PURPOSE Previous studies suggest that external-beam partial breast irradiation (PBI) delivered twice a day can lead to increased adverse cosmesis (AC). The objective of our trial was to determine whether two regimens for PBI given once daily over 1 week resulted in acceptable AC to inform a phase III trial. METHODS Patients age ≥50 years with invasive breast cancer or ductal carcinoma in situ, ≤3 cm in size treated by lumpectomy with negative axillary nodes were randomly assigned to external-beam PBI of 30 Gy or 27.5 Gy, each given in five fractions once daily. The primary outcome was AC (fair or poor) by photographic assessment at 2 years. Secondary outcomes included AC assessed by nurse at 2 years, by patient self-assessment at 3 years, and late toxicity. On the basis of a 17% risk of AC with whole-breast irradiation, the upper bound of a two-sided 90% CI, 23% was set as the tolerance margin (OPAR, ClinicalTrials.gov identifier: NCT02637024 ). RESULTS In total, 142 patients were randomly assigned to 30 Gy and 139 to 27.5 Gy. The median follow-up was 5 years. The mean age was 65 years, and the mean tumor size was 1.2 cm. Both schedules met acceptability criteria by photographic assessment (AC, 12.1% [90% CI, 8.2 to 17.6] for 30 Gy and 15.2% [90% CI, 10.8 to 21.1] for 27.5 Gy) and by nurse assessment. AC by patient self-assessment exceeded the 90% CI for the 30 Gy regimen. At 5 years, 16 (11.3%, 90% CI, 7.6 to 16.4) patients treated with 30 Gy and eight (5.8%, 90% CI, 3.3 to 9.9) patients treated with 27.5 Gy were observed to have grade 2 or more late toxicity. CONCLUSION According to the study design, 30 Gy and 27.5 Gy resulted in acceptable cosmetic outcomes. In light of recent studies, a lower dose was chosen for the phase III trial.

Death is a crucial outcome in retrospective cohort studies, serving as a criterion for analyzing mortality in a database. This study aimed to assess the quality of extracted death data and investigate the potential of the final-administered medication as a variable to quantify accuracy for the validation dataset. Electronic health records from both an in-hospital and the Korean Central Cancer Registry were used for this study. The gold standard was established by examining the differences between the dates of in-hospital deaths and cancer-registered deaths. Cosine similarity was employed to quantify the final-administered medication similarities between the gold standard and other cohorts. The gold standard was determined as patients who died in the hospital after 2006 and whose final hospital visit/discharge date and death date differed by 0 or 1 day. For all three criteria-(a) cancer stage, (b) cancer type, and (c) type of final visit-there was a positive correlation between mortality rates and the similarities of the final-administered medication. This study introduces a measure that can provide additional accurate information regarding death and differentiates the reliability of the dataset.

The growing incidence of differentiated thyroid cancer (DTC) demands dependable prognostic factors to guide follow-up and treatment plans. This study investigated the prognostic value of response to therapy (RTT) assessment using TSH stimulated-thyroglobulin (sti-Tg) and nonstimulated-thyroglobulin (nonsti-Tg) and evaluates whether RTT using nonsti-Tg (nonstiRTT) can replace RTT using sti-Tg (stiRTT) in clinical practice to improve patients’ quality of life during assessment. We enrolled 419 DTC patients who underwent total thyroidectomy, radioactive iodine (RAI) therapy, and Tg assessment. Patients with structural incomplete responses were excluded. Initial RTT assessments based on the 2015 American Thyroid Association guidelines (excellent response; ER, indeterminate response, biochemical incomplete response) were performed 6–24 months after RAI therapy. The second RTT assessments were performed 6–24 months after the first assessment. Statistical analysis for recurrence-free survival (RFS) was done with the log-rank test for stiRTT and nonstiRTT. Although initial stiRTT and nonstiRTT were significant predictors for RFS (p < 0.0001), stiRTT provided better RFS prediction than nonstiRTT. The RFS analysis of the second RTT assessment demonstrated statistical significance only for stiRTT (p < 0.0001). In 116 patients classified as ER on initial stiRTT, there was no RFS difference between patients classified as ER on either second stiRTT or nonstiRTT. The prognostic power of stiRTT surpasses that of nonstiRTT in both the initial and second RTT assessment. Nevertheless, among patients classified as ER on initial stiRTT, a second stiRTT may not be required for those classified as ER on the second nonstiRTT.

Abstract Background Death is a crucial measure in electronic medical record (EMR) studies, where it has significance as a criterion for analyzing mortality in the database. This study aimed to assess extracted death data quality and investigate the potential of a final administered medication variable as an indicator to quantify the accuracy of a newly extracted control group’s death data. Methods Data were collected through Asan Biomedical Research Environment, which comprised data from both the Asan Medical Center and The Korean Central Cancer Registry. The gold standard was established by examining differences according to death information sources through a chart review. Cosine similarity was employed to quantify the final administered medication similarities between the gold standard and other cohorts using the Anatomical Therapeutic Chemical classification system code. Results The gold standard was determined as patients who died in hospital after 2006, when the final hospital visit/discharge date and death date differed by 0 or 1. For all three criteria, a) Seer Stage, b) cancer type c) type of final visit; as the mortality rate increased, the final administered medication cosine similarity with the golden standard increased. Conclusion This study introduced an indicator that can provide additional accurate death information and differentiate reliability. In the future, variables other than EMR could be used to further determine death information quality, in addition to the final administered medication.

Genetic testing has become increasingly integrated into all areas of healthcare, and complex genetic testing usage continues to grow; thus, the demand for genetic counseling (GC) is likely to increase. However, it is unclear whether the current clinical GC capacity is sufficient for meeting the existing demand. This review describes the current issues, challenges, and future perspectives of GC in Korea based on a professional survey conducted among laboratory physicians. In view of the growing GC demand in the clinical setting, participants expressed a concern about the lack of support from the national healthcare insurance policy and legal requirements, such as certification, for GC practice. The implementation of genetic testing in the overall healthcare system in Korea is in an early phase. Proper implementation can be achieved through education and training of specialists, collaboration among healthcare personnel, proper regulatory oversight, genomic policies, and public awareness. Understanding the current GC capacity, issues, and challenges is a prerequisite for effective strategic planning by healthcare systems considering the expected growth in the demand for clinical genetic services over the next few decades.

This study aimed to investigate deep convolutional neural network- (DCNN-) based artificial intelligence (AI) model using cephalometric images for the classification of sagittal skeletal relationships and compare the performance of the newly developed DCNN-based AI model with that of the automated-tracing AI software. A total of 1574 cephalometric images were included and classified based on the A-point-Nasion- (N-) point-B-point (ANB) angle (Class I being 0–4°, Class II > 4°, and Class III < 0°). The DCNN-based AI model was developed using training (1334 images) and validation (120 images) sets with a standard classification label for the individual images. A test set of 120 images was used to compare the AI models. The agreement of the DCNN-based AI model or the automated-tracing AI software with a standard classification label was measured using Cohen’s kappa coefficient (0.913 for the DCNN-based AI model; 0.775 for the automated-tracing AI software). In terms of their performances, the micro-average values of the DCNN-based AI model (sensitivity, 0.94; specificity, 0.97; precision, 0.94; accuracy, 0.96) were higher than those of the automated-tracing AI software (sensitivity, 0.85; specificity, 0.93; precision, 0.85; accuracy, 0.90). With regard to the sagittal skeletal classification using cephalometric images, the DCNN-based AI model outperformed the automated-tracing AI software.

Hyein Kang, M.D., Sunggyun Park, M.D., Do-Hoon Kim, M.D., Wonmok Lee, M.D., Namhee Ryoo, M.D., Dong-Seok Jeon, M.D., Seok Jin Kang, M.D., Jung Sook Ha, M.D.. Lab Med Online 2021;11:132-4. https://doi.org/10.47429/lmo.2021.11.2.132

Background: The effects of nonsteroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase (COX)-2 inhibitors on postoperative fracture-healing are controversial. Thus, we investigated the association between NSAID/COX-2 inhibitor administration and postoperative nonunion or delayed union of fractures. We aimed to determine the effects of NSAID/COX-2 inhibitor administration on postoperative fracture-healing with use of a common data model. Methods: Patients who underwent operative treatment of a fracture between 1998 and 2018 were included. To determine the effects of NSAID/COX-2 inhibitor administration on fracture-healing, postoperative NSAID/COX-2 inhibitor users were compared and 1:1 matched to nonusers, with 3,264 patients matched. The effect of each agent on bone-healing was determined on the basis of the primary outcome (nonunion/delayed union), defined as having a diagnosis code for nonunion or delayed union ≥6 months after surgery. The secondary outcome was reoperation for nonunion/delayed union. To examine the effect of NSAIDs/COX-2 inhibitors on bone union according to medication duration, a Kaplan-Meier survival analysis was performed. Results: Of the 8,693 patients who were included in the analysis, 208 had nonunion (178 patients; 2.05%) or delayed union (30 patients; 0.35%). Sixty-four (30.8%) of those 208 patients had a reoperation for nonunion or delayed union. NSAID users showed a significantly lower hazard of nonunion compared with the matched cohort of nonusers (hazard ratio, 0.69 [95% confidence interval, 0.48 to 0.98]; p = 0.040) but did not show a significant difference in the other matched comparison for any other outcomes. Kaplan-Meier survival analysis revealed significantly lower and higher nonunion/delayed union rates when the medication durations were ≤3 and >3 weeks, respectively (p = 0.001). For COX-2 inhibitors, the survival curve according to the medication duration showed no significant difference among the groups (p = 0.9). Conclusions: Our study demonstrated no short-term impact of NSAIDs/COX-2 inhibitors on long-bone fracture-healing. However, continued use of these medications for a period of >3 weeks may be associated with higher rates of nonunion or delayed union. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Antipsychotic drugs raise seizure risk in adults, and antipsychotic drug use is increasing among pediatric psychiatric disorder patients. However, few studies have examined seizure risk in this younger patient population. To evaluate seizure risk in pediatric patients on antipsychotics, we conducted a nested case–control study using a nationwide database. Patient information was retrieved from the Korean Health Insurance Review and Assessment (HIRA) database from 2008–2018. Antipsychotic use among newly diagnosed psychiatric patients was gathered starting 1 year before the index date and categorized as recent, past, consistent, or none. Seizure cases among these patients were defined based on (1) prescription of antiepileptic drugs or (2) an electroencephalography (EEG) examination among patients with seizure diagnostic code. A conditional logistic regression model was constructed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for seizure risk due to antipsychotic use. In total, 1523 seizure cases and 6092 seizure-free controls aged 8–19 years with newly diagnosed psychiatric disorders were included for analysis. Logistic regression revealed a significant association between antipsychotic use and seizure development (recent users OR = 4.03, 95% CI 3.4–4.79; consistent users: OR = 2.84, 95% CI 2.44–3.3). Seizure risk enhanced further with an increase in the number of antipsychotic drugs used. Risperidone, aripiprazole, quetiapine, olanzapine, paliperidone, and blonanserin were independently associated with greater seizure risk. Pediatric patients receiving antipsychotics, especially new or multiple antipsychotic users, should be carefully monitored for seizure development.

BACKGROUND:Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. METHODS:We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. FINDINGS:Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). INTERPRETATION:External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. FUNDING:Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

Background: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a disease involving the intestine and is often diagnosed in surgically resected specimens. The disease prognosis of MEITL is fatal because of rapid recurrence and leakage after excision. Recently, in microscopic finding of MEITL, intraepithelial lymphocytosis in mucosa that were grossly intact has been reported. In this study, we evaluated the intraepithelial lymphocytosis of the resection margin to determine the reason for the early recurrence or leakage in MEITL.

This study aims to evaluate the reduction of cardiac radiation dose and volume with deep inspiration breath hold (DIBH) technique compared to free breathing (FB) in patients with left-sided breast cancer. The study also aims to evaluate whether the benefits of DIBH vary in patients who had whole breast radiotherapy (RT) after breast-conserving surgery (BCS) and those who had chest wall RT post-mastectomy (M).

To evaluate the prevalence of and factors associated with internal mammary node (IMN) adenopathy on MRI and PET/CT used for initial staging in patients with operable breast cancer.

Objective: Schizophrenia and bipolar disorder are characterized by the presence of neurocognitive impairments on the psychosis continuum. The present study aimed to explore the shared and distinct endophenotypes between these disorders.Methods: The study included 34 probands with remitted schizophrenia and 34 probands with euthymic bipolar disorder who had a history of psychotic symptoms that met the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria, unaffected first degree relatives of probands (31 relatives of probands with schizophrenia and 29 relatives of probands with bipolar disorder), and 34 healthy controls. Cognitive assessments were performed using the digit span, continuous performance, Rey auditory and visual learning, complex figure, verbal fluency, Wisconsin card sorting, and finger tapping tests.Results: Probands with schizophrenia showed the most generalized and severe cognitive deficits across cognitive domains (working memory, verbal learning and memory, visual memory, verbal fluency, and executive function). Some domains of cognitive function (working memory, verbal learning, and memory) were also impaired in probands with bipolar disorder, but to a lesser degree than in probands with schizophrenia. All probands and relatives showed a common deficit in working memory compared to healthy controls, Relatives of probands with schizophrenia also showed verbal fluency dysfunction. Cognitive performance of all relatives was intermediate to the performance of both patients and healthy controls.Conclusion: These findings suggest that a deficit in working memory could be a shared endophenotype of genetic vulnerability to schizophrenia and psychotic bipolar disorder, and verbal fluency could be a candidate endophenotype for schizophrenia specifically.

1353 Objectives Extranodal involvement in malignant lymphoma is known as one of the poor prognostic factors. However, prognostic factors in the diffuse large B-cell lymphoma (DLBCL) patients with extranodal involvement are not well known. This study was performed to determine which clinical factor or PET parameter could be the best predictor for prognosis of DLBCL patients with extranodal involvement. Methods Nineteen DLBCL patients with extranodal involvement who underwent pretreatment 18F-FDG PET/CT were enrolled. Clinical parameters [age, Ann Arbor staging, Eastern Cooperative Oncology Group (ECOG) performance status, serum LDH level, International Prognostic Index (IPI) score, metabolic complete response (mCR) status] and metabolic PET parameters [nodal metabolic tumor volume (NMTV), extranodal MTV (ENMTV), total MTV (TMTV)] were analyzed for their usefulness in predicting disease specific survival (DSS). Results Ten of 19 patients (52.6%) died during follow-up period (mean, 40.3 months). Non-survivors had higher TMTV than survivors (768.9±778.8 cm3 vs. 158.1±194.0 cm3, p=0.0355). ENMTV was also higher in non-survivors (594.2±738.4 cm3 vs. 83.6±133.1 cm3), but there was no statistical significance (p=0.0573). Optimal cutoff values of NMTV, ENMTV, and TMTV for disease specific survival (DSS) were 2.89, 69.63, and 73.93 cm3, respectively. On univariate survival analysis, ECOG performance status (≥2, p=0.0130), mCR+ status (p=0.0033), NMTV (≥2.89, p=0.0427), ENMTV (≥69.63, p=0.0127), TMTV (≥73.93, p=0.0295) were significant prognostic factors for DSS, whereas other clinical factors including IPI score were not. On multivariate survival analysis, TMTV was the best predicting factor for DSS (HR=14.8; p=0.0289), followed by mCR+ status and ECOG performance status. Conclusions The TMTV on pretreatment 18F-FDG PET/CT could be a powerful prognostic factor for DSS in DLBCL patients with extranodal involvement. Patients with high TMTV, mCR- status, high ECOG performance status are at higher risk of shorter survival.

To determine the optimal levels of thyroid-stimulating hormone (TSH) levels after administration of recombinant human TSH (rhTSH) to patients with differentiated thyroid cancer (DTC), we have analyzed the clinical parameters that affected the degree of the increase in serum levels of TSH.