Background: Following success of the phase III PROfound trial, the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib was approved by the US Food and Drug Administration in May 2020 for adult patients with deleterious homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). As locally adopted multigene panel next-generation sequencing (NGS) assays for selecting PARP inhibitor candidates have not been thoroughly evaluated, we compared the analytical performance of the FoundationOne CDx (Foundation Medicine, Inc., Cambridge, MA, USA) (central laboratory) and other NGS assays (local laboratory) with samples from the PROfound trial in Korea. Methods: One hundred PROfound samples (60 HRR mutation [HRRm] cases and 40 non-HRRm cases) were analyzed. The results of HRR gene mutation analysis were compared between the FoundationOne CDx and two other NGS assays [SureSelect Custom Design assay (Agilent Technologies, Inc., Santa Clara, CA, USA) and Oncomine Comprehensive assay (Thermo Fisher Scientific, Inc., Waltham, MA, USA)]. Results: The positive percent agreement for single nucleotide variants (SNVs) and insertion/deletions (indels) between the central laboratory and local laboratory was 98.7%–100.0%. The negative percent agreement and overall percent agreement (OPA) for SNVs and indels between central and local laboratories were both 100%. Compared with that of the FoundationOne CDx assay, the OPA for copy number variations of the Oncomine Comprehensive and SureSelect Custom assays reached 99.8%–100%. Most mCRPC patients harboring a deleterious genetic variant were successfully identified with both local laboratory assays. Conclusions The NGS approach at a local laboratory showed comparable analytical performance for identifying HRRm status to the FoundationOne CDx assay used at the central laboratory.

Artifacts ; Blood Buffy Coat ; Gene Frequency ; Hematologic Tests ; High-Throughput Nucleotide Sequencing ; Humans ; Mass Screening ; Ovarian Neoplasms ; Sensitivity and Specificity ; Tissue Preservation

Objective: A simultaneous detection of germline and somatic mutations in ovarian cancer (OC) using tumor materials is considered to be cost-effective for BRCA1/2 testing. However, there are limited studies of the analytical performances according to various sample types. The aim of this study is to propose a strategy for routine BRCA1/2 next-generation sequencing (NGS) screening based on analytical performance according to different sample types. Methods: We compared BRCA1/2 NGS screening assay using buffy coat, fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) from 130 samples. Results: The rate of repeated tests in a total of buffy coat, FF and FFPE was 0%, 8%, and 34%, respectively. The accuracy of BRCA1/2 NGS testing was 100.0%, 99.9% and 99.9% in buffy coat, FFPE and FF, respectively. However, due to the presence of variant allele frequency (VAF) shifted heterozygous variants, tumor materials (FFPE and FF) showed lower sensitivity (95.5%–99.0%) than buffy coat (100%). Furthermore, FFPE showed 51.4% of the positive predictive value (PPV) on account of sequence artifacts. When performed in the post-filtration process, PPV was increased by approximately 20% in FFPE. Buffy coat showed 100% of sensitivity, specificity and accuracy in BRCA1/2 NGS test. Conclusions On the comparison of the analytical performance according to different sample types, the buffy coat was not affected by sequencing artifacts and VAF shifted variants. Therefore, the blood test should be given priority in detecting germline BRCA1/2 mutation, and tumor materials could be suitable to detect somatic mutations in OC patients without identifying germline BRCA1/2 mutation.

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well.
Humans ; Korea* ; Lung Diseases ; Medical Overuse ; Pulmonary Disease, Chronic Obstructive*

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.
Cohort Studies ; Disease-Free Survival ; Education ; Follow-Up Studies ; Humans ; Nasopharyngeal Neoplasms ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Retrospective Studies* ; Treatment Outcome

PURPOSE: A hybrid-dynamic conformal arc therapy (HDCAT) technique consisting of a single half-rotated dynamic conformal arc beam and static field-in-field beams in two directions was designed and evaluated in terms of dosimetric benefits for radiotherapy of lung cancer. MATERIALS AND METHODS: This planning study was performed in 20 lung cancer cases treated with the VERO system (BrainLAB AG, Feldkirchen, Germany). Dosimetric parameters of HDCAT plans were compared with those of three-dimensional conformal radiotherapy (3D-CRT) plans in terms of target volume coverage, dose conformity, and sparing of organs at risk. RESULTS: HDCAT showed better dose conformity compared with 3D-CRT (conformity index: 0.74 ± 0.06 vs. 0.62 ± 0.06, p < 0.001). HDCAT significantly reduced the lung volume receiving more than 20 Gy (V20: 21.4% ± 8.2% vs. 24.5% ± 8.8%, p < 0.001; V30: 14.2% ± 6.1% vs. 15.1% ± 6.4%, p = 0.02; V40: 8.8% ± 3.9% vs. 10.3% ± 4.5%, p < 0.001; and V50: 5.7% ± 2.7% vs. 7.1% ± 3.2%, p < 0.001), V40 and V50 of the heart (V40: 5.2 ± 3.9 Gy vs. 7.6 ± 5.5 Gy, p < 0.001; V50: 1.8 ± 1.6 Gy vs. 3.1 ± 2.8 Gy, p = 0.001), and the maximum spinal cord dose (34.8 ± 9.4 Gy vs. 42.5 ± 7.8 Gy, p < 0.001) compared with 3D-CRT. CONCLUSIONS: HDCAT could achieve highly conformal target coverage and reduce the doses to critical organs such as the lung, heart, and spinal cord compared to 3D-CRT for the treatment of lung cancer patients.
Heart ; Humans ; Lung Neoplasms ; Lung ; Organs at Risk ; Radiotherapy ; Radiotherapy, Conformal ; Spinal Cord

BACKGROUND: Cervical cytology for uterine cervical cancer screening has transitioned from conventional smear (CS) to liquid-based cytology (LBC), which has many advantages. The aim of this study was to compare the proportion of unsatisfactory specimens from CS versus LBC at multiple institutions including general hospitals and commercial laboratories. METHODS: Each participating institution provided a minimum of 500 Papanicolaou (Pap) test results for analysis. Pap tests were classified according to the participating institution (commercial laboratory or general hospital) and the processing method (CS, ThinPrep, SurePath, or CellPrep). The causes of unsatisfactory results were classified as technical problems, scant cellularity, or complete obscuring factors. RESULTS: A total of 38,956 Pap test results from eight general hospitals and three commercial laboratories were analyzed. The mean unsatisfactory rate of LBC was significantly lower than that of CS (1.26% and 3.31%, p = .018). In the LBC method, samples from general hospitals had lower unsatisfactory rates than those from commercial laboratories (0.65% vs 2.89%, p = .006). The reasons for unsatisfactory results were heterogeneous in CS. On the other hand, 66.2% of unsatisfactory results in LBC were due to the scant cellularity. CONCLUSIONS: Unsatisfactory rate of cervical cancer screening test results varies according to the institution and the processing method. LBC has a significantly lower unsatisfactory rate than CS.
Hand ; Hospitals, General ; Mass Screening* ; Methods ; Papanicolaou Test ; Uterine Cervical Neoplasms*

PURPOSE: To investigate the predictive role of maximum standardized uptake value (SUVmax) of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Between October 2006 and April 2016, 53 patients were treated with IMRT in two institutions and their PET/CT at the time of diagnosis was reviewed. The SUVmax of their nasopharyngeal lesions and metastatic lymph nodes (LN) was recorded. IMRT was delivered using helical tomotherapy. All patients except for one were treated with concurrent chemoradiation therapy (CCRT). Correlations between SUVmax and patients’ survival and recurrence were analyzed. RESULTS: At a median follow-up time of 31.5 months (range, 3.4 to 98.7 months), the 3-year overall survival (OS) and disease-free survival (DFS) rates were 83.2% and 77.5%, respectively. In univariate analysis, patients with a higher nodal pre-treatment SUVmax (≥ 13.4) demonstrated significantly lower 3-year OS (93.1% vs. 55.5%; p = 0.003), DFS (92.7% vs. 38.5%; p < 0.001), locoregional recurrence-free survival (100% vs. 50.5%; p < 0.001), and distant metastasis-free survival (100% vs. 69.2%; p = 0.004), respectively. In multivariate analysis, high pre-treatment nodal SUVmax (≥ 13.4) was a negative prognostic factor for OS (hazard ratio [HR], 7.799; 95% confidence interval [CI], 1.506–40.397; p = 0.014) and DFS (HR, 9.392; 95% CI, 1.989–44.339; p = 0.005). CONCLUSIONS: High pre-treatment nodal SUVmax was an independent prognosticator of survival and disease progression in nasopharyngeal carcinoma patients treated with IMRT in our cohort. Therefore, nodal SUVmax may provide important information for identifying patients who require more aggressive treatment.
Cohort Studies ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Electrons ; Fluorodeoxyglucose F18* ; Follow-Up Studies ; Humans ; Lymph Nodes ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; Positron-Emission Tomography and Computed Tomography* ; Radiotherapy, Intensity-Modulated* ; Recurrence

The associations between storm events, urban runoff and costal water quality have not been well investigated in Korea. A temporal and spatial analysis during summer, 2015 was conducted to determine associates between urban runoff and fecal indicator bacteria (Escherichia coli, Enterococcus) levels at two popular coastal beaches (Gwanganri beach and Haundae beach) in Busan. In this study, a clear relationship between rainfall and elevated number of indicators was observed. Two beaches met the costal beach water health standards after less than 3.0 mm of rain. Only for storms less than 2.5 mm was no observable rainfall effect. Our results revealed that exceedances were greatest in 5 hours following 41.0~45.5 rainfall, then declined the bacterial concentrations in 8 hours after the storm and they generally returned to levels below water health standards within 10~14 hours. But it took 2.7 days to get the level of water quality of dry days. The time required for water quality recovery depends on the intensity and duration of rainfall. In the event of intense rainfall issuance of beach closure by public authorities is warranted to protect public health.
Bacteria ; Busan ; Enterococcus ; Korea ; Public Health ; Rain ; Spatial Analysis ; Swimming* ; Water Quality* ; Water*

Mucormycosis (formerly known as zygomycosis) is a life-threatening opportunistic mycosis that infects a broad range of hosts with qualitative or quantitative defects in innate immunity. The overall mortality rate of pulmonary mucormycosis is above 70%. The prognosis and outcome of pulmonary mucormycosis have not improved significantly over the last decade, mainly because of difficulty in early diagnosis and the limited activity of current antifungal agents against members of the order Mucorales. We report a case of pulmonary mucormycosis treated successfully with posaconazole as salvage therapy. We suggest that posaconazole may be considered as an alternative therapeutic approach in patients with invasive pulmonary mucormycosis who are unable to tolerate surgical treatment.
Antifungal Agents ; Early Diagnosis ; Humans ; Immunity, Innate ; Mortality ; Mucorales ; Mucormycosis* ; Prognosis ; Salvage Therapy*