Since the FDA approval of ibrutinib in 2012, the treatment landscape for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has undergone a paradigm shift. Nevertheless, the disease remains incurable, posing ongoing clinical challenges. In Korea, these challenges are further compounded by unique characteristics of patients and national healthcare system. The multicenter retrospective analysis included 519 patients diagnosed with CLL/SLL between 2006 and 2024 across three major Korean institutions. The median age at diagnosis was 62 years. Among 267 patients who received first-line therapy, 68.9% (184/267) were treated with immunochemotherapy, 19.4% (52/267) with cytotoxic chemotherapy, and 11.2% (30/267) with a Bruton tyrosine kinase (BTK) inhibitors. Since the Korean approval of ibrutinib in 2016, BTK inhibitor use has steadily increased. Subgroup analyses demonstrated that patients receiving BTK inhibitor-based therapy had more favorable outcomes compared to those treated with immunochemotherapy. This study provides the most comprehensive real-world reflection of current diagnostic and therapeutic practices in Korea. Through comparative analysis with international data, it offers valuable insights into the limitations of current CLL/SLL care and may inform future strategies to optimize management in the Korean context.

Breast cancer (BRCA)'s molecular heterogeneity complicates prognosis and treatment. Tumor Doubling Time (TDT), a critical growth rate metric with clinical and prognostic significance, offers untapped potential as a biomarker to decode heterogeneity and improve therapeutic strategies. Based on transcriptomic and clinical data from TCGA and GEO, this study analyzed BRCA. Through differential expression and survival analyses, differentially expressed tumor doubling time-related genes (TDTRGs) with prognostic significance were identified. Consensus clustering using these genes defined two molecular subtypes. A prognostic risk model was constructed and validated through LASSO and multivariate Cox regression. Comprehensive evaluation was performed on these molecular subtypes and risk groups, encompassing immune infiltration (ssGSEA, CIBERSORT, ESTIMATE), mutational burden, response to immunotherapy (IMvigor210), and drug sensitivity (CellMiner, pRRophetic). This study constructed and validated an 8 gene prognostic risk model demonstrating robust predictive performance in both training (AUCs: 1-year=0.703, 3-year=0.693, 5-year=0.671) and validation cohorts. The low-risk group showed significantly enhanced immune cell infiltration, elevated immune checkpoint expression, and improved response to immunotherapy. Conversely, the high-risk group displayed increased tumor purity, metabolic reprogramming (e.g., respiratory electron transport), genomic instability, higher tumor mutational burden, and differential drug sensitivity (e.g., resistance to Gemcitabine/Tamoxifen). This study establishes a novel TDTRGs framework for BRCA molecular classification and validated prognostic stratification. It reveals key disparities in immune microenvironment and genomic stability, enhancing understanding and guiding personalized therapeutic strategies.

Metastatic breast cancer (MBC) with severe hepatic dysfunction due to liver crisis presents a significant treatment challenge, as conventional chemotherapy often requires dose modifications, leading to reduced efficacy. The combination of platinum, 5-fluorouracil (5FU), and folinate (PFL) offers a rational treatment strategy. This study evaluates the efficacy and safety of PFL in MBC patients with liver crisis and explores predictive markers for treatment response. This retrospective cohort study, conducted at Taipei Veterans General Hospital, Taiwan, included 44 MBC patients with bilirubin ≥3 mg/dL treated between January 2015 and June 2024. Outcomes included bilirubin response rate (≥50% reduction from baseline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. The AUC analysis was used to determine the optimal cutoff for liver function assessment model, and Cox regression identified independent prognostic factors. Among the 44 patients, 47.7% achieved a bilirubin response within a median of 19 days. Overall, the median PFS and OS were 1.4 and 1.9 months, respectively, but improved to 4.6 and 7.8 months in those achieving bilirubin response. The ORR was 22.7%, and the DCR was 29.5%. A FIB-4 score <9.1 predicted a 65% bilirubin response rate, while FIB-4 >9.1 was also an independent predictor of OS. Grade 3 adverse events occurred in 36.4% of patients. The PFL regimen is effective in MBC patients with severe liver crisis with hyperbilirubinemia. A FIB-4 score <9.1 may serve as a potential prognostic factor for bilirubin response and is associated with improved survival outcomes.

Low-dose computed tomography (LDCT) is effective in reducing lung cancer mortality among high-risk smokers. The Korean National Lung Cancer Screening Program (KNLCS), the world's first nationwide lung cancer screening initiative using LDCT, was launched in 2019. This study aimed to evaluate the KNLCS uptake rates in relation to participants' economic status and changes in positive screening rates across screening rounds. Data from the National Health Insurance Service (NHIS) and National Cancer Screening Information System for 2019-2023 were analyzed. Eligible participants in the KNLCS were current smokers aged 54-74 years with a smoking history of at least 30 pack-years. The KNLCS provides counseling by physicians on screening results and smoking cessation. Screening uptake rates, counseling rates, and Lung CT Screening Reporting and Data System (Lung-RADS) distributions were assessed. Screening uptake rates increased from 24.7% in 2019 to 51.2% in 2023 (p < 0.001). Economic disparities were observed, with higher-income groups showing consistently higher uptake rates than lower-income group. Screening positive rates has been decreased from 9.1% in 2019 to 7.0% in 2023 according to increasing the proportion of subsequent screening participants. The inter-institutional variance in Lung-RADS category 4 decreased significantly over the years (p < 0.001). The KNLCS rapidly increased screening uptake rates by systematically inviting eligible participants. Positive screening rates decreased primarily due to a reduction in Lung-RADS category 3 findings in subsequent rounds.

Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study investigated the clinical characteristics, oncologic outcomes, and histologic subtype-specific features of oligometastatic STS. We reviewed records of 1,243 patients with extremity/trunk STS who underwent curative surgery between 2000 and 2023. Oligometastatic recurrence occurred in 170 (13.6%), 149 of whom received local ablative therapy (LAT). Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed, along with prognostic factors and subtype-specific characteristics. The median follow-up was 52.5 months. Surgery alone was the most common LAT (71.2%), followed by surgery with radiotherapy, radiotherapy alone and radiofrequency ablation. The median DSS was 50.0 months (95% confidence interval [CI], 31.5-68.5), with a 5-year DSS rate of 45.2%. The median PFS was 12.0 months (95% CI, 7.6-16.4), with a 5-year PFS of 28.1%. On multivariate analysis, LAT was independently associated with longer DSS (hazard ratio [HR], 9.629; p<0.001). Smaller oligometastatic lesion size and adequate local control of the primary tumor were also independently associated with longer DSS. Metastasis-free interval > 6 months independently predicted longer PFS. Histologic subtypes demonstrated distinct clinical behaviors; for example, myxofibrosarcoma had a lower metastatic rate but poorer DSS, whereas synovial sarcoma showed relatively favorable long-term survival. Oligometastatic STS represents an intermediate disease state in which LAT can provide meaningful survival benefit. Subtype-specific differences in metastatic behavior and survival outcomes would support individualized, multimodal, and potentially curative treatment strategies.

In 2006, the IARC reported that inorganic lead is carcinogenic in animals but with limited evidence in humans. In addition, some studies have reported that exposure to lead increases the risk of lung cancer, but this remains controversial. Therefore, we aimed to assess the risk of developing lung cancer according to blood lead levels in workers with occupational lead exposure. A retrospective cohort study of male workers with 2009 blood lead (PbB) concentrations was conducted using nationwide special health examination data (SHED) from 2009 to 2021 and cancer registry data from 1999 to 2020 from the Republic of Korea. Standardized incidence ratios (SIRs) for lung cancer risk at each PbB level were calculated with a five-year wash-out period, adjusting for age, smoking status, duration of exposure, and the number of co-exposures to lung carcinogens. The study included 26,092 workers with an average follow-up period of 9.98 years. Compared with workers with PbB levels <3.130 µg/dL, the adjusted SIRs for lung cancer risk were 2.95 (95% confidence interval [CI]: 1.47-5.27) and 3.13 (95% CI: 1.82-5.00) for workers with PbB levels of 3.130-4.899 and ≥4.900 µg/dL, respectively, indicating a significant dose-response trend. This study demonstrates a significant association between lead exposure and an increased risk of lung cancer, highlighting the need for stronger occupational health policies and ongoing monitoring of workers exposed to lead. The observed dose-response relationship underscores the importance of reassessing current occupational safety standards and strengthening measures to reduce lead exposure in the workplace.

Leucine-rich repeats (LRR) play important roles in tumorigenesis and may serve as novel biomarkers for cancer therapy. The expression of leucine-rich repeat-containing protein 15 (LRRC15) is increased in several cancers. However, it is still unknown whether LRRC15 is involved in breast cancer and autophagy. This study conducted bioinformatic analysis on LRRC15 expression and prognosis in breast cancer. Clinical samples were collected and subjected to immunohistochemistry and qRT-PCR to analyze LRRC15 expression in tissues and serum. Clonal formation, MTT, wound healing, and Transwell assays were used to examined breast cancer cell proliferation, migration, and invasion. Western blotting detected autophagy-related and PI3K/AKT/mTOR signaling pathway proteins. Patients with breast cancer having elevated expression of LRRC15 have a markedly worse prognosis compared with those having lower levels. Furthermore, LRRC15 expression was strongly correlated with tumor aggressiveness and poor differentiation in breast cancer cell lines. Functionally, LRRC15 drives cancer cell proliferation, migration, and invasion. LRRC15 inhibited autophagy in breast cancer cells, thus modulating their proliferative capacity. Mechanistically, LRRC15 exerted these effects by activating the PI3K/AKT/mTOR signaling cascade. LRRC15 regulates autophagy-induced proliferation and other biological activities of breast cancer cells through the PI3K/AKT/mTOR signaling pathway.

This study aimed to investigate alteration of HER2 status after neoadjuvant chemotherapy (NAC) in breast cancer and its impact on clinical outcomes of patients, focusing on HER2-low status. We retrospectively reviewed clinicopathological data of 1,063 breast cancer patients who underwent NAC between 2013 and 2020. Using paired samples of 670 patients with residual disease after NAC, we analyzed HER2 discordance rates between pre- and post-NAC samples, relationships between HER2 discordance and clinicopathological characteristics of tumors, and clinical outcomes of the patients. Pre-NAC HER2-low status was associated with a lower pathological complete response rate and higher Residual Cancer Burden class compared with HER2-zero and HER2-positive status. However, in subgroup analysis by hormone receptor (HR) status, no statistical differences were found in chemo-responsiveness between them. Following NAC, the overall HER2 discordance rate was 21.2% (κ = 0.676), and the most common type of alteration was zero-to-low (11.5%) conversion, followed by low-to-positive (3.6%) conversion. HER2 discordance was significantly associated with lower HER2 levels and HR positivity before NAC, as well as lymphovascular invasion, higher ypT stage, and axillary node metastasis in residual disease after NAC. In survival analyses, HER2 discordance was found to be an independent prognostic factor for poor disease-free survival of the patients, particularly within the HR-positive subgroup. Given the prognostic implications of HER2 discordance which primarily involves zero-to-low conversion and the therapeutic benefits of newly developed antibody-drug conjugates in HER2-low breast cancers, HER2 status should be re-evaluated in surgical resection specimens following NAC.

The incidence, prevalence and survival rates of gastric cancer are high, and the prognostic effects of healthy behaviors among survivors have not been well investigated. Therefore, We aimed to assess the effects of postdiagnosis healthy behaviors and behavior changes after gastric cancer diagnosis on all-cause mortality. As a population-based retrospective cohort study, we used a cancer public library sample DB of gastric cancer patients between 2012 and 2019. Information from regular health check-up examinations were used to investigate their anthropometric measures, physical activities, alcohol consumption, and smoking status before and after cancer diagnosis. Hazard ratios (HRs) for all-cause deaths with 95% confidence intervals (CIs) were estimated via the Cox proportional hazards model. We analyzed 9,717 gastric cancer patients and 5,929 of those as a subgroup to assess the effects of behavior changes. Reduced mortality was shown among cancer patients who met the recommended criteria after the cancer diagnosis for physical activity (adjusted HR = 0.67 [95% CI=0.49-0.93], mean frequencies of moderate to vigorous physical activity per week: ≥5 days vs. 0 days) and smoking cessation (0.77 [0.61-0.97], smoking status: never-smokers vs. current smokers). Participants who reported enhancement in behaviors had significantly lower mortality than the others who reported no or limited changes in physical activity (0.73 [0.55-0.96]) and smoking status (0.56 [0.38-0.83]). The current study highlights the advantages of physical activity and smoking cessation in reducing mortality, and these benefits are even greater when patients improve their behavior after cancer diagnosis.

Neoadjuvant systemic therapy (NST) is a systemic treatment for locally advanced or initially unresectable breast cancer before surgery. Patients achieved total pathological complete response (tpCR) after NST exhibited significantly better overall prognosis than patients with non-pCR. This study collected baseline indicators, body composition indicators and tpCR results of breast cancer patients at the First Affiliated Hospital of Nanjing Medical University. Patients were divided into training set and validation set in a ratio of 7:3. Univariate and multivariate logistic regression analyses were performed, and the probability of tpCR was predicted by constructing nomograms based on the results of the multivariate logistic regression analysis. The study included 500 patients between 2014 and 2022 with breast cancer who underwent NST. The training set and validation set consist of 350 and 150 patients respectively. Patients with progesterone receptor-negative status (p < 0.001), HER2 receptor-positive status (p < 0.001), large body surface area (p=0.091), low skeletal muscle index (p=0.008), and high skeletal muscle density (p < 0.004) were more likely to achieve tpCR. Patients with American Joint Committee on Cancer (AJCC) T-stage 4 (p=0.126), AJCC N-stage 1 (p=0.026) were less likely to achieve tpCR. Existing tpCR prediction models mostly focus on tumor biological characteristics and ignore the effect of body compositions. This study constructed a nomogram to predict tpCR in patients with breast cancer undergoing NST based on baseline and body composition indicators. This nomogram can help assess efficacy and optimize treatment strategies, thus improving the overall prognosis of patients.