Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.

Lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor antagonist, ameliorates disease progression in amyotrophic lateral sclerosis model mice.

Nogo-Nogo receptor 1 (NgR1) signaling is significantly implicated in neurodegeneration in amyotrophic lateral sclerosis (ALS). We previously showed that lateral olfactory tract usher substance (LOTUS) is an endogenous antagonist of NgR1 that prevents all myelin-associated inhibitors (MAIs), including Nogo, from binding to NgR1. Here we investigated the role of LOTUS in ALS pathogenesis by analyzing G93A-mutated human superoxide dismutase 1 (SOD1) transgenic (Tg) mice, as an ALS model, as well as newly generated LOTUS-overexpressing SOD1 Tg mice. We examined expression profiles of LOTUS and MAIs and compared motor functions and survival periods in these mice. We also investigated motor neuron survival, glial proliferation in the lumbar spinal cord, and neuromuscular junction (NMJ) morphology. We analyzed downstream molecules of NgR1 signaling such as ROCK2, LIMK1, cofilin, and ataxin-2, and also neurotrophins. In addition, we investigated LOTUS protein levels in the ventral horn of ALS patients. We found significantly decreased LOTUS expression in both SOD1 Tg mice and ALS patients. LOTUS overexpression in SOD1 Tg mice increased lifespan and improved motor function, in association with prevention of motor neuron loss, reduced gliosis, increased NMJ innervation, maintenance of cofilin phosphorylation dynamics, decreased levels of ataxin-2, and increased levels of brain-derived neurotrophic factor (BDNF). Reduced LOTUS expression may enhance neurodegeneration in SOD1 Tg mice and ALS patients by activating NgR1 signaling, and in this study LOTUS overexpression significantly ameliorated ALS pathogenesis. LOTUS might serve as a promising therapeutic target for ALS.

Comparing Dose Calculation Algorithms for Heterogeneous Media: Analytical Anisotropic Algorithm Versus Acuros XB (Dm/Dw) With Continuous CT Value Variation.

BACKGROUND: To compare the doses calculated by the analytical anisotropic algorithm (AAA) and two dose reporting modes of Acuros XB (AXB(Dm) and AXB(Dw)) with varied CT values on the Eclipse (Varian Medical Systems, Palo Alto, CA). MATERIALS AND METHODS: Virtual phantoms with a central layer of heterogeneous material (thickness = 2 or 5 cm) were created with Eclipse. Using single or opposed fields, the field sizes were 5 x 5 cm2 or 10 x 10 cm2. The photon energies were 6 or 10 MV, and the source-to-target distance was 100 cm. The relative doses at the center of the heterogeneous material layer were evaluated with varied CT values, from -1000 to 3000 HU. Values were normalized with the dose at 0 HU (100%) for comparative analysis. RESULTS: The results obtained from continuous data for a single field, 6 MV, 5 x 5 cm2, and the heterogeneous material 5 cm, where the differences between algorithms were most pronounced, were as follows. In the low-density region (-1000 HU and -800 HU), the dose differences for AXB with reference to AAA were, respectively, -54.5% and +4.6% (AXB(Dm)) and -47.0% and +3.5% (AXB(Dw)), and in the high-density regions (1000 HU and 3000 HU) were -5.7% and -8.8% (AXB(Dm)) and +7.4% and +3.5% (AXB(Dw)), respectively. Consequently, dose differences at arbitrary CT values could be obtained. CONCLUSION: Dose differences between these algorithms were clarified for heterogeneous materials. The risk of dose reduction or escalation in clinical use was clearly visible between CT values from -1000 to 3000 HU.

Clinical outcomes and failure patterns after postoperative radiotherapy for oral cavity squamous cell carcinoma.

PURPOSE: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). METHODS: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50-66) administered in 30 fractions (range 25-33). RESULTS: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC.

Clinical course of longer than five years after definitive radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.

Dose difference between anisotropic analytical algorithm (AAA) and Acuros XB (AXB) caused by target's air content for volumetric modulated arc therapy of head and neck cancer.

Background: We clarified the dose difference between the anisotropic analytical algorithm (AAA) and Acuros XB (AXB) with increasing target's air content using a virtual phantom and clinical cases. Materials and methods: Whole neck volumetric modulated arc therapy (VMAT) plan was transferred into a virtual phantom with a cylindrical air structure at the center. The diameter of the air structure was changed from 0 to 6 cm, and the target's air content defined as the air/planning target volume (PTV) in percent (air/PTV) was varied. VMAT plans were recalculated by AAA and AXB with the same monitor unit (MU) and multi-leaf collimator (MLC) motions. The dose at each air/PTV (5%-30%) was compared between each algorithm with D98%, D95%, D50% and D2% for the PTV. In addition, MUs were also compared with the same MLC motions between the D95% prescription with AAA (AAA_D95%), AXB_D95%, and the prescription to 100% minus air/PTV (AXB_D100%-air/PTV) in clinical cases of head and neck (HNC). Results: When air/PTV increased (5-30%), the dose differences between AAA and AXB for D98%, D95%, D50% and D2% were 3.08-15.72%, 2.35-13.92%, 0.63-4.59%, and 0.14-6.44%, respectively. At clinical cases with air/PTV of 5.61% and 28.19%, compared to AAA_D95%, the MUs differences were, respectively, 2.03% and 6.74% for AXB_D95% and 1.80% and 0.50% for AXB_D100%-air/PTV. Conclusion: The dose difference between AAA and AXB increased as the target's air content increased, and AXB_D95% resulted in a dose escalation over AAA_D95% when the target's air content was ≥ 5%. The D100%-air/PTV of PTV using AXB was comparable to the D95% of PTV using AAA.

Long-read sequencing revealing intragenic deletions in exome-negative spastic paraplegias.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower extremities. To date, a total of 88 types of SPG are known. To diagnose HSP, multiple technologies, including microarray, direct sequencing, multiplex ligation-dependent probe amplification, and short-read next-generation sequencing, are often chosen based on the frequency of HSP subtypes. Exome sequencing (ES) is commonly used. We used ES to analyze ten cases of HSP from eight families. We identified pathogenic variants in three cases (from three different families); however, we were unable to determine the cause of the other seven cases using ES. We therefore applied long-read sequencing to the seven undetermined HSP cases (from five families). We detected intragenic deletions within the SPAST gene in four families, and a deletion within PSEN1 in the remaining family. The size of the deletion ranged from 4.7 to 12.5 kb and involved 1-7 exons. All deletions were entirely included in one long read. We retrospectively performed an ES-based copy number variation analysis focusing on pathogenic deletions, but were not able to accurately detect these deletions. This study demonstrated the efficiency of long-read sequencing in detecting intragenic pathogenic deletions in ES-negative HSP patients.

Standardization of knowledge-based volumetric modulated arc therapy planning with a multi-institution model (broad model) to improve prostate cancer treatment quality.

PURPOSE: To evaluate whether knowledge-based volumetric modulated arc therapy plans for prostate cancer with a multi-institution model (broad model) are clinically useful and effective as a standardization method. METHODS: A knowledge-based planning (KBP) model was trained with 561 prostate VMAT plans from five institutions with different contouring and planning policies. Five clinical plans at each institution were reoptimized with the broad and single institution model, and the dosimetric parameters and relationship between Dmean and the overlapping volume (rectum or bladder and target) were compared. RESULTS: The differences between the broad and single institution models in the dosimetric parameters for V50, V80, V90, and Dmean were: rectum; 9.5% ± 10.3%, 3.3% ± 1.5%, 1.7% ± 1.6%, and 3.6% ± 3.6%, (p < 0.001), bladder; 8.7% ± 12.8%, 1.5% ± 2.6%, 0.7% ± 2.4%, and 2.7% ± 4.6% (p < 0.02), respectively. The differences between the broad model and clinical plans were: rectum; 2.4% ± 4.6%, 1.7% ± 1.7%, 0.7% ± 2.4%, and 1.5% ± 2.0%, (p = 0.004, 0.015, 0.112, and 0.009) bladder; 2.9% ± 5.8%, 1.6% ± 1.9%, 0.9% ± 1.7%, and 1.1% ± 4.8%, (p < 0.018), respectively. Positive values indicate that the broad model has a lower value. Strong correlations were observed (p < 0.001) in the relationship between Dmean and the rectal and bladder volume overlapping with the target in the broad model (R = 0.815 and 0.891, respectively). The broad model had the smallest R2 of the three plans. CONCLUSIONS: KBP with the broad model is clinically effective and applicable as a standardization method at multiple institutions.

Comparison of the Characteristics of Two Types of Parallel-plate Ionization Chamber Under Small-field Electron Irradiation.

BACKGROUND/AIM: This study compared two types of parallel-plate ionization chamber to clarify the pitfalls of dosimetry in electron radiation therapy. MATERIALS AND METHODS: The ion recombination correction factor and polarity effect correction factor, sensitivity, and percentage depth doses (PDDs) of PPC05 and PPC40 parallel-plate ionization chambers were compared in a small-field electron beam. The output ratios were measured for 4-20 MeV electron beams with field sizes of 10 cm × 10 cm, 6 cm × 6 cm, and 4 cm × 4 cm. Furthermore, the films were placed in water and positioned in the beam with their surface perpendicular to the beam axis, and lateral profiles were obtained for each beam energy and each field. RESULTS: Regarding PDDs, at depths greater than the peak dose, the percentage depth dose for PPC40 was smaller than that for PPC05 in small fields and at beam energies greater than 12 MeV, which could be attributed to the lack of lateral electron equilibrium at small depths and multiple scattering events at large depths. The output ratio of PPC40 was approximately 0.025-0.038, which was lower than that of PPC05 in a 4 cm × 4 cm field. For large fields, the lateral profiles were similar, regardless of the beam energy, however, for small fields, the flatness of the lateral profile was beam energy dependent. CONCLUSION: The PPC05 chamber, which has a smaller ionization volume, is therefore more suitable than the PPC40 chamber for small-field electron dosimetry, in particular at high beam energies.

Impact of rectal gas on the planning target volume margin for pelvic bone and prostate matching in prostate cancer patients receiving volumetric-modulated arc therapy.

We performed daily cone-beam computed tomography (CBCT) to determine the impact of rectal gas on the movements of prostate and seminal vesicles (SVs). We aimed to determine the relationship between planning target volume (PTV) margins and rectal gas. In 30 treatments of 15 prostate cancer patients, excessive rectal gas was removed and CBCT images were analyzed. Image registration between planning CT and daily CBCT images before and after rectal gas removal was performed for pelvic bone and prostate matching. The couch movement distance between each matching was considered the prostate movement. In addition, we measured SV tip movement between each matching. The anterior-posterior movement of the prostate before rectal gas removal (3.1 ± 2.9 mm) was significantly greater than that after rectal gas removal (1.2 ± 1.2 mm; p < 0.01). The left-right and superior-inferior movements were similar regardless of the presence or absence of rectal gas. The SV movement distances before and after rectal gas removal were 11.0 ± 5.8 mm and 4.6 ± 3.8 mm, respectively (p < 0.01), in pelvic bone matching, and 8.0 ± 4.2 mm and 3.8 ± 3.2 mm, respectively (p < 0.01), in prostate matching. After rectal gas removal, the SV position did not differ significantly between each matching. In 26 of the 30 treatments, SV movement distance in the presence of rectal gas was >6 mm, which is the minimum PTV margin at our institution. In comparison, after rectal gas removal and prostate matching, only 6 treatments demonstrated an SV movement distance of >6 mm. In the presence of rectal gas, the SVs require greater PTV margins than the prostate. Rectal gas removal should be considered if the movement distance on prostate matching is greater than the minimum PTV margin at treating institution.

Reduced likelihood of the Poggendorff illusion in cerebellar strokes: a clinical and neuroimaging study.

This study aimed to test our hypothesis that the cerebellum plays an important role in the generation of the optical-geometric illusion known as the Poggendorff illusion, the mechanism of which has been explained by accumulated experience with natural scene geometry. A total of 79 participants, comprising 28 patients with isolated cerebellar stroke, 27 patients with isolated cerebral stroke and 24 healthy controls, performed Poggendorff illusion tasks and 2 different control tasks. We also investigated core brain regions underpinning changes in the experience of the illusion effect using multivariate lesion-symptom mapping. Our results indicate that patients with isolated cerebellar stroke were significantly less likely to experience the Poggendorff illusion effect than patients with isolated cerebral stroke or healthy controls (74.6, 90.5 and 89.8%, respectively; F(2,76) = 6.675, P = 0.002). However, there were no inter-group differences in the control tasks. Lesion-symptom mapping analysis revealed that the brain lesions associated with the reduced frequency of the Poggendorff illusion effect were mainly centred on the right posteromedial cerebellar region, including the right lobules VI, VII, VIII, IX and Crus II. Our findings demonstrated, for the first time, that patients with cerebellar damage were significantly less likely to experience the Poggendorff illusion effect and that right posteromedial cerebellar lesions played an important role in this effect. These results provide new insight into alterations of a geometric illusion effect in patients with cerebellar disorders and pave the way for future clinical use of the illusion task to detect cerebellar abnormalities.

Factors associated with osteoporosis and fractures in patients with systemic lupus erythematosus: Kyoto Lupus Cohort.

OBJECTIVES: Osteoporosis and compression fractures of the lumbar spine are some of the major adverse effects of glucocorticoid therapy in patients with systemic lupus erythematosus (SLE). This study examined the association between bone mineral density, bone turnover markers, presence of vertebral fractures, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in SLE patients. METHODS: This was a cross-sectional study of 246 outpatients with SLE at the Kyoto University Hospital. Lumbar and femoral bone mineral density was measured with dual-energy X-ray absorptiometry, and the presence of vertebral fractures was determined using X-ray, computed tomography, or magnetic resonance imaging. RESULTS: On multiple regression analysis, both high lumbar and femoral T-scores were associated with the concomitant use of hydroxychloroquine (P = .018 and P = .037, respectively), no use of bisphosphonate or denosumab (P = .004 and P = .038, respectively), high body mass index (P < .001), and low bone-specific alkaline phosphatase level (P = .014 and P = .002, respectively). Vertebral fractures showed a significant association with Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P < .001) and femoral T-score (P < .001). CONCLUSION: Vertebral fracture was associated with SLE-associated organ damage, and serum bone-specific alkaline phosphatase level is a potentially useful marker for osteoporosis monitoring in SLE patients.

Association of biallelic RFC1 expansion with early-onset Parkinson's disease.

BACKGROUND AND PURPOSE: The biallelic repeat expansion (AAGGG)exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late-onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found. METHODS: A nationwide cohort of 273 Finnish patients with early-onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)exp was first screened using extra long polymerase chain reactions (Extra Large-PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)exp was then confirmed by repeat-primed PCR and, finally, the repeat length was determined by long-read sequencing. RESULTS: Three patients were found with the biallelic (AAGGG)exp in RFC1 giving a frequency of 1.10% (0.23%-3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40-48 years and their disease course had been unremarkable apart from the early onset. CONCLUSIONS: Our results suggest that (AAGGG)exp in RFC1 is a rare cause of early-onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population.

Visualization of tumor hypoxia and re-oxygenation after stereotactic body radiation therapy in early peripheral lung cancer: A prospective study.

BACKGROUND AND PURPOSE: In this study, fluoromisonidazole positron emission tomography (F-MISO PET/CT) was used to evaluate tumor hypoxia and re-oxygenation in patients with lung tumors treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Patients with T1-2 N0 lung cancer were included in this study. The prescribed dose was 48-52 Gy in four fractions. F-MISO PET/CT was performed twice, before SBRT and 1-3 days after the first irradiation. The maximum standardized uptake value (SUVmax) and tumor/muscle ratio (TMR) were evaluated as indicators of hypoxia. The threshold for hypoxia was defined as a TMR of 1.30 or more. RESULTS: Between 2016 and 2021, 15 patients were included. Pre-treatment tumor hypoxia was observed in nine tumors (60 %). TMR in all six tumors without pre-treatment hypoxia rose after single high-dose irradiation. In contrast, TMR in six of nine tumors with pre-treatment hypoxia dropped after irradiation, suggesting re-oxygenation. Although no local recurrence was noted, regional and/or distant relapses were seen in four patients (27 %). Of these, three had tumors with abnormal F-MISO uptake. The remaining patient had a tumor without signs of hypoxia on pre-treatment PET/CT. The 2-year progression free survival of patients with tumors with and without pre-treatment hypoxia were 30 % and 63 %, respectively (p = 0.319). CONCLUSION: Tumor hypoxia reduced after single high-dose irradiation. Tumor with F-MISO uptake seems to be an unfavorable prognostic factor in lung SBRT.

Primary results of mechanical thrombectomy for acute ischemic stroke: The K-NET registry in the Japanese metropolitan area.

BACKGROUND: Endovascular treatment (EVT) for acute large vessel occlusion has proven to be effective in randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in a metropolitan area with a large number of comprehensive stroke centers and to compare it with the results of other registries and randomized controlled trials (RCTs). METHODS: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA). Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis. RESULTS: The median age was 77 years, and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 min. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Overall mortality was 12.6%. Significant predictors for a good outcome were as follows: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization. CONCLUSION: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous studies, despite the high proportion of patients with older age, pretreatment mRS score of >2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.

Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical T stage based on 4D computed tomography.

PURPOSE: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical T stage. METHODS: A total of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. RESULTS: Median follow-up time was 27.5 months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8 months, respectively. The 3­year PFS and OS rates were 50.7% and 60.3%, respectively. A significant difference was observed in PFS according to the clinical T stage (p = 0.001). No significant differences were observed in OS according to the clinical T stage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). CONCLUSION: Clinical T stage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to T stage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

Upper-Arm SBP Decline Associated with Repeated Cuff-Oscillometric Inflation Significantly Correlated with the Arterial Stiffness Index.

We evaluated the clinical significance of the new non-invasive vascular indices to explore their potential utility using repeated cuff-oscillometric inflation. In 250 consecutive outpatients, we performed a cross-sectional, retrospective, single-center, observational study to investigate sequential differences in arterial stiffness using blood pressure, arterial velocity pulse index (AVI), and arterial pressure volume index (API) with repeated measurements. Males accounted for 62.7% of the patients, and the mean age was 68.1 ± 12.1 years. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the first reading in repeated measurements were 133.07 ± 21.20 mmHg and 73.94 ± 13.56 mmHg, respectively. The mean AVI and API were 23.83 ± 8.30 and 31.12 ± 7.86, respectively. In each measurement of these parameters, although DBP and AVI did not show significant changes throughout repeated measurements, SBP and API decreased significantly according to the measurement orders. Furthermore, changes in SBP and API were significantly correlated in several of the models. In this study, it was concluded that upper-arm SBP decline associated with repeated cuff-oscillometric inflation was significantly correlated with the arterial stiffness index. The findings of this study will allow clinicians to easily recognize the progression of atherosclerosis through regular, routine practice. In conclusion, this study suggests that changes in repeated SBP measurements may be predictive of arterial stiffness and atherosclerosis.

[Chronic Cough in CANVAS].

Among patients with RFC1 spectrum disorders represented by the phenotype of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS), at least 60% are known to manifest chronic, paroxysmal, and spasmodic dry cough. Chronic cough is a key diagnostic feature of RFC1-related diseases. It is often the first symptom and, in some cases, precedes neurological symptoms such as ataxia and sensory disturbance for more than 30 years. Although the pathogenesis of the cough remains unclear, it is possible that impairment of the vagus nerve, which includes an afferent pathway of the cough reflex, or the cerebellum would have contributed to the generation of the cough.

[Motor Neuron Involvement in RFC1 CANVAS/Spectrum Disorders].

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by the triad of cerebellar ataxia, bilateral vestibular impairment, and sensory neuropathy. The responsible anatomical region for the sensory disturbance in CANVAS is reportedly the dorsal root ganglion, which suggests neuronopathy rather than neuropathy as the pathomechanism of this peripheral nervous system disorder. Early on, motor neuron involvement was considered rare in CANVAS. The etiology of CANVAS includes the homozygous pentanucleotide repeat expansion within the RFC1 gene, resulting in diverse phenotypes and motor deficits such as brisk reflex, extensor plantar responses, or spasticity of the upper motor neurons and muscle wasting, weakness, cramp, or fasciculation of the lower motor neurons. CANVAS patients with AAGGG repeat expansions may show motor neuron involvement, with considerable variation in the reported frequencies. In contrast, although some patients with ACAGG repeat expansions also show motor neuron involvement, its frequency remains elusive.