Impact of proficiency in the transcatheter aortic valve implantation procedure on clinical outcomes: a single center retrospective study.

BACKGROUND: We used transcatheter aortic valve implantation (TAVI) procedure time to investigate the association between surgical team maturity and outcome. METHODS: Among patients who underwent TAVI between October 2015 and November 2019, those who had Sapien™ implanted with the transfemoral artery approach were included in the analysis. We used TAVI procedure time and surgery number to draw a learning curve. Then, we divided the patients into two groups before and after the number of cases where the sigmoid curve reaches a plateau. We compared the two groups regarding the surveyed factors and investigated the correlation between the TAVI procedure time and survey factors. RESULTS: Ninety-nine of 149 patients were analysed. The sigmoid curve had an inflection point in 23.2 cases and reached a plateau in 43.0 cases. Patients in the Late group had a shorter operating time, less contrast media, less radiation exposure, and less myocardial escape enzymes than the Early group. Surgical procedure time showed the strongest correlation with the surgical case number. CONCLUSION: The number of cases required for surgeon proficiency for isolated Sapien™ valve implantation was 43. This number may serve as a guideline for switching the anesthesia management of TAVI from general to local anesthesia.

Analysis of Antipsychotic Dosage in Patients With Tardive Dyskinesia: A Case-Control Study Using the Claims Database of the Corporate Health Insurance Association.

PURPOSE: This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020. METHODS: The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age. RESULTS: The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively. CONCLUSIONS: In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.

Does childhood maltreatment affect hikikomori via traits of modern-type depression?

BACKGROUND: In the 1990s, the concepts of hikikomori and modern-type depression (MTD) emerged in Japan. Hikikomori is a condition of social avoidance or isolation, characterized by staying at home and being physically isolated for at least six months. MTD is characterized by depressive symptoms-mainly in stressful work or school situations during adolescence and early adulthood-which tend to rapidly reduce or disappear after leaving the stressful situation. We hypothesized that childhood maltreatment can form MTD traits that lead to hikikomori. METHODS: As a first step, we conducted a multigroup path analysis between childhood maltreatment, MTD traits, and physical isolation in the hikikomori group. This study utilized the nine-item Patient Health Questionnaire (PHQ-9), Home Environment Questionnaire (HEQ), 22-item Tarumi Modern-Type Depressive Trait Scale (TACS-22), 25-item Hikikomori Questionnaire (HQ-25), and Hamilton Depression Rating Scale (HDRS). The HQ-25 contains three factors: physical isolation, lack of socialization, and lack of emotional support. RESULTS: The hikikomori group included 92 patients and the control group comprised 137 healthy individuals. All total and subscale scores of PHQ-9, HEQ, TACS-22, HQ-25, and HDRS were significantly higher in the hikikomori group than in the control group. The risk model of childhood maltreatment for physical isolation via MTD traits obtained good fit with a goodness-of-fit index of.982. LIMITATIONS: The study's limitations were its sample selection bias, cross-sectional design, and use of self-report scales. CONCLUSIONS: Our findings support the hypothesis that childhood maltreatment is an important risk factor for hikikomori via MTD traits.

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.

ATP1A3 regulates protein synthesis for mitochondrial stability under heat stress.

Pathogenic variants in ATP1A3, the gene encoding the α3 subunit of the Na+/K+-ATPase, cause alternating hemiplegia of childhood (AHC) and related disorders. Impairments in Na+/K+-ATPase activity are associated with the clinical phenotype. However, it remains unclear whether additional mechanisms are involved in the exaggerated symptoms under stressed conditions in patients with AHC. We herein report that the intracellular loop (ICL) of ATP1A3 interacted with RNA-binding proteins, such as Eif4g (encoded by Eif4g1), Pabpc1 and Fmrp (encoded by Fmr1), in mouse Neuro2a cells. Both the siRNA-mediated depletion of Atp1a3 and ectopic expression of the p.R756C variant of human ATP1A3-ICL in Neuro2a cells resulted in excessive phosphorylation of ribosomal protein S6 (encoded by Rps6) and increased susceptibility to heat stress. In agreement with these findings, induced pluripotent stem cells (iPSCs) from a patient with the p.R756C variant were more vulnerable to heat stress than control iPSCs. Neurons established from the patient-derived iPSCs showed lower calcium influxes in responses to stimulation with ATP than those in control iPSCs. These data indicate that inefficient protein synthesis contributes to the progressive and deteriorating phenotypes in patients with the p.R756C variant among a variety of ATP1A3-related disorders.

Actual Clinical Practice Assessment: A Rapid and Easy-to-Use Tool for Evaluating Cognitive Decline Equivalent to Dementia.

Background Screening tests reveal the early signs of cognitive decline, enabling better self-care and preparation for the future. We developed and evaluated the accuracy of a rapid (20 s) and easy-to-use tool called ONSEI, assessing the cognitive decline equivalent to dementia in actual clinical practice by correlating clinical diagnoses with the ONSEI classification. Methods In this retrospective observational study, data were collected from individuals who visited three neurosurgical clinics in neighboring prefectures of Tokyo, Japan. ONSEI analysis was performed using a smartphone or tablet. The tool adopts a machine-learning algorithm using the speaker's age, time-orientation task score, and acoustic features of spoken responses to that task. Significant differences in accuracy, sensitivity, and specificity were evaluated by Fisher's exact test. Results The overall classification accuracy of ONSEI was 98.1% (p<0.001). The sensitivity and specificity were 97.3% (p<0.001) and 98.5% (p<0.001), respectively. The proportion of correct classifications was consistent across different age groups. Conclusion ONSEI showed high classification accuracy for dementia in cognitively normal individuals in actual clinical practice, regardless of the facility at which the tests were conducted or the age of the participants. Thus, ONSEI can be useful for dementia screening and self-care.

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.

Anesthetic management with remimazolam for a patient with hereditary angioedema:a case report.

BACKGROUND: Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation and extubation. CASE REPORT: A 57-year-old man with HAE and a history of laryngeal edema, scheduled to undergo cervical laminoplasty under general anesthesia. General anesthesia was induced by continuous injection of remimazolam and remifentanil, during which manual mask ventilation and intubation were performed without difficulty. The patient was extubated under deep anesthesia. After emergence from general anesthesia, he had no significant upper airway edema and was treated with a C1-inhibitor seven hours post-surgery because of slight tongue swelling. No additional airway edema was observed, and the patient was discharged from the intensive care unit the following day. CONCLUSIONS: Deep anesthesia tracheal extubation with remimazolam may be effective in preventing upper airway edema during anesthetic management in patients with HAE. J. Med. Invest. 71 : 184-186, February, 2024.

The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain.

Refractory peripheral neuropathy can occur as a side effect in 60-70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]1A receptor antagonist) and Ketanserin (5-HT2A/2C receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths.

PURPOSE: We investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. METHODS: Plans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. RESULTS: The mean/minimum CTV ΔD99% values for FB were -1.0%/-4.9%, -0.8%/-4.3%, and -0.1%/-1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were -0.3%/-1.7%, -0.1%/-1.0%, and 0.0%/-0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. CONCLUSIONS: FB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

Elastic Banding Compression as a Novel Treatment to Maintain Hemodynamics in a Patient With Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is also associated with venous thrombosis originating from varicose veins in the lower extremities, pulmonary embolism, and pulmonary hypertension. This study describes the anesthetic management of laparoscopic cholecystectomy in a 54-year-old male KTS patient with orthostatic hypotension due to massive varicose veins in the lower extremities and pulmonary thromboembolism. Compressing the varicosities with an elastic bandage can maintain stable circulatory dynamics even under general anesthesia management to prevent position and insufflation-induced changes that can occur spontaneously.

Predominant affective temperaments in depressive patients with severe social withdrawal.

BACKGROUND: Hikikomori (HK) is characterized by self-isolation and social refusal, being more likely also associated with affective disorders, including depression. This case-control study primarily aimed at identifying (if any) predominant affective temperaments are associated with HK in depressed versus not-depressed individuals. Secondary objectives comprise assessing which other psychopathological dimensions (e.g., boredom, anxiety) are associated with the HK specifier in depressed individuals. METHODS: From the larger SWATCH study, 687 Italian young people were screened for depression, as measured by 9 items-Patient Health Questionnaire (PHQ-9) and HK-like social withdrawal, through the Hikikomori Questionnaire-25 (HQ-25). All subjects were administered a brief-Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-M), the 7 items-Generalized Anxiety Disorder (GAD-7) and the Multidimensional State Boredom Scale (MSBS). RESULTS: Males reported significantly higher scores at HQ-25 total score than females (p = 0.026). In the total sample, HK social withdrawal is positively predicted by MSBS low arousal, disengagement, depressive levels, depressive and irritable affective temperaments, while negatively by anxiety (F(6, 680) = 82.336, p < 0.001, R2 = 0.421). By selecting only depressed sample, HQ-25 is positively predicted by MSBS total score, low arousal and depressive affective temperament, while negatively by MSBS high arousal (F(4, 383) = 48.544, p < 0.001, R2 = 0.336). The logistic regression model found that the likelihood of developing depression with the HK specifier is significantly predicted by depressive and cyclothymic affective temperaments. CONCLUSIONS: These preliminary findings could help in clinically characterizing the relationship between specific affective temperamental profiles among individuals with depression with/without HK specifier, in order to provide a more tailored and personalized therapeutic approach. Our Italian study should be extensively replicated in larger, longitudinal and multicentric pan-European studies, by specifically assessing the impact of these findings on depression clinical course, prognosis and treatment outcomes.

Shifting the paradigm of social withdrawal: a new era of coexisting pathological and non-pathological hikikomori.

PURPOSE OF REVIEW: Social withdrawal syndrome, known as "hikikomori," has been highlighted since the late 1990 s in Japan. Hikikomori is more common in urban areas, and often comorbid with mental disorders, and now spreading throughout the world. In the post-COVID-19 era, not outing is no longer considered pathological in itself as the "new normal," and a novel concept of hikikomori is needed. This review summarizes the concept of hikikomori, and presents the latest methods for identification of hikikomori. RECENT FINDINGS: The novel definition can distinguish between pathological and non-pathological hikikomori using the scale of "Hikikomori Diagnostic Evaluation (HiDE)," which has been developed in the hikikomori research lab at Kyushu University. An online survey among non-working adults has revealed that persons who have become pathological hikikomori for less than three months showed a particularly strong tendency toward gaming disorder and depression. SUMMARY: Now, physical isolation itself is not pathological, but when dysfunction and distress are present, rapid mental health support should be provided. In the novel urban society, the establishment of a checkup system to assess whether persons who stay home are happy or suffering is important for prevention against mental disorders triggered by social isolation.

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.

Could the Construct of Modern-Type Depression Predict Internet Gaming Disorder in Italian Video Gamers? A Case-Control Study.

A new postmodern depression type, named "Modern-Type Depression" (MTD), is emerging in Western countries. MTD is often underdiagnosed, mainly due to potentially higher comorbidity with technology-based addictions, including Internet Gaming Disorder (IGD). However, the definition of the relationship between MTD and IGD is still controversial, as few data have been published thus far. In particular, there are no data specifically investigating the prevalence of MTD within Italian young subjects with IGD, as well as their mutual association. Hence, within the SWATCH (Social Withdrawal and TeCno-mediated mental Health issues) project, our study aimed to identify the prevalence of MTD in a sample of Italian young adults who play video games by providing a clinical characterization of MTD within a group of IGD individuals (IGD+) versus a group without IGD (IGD-) who play video games. Our cross-sectional case-control study recruited a sample of 543 Italian young video-gaming players (aged 18-35) from the larger SWATCH database, stratified as IGD+ versus IGD-. Subjects were administered the 22-item Tarumi's Modern-Type Depression Trait Scale (TACS-22), the Motives for Online Gaming Questionnaire (MOGQ), and the Internet Gaming Disorder Scale-Short Form (IGDS9-SF). Around 21.7% of the total sample was represented by MTD individuals, while within the IGD sample, around 34% of subjects had MTD. Within the MTD group, significantly higher scores at IGDS-9SF (p < 0.001), MOGQ "Escape from reality" (p < 0.001), "Fantasy" (p < 0.001), and MOGQ total score (p = 0.003) were found compared to MTD-. According to the multivariate regression model, controlled for sex and age, higher scores in the TACS-22 were positively predicted by the total score of IGDS9-SF (p = 0.003), the MOGQ "Escape from Reality" subscale (p = 0.014), and MOGQ "Fantasy" (p = 0.011), and negatively predicted by the MOGQ "Competition" subscale (p = 0.035) [F (4538) = 17.265; p < 0.001]. Our findings suggested that MTD displays a strong association with IGD. Video-gaming players who do not have IGD appear to be less prone to MTD; this suggests that further studies could be carried out to specifically investigate whether pathological use of video games could also be determined by the presence of MTD.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Experimental validation of a 4D dynamic dose calculation model for proton pencil beam scanning without spot time stamp considering free-breathing motion.

PURPOSE: We developed a 4-dimensional dynamic dose (4DDD) calculation model for proton pencil beam scanning (PBS). This model incorporates the spill start time for all energies and uses the remaining irradiated spot time model instead of irradiated spot time logs. This study aimed to validate the calculation accuracy of a log file-based 4DDD model by comparing it with dose measurements performed under free-breathing conditions, thereby serving as an alternative approach to the conventional log file-based system. METHODS: Three cubic verification plans were created using a heterogeneous block phantom; these plans were created using 10 phase 4D-CT datasets of the phantom. The CIRS dynamic platform was used to simulate motion with amplitudes of 2.5, 3.75, and 5.0 mm. These plans consisted of eight- and two-layered rescanning techniques. The lateral profiles were measured using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films at four starting phases, including three sinusoidal curves (periods of 3, 4, and 6 s) and a representative patient curve during actual treatment. 4DDDs were calculated using in-house scripting that assigned a time stamp to each spot and performed dose accumulation using deformable image registration. Furthermore, to evaluate the impact of parameter selection on our 4DDD model calculations, simulations were performed assuming a ±10% change in irradiation time stamp (0.8 ± 0.08 s) and spot scan speed. We evaluated the 2D gamma index and the absolute point doses between the calculated values and the measurements. RESULTS: The 2D-array measurements revealed that the gamma scores for the static plans (no motion) and 4DDD plans exceeded 97.5% and 93.9% at 3%/3 mm, respectively. The average gamma score of the 4DDD plans was at least 96.1%. When using EBT3 films, the gamma scores of the 4DDD model exceeded 92.4% and 98.7% at 2%/2 mm and 3%/3 mm, respectively. Regarding the 4DDD point dose differences, more than 95% of the dose regions exhibited discrepancies within ±5.0% for 97.7% of the total points across all plans. The spot time assignment accuracy of our 4DDD model was acceptable even with ±10% sensitivity. However, the accuracy of the scan speed, when varied within ±10% sensitivity, was not acceptable (minimum gamma scores of 82.6% and maximum dose difference of 12.9%). CONCLUSIONS: Our 4DDD calculations under free-breathing conditions using amplitudes of less than 5.0 mm were in good agreement with the measurements regardless of the starting phases, breathing curve patterns (between 3 and 6 s periods), and varying numbers of layered rescanning. The proposed system allows us to evaluate actual irradiated doses in various breathing periods, amplitudes, and starting phases, even on PBS machines without the ability to record spot logs.

Dose-volume comparisons of proton therapy for pencil beam scanning with and without multi-leaf collimator and passive scattering in patients with lung cancer.

This study evaluated the dose distributions of proton pencil beam scanning (PBS) with/without a multileaf collimator (MLC) compared to passive scattering (PS) for stage I/II lung cancers. Collimated/uncollimated (PBS+/PBS-) and PS plans were created for 20 patients. Internal-clinical-target-volumes (ICTVs) and planning-target-volumes (PTVs) with a 5 mm margin were defined on the gated CTs. Organs-at-risk (OARs) are defined as the normal lungs, spinal cord, esophagus, and heart. The prescribed dose was 66 Gy relative-biological-effectiveness (RBE) in 10 fractions at the isocenter and 50% volume of the ICTVs for the PS and PBS, respectively. We compared the target and OAR dose statistics from the dose volume histograms. The PBS+ group had a significantly better mean PTV conformity index than the PBS- and PS groups. The mean dose sparing for PBS+ was better than those for PBS- and PS. Only the normal lung doses of PBS- were worse than those of PS. The overall performance of the OAR sparing was in the order of PBS+, PBS-, and PS. The PBS+ plan showed significantly better target homogeneity and OAR sparing than the PBS- and PS plans. PBS requires collimating systems to treat lung cancers with the most OAR sparing while maintaining the target coverage.