BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.

Clinicopathological importance of Bcl-2 and p53 in postmenopausal triple-negative breast carcinoma and association with age.

Appropriate biomarkers are required to predict the clinical outcome of triple-negative breast cancer (TNBC). In this study, we focused on the clinical importance of two representative tumor-associated proteins, Bcl-2 and p53. Bcl-2 expression is usually related to estrogen receptor expression and a favorable outcome in breast cancer. TNBC has been reported to show a high frequency of p53 positivity suggesting TP53 mutations. The expressions of Bcl-2 and p53 were immunohistochemically examined in TNBC involving two age groups of postmenopausal women (≥75 y/o, n = 75; 55-64 y/o, n = 47), who underwent surgery without neoadjuvant therapy. We examined their associations with each other, or with clinicopathological factors including the outcome. Bcl-2 expression was inversely correlated with androgen receptor, apocrine morphology, and p53 expressions, and was an independent predictor of a poor outcome in total or in younger women. p53 positivity was associated with a more favorable outcome than p53 negativity in the younger group. In combined analyzes, none of the twenty Bcl-2-negative/p53-positive cases in the younger group exhibited recurrence, resulting in the independent favorable predictive value of Bcl-2-negative/p53-positive. The anti-apoptotic nature of Bcl-2 may be apparent in TNBC. The excellent outcome of Bcl-2-negative/p53-positive cases in the younger group warrants further combined investigation of Bcl-2/p53 in TNBC.

ssDNA is not superior to dsDNA as long HDR donors for CRISPR-mediated endogenous gene tagging in human diploid RPE1 and HCT116 cells.

BACKGROUND: Recent advances in CRISPR technology have enabled us to perform gene knock-in in various species and cell lines. CRISPR-mediated knock-in requires donor DNA which serves as a template for homology-directed repair (HDR). For knock-in of short sequences or base substitutions, ssDNA donors are frequently used among various other forms of HDR donors, such as linear dsDNA. However, partly due to the complexity of long ssDNA preparation, it remains unclear whether ssDNA is the optimal type of HDR donors for insertion of long transgenes such as fluorescent reporters in human cells. RESULTS: In this study, we established a nuclease-based simple method for the preparation of long ssDNA with high yield and purity, and comprehensively compared the performance of ssDNA and dsDNA donors with 90 bases of homology arms for endogenous gene tagging with long transgenes in human diploid RPE1 and HCT116 cells. Quantification using flow cytometry revealed lower efficiency of endogenous fluorescent tagging with ssDNA donors than with dsDNA. By analyzing knock-in outcomes using long-read amplicon sequencing and a classification framework, a variety of mis-integration events were detected regardless of the donor type. Importantly, the ratio of precise insertion was lower with ssDNA donors than with dsDNA. Moreover, in off-target integration analyses using donors without homology arms, ssDNA and dsDNA were comparably prone to non-homologous integration. CONCLUSIONS: These results indicate that ssDNA is not superior to dsDNA as long HDR donors with relatively short homology arms for gene knock-in in human RPE1 and HCT116 cells.

Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions.

BACKGROUND: Differences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. METHODS: Forty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. RESULTS: 1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). CONCLUSIONS: Because characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.

Suprapapillary placement of plastic versus metal stents for malignant biliary hilar obstructions: a multicenter, randomized trial.

BACKGROUND AND AIMS: The efficacy of the suprapapillary placement of inside plastic stents (iPSs) for unresectable malignant hilar biliary obstructions (MHOs) is unknown compared with that of uncovered inside metal stents (iMSs). This randomized controlled trial was designed to evaluate the outcomes of endoscopic placement of these stents for unresectable MHOs. METHODS: This open-label, randomized study was conducted at 12 Japanese institutions. The enrolled patients with unresectable MHOs were allocated to iPS and iMS groups. The primary outcome was defined as the time to recurrent biliary obstruction in patients for whom the intervention was both technically and clinically successful. RESULTS: Among 87 enrollments, 38 patients in the iPS group and 46 patients in the iMS group were analyzed. Technical success rates were 100% (38 of 38) and 96.6% (44 of 46), respectively (P = 1.00). After transferring 1 unsuccessful iMS-group patient to the iPS group (since iPSs were deployed), the clinical success rates were 90.0% (35 of 39) for the iPS group and 88.9% (40 of 45) for the iMS group from a per-protocol analysis (P = 1.00). Among the patients with clinical success, the median times to recurrent biliary obstruction were 250 (95% confidence interval, 85-415) and 361 (95% confidence interval, 107-615) days (log-rank test, P = .34). No differences were detected in rates of adverse events. CONCLUSIONS: This Phase II randomized trial did not show any statistically significant difference in stent patency between suprapapillary plastic versus metal stents. Considering the potential advantages of plastic stents for malignant hilar obstruction, these findings suggest that suprapapillary plastic stents could be a viable alternative to metal stents for this condition.

Accelerated hypofractionated radiotherapy with 3 Gy per fraction for central/ultra-central lung tumors: toxicity to mediastinal organs.

BACKGROUND: Accelerated hypofractionated radiotherapy with 3 Gy per fraction is routinely performed for central lung tumors in Japan. However, the tolerable doses to mediastinal organs at risk during this procedure are unclear. This study aimed to clarify the rate of toxicities and tolerable doses to mediastinal organs. METHODS: Patients treated with accelerated hypofractionated radiotherapy using a total dose of 60-75 Gy, with 3 Gy per fraction, for central lung tumors (July 2009-April 2021) were retrospectively reviewed. We extracted patients who received ≥30 Gy irradiation to each mediastinal organ and analyzed dosimetric factors, including doses to 0.03, 0.5, 1, 4 and 10 mL of each organ, in relation to grade 3-5 toxicities, except for radiation pneumonitis. RESULTS: In total, 251 organs in 91 (ultra-central, 24) lesions were analyzed, with a median follow-up duration of 26 months (range, 4-94). The prescribed doses were 75/72/69/66/63/60 Gy for 52/14/16/3/2/4 lesions, respectively. Grade 3 bronchopulmonary hemorrhage was confirmed in two (2.2%) patients, whose tumors were located ultra-centrally. The two patients with toxicity received up to 74.5 and 71.6 Gy to the bronchus. Among patients who received 70 Gy or more to the bronchus, the incidence rate was 7% (2/28 patients). CONCLUSION: The rate of severe toxicities was low (2.2%). Although we did not identify the dose tolerance of the organs, because of the low incidence rate, we did note that doses of >70 Gy to the bronchus were likely to cause bronchopulmonary hemorrhage.

Evaluation of the MVCT-based radiomic features as prognostic factor in patients with head and neck squamous cell carcinoma.

BACKGROUND: Megavoltage computed tomography (MVCT) images acquired during each radiotherapy session may be useful for delta radiomics. However, no studies have examined whether the MVCT-based radiomics has prognostic power. Therefore, the purpose of this study was to examine the prognostic power of the MVCT-based radiomics for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 100 HNSCC patients who received definitive radiotherapy were analyzed and divided into two groups: training (n = 70) and test (n = 30) sets. MVCT images obtained using TomoTherapy for the first fraction of radiotherapy and planning kilovoltage CT (kVCT) images obtained using Aquilion LB CT scanner were analyzed. Primary gross tumor volume (GTV) was propagated from kVCT to MVCT images using rigid registration, and 107 radiomic features were extracted from the GTV in MVCT and kVCT images. Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to examine the association between overall survival (OS) and rad score calculated for each patient by weighting the feature value through the coefficient when features were selected. Then, the predictive values of MVCT-based and kVCT-based rad score and patient-, treatment-, and tumor-specific factors were evaluated. RESULTS: C-indices of the rad score for MVCT- and kVCT-based radiomics were 0.667 and 0.685, respectively. The C-indices of 6 clinical factors were 0.538-0.622. The 3-year OS was significantly different between high- and low-risk groups according to the MVCT-based rad score (50% vs. 83%; p < 0.01). CONCLUSIONS: Our results suggested that MVCT-based radiomics had stronger prognostic power than any single clinical factor and was a useful prognostic factor when predicting OS in HNSCC patients.

Recurrent distal cholangiocarcinoma and humoral hypercalcemia of malignancy: report of a rare case and literature review.

A 61-year-old Japanese woman presented with epigastric pain and jaundice. Imaging showed the presence of primary distal cholangiocarcinoma (DCC). A subtotal stomach-preserving pancreaticoduodenectomy was performed, followed by chemotherapy using S-1. However, second-line chemotherapy with gemcitabine and cis-diamminedichloroplatinum was required for the treatment of hepatic metastasis of the DCC 3 months following the surgery. Nine months after the surgery, the serum calcium and parathyroid hormone-related peptide concentrations were high, at 16.5 mg/dL and 28.7 pmol/L, respectively, which suggested the presence of humoral hypercalcemia of malignancy (HHM) secondary to the DCC. Moreover, marked leukocytosis, with a white blood cell count of 40,400/µL, was also present. The patient died 11 months after the diagnosis of DCC. Because hypercalcemia of malignancy is associated with a poor prognosis, and HHM and leukocytosis caused by DCC are very rare, we have presented the present case in detail and provide a review of the existing literature.

A decreased preoperative platelet-to-lymphocyte ratio, systemic immune-inflammation index, and pan-immune-inflammation value are associated with the poorer survival of patients with a stent inserted as a bridge to curative surgery for obstructive colorectal cancer.

PURPOSE: Inflammation is one of the hallmarks of cancer, and inflammation-based markers that are calculated easily from laboratory results have shown predictive abilities. We investigated the prognostic values of the preoperative platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) in patients with non-metastatic obstructive colorectal cancer (OCRC) and a self-expandable metallic stent inserted as a bridge to curative surgery. METHODS: The subjects of this retrospective study were 86 patients with pathological stage I to III OCRC. We examined the associations of these biomarkers with short- and long-term outcomes. RESULTS: Multivariate analyses revealed that a preoperative PLR < 149, SII < 597, and PIV < 209 were independently associated with poorer relapse-free survival (RFS) (P = 0.007, P < 0.001, and P = 0.002, respectively) and that a PIV < 209 was independently associated with poorer cancer-specific survival (P = 0.030). A platelet count < 240 was significantly associated with worse RFS, whereas the lymphocyte count was not. Pre-stenting PLR < 221 was an independent poor prognostic factor for RFS (P = 0.045). CONCLUSION: This study showed that decreased preoperative PLR, SII, PIV, and pre-stenting PLR were associated with poorer RFS, contrary to the findings of most previous studies. Our results suggest that platelets and obstruction contributed primarily to the opposite relationships, which might provide new insight into the possible pathophysiology of platelet-tumor interactions generated in the OCRC environment.

Prognostic significance of Ishii's sarcopenia screening score for patients undergoing curative surgery for obstructive colorectal cancer after intraluminal decompression.

PURPOSE: Sarcopenia influences the short- and long-term outcomes of various medical conditions including malignancy. Ishii's screening test estimates the probability of sarcopenia based on a score calculated by three simple variables: age, grip strength, and calf circumference. We investigated the clinical significance of Ishii's score for patients with non-metastatic obstructive colorectal cancer (OCRC) who underwent curative surgery after intraluminal decompression. METHODS: Ishii's score was calculated in 79 patients with OCRC. Muscle volume loss and decreased muscle quality were evaluated by computed tomography (CT) images as skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. RESULTS: There were 46 men and 33 women, with a median age of 70 years old. The cutoff value for Ishii's score was 155.1 and 15 patients were in the high-score group. The high-score group was significantly associated with worse time to recurrence (TTR) and overall survival (OS), and a high Ishii's score was an independent negative prognostic factor for TTR (hazard ratio = 2.93, P = 0.015). A high Ishii's score was significantly associated with a low SMI value but not with the IMAC value. CONCLUSION: A high Ishii's score was independently associated with poorer TTR in patients with non-metastatic OCRC.

Reactive Oxygen Species in the Aorta and Perivascular Adipose Tissue Precedes Endothelial Dysfunction in the Aorta of Mice with a High-Fat High-Sucrose Diet and Additional Factors.

Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.

Improved upper extremity function following low-frequency hybrid assistive neuromuscular dynamic stimulation therapy in a patient with hemiplegia: A case report.

BACKGROUND: Although hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy may improve upper extremity functionality in patients with paralysis or paresis due to stroke, it is usually only provided in hospitals as a frequent intervention during the phase of early recovery in stroke. Home-based rehabilitation is limited by frequency and duration of visits. PURPOSE: To investigate the effectiveness of low-frequency HANDS therapy using motor function assessment. STUDY DESIGN: Case report. METHODS: We performed HANDS therapy for 1 month on the patient, who was a woman in her 70s with left-sided hemiplegia. It was initiated on day 183 post the onset of stroke. Movement and motor function were evaluated using the Fugl-Meyer Assessment upper-extremity (FMA-UE) motor items and the Motor Activity Log consisting of Amount of Use (MAL-AOU), as well as Quality of Movement (MAL-QOM) scales. This evaluation was performed before starting HANDS therapy and after its conclusion. RESULTS: Following HANDS therapy, there was improvement in the FMA-UE (21 points â†’ 28 points), MAL-AOU (0.17 points â†’ 0.33 points), and MAL-QOM (0.08 points â†’ 0.33 points) scores when compared to the scores before therapy, and the patient was able to use both hands for activities of daily living (ADLs). CONCLUSIONS: Low-frequency HANDS therapy combined with encouragement to include the affected hand in ADLs may improve upper extremity function in cases of paralysis.

Risk of Pancreatitis Following Biliary Stenting With/Without Endoscopic Sphincterotomy: A Randomized Controlled Trial.

BACKGROUND & AIMS: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP. METHODS: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement. RESULTS: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups. CONCLUSION: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm.

Early and long-term clinical outcomes of endoscopic interventions for benign pancreatic duct stricture/obstruction-the possibility of additional clinical effects of endoscopic ultrasonography-guided pancreatic drainage.

OBJECTIVES: For benign pancreatic duct strictures/obstructions (BPDS/O), endoscopic ultrasonography-guided pancreatic drainage (EUS-PD) is performed when endoscopic transpapillary pancreatic drainage (ETPD) fails. We clarified the clinical outcomes for patients with BPDS/O who underwent endoscopic interventions through the era where EUS-PD was available. METHODS: Forty-five patients with BPDS/O who underwent ETPD/EUS-PD were included. We retrospectively investigated overall technical and clinical success rates for endoscopic interventions, adverse events, and clinical outcomes after successful endoscopic interventions. RESULTS: The technical success rates for ETPD and EUS-PD were 77% (35/45) and 80% (8/10), respectively, and the overall technical success rate using two drainage procedures was 91% (41/45). Among the 41 patients who underwent successful endoscopic procedures, the clinical success rates were 97% for the symptomatic patients (35/36). The rates of procedure-related pancreatitis after ETPD and EUS-PD were 13% and 30%, respectively. After successful endoscopic interventions, the cumulative 3-year rate of developing recurrent symptoms/pancreatitis was calculated to be 27%, and only two patients finally needed surgery. Continuous smoking after endoscopic interventions was shown to be a risk factor for developing recurrent symptoms/pancreatitis. CONCLUSIONS: By adding EUS-PD to ETPD, the technical success rate for endoscopic interventions for BPDS/O was more than 90%, and the clinical success rate was nearly 100%. Due to the low rate of surgery after endoscopic interventions, including EUS-PD, for patients with BPDS/O, EUS-PD may contribute to their good clinical courses as a salvage treatment for refractory BPDS/O.

Treatment response after palliative radiotherapy for bleeding gastric cancer: a multicenter prospective observational study (JROSG 17-3).

BACKGROUND: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. METHODS: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. RESULTS: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/ß = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSIONS: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding.

Artificially Created Reentry Circuit by Laser Irradiation Causes Atrial Tachycardia to Persist in Murine Atria.

BACKGROUND: There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin. CONCLUSIONS: Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.

Palliative radiotherapy for multiple liver metastases: a retrospective analysis of 73 cases.

BACKGROUND: Whole-liver radiotherapy for diffuse liver metastases can improve symptoms and abnormal liver-related blood data. However, whole-liver radiotherapy is uncommonly used in clinical practice in Japan. Therefore, we aimed to clarify palliative radiotherapy outcomes in Japanese patients with liver metastases. METHODS: We retrospectively reviewed databases in our institution to identify patients treated with radiotherapy (8 Gy in a single fraction) for multiple liver metastases between December 2014 and April 2021. The endpoints included pain response, liver-related blood data and adverse effects. We investigated aspartate transaminase, alanine transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl transpeptidase and albumin. The mean values at whole-liver radiotherapy and after 2-4 weeks were compared using the Wilcoxon rank-sum test. RESULTS: A total of 73 cases in 71 patients were included. The median clinical target volume was 2118 ml (range, 133-7867 ml). Fifty-seven patients (78%) had finished aggressive treatment at the time of radiotherapy. The median follow-up period was 6 weeks. The pain response rate was 64% (18/28). The mean values of five parameters significantly improved 2-4 weeks after radiotherapy compared to those at baseline: aspartate transaminase (118 vs. 83 U/l P < 0.01); alanine transaminase (84 vs. 61 U/l P < 0.01); lactate dehydrogenase (1351 vs. 1007 U/l P = 0.027); alkaline phosphatase (1624 vs. 1216 U/l P < 0.01) and γ-glutamyl transpeptidase (663 vs. 450 U/l P = 0.037). No patients experienced radiation-induced liver disease. CONCLUSIONS: Palliative radiotherapy is efficient and safe in Japanese patients with liver metastases. These findings will help encourage whole-liver radiotherapy use in Japan.

Fracture risk following stereotactic body radiotherapy for long bone metastases.

BACKGROUND: Stereotactic body radiotherapy is a new treatment modality for long bone metastasis and has not been discussed in literature. We aimed to clarify stereotactic body radiotherapy outcomes for long bone metastases. METHODS: Data of patients receiving stereotactic body radiotherapy for long bone metastases (July 2016-November 2020) were retrospectively reviewed. The prescribed dose was 30 or 35 Gy in five fractions. The endpoints were local failure and adverse effects. Local failure was defined as radiological tumor growth within the irradiation field. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5. RESULTS: Nineteen osseous lesions in 17 patients were assessed. The target lesions included 13 femoral, 4 humeral and 2 radial lesions. The median follow-up duration was 14 (range, 3-62) months. The 12- and 18-month local failure rates were 0 and 11%, respectively. Following 2 and 46 months of stereotactic body radiotherapy, two lesions (11%) resulted in painful femoral fractures (grade 3). Both patients underwent bipolar hip arthroplasty and could walk normally after surgery. In the late phase, one patient developed radiculopathy (almost complete paralysis of grasp) and another developed grade 2 limb edema. Other grade 2 or more severe acute and late toxicities were not observed during the follow-up period. CONCLUSIONS: Stereotactic body radiotherapy for long bone metastases achieved excellent local control and caused two femoral fractures. We argue that stereotactic body radiotherapy for curative intent should not be contraindicated in long bone oligometastasis because fractures do not directly contribute to life expectancy.

Risk of radiculopathy caused by second course of spine stereotactic body radiotherapy.

OBJECTIVE: Stereotactic body radiotherapy is used to treat spinal metastases; however, 10% of patients experience local failure. We aimed to clarify the outcomes of the second course of stereotactic body radiotherapy for spinal metastases with a uniform fractionation schedule at our institution. METHODS: Data of patients treated with a second salvage stereotactic body radiotherapy course at the same spinal level or adjacent level from July 2018 to December 2020 were retrospectively reviewed. The initial prescribed dose was 24 Gy in two fractions, and the second dose 30 or 35 Gy in five fractions. The spinal cord dose constraint at the second course was 15.5 Gy at the maximum point dose. The endpoints were local failure and adverse effects. Local failure was defined as tumor progression using imaging. RESULTS: We assessed 19 lesions in 17 patients, with radioresistant lesions in 14 (74%) cases, the second stereotactic body radiotherapy to the same/adjacent spinal level in 13/6 cases, the median interval between stereotactic body radiotherapy of 23 (range, 6-52) months, and lesions compressing the cord in 5 (26%) cases. The median follow-up period was 19 months. The 12- and 18-month local failure rates were 0% and 8%, respectively. Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 0 (0%), 4 (21%) and 2 (11%) lesions, respectively. Three patients with radiculopathy experienced almost complete upper or lower limb paralysis. CONCLUSIONS: The second course of salvage stereotactic body radiotherapy for spinal metastases achieved good local control with a reduced risk of myelopathy. However, a high occurrence rate of radiation-induced radiculopathy has been confirmed.

Local control of stereotactic body radiotherapy with dynamic tumor tracking for lung tumors: a propensity score-matched analysis.

BACKGROUND: Dynamic tumor tracking (DTT) is a method of respiratory motion management in radiotherapy. It reduces the radiation field but risks delivering an insufficient radiation dose to the tumor. We investigated the local control of DTT-stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Patients treated with SBRT for early-stage, non-small-cell lung cancer and lung metastases (2013-18) were retrospectively reviewed. Patients with tumor motion >1 cm were treated with DTT-SBRT (DTT group); those with tumor motion ≤1 cm were treated with static-SBRT (static group). A static planning target volume for the static-SBRT plan was also created for patients in the DTT group, and planning target volume reduction relative to the planning target volume for the DTT-SBRT plan was assessed. Patients were matched in a 1:1 ratio using a propensity score predictive of the SBRT technique. RESULTS: Of the 245 lesions in 218 patients (median follow-up, 25.4 months), 69 were treated with DTT-SBRT and 176 with static-SBRT. The median planning target volume reduction in the DTT group was 30.3%. After propensity score matching, 124 lesions were included (62 per group). Two-year local control rates for the DTT and static groups were 94.2 and 95.9%, respectively, for all lesions (P = 0.19) and 96.3 and 94.5%, respectively, for matched lesions (P = 0.79). In univariate analysis, DTT-SBRT was not associated with local control for all lesions (hazard ratio, 2.06; P = 0.20) or matched lesions (hazard ratio, 1.22; P = 0.79). No grade 4/5 toxicities were observed. CONCLUSIONS: DTT-SBRT for lung tumors reduced the planning target volume, but not local control rates. DTT was useful for respiratory motion management.