling plan with 10 × 10 × 5 cm3 volume was also evaluated. RESULTS: The lateral penumbra width using MLC was reduced by 23.2% on average, up to a maximum of 32.2%, over the four depths evaluated. The ambient neutron dose equivalent was 18.52% of that of the wobbling beam but was 353.1% larger than the scanning open field. CONCLUSIONS: MLC field shaping with line scanning reduced the lateral penumbra and should be effective in sparing normal tissue. However, it is important to investigate the increase in neutron dose.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma.

PURPOSE: This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. MATERIALS AND METHODS: HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62-92 GyE10. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. CONCLUSION: PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

Sparse-view proton computed tomography using modulated proton beams.

PURPOSE: Proton imaging that uses a modulated proton beam and an intensity detector allows a relatively fast image acquisition compared to the imaging approach based on a trajectory tracking detector. In addition, it requires a relatively simple implementation in a conventional proton therapy equipment. The model of geometric straight ray assumed in conventional computed tomography (CT) image reconstruction is however challenged by multiple-Coulomb scattering and energy straggling in the proton imaging. Radiation dose to the patient is another important issue that has to be taken care of for practical applications. In this work, the authors have investigated iterative image reconstructions after a deconvolution of the sparsely view-sampled data to address these issues in proton CT. METHODS: Proton projection images were acquired using the modulated proton beams and the EBT2 film as an intensity detector. Four electron-density cylinders representing normal soft tissues and bone were used as imaged object and scanned at 40 views that are equally separated over 360°. Digitized film images were converted to water-equivalent thickness by use of an empirically derived conversion curve. For improving the image quality, a deconvolution-based image deblurring with an empirically acquired point spread function was employed. They have implemented iterative image reconstruction algorithms such as adaptive steepest descent-projection onto convex sets (ASD-POCS), superiorization method-projection onto convex sets (SM-POCS), superiorization method-expectation maximization (SM-EM), and expectation maximization-total variation minimization (EM-TV). Performance of the four image reconstruction algorithms was analyzed and compared quantitatively via contrast-to-noise ratio (CNR) and root-mean-square-error (RMSE). RESULTS: Objects of higher electron density have been reconstructed more accurately than those of lower density objects. The bone, for example, has been reconstructed within 1% error. EM-based algorithms produced an increased image noise and RMSE as the iteration reaches about 20, while the POCS-based algorithms showed a monotonic convergence with iterations. The ASD-POCS algorithm outperformed the others in terms of CNR, RMSE, and the accuracy of the reconstructed relative stopping power in the region of lung and soft tissues. CONCLUSIONS: The four iterative algorithms, i.e., ASD-POCS, SM-POCS, SM-EM, and EM-TV, have been developed and applied for proton CT image reconstruction. Although it still seems that the images need to be improved for practical applications to the treatment planning, proton CT imaging by use of the modulated beams in sparse-view sampling has demonstrated its feasibility.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.

PURPOSE: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. MATERIALS AND METHODS: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. RESULTS: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. CONCLUSION: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Proton-radiography-based quality assurance of proton range compensator.

The aim of this work was to study the feasibility of proton radiography (pRad) as a patient-specific range compensator (RC) quality assurance (QA) tool and to validate its clinical utility by performing QA on RCs having three kinds of possible defects. In order to achieve pRad for a single EBT film, proton beam currents were modulated with new weighting factors, maximizing the linearity of optical-density-to-thickness ratio. Two RCs, examined to be accurately manufactured as planned, were selected to estimate the feasibility of our pRad. The optical densities of the EBT film on which the RC was irradiated with the modulated proton beam were digitized to pixel values (pv) and then converted to thickness using a thickness-pv calibration curve. The thickness information on the pRad was compared with plan data that had been extracted from treatment planning system. The mean thickness difference (TD) over the flat RC regions was calculated as 0.39 mm, and the standard deviation as 0.22 mm, and the proton scattering effect was analyzed by step phantom measurement. Even proton scattering effected a TD of over 1 mm in the large gradient region, the percentage of pixels over the acceptance criterion was only within 1.11% and 3.49%, respectively, when a 1 mm distance to agreement tolerance limit was applied. The QA results for both precisely and imprecisely manufactured RCs demonstrated the high potential utility and clinical applicability of the pRad-based RC QA tool.