Cancer Investigation最新文献

Aim: Triple-negative breast cancer (TNBC) lacks targeted therapies and demonstrates heterogeneous outcomes. Tumor-infiltrating lymphocytes (TILs) are candidate prognostic biomarkers that reflect the tumor immune microenvironment. This study evaluated the prognostic value of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, with emphasis on granulysin (GNLY) and granzyme B (GZMB), in TNBC.

Materials & methods: We combined NanoString immune gene profiling with whole-slide immunohistochemistry (IHC) in a TNBC cohort (n = 155). Quantitative and spatial analyses were performed to assess CTL and NK cell infiltration and their associations with clinicopathological features and survival outcomes.

Results: High TIL density (≥10%) and elevated CTL-NK scores (≥2) correlated with lower tumor stage, absence of lymphovascular invasion (LVI), and favorable immune subset ratios (all p < 0.05). In multivariable analysis, absence of LVI, high CD4⁺ and CD8⁺ infiltration, and CTL-NK score ≥2 independently predicted improved disease-free survival (DFS; hazard ratio [HR] range 0.45-0.62, all p < 0.05). CD4⁺ infiltration demonstrated the strongest prognostic effect, while CD8⁺ infiltration and the CTL-NK score also conferred independent benefit.

Conclusion: Quantitative and spatial assessment of CTL and NK infiltration provides independent prognostic information in TNBC. The CTL-NK score can be integrated into routine pathology and may refine risk stratification, supporting personalized immunotherapy strategies.

Background: This study sought to examine survival in HER2-positive breast cancer patients based on their BMI. Furthermore, this study investigated the correlations between several other variables such as race, treatment modality, comorbidities, and overall survival.

Patients and methods: This study was a retrospective review of data obtained from the cancer registry of a single academic center between 2015 and 2022. All patients with HER2-positive breast cancer were included. Patients were stratified into four groups based on body mass index: BMI < 25; 25-29.9; 30-39.9; ≥40. Demographic data and clinical outcomes were compared between the groups.

Results: Multivariable Cox-proportional hazard analysis showed that BMI did not have any significant effect on patient mortality in this cohort of patients while adjusting for the effect of other covariates. However, in adjusted analysis, White patients in this cohort had a significantly lower risk of death than Black patients (HR: 0.34, 95% CI: [0.15, 0.78], p = 0.011).

Conclusion: In our cohort, BMI was not found to be a significant predictor of mortality in patients with HER2-positive breast cancer. In multivariate analysis, White race was associated with improved mortality outcomes. More research is needed to eliminate potential disparities in screening and treating cancer.

Background: KRAS p.G12C (c.34G > T) inhibitors have been reported to have varying survival outcomes in CRC patients across studies. Hence, our review aimed to provide a comprehensive understanding of the efficacy and safety of these agents among the CRC population.

Methods: Major databases, including but not limited to PubMed and Ovid, were searched for original clinical trials assessing the efficacy or safety of KRAS p.G12C (c.34G > T) inhibitors in CRC patients through May 2025. Studies with non-G12C KRAS-mutated populations were excluded. Data on patient demographics and various variables, including but not limited to OS, PFS, and TRAE incidence, were extracted from included studies.

Results: Our systematic review analyzed 18 trials and 1011 patients. Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%. Sotorasib monotherapy (960 mg) reported a PFS of 4 months, an OS of 10.6 months, and an ORR of 9.7. When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively. Olomorasib with cetuximab also showed a PFS of 6.6-7.5 months. Nausea, vomiting, diarrhea, rash, and increased AST/ALT were the most common TRAEs.

Conclusions: Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.

We analyzed survival rates and prognostic factors for renal sarcoma using Japan's National Cancer Registry data. We conducted a retrospective cohort study of patients diagnosed with renal sarcoma (2016-2019). Prognostic factors were evaluated using Cox regression analyses. Among 235 patients, female sex (HR, 0.43; 95% CI, 0.23-0.83; p = 0.012), older age (≥60 years: HR, 5.87; p < 0.001), histologic subtype (angiosarcoma: HR, 12.65; p < 0.001), and distant disease (HR, 6.32; p < 0.001) were significant independent prognostic factors. Surgical resection (HR, 0.41; p = 0.004) and radiation therapy (HR, 0.39; p = 0.010) were associated with improved survival. Histologic subtype is the most critical prognostic factor for renal sarcoma in Japan's aging population, with dramatic survival differences: clear cell sarcoma (94.4% 3-year survival) versus angiosarcoma (19.0%). This heterogeneity mandates histology-specific treatment protocols rather than organ-based approaches, with particular relevance for aging societies in Asia.

This randomized controlled trial aimed to evaluate the effect of Swedish hand massage on the quality of life of women undergoing mastectomy. The study was conducted on 42 women who referred to oncology centers in Kerman from February 18 to June 22, 2023. Participants were randomly assigned to intervention and sham groups through block randomization. Data were collected using a demographic and background information questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The intervention group received Swedish massage twice a week for three weeks, with each session lasting 20 min, while the sham group received only light surface touch for the same duration. The quality of life was evaluated at three time points: before the intervention, immediately after the end of the intervention, and one month later. Data were analyzed using SPSS version 25, with a significance level set at p < 0.05. The findings showed that the mean functioning score significantly increased in the intervention group compared with the sham group immediately after the massage (72.66 ± 7.14 vs. 59.98 ± 12.97; p = 0.007), and the mean symptom score significantly decreased (11.79 ± 6.84 vs. 22.62 ± 5.02; p = 0.002). Moreover, the global health status improved significantly in the intervention group immediately after the intervention (74.57 ± 8.92 vs. 52.36 ± 10.91; p < 0.001). Therefore, Swedish hand massage can be considered a safe, effective, and low-cost non-pharmacological method to improve the quality of life in women after mastectomy surgery.

Osteosarcoma is an aggressive bone cancer primarily affecting children and adolescents, with low survival rates in advanced stages. A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the impact of ICIs on survival and toxicity in advanced osteosarcoma. ICIs show potential in treating advanced osteosarcoma but are associated with significant toxicity and uncertain survival benefits. Further research is needed to define their role and identify biomarkers for predicting response. Close monitoring for adverse events is essential.

Background: Non-small cell lung cancer (NSCLC) treatment often involves a combination of first-line immunotherapy (IO) and chemotherapy, with platinum-based regimens as alternatives. Nivolumab monotherapy is a widely used second-line treatment post-platinum chemotherapy. This is the first study to explore the immunomodulatory effects of cisplatin in advanced NSCLC patients receiving nivolumab.

Methods: This retrospective study included 186 metastatic NSCLC patients from four centers in Turkey. All patients received nivolumab after progression on platinum-based chemotherapy. Multivariate Cox regression was performed to identify independent prognostic factors for progression-free survival (PFS) and overall survival (OS).

Results: Patients treated with cisplatin-based chemotherapy (n = 91) had significantly longer median PFS (7.2 months vs. 4.9 months, p = 0.034) and OS (16.0 months vs. 9.9 months, p = 0.014) compared to those treated with carboplatin (n = 95). Cisplatin-based chemotherapy and ECOG performance status were identified as independent prognostic factors for both PFS and OS.

Conclusion: This study highlights the potential immunomodulatory effects of cisplatin, demonstrating improved survival outcomes in NSCLC patients treated with nivolumab. Specifically, our results reveal cisplatin's unique capacity to modulate the tumor microenvironment, offering a novel avenue for optimizing checkpoint inhibitor therapy. These findings underscore the importance of platinum selection in enhancing immunotherapy efficacy and provide a basis for prospective studies to refine clinical guidelines.

Acute myeloid leukemia (AML)'s treatment and remission remains unsatisfactory. A prognostic risk-scoring model containing seven signature genes (POU3F1, RPGR, PTP4A3, SOCS1, FAM83G, GREB1 and COL2A1), was developed by LASSO-Cox regression analysis. In the training set, the test group, area under the curve values of 1, 3, and 5 years were 0.876, 0.877, 0.937, and 0.974, 0.878, 0.976 respectively, which indicates a good predictive efficacy. In the two external GEO (GSE71014 and GSE6891) datasets, area under the curve values of 1, 3, 5 years were 0.847, 0.857, 0.822, and 0.830, 0.863, 0.891 respectively. Our seven signature genes containing risk-scoring model performed excellently in evaluating the OS of AML patients.

Background: Tazemetostat is an oral inhibitor of enhancer of zeste homolog 2 (EZH2) and is used for the treatment of epithelioid sarcoma (ES) and follicular lymphoma (FL). In this study, we investigated the adverse events (AEs) of tazemetostat based on real data from the U.S Food and Drug Administration(FDA) Adverse Event Reporting System (FAERS).

Methods: To quantify the signals of AEs associated with tazemetostat, we employed disproportionality analyze, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms.

Results: A total of 7,133,678 reports of AEs were collected from the FAERS database, of which 1,110 reports were identified with tazemetostat as the "primary suspect (PS)". A total of 32 significant disproportionality preferred terms(PTs) conforming to the four algorithms were simultaneously retained. There were multiple unexpected AEs caused by tazemetostat that were not mentioned in the label yet, including pleural effusion (ROR = 3.84, PRR = 3.83, IC = 3.83, IBGM = 1.94), lymphadenopathy (ROR = 3.88, PRR = 3.88, IC = 3.87, IBGM = 1.95) and taste disorder(ROR = 20.48, PRR = 20.23, IC = 20.16, IBGM = 4.33). Additionally, the majority of tazemetostat-associated AEs occurred within the first month of treatment initiation (n = 126, 49.8%).

Conclusion: Clinicians need to monitor safety for tazemetostat during the first 30 days and pay more attention to new AE signals.

This study investigated the mechanism of action and in vitro efficacy of an anti-hormonal combination drug regimen in treating adult-type granulosa cell tumors of the ovary (AGCT). Using patient-derived and commercial AGCT cell lines, the IC₅₀ values of bicalutamide, anastrozole, and leuprolide acetate were established alone and in combination via cell proliferation assays. Averaged across cell lines, IC₅₀ was determined for bicalutamide (IC₅₀: 7.3 µM) and anastrozole (IC₅₀: 6.2 µM). Minimal effect was seen with leuprolide acetate alone. Suppression of proliferation was increased with the combination of an antiandrogen and an aromatase inhibitor. RNA was extracted from treated and untreated cells. RNA sequencing of cells treated with both anastrozole and darolutamide suggested downregulation of pathways involved in DNA synthesis, cell cycle regulation, and chromosomal organization. MHC I activity and DNA damage response were upregulated. This anti-hormonal drug regimen for AGCT merits prospective investigation.