Background:Small-molecule tyrosine kinase inhibitors (TKIs) have been extensively investigated in the management of advanced or metastatic gastric cancer (GC); however, their specific efficacy and optimal therapeutic role remain subjects of ongoing debate. Given the accumulation of new trial evidence and persistent uncertainty regarding patient subgroups most likely to benefit, we conducted an updated systematic review and meta-analysis to comprehensively evaluate the impact of TKIs on clinical outcomes in advanced GC. Methods:We systematically searched PubMed, Web of Science, and Embase databases for articles published up to March 1, 2026, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing TKI-containing regimens versus non-TKI regimens in patients with cytologically or pathologically confirmed advanced GC were eligible. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled for progression-free survival (PFS) and overall survival (OS) using random-effects models. Risk ratios (RRs) with 95% CIs were calculated for objective response rate (ORR) and disease control rate (DCR). Study quality was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and evidence certainty was evaluated using the GRADE framework. Results:Ten RCTs comprising 1810 patients (1169 experimental, 641 control) met inclusion criteria. TKI-containing regimens significantly improved OS (HR 0.76, 95% CI 0.63-0.92, P = 0.005; moderate certainty) and prolonged PFS (HR 0.51, 95% CI 0.35-0.73, P = 0.0003; low certainty) compared to non-TKI regimens. DCR was markedly improved (RR 3.98, 95% CI 2.08-7.58, P < 0.0001; moderate certainty), whereas ORR did not reach statistical significance (RR 2.03, 95% CI 0.83-5.01, P = 0.12; low certainty). Subgroup analyses revealed that TKI monotherapy significantly improved both OS and PFS, whereas combination with chemotherapy did not demonstrate additive survival benefits. Grade ≥3 adverse events, including hypertension (RR 31.5, 95% CI 11.71-84.73) and hand-foot syndrome (RR 55.0, 95% CI 7.65-395.32), were more frequent with TKIs but were largely predictable and clinically manageable. Conclusions:This updated meta-analysis provides moderate-certainty evidence that TKI-containing regimens confer significant survival benefits in advanced GC, with a manageable safety profile. The differential efficacy observed between monotherapy and combination regimens underscores the need for biomarker-driven patient selection and optimization of treatment sequencing. These findings refine the current evidence base and support the continued role of TKIs in treatment algorithms for advanced GC, while highlighting critical knowledge gaps requiring further investigation. Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024544568, identifier CRD42024544568.

Background:CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) have become the standard of care for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, real-world data from China's central regions remain limited. This study aimed to evaluate the real-world treatment patterns and efficacy of CDK4/6i in HR+/HER2- MBC patients across the Dongting Lake region in China. Methods:This multicenter retrospective study included 590 HR+/HER2- MBC patients treated with CDK4/6i between 2016 and 2025 in five tertiary cancer centers in the Dongting Lake area of Hunan province, China. Patient demographics, treatment patterns, progression-free survival (PFS), and prognostic factors were analyzed. Results:Among 616 initially screened patients, 590 met eligibility criteria. Of these, 63.39% received CDK4/6i as first-line treatment and 25.59% as second-line. The most commonly used CDK4/6i were abemaciclib (33.39%), dalpiciclib (28.98%), palbociclib (25.76%), and ribociclib (10.85%). Median PFS was significantly longer in the first-line group than in the second-line group (32.3 vs. 17.6 months, P<0.001). While the objective response rate (ORR) was numerically higher in the first-line setting (49.52% vs. 42.31%), only the disease control rate (DCR) showed statistical significance (97.14% vs. 91.03%). Multivariate Cox analysis identified several independent predictors of shorter PFS: de novo stage IV disease (HR =1.50), Ki-67 ≥30% (HR =1.60), liver metastasis (HR =2.26), lung metastasis (HR =1.53), and use of CDK4/6i as second-line (HR =2.24), while disease-free interval ≥5 years was protective (HR =0.65, P=0.01). Conclusions:CDK4/6i demonstrates favorable real-world efficacy in HR+/HER2- MBC patients in central China, particularly in the first-line setting. Several clinical factors may aid in treatment selection and risk stratification.

Therapeutic options for patients with poor-prognosis invasive triple-negative breast cancer (TNBC) remain lacking. Although novel treatment strategies have demonstrated improved efficacy, they are frequently associated with substantial financial costs. Consequently, rigorous economic evaluation is essential to inform clinical and policy decisions. A three-state Markov model with a lifetime horizon was developed using clinical efficacy data from the ASCENT-04/KEYNOTE-D19 trial, along with treatment-related cost inputs. Lifetime costs and health outcomes in cases of advanced TNBC for patients undergoing treatment with either sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab were estimated with the developed model. Model uncertainty and structural stability were examined via probabilistic and deterministic sensitivity analyses. Total costs, quality-adjusted life-years (QALYs), incremental net health benefit (INHB), incremental net monetary benefit (INMB), and incremental cost-effectiveness ratios (ICERs) were examined at a willingness-to-pay (WTP) threshold of 150,000/QALY in the USA. The estimated lifetime cost was1,831,187 for sacituzumab govitecan plus pembrolizumab and 574,011 for chemotherapy plus pembrolizumab. Corresponding health outcomes were 5.28 QALYs and 4.74 QALYs, respectively. The resulting ICER was2,323,487 per QALY gained. The INHB and INMB were -7.84 QALYs and -1,176,175, respectively. The most influential variables in the model included the utility value assigned to progression-free survival, patient body weight, and the cost-effectivness of sacituzumab govitecan. Sensitivity analysis demonstrated that the model findings were robust. At current market prices, sacituzumab govitecan plus pembrolizumab showed limited cost-effectiveness as a first-line option relative to chemotherapy plus pembrolizumab for treating advanced TNBC.

2508 Background: Advanced hepatocellular carcinoma (HCC) remains a high unmet-medical-need malignancy with limited therapeutic options. Ori-C101 is a novel, armored, autologous GPC3-directed CAR-T cell therapy. Following promising results from early-phase trials (ChiCTR190028121; NCT05652920, BEACON study), we shall herein update outcomes from the BEACON study with focusing on long-term safety, durability of response, and survival after more than 2 years of follow-up. Methods: This is an open-label, multi-center, phase Ib dose-escalation and expansion study enrolled patients (pts) with GPC3 + advanced HCC who had progressed on ≥2 prior lines of systemic therapy (including ICIs and TKIs). A single dose of Ori-C101 was administered via hepatic arterial infusion to enhance regional cell delivery. Integrated analyses assessed safety, tolerability, PK, and efficacy (per RECIST v1.1)，aiming to determine the RP2D. Results: As of Dec 24, 2025, 19 pts received Ori-C101 infusion across 4 dose levels (DLs). All pts had BCLC stage B/C disease and 31.6% (6/19) had extrahepatic metastases. Pts were previously treated with a median of 3 lines (range 2–8) therapies. Safety: Safety remained manageable; no late-onset nor cumulative toxicities were observed through the extended follow-up period. The most common ≥G3 TEAEs (≥10.0%) were transient hematologic toxicities and hepatic laboratory abnormalities. CRS occurred in 100.0% (19/19) of pts; while ≥G3 CRS observed in 42.1% (8/19). No ICANS occurred. One pt at DL4 experienced a DLT of G4 CRS complicated by secondary DIC. Efficacy: In 18 efficacy-evaluable pts, Ori-C101 demonstrated a robust dose-dependent response. Confirmed ORR was 50.0% (9/18); DCR was 77.8% (14/18). At RP2D (DL3), the confirmed ORR and DCR were 66.7% (6/9) and 88.9% (8/9), respectively. Critically, responses were not only rapid but also remarkably durable. 88.9% (8/9) of responders achieved objective response within 1.1 months; at M3, 83.3% (5/6) of responders at the RP2D remained PR. Notably, 1 pt at DL4 achieved CR with a duration exceeding 20 months. Preliminary overall survival data indicate a substantial long-term survival benefit with a median OS of 14.4 months (range 2.6–22.0). In addition, Dose-Exposure-Responses analysis showed dose-dependent CAR-T cells expansion, pharmacodynamic effects and improved tumor response. Conclusions: Ori-C101 demonstrates a manageable safety profile and compelling, durable anti-tumor activity in GPC3 + advanced HCC. The combination of high ORR and prolonged survival benefit distinguishes Ori-C101 as a potential paradigm-shifting therapy for patients who have failed standard-of-care treatments. A phase II/III study is currently underway to further confirm the efficacy and asses the safety of Ori-C101. Clinical trial information: NCT05652920 .

Accurately predicting axillary pathological complete response (ypN0) after neoadjuvant chemotherapy (NACT) is of vital importance for making decisions regarding the axillary treatment plan for breast cancer patients. This study aimed to identify factors influencing ypN0 and to develop a predictive nomogram to evaluate the probability of ypN0 in NACT-treated patients with breast cancer. Overall, 1559 patients with cT1-4N1-2M0 breast cancer who received NACT and mastectomy between 2000 and 2014 in 12 institutions in China were analyzed retrospectively. Patients treated in three cancer hospitals (training set, n = 1072) were used to construct a nomogram based on multivariate logistic regression analyses. The nomogram was validated by determining the area under the receiver operating characteristic curve (AUC) and calibration curve values in patients from nine other general hospitals (validation set, n = 487). In the training and validation sets, 26.8

Purpose:Deep inspiration breath-hold (DIBH) is widely used in breast cancer radiation therapy to reduce cardiac radiation exposure. However, not all patients benefit from it. This study evaluated the performance of a convolutional neural network (CNN) model to predict cardiac doses under free-breathing (FB) and DIBH conditions for left-sided breast cancer radiation therapy, aiming to identify patients most likely to benefit from DIBH based on cardiac dosimetry. Methods and Materials:A total of 265 left-sided breast cancer patients undergoing whole-breast irradiation were included, with 200 retrospectively assigned to the training set and 65 prospectively assigned to the test set. The CNN model incorporated anatomic data, including organ structures and distance-to-target volume maps, to predict 3-dimensional dose distributions. Predicted dosimetric parameters were compared with clinical data to assess accuracy, and agreement between model-based and clinical classifications of DIBH benefit was evaluated using kappa statistics. Results:The CNN model demonstrated high accuracy in predicting cardiac dosimetric parameters, with correlation coefficients ranging from 0.84 to 0.99 for mean dose (Dmean) and D2% in the heart, left anterior descending coronary artery, and ventricles under both FB and DIBH conditions. The model also accurately predicted dose-volume histograms for these structures, with no significant differences between clinical and predicted values. Using a classification approach based on heart Dmean in FB and its reduction via DIBH, the model correctly identified 90.8% of patients as DIBH beneficiaries (kappa value, 0.876). When applying a threshold of ΔHeart Dmean ≥1 Gy, the model identified significant DIBH benefits in 63.1% of patients, with 96.9% agreement between predicted and clinical classifications. Conclusions:The CNN-based model provides an efficient and accurate framework for predicting cardiac dose and identifying patients most likely to benefit from DIBH. Future studies should explore its applicability across broader radiation therapy scenarios and evaluate its long-term impact on cardiac outcomes.

Target trial emulation (TTE) has demonstrated popularity because of its ability to improve the reliability of causal inference from observational data. Nevertheless, knowledge about the current use, potential challenges, and insights of target trials in oncology is scarce. A total of 90 TTE studies in cancer areas were identified through systematic reviews in PubMed and Embase. Among the 54 applications in cancer treatment, registry databases (44.4%) and overall survival (OS, 63.0%) were predominantly used as data sources and primary endpoints, respectively. Approximately 30 (55.6%) of the included TTE cases were associated with immortal time bias, and 21 (38.9%) were associated with prevalent user bias. Among the 21 trials from 13 studies that aimed to calibrate the results from preexisting randomized controlled trials (RCTs), only 42.9% met both statistical agreement and estimate agreement. The availability of fit-for-purpose data sources and uncertainty about result concordance were the main hurdles limiting the quantity and quality of TTE in oncology areas. Promoting regulatory acceptance by initiating special projects could be crucial for the expanded application of real-world data (RWD) using TTE. Potential solutions, such as the integration of electronic medical records at the regional or country level, linkage with insurance claims databases, the modernization of eligibility criteria, the use of OS as the primary endpoint, and other best practices, were recommended for improving the feasibility and quality of oncology TTE.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis, underscoring the urgent need to identify novel therapeutic targets. The epigenetic regulator TET1, a key enzyme involved in active DNA demethylation, has been implicated in various cancers, however, its precise role in HCC remains controversial and poorly defined. This study demonstrates that TET1 is significantly upregulated in HCC tissues, and elevated TET1 expression is associated with advanced tumor stage, shorter overall survival and reduced disease-free survival in patients. Functional assays revealed that TET1 knockdown significantly suppressed HCC cell proliferation and induced apoptosis; it also triggered G1-phase cell cycle arrest. Mechanistically, we found that the oncogenic effects of TET1 are mediated through activation of the PI3K/Akt signaling pathway. In summary, our results establish TET1 as a critical promoter of HCC progression and elucidate its role in regulating the PI3K/Akt pathway. These findings highlight its value as both a prognostic biomarker and a potential therapeutic target in HCC.

Claudin 18.2 (CLDN18.2) is a functional subtype generated by alternative splicing of the CLDN18 gene. It is aberrantly overexpressed in a variety of gastrointestinal solid tumors such as gastric cancer and pancreatic cancer, and has emerged as a promising target for tumor targeted therapy. To date, zolbetuximab, a monoclonal antibody targeting CLDN18.2, has demonstrated survival benefits in phase III clinical trials. Antibody-drug conjugates, bispecific antibodies and chimeric antigen receptor T cell therapies also exhibit favorable application potential. Nevertheless, multiple challenges remain in this field. Distinction between CLDN18.1 and CLDN18.2 subtypes is often ambiguous, and the lack of unified immunohistochemistry testing criteria, including antibody selection and specimen types, leads to conflicting findings on prognostic research. Additionally, intratumoral heterogeneity, differential functions across tumor types and tumor microenvironment limitations further compromise the efficacy of targeted therapy. As a narrative review, this article systematically elaborates the molecular structure, expression regulatory mechanisms and clinicopathological value of CLDN18.2. Based on the data of 58 global clinical trials, it analyzes the current status, existing problems in testing standardization and drug development. Future directions are proposed, including standardizing detection protocols, developing differentiated drugs, optimizing combination regimens and overcoming drug resistance, aiming to provide references for the clinical translation and standardized application of CLDN18.2-targeted therapies.

Objective As neoadjuvant immunotherapy becomes increasingly incorporated into clinical trial protocols for lung cancer, patients are required to make complex decisions under conditions of uncertainty. However, the dynamic processes underlying their decision-making remain insufficiently understood. Methods A qualitative study informed by grounded theory methodology was conducted at the Clinical Trial Center of the Cancer Hospital, Chinese Academy of Medical Sciences. In-depth, semi-structured interviews were performed with 16 patients with lung cancer who were undergoing neoadjuvant immunotherapy within clinical trials. Data were analyzed using open, axial, and selective coding to construct a theoretical model of the decision-making process. Results The decision-making process evolved through five interrelated phases: initiation, deliberation and trade-off, commitment formation, adjustment, and post-decision evaluation. Decision-making satisfaction was shaped by both internal factors (e.g., personal beliefs, perceived risk tolerance, treatment expectations) and external influences (e.g., physician communication, family involvement, trial-related information). Conclusions We developed a grounded theoretical model describing how patients with lung cancer navigate decisions regarding participation in neoadjuvant immunotherapy clinical trials. The findings highlight the need for stage-specific and culturally sensitive decision support strategies delivered by clinical research teams. Addressing both internal and contextual determinants may enhance decision quality and satisfaction among treatment-naïve patients considering trial participation.

Gynecomastia is a benign proliferation of glandular tissue in the male breast, with incidence rate of 30–60 www.springer.com/00266 .

ObjectiveTo lay a foundation for formulating clinical evaluation and regulatory policies regarding radiotherapy equipment in China. Methods Comprehensive retrieval and comparison of the regulatory requirements for radiotherapy equipment from regulatory agencies in the United States, the European Union, and China are conducted, and their similarities and differences are analyzed. ResultsFor mature radiotherapy systems in the European and American regions, the comparison of performance parameters serves as an important basis for determining whether a product can be marketed. Both the European Union and China regard the clinical evaluation report as a crucial part of the medical device review and submission process. Conclusion Identifying clear state of the art standards, performance parameters, and clinical indicator parameters, and establishing relevant technical guidelines are important directions for promoting the standardized development of radiotherapy equipment supervision.

BACKGROUND AND PURPOSE:Breast cancer (BC) is the primary cause of cancer-related deaths among women worldwide, with increasing evidence pointing to the effect of metabolic factors, particularly lipid levels, in its pathogenesis. In this research, Mendelian randomization (MR) was employed to explore the causality between four plasma lipid traits-total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)-and the risk of BC. Additionally, we explored the potential mediating effects of coronary artery disease (CAD), total testosterone (TT) on these associations and possible mechanisms through bioinformatics analyses. METHODS:Data of genome-wide association study (GWAS) on lipids, CAD, TT and BC were obtained from public sources and websites as part of a genome-wide association research. The inference of causality was primarily assessed through the inverse variance weighting (IVW) approach, with supplementary tests for horizontal pleiotropy and heterogeneity. To verify the directionality of causal relationships, the MR Steiger test was applied. Additionally, reverse causality was evaluated by regarding BC as the exposure. To adjust for confounders, multivariate MR (MVMR) was performed, followed by a two-step mediation analysis to investigate the mediating roles of CAD in the lipid-BC association, and of TT in the CAD-BC relationship. The intersecting SNP (rs11556924) between causal pathways was established through a Venn diagram and its associated gene (Zinc Finger C3HC-Type Containing 1, ZC3HC1) was identified through the g:Profiler database. The expression of ZC3HC1 was further explored using the TIMER, GEPIA2 and HPA database. Finally, enrichment analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interactions (PPI) network analysis were conducted on ZC3HC1 and its related genes. RESULTS:The random-effects IVW analysis yielded the following results: HDL-C on CAD (OR = 0.843, 95% CI 0.771-0.921, P < 0.001), CAD on BC (OR = 0.935, 95% CI 0.892-0.980, P = 0.005), HDL-C on BC (OR = 1.127, 95% CI 1.059-1.199, P < 0.001), CAD on TT (OR = 0.987, 95% CI 0.975-0.998, P = 0.020) and TT on BC (OR = 1.354, 95% CI 1.148-1.598, P < 0.001). The MR Steiger test results support the validity of the inferred causal direction (P < 0.001). There were no discernible causal relationships between BC and HDL-C/CAD according to reverse MR analysis (P > 0.05). Following MVMR adjustment, the causal effects of HDL-C, CAD, and TT on BC were still statistically significant (P < 0.05). Besides, the two-step mediation analysis indicated that CAD mediated 7.8% of the causal effect of HDL-C on BC, whereas TT mediated 6.1% of the causal effect between CAD and BC. The expression of ZC3HC1 showed no significant expression difference between normal and BC tissues (P > 0.05), which might indicate a carcinogenic effect independent of expression levels but driven by functional alterations induced by variants (C > T). Functional network analysis suggested that ZC3HC1 was associated with multiple signal pathways in cancers, such as PI3K-Akt and MAPK signal pathways. CONCLUSIONS:From a genetic perspective, our study reveals that there is causality between HDL-C levels and BC risk, with CAD and TT acting as partial mediators in this relationship. Moreover, our study firstly establishes a potential link between CAD-associated SNP (rs11556924), the corresponding gene (ZC3HC1) functional dysregulation, and the initiation of BC. These findings shed light on the biological links between lipids and BC, potentially contributing to future prevention and treatment strategies.

Cancer cells are characterized by their altered energy metabolism. A hallmark of cancer metabolism is aerobic glycolysis, also called the Warburg effect. Hexokinase 2 (HK2), a crucial glycolytic enzyme converting glucose to glucose-6-phosphate, has been identified as a central player in the Warburg effect. Deletion of HK2 decreases cancer cell proliferation in animal models without explicit side effects, suggesting that targeting HK2 is a promising strategy for cancer therapy. In this study, we discovered a correlation between HK2 and the tumor immune response in triple-negative breast cancer. Inhibition of HK2 led to a reduction in G-CSF expression in 4T1 cells and a decrease in the development of myeloid-derived suppressor cells which, in turn, enhanced T cell immunity and prolonged the survival of 4T1 tumor-bearing mice. Furthermore, the HK2 inhibitor 3-BrPA improved the therapeutic efficacy of anti-PD-L1 therapy in 4T1 tumor-bearing mouse models. This study highlights the potential of glycolysis-targeting interventions as a novel treatment strategy, which can be combined with immunotherapy for the treatment of triple-negative breast cancer.

Background:The role of postmastectomy radiotherapy (PMRT) in breast cancer patients achieving pathologically negative lymph nodes (ypN0) after neoadjuvant chemotherapy (NAC) remains controversial due to heterogeneous recurrence risks and lack of prospective evidence. Objectives:To evaluate the effects of PMRT in ypN0 patients after NAC. Design:Multicenter retrospective study. Methods:Data of 624 breast cancer patients with ypN0 was assessed to establish a recurrence risk score model based on a disease-free survival (DFS) rate-based multivariate Cox model. Moreover, the locoregional control (LRC), DFS, and overall survival (OS) rates in PMRT and non-PMRT patients were calculated using the Kaplan-Meier method. Results:All patients received a median of four NAC cycles, followed by mastectomy and axillary lymph node dissection; moreover, 257 (41.2%) patients underwent PMRT. Over a median follow-up duration of 74 months, the 5-year LRC, DFS, and OS rates for all patients were 96.6%, 90.1%, and 95.7%, respectively. The differences in the LRC, DFS, and OS rates between PMRT and non-PMRT patients were nonsignificant in the univariate and multivariate analyses. By using our recurrence risk score model based on four factors (i.e., age, clinical N stage, NAC cycle number, and pathological tumor stage after NAC), we stratified the patients into low- and high-risk groups; their 5-year rates of LRC (98.8% vs 93.9%), DFS (95.1% vs 83.8%), and OS (98.4% vs 92.4%) were significantly different (all p < 0.05). PMRT improved LRC (97.6% vs 90.8%, p = 0.027) but not DFS or OS in high-risk patients and had no benefit in low-risk patients. Conclusion:Our recurrence risk score model effectively distinguished ypN0 patients with different recurrence risk stratifications. PMRT improved LRC but not DFS or OS in high-risk patients and low-risk patients did not benefit from PMRT.

Purpose: Radiation-induced lymphopenia (RIL) correlates with poor prognoses in solid tumors. This study aimed to investigate the post–radiation therapy (RT) longitudinal lymphocyte changes and the impact of different RT techniques on RIL in breast cancer patients. Methods and Materials: We prospectively assessed 607 breast cancer patients who received hypofractionated postmastectomy RT in 8 hospitals. Radiation therapy techniques included integrated photon-based intensity modulated technique (integrated RT) and a combination of photon irradiation of supraclavicular nodes and electron irradiation of the chest wall and/or the internal mammary node (hybrid RT). Peripheral lymphocyte counts (PLC) were determined before RT, weekly during RT, at 1 and 2 weeks, 3 and 6 months post–RT, and then every 6 months. The primary outcome was the nadir PLC during RT, for which associated factors were analyzed. Univariate, multivariable linear regression and propensity score matching analyses were performed to evaluate the effect of different RT techniques on nadir PLC. Results: During RT, 121 (19.9%) patients had grade ≥3 RIL with a nadir PLC of 0.75 ± 0.33 × 109/L. The PLC started to recover at 1 week and reached pre–RT levels 1 year after RT and higher than pre–RT levels 2 years later. Multivariate analysis identified young age, low body mass index, radiation therapy targets involving multiple regions, integrated RT, and low pre–radiation therapy PLC as independent risk factors for nadir PLC (P < .005). The PLC at each time point during and after radiation therapy was lower in patients receiving integrated RT than in those receiving hybrid RT (P < .05). Before and after propensity score matching, integrated RT was significantly associated with lower nadir PLC after adjusting for radiation therapy targets and age (P < .001). Conclusions: Breast cancer patients had prolonged lymphopenia post–RT. Integrated RT increased the risk of RIL and adversely affected recovery. Therefore, an appropriate RT technique should be considered to minimize RIL.

Dear Editor, On July 25,2024,an Oncologic Drugs Advisory Committee meeting was held to discuss the design of the AEGEAN trial,which evaluated the perioperative use of durvalumab for resectable non-small cell lung cancer(NSCLC)[1].

Basal-like breast cancer (BLBC), overlapping with the subgroup of estrogen receptor (ER), progesterone receptor (PR), and HER2 triple-negative breast cancer, has the worst prognosis and limited therapeutics. The XPO1 gene encodes nuclear export protein 1, a promising anticancer target which mediates nucleus-cytoplasm transport of nuclear export signal containing proteins such as tumor suppressor RB1 and some RNAs. Despite drugs targeting XPO1 are used in clinical, the regulation of XPO1 expression and functional mechanism is poorly understood, especially in BLBC. This study finds that KLF5 is a transcription factor of XPO1, which increases RB1 nuclear export and cell proliferation in BLBC cells. Furthermore, XPO1 interacts with the RNA-binding protein PTBP1 to export FOXO1 mRNA to cytoplasm and thus activates the FOXO1-KLF5 axis as a feedback. This work demonstrates that XPO1 inhibitor KPT-330 in combination with CDK4/6 inhibitor additively suppressed BLBC tumor growth in vivo. These results reveal a novel positive feedback regulation loop between KLF5 and XPO1 and provide a novel treatment strategy for BLBC.