Cancer Research and Treatment最新文献

Purpose: Guidelines from the aromatase inhibitor era for early breast cancer (EBC) treatment recommend maintaining a body mass index (BMI) below 25. In the current era of cyclin-dependent kinase (CDK) 4/6 inhibitors, now standard in metastatic breast cancer (MBC), limited data exist on treatment outcomes in obese patients. This study investigates how adiposity affects the treatment outcome of CDK 4/6 inhibitors in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative MBC.

Materials and methods: We searched PubMed, MEDLINE, and Embase databases, assessing efficacy outcomes such as progression-free survival (PFS) based on obesity markers, including BMI and visceral adipose tissue (VAT) index.

Results: Twelve studies were reviewed, with seven studies and 1,812 patients included in a pooled meta-analysis. Among patients with BMI ≥ 25, modest improvement in PFS was observed, with a pooled hazard ratio (HR) of 0.944 (95% confidence interval [CI], 0.909 to 0.980; p=0.003). Besides, add-on analysis using VAT to define obesity revealed a notable PFS improvement, with a pooled HR of 0.452 (95% CI, 0.256 to 0.798; p=0.006).

Conclusion: While BMI-defined obesity showed slight PFS improvement with CDK 4/6 inhibitors and endocrine therapy, using VAT to define obesity revealed significant PFS gains. This highlights the need for further research on biomarker to clarify the role of adiposity in MBC, which may differ from its impact in EBC.

Purpose: This retrospective study evaluated the efficacy and safety of a weekly carfilzomib, cyclophosphamide, and dexamethasone (KCd) regimen in patients with relapsed or refractory multiple myeloma (RRMM) who had been previously treated with both bortezomib- and lenalidomide-containing regimens.

Materials and methods: We conducted a retrospective analysis of 33 patients with RRMM who received the KCd regimen between March 2020 and February 2024. All patients had prior exposure to both bortezomib and lenalidomide, and the majority (93.9%) were refractory to lenalidomide. Carfilzomib was administered once weekly at 70 mg/m2 (after a step-up dose), along with oral cyclophosphamide and dexamethasone. Treatment response was assessed according to the International Myeloma Working Group criteria, and survival outcomes were analyzed.

Results: The overall response rate was 66.7%, including a complete response or better in 15.1% of patients and a very good partial response or better in 42.4%. With a median follow-up of 31.7 months, the median progression-free survival was 13.5 months (95% confidence interval, 11.47 to 15.53), while the median overall survival was not reached. The most common grade ≥ 3 adverse event was neutropenia (15.2%). Non-hematologic grade ≥ 3 toxicities were infrequent and manageable.

Conclusion: The weekly KCd regimen demonstrated encouraging efficacy and tolerability in a heavily pretreated RRMM population. These findings support its use as a feasible treatment option, particularly in patients refractory to lenalidomide.

Purpose: This study aimed to investigate the potential association between thyroid disorders and breast cancer (BC) risk in a cohort of Korean women.

Materials and methods: Data for this retrospective cohort study were obtained from the Korean National Health Insurance database, including all women aged ≥ 40 who underwent BC screening from 2009 to 2010 in Korea. Thyroid disorders were identified using medical records from 2009 to 2010 and extracted using the International Classification of Diseases, 10th revision (ICD-10) codes for thyroid nodules, hypothyroidism, and hyperthyroidism. BC cases were defined using the ICD-10 codes and tracked until December 2021. A Cox regression model was used to evaluate the association between thyroid disorders and the risk of BC. Additionally, we evaluated the association between well-known risk factors of BC and thyroid disorders using logistic regression analysis.

Results: Among 5,051,633 women, the mean±standard deviation age was 55.2±10.7 years, and the median follow-up was 11.6 years, with 87,784 BC cases recorded. The proportions of patients with thyroid nodules, hypothyroidism, and hyperthyroidism were 2.5%, 1.8%, and 0.9%, respectively. The hazard ratio for BC risk associated with thyroid nodules was 1.16 (95% confidence interval [CI], 1.11 to 1.20), for hypothyroidism was 0.98 (95% CI, 0.93 to 1.03), and for hyperthyroidism was 1.13 (95% CI, 1.06 to 1.21). In both premenopausal and postmenopausal women, an increased risk of BC was significantly associated with thyroid nodules (adjusted hazard ratio [aHR], 1.16 and 1.13) and hyperthyroidism (aHR, 1.11 and 1.16). History of benign breast disease, oral contraceptive use, breastfeeding, menopausal status, and hormone replacement therapy were associated with thyroid nodules and hyperthyroidism.

Conclusion: Our findings suggest an increased risk of BC in women with a history of thyroid nodules and hyperthyroidism, whereas no such association was found in women with hypothyroidism.

Purpose: Older cancer patients face unique challenges due to age-related physiological changes, increasing their vulnerability to treatment-related toxicities. Geriatric assessment (GA) is a validated tool for optimizing care, yet there is no consensus on integrating geriatric interventions into oncology. This study evaluates the feasibility of a tailored onco-geriatric intervention model incorporating the KG-7 screening tool.

Materials and methods: This prospective study included 30 patients aged ≥ 70 years with solid tumors undergoing adjuvant or palliative chemotherapy. Patients scoring ≤ 5 of KG-7 were eligible. Tailored interventions incorporating KG-7 included polypharmacy, functional status, mobility, nutrition, cognition, emotional well-being, insomnia, social support, and medical problem. KG-7, GA, and quality of life (QoL) were followed at 12 weeks.

Results: Participants (median age, 79.5 years) had colon (43.3%), pancreatic (23.3%), or gastric cancer (23.3%). At baseline, most patients showed independent activities of daily living (100%)/instrumental activities of daily living (90%). However, 93.3% had abnormal GA. Particularly, 86.7% were either malnourished or at risk of malnutrition. The most frequently identified intervention needs included polypharmacy (70.0%), nutritional support (60.0%), and emotional well-being (50.0%) with high adherence (100.0%, 88.9%, and 46.7%, respectively). At 12 weeks, KG-7 scores improved in 43.8% of patients, and 69.2% of GA domains were improved. QoL analysis revealed modest improvement in Global Health Status (mean difference, 6.3; p=0.176). One-year survival rates were 92.3% and 79.4% for adjuvant and palliative groups, respectively.

Conclusion: The onco-geriatric intervention model incorporating KG-7 demonstrated high feasibility and potential to enhance clinical outcomes. Future studies should validate this approach in randomized trials to optimize care for older cancer patients.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ).

Materials and methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire.

Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ.

Conclusion: KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: 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.

Materials and methods: 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).

Results: 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).

Conclusion: 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.

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Purpose: The Asia Pacific region is marked by healthcare diversity and economic disparity.

Materials and methods: To understand the utilization and reimbursement practices of next-generation sequencing (NGS) and other sequencing methods relevant to oncology clinical practice in the region, a semi-structured survey was undertaken of respondents from 11 countries represented by the Korean Society of Medical Oncology (KSMO) 2024 Young Oncologist Forum alumni.

Results: While 79% of respondents reported access to NGS at their institution, full government reimbursement was uncommon and varied by test type and clinical setting. Japan and South Korea offered the most comprehensive public coverage, including for circulating tumor deoxyribonucleic acid (ctDNA)-based liquid biopsy. Lower- and upper-middle-income countries, such as the Philippines, Indonesia, and India, reported no government reimbursement, thus relying on user-pay methods or private insurance payments. One marked barrier to NGS reimbursement was the prohibitive cost of tests (100%), followed by a limited budget to fund testing (79%), and then by policy or regulatory restrictions (50%). On a similar note, insurance coverage (93%) and patient income (86%) were key concerns regarding access and equity to tests. Test reimbursement (or lack thereof) and cost were cited almost universally as the most elevated concerns by the respondents.

Conclusion: The findings demonstrated a wide disparity in access, funding and reimbursement of sequencing tests across the region. Addressing cost, improving reimbursement mechanisms, and building infrastructure capacity will be critical for the equitable integration of NGS into routine cancer care in the Asia-Pacific.

Purpose: Colorectal cancer (CRC) lung metastases exhibit high recurrence rates after resection, underscoring the need for improved therapeutic strategies. This study aimed to characterize the tumor microenvironment (TME) of CRC lung metastases and identify the factors associated with recurrence.

Materials and methods: Fifteen CRC patients who underwent lung metastasectomy were enrolled. Multiplex immunohistochemistry (IHC), whole exome sequencing, transcriptome profiling, and single-cell RNA sequencing (scRNA-seq) were conducted on matched tumor, adjacent and distant normal lung tissues. Immune cell populations and gene expression profiles were analyzed and correlated with clinical recurrence outcomes.

Results: Exome and transcriptome analyses revealed frequent TP53, KRAS, and APC mutations. Most tumors corresponded to consensus molecular subtypes 2 and 4, characterized by immune-depleted and fibrotic features. Tumors showed downregulation of effector T and NK cell signatures. IHC revealed reduced density and increased distance of CD8+ T cells and macrophages from the epithelial cells. scRNA-seq demonstrated increased regulatory T cells and decreased NK and effector T cells in tumor. Tumor-associated macrophages (TAMs), particularly SPP1 (osteopontin)-expressing subsets, were markedly enriched in tumor and correlated with suppressed effector T cella activity. High SPP1 expression was associated with early recurrence and poor overall survival. Patients with recurrence had higher proportion of PD-1+ CD8+ T cells in adjacent normal tissues.

Conclusion: Immunosuppressive features including enrichment of SPP1+ TAMs and depletion of effector T and NK cells contribute to recurrence after CRC lung metastasectomy. Therapeutic strategies targeting both TAMs and T cells may enhance clinical outcomes in this patient population.

Purpose: Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to evaluate the effect of TMC5 silence on the proliferation, apoptosis, migration, and invasion of breast cancer cell lines.

Materials and methods: TMC5-specific small interfering RNA (siTMC5) and siNC were transfected into MDA-MB-231 and MCF-7 cell lines; subsequently, the 740Y-P was co-cultured. Then, the proliferation, apoptosis, migration, invasion, and p-AKT expression were determined.

Results: In MDA-MB-231 and MCF-7 cell lines, silence of TMC5 could reduce the proliferation rate at 48 hours (h) and 72 h, migration rate, and invasion rate, while elevate the apoptosis rate. Besides, silence of TMC5 could decrease the p-AKT/AKT expression. The combination of 740Y-P with the silence of TMC5 could reversely increase the proliferation rate at 48h and 72h, migration rate, and invasion rate compared with the silence of TMC5 only. The apoptosis rate showed the opposite trend.

Conclusion: The silence of TMC5 could inhibit the proliferation, migration, and invasion while promoting the apoptosis of breast cancer, while more in vivo validation is needed to explore its potential to be a treatment target for patients with breast cancer.