The field of genetic counseling (GC) in the Republic of Korea has evolved from a single medical doctor's clinic to a multidisciplinary service with medical geneticists and non-medical professionals ...working as a team. Here, we assessed the current status of GC in the Republic of Korea based on professional surveys from the perspective of laboratory physicians. An electronic survey was designed and conducted, with the respondents being 50 certified laboratory physicians who were members of the Korean Society for Genetic Diagnostics. Among the 50 respondents, 12 (24%) operated GC clinics. The number of sessions and cases of GC have been on the rise over the last few years, and counseling for cancer genetics was the most common request. Most respondents considered a good understanding of the genetic test and the ability to interpret the test results as strengths of laboratory physicians as medical geneticists, while the lack of clinical experience was a weakness. Education programs regarding laboratory physicians' needs should be provided for high-quality counseling. Lastly, improving the efficiency of GC by strengthening the workforce through a multidisciplinary team is necessary.
For an effective dispatcher-assisted cardiopulmonary resuscitation (CPR) program, recognition of out-of-hospital cardiac arrest (OHCA) by a dispatcher is the first step in initiating bystander CPR. ...This study evaluated whether CPR awareness in the community is associated with recognition of arrest, dispatcher-provided CPR instructions, and bystander CPR.
All emergency medical services (EMS)-treated adult OHCAs with cardiac etiology were enrolled between 2013 and 2015, excluding cases witnessed by EMS providers. Exposure was CPR awareness in the community where the OHCA occurred. Endpoints were recognition of arrest, dispatcher-provided CPR instructions, and bystander CPR. Multilevel logistic regression analysis was performed to calculate adjusted odds ratios (AORs) per 10% increment in community CPR awareness adjusting for potential confounders.
Of 44,185 eligible OHCAs, 20,255 (45.8%) cases were recognized by a dispatcher, 17,858 (40.4%) received dispatcher-provided CPR instructions, and 22,255 (50.4%) received bystander CPR (39.8% with dispatcher assistance and 10.6% without dispatcher assistance). Compared with OHCAs that occurred in the communities with low awareness, dispatchers were more likely to provide CPR instructions to the caller, and bystanders were more likely to perform CPR for OHCAs that occurred in the communities with high CPR awareness. AORs (95% CIs) per 10% increment in public awareness of CPR in the community were 1.05 (1.01–1.10) for recognition of arrest, 1.11 (1.06–1.16) for dispatcher-provided CPR instructions, and 1.07 (1.03–1.11) for bystander CPR.
Public CPR awareness of the communities where OHCAs occurred was associated with recognition of arrest during an emergency call, dispatcher-provided CPR instructions, and bystander CPR.
In this study, we performed a comprehensive analysis of BRCA1/2 variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic ...or likely pathogenic variants (PLPVs) in BRCA1 and BRCA2. This study included 5433 Korean participants who were tested for BRCA1/2 genes. The BRCA1/2 variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had BRCA1 or BRCA2 PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for BRCA2 VUS than those of BRCA1 VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1–73.6%) for BRCA1 and 58.3% (95% CI: 43.2–73.0%) for BRCA2 carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4–53.9%) for BRCA1 and 14.9% (95% CI: 7.4–28.5%) for BRCA2 carriers.
Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient ...samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.
Background
This study evaluated the effects of body mass index (BMI) before the diagnosis of the first primary cancer on the development of secondary primary cancers (SPCs) in female cancer ...survivors.
Methods
This study population included 146 377 Korean female cancer survivors whose first primary cancer was diagnosed between 2002 and 2010. The incidence of SPCs was evaluated throughout follow‐up until December 2011. We used Cox proportional hazards models to calculate the hazard ratios of SPCs with prediagnosis BMI and compared it to those of first cancers in the general population.
Results
After 565 877 person‐years of follow‐up, 2222 patients with SPC were observed. The higher BMI was more in female cancer survivors than in general population. The age‐standardized incidence rate of cancer in cancer survivors was 2.02 times higher than that of the general population. There were positive linear trends between prediagnosis BMI and risk of overall, colorectal, ovary, thyroid, and obesity‐related SPCs. In addition, the BMI‐SPC risk association was statistically significant in female cancer survivors without smoking history (Ptrend = 0.001) and with a localized first primary cancer (Ptrend = 0.014). However, the magnitude of the BMI‐SPC risk association was similar to that for first cancers in the general population (Pheterogeneity = 0.403 in BMI ≥ 30.0 kg/m2).
Conclusions
In female cancer survivors, prediagnosis obesity was a risk factor for overall, individual, and obesity‐related SPCs. However, the magnitude of the BMI‐SPC risk association was similar to that for first cancers in the general population.
In this Korean national cohort study, which included 146 377 Korean female cancer survivors whose first primary cancer was diagnosed between 2002 and 2010, the age‐standardized incidence rate of cancer in cancer survivors was higher than that of the general population. However, the magnitude of the body mass index (BMI)‐SPC risk association was similar to that for first cancers in the general population.
In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (
) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to ...detect
mutation. We compared the cost and clinical effect of three strategies according to the application of the
test.
Decision models were developed to compare the cost-effectiveness of tissue-only, tissue-first, and plasma-first diagnostic strategies as first- and second-line treatments for NSCLC from the perspective of the Korean national healthcare payer. Progression-free survival (PFS), overall survival (OS), and direct medical costs were assessed. A one-way sensitivity analysis was performed.
The plasma-first strategy correctly identified numerous patients in the first- and second-line treatments. This strategy also decreased the cost of biopsy procedures and complications. Compared with that when using the other two strategies, the plasma-first strategy increased PFS by 0.5 months. The plasma-first strategy increased OS by 0.9 and 1 month compared with that when using the tissue-only and tissue-first strategies, respectively. The plasma-first strategy was the least expensive first-line treatment but the most expensive second-line treatment. First-generation tyrosine kinase inhibitor and the detection rate of the T790M mutation in tissues were the most cost-influential factors.
The plasma-first strategy improved PFS and OS, allowing for a more accurate identification of candidates for targeted therapy for NSCLC and decreased biopsy- and complication-related costs.
The heterogeneity of triple-negative breast cancer (TNBC) poses difficulties for suitable treatment and leads to poor outcome. This study aimed to define a consensus molecular subtype (CMS) of TNBC ...and thus elucidate genomic characteristics and relevant therapy. We integrated the expression profiles of 957 TNBC samples from published datasets. We identified genomic characteristics of subtype by exploring the pathway activity, microenvironment, and clinical relevance. In addition, drug response (DR) scores (
= 181) were computationally investigated using chemical perturbation gene signatures and validated in our own patient with TNBC (
= 38) who received chemotherapy and organoid biobank data (
= 64). Subsequently, cooperative functions with drugs were also explored. Finally, we classified TNBC into four CMSs: stem-like; mesenchymal-like; immunomodulatory; luminal-androgen receptor. CMSs also elucidated distinct tumor-associated microenvironment and pathway activities. Furthermore, we discovered metastasis-promoting genes, such as secreted phosphoprotein 1 by comparing with primary. Computational DR scores associated with CMS revealed drug candidates (
= 18), and it was successfully evaluated in cisplatin response of both patients and organoids. Our CMS recapitulated in-depth functional and cellular heterogeneity encompassing primary and metastatic TNBC. We suggest DR scores to predict CMS-specific DRs and to be successfully validated. Finally, our approach systemically proposes a relevant therapeutic prediction model as well as prognostic markers for TNBC. IMPLICATIONS: We delineated the genomic characteristic and computational DR prediction for TNBC CMS from gene expression profile. Our systematic approach provides diagnostic markers for subtype and metastasis verified by machine-learning and novel therapeutic candidates for patients with TNBC.
Introduction
Autologous peripheral blood stem cell (PBSC) transplantation has become a standard treatment option for many oncology patients. The aim of this study was to evaluate the performance of ...two cell separators, Spectra Optia (Terumo BCT, Japan) and Amicus (Fresenius‐Kabi) for autologous PBSC collection.
Methods
We retrospectively evaluated 56 apheresis by Spectra Optia with Continuous Mononuclear Cell Collection (cMNC) from 20 patients, and 50 apheresis by Amicus from 27 patients between December 2018 and December 2019. CD34+ collection efficiency (CE2) and platelet (PLT) loss were evaluated.
Results
There was no significant difference in CD34+ CE2 between Spectra Optia with cMNC (median, 28.8%) and Amicus (median, 33.1%; P = 0.537). PLT loss was significantly lower in Amicus (median, 28.6%) than in Spectra Optia with cMNC (median, 37.8%; P = 0.009).
Conclusion
CD34+ CE2 was comparable between Spectra Optia and Amicus, and PLT loss was significantly lower in Amicus. To the best of our knowledge, this is the first report comparing autologous PBSC collection of the Spectra Optia and Amicus. These results may provide general guidance with regard to device selection to apheresis clinics that use both separators for optimal outcomes depending on each patient's characteristics.
Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this ...study was to evaluate the clinical applicability of quantitative analysis of multiplex
mutations in cell-free DNA from patients with PDAC.
A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of
mutations were determined through multiplex detection of
mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad).
mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored
mutations in cfDNA, with a median
mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the
mutation concentration hazard ratio (HR), 2.08; 95% CI, 1.20-3.63 and
fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival.
mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that
mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (
= 0.016). Moreover, when combined with the cancer biomarker CA19-9, the
mutation concentration in cfDNA showed additive benefits for the prediction of overall survival.
This study demonstrates that multiplex detection of
mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.
Natural killer (NK) cells are a part of the innate immune system, providing the first line of defense against cancer cells and pathogens at an early stage. Hence, they are attracting attention as a ...valuable resource for allogeneic cell immunotherapy. However, NK cells exist with limited proportion in blood, and obtaining sufficient clinical-grade NK cells with highly viable and minimal stress is critical for successful immune cell therapy. Conventional purification methods via immunoaffinity or density gradient centrifugation had several limitations in yield, purity, and cellular stress, which might cause an increased risk for graft versus host disease and reduced efficacy due to NK cell malfunction, exhaustion, and apoptosis. Moreover, reducing the variations of isolation performance caused by the manual process is another unmet need for uniform quality of the living drug. Here, an automated system using an NK disc (NKD) based on continuous centrifugal microfluidics (CCM) technology was developed to isolate NK cells from whole blood with high yield, purity, reproducibility, and low stress. The CCM technology, which operates fluidic manipulation under disc rotation, enabled precise extraction of the ultra-thin target fluid layer generated by blood centrifugation. Compared to the conventional manual method, the CCM-NKD isolated NK cells with higher yield (recovery rate) and purity, while maintaining better reproducibility. Furthermore, since the CCM-NKD maintained substantially milder centrifugation conditions (120 ×g for 10 min) compared to the conventional approach (1200 ×g for 20 min), it showed reduced cellular stress and increased antioxidant capacity in the isolated NK cells. Based on the results, the CCM-NKD is expected to be a useful tool to provide highly intact and viable cell weapons for successful immune cell therapy.
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