Cancer Research and Treatment最新文献

Antibody Drug Conjugates (ADCs) are a novel class of therapeutics that structurally are composed by an antibody directed to a tumour epitope connected via a linker to a cytotoxic payload, and that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology and design of ADCs, as well as we describe the results of different studies evaluating ADCs in lung cancer directed to several targets including HER2, HER3, TROP2, MET, CEACAM5 and DLL3, among others.

Purpose: Previous research showed the benefits of mindfulness meditation on the mental health and quality of life of breast cancer patients. Traditionally, these programs relied on in-person interactions, but the COVID-19 pandemic necessitated alternative delivery methods. This study evaluated the effectiveness and feasibility of a mindfulness-based self-help (MBSH) program via Netflix for breast cancer patients undergoing radiotherapy.

Materials and methods: This prospective non-randomized controlled study assigned patients to a control or MBSH group based on age and preference. The MBSH group watched episodes of "Headspace Guide to Meditation" on Netflix and practiced guided meditation at least twice per week for four weeks. Participants completed questionnaires assessing depression, anxiety, stress, insomnia, mindfulness, mental adjustment to cancer, and quality of life at weeks 0 and 8. Data were analyzed using a two-way repeated measures ANOVA.

Results: Ninety-six patients participated, with 84 eligible for final analysis (44 control, 40 MBSH). Intention-to-treat analysis revealed a significant improvement in depression (f=4.306, p=0.041). Half of the experimental group (n = 20) adhered to the study protocol. At week 8, the experimental group showed significant improvement compared to the control group in cognitive avoidance (f=8.530, p=0.005) and positive attitude (f=5.585, p=0.021), both indicative of adaptive coping strategies.

Conclusion: This study firstly investigated the effect and feasibility of a Netflix-based MBSH program for breast cancer patients undergoing radiotherapy. Findings suggest MBSH on Netflix can improve mental health and adaptive mental adjustment, highlighting the potential of self-help mindfulness interventions to enhance the well-being of cancer patients and need for further research.

Purpose: This study aimed to assess the association between inflammatory cytokines and the risk of gastric cancer (GC).

Materials and methods: We conducted a case-cohort study using Korean National Cancer Center Community (KNCCC) cohort data to investigate the associations between pro-inflammatory, anti-inflammatory cytokines, inflammatory mediators, and GC risk in the Korean general population (GC cases: n=159, subcohort: n=822). Serum levels of inflammatory cytokines were measured using Quantikine® ELISA and analyzed using a Cox proportional hazards regression model.

Results: Compared to those with the lowest serum interleukin 6 (IL-6) levels, the risk of GC significantly increased in the second (HR: 3.48 [1.73-6.99]), third (HR: 3.74 [1.91-7.29], and fourth quartiles (HR: 3.79 [1.93-7.48]). Elevated levels of interleukin 1β (IL-1β) (HR: 1.57 [1.12-2.21]) and interferon gamma (IFN-γ) (HR: 2.49 [1.73-3.58]) were also associated with an increased risk of GC.

Conclusion: The findings of this study indicate associations between pro-inflammatory cytokines (IL-6, IL-1β, and IFN-γ) and the risk of GC, suggesting that regulating these cytokine levels may aid in GC prevention.

Purpose: This study aimed to develop a machine learning-based approach to identify prognostic gene signatures for early-stage Triple Negative Breast Cancer (TNBC) using next-generation sequencing data from Asian populations.

Materials and methods: We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures.

Results: We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve (AUROC) of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis.

Conclusion: This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.

Purpose: Population attributable fractions (PAFs) for hormone and reproductive factors have been estimated in several countries. IARC designated as Group 1 and Group 2A carcinogen for hormone factors in breast, ovarian, endometrial and uterine cervix cancer. This study aimed to estimate the PAFs of hormone/reproductive factor attributed to cancer incidence and deaths in Korean women and projected trends from 2015 to 2030.

Materials and methods: The PAF was estimated with using the 2005 standardized prevalence rates and 2020 incidence and deaths with a 15-year latency. Based on the Levin's formula, prevalence rates were calculated using the Korea National Health and Nutrition Examination Survey (KNHANES) and the relative risks (RRs), which were the risk of selected female cancer associated with oral contraceptive, hormone replacement therapy and duration of breastfeeding, were estimated from the meta-analysis of studies performed in Korean women population. Studies based on the Asian and Global populations were calculated as a sensitivity analysis.

Results: The estimation PAFs for hormone was 1.02% with 1,192 cases and reproductive was 2.67% with 3,112 cases. Moreover, 0.40% (125 deaths) and 1.09% (342 deaths) in female-related cancer deaths in order. EP combined HRT accounted the most proportion in hormone factors and breastfeeding in reproductive factors. Also, the breast cancer had the highest percent in both hormone and reproductive factors.

Conclusion: Through this study, 1.02% and 2.67% of female-related cancer incidence will be reduced by encouraging avoiding the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) and breastfeeding for more than 6 months in reproductive factors. Additionally, among four selected female cancers in this study, breast cancer was observed to be a significant level of prevention.

Purpose: This study aimed to examine the real-world effectiveness and safety of regorafenib and trifluridine/tipiracil (TAS-102) in metastatic colorectal cancer (mCRC) patients in Taiwan.

Materials and methods: Data were extracted from Taiwan's National Health Insurance Research Database to evaluate the clinical outcomes of mCRC patients treated with either regorafenib or TAS-102 between 2016 and 2019. Overall survival (OS) was compared using Kaplan-Meier curves and Cox's proportional hazard models, adjusting for age, gender, Quan-CCI score, liver metastases, number of metastatic sites, and the use of anti-EGFR medications. Additionally, OS was compared between regorafenib monotherapy and TAS-102 monotherapy, excluding patients who had received both regorafenib and TAS-102.

Results: A total of 2,608 patients in the regorafenib group and 521 patients in the TAS-102 group were identified. The median OS was 6.5 months for regorafenib and 7.5 months for TAS-102, with a significant difference observed (p=0.001). The mean duration of treatment was similar for regorafenib and TAS-102 (108 days vs. 101 days) with no significant difference. The safety profiles of the two drugs were distinct; a higher proportion of patients in the regorafenib group had hypertension and hand-foot skin reaction while nausea and vomiting were more common in the TAS-102 group. In the subgroup analysis, patients receiving TAS-102 monotherapy showed significantly longer OS than those receiving regorafenib monotherapy.

Conclusion: The findings of this study indicated that TAS-102 had superior survival outcomes compared to regorafenib in mCRC patients. This study provides insights into the effectiveness and safety profiles of regorafenib and TAS-102 in Taiwan.

Purpose: The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.

Materials and methods: The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.

Results: Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.

Conclusion: The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

Purpose: To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).

Materials and methods: Newly diagnosed patients with IDH wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.

Results: During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p<0.001), Karnofsky Performance Status ≥60 (p=0.033), and age ≤75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months, p=0.014).

Conclusion: The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

Purpose: To investigate the potential role of low‒dose cyclophosphamide (Cy) as a radiosensitizer by evaluating its impact on the immune response and the abscopal effect of stereotactic ablative radiotherapy (SABR) through preclinical models.

Materials and methods: CT26 tumors (immunologically hot) and 4T1 tumors (immunologically cold), grown in immunocompetent BALB/c and immunodeficient BALB/c‒nude mice, were irradiated with 20 Gy in two fractions with 5‒day spacing followed by intraperitoneal injections of 9 mg/kg Cy every 3 days. Immunological changes in CT26 tumors caused by the treatments were assessed using flow cytometry. Changes in the expression of HIF‒1α in tumors were also assessed. Splenocytes and bone marrow‒derived dendritic cells (DCs) were exposed to various concentrations of Cy to assess T cell proliferation and DC differentiation.

Results: The combination of Cy with RT (RT+Cy) significantly suppressed tumor growth compared to RT alone in immunocompetent mice, while that effect was not observed in immunodeficient mice. Additionally, RT+Cy effectively induced abscopal effects in hot and cold tumors, with increased CD8+ T cells in blood and tumors. Significantly higher expression levels of Granzyme B, IFN‒γ, and TNF‒α were observed in RT+Cy group compared to the RT alone group. In vitro data indicated that low‒dose Cy promotes DC differentiation. Low‒dose Cy suppressed the radiation‒induced upregulation of HIF‒1α in the tumors.

Conclusion: Low‒dose Cy enhances tumoricidal effects of 5‒day spacing high‒dose RT by increasing anti-tumor immune responses.

Purpose: This study aims to estimate and project the Population Attributable Fraction (PAF) of cancer incidence and death due to carcinogenic drug use in Korea from 2015 to 2030, to estimate the degree of cancer prevention from exposure to carcinogenic drugs in Korea. Selected carcinogenic drugs were immunosuppressive and antineoplastic drugs classified as group I by the International Agency for Research on Cancer (IARC).

Materials and methods: Systematic review and meta-analyses were conducted to estimate the relative risk (RR) of cancer associated with carcinogenic drug use. Age was standardized using the annual prevalence rate of the National Health Insurance Service sample cohort (NHIS-NSC) from 2002 to 2013 to calculate the standardized prevalence rate of carcinogenic drug use each year. The PAF of specific cancer incidence and death were calculated using Levin's formula and Monte Carlo methods. The prevalence rates were extrapolated to estimate the trend of PAF from 2015 to 2030.

Results: In 2015, carcinogenic drugs attributed to 0.003% and 0.002% among the causes of cancer incidence and death in Korea. However, carcinogenic drugs attributed to 1.1% among the causes of both cancer incidence and death in patients with clinical indications of carcinogenic drugs.

Conclusion: The PAF in patients with clinical indications of carcinogenic drugs were significantly high and expected to increase rapidly over time. Since these drugs are listed as essential by the World Health Organization (WHO), and may be difficult to replace, a surveillance system on susceptible populations using group I carcinogenic drugs must be discussed and implemented.