Background: Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC. Methods: Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer CellFree Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively. Results: Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most. Conclusions Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.

Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an indepth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.

Background: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. Materials and Methods: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. Results: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization ( P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12–4.11) and male gender (OR, 2.62; 95% CI, 1.26– 5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24–0.79) was associated with better outcomes. Conclusion Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Background: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. Materials and Methods: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. Results: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization ( P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12–4.11) and male gender (OR, 2.62; 95% CI, 1.26– 5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24–0.79) was associated with better outcomes. Conclusion Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Background: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. Materials and Methods: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. Results: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization ( P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12–4.11) and male gender (OR, 2.62; 95% CI, 1.26– 5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24–0.79) was associated with better outcomes. Conclusion Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their cost-effectiveness from patients’ perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PF-LYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions Considering the importance of knowing a patient’s BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option.

Background: In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to detect EGFR mutation. We compared the cost and clinical effect of three strategies according to the application of the EGFR test. Methods: 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. Results: 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. Conclusions 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.

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