Background Gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy (AC) with S-1 or capecitabine/oxaliplatin (CAPOX) is the standard treatment for stage II and III gastric cancer (GC). However, there is no established guideline for the start timing of AC. Methods We analyzed data from the Korean Health Insurance Review and Assessment Service on 19 140 GC patients who received AC with S-1 (n = 10 442) or CAPOX (n = 8698) between January 2014 and December 2018. Patients were categorized based on AC initiation timing: within 6 weeks (n = 12 843), 6-8 weeks (n = 5386), and >8-16 weeks (n = 911). Results Initiating AC within 6 weeks significantly improved 5-year disease-free survival (DFS) and overall survival (OS) compared to later initiation, with consistent findings across both S-1 and CAPOX groups (all P < .005). These associations remained significant in multivariable analysis and after propensity score matching (all P < .0001). However, this nationwide big-data analysis has limitations, including potential survival status misclassification and the absence of some important variables such as pathologic stage, performance status, and postoperative complications. Conclusion To optimize outcomes, AC for GC should be initiated within 6 weeks after gastrectomy, provided patients have fully recovered.

Complete cell cycle arrest (CCCA) has been regarded as a biomarker associated with endocrine responsiveness and recurrence-free survival in HR+HER2- breast cancer. We evaluated a prognostic influence CCCA in patients with HR+HER2- breast cancer who had residual tumors after neoadjuvant chemotherapy (NAC). Between 2007 January and 2021 June, we retrospectively identified 1,178 patients with ER+HER2- breast cancer who underwent NAC in two academic institutes. Among these, 918 who had Ki67 index in surgical specimen with residual invasive cancer were included. CCCA was defined as Ki67 less than or equal to 2.7%. We investigated the recurrence-free survival (RFS). In 918 patients, the CCCA rate was 60.1% (552/918). The rate was 63.7% in grade 1/2, whereas it was 37.0% in grade 3. At a median follow-up of 57.8 months, the RFS differed significantly according to the CCCA (p<0.001); The 7-year RFS of the CCCA group was 75.8% (95% CI, 71.3-80.6%), whereas that of the non-CCCA group was 63.9% (95% CI, 58.0-70.4%). CCCA was associated with superior RFS in both grade 3 and clinical stage 3 groups. In multivariable analyses, achieving CCCA was demonstrated as a prognostic factor for RFS (hazard ratio 0.50, 95% CI, 0.37-0.67) independent of stage, age, and grade. Among patients with HR+HER2- breast cancer who had residual invasive disease after NAC, achieving CCCA could serve as a significant prognostic marker.

BACKGROUND:The Murray law-based quantitative flow ratio (μFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of μFR and the safety of deferring non-IRA lesions with μFR >0.80 in the setting of AMI. METHODS:μFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of μFR was compared with QFR and FFR. Patients were classified by the non-IRA μFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS:μFR and QFR analyses were feasible in 443 patients (552 lesions). μFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (μFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with μFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS:In patients with multivessel AMI, μFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with μFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

OBJECTIVE:This study aimed to evaluate the association between tumor necrosis factor-α inhibitor (TNFi) therapy and cardiovascular (CV) outcomes, as well as all-cause mortality, in patients with ankylosing spondylitis (AS). PATIENTS AND METHODS:This retrospective cohort study included 24,986 patients newly diagnosed with AS between 2010-2019 without a history of CV diseases, using data from the Korean National Health Insurance Service. CV events were observed through the end of 2021. After exposure density sampling (1:1), we investigated the association among use of TNFi, duration of TNFi use, and risk of the composite CV outcome (ischemic stroke, heart failure, ischemic heart disease, or CV death) and all-cause mortality. RESULTS:Overall, TNFi users (N = 8,650) and non-users (N = 8,580) had a comparable risk of the composite CV outcome. However, prolonged TNFi use (≥ 1 year) was associated with a significantly lower risk of the composite CV outcome [adjusted hazard ratio (aHR): 0.72, 95% CI: 0.55-0.93, p = 0.012] and all-cause mortality (aHR: 0.37, 95% CI: 0.21-0.66, p < 0.001) compared to discontinued TNFi use (< 1 year), with adjustments made for age, sex, disease duration, hypertension, diabetes, hyperlipidemia, chronic kidney disease, non-steroidal anti-inflammatory drug (NSAID) use, body mass index (BMI), and smoking status. CONCLUSIONS:TNFi therapy did not reduce CV events in AS patients. However, long-term TNFi therapy is likely to be beneficial in reducing CV events and all-cause mortality compared to discontinuing TNFi therapy in patients with AS.

Background: Recent studies have highlighted the prognostic significance of changes in Ki-67 during the neoadjuvant systemic therapy (NAST) for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. While pathologic complete response (pCR) also serves as a valuable prognostic marker for HR+HER2+ breast cancer, its relevance is comparatively lower than in HR-HER2+ breast cancer. This study aimed to explore the potential of post-NAST Ki-67 level, in addition to pCR, in predicting survival outcomes for HR+HER2+ breast cancer.

Abstract Background Discrepancies between quantitative coronary angiography (QCA) and fractional flow reserve (FFR) or intravascular ultrasound (IVUS) are often observed in coronary lesions with intermediate stenosis. Objectives We investigated the impact of physiology- or intracoronary imaging-directed revascularization strategies on clinical outcomes in patients with discordant coronary lesions between QCA and FFR or IVUS. Methods This study was a post hoc analysis of the FLAVOUR study, an investigator-initiated, prospective, randomized, open-label, multinational trial performed at 18 sites in Korea and China. In the FLAVOUR study, 200 patients with ≥60% diameter stenosis (DS) deferred percutaneous coronary intervention (PCI) according to FFR > 0.8 (n=141) or a minimal lumen area > 3 mm2 or 3-4 mm2 with a plaque burden <70% on IVUS whereas 351 patients with <60% DS performed PCI according to positive FFR (n=118) or positive IVUS (n=233) results. The primary outcome was a patient-oriented composite outcome (POCO), a composite of death, myocardial infarction, or revascularization. Results The incidence of discordance was 28.1% in the FFR group and 32.4% in the IVUS group. At 24 months, among patients with ≥60% DS, the incidence of POCO was similar between FFR-guided and IVUS-guided deferral strategies (4.4% vs. 3.4%, p=0.757). Among patients with <60% DS, FFR-directed or IVUS-directed PCI did not differ in the POCO incidence (5.2% vs. 2.6%, p=0.207). However, FFR-guided PCI showed a higher incidence of periprocedural myocardial infarction than IVUS-guided PCI in <60% DS lesions (2.6% vs. 0.0%, p=0.014). Conclusions In patients with discordant intermediate stenosis between QCA and FFR or IVUS, physiology- and imaging-directed revascularization strategies are comparable concerning POCO at 24 months.

Introduction: Despite the prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) assessment has important implications on determining the response-adapted therapy in patients with peripheral T-cell lymphomas (PTCLs), an optimal timing of the use and clinical application of PET/CT-based response are still up in the air. The aim of this study was to explore the prognostic impact of sequential 18F-FDG PET/CT analysis in patients with newly diagnosed PTCLs who treated with frontline anthracycline-based chemotherapy. Methods: Between February 2006 and September 2022, 143 patients with newly diagnosed PTCLs were included. All patients were treated with 6 cycles of anthracycline-containing chemotherapy. Sequential 18F-FDG PET/CT were obtained at the time of diagnosis, after three cycles of chemotherapy and finally at the end of chemotherapy. Baseline total metabolic tumor volume (TMTV) was computed with the sum of SUV2.5 threshold method, and the PET/CT response were assessed using the five-point scale (5-PS) of Deauville criteria. Results: Baseline MTV could be calculated in 126 patients, and the cut-off value of TMTV according to ROC analysis was 457.0 cm3 (Sensitivity 45.0%, specificity 74.0%). With a median follow-up of 52.0 months (range 3.8–153.9 months), patients with high TMTV more than cut-off value had inferior PFS and OS than those with low TMTV (PFS, 9.8 months vs. 26.5 months, HR 1.600, 95% CI 1.010–2.671, p = 0.043; OS, 18.9 months vs. 71.2 months, HR 2.135, 95% CI 1.261–3.615, p = 0.004, Figure 1A, B). Interim 18F-FDG PET/CT assessment was available in all 143 patients. When patients were categorized with three subgroups as response with grade 1, grade 2 and 3, and grade 4–5, PFS and OS showed significant difference according to interim visual assessment (PFS, 120.7 months vs. 34.1 months vs. 5.1 months, p < 0.001; OS, not reached vs. 61.1 months vs. 12.1 months, p < 0.001, Figure 1C, D), respectively. Among 77 patients who were assessed as grade 2 or 3 in interim PET/CT analysis, 19 patients (26.3%) turned over a remnant tumor metabolism or progressed at final PET response assessment. Moreover, the outcome of patients with interim grade 2 or 3 showed the significant differences based on the final achievement of complete metabolic response or not in PFS and OS (PFS, 59.9 months vs. 7.2 months, HR 4.754, 95% CI 2.267–9.971, p < 0.001; OS, not reached vs. 24.0 months, HR 3.706, 95% CI 1.592–8.630, p = 0.001), respectively. Keywords: aggressive T-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers No conflicts of interests pertinent to the abstract.

Low level of HER2+ breast cancer, a subset of HER-2 negative, accounts for about 50-60% of breast cancer. A recent publication highlighting the improved survival outcomes with trastuzumab deruxtecan in this group has raised the need to redefine low HER2+ breast cancer in the context of molecular characterization. In triple-negative breast cancer (TNBC), we compared molecular TNBC subtype, PAM50 subtypes, and clinical-pathological characteristics between the low HER2 and zero HER2 groups. A study population included two cohorts with early TNBC. The adjuvant cohort consisted of 199 TNBC patients who underwent upfront surgery, while the neoadjuvant cohort comprised 124 TNBC patients treated with neoadjuvant chemotherapy (NAC). Transcriptome analysis was conducted in the adjuvant cohort to determine the TNBC molecular subtype and PAM50 types. Tumor-infiltrating lymphocyte (TIL) levels, PD-L1, and Ki67 expression were evaluated in both cohorts, along with recurrence-free survival (RFS) and event-free survival (EFS) investigations in each cohort. In 199 patients with transcriptome analysis, 66 (33.2%) had low HER2 disease, while 133 (66.8%) had zero HER2 tumors. The rates of luminal androgen receptor (LAR) and HER2-E subtypes were 13.1% (26/199) and 7.0% (14/199), respectively. Comparing the two groups, low HER2 tumors showed higher rates of LAR (22.7% vs. 8.5%, p=0.006) and HER2-E (15.2% vs. 3.3%, p=0.016), while other characteristics such as TIL, PD-L1, ROR-P score, and Ki67 did not differ between the two groups. In the neoadjuvant cohort, 31 (25.0%) had low HER2 disease while 93 (75.0%) had zero HER2 tumors, and there were no significant differences in TIL, PD-L1, and Ki67 expression between the two groups. Furthermore, low HER2 status did not significantly affect RFS and EFS in either cohort. Low HER2 status in TNBC is distinctly associated with enriched LAR and HER2-E subtypes. However, other characteristics such as TIL, PD-L1, and Ki67 expression, as well as survival outcomes, were found to be similar between the two groups.

Premenopausal women experience temporary ovarian function suppression (OFS) during the period of chemotherapy. In ER+ breast cancer, chemotherapy-induced temporary OFS may offer anti-estrogenic effect in addition to direct cytotoxic anti-tumor effect. It is unclear whether anti-estrogenic effect by temporary OFS during neo-adjuvant chemotherapy (NAC) enhance anti-tumor effect. Based on pathologic complete response (pCR) and complete cell-cycle arrest (CCCA), we compared pathologic response and outcomes between younger and older patients with ER+HER2- breast cancer treated with NAC. Between 2007 January and 2021 June, we retrospectively identified 1,178 patients with ER+HER2- breast cancer who underwent NAC in the Gangnam Severance Hospital and the Asan Medical Center. We compared the pCR rate according to age under 45 and over 55 and investigated durations of NAC, clinical stage, and Ki-67. Pathologic complete response was defined as no invasive residual disease in both breast and axillae. In addition, we collected available Ki67 expression in surgical specimen after NAC. We defined low Ki67 with a cutoff of 2.7%. The recurrence-free survival was evaluated in patients with post-NAC Ki67. In all 1,178 patients, the pCR rate was 1.9% (22/1,178). The rate was 1.4% (8/552) in younger patients (age ≤45), whereas it was 3.6% (9/250) in older patients (age ≥55) (p= 0.063, Chi-square test). In 524 patients who received NAC consisting of anthracyclines and taxanes with a duration of NAC longer than 6 months, the pCR rate did not differ between the younger patients and the older (2.1%, 5/243 vs. 2.8%, 3/106; p= 0.703). In patients with post-NAC Ki67, the CCCA rates were 66.2% (307/464) in the younger and 39.8% (86/216) in the older, respectively (p<0.001). Survival analyses showed that, compared to patients with CCCA, those without CCCA experienced a significant decrease in RFS in both younger and older women. While short-term OFS resulting from NAC led to a higher rate of CCCA in premenopausal women, younger women had notably poorer survival outcomes compared to older women. Among premenopausal women, achieving CCCA was associated with a slight improvement in treatment outcomes.

Abstract Background Incomplete revascularization of non-infarct related arteries (IRA) leads to worse outcomes in patients with acute myocardial infarction (AMI) and multivessel coronary artery disease (MVD). Outcomes of fractional flow reserve (FFR)- and angiography-guided percutaneous coronary intervention (PCI) for non-IRA may differ according to their location between the anterior descending artery (LAD) and non-LAD. Aims We investigated the impact of FFR- versus angiography-guided PCI on clinical outcomes according to the location of non-IRA (LAD versus non-LAD) in AMI patients with MVD. Methods This trial was a pre-specified post-hoc analysis of the FRAME-AMI study, an investigator-initiated, randomized, open-label, multicenter trial at 14 sites in Korea. In the FRAME-AMI trial, PCI was performed for non-IRA in 64.1% (FFR £0.80) and 97.1% (diameter stenosis of >50%) in FFR-guided PCI and angiography-guided PCI groups, respectively. We grouped the patients into four according to treatment strategy (FFR versus angiography) and location of non-IRA (LAD vs. non-LAD). The primary endpoint was a composite of time to death, MI, or repeat revascularization. Results Patients with non-IRA involving LAD and non-LAD were 55.0% and 45.0%, respectively. The proportion of performed PCI (82.2% vs. 78.3%, p=0.242) and the rate of the primary outcome (9.4% vs. 11.5%, p=0.421) were similar between LAD and non-LAD. Among patients with non-IRA involving LAD, the FFR-guided group had a fewer events rate of the primary outcome than the angiography-guided group (5.7% vs. 14.3%, p=0.010). Among those with non-IRA not involving LAD, the FFR-guided group tended to the lower incidence of the primary outcome compared to the angiography-guided group (7.4% vs. 14.5%, p=0.081). However, the effect of the interaction between LAD and non-LAD on the primary outcome was not found (p for interaction 0.667). Conclusions In AMI patients with MVD, FFR-directed PCI for non-IRA was superior to angiography-guided PCI regardless of the location of non-IRA. The benefit of an FFR-directed revascularization strategy for non-IRA is likely enhanced in LAD.