BackgroundParaquat is associated with a high rate of fatalities in acute poisoning. This study aimed to examine the association between the national public health policy that banned the use of paraquat and the incidence of pesticide-associated mortality.MethodsAll external causes of death from 2009 to 2013 of Korea were analyzed. The intervention was a national public health policy that annulled the authorized use (2011) and banned the purchase of paraquat (2012). Two periods were compared as follows: before (2009-2010) and after (2012-2013) the intervention period. The main outcome was pesticide-associated death coded on the death certificate. Multivariable logistic regression analysis adjustment for gender, age, season and weekday of death, province, education level, marital status, and occupation was performed to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for pesticide-associated mortality. The effect sizes of the intervention across all intents (Accident, Suicide, Homicide, and Undetermined) were compared by adding an interaction term (intervention*intent group) to the above model.ResultsA total of 127,866 deaths from for all external causes were analyzed, including 65,538 from 2009 to 2010 and 62,373 from 2012 to 2013. Pesticide-associated mortality decreased from 9.7% (2009-2010) to 6.5% (2012-2013) (p < 0.001). The AOR (95% CI) of the intervention on pesticide-associated mortality was 0.59 (0.56-0.62). The AORs of the intervention according to intent were 0.72 (0.55-0.96) in the Accident group, 0.61 (0.58-0.64) in the Suicide group, 1.29 (0.43-3.87) in the Homicide group, and 0.44 (0.38-0.50) in the Undetermined group.ConclusionThe national public health policy that banned paraquat resulted in a significant decrease in pesticide-associated mortality.

Background Germline mutations of breast cancer susceptibility gene BRCA1 and BRCA2 (gBRCA1/2) are associated with elevated risk of breast cancer in young women in Asia. BRCA1 and BRCA2 proteins contribute to genomic stability through homologous recombination (HR)-mediated double-strand DNA break repair in cooperation with other HR-related proteins. In this study, we analyzed the targeted sequencing data of Korean breast cancer patients with gBRCA1/2 mutations to investigate the alterations in HR-related genes and their clinical implications. Materials and methods Data of the breast cancer patients with pathogenic gBRCA1/2 mutations and qualified targeted next-generation sequencing, SNUH FiRST cancer panel, were analyzed. Single nucleotide polymorphisms, small insertions, and deletions were analyzed with functional annotations using ANNOVAR. HR-related genes were defined as ABL1, ATM, ATR, BARD1, BRCA1, BRCA2, CDKN1A, CDKN2A, CHEK1, CHEK2, FANCA, FANCD2, FANCG, FANCI, FANCL, KDR, MUTYH, PALB2, POLE, POLQ, RAD50, RAD51, RAD51D, RAD54L, and TP53. Mismatch-repair genes were MLH1, MSH2, and MSH6. Clinical data were analyzed with cox proportional hazard models and survival analyses. Results Fifty-five Korean breast cancer patients with known gBRCA1/2 mutations and qualified targeted NGS data were analyzed. Ethnically distinct mutations in gBRCA1/2 genes were noted, with higher frequencies of Val1833Ser (14.8%), Glu1210Arg (11.1%), and Tyr130Ter (11.1%) in gBRCA1 and Arg2494Ter (25.0%) and Lys467Ter (14.3%) in gBRCA2. Considering subtypes, gBRCA1 mutations were associated with triple-negative breast cancers (TNBC), while gBRCA2 mutations were more likely hormone receptor-positive breast cancers. At least one missense mutation of HR-related genes was observed in 44 cases (80.0%). The most frequently co-mutated gene was TP53 (38.1%). In patients with gBRCA1/2 mutations, however, genetic variations of TP53 occurred in locations different from the known hotspots of those with sporadic breast cancers. The patients with both gBRCA1/2 and TP53 mutations were more likely to have TNBC, high Ki-67 values, and increased genetic mutations, especially of HR-related genes. Survival benefit was observed in the TP53 mutants of patients with gBRCA2 mutations, compared to those with TP53 wild types. Conclusion Our study showed genetic heterogeneity of breast cancer patients with gBRCA1 and gBRCA2 mutations in the Korean populations. Further studies on precision medicine are needed for tailored treatments of patients with genetic diversity among different ethnic groups.

The vascular complications have been a major cause of morbidity and mortality among all subtypes of BCR-ABL1 negative myeloproliferative neoplasms (MPN), but the ethnicity-specific data was limited. We therefore conducted a multi-center retrospective, longitudinal cohort study to evaluate the incidence, characteristics and risk factors of thromboembolic events of MPN patients. Of 256 patients, 27.3% experienced thromboembolic events, majority of which occurred before or within 12 months of MPN diagnosis. The multivariable Cox proportional analyses identified leukocytosis (HR 2.67, 95% CI 1.36–5.24, q = 0.004) and history of thrombosis (HR 9.68, 95% CI 2.00–46.88, q = 0.005) as the risk factors for thromboembolism. In subgroup analysis of polycythemia vera and hemoglobin concentration (HR 1.97, 95% CI 1.28–3.04, q = 0.002) appeared to be a significant risk factor of thrombosis, along with age and thrombosis history. In essential thrombocythemia, severity of the established IPSET score was closely correlated with the frequency of thromboembolic events. In primary myelofibrosis, history of thrombosis was associated with thrombosis events (HR 13.85, 95% CI 1.2–159.5, q = 0.035). Overall survival was worse in patients who experienced thromboembolic events. Our study highlighted the importance of recognizing high risk patients and implementing personalized intervention.

Background Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. Materials and Methods In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. Results Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. Conclusion Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.

Introduction: ALK-positive ALCL accounts for 0.8% of Korean lymphoma patients. ALK TKIs are effective and durable, but clinical outcomes after treatment discontinuation are unknown. We analyzed outcomes and minimal residual disease (MRD) in adult ALK-positive ALCL patients who discontinued ALK TKIs after achieving treatment-free remission. Methods: Six patients who achieved responses to crizotinib (N=5) and ceritinib (N=1) were analyzed. RNA extracted from the blood or tissues before TKI treatment were subjected to multiplex PCR-based next generation sequencing (NGS) using ARCHER® RNA Fusionplex® to detect NPM-ALK fusion. MRD was assessed by droplet digital PCR (ddPCR) of peripheral blood mononuclear cells (PBMCs) after the treatment discontinuation. Undetectable MRD was defined as less than one lymphocytic cell per 10,000 leukocytes (10-4) in peripheral blood. Results: Patients received ALK TKIs as second line (N=3) or third line and beyond (N=3). All achieved complete metabolic responses after median 28.5 months (range, 1.7-93.9) of treatments (Table 1). Before TKI, LY1 patient had no morphologic evidence of bone marrow involvement, but NPM1-ALK fusions were detected by NGS and ddPCR in blood, bone marrow, and tissue. LY1 patient remained in remission at 27.8 months after crizotinib discontinuation. In all patients, NPM1-ALK fusion were not detected in the PBMCs after discontinuing ALK TKIs for median 38.2 months (range, 0-61.9). No patient re-initiated anti-lymphoma therapies. Conclusion: Out data demonstrated that treatment-free remission was durable for more than two years in ALK-positive ALCL patients following the cessation of ALK TKIs. MRD-guided discontinuation decision may be considered for ALK-positive ALCL patients treated with ALK inhibitors who had undetectable MRD. Table 1. Summary of patient characteristics and outcomes of ALK TKI discontinuation No. Sex Age at diagnosis Ann Arbor stage ALK TKI Lines of prior therapy Treatment duration of ALK TKI (months) Reason for cessation Duration of ALK TKI cessation (months) Best response to ALK TKI Time of MRD assessment after TKI cessation MRD after TKI cessation 1 M 22 IIB Crizotinib 3 93.9 Fertility 27.8 CR 5.6 Negative 2 F 20 IVB Crizotinib 1 90.9 Fertility 25.9 CR 0.0 Negative 3 M 23 IV Ceritinib 1 42.7 Adverse event 61.9 CR 61.9 Negative 4 F 58 IV Crizotinib 3 1.7 Cost 86.6 CR 72.1 Negative 5 F 64 IVB Crizotinib 1 13.6 Cost 31.0 CR 14.4 Negative 6 M 75 IV Crizotinib 2 11.7 Cost 80.2 CR 62.0 Negative Citation Format: Jinyong Kim, Soyeon Kim, Tae Min Kim, Jeonghwan Youk, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo. Treatment-free remission after discontinuation of ALK tyrosine kinase inhibitors (TKIs) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2181.