Cancer Research and Treatment最新文献

Purpose: The study aims to explore the predictive value of the Ki67 index for everolimus efficacy in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).

Materials and methods: We collected data on 2,518 cancer patients who received everolimus treatment from three cancer centers in China. Their clinicopathologic characteristics were retrospectively collected. A training cohort and a validation cohort were developed.

Results: A total of 300 patients with HR+/HER2- ABC were included in the study, with 200 patients in the training cohort and 100 patients in the validation cohort. When analyzing the Ki67 index from 14% to 50%, only the Ki67 cut-off of 40% was found to be significantly correlated with progression-free survival (PFS) for patients in the training cohort. Multivariate Cox analyses further showed that Ki67 index of 40% (p=0.03) was significantly associated with PFS in patients treated with everolimus. Patients with Ki67 less than 40% had an improved PFS of 7.0 months, significantly better than 4.6 months for patients with Ki67 more than 40% (p=0.03, HR=0.67, 95CI%=0.46-0.97). In the validation cohort, patients with a Ki67 index of less than 40% had a significantly longer PFS of 4.3 months (2.1 months versus 4.3 months, p<0.001, HR=0.29, 95CI%=0.17-0.51).

Conclusion: The Ki67 cut-off value of 40% was identified as an optimal index for predicting the efficacy of everolimus, which may help with the management of everolimus in Chinese patients with HR+/HER2- ABC.

Purpose: To elucidate how Salidroside-loaded, oligopeptide-modified tumor exosomes (Salidroside@T-exo) rewire the PI3K/AKT/mTOR axis to remodel the immune microenvironment (IME) and reverse acquired PD-1 resistance in breast cancer.

Materials and methods: CSC-exosomes were surface-engineered with TMTP1 peptide and electroporated with Salidroside. PD-1-resistant MA782/5s-8101-R cells and an orthotopic mouse model were used. Multi-omics, flow cytometry, ELISA, immunofluorescence, in vivo imaging, and molecular assays examined immune and signaling outcomes.

Results: Salidroside@T-exo restored T-cell IFN-γ and GZMB secretion, suppressed CD8+ T-cell apoptosis, and inhibited p-PI3K/p-AKT/p-mTOR in T cells. CSC migration, invasion, and stemness (OCT4, NANOG, SOX2) were markedly reduced. Tumor growth, Ki-67 index, and CSC frequency dropped while TUNEL-positive cells rose.

Conclusion: Salidroside@T-exo reverses PD-1 blockade resistance by simultaneously inhibiting PI3K/AKT/mTOR signaling in T cells and eradicating breast CSCs, offering a clinically translatable strategy for refractory breast cancer immunotherapy.

Purpose: Arm lymphedema is a common, debilitating complication in patients with breast cancer undergoing postoperative radiotherapy (PORT). Although clinical and dosimetric factors have been used for risk prediction, radiomics offers a novel approach for improving the predictive accuracy.

Materials and methods: We designed a predictive model for lymphedema using clinical, dosimetric, and radiomic features. We included 532 patients (399 training and 133 testing) who underwent breast cancer surgery followed by PORT. Radiomic features were extracted from axillary levels I, II, III, and supraclavicular regions, which were automatically contoured on PORT-planning computed tomography scans. Least absolute shrinkage and selection operator regression was used for feature selection. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity.

Results: The Combined model integrating clinical, dosimetric, and radiomic features showed higher predictive performance (AUC: training 0.783, test 0.767, total 0.779) than the Clinical/Dosimetric (AUC: training 0.730, test 0.671, total 0.717) and Radiomics-only (AUC: training 0.721, test 0.668, total 0.708) models. The Combined model also achieved a higher accuracy (training 78.9%, test 78.2%, total 78.8%), sensitivity (training 74.6%, test 62.5%, total 72.0%), and specificity (training 79.7%, test 80.3%, total 79.9%) than the other models. DeLong's test confirmed that the Combined model significantly outperformed the Clinical/Dosimetric model (p=0.036 in training and p=0.010 in all datasets).

Conclusion: Integrating radiomic features with clinical and dosimetric factors showed potential to enhance lymphedema prediction in patients with breast cancer receiving PORT. This model can potentially guide personalized treatment strategies and improve patient outcomes.

Purpose: Patients undergoing adjuvant chemotherapy often utilize non‑treating medical institutions (NTMIs) for supportive care. We investigated utilization patterns and associated clinical factors.

Materials and methods: In this prospective observational study, patients with solid tumors receiving adjuvant chemotherapy after curative resection were surveyed using SCNS-SF34, FACT-G, MDASI-K, and HADS at multiple timepoints. Associations between facility usage and survey scores were analyzed.

Results: Forty-four percent of participants used non-treating medical institutions during adjuvant chemotherapy. Patients with breast cancer and those with an ECOG performance status of 0 were more likely to use NTMIs. Higher SCNS-SF34 scores in the Physical & Daily Living domain were significantly associated with the number of NTMI use days. FACT-G, MDASI, and HADS-anxiety scores also showed associations, while dose intensity and emergency room visits did not.

Conclusion: Patients receiving adjuvant chemotherapy frequently use NTMIs for unmet physical or emotional needs. Systematic approaches to symptom control and patient education within oncology settings may reduce unnecessary healthcare utilization.

Purpose: Unplanned readmissions of patients with cancer increase healthcare costs and disrupt care. Although well-studied in surgical oncology, data on patients receiving active treatment for advanced cancer remain limited. This study examined the causes, clinical characteristics, and outcomes of unplanned readmissions.

Materials and methods: This retrospective, multicenter study included patients with advanced solid tumors from six South Korean university hospitals who had unplanned readmissions within 1 month of prior hospitalization in 2019. Patients with terminal cancer who did not receive active treatment were excluded. Readmissions were categorized as Cancer Progression (e.g., worsening symptoms), treatment-related (e.g., therapy complications), or other (e.g., non-cancer conditions). Additional unplanned hospital use within 1 month post-discharge was analyzed in survivors with 6-month follow-up data.

Results: Among the 542 patients, readmissions were classified as cancer progression (42.6%), treatment-related (37.3%), or other (20.1%). The cancer progression group had the longest hospital stay (median, 12 days) and the highest mortality (23.4%). The Treatment-Related group had shorter stays (8 days) and lower mortality (8.4%). Among the 445 survivors, 24.9% had unplanned hospital visits within 1 month post-discharge. Home discharge increased the likelihood of these events (adjusted odds ratio: 4.82 for readmissions, 2.65 for emergency department visits).

Conclusion: Cancer progression was the leading cause of readmission and was associated with prolonged hospital stays and high mortality rates. Home discharge is a key predictor of early additional unplanned hospital visits, indicating the need for careful post-discharge monitoring in this population.

Purpose: Childhood cancers are rare but clinically significant. Monitoring incidence and survival trends is essential for evaluating progress in cancer control and identifying areas for improvement.

Materials and methods: We analyzed cancer incidence and survival trends among individuals aged 0-19 years in Korea using data from the Korea Central Cancer Registry from 2001 to 2020. Cancer types were classified according to the International Classification of Childhood Cancer, third edition (ICCC-3). Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Relative survival rates (RSRs) were estimated and compared with data from the US.

Results: A total of 34,223 cancer cases were identified during the study period. The overall ASR was 151.3 per million person-years, with a significant increasing trend (APC 1.5%). Leukemias were the most common diagnostic group (ASR 43.7), followed by central nervous system tumors and lymphomas. Between 2001-2010 and 2011-2020, the 5-year and 10-year RSRs improved from 75.2% to 84.8% and from 72.7% to 82.7%, respectively. The largest survival gains were observed in leukemia (14.9 percentage points) and neuroblastoma (13.1 percentage points). Compared to SEER data, Korea showed similar overall survival trends, although differences remained by cancer type and age group.

Conclusion: The incidence of childhood and adolescent cancers in Korea has increased, while survival has significantly improved over the past two decades. These findings highlight substantial progress in pediatric cancer care, while underscoring the need for targeted efforts for specific cancer subtypes and age groups.

Purpose: Helicobacter pylori is the single most important risk factor for gastric cancer (GC). However, H. pylori eradication (HPE) does not eliminate risk of GC. To clarify the association of lifestyle factors with GC risk after HPE.

Materials and methods: Using the Korean National Health Insurance Services (NHIS) database, adult individuals who claimed HPE between 2010 and 2016 were analyzed. The adjusted hazard ratios (aHR) for GC were analyzed according to the lifestyle status including smoking (never; light [<10PY]; moderate [10-20PY]; heavy [≥20PY]), alcohol (none; mild [<30g/day]; heavy [30g/day]), and abdominal obesity by using Cox proportional hazard model.

Results: During a median follow-up period of 6.7 years, 9,754 individuals were newly diagnosed with GC among the total of 1,282,702 subjects. Compared with never smokers, moderate (aHR 1.12 [95%CI 1.04-1.20]) and heavy smokers (1.34 [1.27-1.42]) had greater risks of post-HPE GC with dose-response manner. Heavy drinkers had increased risk of GC (1.23 [1.15-1.32]) compared with non-drinkers, and those with abdominal obesity had slightly elevated GC risk compared with those without that (1.11 [1.06-1.15]). In subgroup analyses, those who had HPE at age ≥ 55 were shown to be more affected by the unhealthy lifestyles (smoking [p-for-interaction <0.01], alcohol [0.03], and abdominal obesity [0.03]). Also, male showed greater risk increase by smoking habit [p-for-interaction 0.02] than female.

Conclusion: Unhealthy lifestyles like smoking, alcohol, and abdominal obesity were shown as risk factors for post-HPE GC. Those with late HPE were more likely to be affected by unhealthy lifestyles.

Purpose: There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation.

Materials and methods: A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.

Results: In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.

Conclusion: We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis.

Materials and methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic-clinical characteristics were analyzed. LC-WGS-based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted.

Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases.

Conclusion: CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.

Materials and methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.

Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.

Conclusion: Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.