Passive Scattering Proton Beam Research Articles

Radioactivation effects of titanium caused by clinical proton beam: a simulation study

Objective. In proton beam therapy (PBT), metals in the patient body perturb the dose distribution, and their radioactivation may affect the dose distribution around the metal; however, the radioactivation effect has been not clarified with PBT. In this study, we aimed to evaluate the radioactivation effect of metal depending on proton energies and secondary neutrons with a clinical proton beam using a Monte Carlo (MC) simulation. Approach. The radionuclides produced from a titanium alloy (Ti-6Al-4V) and their radioactivity were calculated using a 210-MeV passive scattering proton beam with a 60-mm Spread-out Bragg Peak, and the deposited doses caused by the radioactivation were computed using the MC simulation. The position of metal was changed according to the proton mean energy in water. To assess neutron effects on the radioactivation, we calculated the radioactivation in following three situations: (i) full MC simulation with neutrons, (ii) simulation without secondary neutrons generated from the beamline components, and (iii) simulation without any secondary neutrons. Main results. Immediately after the irradiation, the radionuclide with the largest activity was Sc-45 m (half-life of 318 ms) regardless of the proton energy and the presence of neutrons. Total radioactivity tended to increase according to the proton energy. The accumulated dose for 24 h caused by the metal activation showed an increasing trend with the proton energy, with a maximum increase rate of 0.045% to the prescribed dose. The accumulated dose at a distance of 10 mm from the metal was lower than 1/10 of that at a distance of 1 mm. Significance. The radioactivation effect of the titanium was comprehensively evaluated in the clinical passive scattering proton beam. We expect that radioactivation effects on the clinical dose distribution would be small. We consider that these results will help the clinical handling of high-Z metals in PBT.

The Impact of Dose Calibration Point Differences Between the Treatment Plan and Patient-specific Quality Assurance in Passive Scattering Proton Beam Therapy.

Passive scattering proton beam therapy (PSPT) is performed by taking actual measurements of all pre-designated fields in a treatment plan followed by appropriate adjustments to the prescribed dose. For this reason, it is necessary to ensure precision management of the measurements (patient-specific calibration) in the administration of a planned dose. Therefore, this study investigated the impact on dose distribution in treatment planning when the patient calibration point differs from the normalized point in a treatment plan. A total of 16 cases were selected, where the patient calibration point and normalized point did not match, and the normalized point used in the treatment plan was changed to the patient calibration point using a treatment planning system (VQA ver. 2.01, HITACHI). At this point, the displacement of the relative dose at the isocenter was estimated as an error owing to the difference compared to the patient calibration point. Overall, the error was within the range of ±1.5%, with the exception of orbit cases. Calibrated points also tended to be lower than the normalized points in the treatment plan. In terms of treatment sites, a greater deviation was observed for head cases. Cases with a large deviation in sites other than the head were attributed to poor flatness within the radiation field owing to a narrower opening of the patient collimator. Dose measurement errors in PSPT due to differing calibration points were generally within ±1.5%, with higher deviations observed in head treatments because of complex structures and narrow collimator openings. A γ analysis for significant deviations showed a 98.7% passing rate, suggesting limited overall impact. It is important to select stable calibration points in dosimetry to ensure high precision in dose administration, particularly in complex treatment areas.

The Incidence of Severe Radiation-Induced Lymphopenia during Chemoradiotherapy for Stage Ⅲ Non-Small Cell Lung Cancer: A Comparative Study of Proton Versus Photon-Based Radiotherapy

To investigate the incidence of severe radiation-induced lymphopenia (SRL) and the survival in patients with stage Ⅲ non-small cell lung cancer treated with concurrent chemoradiotherapy with passive scattering proton beam (PSPT) or photon-based radiotherapy (XRT) including 3D-CRT and IMRT. We conducted a retrospective cohort study including 355 patients who received definitive concurrent chemoradiotherapy with PSPT (n = 38) or XRT (n = 317) at our institution between January 2010 and December 2020. SRL during concurrent chemoradiotherapy was defined as absolute lymphocyte counts (ALCs) of <500 cells/mm3. Propensity score matching (PSM) analysis was performed to adjust for the patient characteristics between the PSPT and XRT groups. Propensity scores were calculated using age, sex, PS (0-1 vs. 2), primary tumor location (upper/middle vs. lower lobe), pathology (Adeno vs. Others), PTV volume, ALCs at pretreatment, year of treatment (before vs. after July 2018, when durvalumab approved in Japan), and platinum-based chemotherapy regimen (CDDP based vs. CBDCA based). After PSM, the incidence of SRL and the overall survival (OS) were analyzed. The GTV and PTV volumes were significantly lower in the PSPT group than in the XRT group (median, 57 vs. 103 mm3; p < 0.05, 322 vs. 399 mm3; p < 0.05, respectively). ALCs at pretreatment were significantly lower in the PSPT group than in the XRT group (median, 1531 vs. 1718 cells/mm3; p < 0.05). SRL was observed in 275 patients (87%) in the XRT group and 27 patients (71%) in the PSPT group (p < 0.05). After PSM, PSPT significantly reduced the incidence of SRL compared to XRT (68.6 % vs. 88.6 %, p < 0.05), and the patients without SRL may have better 3-year OS than those with SRL (71.1 % vs. 55.3 %; p = 0.062). Compared with XRT, PSPT significantly reduced the incidence of SRL, and the patients without SRL had a good prognosis.

Identification of Induced Radionuclides Produced from Dental Metals in Proton Beam Therapy for Head and Neck Cancer

To identify the induced radionuclides produced from dental metals in proton beam therapy and investigate the accuracy of the Monte Carlo (MC) simulation by comparing the measured radioactivity. Two dental metals of pure titanium and gold-silver-palladium alloy, commonly used in Japan, were used in this study. The dental metal placed at the center of Spread-out Bragg Peak was irradiated by 150-MeV passive scattering proton beam. The gamma rays emitted from the activated dental metals were measured using a high purity germanium (HPGe) detector. The induced radionuclides were identified from the measured gamma-ray energies. Furthermore, the Particle and Heavy Ion Transport code System v.3.24 and DCHAIN were used for the MC simulation. The measured radionuclides and their radioactivity were compared with the simulation results. In the MC simulation for the activated titanium, vanadium-47, with a half-life of 32.6 minutes had the strongest radioactivity among the induced radionuclides. The energy peaks of gamma rays emitted from titanium-51, scandium-43, scandium-44, and annihilation gamma rays were observed for the activated titanium in the HPGe detector. In the MC simulation for the activated gold-silver-palladium alloy, silver-108, with a half-life of 2.4 minutes had the strongest radioactivity. The energy peaks of gamma rays emitted from silver-104, silver-104 m, silver-108, and annihilation gamma rays were observed for the activated gold-silver-palladium alloy in the HPGe detector. Furthermore, the induced radionuclides and their radioactivity in the MC simulation were consistent with the measurement results for both dental metals, except for a few radionuclides. We identify the induced radionuclides produced from 2 dental metals and compared their radioactivity between the measurements and the MC simulation. Although the identification of the induced radionuclides using the MC simulation remains uncertain, the MC simulation can be clinically effective for pre-estimating the induced radionuclides in proton beam therapy.

Dynamic Hepatic Blood Flow Model Shows Greater Impact of Total Treatment Time Than Integral Dose for Assessing Dose to Circulating Lymphocytes

<h3>Purpose/Objective(s)</h3> Radiation-induced lymphocyte depletion has been reported to correlate with survival rate in post-radiotherapy patients with hepatocellular carcinoma. This study aims to assess the impact of integral dose and treatment time on the dose to circulating lymphocytes (CL) with active scanning and passive scattering proton beam therapy (PBS, SOBP), intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). <h3>Materials/Methods</h3> Four plans based on VMAT, IMRT, PBS and SOBP were created for the same hepatocellular carcinoma patient delivering 52.5 Gy in 15 fractions. Six fields, 1 arc, and 2 fields were used for IMRT, VMAT and proton plans, respectively. The dose to CLs after one RT fraction was computed with a novel 4D dynamic blood flow liver model using realistic treatment times (Table 1), which takes into account hepatic vasculature (arterial, portal venous and hepatic venous trees), blood recirculation and time structure of dose delivery. We varied the delivery speed for each modality to achieve total treatment times in the range of 50-250s. The impact of integral dose and treatment time on dose to CLs across different modalities was quantified by the mean dose to CL, the % CL receiving non-zero dose (V_0Gy), the % CL receiving > 0.5 Gy dose (V_0Gy) and the dose received by highest 2% of CLs (D_2%). <h3>Results</h3> Mean liver dose ranges from 19.4 - 22.2 Gy and treatment time from 60 - 3255s depending on the modality. The PBS and SOBP treatments yield 15% and 10% lower mean dose to CLs compare to VMAT, respectively (Table 1). However, the fraction of lymphocytes receiving any dose varies widely from 37.0% for VMAT to 80.8% for PBS, uncorrelated to integral dose. The fraction of lymphocytes receiving a significant dose (V0.5%) also varies considerably with the highest fraction in VMAT (14.6%) and the lowest for PBS (0.6%). Further analysis indicates that V_0Gy depends on both the mean dose and the total treatment time, which explains the large variations observed among various modalities. Every 10s increase in treatment time leads to approximately 3% increase in V_0Gy. The opposite trend was found for V_0.5Gy and D_2%, both decreasing with increasing treatment time. V_0.5Gy and D_2% decrease approximately 0.6% and 0.01Gy for every 10s increase in treatment time, respectively. <h3>Conclusion</h3> We studied dose to CLs across 4 different treatment modalities and found that to minimize the fraction of CL irradiated, it might be more important to shorten the delivery time than to reduce the dose bath. Further investigation is required to find the dose levels most correlated to lymphocyte depletion to optimize delivery time and to design immune-sparing RT regimen.

Treatment outcomes of passive scattering proton beam therapy\xa0for stage I non-small cell lung cancer

IntroductionTo investigate the treatment outcomes of passive scattering proton beam therapy using stereotactic ablative radiotherapy (SABR) or hypofractionated radiation therapy (RT) for inoperable patients or those who refused surgery for stage I non-small cell lung cancer (NSCLC).MethodsFrom January 2016 to December 2019, we retrospectively analyzed 42 patients with stage I NSCLC treated with proton beam therapy. The initially intended dose regimen was 60 cobalt Gray equivalents (CGE) in 4 fractions; however, sequentially modified dose regimens were used when the dose-volume constraints could not be met. The median total dose was 50 CGE (range 50–70 CGE), while the corresponding median biologically effective dose using alpha{/}beta= 10 (BED10) was 112.5 CGE (range 96–150 CGE).ResultsThe median follow-up time was 40 months (interquartile range 32–48 months). Among the 42 treated patients, 33 had pathologically proven cancers of which most were adenocarcinoma (n = 21, 64%). The 3-year overall survival rate was 71.8%. The estimated rates of local control and progression free survival at 3 years were 91.5% and 66.9%, respectively. Thirteen patients experienced disease progression consisting of three local, six regional, and nine distant failures. No grade 4 or 5 toxicities were observed.ConclusionPassive scattering proton beam therapy for stage I NSCLC using SABR or hypofractionated RT was safe and showed high LC rates.

Reduction of superficial radiation dose with bolus in passive scattering proton beam therapy.

PurposeIn passive scattering proton beam therapy, scattered protons from the snout and aperture increase the superficial dose, however, treatment planning systems (TPSs) based on analytic algorithms (such as proton convolution superposition) are often inaccurate in this aspect. This additional dose can cause permanent alopecia or severe radiation dermatitis. This study aimed to evaluate the effect of bolus on the superficial radiation dose in passive scattering proton beam therapy.MethodsWe drew a clinical target volume (CTV) and a scalp‐p (phantom), and created plans using a TPS for a solid water phantom with and without bolus. We calculated the dose distribution in the established plans independently with Monte Carlo (MC) simulation and measured the actual dose distribution with an array of ion chambers and radiochromic films. To assess the clinical impact of bolus on scalp dose, we conducted independent dose verification using MC simulation in a clinical case.ResultsIn the solid water phantom without bolus, the calculated scalp‐p volume receiving 190 cGy was 20% with TPS but 80% with MC simulation when the CTV received 200 cGy. With 2 cm bolus, this decreased from 80% to 10% in MC simulation. With the measurements, average superficial dose to the scalp‐p was reduced by 5.2% when 2 cm bolus was applied. In the clinical case, the scalp‐c (clinical) volume receiving 3000 cGy decreased from 74% to 63% when 2 cm bolus was applied.ConclusionThis study revealed that bolus can reduce radiation dose at the superficial body area and alleviate toxicity in passive scattering proton beam therapy.

Treatment Outcomes of Passive Scattering Proton Beam Therapy for Stage I Non-Small Cell Lung Cancer

The purpose of this study is to investigate treatment outcomes of passive scattering proton beam therapy for medically inoperable or patients who refused to undergo surgery with stage I non-small cell lung cancer (NSCLC). From April 2015 to May 2019, medical records of 52 stage I NSCLC patients treated with proton beam therapy were retrospectively analyzed. The median age was 79 years (range, 58-92 years), and 39 patients were 75 years or older. Of 52 treated patients, 44 had pathologically proven cancer, and most of them were adenocarcinoma (n = 23, 52%). Sixteen, 13, 6, and 17 patients presented with T1a, T1b, T1c, and T2a tumors, respectively. Four and 17 patients had interstitial lung disease and chronic obstructive pulmonary disease, respectively. Six patients had other respiratory disorders such as asthma or bronchiectasis, and the other six patients had a history of cardiovascular or neurovascular disease. Eleven patients with peripherally located tumor and 26 patients with centrally located tumors or tumors adjacent chest wall had received 60 Gy (relative biological effectiveness, RBE) and 50 Gy (RBE) in 4 fractions, respectively. For tumors abutted to great vessels or the proximal bronchial tree, 60-70 Gy (RBE) in 10 fractions (n = 7) or 60 Gy (RBE) in 15 or 20 fractions (n = 8) were delivered. The median follow-up time for alive patients was 20 months (range, 5-40 months). The 2-year overall survival rate was 89.7%. The estimated rates of local control (defined as the absence of infield failure) and progression-free survival at 2 years were 92.2% and 56.5%, respectively. The histology of adenocarcinoma showed a tendency for a better local control (2-year local control rate, 100% versus 86.4%, p = 0.061). A biologically effective dose of 105 Gy10 (RBE) or higher showed better 2-year local control rate, however, this was not statistically significant (94.6% versus 75.0%, p = 0.364). Nineteen patients experienced disease progression, which consisted of 4 local, 6 regional, and 15 distant failures. No grade 3 or higher toxicity was observed. The proton beam therapy for stage I NSCLC resulted in acceptable local control even in centrally located tumors.

A new concept for verifying the isocentric alignment of the proton-rotational gantry for radiation control.

The purpose of this study was to introduce the modified Winston-Lutz (mWL) test and to evaluate its feasibility. This is a new method to completely absorb the proton beam around the isocenter inside a phantom for radiation control. The mWL test was performed using a 14-cm-diameter acrylic Lucy 3D QA Phantom for a passive-scattering proton beam gantry. The energy of the unmodulated proton beam was adjusted such that the residual range was < 130mm, and the energy of the proton beam was completely lost around the isocenter. The radiation field was formed with a multi-leaf collimator at 8.6 × 8.6mm2 in the isocenter plane. The phantom was loaded with a 4-mm-diameter tungsten ball, and the EBT3 was set up at the isocenter. The proton beam was irradiated at gantry angles with 45° steps, and the isocenter deviation of the proton beam was measured and subsequently analyzed. Although the radiation field penumbra was blurred under the influence of scattered radiation due to placement in the phantom compared to the traditional WL test placed in the air, evaluation of the beam axis accuracy was possible. The results confirmed that the maximum total displacement was less than 0.9mm, and the specifications of the device were met. The mWL test is feasible and effective to reduce the building activation in proton beam treatment facilities. Thus, it can be considered a useful method that sufficiently satisfies the shielding calculation conditions.

Biological Effects of Spot Scanning and Passive Scattering Proton Beams at the Distal End of the Spread-Out Bragg Peak (SOBP) in Single Cells and Multicell Spheroids

Biological Effects of Spot Scanning and Passive Scattering Proton Beams at the Distal End of the Spread-Out Bragg Peak (SOBP) in Single Cells and Multicell Spheroids

Range optimization for target and organs at risk in dynamic adaptive passive scattering proton beam therapy – A proof of concept

PurposeThe purpose of this study was to design and develop a new range optimization for target and organs at risk (OARs) in dynamic adaptive proton beam therapy (PBT). MethodsThe new range optimization for target and OARs (RO-TO) was optimized to maintain target dose coverage but not to increase the dose exposure of OARs, while the other procedure, range optimization for target (RO-T), only focused on target dose coverage. A retrospective analysis of a patient who received PBT for abdominal lymph node metastases was performed to show the effectiveness of our new approach. The original plan (OP), which had a total dose of 60 Gy (relative biological effectiveness; RBE), was generated using six treatment fields. Bone-based registration (BR) and tumor-based registration (TR) were performed on each pretreatment daily CT image dataset acquired once every four fractions, to align the isocenter. ResultsBoth range adaptive approaches achieved better coverage (D95%) and homogeneity (D5%−D95%) than BR and TR only. However, RO-T showed the greatest increases in D2cc and Dmean values of the small intestine and stomach and exceeded the limitations of dose exposure for those OARs. RO-TO showed comparable or superior dose sparing compared with the OP for all OARs. ConclusionsOur results suggest that BR and TR alone may reduce target dose coverage, and that RO-T may increase the dose exposure to the OARs. RO-TO may achieve the planned dose delivery to the target and OARs more efficiently than the OP. The technique requires testing on a large clinical dataset.

Long-Term Follow-up of Patients Treated at a Single Institution Using a Passively Scattered Proton Beam; Observations Around the Occurrence of Second Malignancies

To investigate the occurrence of second malignancies resulting from the secondary radiation from a passively scattered proton beam. A cohort of patients with long-term follow-up was defined. All were treated at the same institution with the same proton delivery system, consisting of a 200MeV fixed, horizontal, passively scattered beam combined with a robotic chair. This setup allows for stereotactic positioning and permits fractionated treatments. The majority of patients underwent cranial or intracranial stereotactic radiation therapy. Patients with previous photon therapy or a follow-up of 24months or less were excluded. For out-of-field secondary malignancies (SMs), the observed incidence in the study population was compared to the risk of developing a malignancy in the general population, taking patient sex into account. From September 1993 to May 2016, a total of 524 patients received proton beam therapy, and 322 patients could be evaluated for this study (164 female and 158 male). Age ranged from 2 to 85years, with a median of 40years. Follow-up ranged from 25 to 276months, with a median of 150months (12.5years). During the study observation period, 7 patients had out-of-field new malignant disease. Three female patients developed a malignancy, compared with an expected incidence of 4.09 (standardized incidence ratio, 0.73 [95% confidence interval, 0.24-2.27]); 4 male patients developed a malignancy, versus an expected incidence of 3.99 (standardized incidence ratio, 1.00 [95% confidence interval, 0.38-2.67]). New intracranial disease developed in 9 patients: 8 meningiomas and 1 carcinoma. For out-of-field SMs, no increased risk of developing a variety of malignancies was observed. For in-field SMs, only 1 malignant histology was noted 15years after the original proton therapy. No SM was observed in children and young adults.

Long Term Follow Up of Patients Treated at a Single Institution using a Passively Scattered Proton Beam; Observations Around the Occurrence of Second Malignancies

To report our observations around whether any patterns of secondary malignancies occurred in patients treated at a single institution, all with the same passively scattered proton beam delivery system. We examined case records from a single national particle therapy facility offering proton and neutron therapy over a 23 year period. Proton beam treatment at the institution started in October 1993 and uses a 200 MeV fixed horizontal beam line combined with a robotic chair. The vast majority of patients was treated for intracranial and cranial lesions and positioned using the stereophotogrammetric positioning system (SPG). Follow up was achieved by way of medical records, telephone calls to patients, and home visits by social workers or community nurses. All patients with 24 or fewer months of follow up were excluded, as well as patients who had previous photon therapy. Rates of observed malignancies in the patient population were compared with expected rates, which were obtained from the national cancer statistics. We analyzed the group as a whole, and also particular sub-populations, including children who were treated with the proton therapy. From October 1993 to May 2016 a total of 524 patients received proton beam therapy, with 322 patients evaluable (164 females & 158 males). Age ranged from 2 – 85 years, with a median of 40 years. Their follow up ranged from 25 to 276 months, with a median of 150 months (12.5 years). 9 patients developed new intracranial lesions consisting of 8 meningiomas and 1 carcinoma. Eight patients had new extracranial primary malignancies. No significant increased risk was observed in the patients who received proton therapy when compared with the expected risk in the general population. 37 pediatric patients (<20 years of age) were treated. No observed second malignancies were seen in this subgroup after a median follow-up of 15 years. No patient developed a second in field malignancy, and no apparent increased risk for a second out of field malignancy was observed. This is reassuring, especially in children and young adults. A solitary patient developed an intracranial carcinoma but this followed combined modality treatment with neutrons plus a proton boost. All other observed intracranial lesions were meningiomas. The findings of this study bode well for patients treated with pencil beam scanning systems, given the lower secondary neutron dose associated with that technique.

Fruit Fly Helps Elucidate the Biological Effects of Proton Therapy: In Vivo Model of Normal Tissue Response

While the biological effects of proton beams on tumors have been well studied at the cellular and molecular levels, the effects on normal tissues have not been sufficiently investigated. Drosophila melanogaster , an organism well-suited for genetic analysis, is commonly used as a screening tool in basic medical science. To our knowledge, however, no studies have used this organism to elucidate biological aspects of proton beams. The purpose of this study was to demonstrate the usefulness of Drosophila melanogaster as a non-malignant model organism to investigate the biological effects of proton beams. Late third-instar larvae of wild-type Drosophila melanogaster (Oregon-R) were irradiated with 6-MV X rays (X group) or passive scattering proton beams at the center of the spread-out Bragg peak (P group). The larvae were exposed to single doses of 0, 10, 20, 30, 40 and 50 Gy to the total body and were observed for up to 48 hours after eclosion. All adults that subsequently emerged were collected and counted. Real-time quantitative PCR was performed to find mRNA levels of genes associated with angiogenesis, apoptosis, autophagy, inflammation and DNA repair response, using 40-Gy irradiated samples obtained at 2 or 24 hours after irradiation. The surviving fraction of flies at 48 hours after irradiation was: control (0 Gy), 0.87; 10 Gy, 0.75/0.92 (photon/proton); 20 Gy, 0.81/0.73; 30 Gy, 0.73/0.37; 40 Gy, 0.52/0.30; and 50 Gy, 0.12/0.05. Two-way ANOVA revealed significant differences between the radiation types (f1) and doses (f2); p -values were 0.023 for f1, <0.001 for f2, and 0.015 for f1f2. In the analysis of mRNA expression levels of 26 genes, remarkable differences were observed between the X and P groups in genes associated with DNA repair response such as Irbp, the homolog of Ku70 (mean number of folds changed at 2 hours, X 3.5 vs. P 8.0, p = 0.008; at 24 hours, X 3.1 vs. P 2.2, p = 0.11), Ku80 (2 hours, X 3.1 vs. P 4.9, p =0.015; 24 hours, X 2.4 vs. P 1.6, p =0.012), spn-A, the homolog of Rad51 (2 hours, X 1.3 vs. P 2.1, p =0.14; 24 hours, X 1.6 vs. P 1.4, p =0.39) and BRCA2 (2 hours, X 1.4 vs. P 2.0, p =0.23; 24 hours, X 2.1 vs. P 1.5, p =0.52). To date, this is the first study using Drosophila to investigate the biological effects of proton beams. We demonstrated the difference between photons and protons in both the surviving fractions and the levels of mRNA expression in the in vivo model. Due to the recent rapid increase of proton therapy facilities, biological evaluation from multiple aspects is needed. Since various research methods can be used for Drosophila, this experimental model may be useful in elucidating biological effects of proton therapy.

Hypofractionated Proton Beam Therapy for Centrally Located Lung Cancer

To clarify the efficacy and safety of hypofractionated proton beam therapy (PBT) for centrally located lung cancer. We retrospectively reviewed 39 patients who received hypofractionated (≧3 Gy [relative biological effectiveness: RBE] / fraction) PBT for centrally located cT1-2N0M0 (UICC 8th edition) lung cancer at one institution between 1999 and 2015. A tumor within 2 cm of the proximal bronchial tree (the distal 2 cm of the trachea, carina, main bronchi, and named major lobar bronchi up to their first bifurcation) was defined as a centrally located tumor. The median age of the included patients was 74 years (range: 48-88). Twenty-one patients (54%) had T1 disease. Sixteen patients (41%) had adenocarcinoma, eight (21%) had squamous cell carcinoma, three (8%) were diagnosed with non-small cell carcinoma, and twelve (31%) were clinically diagnosed without pathological confirmation. All patients were treated by passive scattering proton beam therapy with two or three ports. Twenty-four patients (62%) were treated with 80 Gy (RBE) in 20 fractions, whereas eight (21%) were treated with 66 Gy (RBE) in 10 fractions. The median biological equivalent dose was 112 Gy10 (range: 78-127). The median follow-up period for censored patients was 48 months (range: 4-140). The 3- and 5-year overall survival rates were 94 and 85%, respectively. The 3- and 5-year progression-free survival rates were 56 and 42%, respectively. Disease progression was noted in 22 patients (56%). The sites of the first recurrence was local in six patients (27%), regional in seven (32%), distant in seven (32%), and local and distant in two (9%). Of 13 patients who had the first recurrence in the locoregional area, only two patients (15%) received salvage treatment with radical intent. Dyspnea of grade 3 was noted in one patient (3%), and pneumonitis of grade 2 was noted in four patients (10%). No other grade 2 or more severe late adverse events were found. On multivariate analysis, T2 disease was a significant predictor of more frequent disease progression (p = 0.01; odds ratio: 13.7, 95% confidence interval: 1.8-101.6). Hypofractionated PBT for centrally located lung cancer was effective and safe.

Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer.

This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non–small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6–12 months, (ii) 12–24 months, (iii) 24–36 months, (iv) 36–48 months and (v) 48–60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383–8.). CT scans of 113 patients (median follow-up, 36 months; range, 24–137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6–62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12–21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.

Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects.

Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additional 1.5 cm clinical target volume (CTV) was treated with two or three passively-scattered proton beams to a dose of 34 Gy in 10 fractions in one week. Photographs were taken at the end of radiation, at two weeks, six weeks, and every six months thereafter. Mammography was obtained at six months after radiation and annually thereafter. All visual changes were categorized using the smallest meaningful gradations in findings and are demonstrated herein. All treatment-related mammographic findings are reported. Findings: Visual and mammographic findings showed a clear time-dependent relationship and significant variation between individuals. Peak skin reaction occurred at two to six weeks after completion of therapy. At two weeks most patients had either no visible effects and patchy erythema involving <50% of the treated skin (60%). At six weeks most patients had either patchy erythema involving <50% of the overlying skin (33%) or patchy erythema involving >50% of the treated skin (28%). Only one patient developed any moist desquamation. At six months most patients had no visible skin changes (57%) or a small, circular area of mild hyperpigmentation (33%). Mammographic changes seen at six months were regional skin thickening (40%), residual seroma (14%), localized retraction (26%), and fat necrosis (2%). A subcategorized variant on the CTCAE 4.0 was developed to foster granular recording of these findings.

Characteristics of fiber-optic radiation sensor for passive scattering proton beams

The aims of this study were to investigate the characteristics of a fiber-optic radiation sensor (FORS) that detects the fluorescence light produced by proton beam and to verify its effectiveness in proton therapy quality assurance (QA). Various characteristics of the FORS were investigated, such as the linearity of its relationships to the sensitive length of fiber for the proton beams of intermediate ranges (165.46 and 178.37 MeV) and to the measured dose, as well as its dose rate dependence. In addition, patient specific precription dose QA was conducted for five patients actually undergoing proton therapy and the results were compared with the doses measured using an ion chamber. The results show that the signal of the FORS is linearly related to the sensitive length of fiber and to the irradiated dose in the range from 1 to 500 cGy. The QA results obtained using the FORS system showed good agreement with the corresponding ion chamber results, with an average difference of 0.40% and a standard deviation of 0.35%. The FORS was dose-rate independent for proton currents up to 5 Gy/min. The profiles of various proton beams obtained using an array of FORS, which were measured as an application of the developed dosimetric system, closely agreed with the profiles acquired using EBT3 film. In summary, the experimental results of FORS demonstrated its effectiveness for use in various proton therapy QA tests.

Development of a synthetic single crystal diamond dosimeter for dose measurement of clinical proton beams

The scope of this work was to develop a synthetic single crystal diamond dosimeter (SCDD-Pro) for accurate relative dose measurements of clinical proton beams in water. Monte Carlo simulations were carried out based on the MCNPX code in order to investigate and reduce the dose curve perturbation caused by the SCDD-Pro. In particular, various diamond thicknesses were simulated to evaluate the influence of the active volume thickness (eAV) as well as the influence of the addition of a front silver resin (250 µm in thickness in front of the diamond crystal) on depth-dose curves. The simulations indicated that the diamond crystal alone, with a small eAV of just 5 µm, already affects the dose at Bragg peak position (Bragg peak dose) by more than 2% with respect to the Bragg peak dose deposited in water. The optimal design that resulted from the Monte Carlo simulations consists of a diamond crystal of 1 mm in width and 150 µm in thickness with the front silver resin, enclosed by a water-equivalent packaging. This design leads to a deviation between the Bragg peak dose from the full detector modeling and the Bragg peak dose deposited in water of less than 1.2%. Based on those optimizations, an SCDD-Pro prototype was built and evaluated in broad passive scattering proton beams. The experimental evaluation led to probed SCDD-Pro repeatability, dose rate dependence and linearity, that were better than 0.2%, 0.4% (in the 1.0–5.5 Gy min−1 range) and 0.4% (for dose higher than 0.05 Gy), respectively. The depth-dose curves in the 90–160 MeV energy range, measured with the SCDD-Pro without applying any correction, were in good agreement with those measured using a commercial IBA PPC05 plane-parallel ionization chamber, differing by less than 1.6%. The experimental results confirmed that this SCDD-Pro is suitable for measurements with standard electrometers and that the depth-dose curve perturbation is negligible, with no energy dependence and no significant dose rate dependence.

Determination of the Range and Spread-Out Bragg Peak Width of Proton Beams Using a Large-Volume Liquid Scintillator.

To determine the range, spread-out Bragg peak (SOBP) width, and output of a passive-scattering proton beam with a liquid scintillator detector, without the need for quenching correction. The depth-light profiles of 3 beam energies (140, 160, and 180 MeV) with 6 SOBP widths at each energy, produced in a 20 × 20 × 20-cm3 liquid scintillator tank, were collected by a charge-coupled device camera. By defining landmarks on the light signals, measured ranges and SOBP widths were acquired. A linear dependence was found between nominal and measured properties, and calibration factors were obtained by comparing those properties. The daily output stability and reproducibility of the liquid scintillator detector were studied by conducting 8 repeated measurements over 2 weeks in a 60Co beam. The beam ranges were determined with submillimeter accuracy without the need for any correction. The maximum difference between the measured and nominal range was 1.0 mm. The mean difference between the measured and nominal SOBP widths after correction was 0.1 mm (σ = 1.8 mm), with a maximum difference of 3.5 mm. The light output was reproducible with an SD of 0.14%. The method described here makes it possible to quickly and accurately determine the range and SOBP width of a passive-scattering proton beam in a liquid scintillator, without the need for quenching correction. In addition, the detector proved to be reliable over time, showing good output consistency with a high degree of precision.