Uncommon Adverse Events of Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Systematic Review of Case Reports.

BACKGROUND: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). METHODS: A systematic literature review was conducted to identify case reports detailing previously unreported adverse drug reactions to ICIs in patients with SCLC. The scope of the literature reviewed was restricted to case studies on SCLC published up to 31 December 2023. RESULTS: We analyzed twenty-four studies on ICI use for patients with SCLC. There were six reports on atezolizumab, four on durvalumab, and three on adverse events from monotherapy with nivolumab. Reports involving combination treatments were the most frequent, with a total of six, predominantly involving using nivolumab in combination with ipilimumab. Additionally, there was one report each on using pembrolizumab, nofazinilimab, sintilimab, tislelizumab, and toripalimab. We collected detailed information on the clinical course, including patient and disease characteristics, symptoms, treatment for each adverse event, and recovery status. Among the patients included in the case reports, 21 out of 24 (87.5%) had extensive-stage SCLC when initiating ICI therapy, with only 1 patient diagnosed with limited-stage SCLC. Respiratory system adverse events were most common, with seven cases, followed by neurological, endocrinological, and gastroenterological events. Three case reports documented adverse events across multiple systems in a single patient. In most cases, patients showed symptom improvement; however, four studies reported cases where patients either expired without symptom improvement or experienced sequelae. CONCLUSIONS: Efforts to develop reliable biomarkers for predicting irAEs continue, with ongoing research to enhance predictive precision. Immunotherapy presents diverse and unpredictable adverse events, underscoring the need for advanced diagnostic tools and a multidisciplinary approach to improve patient management.

Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy.

BACKGROUND: We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT). METHODS: We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)2, ANC/ALC, platelet count/ALC, and (10 × albumin + 0.05 × ALC), respectively. The cutoff for low muscle mass was 43.0 cm2/m2 for BMI below 25 kg/m2 and 53.0 cm2/m2 for BMI 25 kg/m2 or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)2 (cm2/m2). The ΔSMI (%/50 days) was defined as (SMI after NACRT - SMI before NACRT)/interval (days) × 50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤-10% following NACRT. An elderly patient was defined as aged ≥65 years. The primary outcome measure was overall survival (OS). RESULTS: During a median follow-up of 32.8 months (range, 2.0-176.2), 192 patients died, with a median OS of 50.2 months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3 years, P = 0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (P = 0.270 and P = 0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3 years, P < 0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (P < 0.0001) in elderly patients, and 47.4% and 62.1% (P = 0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (P = 0.008). CONCLUSIONS: EML may be strongly associated with a deteriorated OS in elderly patients undergoing NACRT, followed by surgery for LAEC. The strategies for decreasing muscle loss in these patients should be investigated.

Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center.

BACKGROUND: Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. METHODS: We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. RESULTS: This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. CONCLUSIONS: In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

Contribution of Enhanced Locoregional Control to Improved Overall Survival with Consolidative Durvalumab After Concurrent Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: Insights from Real-World Data.

Purpose: This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy. Materials and Methods: This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis free survival (DMFS), progression free survival (PFS), and overall survival (OS). Results: Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria. Conclusion: The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1-positive tumors, thereby validating the role of durvalumab in standard care.

Surface decontamination of radioactive cesium by a reversibly cross-linkable hydrogel using poly(vinyl alcohol) and phenylboronic acid-grafted poly(methyl vinyl ether-alt-mono-sodium maleate).

Wide-area surface decontamination is essential during the sudden release of radioisotopes to the public, such as nuclear accidents or terrorist attacks. A self-generated hydrogel comprising a reversible complex between poly(vinyl alcohol) (PVA) and phenylboronic acid-grafted poly(methyl vinyl ether-alt-mono-sodium maleate) (PBA-g-PMVE-SM) was developed as a new surface decontamination coating agent to remove radioactive cesium from surfaces. The simultaneous application of PVA and PBA-g-PMVE-SM aqueous polymer solutions containing sulfur-zeolite to contaminated surfaces resulted in the spontaneous formation of a PBA-diol ester bond-based hydrogel. The sulfur-zeolite suspended in the hydrogel selectively removed 137Cs from the contaminated surface and was easily separated from the dissociable used hydrogel. This removal was performed by simple water rinsing without costly incineration to remove the organic materials for final disposal/storage of the radioactive waste, making it suitable for practical wide-area surface decontamination. In radioactive tests, the hydrogel containing sulfur-chabazite (S-CHA) showed substantial 137Cs removal efficiencies of 96.996% for painted cement and 63.404% for cement, which are 2.33 times better than the values for the commercial surface decontamination coating agent DeconGel. Due to its excellent zeolite ion-exchange ability, our hydrogel system has great potential for removing various hazardous contaminants, including radionuclides, from the surface.

Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience.

PURPOSE: The detection rate of early-stage lung cancer with ground-glass opacity (GGO) has increased, and stereotactic body radiotherapy (SBRT) has been suggested as an alternative to surgery in inoperable patients. However, reports on treatment results are limited. Therefore, we performed a retrospective study to investigate the clinical outcome after SBRT in patients with early-stage lung cancer with GGO-predominant tumor lesions at a single institution. MATERIALS AND METHODS: This study included 89 patients with 99 lesions who were treated with SBRT for lung cancer with GGO-predominant lesions that had a consolidation-to-tumor ratio of ≤0.5 at Asan Medical Center between July 2016 and July 2021. A median total dose of 56.0 Gy (range, 48.0-60.0) was delivered using 10.0-15.0 Gy per fraction. RESULTS: The overall follow-up period for the study was median 33.0 months (range, 9.9 to 65.9 months). There was 100% local control with no recurrences in any of the 99 treated lesions. Three patients had regional recurrences outside of the radiation field, and three had distant metastasis. The 1-year, 3-year, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively. Univariate analysis revealed that advanced age and a low level of diffusing capacity of the lungs for carbon monoxide were significantly associated with overall survival. There were no patients with grade ≥3 toxicity. CONCLUSION: SBRT is a safe and effective treatment for patients with GGO-predominant lung cancer lesions and is likely to be considered as an alternative to surgery.

Fabrication of aluminum beads derived from selectively recovered Al-rich precipitates and their application into defluoridation.

This work introduced a new way of fabricating a granular material with the supply of Al-rich precipitates selectively obtained from acid mine drainage (AMD), and its potential as a promising adsorbent for fluoride (F) was evaluated. Through the selective sequential precipitation (SP) process in the field, Al-rich precipitates with high purity (>81%) were collected at the high recovery rate (>99.8%) as a raw material for adsorbent fabrication. The granular adsorbent (ALB) was synthesized through encapsulation of precipitate powders by chemically inducing polymeric bead formation. The characterization results revealed that ALB possessed a highly porous structure and embedded a large number of nanoparticles of amorphous Al hydroxides inside its framework. Less adsorption of F occurred at an alkaline pH condition due to the competitive effect of hydroxyl ions. The adsorption process can be divided into fast adsorption by the outer surface and slow diffusion in the inner phase. The maximum adsorption capacity of ALB for F was calculated to be 17.7 mg g-1 in the Langmuir isotherm model fitting results. By the repetitive adsorption/desorption and XPS results, it turned out that both chemisorption and physisorption gave a contribution in the removal of F, and the regeneration of adsorbent using NaOH was effective to restore the adsorption capability but accompanied the loss of adsorption sites. As a result, it can be concluded that a granule-type material fabricated using Al-rich precipitates selectively recovered from AMD neutralization can be considered as a promising adsorbent for F removal in aqueous solution.

Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: a retrospective observational study.

Background/Aim: We aimed to investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) in elderly patients with small hepatocellular carcinomas (HCC). Methods: Eighty-three patients (89 lesions) with HCC who underwent SBRT between January 2012 and December 2018 were reviewed in this retrospective observational study. The key inclusion criteria were as follows: 1) age ≥75 years, 2) contraindications for hepatic resection or percutaneous ablative therapies, 3) no macroscopic vascular invasion, and 4) no extrahepatic metastasis. Results: The patients were 75-90 years of age, and 49 (59.0%) of them were male. Most patients (94.0%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Seventy-four patients (89.2%) had Child-Pugh class A hepatic function before SBRT. The median tumor size was 1.6 cm (range, 0.7-3.5). The overall median follow-up period was 34.8 months (range, 7.3-99.3). The 5-year local tumor control rate was 90.1%. The 3-year and 5-year overall survival rate was 57.1% and 40.7%, respectively. Acute toxicity grade ≥3 was observed in three patients (3.6%) with elevated serum hepatic enzymes; however, no patient experienced a worsening of the Child-Pugh score to ≥2 after SBRT. None of the patients developed late toxicity (grade ≥3). Conclusions: SBRT is a safe treatment option with a high local control rate in elderly patients with small HCC who are not eligible for other curative treatments.

Role of Esophagectomy after Chemoradiation Therapy in Patients with Locally Advanced Squamous Cell Carcinoma: A Comparative Analysis Stratified by Clinical Response to Chemoradiation Therapy.

PURPOSE: This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery. MATERIALS AND METHODS: We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW). RESULTS: The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001). CONCLUSION: In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

Radiation pneumonitis in patients with non-small-cell lung cancer receiving chemoradiotherapy and an immune checkpoint inhibitor: a retrospective study.

BACKGROUND: Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients. METHODS: We evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated. RESULTS: After CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0-28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed. CONCLUSIONS: Patients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.

Definitive chemoradiotherapy versus esophagectomy in patients with clinical T1bN0M0 esophageal squamous cell carcinoma: A retrospective study.

BACKGROUND AND PURPOSE: This study aimed to determine the equivalence between definitive chemoradiotherapy (DCRT) and radical esophagectomy in clinical T1bN0M0 esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Among 282 patients with cT1bN0M0 ESCC, 238 underwent radical esophagectomy and 44 underwent DCRT. Both treatments were retrospectively compared overall survival (OS), progression-free survival (PFS), and complications. RESULTS: The DCRT group exhibited poorer patient characteristics than the surgery group, especially with mean age (73 vs. 63 years), Eastern Cooperative Oncology Group (ECOG) status, and Charlson Comorbidity Index (p < 0.001, each). The median follow-up duration was 49.5 (range, 0.4-97.0) and 45.5 months (range, 5.0-112.0) in the surgery and DCRT groups, respectively. In the DCRT group, clinical complete response was achieved in 43 patients (97.7%) at 1 month after treatment. The 5-year OS rates were 75.8% and 68.8% (p = 0.135) and the 5-year PFS were 63.8% and 57.8% (p = 0.637) for the surgery and DCRT groups, respectively. Local recurrence rates were identical between the two groups (11.4% and 11.4%), but the distant metastasis rate was lower in the DCRT group (n = 1, 2.27% vs. n = 29, 12.15%). Grade 3-4 hematologic toxicities were observed in 11 patients (25%) of the DCRT group, and 56 patients (23.5%) in the surgery group showed grade 3-5 surgical complications, including mortality (n = 5). CONCLUSION: Based on the non-inferior survival rates, recurrence patterns, and complication rates without critical surgical mortality, DCRT was comparable to esophagectomy for cT1bN0 esophageal squamous cell carcinoma.

Short caregiver interview and play observation for early screening of autism spectrum disorder: Behavior development screening for toddlers (BeDevel).

This study validates behavior development screening for toddlers (BeDevel), which utilizes a combination of short caregiver interviews (BeDevel-I) and semistructured play observations (BeDevel-P). The data of 431 toddlers (male 66.2%; mean age (SD) = 29.11 (8.59) months; ASD, n = 201; developmental delay, n = 46; typically developing, n = 184), aged 18 ~ 42 months, were included in the validation of BeDevel. The best clinical estimate diagnosis, screening rate, validity, sensitivity, and reliability of BeDevel were determined based on data cross-sectionally collected using BeDevel and existing diagnostic/screening instruments: autism diagnostic observation schedule (ADOS), autism diagnostic interview (ADI-R), Vineland adaptive behavior scales-II (VABS-II), social response scales (SRS), sequenced language scale for infants (SELSI), Korean childhood autism rating scale (K-CARS), and Korean social communication questionnaire (K-SCQ). The k values of BeDevel-I and BeDevel-P were 0.055 ~ 0.732 and 0.291 ~ 0.752, respectively. Items related to social referencing in BeDevel-P had a particularly high diagnostic validity (k = 0.483 ~ 0.684). Reliabilities of BeDevel-I and BeDevel-P were sufficient (Cronbach's alpha = 0.86 ~ 0.88 and 0.92 ~ 0.95, respectively). BeDevel-I and BeDevel-P showed high sensitivity (BeDevel-I: 85.00 ~ 89.29%; BeDevel-P: 85.00 ~ 91.75%), specificity (BeDevel-I: 77.55 ~ 89.55%; BeDevel-P: 85.09 ~ 97.01%), PPV (BeDevel-I: 70.83 ~ 88.54%; BeDevel-P: 81.52 ~ 94.68%), and NPV (BeDevel-I: 76.00 ~ 95.24%; BeDevel-P: 84.62 ~ 95.45%). The agreement between the composite BeDevel score and ADOS, ADI-R, K-CARS, and K-SCQ was >67.6% (range = 67.6 ~ 90.8%). Combining a short caregiver interview and direct play observation is a valid and reliable screening process. More studies on social referencing as an important early marker are needed. BeDevel can be utilized as a secondary screening instrument before diagnostic confirmation in clinical and community settings. LAY SUMMARY: BeDevel, which consists of a short caregiver interview and direct play observation, is a valid and reliable screening instrument for autism spectrum disorder (ASD). We suggest that BeDevel can be utilized as a secondary instrument before administering diagnostic assessments in clinical and community settings. More studies examining social referencing as a potential behavioral marker of ASD are needed.

Prognostic significance of lymph node ratio after neoadjuvant chemoradiation therapy for esophageal squamous cell carcinoma.

PURPOSE: We retrospectively evaluated the prognostic significance of lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma who underwent neoadjuvant concurrent chemoradiation therapy (NCRT) followed by surgery. MATERIALS AND METHODS: In total, 270 patients who underwent NCRT followed by surgery between August 2005 and December 2015 were included. They were divided into three groups: LNR 0 (n = 196), LNR low (0 < LNR ≤ 0.1; n = 63), and LNR high (>0.1; n = 11). The primary endpoint was overall survival (OS), and the secondary endpoints were freedom from local recurrence (FFLR), distant metastasis-free survival (DMFS), and disease-free survival (DFS). RESULTS: The median number of retrieved lymph nodes per patient was 33. Pathologically, 74 patients had positive lymph nodes. The median follow-up duration was 36.1 months, and the median survival period was 68.4 months. There was a significant correlation between LNR and the number of positive lymph nodes (correlation coefficient = 0.763, p < 0.001). There was a substantial difference in the OS among the LNR groups, with 2-year survival rates of 79.0%, 54.0%, and 9.1% in the LNR 0, LNR low, and LNR high groups, respectively (p < 0.001). A marked decrease in FFLP, DMFS, and DFS was observed with the increasing LNR. In subgroup analysis, the survival results of patients with clinically positive lymph node were similar from those of entire cohort. CONCLUSION: LNR is a significant prognostic factor in patients with esophageal squamous cell carcinoma who underwent NCRT followed by surgery. Additional treatment and closer follow-up would be necessary for patients with a high LNR.

Abdominal multi-organ auto-segmentation using 3D-patch-based deep convolutional neural network.

Segmentation of normal organs is a critical and time-consuming process in radiotherapy. Auto-segmentation of abdominal organs has been made possible by the advent of the convolutional neural network. We utilized the U-Net, a 3D-patch-based convolutional neural network, and added graph-cut algorithm-based post-processing. The inputs were 3D-patch-based CT images consisting of 64 × 64 × 64 voxels designed to produce 3D multi-label semantic images representing the liver, stomach, duodenum, and right/left kidneys. The datasets for training, validating, and testing consisted of 80, 20, and 20 CT simulation scans, respectively. For accuracy assessment, the predicted structures were compared with those produced from the atlas-based method and inter-observer segmentation using the Dice similarity coefficient, Hausdorff distance, and mean surface distance. The efficiency was quantified by measuring the time elapsed for segmentation with or without automation using the U-Net. The U-Net-based auto-segmentation outperformed the atlas-based auto-segmentation in all abdominal structures, and showed comparable results to the inter-observer segmentations especially for liver and kidney. The average segmentation time without automation was 22.6 minutes, which was reduced to 7.1 minutes with automation using the U-Net. Our proposed auto-segmentation framework using the 3D-patch-based U-Net for abdominal multi-organs demonstrated potential clinical usefulness in terms of accuracy and time-efficiency.

The Feasibility and Validity of Autism Spectrum Disorder Screening Instrument: Behavior Development Screening for Toddlers (BeDevel)-A Pilot Study.

Although early screening is critical for individuals with autism spectrum disorder (ASD) in order to receive early intervention and improve function later in life, screening is often delayed. Limitations of existing screening instruments, and the need for a culturally appropriate early screening tool in Korean children, led us to develop Behavior Development Screening for Toddlers (BeDevel). The BeDevel assessment consists of two parts: BeDevel-Interview, a structured interview measure for parents/primary caregivers; and BeDevel-Play, a play-based semi-structured observational measure in children. To examine the feasibility and validity of BeDevel, 155 children (N = 75 ASD, N = 55 typical development, N = 25 developmentally delayed) aged 18-42 months (M = 31.54 months, SD = 7.60) were examined through parent-reported screening questionnaires, BeDevel, and standard diagnostic assessments. When BeDevel items were analyzed using Cohen's kappa statistics, most items in BeDevel-Interview and all items in BeDevel-Play were reasonably consistent with diagnoses. We identified primary items, which were significantly interacted with actual diagnosis in the chi-squared test (P < 0.05, range = 0.000-0.032). Using cutoff numbers of items determined using the receiver operating characteristics curve, BeDevel showed satisfactory levels of sensitivity (83.33%-100%), specificity (81.25%-100%), positive predictive values (80.65%-100%), and negative predictive values (83.87%-100%), as well as high internal consistency (Cronbach's α = 0.866-959). The agreement between BeDevel and most other screening/diagnostic instruments was moderate (k = 0.419-1.000). These results suggest that BeDevel can be a useful instrument for early screening of ASD. Autism Res 2019, 12: 1112-1128. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Although early screening is critical for individuals with autism spectrum disorder (ASD) in order to receive early intervention and improve function later in life, screening is often delayed. Limitations of existing screening instruments and the need for a culturally appropriate early screening tool in Korean children led us to develop Behavior Development Screening for Toddlers (BeDevel). The BeDevel assessment consists of two parts: BeDevel-Interview, a structured interview measure for parents/primary caregivers; and BeDevel-Play, a play-based, semi-structured observational measure in children. In order to test the feasibility and validity of BeDevel, we analyzed preliminary data of total 155 children aged 18-42 months, examined through parent-reported screening questionnaires, BeDevel, and standard diagnostic assessments. When individual items were analyzed, responses of all BeDevel-Interview items and of most BeDevel-Play items well matched actual diagnoses, and we identified primary items, which were particularly useful in differentiating between the ASD group and the non-ASD group. With the optimal screening criteria determined, the BeDevel was able to identify individuals with a diagnosis of ASD and those without it, all at satisfactory levels. Lastly, BeDevel items were closely related as a set, and the BeDevel screening results were reasonably consistent with the results of most other screening/diagnostic instruments. These results suggest that BeDevel can be a useful instrument for early screening of ASD.

Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

Esculetin, a Coumarin Derivative, Exhibits Anti-proliferative and Pro-apoptotic Activity in G361 Human Malignant Melanoma.

BACKGROUND: Although esculetin, a coumarin compound, is known to induce apoptosis in human cancer cells, the effects and molecular mechanisms on the apoptosis in human malignant melanoma (HMM) cells are not well understood yet. In this study, we investigated the anti-proliferative effects of esculetin on the G361 HMM cells. METHODS: We analyzed the anti-proliferative effects and molecular mechanisms of esculetin on G361 cells by a 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, 4',6-diamidino-2-phenylindole staining and Western blotting. RESULTS: Esculetin exhibited significant anti-proliferative effects on the HMM cells in a dose-dependent manner. Interestingly, we found that esculetin induced nuclear shrinkage and fragmentation, typical apoptosis markers, by suppression of Sp1 transcription factor (Sp1). Notably, esculetin modulated Sp1 downstream target genes including p27, p21 and cyclin D1, resulted in activation of apoptosis signaling molecules such as caspase-3 and PARP in G361 HMM cells. CONCLUSIONS: Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels. Thus, we suggest that esculetin may be a potential anti-proliferative agent that induces apoptotic cell death in G361 HMM cells.