Analysis of respiratory-induced motion trajectories of individual liver segments in patients with hepatocellular carcinoma.

PURPOSE: To analyze the respiratory-induced motion trajectories of each liver segment for hepatocellular carcinoma (HCC) to derive a more accurate internal margin and optimize treatment protocol selection. MATERIALS AND METHODS: Ten-phase-gated four-dimensional computed tomography (4DCT) scans of 14 patients with HCC were analyzed. For each patient, eight representative regions of interest (ROI) were delineated on each liver segment in all 10 phases. The coordinates of the center of gravity of each ROI were obtained for each phase, and then the respiratory motion in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions was analyzed. Two sets of motion in each direction were also compared in terms of only two extreme phases and all 10 phases. RESULTS: Motion of less than 5 mm was detected in 12 (86%) and 10 patients (71%) in the LR and AP directions, respectively, while none in the CC direction. Motion was largest in the CC direction with a maximal value of 19.5 mm, with significant differences between liver segment 7 (S7) and other segments: S1 (p < 0.036), S2 (p < 0.041), S3 (p < 0.016), S4 (p < 0.041), and S5 (p < 0.027). Of the 112 segments, hysteresis >1 mm was observed in 4 (4%), 2 (2%), and 15 (13%) in the LR, AP, and CC directions, respectively, with a maximal value of 5.0 mm in the CC direction. CONCLUSION: A significant amount of respiratory motion was detected in the CC direction, especially in S7, and S8. Despite the small effect of hysteresis, it can be observed specifically in the right lobe. Therefore, caution is required when using 4DCT to determine IM using only end-inspiration and end-expiration. Understanding the respiratory motion in individual liver segments can be helpful when selecting an appropriate treatment protocol.

Clinical outcomes and factors involved in the local control of proton beam therapy for oligometastatic liver tumors in patients with colorectal cancer.

BACKGROUND AND PURPOSE: There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate. MATERIALS AND METHODS: Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated. RESULTS: This study included 23 men and 18 women, with a median age of 66 (range 24-87) years. A total of 63 lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22 fractions. The median follow-up period was 27.6 months. The 3­year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as a factor associated with LC (P = 0.02). No grade ≥ 3 AEs were observed. None of the patients experienced liver failure during the acute or late phase. CONCLUSION: Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

Dosimetric effect of six degrees of freedom couch top with rotational setup error corrections in proton therapy.

PURPOSE: To investigate the dosimetric effect of six degrees of freedom (6DoF) couch top with rotational corrections in proton therapy (PT). METHODS: The water equivalent thickness (WET) was measured using a proton beam with a 6DoF couch top and patient immobilization base plate (PIBP) placed in front of a motorized water phantom. The accuracy verification was performed with the beam axis set perpendicular to the 6DoF couch top and tilted in 10° steps from 10° to 30°. Up to 3° rotational correction may be added during the actual treatment to correct the rotational setup error on our system. The measured and calculated values using the treatment planning system were compared. Additionally, the effect of the 3° difference was evaluated using actual measurements concerning each angle on the proton beam range. RESULTS: The WET of the 6DoF couch top and PIBP were 8.5 ± 0.1 mm and 6.8 ± 0.1 mm, respectively. The calculation and the actual measurement at each angle agreed within 0.2 mm at the maximum. A maximum difference of approximately 0.6 mm was confirmed when tilted at 3° following 30° with the 6DoF couch top plus PIBP. CONCLUSIONS: The dosimetric effect of the 6DoF couch top with rotational corrections in PT differs depending on the incidence angle on the couch top, and it increased with the increased oblique angle of incidence. However, the effect on the range was as small as 0.6 mm at the maximum. The amount of rotational correction, the angle of incidence of the beam, and the effect of rotational corrections on the proton beam range may differ depending on the structure of the couch top. Therefore, sufficient prior confirmation, and subsequent periodical quality assurance management are important.

Dosimetric impact of simulated changes in large bowel content during proton therapy with simultaneous integrated boost for locally advanced pancreatic cancer.

PURPOSE: To investigate the dosimetric impact of changes in the large bowel content during proton therapy (PT) with simultaneous integrated boost (SIB) for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Fifteen patients with LAPC were included in this study. The SIB method was performed using five fields according to our standard protocol. A total dose of 67.5 Gy(relative biological effectiveness [RBE]) was prescribed in 25 fractions using the SIB method. A dose of 45 Gy(RBE) was prescribed for the entire planning target volume (PTV) by using four main fields. The remaining 22.5 Gy(RBE) was prescribed to the PTV excluding for the gastrointestinal tract using one subfield. Five simulated doses were obtained by the forward dose calculations with the Hounsfield units (HU) override to the large bowel to 50, 0, -100, -500, and -1000, respectively. The dose-volume indices in each plan were compared using the 50 HU plan as a reference. RESULTS: At D98 of the clinical target volume (CTV) and spinal cord-D2cc , when the density of the large bowel was close to that of gas, there were significant differences compared to the reference plan (p < 0.05). By contrast, no significant difference was observed in stomach-D2cc duodenum-D2cc , small bowel-D2cc , kidneys-V18 , and liver-Dmean under any of the conditions. There were no cases in which the dose constraint of organs at risk, specified by our institution, was exceeded. CONCLUSION: Density change in the large bowel was revealed to significantly affect the doses of the CTV and spinal cord during PT with SIB for LAPC. For beam arrangement, it is important to select a gantry angle that prevents the large bowel from passing as much as possible. If this is unavoidable, it is important to carefully observe the gas image on the beam path during daily image guidance and to provide adaptive re-planning as needed.

Trend analysis of the dosimetric impact of anatomical changes during proton therapy for maxillary sinus carcinoma.

PURPOSE: Anatomical changes, such as shrinkage and aeration, can affect dose distribution in proton therapy (PT) for maxillary sinus carcinoma (MSC). These changes can affect the dose to the target and organs at risk (OARs); however, when these changes occur during PT is unclear. This study aimed to investigate the dosimetric impact of anatomical changes during PT. MATERIALS AND METHODS: Fifteen patients with MSC were enrolled in this study. Initial PT plans were generated based on initial computed tomography (CT) images. Several repeat CT images were obtained to confirm anatomical changes during PT. Evaluation PT plans were generated by copying initial PT plans to repeat CT images. The dose differences of the target and OARs were evaluated by comparing both the plans. RESULTS: At 3-4 weeks after the initiation of PT, the target volume reduced by approximately 10% as compared with the initial volume. Consequently, the target volumes gradually varied until the end of treatment. The value of V95 (volume that received 95% of the prescription dose) in the clinical target volume of the evaluation PT plan was similar to that of the initial PT plan. However, the dose to OARs, such as the contralateral optic nerve, contralateral eyeball, brainstem, and optic chiasm, increased significantly from the middle to the later phases of the treatment course. In contrast, there was a slight dose difference in the ipsilateral optic apparatus. CONCLUSION: The trend analysis in this study showed that anatomical changes appeared 3-4 weeks after the start of PT, and the dose to the OARs tended to increase. Therefore, it is recommended to check the status of tumor 3-4 weeks after the start of treatment to avoid the deterioration of dose distribution due to these changes.

The impact of different setup methods on the dose distribution in proton therapy for hepatocellular carcinoma.

PURPOSE: To investigate the impact of different setup methods, vertebral body matching (VM), diaphragm matching (DM), and marker matching (MM), on the dose distribution in proton therapy (PT) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-eight HCC lesions were studied retrospectively to assess changes in the dose distribution on two computed tomography (CT) scans. One was for treatment planning (1st-CT), and the other was for dose confirmation acquired during the course of PT (2nd-CT). The dose coverage of the clinical target volume (CTV-D98 ) and normal liver volume that received 30 Gy relative biological effectiveness (RBE) (liver-V30 ) were evaluated under each condition. Initial treatment planning on the 1st-CT was defined as reference, and three dose distributions recalculated using VM, DM, and MM on the 2nd-CT, were compared to it, respectively. In addition, the relationship between the CTV-D98 of each method and the distance between the center of mass (COM) of the CTV and the right diaphragm top was evaluated. RESULTS: For CTV-D98 , significant differences were observed between the reference and VM and DM, respectively (P = 0.013, P = 0.015). There were also significant differences between MM and VM and DM, respectively (P = 0.018, P = 0.036). Regarding liver-V30 , there was no significant difference in any of the methods, and there were no discernable difference due to the different setup methods. In DM, only two out of 34 cases with a distance from right diaphragm top to COM of CTV of 90 mm or less that CTV-D98 difference was 5% or more and CTV-D98 was worse than VM were confirmed. CONCLUSION: Although MM is obviously the most effective method, it is suggested that DM may be particularly effective in cases where the distance from right diaphragm top to COM of CTV of 90 mm or less.

The effectiveness of proton beam therapy for liver metastatic recurrence in gastric cancer patients.

OBJECTIVE: The purpose of this cross-sectional study was to evaluate the efficacy and safety of proton beam therapy for liver metastatic recurrence in gastric cancer patients. METHODS: Consecutive patients who underwent proton beam therapy from 2010 to 2015 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. Seven patients were enrolled. The median diameter of target lesions was 31 mm (13-68 mm). The most frequent dosage was 72.6 Gy equivalent in 22 fractions. The effectiveness was assessed based on the local control, overall survival and progression-free survival rates. The local control, overall survival and progression-free survival rates were calculated using the Kaplan-Meier method. Adverse events were described according to the patients' medical records. RESULTS: The median follow-up period was 41.7 months (20.7-66.3 months). The 3-year local control, overall survival and progression-free survival rates were 85.7, 68.6 and 43%, respectively. All patients completed proton beam therapy without interruption. No grade ≥3 adverse events were observed. CONCLUSIONS: Proton beam therapy might be a treatment option for patients with liver metastasis of gastric cancer.

[Conversion Surgery for Locally Advanced Unresectable Pancreatic Cancer Treated with FOLFIRINOX Therapy and Proton Beam Therapy Combined with S-1 Chemotherapy-A Case Report].

We report a case of locally advanced unresectable(UR-LA)pancreatic cancer in a patient who underwent conversion surgery after FOLFIRINOX and proton beam therapy(PBT)combined with S-1. A 68-year-old woman was referred to our hospital for a pancreatic tumor. The abdominal CT scan revealed a 40mm pancreatic body tumor with an abutment(>180°) of the celiac artery and the superior mesenteric artery. Moreover, the tumor was classified as UR-LA with a contact to the abdominal aorta. The tumor was histologically diagnosed as adenocarcinoma via an endoscopic ultrasound-guided fine-nee- dle aspiration. After 2 courses of FOLFIRINOX, PBT(50 GyE/25 Fr)combined with S-1 were administered. The tumor shrunk to 30mm at the CT scan. After 5 courses of FOLFIRINOX, the tumor reduced to 20 mm. No distant metastasis or malignant cells in abdominal washing cytology was detected using staging laparoscopy. Then, distal pancreatectomy with celiac axis resection(DP-CAR)was performed. According to the General Rules for the Study of Pancreatic Cancer(7th edition)from Japan Pancreas Society, the histological findings were suggestive of ypT3, ypN0, R0, and Grade 3 histological effect. The patient had a Grade A delayed gastric emptying post-operation. He was discharged 35 days after the surgery and has been alive without recurrence on imaging for 11 months post-operation.

[Influence and Countermeasure of Respiratory Motion on Matchline Profile of Field Matching Technique in Passive Scattering Proton Therapy for Esophageal Cancer].

This study aimed to evaluate the influence of change in respiratory motion on matchline (ML) and reduction of the effect by increasing ML levels of field matching technique in passive scattering proton therapy for esophageal cancer. To evaluate the influence of respiratory motion in terms of stability, we measured relative dose around ML using a respiratory motion phantom. The relative error was -0.5% when the respiratory motion phantom worked stable, whereas there was obvious change that the relative error was -25.5% when the difference of amplitude between upper field and lower field was one side 3 mm on each cranially and caudally direction. In clinical case of the seven esophageal cancer patients simulated by the treatment planning system, assuming the difference of amplitude was 3 mm, the relative error of maximum (minimum) dose in clinical target volume around ML against the original treatment plan were 5.8±1.2% (-6.0±2.7%), 3.3±0.9% (-3.8±1.0%), and 2.4±0.5% (2.6±0.8%) on average (±SD) when ML levels were 2, 4, and 6, respectively. Increasing ML levels can reduce the influence of respiratory motion.

Hippo pathway effector Yap promotes cardiac regeneration.

The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation and quiescence represents an important step toward potential regenerative therapies. Yes-associated protein (Yap), a transcriptional cofactor in the Hippo signaling pathway, promotes proliferation of embryonic cardiomyocytes by activating the insulin-like growth factor and Wnt signaling pathways. Here we report that mice bearing mutant alleles of Yap and its paralog WW domain containing transcription regulator 1 (Taz) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function. Cardiac-specific deletion of Yap impedes neonatal heart regeneration, resulting in a default fibrotic response. Conversely, forced expression of a constitutively active form of Yap in the adult heart stimulates cardiac regeneration and improves contractility after myocardial infarction. The regenerative activity of Yap is correlated with its activation of embryonic and proliferative gene programs in cardiomyocytes. These findings identify Yap as an important regulator of cardiac regeneration and provide an experimental entry point to enhance this process.

Particle therapy for clinically diagnosed stage I lung cancer: comparison with pathologically proven non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to present the treatment outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed as stage I non-small cell lung cancer, including a comparative analysis involving pathologically proven lung cancer (PPLC). MATERIAL AND METHODS: A total of 54 patients (57 lesions) who underwent particle therapy for IPNs were enrolled in this study. Median patient age was 76 (range 52-87) years. T-classification was: T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was delivered at total doses of 52.8-80 Gy equivalent in 4-26 fractions. The PPLC cohort included 111 patients. RESULTS: The median follow-up time was 41 (range 7-90) months. For all IPN patients, the three-year overall survival, progression-free survival, local control and distant progression-free survival rates were 90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and neuropathy (2%). No ≥grade 3 toxicities were observed. In univariate analysis, the IPN group showed significantly better survival relative to the PPLC group. However, after adjustment for baseline imbalances between these two groups in multivariate analysis, pathological confirmation did not correlate with survival. CONCLUSIONS: Particle therapy for IPNs provided favorable outcomes with minimal toxicities, which may be comparable to those for PPLC patients. Further studies are needed to clarify the optimal management of IPN patients.

Developmental capacity and implantation potential of the embryos with multinucleated blastomeres.

The presence of multinucleated blastomeres (MNBs) in embryos is associated with poor developmental competence in assisted reproductive technologies. This phenomenon is observed not only in humans but also in other animal species. The purpose of the present study was to investigate the characteristics of embryos with MNBs (MNB embryos) that could be utilized in embryo transfer. The developmental rate of MNB embryos to the blastocyst stage (50.8%) was significantly lower than that of normal embryos (73.3%) (P < 0.05). The clinical pregnancy rates of fresh embryo transfer (ET) using day 2 or day 3 embryos were significantly lower in MNB embryos (5.1%) compared with normal embryos (24.0%) (P < 0.05). In the case of frozen-thawed ET using a single vitrified/warmed blastocyst, however, the clinical pregnancy rate of MNB embryos was close to that of normal embryos (59.1% vs. 52.8%). Thus, the findings of the present study suggest that the frozen-thawed ET of MNB embryos might improve the potential for implantation followed by successful pregnancy.

Particle radiotherapy using protons or carbon ions for unresectable locally advanced head and neck cancers with skull base invasion.

OBJECTIVE: To study the oncological outcome of the patients with unresectable locally advanced primary head and neck cancers invading the skull base, treated with particle radiotherapy. METHODS: Fifty-seven patients with unresectable primary head and neck cancers invading the skull base received proton or carbon ion radiotherapy as definitive treatment at Hyogo Ion Beam Medical Center between 2003 and 2009. Forty-seven patients were treated with proton radiotherapy and 10 patients were treated with carbon ion radiotherapy. A retrospective review was performed with clinical charts and recorded imagings. RESULTS: With a median follow-up of 32 months, the 3-year actual survival and local progression-free rates of all the patients were 61 and 56%, respectively. The 3-year actual survival rates of adenoid cystic carcinoma, squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma and malignant melanoma were 83, 44, 75, 0 and 38%, respectively. The 3-year actual local control rates of adenoid cystic carcinoma, squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma and malignant melanoma were 63, 31, 83, 50 and 0%, respectively. Distant metastasis was observed in 13 of 25 patients in adenoid cystic carcinoma, two of 14 patients in squamous cell carcinoma, one of six patients with olfactory neuroblastoma, two of four patients with adenocarcinoma, three of four patients with malignant melanoma and two of three patients with undifferentiated carcinoma. Mucositis and dermatitis were seen as acute toxicities. The most common late toxicity was visual disorder. Grades 2, 3 and 4 visual disorders were observed in seven, five and two patients, respectively. CONCLUSIONS: Proton and carbon ion radiotherapy resulted in satisfactory local control in patients with locally advanced unresectable primary head and neck cancers invading the skull base.

Perinatal outcomes for transfer of blastocysts vitrified and warmed in defined solutions with recombinant human albumin: 374 babies born after 898 embryo transfers.

PURPOSE: To assess the efficacy of a novel, defined vitrification procedure using recombinant human albumin (rHA) for cryopreservation of human blastocysts. DESIGN: Retrospective study. SETTING: Private IVF clinic. PATIENTS: 1,496 patients received vitrified/warmed embryo transfer (ET). METHODS: Surplus blastocysts, and blastocysts from patients undergoing elective embryo cryopreservation, were vitrified/warmed using Cryotop carriers in homemade solutions containing either human serum albumin (HSA) or rHA. MAIN OUTCOME MEASURES: Clinical and neonatal outcomes regarding the vitrified/warmed ET procedures. RESULTS: The HSA and rHA groups had a total of 1,163 and 898 vitrified/warmed cycles, respectively. Embryo survival rates (98.7% vs. 98.9%, respectively) and the number of embryos transferred (1.08 ± 0.01 vs. 1.06 ± 0.01, respectively) were similar in the HSA and rHA groups. Clinical pregnancy rates/ET were higher (P < 0.05) in the rHA group (56.0%) than in the HSA group (51.5%). The HSA and rHA groups had similar live delivery rates/pregnancy (72.2% vs. 72.3%, respectively) and perinatal outcomes, including birth weight (2,988 ± 28 vs. 3,046 ± 26 g, respectively). Birth defects occurred in 0.9% and 1.6% of neonates in the HSA and rHA groups, respectively. CONCLUSIONS: rHA effectively replaced HSA for human embryo vitrification procedures, and yielded high rates of pregnancy and live births after vitrified/warmed ET. This new approach will support the development of defined ART systems, which will eliminate the variation and risks associated with the use of blood-derived products.

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.

Long-Term Control With Proton Beam Therapy for Recurrent Prostate Cancer in the Right Perineum Following Intensity-Modulated Radiation Therapy: A Case Report.

Radiation therapy (RT) is commonly used for the treatment of prostate cancer, with intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) being the utilized modalities. This case report outlines the treatment course of a recurrent prostate cancer lesion in the right perineal musculature managed with proton therapy following IMRT. A 64-year-old Japanese man, diagnosed with prostate cancer and categorized as high risk according to the National Comprehensive Cancer Network guidelines, underwent six months of androgen deprivation therapy, which included bicalutamide and degarelix acetate. Six months after completing 78 Gy in 39 fractions of IMRT, the patient reported perineal to anal pain. Laboratory tests showed an elevated serum prostate-specific antigen (PSA) level, and pelvic MRI showed a mass lesion in the right perineal musculature. Consequently, the patient was diagnosed with recurrent prostate cancer. Thereafter, the patient underwent eight cycles of systemic chemotherapy with docetaxel; however, his pain progressively worsened. Subsequently, the treatment was switched to 12 cycles of cabazitaxel, which led to gradual pain relief. The patient received PBT at 60 Gy relative biological effectiveness in 30 fractions for the recurrent lesion. Five years after PBT, pelvic MRI showed no mass lesions in the prostate or surrounding tissues. The PSA levels remained low, less than 0.008 ng/ml, and there were no apparent late complications.

Evaluation of Diaphragm Position Variations During Proton Therapy for Pediatric Patients With Neuroblastoma.

Background To evaluate the respiratory-induced intrafractional diaphragm motion and interfractional diaphragm displacement in pediatric patients with neuroblastoma (NBL). Materials and methods Ten pediatric patients with a mean age of 4.5 years (range: 1.8-8.7 years) with abdominal NBL treated with proton therapy (PT) have been evaluated. Intrafractional motion and interfractional displacement have been analyzed by using cine radiography and orthogonal X-ray images, respectively. In each case, the cranio-caudal positions of the diaphragm have been measured as an index. This study has investigated the possible correlations between intrafractional diaphragm motion and height. Additionally, interfractional displacement and its time trend during the treatment course have been analyzed. Results The average right and left diaphragm intrafractional motions of 8.3 mm (range: 4.4-11.5 mm) and 6.4 mm (range: 2.2-11.8 mm) were observed, respectively; however, no significant correlation has been observed with height. An interfractional displacement of 5 mm or more has been observed in 20 out of 152 fractions (13%). The average absolute value of the interfractional displacement was 2.5 mm (range: 0-8.6 mm). Interfractional displacement did not show a peculiar tendency throughout the treatment period. Conclusions It was suggested that respiratory-induced diaphragm position variation in children varies greatly among individuals, and accurately estimating it based on height is difficult. Thus, these individual evaluations are considered indispensable.

Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. RESULTS: Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. CONCLUSION: PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.

Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan.

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age: 71 years; range: 41-91 years) had PS of 0 (n = 47), 1 (n = 10), and 2 (n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n = 46), B (n = 7), and unknown (n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (n = 12), II (n = 19), III (n = 10), and IV (n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. Conclusion: PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.