Cancer Research and Treatment最新文献

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.

Purpose: Nausea and vomiting are major non-hematological adverse events associated with niraparib maintenance therapy. This study aimed to investigate the time-trend patterns of niraparib-induced nausea and vomiting (NINV) and the associated risk factors in patients with ovarian cancer.

Materials and methods: In this prospective study, we enrolled patients with stage III-IV epithelial ovarian cancer who received niraparib as frontline maintenance therapy. The clinicopathological characteristics and time-trend patterns of patients with NINV were collected through in-person surveys and electronic medical records from the National Cancer Center.

Results: Of 53 patients, 50 (94.3%) were diagnosed with high-grade serous ovarian carcinoma. BRCA mutations and homologous recombination deficiency (HRD) were identified in 23 (43.4%) and 32 (60.4%) patients, respectively. Thirty-one patients (58.5%) had NINV. Time-trend analyses revealed that the first peak intensity of NINV was reached at 3 h post-dose, and the second peak intensity was reached at 11 h post-dose. NINV significantly decreased from week 1 to weeks 8 and 12. In multivariate analyses of risk factors for NINV, HRD-positive tumors (p<0.001) and prior experience of chemotherapy-induced nausea and vomiting (p=0.004) were associated with the occurrence of NINV.

Conclusion: Pre-emptive treatment with antiemetics are required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confirm these findings and to develop optimal preventive strategies for NINV.

Purpose: Exercise is an effective non-pharmacological approach for alleviating treatment-related adverse effects and enhancing physical fitness in breast cancer survivors. A Kinect-based mixed reality device (KMR), with real-time feedback and user data collection, is an innovative exercise intervention for breast cancer survivors. This study aimed to investigate the effect of KMR exercise program on quality of life (QOL) and physical function in breast cancer survivors.

Materials and methods: Seventy-seven participants were randomly assigned to either the KMR exercise group or home stretching group with an 8-week intervention. Physical function (shoulder range of motion [ROM], body composition, aerobic capacity, and hand grip strength) was evaluated before and after the intervention period. Participants completed questionnaires such as the Disabilities of the Arm, Shoulder, and Hand (DASH), Functional Assessment of Cancer Therapy-Breast, and International Physical Activity Questionnaire (IPAQ) to assess upper extremity disabilities, QOL, and physical activity levels.

Results: Significant group-by-time interaction was found for flexion of the operated arm (154.3±12.5 to 165.8±11.2), and the non-operated arm (158.2±13.8 to 166.5±12.2), abduction of the non-operated arm (154.8±31.6 to 161.1±28.1), and adduction of the operated arm (46.5±9.1 to 52.6±7.2). Significant improvements were also observed in DASH (46.8±9.1 to 40.8±9.3) and IPAQ (1136.3±612.8 to 1287±664.1).

Conclusion: The KMR exercise program effectively improved the physical function, alleviated edema, reduced upper extremity disability, and enhanced the QOL in breast cancer survivors. Coupled with significant group-by-time interactions for various outcomes, the results emphasize the potential benefits of incorporating the KMR exercise program to improve the QOL in breast cancer survivors.

Purpose: Sarcopenia is a poor prognostic factor in non-small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.

Materials and methods: We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.

Results: Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.

Conclusion: Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.

Purpose: Research on the prevalence of prostate cancer (PCa) screening and reasons for undergoing screening is limited. We aimed to identify the factors influencing PCa screening behavior and explore the underlying motivations among Korean men.

Materials and methods: This cross-sectional study used data from the 2023 Korean National Cancer Screening Survey, which employs a nationally representative random sampling method. This study included 1,784 men aged 40-74 years. The respondents reported their experiences with PCa screening. Multivariable logistic regression analysis was conducted to identify the factors associated with participation in PCa screening.

Results: The lifetime PCa screening rate was 18.6%. Among screening modalities, transrectal ultrasonography was the most frequently used (31.9%), followed by prostate-specific antigen tests (25.6%) and digital rectal examinations (21.5%). The multivariable analysis identified several factors that significantly increased the likelihood of screening participation, including older age, living with a spouse, poor self-reported health, and abstinence from alcohol consumption in the previous 12 months. Men who had undergone colorectal cancer screening were more likely to participate in PCa screening (adjusted odds ratio, 4.01; 95% confidence interval, 2.03-7.93) than those who had not. The primary motivations for screening were recommendations from family or social networks (31.9%) and inclusion in health examination packages (24.3%), whereas healthcare provider recommendations (18%) and symptomatic concerns (5.7%) were the least influential.

Conclusion: Our findings highlight the importance of providing evidence-based information for PCa screening recommendations and the need for improved communication and implementation of a shared decision-making approach for PCa screening in Korea.