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Background and Purpose: This study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC)., Materials and Methods: This single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score., Results: We enrolled 43 patients (median age: 68 years; range, 47-79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83-99), 95 % (82-99), and 86 % (72-94), respectively, at 3 years, and 83 % (66-92), 95 % (82-99), and 77 % (60-88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months., Conclusion: Our findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The reference dose for clinical proton beam therapy is based on ionization chamber dosimetry. However, data on uncertainties in proton dosimetry are lacking, and multifaceted studies are required. Monte Carlo simulations are useful tools for calculating ionization chamber dosimetry in radiation fields and are sensitive to the transport algorithm parameters when particles are transported in a heterogeneous region. We aimed to evaluate the proton transport algorithm of the Particle and Heavy Ion Transport Code System (PHITS) using the Fano test. The response of the ionization chamber f Q and beam quality correction factors k Q were calculated using the same parameters as those in the Fano test and compared with those of other Monte Carlo codes for verification. The geometry of the Fano test consisted of a cylindrical gas-filled cavity sandwiched between two cylindrical walls. f Q was calculated as the ratio of the absorbed dose in water to the dose in the cavity in the chamber. We compared the f Q calculated using PHITS with that of a previous study, which was calculated using other Monte Carlo codes (Geant4, FULKA, and PENH) under similar conditions. The flight mesh, a parameter for charged particle transport, passed the Fano test within 0.15%. This was shown to be sufficiently accurate compared with that observed in previous studies. The f Q calculated using PHITS were 1.116 ± 0.002 and 1.124 ± 0.003 for NACP-02 and PTW-30013, respectively, and the k Q were 0.981 ± 0.008 and 1.027 ± 0.008, respectively, at 150 MeV. Our results indicate that PHITS can calculate the f Q and k Q with high precision., (© 2024. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Objective. FLASH radiation therapy with ultrahigh dose rates (UHDR) has the potential to reduce damage to normal tissue while maintaining anti-tumor efficacy. However, rapid and precise dose distribution measurements remain difficult for FLASH radiation therapy with proton beams. To solve this problem, we performed luminescence imaging of water following irradiation by a UHDR proton beam captured using a charge-coupled device camera. Approach . We used 60 MeV proton beams with dose rates of 0.03-837 Gy s -1 from a cyclotron. Therapeutic 139.3 MeV proton beams with dose rates of 0.45-4320 Gy s -1 delivered by a synchrotron-based proton therapy system were also tested. The luminescent light intensity induced by the UHDR beams was compared with that produced by conventional beams to compare the dose rate dependency of the light intensity and its profile. Main results . Luminescence images of water were clearly visualized under UHDR conditions, with significantly shorter exposure times than those with conventional beams. The light intensity was linearly proportional to the delivered dose, which is similar to that of conventional beams. No significant dose-rate dependency was observed for 0.03-837 Gy s -1 . The light-intensity profiles of the UHDR beams agreed with those of conventional beams. The results did not differ between accelerators (synchrotron or cyclotron) and beam energies. Significance . Luminescence imaging of water is achievable with UHDR proton beams as well as with conventional beams. The proposed method should be suitable for rapid and easy quality assurance investigations for proton FLASH therapy, because it facilitates real-time, filmless measurements of dose distributions, and is useful for rapid feedback., (© 2023 Institute of Physics and Engineering in Medicine.)

Purpose: Proton-induced secondary-electron-bremsstrahlung (SEB) imaging is a promising method for estimating the ranges of particle beam. However, SEB images do not directly represent dose distributions of particle beams. In addition, the ranges estimated from measured images were deviated because of limited spatial resolutions of the developed x-ray camera as well as statistical noise in the images. To solve these problems, we proposed a method for predicting high-resolution dose images from SEB images with various count level using a deep learning (DL) approach for range and width verification., Methods: In this study, we adopted the double U-Net model, which is a previously proposed deep convolutional network model. The first U-Net model in the double U-Net model was used to denoise the SEB images with various count level. The first U-Net model for denoising was trained on 8000 pairs of SEB images with various count level and noise-free images which were created by a sophisticated in-house developed model function. The second U-Net model for dose prediction was trained using 8000 pairs of denoised SEB images from the first U-Net model and high-resolution dose images generated by Monte Carlo simulation., Results: For both simulation and measurement data, the trained DL model could successfully predict high-resolution dose images which showed a clear Bragg peak and no statistical noise. The difference of the range and width was less than 2.1 mm, even from the SEB images measured with a decrease in the number of irradiated protons to less than 11% of 3.2 × 10 11 protons., Conclusions: High-resolution dose images from measured and simulated SEB images were successfully predicted by using the trained DL model for protons. Our proposed DL model was feasible to predict dose images accurately even with smaller number of irradiated protons., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Interstitial pneumonia (IP) is a disease with a poor prognosis. In addition, IP patients are more likely to develop lung cancer. Since IP patients frequently develop toxicities during cancer treatment, minimally invasive cancer treatment is warranted for such patients to maintain their quality of life. This study retrospectively investigated the efficacy and safety of proton therapy (PT) for non-small cell lung cancer (NSCLC) in patients with IP., Methods: Twenty-nine NSCLC patients with IP were treated with PT between September 2013 and December 2019. The patients had stage IA to IIIB primary NSCLC. Ten of the 29 patients exhibited the usual interstitial pneumonia pattern. The prescribed dose was 66-74 Grays (relative biological effectiveness) in 10-37 fractions., Results: The median follow-up period was 21.1 months [interquartile range (IQR), 15.6-37.3] for all patients and 37.2 months (IQR, 24.0-49.9) for living patients. The median patient age was 77 years (IQR, 71-81). The median planning target volume was 112.0 ml (IQR, 56.1-246.3). The 2-year local control, progression-free survival, and overall survival rates were 85% (95% confidence interval: 57-95), 30% (15-47), and 45% (26-62), respectively. According to the Common Terminology Criteria for Adverse Events (version 4.0), grade 3 acute radiation pneumonitis (RP) was observed in 1 patient. Two patients developed grade 3 late RP, but no other patients experienced serious toxicities. The patients' quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 and SF-36) scores had not changed after 3 months., Conclusions: PT may be a relatively safe treatment for NSCLC patients with IP, without deteriorating quality of life scores within 3 months., (© 2022. The Author(s).)

Purpose: Accurate calculation of the proton beam range inside a patient is an important topic in proton therapy. In recent times, a computed tomography (CT) image reconstruction algorithm was developed for treatment planning to reduce the impact of the variation of the CT number with changes in imaging conditions. In this study, we investigated the usefulness of this new reconstruction algorithm (DirectDensity™: DD) in proton therapy based on its comparison with filtered back projection (FBP)., Methods: We evaluated the effects of variations in the X-ray tube potential and target size on the FBP- and DD-image values and investigated the usefulness of the DD algorithm based on the range variations and dosimetric quantity variations., Results: For X-ray tube potential variations, the range variation in the case of FBP was up to 12.5 mm (20.8%), whereas that of DD was up to 3.3 mm (5.6%). Meanwhile, for target size variations, the range variation in the case of FBP was up to 2.2 mm (2.5%), whereas that of DD was up to 0.9 mm (1.4%). Moreover, the variations observed in the case of DD were smaller than those of FBP for all dosimetric quantities., Conclusion: The dose distributions obtained using DD were more robust against variations in the CT imaging conditions (X-ray tube potential and target size) than those obtained using FBP, and the range variations were often less than the dose calculation grid (2 mm). Therefore, the DD algorithm is effective in a robust workflow and reduces uncertainty in range calculations., (Copyright © 2021 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: Because most previous data on proton therapy for hepatocellular carcinoma (HCC) were retrospectively collected from inoperable or previously treated cases, our aim was to evaluate the outcome of image-guided proton therapy (IGPT) for operable or radiofrequency ablation-treatable primary HCC., Methods and Materials: This phase 2 study prospectively investigated the efficacy and safety of IGPT and quality of life (QoL) after IGPT for operable/ablatable HCC. The primary endpoint was overall survival, and the secondary endpoints were local control, incidence of grade ≥3 adverse events, and changes in QoL. Toxicities were evaluated with Common Terminology Criteria for Adverse Events, version 4.0. QoL scores were assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0, and Quality of Life Questionnaire-Hepatocellular Carcinoma/Primary Liver Cancer Module. IGPT was performed using respiratory-gated techniques., Results: Forty-five patients (median age: 68 years; range, 36-80 years) were enrolled between June 2013 and February 2016; 38 were considered operable and 14 were indicated for radiofrequency ablation. The major underlying liver diseases were hepatitis B (n = 16), hepatitis C (n = 13), alcoholic hepatitis (n = 3), and nonalcoholic fatty liver disease (n = 13). The Child-Pugh score was A5 in 32 patients, A6 in 9 patients, and B7 in 4 patients. Thirty-seven patients with a peripherally located tumor were given 66 Gy relative biological effectiveness in 10 fractions, and 8 patients with a centrally located tumor received 72.6 Gy relative biological effectiveness in 22 fractions. The median follow-up period of surviving patients was 60 months (range, 42-75 months). Two- and 5-year overall survival rates were 84% (95% confidence interval [CI], 74%-95%) and 70% (95% CI, 56%-84%), respectively, and local control rates were 95% (95% CI, 89%-100%) and 92% (95% CI, 84%-100%), respectively. Grade 3 radiation-induced liver disease was observed in 1 patient. No significant changes were noted in QoL scores 1 year after treatment, except for body image., Conclusions: Although the primary endpoint did not meet statistical significance as planned in the study design, IGPT is a safe and effective treatment for solitary primary HCC and may become a treatment option., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A radiophotoluminescent glass dosimeter (RGD) is used for a postal audit of a photon beam because of its various excellent characteristics. However, it has not been used for scanning proton beams because its response characteristics have not been verified. In this study, the response of RGD to scanning protons was investigated to develop a dosimetry protocol using the linear energy transfer (LET)-based correction factor. The responses of RGD to four maximum-range-energy-pattern proton beams were verified by comparing it with ionization chamber (IC) dosimetry. The LET at each measurement depth was calculated via Monte Carlo (MC) simulation. The LET correction factor ( k LET RGD ) was the ratio between the uncorrected RGD dose ( D raw RGD ) and the IC dose at each measurement depth. k LET RGD can be represented as a function of LET using the following equation: k LET RGD LET = - 0.035 LET + 1.090 . D raw RGD showed a linear under-response with increasing LET, and the maximum dose difference between the IC dose and D raw RGD was 15.2% at an LET of 6.07 keV/μm. The LET-based correction dose ( D LET RGD ) conformed within 3.6% of the IC dose. The mean dose difference (±SD) of D raw RGD and D LET RGD was -2.5 ± 6.9% and 0.0 ± 1.6%, respectively. To achieve accurate dose verification for scanning proton beams using RGD, we derived a linear regression equation based on LET. The results show that with appropriate LET correction, RGD can be used for dose verification of scanning proton beams., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Since sexual function and testosterone levels after image-guided proton therapy (IGPT) have not yet been examined in detail, we prospectively evaluated changes before and after IGPT. Among patients treated with IGPT with or without combined androgen blockade (CAB) therapy between February 2013 and September 2014, patients who agreed to participate in the study and were followed up for >3 years after IGPT were evaluated. Serum testosterone levels were regularly measured together with prostate-specific antigen (PSA) levels before and after IGPT. The Erection Hardness Score (EHS) and the sexual domain summary, function subscale and bother subscale of the sexual domain in the Expanded Prostate Cancer Index Composite (EPIC) were assessed. There were 38 low-risk, 46 intermediate-risk and 43 high- or very-high-risk patients (NCCN classification). Although serum testosterone levels in low-risk patients did not decrease after IGPT, reductions were observed in the average EHS and the sexual domain summary score of the EPIC. In intermediate-, high- and very-high-risk patients, testosterone and PSA levels both increased following the termination of CAB after IGPT, and the average EHS increased. The sexual domain summary score gradually increased, but not above minimally important differences. In intermediate-risk patients, the function subscale increased from 4.4 to 14.8 (P < 0.05) 12 months after IGPT and reached a plateau after 60 months. The results of the present study would suggest the potential of IGPT, and further prospective studies to directly compare IGPT with other modalities are warranted., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: This study prospectively evaluated the efficacy and safety of concurrent chemo-proton therapy (CCPT) using adaptive planning for unresectable stage III non-small cell lung cancer (NSCLC)., Methods and Materials: The primary endpoint was overall survival (OS). Secondary endpoints were local control rate (LCR), progression-free survival (PFS), incidence of grade 3 or higher adverse events, and changes in quality of life (QOL). Patients received cisplatin (60 mg/m 2 ) on day 1 and S-1 (∼40 mg/m 2 twice daily) on days 1 to 14, q4w, for up to 4 cycles, plus concurrent proton therapy at a total dose of 70 GyRBE for the primary lesion and 66 GyRBE for lymph node metastasis with 2 GyRBE per day. Proton therapy was performed using respiratory-gated and image guided techniques, and adaptive plans were implemented., Results: Forty-seven patients were enrolled between August 2013 and August 2018. Four cycles of cisplatin plus S-1 were completed in 34 patients. The mean number of cycles was 4 (range, 1-4). The median follow-up of all and surviving patients was 37 (range, 4-84) and 52 months (range, 26-84), respectively. The mean number of replanning sessions was 2.5 (range, 1-4). The 2- and 5-year OS, LCR, and PFS were 77% (95% confidence interval 64%-89%) and 59% (43%-76%), 84% (73%-95%) and 61% (44%-78%), and 43% (28%-57%) and 37% (22%-51%), respectively. The median OS was not reached. No grade 3 or higher radiation pneumonitis was observed. There was no significant deterioration in the QOL scores after 24 months except for alopecia., Conclusions: CCPT with adaptive planning was well tolerated and yielded remarkable OS for unresectable stage III NSCLC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A radiophotoluminescent glass dosimeter (RGD) is widely used in postal audit system for photon beams in Japan. However, proton dosimetry in RGDs is scarcely used owing to a lack of clarity in their response to beam quality. In this study, we investigated RGD response to beam quality for establishing a suitable linear energy transfer (LET)-corrected dosimetry protocol in a therapeutic proton beam. The RGD response was compared with ionization chamber measurement for a 100-225 MeV passive proton beam. LET of the measurement points was calculated by the Monte Carlo method. An LET-correction factor, defined as a ratio between the non-corrected RGD dose and ionization chamber dose, of 1.226×(LET) -0.171 was derived for the RGD response. The magnitude of the LET-dependence of RGD increased with LET; for an LET of 8.2 keV/μm, the RGD under-response was up to 16%. The coefficient of determination, mean difference ± SD of non-corrected RGD dose, residual range-corrected RGD dose, and LET-corrected RGD dose to the ionization chamber are 0.923, 3.7 ± 4.2%, -2.4 ± 7.5%, and 0.04 ± 2.1%, respectively. The LET-corrected RGD dose was within 5% of the corresponding ionization chamber dose at all energies until 200 MeV, where it was 5.3% lower than the ionization chamber dose. A corrected LET-dependence of RGD using a correction factor based on a power function of LET and precise dosimetric verification close to the maximum LET were realized here. We further confirmed establishment of an accurate postal audit under various irradiation conditions., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: In Japan, the first domestic clinical trial of proton beam therapy for the liver was initiated as the Japan Clinical Oncology Group trial (JCOG1315C: Non-randomized controlled study comparing proton beam therapy and hepatectomy for resectable hepatocellular carcinoma). Purposes of this study were to develop a new dosimetric verification system and to carry out a credentialing for the JCOG1315C clinical trial., Materials and Methods: Accuracy and differences in doses in proton treatment planning among participating institutions were surveyed and investigated. We designed and developed a suitable water tank-type liver phantom for a dosimetric verification of proton beam therapy for liver. In a visiting survey of five institutions participating in the clinical trial, we performed the dosimetric verification using the liver phantom and an air-filled ionization chamber., Results: The shape of the dose distributions calculated in proton treatment planning was characteristic and dependent on the manufacturers of the proton beam therapy system, the proton treatment planning system and the setup at the participating institutions. Widths of the lateral penumbra were 5.8-12.7 mm among participating institutions. The accuracy between the calculated and the measured doses in the proton irradiation was within 3% at five measurement points including both points on the isocenter and off the isocenter., Conclusions: These findings confirmed the accuracy of the delivery doses in the institutions participating in the clinical trial, and the clinical trial with integration of all institutions (five institutions) could be initiated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To investigate optimal treatment planning using proton beams for non-squamous cell carcinoma of the head and neck (NSCHN), the dose distributions of plans involving pencil beam scanning (PBS) with or without a patient-specific aperture system (PSAS), passive-scattering proton therapy (PSPT) and X-ray intensity-modulated radiotherapy (IMRT) were compared. As clinical results, toxicities of PBS with PSAS, including changes in quality of life, were reported. Between April 2014 and August 2016, a total of 30 patients were treated using PBS with PSAS. In 20 patients selected at random, the dose distributions of PBS with or without the PSAS, PSPT and IMRT plans were compared. Neutron exposure by proton therapy was calculated using a Monte Carlo simulation. Toxicities were scored according to CTCAE ver. 4.0. Patients completed EORTC quality of life survey forms (QLQ-C30 and QLQ-HN35) before and 0-12 months after proton therapy. The 95% conformity number of PBS with the PSAS plan was the best, and significant differences were detected among the four plans (P < 0.05, Bonferroni tests). Neutron generation by PSAS was ~1.1-fold higher, but was within an acceptable level. No grade 3 or higher acute dermatitis was observed. Pain, appetite loss and increased weight loss were more likely at the end of treatment, but recovered by the 3 month follow-up and returned to the pretreatment level at the 12 month follow-up. PBS with PSAS reduced the penumbra and improved dose conformity in the planning target volume. PBS with PSAS was tolerated well for NSCHN., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The purpose of this study was to propose a verification method and results of intensity-modulated proton therapy (IMPT), using a commercially available heterogeneous phantom. We used a simple simulated head and neck and prostate phantom. An ionization chamber and radiochromic film were used for measurements of absolute dose and relative dose distribution. The measured doses were compared with calculated doses using a treatment planning system. We defined the uncertainty of the measurement point of the ionization chamber due to the effective point of the chamber and mechanical setup error as 2 mm and estimated the dose variation base on a 2 mm error. We prepared a HU-relative stopping power conversion table and fluence correction factor that were specific to the heterogeneous phantom. The fluence correction factor was determined as a function of depth and was obtained from the ratio of the doses in water and in the phantom at the same effective depths. In the simulated prostate plan, composite doses of measurements and calculations agreed within ±1.3% and the maximum local dose differences of each field were 10.0%. Composite doses in the simulated head and neck plan agreed within 4.0% and the maximum local dose difference for each field was 12.0%. The dose difference for each field came within 2% when taking the measurement uncertainty into consideration. In the composite plan, the maximum dose uncertainty was estimated as 4.0% in the simulated prostate plan and 5.8% in the simulated head and neck plan. Film measurements showed good agreement, with more than 92.5% of points passing a gamma value (3%/3 mm). From these results, the heterogeneous phantom should be useful for verification of IMPT by using a phantom-specific HU-relative stopping power conversion, fluence correction factor, and dose error estimation due to the effective point of the chamber., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The purpose of this study was to provide periodic quality assurance (QA) methods for respiratory-gated proton beam with a range modulation wheel (RMW) and to clarify the characteristics and long-term stability of the respiratory-gated proton beam. A two-dimensional detector array and a solid water phantom were used to measure absolute dose, spread-out Bragg peak (SOBP) width and proton range for monthly QA. SOBP width and proton range were measured using an oblique incidence beam to the lateral side of a solid water phantom and compared between with and without a gating proton beam. To measure the delay time of beam-on/off for annual QA, we collected the beam-on/off signals and the dose monitor-detected pulse. We analyzed the results of monthly QA over a 15-month period and investigated the delay time by machine signal analysis. The dose deviations at proximal, SOBP center and distal points were -0.083 ± 0.25%, 0.026 ± 0.20%, and -0.083 ± 0.35%, respectively. The maximum dose deviation between with and without respiratory gating was -0.95% at the distal point and other deviations were within ±0.5%. Proximal and SOBP center doses showed the same trend over a 15-month period. Delay times of beam-on/off for 200 MeV/SOBP 16 cm were 140.5 ± 0.8 ms and 22.3 ± 13.0 ms, respectively. Delay times for 160 MeV/SOBP 10 cm were 167.5 ± 15.1 ms and 19.1 ± 9.8 ms. Our beam delivery system with the RMW showed sufficient stability for respiratory-gated proton therapy and the system did not show dependency on the energy and the respiratory wave form. The delay times of beam-on/off were within expectations. The proposed QA methods will be useful for managing the quality of respiratory-gated proton beams and other beam delivery systems., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Two prospective phase II trials were designed to assess the efficacy and safety of image-guided proton therapy (IGPT) for either medically inoperable or operable stage I non-small cell lung cancer (NSCLC). The present study reports the interim results of these trials., Methods: Fifty-five patients with histologically confirmed stage I NSCLC (IA in 33 patients and IB in 22 patients; inoperable in 21 patients and operable in 34 patients) who received IGPT between July 2013 and February 2017 were analyzed. The median patient age was 71 years (range: 48-88 years). IGPT with fiducial metallic marker matching was performed for suitable patients, and a respiratory gating method for motion management was used for all treatments. Peripherally located tumors were treated with 66 Gy relative biological effectiveness equivalents (Gy(RBE)) in 10 fractions (n = 49) and centrally located tumors were treated with 72.6 Gy(RBE) in 22 fractions (n = 6). Treatment associated toxicities were evaluated using Common Toxicity Criteria for Adverse Events (v.4.0)., Results: Median follow-up was 35 months (range: 12-54 months) for survivors. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 87% (95% confidence interval: 73-94%), 74% (58-85%), and 96% (83-99%), respectively. Fiducial marker matching was used in 39 patients (71%). Grade 2 toxicities observed were radiation pneumonitis in 5 patients (9%), rib fracture in 2 (4%), and chest wall pain in 5 (9%). There were no grade 3 or higher acute or late toxicities., Conclusions: IGPT appears to be effective and well tolerated for all patients with stage I NSCLC., Trial Registration: Lung-001, 13-02-09 (9), registered 11 June 2013 and Lung-002, 13-02-10 (10), registered 11 June 2013.

Although luminescence of water lower in energy than the Cerenkov-light threshold during proton and carbon-ion irradiation has been found, the phenomenon has not yet been implemented for Monte Carlo simulations. The results provided by the simulations lead to misunderstandings of the physical phenomenon in optical imaging of water during proton and carbon-ion irradiation. To solve the problems, as well as to clarify the light production of the luminescence of water, we modified a Monte Carlo simulation code to include the light production from the luminescence of water and compared them with the experimental results of luminescence imaging of water. We used GEANT4 for the simulation of emitted light from water during proton and carbon-ion irradiation. We used the light production from the luminescence of water using the scintillation process in GEANT4 while those of Cerenkov light from the secondary electrons and prompt gamma photons in water were also included in the simulation. The modified simulation results showed similar depth profiles to those of the measured data for both proton and carbon-ion. When the light production of 0.1 photons/MeV was used for the luminescence of water in the simulation, the simulated depth profiles showed the best match to those of the measured results for both the proton and carbon-ion compared with those used for smaller and larger numbers of photons/MeV. We could successively obtain the simulated depth profiles that were basically the same as the experimental data by using GEANT4 when we assumed the light production by the luminescence of water. Our results confirmed that the inclusion of the luminescence of water in Monte Carlo simulation is indispensable to calculate the precise light distribution in water during irradiation of proton and carbon-ion.

Background: Hypofractionated proton therapy (HFPT) is expected to become an effective treatment approach for localized prostate cancer (PCa). The purpose of this study was to evaluate differences in acute toxicity among patients with localized PCa treated with either conventional fractionated proton therapy (CFPT) or HFPT., Methods: A total of 526 eligible patients treated with proton therapy between February 2013 and May 2016 in three phase II trials were analyzed. We prescribed 74 gray relative biological effectiveness equivalents [Gy (RBE)]/37 fractions for low-risk patients and 78 Gy (RBE)/39 fractions for intermediate- and high-risk patients in the CFPT group (n = 254) and 60 Gy (RBE)/20 fractions for low-risk and 63 Gy (RBE)/21 fractions for intermediate- and high-risk patients in the HFPT group (n = 272). Patients were evaluated for acute toxicity with the Common Terminology Criteria for Adverse Events, version 4.0, and urinary quality-of-life change using the International Prostate Symptom Score (IPSS)., Results: No grade ≥3 acute toxicity was observed in either group. Among acute genitourinary toxicities, grade 2 rates were 15% (n = 38) in CFPT and 5.9% (n = 16) in HFPT (P ≤ 0.001). The median baseline IPSSs of the CFPT and HFPT groups were 7 (0-29) and 6 (0-31), respectively (P = 0.70). One-month post-treatment scores were 9 (0-32) and 11 (0-32), respectively (P = 0.036), and 6-month post-treatment scores were 7 (0-30) and 7 (0-33), respectively (P = 0.88). There were no significant differences in acute gastrointestinal toxicity between the two groups., Conclusion: Our results demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.

Although the luminescence images of water during proton-beam irradiation using a cooled charge-coupled device camera showed almost the same ranges of proton beams as those measured by an ionization chamber, the depth profiles showed lower Bragg peak intensities than those measured by an ionization chamber. In addition, a broad optical baseline signal was observed in depths that exceed the depth of the Bragg peak. We hypothesize that this broad baseline signal originates from the interaction of proton-induced prompt gamma photons with water. These prompt gamma photons interact with water to form high-energy Compton electrons, which may cause luminescence or Cherenkov emission from depths exceeding the location of the Bragg peak. To clarify this idea, we measured the luminescence images of water during the irradiations of protons in water with minimized parallax errors, and also simulated the produced light by the interactions of prompt gamma photons with water. We corrected the measured depth profiles of the luminescence images by subtracting the simulated distributions of the produced light by the interactions of prompt gamma photons in water. Corrections were also conducted using the estimated depth profiles of the light of the prompt gamma photons, as obtained from the off-beam areas of the luminescence images of water. With these corrections, we successfully obtained depth profiles that have almost identical distributions as the simulated dose distributions for protons. The percentage relative height of the Bragg peak with corrections to that of the simulation data increased to 94% from 80% without correction. Also, the percentage relative offset heights of the deeper part of the Bragg peak with corrections decreased to 0.2%-0.4% from 4% without correction. These results indicate that the luminescence imaging of water has potential for the dose distribution measurements for proton therapy dosimetry.

In this study, we evaluate dosimetric advantages of using patient-specific aperture system with intensity-modulated proton therapy (IMPT) for head and neck tumors at the shallow depth. We used four types of patient-specific aperture system (PSAS) to irradiate shallow regions less than 4 g/cm 2 with a sharp lateral penumbra. Ten head and neck IMPT plans with or without aperture were optimized separately with the same 95% prescription dose and same dose constraint for organs at risk (OARs). The plans were compared using dose volume histograms (DVHs), dose distributions, and some dose indexes such as volume receiving 50% of the prescribed dose (V 50 ), mean or maximum dose (D mean and D max ) to the OARs. All examples verified in this study had decreased V 50 and OAR doses. Average, maximum, and minimum relative reductions of V 50 were 15.4%, 38.9%, and 1.0%, respectively. D max and D mean of OARs were decreased by 0.3% to 25.7% and by 1.0% to 46.3%, respectively. The plans with the aperture over more than half of the field showed decreased V 50 or OAR dose by more than 10%. The dosimetric advantage of patient-specific apertures with IMPT was clarified in many cases. The PSAS has some dosimetric advantages for clinical use, and in some cases, it enables to fulfill dose constraints., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The purpose of this paper is to describe an outline of a proton therapy system in Nagoya Proton Therapy Center (NPTC). The NPTC has a synchrotron with a linac injector and three treatment rooms: two rooms are equipped with a gantry and the other one is equipped with a fixed horizontal beamline. One gantry treatment room has a pencil beam scanning treatment delivery nozzle. The other two treatment rooms have a passive scattering treatment delivery nozzle. In the scanning treatment delivery nozzle, an energy absorber and an aperture system to treat head and neck cancer have been equipped. In the passive treatment delivery nozzle, a multi-leaf collimator is equipped. We employ respiratory gating to treat lung and liver cancers for passive irradiation. The proton therapy system passed all acceptance tests. The first patient was treated on February 25, 2013, using passive scattering fixed beams. Respiratory gating is commonly used to treat lung and liver cancers in the passive scattering system. The MLCs are our first choice to limit the irradiation field. The use of the aperture for scanning irradiation reduced the lateral fall off by half or less. The energy absorber and aperture system in scanning delivery is beneficial to treat head and neck cancer.

Purpose: To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons., Methods and Materials: The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions., Results: The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (P<.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05)., Conclusions: The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The main purpose in this study was to present the results of beam modeling and how the authors systematically investigated the influence of double and triple Gaussian proton kernel models on the accuracy of dose calculations for spot scanning technique., Methods: The accuracy of calculations was important for treatment planning software (TPS) because the energy, spot position, and absolute dose had to be determined by TPS for the spot scanning technique. The dose distribution was calculated by convolving in-air fluence with the dose kernel. The dose kernel was the in-water 3D dose distribution of an infinitesimal pencil beam and consisted of an integral depth dose (IDD) and a lateral distribution. Accurate modeling of the low-dose region was important for spot scanning technique because the dose distribution was formed by cumulating hundreds or thousands of delivered beams. The authors employed a double Gaussian function as the in-air fluence model of an individual beam. Double and triple Gaussian kernel models were also prepared for comparison. The parameters of the kernel lateral model were derived by fitting a simulated in-water lateral dose profile induced by an infinitesimal proton beam, whose emittance was zero, at various depths using Monte Carlo (MC) simulation. The fitted parameters were interpolated as a function of depth in water and stored as a separate look-up table. These stored parameters for each energy and depth in water were acquired from the look-up table when incorporating them into the TPS. The modeling process for the in-air fluence and IDD was based on the method proposed in the literature. These were derived using MC simulation and measured data. The authors compared the measured and calculated absolute doses at the center of the spread-out Bragg peak (SOBP) under various volumetric irradiation conditions to systematically investigate the influence of the two types of kernel models on the dose calculations., Results: The authors investigated the difference between double and triple Gaussian kernel models. The authors found that the difference between the two studied kernel models appeared at mid-depths and the accuracy of predicting the double Gaussian model deteriorated at the low-dose bump that appeared at mid-depths. When the authors employed the double Gaussian kernel model, the accuracy of calculations for the absolute dose at the center of the SOBP varied with irradiation conditions and the maximum difference was 3.4%. In contrast, the results obtained from calculations with the triple Gaussian kernel model indicated good agreement with the measurements within ±1.1%, regardless of the irradiation conditions., Conclusions: The difference between the results obtained with the two types of studied kernel models was distinct in the high energy region. The accuracy of calculations with the double Gaussian kernel model varied with the field size and SOBP width because the accuracy of prediction with the double Gaussian model was insufficient at the low-dose bump. The evaluation was only qualitative under limited volumetric irradiation conditions. Further accumulation of measured data would be needed to quantitatively comprehend what influence the double and triple Gaussian kernel models had on the accuracy of dose calculations.

Purpose: In the authors' proton therapy system, the patient-specific aperture can be attached to the nozzle of spot scanning beams to shape an irradiation field and reduce lateral fall-off. The authors herein verified this system for clinical application., Methods: The authors prepared four types of patient-specific aperture systems equipped with an energy absorber to irradiate shallow regions less than 4 g/cm(2). The aperture was made of 3-cm-thick brass and the maximum water equivalent penetration to be used with this system was estimated to be 15 g/cm(2). The authors measured in-air lateral profiles at the isocenter plane and integral depth doses with the energy absorber. All input data were obtained by the Monte Carlo calculation, and its parameters were tuned to reproduce measurements. The fluence of single spots in water was modeled as a triple Gaussian function and the dose distribution was calculated using a fluence dose model. The authors compared in-air and in-water lateral profiles and depth doses between calculations and measurements for various apertures of square, half, and U-shaped fields. The absolute doses and dose distributions with the aperture were then validated by patient-specific quality assurance. Measured data were obtained by various chambers and a 2D ion chamber detector array., Results: The patient-specific aperture reduced the penumbra from 30% to 70%, for example, from 34.0 to 23.6 mm and 18.8 to 5.6 mm. The calculated field width for square-shaped apertures agreed with measurements within 1 mm. Regarding patient-specific aperture plans, calculated and measured doses agreed within -0.06% ± 0.63% (mean ± SD) and 97.1% points passed the 2%-dose/2 mm-distance criteria of the γ-index on average., Conclusions: The patient-specific aperture system improved dose distributions, particularly in shallow-region plans.

Purpose: Proton therapy has the ability to selectively deliver a dose to the target tumor, so the dose distribution should be accurately measured by a precise and efficient method. The authors found that luminescence was emitted from water during proton irradiation and conjectured that this phenomenon could be used for estimating the dose distribution., Methods: To achieve more accurate dose distribution, the authors set water phantoms on a table with a spot scanning proton therapy system and measured the luminescence images of these phantoms with a high-sensitivity, cooled charge coupled device camera during proton-beam irradiation. The authors imaged the phantoms of pure water, fluorescein solution, and an acrylic block., Results: The luminescence images of water phantoms taken during proton-beam irradiation showed clear Bragg peaks, and the measured proton ranges from the images were almost the same as those obtained with an ionization chamber. Furthermore, the image of the pure-water phantom showed almost the same distribution as the tap-water phantom, indicating that the luminescence image was not related to impurities in the water. The luminescence image of the fluorescein solution had ∼3 times higher intensity than water, with the same proton range as that of water. The luminescence image of the acrylic phantom had a 14.5% shorter proton range than that of water; the proton range in the acrylic phantom generally matched the calculated value. The luminescence images of the tap-water phantom during proton irradiation could be obtained in less than 2 s., Conclusions: Luminescence imaging during proton-beam irradiation is promising as an effective method for range estimation in proton therapy.

Purpose: In proton therapy, imaging of proton-induced positrons is a useful method to monitor the proton beam distribution after therapy. Usually, a positron emission tomography (PET) system installed in or near the proton beam treatment room is used for this purpose. However, a PET system is sometimes too large and expensive for this purpose. We developed a small field-of-view (FOV) gamma camera for high-energy gamma photons and used it for monitoring the proton-induced positron distribution., Methods: The gamma camera used 0.85 mm × 0.85 mm × 10 mm Ce:Gd3Al2Ga3O12 (GAGG) pixels arranged in 20 × 20 matrix to form a scintillator block, which was optically coupled to a 1-inch-square position-sensitive photomultiplier tube (PSPMT). The GAGG detector was encased in a 20-mm thick container and a pinhole collimator was mounted on its front. The gamma camera was set 1.2 m from the 35 cm × 35 cm × 5 cm plastic phantom in the proton therapy treatment room, and proton beams were irradiated to the phantom with two proton energies., Results: The gamma camera had spatial resolution of ~6.7 cm and sensitivity of 3.2 × 10(-7) at 1 m from the collimator surface. For both proton energies, positron distribution in the phantom could be imaged by the gamma camera with 10-min acquisition. The lengths of the range of protons measured from the images were almost identical to the simulation results., Conclusions: These results indicate that the developed high-energy gamma camera is useful for imaging positron distributions in proton therapy.

Purpose: In proton therapy, imaging of the positron distribution produced by fragmentation during or soon after proton irradiation is a useful method to monitor the proton range. Although positron emission tomography (PET) is typically used for this imaging, its spatial resolution is limited. Cerenkov light imaging is a new molecular imaging technology that detects the visible photons that are produced from high-speed electrons using a high sensitivity optical camera. Because its inherent spatial resolution is much higher than PET, the authors can measure more precise information of the proton-induced positron distribution with Cerenkov light imaging technology. For this purpose, they conducted Cerenkov light imaging of induced positron distribution in proton therapy., Methods: First, the authors evaluated the spatial resolution of our Cerenkov light imaging system with a (22)Na point source for the actual imaging setup. Then the transparent acrylic phantoms (100 × 100 × 100 mm(3)) were irradiated with two different proton energies using a spot scanning proton therapy system. Cerenkov light imaging of each phantom was conducted using a high sensitivity electron multiplied charge coupled device (EM-CCD) camera., Results: The Cerenkov light's spatial resolution for the setup was 0.76 ± 0.6 mm FWHM. They obtained high resolution Cerenkov light images of the positron distributions in the phantoms for two different proton energies and made fused images of the reference images and the Cerenkov light images. The depths of the positron distribution in the phantoms from the Cerenkov light images were almost identical to the simulation results. The decay curves derived from the region-of-interests (ROIs) set on the Cerenkov light images revealed that Cerenkov light images can be used for estimating the half-life of the radionuclide components of positrons., Conclusions: High resolution Cerenkov light imaging of proton-induced positron distribution was possible. The authors conclude that Cerenkov light imaging of proton-induced positron is promising for proton therapy.

Proton therapy (PT) remains much controversy about its routine use in localized prostate cancer treatment. Particularly, comprehensive data on the efficacy and safety of gold fiducial marker matching in PT is less abundant compared to bone matching. We have previously reported on acute toxicity and quality of life changes of image-guided PT (IGPT) for localized prostate cancer. The aim of this study was to evaluate long-term efficacy and safety of IGPT for localized prostate cancer. We sequentially started prospective studies for normofractionated PT (NFPT: 74-78 GyRBE/37-39 Fr) in February 2013, and moderately hypofractionated PT (MHPT: 60-63 GyRBE/20-21 Fr) in October 2014. After the start of MHPT, patients could choose either NFPT or MHPT. Main eligibility criteria included: (1) histologically confirmed primary prostate cancer; (2) T1-T3bN0M0 staged by UICC; (3) age ≥ 20 years; (4) no serious underlying disease or other cancers, and (5) written informed consent. Patients with castration-resistant prostate cancer or enrolled in other clinical trials were excluded from the analysis. The NCCN classification was used. The biochemical relapse free survival (bRFS) was based on the Phoenix definition (nadir + 2.0 ng/mL). The rates of bRFS, overall survival (OS) and incidence of late gastrointestinal (GI) and genitourinary (GU) toxicities were estimated using the Kaplan-Meier methods. Toxicities were evaluated with the CTCAE version 5.0. The dose constraints were partially changed in August 2014, and hydrogel spacer was introduced in May 2018. In principle, low-risk patients received no androgen-deprivation therapy (ADT), intermediate-risk patients received 6-month neoadjuvant ADT, and high- or very-high-risk patients received two-year neoadjuvant and adjuvant ADT. Patients registered until March 2021, before the transition to the new fractionation protocol, were analyzed. The total number of prostate cancer patients who received PT at our institution until March 2021 was 1,643. A total of 327 patients treated using NFPT and 1243 patients treated using MHPT were analyzed (Total 1570). The number of patients in the low-risk, intermediate-risk, and high- or very-high-risk groups were 228, 715, and 627, respectively. The median follow-up period of surviving patients was 68.0 months (range = 20-130). The 5-year rates of bRFS and OS in the low-risk, intermediate-risk, and high- or very-high-risk patients were 95.7%, 96.5%, 91.8% for bRFS, and 97.1%, 97.5%, 97.7% for OS, respectively. Of the 76 patients who died, 71 of them were due to other disease. Biochemical relapse was observed in 62 patients, 31 of whom showed clinical relapse. Local recurrence was noted in 4 patients. The incidence of grade 2 and 3 late GI and GU toxicities were 4.4%, 0.8% and 2.9%, 0.1%, retrospectively. IGPT with gold fiducial marker for localized prostate cancer is favorable and well tolerated. Further hypofractionated IGPT with hydrogel spacer is expected. [ABSTRACT FROM AUTHOR]

Surgical resection is the standard treatment for soft-tissue sarcomas (STS). However, trunk STS is often unresectable due to its large size and proximity to vital structures. There is limited evidence regarding proton therapy (PT) for trunk STS with definitive intent. We hypothesize that image-guided PT (IGPT) will provide long-term local control and improve survival for patients with unresectable trunk STS. A single institutional retrospective study was conducted on patients who underwent IGPT with definitive intent for unresectable trunk STS from December 2013 to September 2022. In this study, the "trunk" was defined as regions excluding the extremities and head and neck areas. Patients under 18 years old and those with gynecological sarcomas were excluded. PT treatment employed either the passive scattering technique or spot scanning technique. Overall survival (OS), local control (LC), and progression-free survival (PFS) were analyzed using Kaplan-Meier estimates, and radiation-related adverse events were assessed using CTCAE version 5.0. Univariate analysis (UVA) was conducted to assess the association with OS. Thirty-three patients were analyzed. The median age was 61 years (range = 19-85), and the median gross tumor volume (GTV) was 266 cc (range = 10-3017). The most common histological type was dedifferentiated liposarcoma (n = 14; 42%), followed by leiomyosarcoma (n = 6; 18%). The most frequent irradiation site was the retroperitoneum (n = 22; 67%), followed by the gluteal region (n = 5; 15%). The dose fractionation ranged from 57.2 to 70.2 Gy (RBE) in 13 to 33 fractions, with the most common being 70.2 Gy (RBE) in 26 fractions (n = 19; 58%). Spot scanning technique was used in 26 patients (79%). The target was the primary tumor with no prior surgery in 16 patients (48%) and recurrent or metastatic tumor after surgery in 17 patients (52%). Two patients (6%) had previous radiotherapy. Seven patients (21%) had surgical absorbable spacer placement. The median follow-up duration was 21 months (range = 3-106). The 3-year OS, LC, and PFS were 53% (95% CI = 31-70%), 81% (60-92%), and 39% (23-55%), respectively. The most common initial recurrence pattern was distant metastasis. In UVA, GTV exceeding 300cc was identified as a poor prognostic factor for OS. No grade 3 or higher radiation-related adverse events were observed. This study explored the effectiveness of IGPT for unresectable trunk STS, particularly retroperitoneal sarcomas. IGPT demonstrated favorable LC, showing promise as a safe and effective treatment for this challenging condition. [ABSTRACT FROM AUTHOR]

Towards hypofractionated proton therapy for prostate cancer for improving convenience for patients to receive treatment and improving therapeutic efficacy, image-guided technique with hydrogel spacer solved the late gastrointestinal toxicity, but it is unclear whether acute genitourinary (GU) toxicity is acceptable. The aim of this phase II study was to evaluate the safety and efficacy of hypofractionated image-guided proton therapy (IGPT) with 12 fractions for prostate cancer. Eligibility criteria were as follows: (1) histologically confirmed primary prostate cancer; (2) T1-T3bN0M0 staged by (UICC TNM8th); (3) ECOG-PS ≤ 2; (4) age ≥ 20 years; (5) no serious underlying disease or other cancers; (6) technically capable of proton therapy, and (7) written informed consent. Primary endpoint was the ratio of grade 2 or more acute genitourinary toxicity. We used the modified CTCAE grading of grade 2 GU toxicities, in which prescribing two and more types of drugs for dysuria within 3 months of the start of radiation was considered to indicate grade 2 GU toxicity. A phase II trial was planned based on the minimax Simon's two-stage design with a significance level of 0.05 and a power of 90%. The acceptable incidence is considered to be less than 5%, and the unacceptable incidence is considered to be more than 15%. A total of 83 patients is required for completion of the trial (7 patients or fewer). After evaluating the primary endpoint in 83 patients, 217 additional patients were registered and a total of 300 patients were registered in order to further examine the safety and efficacy. The prescribed dose to the isocenter was 51.6 GyRBE in 12 fractions (4 days a week). From January 2020 to March 2021, 30, 53, and 217 patients (total 300) were enrolled. The patient characteristics were as follows: median age, 70 (48-83) years; low/intermediate/high risk, 44/132/124. Forty-nine and 38 patients had benign prostatic hyperplasia and diabetes mellitus, respectively. Grade 2 acute GU toxicities were observed in 1, 5 and 13 patients, respectively (total 6.3%). No grade 3 or higher acute GU toxicities were observed. However, urinary retention during IGPT, which was not previously observed, was observed in 3 cases, and temporary urethral catheterization was performed (Grade 2). Most of the acute GU toxicity tended to improve at 1 month after IGPT, and almost improved at 3 months. Mean score deteriorations beyond the minimum clinically important difference threshold (1/2 SD) were observed only at 1 month in the following scales: summary (-6.0), bother (-7.0), and irritative/obstructive (-6.3). Hypofractionated IGPT with 12 fractions for prostate cancer is well tolerated in acute GU toxicities. Longer follow-up is necessary to evaluate the efficacy and late toxicities. Further investigation of hypofractionated IGPT with 12 fractions for prostate cancer is warranted. Since April 2021, an additional 1000 cases of prospective registration study have been conducted. [ABSTRACT FROM AUTHOR]

Abstract For safe and effective proton therapy, the proton range in a patient's body is characterized by the water equivalent length (WEL), and must be accurately determined. Current treatment planning is based on X-ray computed tomography images, which might cause uncertainty because of the different energy loss processes between protons and X-rays. We develop a simple, novel, and real-time proton CT system. The system uses a CCD camera and scintillator, which is thin enough for protons to penetrate. Since protons lose energy when they pass through a phantom, different emissions corresponding to the proton energy loss are acquired in the scintillator. Images of the scintillator were gathered by the CCD camera with 70 MeV and 200 MeV proton beams. Since blurring due to proton reactions such as multiple Coulomb scattering and nuclear reactions significantly degrades the obtained images in both beams, we developed two kinds of effective correction methods. One method is applied to broad beam systems, while the other is applied to narrow beam systems. We successfully obtain clear images with minor proton reaction effects by applying these correction methods. Moreover, we confirm that the WEL values estimated from the acquired CT images agree well with the theoretical values for materials such as polymethyl methacrylate (PMMA) and isopropyl alcohol, within 1- σ uncertainty. Through simulations, we found that nuclear reactions significantly contribute to the uncertainty of WEL values. [ABSTRACT FROM AUTHOR]

Proton therapy causes less damage to healthy tissue compared to other radiation therapies; however, the possible damage caused by secondary, fast neutrons is almost unknown. In some simulations, neutron dose amounts to 10% of the proton dose; therefore, a real-time visualization of the neutron dose is needed. We have developed a neutron camera that can visualize the direction and intensity of fast neutron sources. The camera consists of eight units of a plastic scintillator (EJ-299-34) coupled with a compact PMT (R9880U). We demonstrate that a 252Cf neutron source is correctly imaged with an angular resolution of 15.5 deg (FWHM). In addition, fast neutrons emitted from the brass block irradiated by 70 MeV were successfully monitored in real time. Finally, we present our prospects for future clinical applications. [ABSTRACT FROM AUTHOR]

Additional treatment options for recurrent hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and/or radiofrequency ablation (RFA) treatment are limited. Although proton therapy provides a more focused dose distribution on the tumor compared with X-ray therapy, the efficacy and safety of proton therapy for recurrent HCC remains unclear. The aim of this study was to evaluate the efficacy and safety of image-guided proton therapy (IGPT) for recurrent HCC after TACE and/or RFA. Eligibility criteria were as follows: (1) histologically-confirmed or image-diagnosed recurrent HCC after TACE and/or RFA treatment; (2) intrahepatic recurrence cases other than treatment site recurrence are not included (3) no previous radiotherapy around the lesion and other HCC; (4) age > 20 and ≤ 80 years; (5) ECOG-PS ≤ 2; (6) Child-Pugh classification A5-B9; (7) dose constraints of the organs at risk achievable; (8) no portal vein or inferior vena cava tumor thrombus; and (9) written informed consent. Overall survival (OS), local control (LC), and progression-free survival rates were estimated using the Kaplan-Meier method. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 5.0. Quality of life (QOL) scores were evaluated with EORTC QLQ-C30 version 3.0, QLQ-HCC18, and SF-36. Prior to treatment planning, the fiducial marker was placed just adjacent to a recurrent tumor. IGPT was performed under respiratory gating. From June 2013 to December 2020, 80 patients were enrolled. Major underlying liver diseases were hepatitis B (n=19), hepatitis C (n=35), alcoholic hepatitis (n=9), and nonalcoholic fatty liver disease (n=17). The Child-Pugh score was A5 in 49 patients, A6 in 16, and B7-9 in 15. The number of Albumin-Bilirubin Grade 1, 2, and 3 were 40, 40, and 0, respectively. Nineteen patients had a history of hepatic resection for other HCC. Fifty-four patients with a peripherally-located tumor were given 66 GyE in 10 fractions and 26 with a central tumor received 72.6 GyE in 22 fractions. Maximum tumor diameter ranged from 10 to 174 mm (median, 31). The median follow-up period of surviving patients was 38.0 months (range: 12.0-96.0). The 3-year OS, LC and PFS were 81% (95% confidence interval: 71-90%), 92% (86-100%), and 38% (26-49%) respectively. In univariate analysis, Child classification, operability, and tumor diameter were associated with better survival, while only Child classification was associated in multivariate analysis. Clinical remission or sustained viral response were significant factors for OS in patients with HCC recurrence derived from hepatitis virus. Non-classic radiation-induced liver disease was observed in only 1 patient with decrease of Child-Pugh score (≥ 2 points). The QOL score did not change after 1 year. IGPT is safe and effective for recurrent HCC after TACE and/or RFA treatment. IGPT may become one of standard treatments as a curative treatment for recurrent HCC. [ABSTRACT FROM AUTHOR]