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Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.

Background\\nUnderstanding the irradiated area and dose correctly is important for the reirradiation of organs that deform after irradiation, such as the liver. We investigated the spatial registration error using the deformable image registration (DIR) software products MIM Maestro (MIM) and Velocity AI (Velocity).\\n\\nMethods\\nImage registration of pretreatment computed tomography (CT) and posttreatment CT was performed in 24 patients with liver tumors. All the patients received proton beam therapy, and the follow-up period was 4–14 (median: 10) months. We performed DIR of the pretreatment CT and compared it with that of the posttreatment CT by calculating the dislocation of metallic markers (implanted close to the tumors).\\n\\nResults\\nThe fiducial registration error was comparable in both products: 0.4–32.9 (9.3 ± 9.9) mm for MIM and 0.5–38.6 (11.0 ± 10.0) mm for Velocity, and correlated with the tumor diameter for MIM (r = 0.69, P = 0.002) and for Velocity (r = 0.68, P = 0.0003). Regarding the enhancement effect, the fiducial registration error was 1.0–24.9 (7.4 ± 7.7) mm for MIM and 0.3–29.6 (8.9 ± 7.2) mm for Velocity, which is shorter than that of plain CT (P = 0.04, for both).\\n\\nConclusions\\nThe DIR performance of both MIM and Velocity is comparable with regard to the liver. The fiducial registration error of DIR depends on the tumor diameter. Furthermore, contrast-enhanced CT improves the accuracy of both MIM and Velocity.

The purpose of this study was to compare the parameters of the dose–volume histogram (DVH) between proton beam therapy (PBT) and X-ray conformal radiotherapy (XCRT) for locally advanced non-small-cell lung cancer (NSCLC), according to the tumor conditions. A total of 35 patients having NSCLC treated with PBT were enrolled in this analysis. The numbers of TNM stage and lymph node status were IIB ( n = 3), IIIA ( n = 15) and IIIB ( n = 17), and N0 ( n = 2), N1 ( n = 4), N2 ( n = 17) and N3 ( n = 12), respectively. Plans for XCRT were simulated based on the same CT, and the same clinical target volume (CTV) was used based on the actual PBT plan. The treatment dose was 74 Gy-equivalent dose (GyE) for the primary site and 66 GyE for positive lymph nodes. The parameters were then calculated according to the normal lung dose, and the irradiation volumes of the doses (Vx) were compared. We also evaluated the feasibility of both plans according to criteria: V5 ≥ 42%, V20 ≥ 25%, mean lung dose ≥ 20 Gy. The mean normal lung dose and V5 to V50 were significantly lower in PBT than in XCRT. The differences were greater with the more advanced nodal status and with the larger CTV. Furthermore, 45.7% of the X-ray plans were classified as inadequate according to the criteria, whereas 17.1% of the proton plans were considered unsuitable. The number of inadequate X-ray plans increased in cases with advanced nodal stage. This study indicated that some patients who cannot receive photon radiotherapy may be able to be treated using PBT.

Introduction It was reported that proton beam therapy (PBT) reduced the normal brain dose compared with X-ray therapy for pediatric brain tumors. We considered whether there was not the condition that PBT was more disadvantageous than intensity modulated photon radiotherapy (IMRT) and 3D conventional radiotherapy (3D-CRT) for treatment of pediatric brain tumors about the dose reduction for the normal brain when the tumor location or tumor size were different. Methods The subjects were 12 patients treated with PBT at our institute, including 6 cases of ependymoma treated by local irradiation and 6 cases of germinoma treated by irradiation of all four cerebral ventricles. IMRT and 3D-CRT treatment plans were made for these 12 cases, with optimization using the same planning conditions as those for PBT. Model cases were also compared using sphere targets with different diameters or locations in the brain, and the normal brain doses with PBT, IMRT and 3D-CRT were compared using the same planning conditions. Results PBT significantly reduced the average dose to normal brain tissue compared to 3D-CRT and IMRT in all cases. There was no difference between 3D-CRT and IMRT. The average normal brain doses for PBT, 3D-CRT, and IMRT were 5.1–34.8% (median 14.9%), 11.0–48.5% (23.8%), and 11.5–53.1% (23.5%), respectively, in ependymoma cases; and 42.3–61.2% (48.9%), 54.5–74.0% (62.8%), and 56.3–72.1% (61.2%), respectively, in germinoma cases. In the model cases, PBT significantly reduced the average normal brain dose for larger tumors and for tumors located at the periphery of the brain. Conclusion PBT reduces the average dose to normal brain tissue, compared with 3D-CRT and IMRT. The effect is higher for a tumor that is larger or located laterally.

Purpose: The purpose of this study is to evaluate the effects of cone-beam computed tomography (CBCT) on dose distribution and normal tissue complication probability (NTCP) by constructing a comprehensive dose evaluation system for prostate intensity-modulated radiation therapy (IMRT). Methods: A system that could combine CBCT and treatment doses with MATLAB was constructed. Twenty patients treated with prostate IMRT were studied. A mean dose of 78 Gy was prescribed to the prostate region, excluding the rectal volume from the target volume, with margins of 4 mm to the dorsal side of the prostate and 7 mm to the entire circumference. CBCT and treatment doses were combined, and the dose distribution and the NTCP of the rectum and bladder were evaluated. Results: The radiation dose delivered to 2% and 98% of the target volume increased by 0.90 and 0.74 Gy on average, respectively, in the half-fan mode and on average 0.76 and 0.72 Gy, respectively, in the full-fan mode. The homogeneity index remained constant. The percent volume of the rectum and bladder irradiated at each dose increased slightly, with a maximum increase of <1%. The rectal NTCP increased by approximately 0.07% from 0.46% to 0.53% with the addition of a CBCT dose, while the maximum NTCP in the bladder was approximately 0.02%. Conclusions: This study demonstrated a method to evaluate a combined dose of CBCT and a treatment dose using the constructed system. The combined dose distribution revealed increases of <1% volume in the rectal and bladder doses and approximately 0.07% in the rectal NTCP.

There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau region (RBEplateau) and the OER value were calculated from the doses corresponding to 10% survival data. Under the normoxic condition, the RBEplateau was 1.00, 0.99 and 1.09 for positions B, C and D, respectively. Under the hypoxic condition, the RBEplateau was 1.10, 1.06 and 1.12 for positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for positions A, B, C and D, respectively. There were no significant differences in either the RBEplateau or the OER between these three positions within the SOBP. In conclusion, biological homogeneity need not necessarily be taken into account for treatment planning for proton beam therapy at the University of Tsukuba.

To investigate the reproducibility of computed tomography (CT) imaging quality in respiratory-gated radiation treatment planning is essential in radiotherapy of movable tumors. Seven series of regular and six series of irregular respiratory motions were performed using a thorax dynamic phantom. For the regular respiratory motions, the respiratory cycle was changed from 2.5 to 4 s and the amplitude was changed from 4 to 10 mm. For the irregular respiratory motions, a cycle of 2.5 to 4 or an amplitude of 4 to 10 mm was added to the base data (i.e. 3.5-s cycle, 6-mm amplitude) every three cycles. Images of the object were acquired six times using respiratory-gated data acquisition. The volume of the object was calculated and the reproducibility of the volume was decided based on the variety. The registered image of the object was added and the reproducibility of the shape was decided based on the degree of overlap of objects. The variety in the volumes and shapes differed significantly as the respiratory cycle changed according to regular respiratory motions. In irregular respiratory motion, shape reproducibility was further inferior, and the percentage of overlap among the six images was 35.26% in the 2.5- and 3.5-s cycle mixed group. Amplitude changes did not produce significant differences in the variety of the volumes and shapes. Respiratory cycle changes reduced the reproducibility of the image quality in respiratory-gated CT.

Purpose To estimate the prediction error and required internal margin provided for irregular respiratory movements. Materials and methods Twenty-eight patterns of irregular movement were prepared using a moving phantom. For irregular cycle movement, a cycle of 2.0–5.0 s was inserted into the baseline movement data (3.5-s cycle, 6-mm amplitude) every four cycles. In addition, a cycle of 2.5–4.5 s was further inserted into one of the irregular data points every four cycles to produce more complicated irregularity. For irregular amplitude movement, an amplitude of 3.0–9.0 mm was inserted into the baseline respiratory movement data. In addition, an amplitude of 4.0–8.0 mm was further inserted into one of the irregular data points every four cycles to produce more complicated irregularity. Images of the moving target were acquired using a real-time position management (RPM) and four-dimensional CT (4DCT) system. The displacement from the baseline image and required margin to compensate for irregular movement were calculated. Results Amplitude irregularity tended to lose stable placement and need larger margins to compensate for the reduction of image reproducibility than cycle irregularity. There was a large displacement and required margin when the target moved with more complicated irregular amplitude. Conclusion The RPM and 4DCT system has a risk of prediction error, which may result from the complicated amplitude irregularity of respiratory movement.

Background Proton-beam therapy (PBT) provides therapeutic advantages over conformal x-ray therapy in sparing organs at risk when treating esophageal cancer because of the fundamental physical dose distribution of the proton-beam. However, cases with extended esophageal lesions are difficult to treat with conventional PBT with a single isocentric field, as the length of the planning target volume (PTV) is longer than the available PBT field size in many facilities. In this study, the feasibility of a practical technique to effectively match PBT fields for esophageal cancer with a larger regional field beyond the available PBT field size was investigated. Methods Twenty esophageal cancer patients with a larger regional field than the available PBT single-field size (15 cm in our facility) were analyzed. The PTV was divided into two sections to be covered by a single PBT field. Subsequently, each PTV isocenter was aligned in a cranial-caudal (CC) axis to rule out any influence by the movement of the treatment couch in anterior-posterior and left-right directions. To obtain the appropriate dose distributions, a designed-seamless irradiation technique (D-SLIT) was proposed. This technique requires the following two adjustments: (A) blocking a part of the PTV by multi-leaf collimator(s) (MLCs); and (B) fine-tuning the isocenter distance by the half-width of the MLC leaf (2.5 mm in our facility). After these steps, the inferior border of the cranial field was designed to match the superior border of the caudal field. Dose distributions along the CC axis around the field junction were evaluated by the treatment-planning system. Dose profiles were validated with imaging plates in all cases. Results The average and standard deviation of minimum dose, maximum dose, and dose range between maximum and minimum doses around the field junction by the treatment-planning system were 95.9 ± 3.2%, 105.3 ± 4.1%, and 9.4 ± 5.2%. The dose profile validated by the imaging plate correlated with the results of the treatment-planning system in each case, with an error range within 4.3%. Conclusions Dose distributions around the field junction were applied using D-SLIT. D-SLIT can be a useful treatment strategy for PBT of extended esophageal cancer.

Charged particle therapy depends on biological information for the dose prescription. Relative biological effectiveness or RBE for this requirement could basically be provided by experimental data. As RBE values of protons and carbon ions depend on several factors such as cell/tissue type, biological end-point, dose and fractionation schedule, a single RBE value could not deal with all different radiosensitivities. However, any biological model with accurate reproducibility is useful for comparing biological effectiveness between different facilities. We used mouse gut crypt survivals as endpoint, and compared the cell killing efficiency of proton beams at three Japanese facilities. Three Linac X-ray machines with 4 and 6 MeV were used as reference beams, and there was only a small variation (coefficient of variance < 2%) in biological effectiveness among them. The RBE values of protons relative to Linac X-rays ranged from 1.0 to 1.11 at the middle of a 6-cm SOBP (spread-out Bragg peak) and from 0.96 to 1.01 at the entrance plateau. The coefficient of variance for protons ranged between 4.0 and 5.1%. The biological comparison of carbon ions showed fairly good agreement in that the difference in biological effectiveness between NIRS/HIMAC and GSI/SIS was 1% for three positions within the 6-cm SOBP. The coefficient of variance was < 1.7, < 0.6 and < 1.6% for proximal, middle and distal SOBP, respectively. We conclude that the inter-institutional variation of biological effectiveness is smaller for carbon ions than protons, and that beam-spreading methods of carbon ions do not critically influence gut crypt survival.