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To estimate the prediction error and required internal margin provided for irregular respiratory movements.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.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.The RPM and 4DCT system has a risk of prediction error, which may result from the complicated amplitude irregularity of respiratory movement.

Background and Aim Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC. Methods Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field. Results In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6–62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred. Conclusions The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.

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.

Anesthesia is often used in proton beam therapy (PBT) for pediatric patients and this may prolong the treatment time. The aim of the study was to examine preparation of pediatric patients to allow smooth performance of PBT.Preparation was initiated 1-2days before treatment planning CT and continued for 10days. The patient first visited the facility to become familiar with the treatment room and staff. As the second step, the patient stayed in the treatment bed for a certain time with their mother, and then stayed on the treatment bed alone. Special fixtures painted with characters, music, and gifts were also prepared.From 2010 to 2014, 111 pediatric patients underwent PBT. These patients were divided into 3 groups: 40 who could follow instructions well (group A, median age: 13.6years old), 60 who could communicate, but found it difficult to stay alone for a long time (group B, median age: 4.6years old), and 11 who could not follow instructions (group C, median age: 1.6years old). Preparation was used for patients in group B. The mean treatment times in groups A, B and C were 13.6, 17.1, and 15.6min, respectively, on PBT treatment days 2-6, and 11.8, 13.0, and 16.9min, respectively, for the last 5days of PBT treatment. The time reduction was significant in group B (p=0.003).Preparation is useful for pediatric patients who can communicate. This approach allows PBT to be conducted more smoothly over a shorter treatment time.

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.

The Child-Pugh score is often used to judge the outcome of radiotherapy for hepatocellular carcinoma (HCC). The retention rate of indocyanine green 15 min after administration (ICG R15) can also be used to predict prognosis after liver resection. We evaluated the utility of ICG R15 for prediction of outcomes after proton beam therapy (PBT) for HCC.A retrospective evaluation was performed in 250 patients who received PBT between 2002 and 2007. The patients (178 males and 72 females) had a median age of 71 years (range: 43-88). Child-Pugh categories were A (score 5-6), B (7-9), and C (10-15) in 197, 51, and 2 patients, respectively. ICG scores were 0-10, 10-20, 20-30, 30-40 and ⩾40 in 27, 99, 59, 28 and 37 patients, respectively; including 26, 92, 45, 16 and 18 Child-Pugh A patients and 1, 8, 14, 11, and 17 Child-Pugh B patients, respectively. Survival times from the start of PBT were compared between Child-Pugh A and B patients, and among each ICG group.The median survival times were 61 months (95% CI: 50-72 months) in all patients, and 64 and 20 months in Child-Pugh A and B patients, respectively (p=0.001), The 3-year survival rates were 72%, 72%, 75%, 63%, and 26% in patients with ICG scores of 0-10, 10-20, 20-30, 30-40, and ⩾40 (p=0.001); 70%, 75%, 77%, 65%, and 38% in these respective groups in Child-Pugh A patients (p=0.02); and 100%, 57%, 67%, 36%, and 14% in Child-Pugh B patients (p=0.173, not significant). Multivariate analysis showed that low ICG R15 and the absence of portal vein tumor thrombus were associated with good survival.Pretreatment ICG R15 is a useful prognostic factor for prediction of outcome of PBT in HCC patients, especially in those with Child-Pugh A liver function.

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.

Introduction This study was conducted to determine disease control rates and prognostic factors associated with recurrence of centrally and peripherally located stage I NSCLC treated using high-dose PBT. Patients and Methods Seventy-four patients with 80 centrally or peripherally located stage I NSCLCs were treated with PBT. A protocol using 72.6 Gy (RBE) in 22 fractions was used for centrally located tumors, and 66 Gy (RBE) in 10 or 12 fractions was used for peripherally located tumors. Data were collected and control rates and prognostic factors for recurrence were evaluated retrospectively. Results The median follow-up period was 31.0 months. The overall survival, disease-specific survival, and progression-free survival rates were 76.7%, 83.0%, and 58.6% at 3 years, respectively. Disease recurrence was noted in 30 patients and local recurrence of 11 tumors occurred. The 3-year local control rate was 86.2% for stage IA tumors and 67.0% for stage IB tumors. Radiation dose was identified as a significant prognostic factor for disease recurrence and local recurrence. Tumor diameter and age were only significantly associated with disease recurrence. The 3-year local control rate was 63.9% for centrally located tumors irradiated with 72.6 Gy (RBE) and 88.4% for peripherally located tumors irradiated with 66 Gy (RBE). Conclusion Radiation dose was shown to be the most significant prognostic factor for tumor control in stage I NSCLC treated using high-dose PBT. Tumor diameter was not significant for local control. Further evaluation of PBT for centrally located tumors is warranted.

Background The effectiveness of proton beam therapy (PBT) as initial treatment for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is unclear, particularly as related to ICC histological subtypes. We performed this study to address this gap in knowledge. Methods Thirty-seven patients with unresectable ICC who underwent PBT as their initial treatment were evaluated. Twenty-seven patients had Child-Pugh class A liver function, 11 exhibited jaundice, and 10 had multiple tumors. Nineteen, 7, and 11 tumors were classified as mass forming (MF), periductal infiltrating (PI), and intraductal growth (IG) types, respectively, based on gross appearance in imaging studies. Patients were classified into the curative group (n = 25) and palliative group (n = 12) depending on whether the planning target volume covered all the macroscopic tumors. Results The 1- and 2-year overall survival rates were 60.3, and 41.4%, respectively; the median survival time (MST) was 15 months for all patients. The MSTs for curative and palliative groups were 25 and 7 months, respectively. Curative treatment and adjuvant chemotherapy significantly improved overall survival, while the presence of periductal infiltrating type tumors was a negative prognostic factor. In the curative group, the 1- and 2-year local control rates were 100 and 71.5%, respectively, while the 1-, and 2-year progression-free survival rates were 58.5, and 37.6%, respectively. No severe acute toxicities were observed. Three patients experienced grade 3 biliary tract infection, although it was unclear whether this was radiotherapy-related. Conclusion PBT may yield to improve survival and local tumor control among patients with unresectable ICC.

Given the growing interest in using proton beam therapy (PBT) for hepatocellular carcinoma (HCC), it is possible that transarterial chemoembolization (TACE) could be used for selected patients who have previously undergone PBT. However, these cases can be technically challenging to treat and require appropriate preparation. Thus, we aimed to identify angiographic findings in this setting. We retrospectively identified 31 patients (28 men and 3 women, mean age: 69 years, range: 43–84 years) who underwent hepatic angiography plus TACE or transarterial infusion chemotherapy (TAI) for HCC that recurred after PBT (July 2007 to June 2018). We discovered four angiographic findings, which we speculate were related to the previous PBT. 18 patients experienced recurrence in the irradiated field, and 13 patients experienced recurrence outside the irradiated field. 29 patients underwent TACE and only 2 patients underwent TAI. The mean number of previous PBT treatments was 1.3 ± 0.6 (range: 1–4). The median interval from the earliest PBT treatment to hepatic angiography was 559 days (range: 34–5,383 days), and the median interval from the latest PBT treatment to hepatic angiography was 464 days (range: 34–5,383 days). Abnormal staining of the irradiated liver parenchyma was observed in 22 patients, which obscured the angiographic tumor staining in 4 patients. Development of a tortuous tumor feeder vessel was observed in 13 patients. Development of an extrahepatic collateral pathway was observed in 7 patients. Development of an arterioportal or arteriovenous shunt was observed in 4 patients. Based on these findings, we conclude that PBT was associated with various angiographic findings during subsequent transarterial chemotherapy for recurrent HCC, and familiarity with these findings will be important in developing appropriate treatment plans.

AIM Proton beam therapy is safe and more effective than conventional radiation therapy for the local control of nodular hepatocellular carcinoma (HCC). However, evaluating therapeutic response by imaging is not accurate during the early post-irradiation period. Therefore, we examined whether the histopathological study of biopsy specimens obtained at 3 weeks after irradiation can be used to more accurately assess therapeutic response. METHODS Fifteen HCC lesions from 13 patients were treated with proton beam irradiation. Tissue biopsy samples were obtained using abdominal ultrasound-guided percutaneous fine-needle aspiration from the center of the tumor before, 3 weeks after and 1 year post-proton therapy. The specimens were examined after staining with hematoxylin-eosin (HE) and a MIB-1 antibody. RESULTS MIB-1 labeling indices (LI) before treatment were 13.0 ± 8.5% (mean ± SD; range, 0.6-27.0), whereas those 3 weeks after proton therapy were significantly reduced to 3.2 ± 2.4% (range, 0.6-8.9) (P

Background Understanding 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). Methods Image 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). Results The 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). Conclusions The 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. Institutional review board approval H28-102; July 14, 2016 approved.

Purpose To evaluate the feasibility and efficacy of repeated proton beam therapy (PBT) and to analyze the dose–volume relationship. Patients and methods A retrospective analysis was performed in 83 patients who received definitive repeated PBT. Proton beams were delivered with expiratory gating. The numbers of treatment courses were 2, 3, and 4 in 68, 12, and 3 patients, respectively. MIM software was used for dose analysis. Results The planned median total dose was 70.5 GyE for all tumors and the median doses for the 1st, 2nd, 3rd and 4th treatments were 71.0, 70.0, 70.0, and 69.3 GyE, respectively. There was no severe acute toxicity, and no radiation-induced liver dysfunction (RILD) was observed. The median overall survival (OS) period from the first PBT was 61 months (95% CI: 50–71 months), and the 2- and 5-year OS rates were 87.5% (95%CI: 80.2–94.8%) and 49.4% (95%CI: 37.6–61.2%), respectively. The maximal delivered dose to the liver ranged from 66.7 to 248.1 GyE (mean: 124.93 GyE) and the mean liver dose ranged from 5.4 to 66.5 GyE (mean: 24.23 GyE). Conclusion Repeated PBT was well tolerated and safe, even though the liver doses in many patients deviated substantially from well-known critical levels for RILD.

Objective We retrospectively elucidated the oncological outcomes, prognostic factors and toxicities of proton beam therapy in trimodal bladder-preserving therapy for muscle-invasive bladder cancer at our institution. Methods From 1990 to 2015, 70 patients with cT2–3N0M0 muscle-invasive bladder cancer underwent trimodal bladder-preserving therapy consisting of maximal transurethral resection of the bladder tumor, small pelvis photon irradiation, intra-arterial chemotherapy and proton beam therapy. The overall survival rate, progression-free survival rate, time to progression, predictive factors for progression and toxicities were analyzed. Progression was defined as when muscle-invasive recurrence, distant metastasis or upper urinary tract recurrence was observed. Results The patients’ median age was 65 (range 36–85) years. The median follow-up period was 3.4 (range 0.6–19.5) years. The 5-year cumulative overall survival rate, progression-free survival rate and time to progression rate were 82%, 77%, and 82%, respectively. In univariate and multivariate analyses, tumor multiplicity and tumor size (≥5 cm) were significant and independent factors associated with progression (hazard ratio 3.5, 95% confidence interval 1.1–12; hazard ratio 5.0, 95% confidence interval 1.3–17; P Conclusions Our bladder-preserving therapy with proton beam therapy was well tolerated and achieved a favorable mortality rate. Tumor multiplicity and tumor size were important risk factors for progression. Our findings indicate that this therapy can be an effective treatment option for selected muscle-invasive bladder cancer patients.

We describe the case of a patient with large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) who was successfully treated with two courses of proton beam therapy (PBT) followed by liver transplantation. The patient was a 69-year-old man with hepatitis C viral infection who was diagnosed with a diffuse HCC, 8 cm in size, and a PVTT that occluded the right portal vein and reached the main trunk of the portal vein. A large tumor in the right lobe and PVTT in the main and right main portal vein were treated by PBT. PVTT in the left main portal vein developed thereafter and was treated with a second course of PBT. Although the tumor was well controlled with two courses of PBT, liver function gradually deteriorated to an irreversible status 20 months after initiation of the first course of PBT. Liver transplantation was successfully performed to maintain liver function. The patient is still alive with no evidence of disease 7 years after the first course of PBT. This case shows that aggressive PBT can be used for treating advanced HCC, with subsequent liver transplantation for hepatic failure that may be caused by PBT.

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.

Between March 2003 and March 2009, five breast cancer patients with single or multiple but localized liver metastases were treated with proton beam therapy (PBT). A total dose of 66 GyE in 10 fractions or 72.6 GyE in 22 fractions was delivered, depending on tumor location. Systemic therapy was administered for more than 1 year before and after PBT. All irradiated tumors were well-controlled until last follow-up (median 33.3 months), but recurrence at other sites was observed for all patients: two patients had intrahepatic recurrence only, one patient had both intrahepatic and extrahepatic recurrence, and two patients had extrahepatic recurrence only. The median time from PBT to first recurrence was 10.8 months. PBT-related toxicity of grade 3 or greater was not observed, and additional PBT was successfully given to two patients who had single intrahepatic recurrence after initial PBT. The results indicate the usefulness of PBT for single or multiple, but localized, liver metastases in patients whose hepatic metastatic tumors are unsuitable for surgical resection or radiofrequency ablation.

Purpose To investigate the clinical features, prognostic factors, and toxicity of treatment for unresectable carcinomas of the nasal cavity and paranasal sinus (NCPS) treated with proton beam therapy (PBT). Methods and Materials Seventeen patients (13 men, 4 women) with unresectable carcinomas of the NCPS who underwent PBT at the University of Tsukuba between 2001 and 2007 were analyzed. The patients' median age was 62 years (range, 30–83 years). The tumors were located in the nasal cavity in 3 patients, the frontal sinus in 1, the ethmoid sinus in 9, and the maxillary sinus in 4. The clinical stage was Stage IVA in 5 cases, IVB in 10, and recurrent in 2. The tumors were deemed unresectable for medical reasons in 16 patients and because of refusal at a previous hospital 4 months earlier in 1 patient. All the patients received PBT irradiation dose of 22–82.5 GyE and a total of 72.4–89.6 GyE over 30–64 fractions (median 78 GyE over 36 fractions) with X-ray, with attention not exceeding the delivery of 50 GyE to the optic chiasm and brainstem. Results The overall survival rate was 47.1% at 2 years and 15.7% at 5 years, and the local control rate was 35.0% at 2 years and 17.5% at 5 years. Invasion of the frontal or sphenoid sinus was a prognostic factor for overall survival or local control. Late toxicity of more than Grade 3 was found in 2 patients (brain necrosis in 1 and ipsilateral blindness in 1); however, no mortal adverse effects were observed. Conclusion Proton beam therapy enabled a reduced irradiation dose to the optic chiasm and brainstem, enabling the safe treatment of unresectable carcinomas in the NCPS. Superior or posterior extension of the tumor influenced patient outcome.

The effectiveness of proton beam (PB) radiosurgery for large lesions is greater than for other treatment modalities. At our institute, PB radiosurgery is used to treat arteriovenous malformations (AVMs). We report the outcome of PB radiosurgery for AVMs over a period of 15 years, focusing on the efficacy of PB radiosurgery combined with embolization for AVMs ≥30 mm in diameter. We retrospectively analyzed 11 patients with AVMs ≥30 mm in diameter who were treated with PB radiosurgery between June 1990 and September 2005 at the Proton Medical Research Center of the University of Tsukuba. The mean irradiation dose was 25.3 gray-equivalent, and the mean duration of clinical follow up was 134.2 months (median 138 months). Pre-radiosurgical embolization was performed in all cases. Complete obliteration was achieved in 9 of the 11 patients. One patient experienced post-radiosurgical hemorrhage, and 1 patient experienced radiation-related aggravation of clinical symptoms due to radiation necrosis. Eight patients had excellent outcomes. The multimodal therapy approach of combining pre-radiosurgical embolization and PB radiosurgery for AVMs yielded a favorable outcome for AVMs ≥30 mm in diameter. Thus, PB radiosurgery is a viable treatment option for AVMs ≥30 mm in diameter.

Langerhans cell sarcoma (LCS), a neoplastic proliferation of Langerhans cells with malignant cytologic features, is a very rare disease. We report the case of a 62-year-old male with LCS arising in a cervical lymph node. Histologic examination of a biopsy specimen of the lymph node demonstrated a proliferation of Langerhans cells with malignant cytologic features. Immunohistochemically, the tumor cells were positive for S-100 protein, CD1a, and Langerin (CD207). These histomorphological findings supported the diagnosis of LCS. The patient underwent radiotherapy. Neither local recurrence nor distant metastasis was observed at 45 months after radiotherapy. Characteristic immunohistochemical findings were helpful to identify LCS, and head and neck surgeons should be aware of this rare disease entity.

Purpose In markerless tumor tracking using X-ray fluoroscopic images for image-guided radiation therapy (IGRT), robustness against mistracking is important. Mistracking is primarily caused by bone structures projected on fluoroscopic images because they generally hide tumor features. We devised a real-time tumor-tracking method. The novelty of this method is to control “importance recognition” in computers, i.e., controlling recognition of image features that are important or unimportant for tumor tracking. This study demonstrates the feasibility of our method using clinical X-ray fluoroscopic images. Methods The strategy of our method was to utilize different positional co-occurrence probabilities in training images for supervised deep learning. A bone digitally reconstructed radiograph (DRR) was randomly overlapped on a soft-tissue DRR to create training images for deep learning, which established positional decorrelation between the bone feature and ground truth, indicating tumor position and shape. As the training of deep learning processed, this decorrelation induced the computer recognition that the bone feature was unimportant for tumor tracking. Moreover, this method was fully optimized for a patient because DRRs were created from patient-specific CT data only, unlike a general medical application of deep learning such as diagnosis that uses a massive amount of patient data. Results The accuracy of lung tumor tracking was within approximately 1 mm although the low-visible tumor and spine were overlapped on X-ray fluoroscopic images. Conclusions Feasibility of robust tumor tracking by our method was demonstrated. This method can be expected as a breakthrough technique that can contribute to the robust and safe implementation of markerless tumor tracking for radiation therapy in future.

To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70–90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62–98 GyE). Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9–30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6–36.3). The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.

The objective of this study was to assess the ability to detect pancreatic metastasis of lung cancer and to clarify the degree of fluorodeoxyglucose (FDG) accumulation and computed tomography (CT) characteristics of pancreatic metastasis from lung cancer.A total of 573 patients (415 men and 158 women) with lung cancer were retrospectively evaluated. All patients underwent FDG-positron emission tomography (PET)/CT with contrast-enhanced CT for first=stage (313 patients; initial study group) or follow-up study (260 patients; follow-up study group). A lesion was regarded as positive for metastasis on the basis of visual judgment of the degree of increased metabolism by two experienced and independent interpreters, supported by semiquantitative evaluation on the basis of calculation of the maximum standardized uptake value (SUV(max)).Abnormal accumulations in the pancreas were detected in 5 of 313 patients (1.60%) in the initial study group, and 6 of 260 patients (2.31%) in the follow-up study group. Seven of these patients had adenocarcinoma, three had small cell carcinoma, and the rest had large cell endocrine carcinoma. Tumor sizes (longitudinal diameter), measured by CT, of these 11 patients ranged from 6 mm to 52 mm (mean +/- SD 8.3 mm +/- 11.9 mm), and SUV(max) for 1 h ranged from 3.37 to 11.1 (mean +/- SD 6.12 +/- 2.43). Three of these pancreatic lesions were difficult to determine by routine transaxial images, and detection was obvious only by thin-slice images or multiplanar reconstruction images. Contrast-enhanced CT showed gradual fill-in from the peripheral portion to the center. In addition, 10 of 11 cases did not show main pancreatic duct dilatation even if the tumor size was large.Metastases to the pancreas in lung cancer patients are not so rare and radiologists first have an important role to detect the pancreatic mass and then suggest to metastasis as the likely diagnosis. For this purpose, FDG-PET/CT has an advantage in depicting unsuspected pancreatic metastasis from lung cancer, particularly that which is not detected by CT alone.

To evaluate the safety and efficacy of postoperative proton beam therapy (PBT) combined with nimustine hydrochloride (ACNU) or temozolomide (TMZ) for glioblastoma multiforme (GBM). The subjects were 46 patients with GBM who were treated with high dose (96.6 GyE) PBT. There were 24 males and 22 females, and the median age was 58 years old (range 24–76). The Karnofsky performance status was 60, 70, 80, 90 and 100 in 5, 10, 12, 11 and 8 patients, respectively. Total resection, partial resection, and biopsy were performed for 31, 14 and 1 patients, respectively. Photon beams were delivered to high intensity areas on T2-weighted magnetic resonance imaging (MRI) in the morning (50.4 Gy in 28 fractions). More than 6 h later, PBT was delivered to the enhanced area plus a 10 mm margin in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume in the second half (23.1 GyE in 14 fraction). Concurrent chemotherapy with ACNU during weeks 1 and 4 or daily TMZ was administered in 23 and 23 patients, respectively. The overall 1 and 2 year survival rates were 82.6 and 47.6 %, respectively. Median survival was 21.1 months (95 % CI 13.1–29.2), with no significant difference in survival between the ACNU and TMZ groups. The patient characteristics were similar in the two groups. Late radiation necrosis occurred in 11 patients (six ACNU, five TMZ), but was controlled by necrotomy and therapy including bevacizumab. PBT concurrent with ACNU or TMZ was tolerable and beneficial for carefully selected patients with GBM.

Purpose The aim of this phase II study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the nasal cavity and para-nasal sinuses. Materials and methods N0M0 mucosal melanoma of the nasal cavity and para-nasal sinuses were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60GyE in 15 fractions. Primary endpoint was local control rate at 1year after treatment. Based on the results of a pilot study, the local control rate was estimated at 75%. Results Thirty-two patients were enrolled from June 2008 through October 2012. Patient characteristics were as follows: median age 73years (range, 36–89years); male/female ratio, 12/20; and T stage 3/4, 11/21. Local control rate at 1year was 75.8% (95% CI: 63.8–92.4%). With a median follow-up period of 36.4months, 3-year overall survival rate was 46.1%. The most frequent pattern of first failure was distant metastasis. The main cause of death was cancer death due to distant metastases (93.3%). Conclusions Proton beam therapy showed sufficient local control benefits for mucosal melanoma as an alternative treatment of surgery.

The aim of the present study was to evaluate the outcomes of proton beam therapy (PBT) concurrently combined with chemotherapy consisting of cisplatin and 5-fluorouracil for esophageal cancer.Forty consecutive patients (stage I in 16 patients, II in 9 and III in 15) treated between 2008 and 2012 were evaluated. A total dose of 60 Gray equivalents (GyE) in 30 fractions was delivered, and an additional boost of 4-10 GyE was given when residual tumors were suspected. The median follow-up time was 24 months (range=7-66 months).No cardio-pulmonary toxicities of grade 3 or higher were observed. Recurrences were observed in 16 patients, and the 2-year rates of disease-specific survival and locoregional control were 77% and 66%, respectively.Irrespective of the small sample size and short follow-up time of the study, proton beam therapy combined with chemo therapy seems to be feasible for esophageal cancer.

Charged particles such as protons and carbon-ions offer advantageous physical properties to radiation therapy (RT) for the treatment of various cancers when compared with photons, because they exhibit a spread-out Bragg peak, and may be utilized to achieve a desirable dose distribution to the target volume by using specified beam modulation. Interestingly, the cytocidal effect of protons is almost equal to that of photons, because both protons and photons are considered low-linear energy transfer radiations. Hence, proton beam therapy (PBT) is an attractive RT option, especially in the treatment of locally advanced cancers, as irradiation doses can be safely escalated while sparing the surrounding normal tissues, and because PBT may be concurrently combined with chemotherapy for treating such cancers. Recent advances in PBT techniques including a spot scanning method, as well as an increase in the number of particle therapy institutes are anticipated to yield favorable results through future multi-institutional prospective studies. The University of Tsukuba has carried out several studies to validate the effectiveness of PBT for many types of cancers since 1983. Here, we present our findings on the clinical outcomes of PBT for esophageal cancer, non-small cell lung cancer, intrahepatic biliary tract cancer, pancreas cancer, and bladder cancer; future aspects of PBT concurrently combined with chemotherapy for treating locally advanced cancers are also discussed.

Purpose To present the results of proton beam therapy for patients with esophageal cancer. Methods and materials This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1–87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75–89.5 Gy). Results The 5-year actuarial survival rate for the 46 patients, patients with T1 ( n = 23), and those with T2–T4 ( n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2–T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2–T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. Conclusion The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

Purpose: To evaluate the clinical results of proton radiotherapy for patients with non–small-cell lung cancer (NSCLC). Methods and Materials: Between 1983 and 2000, 51 NSCLC patients were treated with proton beams at the University of Tsukuba. There were 28 patients in Stage I, 9 in Stage II, 8 in Stage III, 1 in Stage IV, and 5 with recurrent disease. Thirty-three patients had squamous cell carcinoma, 17 had adenocarcinoma, and 1 had large-cell carcinoma. Median fraction and total doses given were 3.0 Gy (range 2.0 – 6.0 Gy), and 76.0 Gy (range 49.0 –93.0 Gy), respectively. Results: The 5-year overall survival rate was 29% for all patients, 70% for 9 Stage IA patients, and 16% for 19 Stage IB patients, respectively (IA vs. IB: p < 0.05). The 5-year in-field local control rate was higher in patients with Stage IA (89%) when compared with those with Stage IB (39%). Forty-seven patients (92%) experienced acute lung toxicity of Grade 1 or less; 3 had Grade 2, 1 had Grade 3, and none experienced Grade 4 or higher. Patients in the present series showed very little late toxicity. Conclusion: Proton therapy is a very safe and effective treatment for patients with NSCLC, especially for those with early stages. The relative merit of proton therapy in comparison with stereotactic photon radiotherapy or three-dimensional conformal photon radiotherapy remains to be defined through future clinical trials. © 2003 Elsevier Inc.

Background. The purpose of this study was to compare a very-high-flow injection-rate method (group A) and a conventional injection-rate method (group B) for visualization of upper abdominal arteries by multidetector helical computed tomography (MDHCT).Methods. The subjects were 240 patients suspected to have abdominal lesions. They were randomly assigned to group A (120 patients) and group B (120 patients). In group A, the bilateral medial cubital veins were punctured, and contrast medium was infused at a rate of 8.6–9.6ml/s. In group B, the unilateral medial cubital vein was punctured, and contrast medium was infused at a rate of 2.0–3.0ml/s. The quality of vascular visualization was graded as poor, good, or excellent by three radiologists.Results. All visualizations of the celiac trunk (CE) and superior mesenteric artery (SMA) were graded as excellent in both group A and group B. Visualization grades of the subsegmental branches of the hepatic artery (HA), right gastric artery (RGA), cystic artery, dorsal pancreatic artery (DPA), and superior pancreaticoduodenal artery (SPDA) were good or excellent in 75% (paging method)/53.3% (three-dimensional method), 85%/30%, 77.7%/18.3%, 76.7%/28.3%, and 88.3%/42.5%, respectively, in group A, and 33.3%/ 11.7%, 46.7%/3.4%, 41.6%/5%, 55%/4.2%, and 72.5%/ 14.2%, respectively, in group B. The appearance rate of intrahepatic portal branches was 28.3% in group A and 66.7% in group B in the arterial dominant phase.Conclusion. Group A showed better visualization results than Group B in upper abdominal arteries according to MDHCT.

Breast cancer is the most common cancer among women in developed countries. Generally, 70% of primary breast cancer patients express estrogen receptor, thus endocrine therapy is often efficient for the disease using antiestrogen such as tamoxifen as well as aromatase inhibitor. During long-term therapy, however, a substantial proportion of women recurrent and acquire resistance to endocrine therapy. Understanding of the mechanism underlying acquired endocrine resistance would be a first step toward overcoming hormone-refractory cancer. In this study, we identified candidate genes that contributed to tamoxifen resistance in MCF-7 breast cancer cells by functional screening based on short hairpin RNA (shRNA) library. We found that several candidate genes were overexpressed in breast cancer patients and their abundance was positively associated with poor prognosis of cancer patients in clinical database. Moreover, the genes associated with poor prognosis also showed positive association with shorter survival for patients treated with tamoxifen. Expression levels of these candidate genes were upregulated in hydroxytamoxifen (OHT)-resistant MCF-7 cells (OHTR) compared with parental cells. Proliferation of OHTR cells was repressed by siRNAs targeting 26S subunits, non-ATPase 1 (PSMD1) and tetraspanin12 (TSPAN12). Furthermore, knockdown of PSMD1 inhibited cell cycle progression and p53 protein degradation. p21 and 14-3-3σ, target genes of p53, were upregulated by PSMD1 knockdown. These findings would be used for the development of alternative diagnostic and therapeutic options for endocrine-resistant breast cancers. Citation Format: Toshiyuki Okumura, Kazuhiro Ikeda, Wataru Sato, Kuniko Horie-Inoue, Satoshi Inoue, Satoru Takeda, Koji Okamoto. Proteasome subunit PSMD1 participates in p53 degradation and regulates proliferation of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3611. doi:10.1158/1538-7445.AM2017-3611

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.

Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC.Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field.In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6-62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred.The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.

Androgen receptor is a primary transcription factor involved in the proliferation of prostate cancer cells. Thus, hormone therapy using antiandrogens, such as bicalutamide, is a first-line treatment for the disease. Although hormone therapy initially reduces the tumor burden, many patients eventually relapse, developing tumors with acquired endocrine resistance. Elucidation of the molecular mechanisms underlying endocrine resistance is therefore a fundamental issue for the understanding and development of alternative therapeutics for advanced prostate cancer. In the present study, we performed short hairpin RNA (shRNA)-mediated functional screening to identify genes involved in bicalutamide-mediated effects on LNCaP prostate cancer cells. Among such candidate genes selected by screening using volcano plot analysis, ribosomal protein L31 (RPL31) was found to be essential for cell proliferation and cell-cycle progression in bicalutamide-resistant LNCaP (BicR) cells, based on small interfering RNA (siRNA)-mediated knockdown experiments. Of note, RPL31 mRNA is more abundantly expressed in BicR cells than in parental LNCaP cells, and clinical data from ONCOMINE and The Cancer Genome Altas showed that RPL31 is overexpressed in prostate carcinomas compared with benign prostate tissues. Intriguingly, protein levels of the tumor suppressor p53 and its targets, p21 and MDM2, were increased in LNCaP and BicR cells treated with RPL31 siRNA. We observed decreased degradation of p53 protein after RPL31 knockdown. Moreover, the suppression of growth and cell cycle upon RPL31 knockdown was partially recovered with p53 siRNA treatment. These results suggest that RPL31 is involved in bicalutamide-resistant growth of prostate cancer cells. The shRNA-mediated functional screen in this study provides new insight into the molecular mechanisms and therapeutic targets of advanced prostate cancer.

Total skin electron beam is a specialized technique that involves irradiating the entire skin from the skin surface to only a few millimetres in depth. In the Stanford technique, the patient is in a standing position and six different directional positions are used during treatment. Our technique uses large electron beams in six directions with an inclinable couch on motorized table and a compensating filter was also used to spread the electron beam and move its intensity peak. Dose uniformity measurements were performed using Gafchromic films which indicated that the surface dose was 2.04 ± 0.05 Gy. This technique can ensure the dose reproducibility because the patient is fixed in place using an inclinable couch on a motorized table.

The aim of this study was to evaluate the efficacy of proton beam therapy for pediatric patients with ependymoma.Proton beam therapy was conducted for six patients (three boys and three girls; age, 2-6 years; median, 5 years) with ependymoma. The tumors were WHO grades 2 and 3 in two and four patients, respectively. All patients underwent surgery (subtotal and gross total resection in three patients each) and proton beam therapy at doses of 50.4-61.2 GyE (median, 56.7 GyE). The mean doses to normal brain tissue in proton beam therapy and photon radiotherapy were simulated using the same treatment planning computed tomography images.All patients completed the planned irradiation. The follow-up period was 13-44 months (median, 24.5 months) from completion of proton beam therapy and all patients were alive at the end of this period. Local recurrence in the treatment field occurred in one patient at 4 months after proton beam therapy at 50.4 GyE. Alopecia and mild dermatitis occurred in all patients, but there was no severe toxicity. One patient had a once-off seizure after proton beam therapy and alopecia persisted in another patient for 31 months, but no patients had difficulty with daily life. The simulation showed that proton beam therapy reduces the dose to normal brain tissue by approximately half compared with photon radiotherapy.Proton beam therapy for pediatric ependymoma is safe, does not have specific toxicities, and can reduce irradiation of normal brain tissue.

Surgical resection is the first choice for treatment of a thymic carcinoid tumor and radiotherapy is often performed as adjuvant therapy. Here, we report a case of an unresectable and chemoresistant thymic carcinoid tumor that was treated successfully using standalone proton beam therapy (PBT). The patient was a 66-year-old woman in whom surgical resection of the tumor was impossible because of cardiac invasion. Therefore, chemotherapy was administered. However, the tumor grew to 15 cm in diameter and she developed severe superior vena cava (SVC) syndrome. She was referred to our hospital and received PBT at a dose of 74 GyE in 37 fractions. PBT was conducted without severe early toxicities. After PBT, the tumor mildly shrunk to 13 cm in diameter and SVC syndrome almost disappeared. Subsequently, the tumor has continued to decrease in size slowly over the last 2 years and late toxicities have not been observed. Our experience with this case suggests that PBT may be effective for an unresectable thymic carcinoid tumor.

Recent advance in the field of radiation oncology, especially in medical physics for radiation therapy (RT), has considerably improved treatment outcomes of various cancers including prostate cancer with regard to both of tumor control and morbidity. Three-dimensionally conformal RT with image-guided radiotherapeutic modalities for accurate tumor localization, such as brachytherapy, intensity-modulated radiation therapy (IMRT), and charged particle beam RT can thereby deliver a large dose to the tumor and allow the sparing of surrounding normal tissues. It is thought that prostate cancer is one of representative cancers which have been treated with RT as a curative intent and benefited from novel conformal RT techniques. Because the number of prostate cancer patients has been increasing year by year in Japan as results from wide spread of PSA screening and rapid change in life style, RT has been recently playing much more important roles in the curative treatment for patients with prostate cancer. Hence, we will review the outcomes of RT for prostate cancer and introduce the benefit of modern RT modalities from clinical aspect. In addition, our future prospect to further yield better disease control with minimum morbidity compared with present RT will be also mentioned in the report.

We have carried out a study involving a model for the diffusion mechanism of group III atoms in an InGaN alloy semiconductor that uses a cell dynamical system (CDS) approach. In this CDS analysis, we focused on gathering information concerning the In-rich region with a dot-like structure that is formed at an early stage in the time evolution of phase separation of this alloy. A similar dot-like structure is known to appear in the active layer of InGaN-based multiquantum well laser diodes. Thus, we can determine the diffusion coefficient of group III atoms in InGaN by comparing the dot-like structures observed by cross-sectional transmission electron microscopy with those obtained by the CDS numerical approach. In order to perform this comparison quantitatively such that we could use it to calculate the diffusion coefficient, we derived a relationship between the rule of mapping used in CDS, and the discretization of the Cahn–Hilliard–Cook equation, which describes the dynamics of phase separation with a c...