Oncology最新文献

Introduction: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients.

Methods: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated.

Results: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis.

Conclusion: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.

Introduction: Breast cancer is the most common cancer in women with a 5-year survival over 90%. However, anthracycline-based chemotherapy causes significant cardiotoxicity often requiring discontinuation of chemotherapeutic regimen among breast cancer survivors. We conducted a systematic review and meta-analysis to evaluate the efficacy of exercise training in mitigating anthracycline-related cardiotoxicity among women with breast cancer.

Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. The outcomes of interest were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), early to atrial filling velocity (E/A) ratio, maximal oxygen consumption (VO2 max), and cardiac output (CO). We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias in individual studies.

Results: We identified a total of 596 articles with 5 trials included in the final analysis. Exercise training was associated with an increase in VO2 max compared with no exercise training (mean difference, 3.95 [95% CI, 0.63-7.26]; I2 = 99.68%). Other cardiovascular outcomes such as LVEF (mean difference, 1.76 [95% CI, -1.95 to 5.46]; I2 = 99.44%), GLS (mean difference, 0.30 [95% CI, -0.49 to 1.10]; I2 = 96.63%), E/A ratio (mean difference, 0.05 [95% CI, -0.05 to 0.15]; I2 = 94.16%), and CO (mean difference, 0.38 [95% CI, -0.91 to 1.66]; I2 = 99.73%) are similar between patients who underwent exercise training and those who did not.

Conclusions: Exercise was associated with an improvement in maximal oxygen uptake among women with breast cancer receiving anthracycline-based chemotherapy.

Introduction: Anticancer drug-induced stomatitis can affect a patient's quality of life and the continuation of drug treatment. Although there have been reports of the occurrence of stomatitis associated with anticancer agents in clinical trials, few Japanese participants have been enrolled in clinical trials and have not been sufficiently investigated. In addition, there has been little attention on research on anticancer drugs associated with stomatitis by patient stratification with different carcinogenic sites. Therefore, the aim of this study was to determine the disproportionality associated with stomatitis for various types of anticancer drugs in different types of cancer patients using the Japanese Adverse Drug Event Report (JADER) database.

Methods: The aim of this study was to identify the disproportionality of stomatitis by analyzing the type of anticancer drug and cancer patients using the Japanese Pharmacovigilance Database. Data obtained from spontaneous reports of adverse events with more than 10 stomatitis outbreaks reported in the JADER database between April 2004 and March 2023 were analyzed. The safety signal for an adverse event was defined as the lower limit of the 95% confidence interval of the reported odds ratio of >1.

Results: There were 6,178 reports of drugs associated with stomatitis. Among these, 41 drugs were suggested to be associated with stomatitis, and 41 drugs were detected as signals. These drugs were classified based on their efficacy: antipyrimidines (six drugs), folate metabolism antagonists (three drugs), alkylating agents (four drugs), platinum (three drugs), topoisomerase inhibitors (three drugs), microtubule inhibitors (three drugs), mammalian target of rapamycin (mTOR) inhibitors (two drugs), kinase inhibitors (seven drugs), anti-growth factor antibodies (five drugs) immune checkpoint inhibitors (one drug), and others (four drugs).

Conclusion: The drugs that may be associated with stomatitis were cell cycle-dependent drugs, epidermal growth factor receptor-tyrosine kinase inhibitors, and mTOR inhibitors. Moreover, this study suggested that anti-growth factor antibodies and immune checkpoint inhibitors may be associated with stomatitis development.

Introduction: Gastric cancer (GC) remains a significant global public health problem, despite the decreasing trends in GC mortality rates in the last 5 decades. Our study aimed to examine the pattern of GC mortality in Montenegro between 1990 and 2018 and to contribute to the future by designing a national long-term strategy for the control and prevention of GC.

Methods: Gastric cancer mortality data in Montenegro from 1990 to 2018 were collected. Mortality rates were age-standardized to the World Standard Population for estimating both the overall and gender-specific trends. The joinpoint regression model was used to assess GC mortality and identified significant changes in the linear time trend. Linear and Poisson regressions were also applied for additional trend analyses.

Results: Joinpoint regression reveals a statistically significant decrease in the age-standardized rate for the overall level, on average by 1.4% per year (AAPC [95% IP] = -1.4 [-2.4 to -0.4]; p = 0.007), which was due to a decrease in the age-standardized rate in men with an average annual change of -1.8% (AAPC [95% IP] = -1.8 [-2.9 to -0.6]; p = 0.003), while in women the rates were stable (p = 0.565). The results for age groups indicate that a decline was registered at the overall level, and among men, as a consequence of the trend of decreasing age-specific rates for the age group 55-64 on average annually by 2% among men (AAPC [95% IP] = -2 [-3.8 to -0.1]; p = 0.035), and for the overall level (AAPC [95% IP] = -2 [-3.7 to -0.3]; p = 0.026).

Conclusion: Our findings indicate a noteworthy decline in age-standardized overall GC mortality rates among men in Montenegro, while rates for women have remained constant. National strategies to further reduce mortality rates for GC are necessary.

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia. The disease progression is majorly affected by genetic defects. However, about 40-50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence, there remains a room to advance the biological understanding and find molecular prognostic markers for cytogenetically normal MDS.

Methods: We performed a high-resolution CGH + SNP array along with next-generation sequencing (NGS) of 77 primary diagnosed MDS patients, and also they were clinically followed up.

Results: Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity, i.e., MDS-biTP53, as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI: 0.37-21) when analyzed by Kaplan-Meier survival analysis.

Conclusion: CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients, respectively, with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact.

Introduction: Malignant brain tumors are malignancies which are known for their low survival rates. Despite advancements in treatments in the last decade, the disparities in malignant brain cancer mortality among the US population remain unclear.

Methods: We analyzed death certificate data from the US CDC WONDER from 1999 to 2020 to determine the longitudinal trends of malignant brain tumor mortality. Malignant brain tumor (ICD-10 C71.0-71.9) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated by standardizing the AAMR to the year 2000 US population.

Results: From 1999 to 2020, there were 306,375 deaths due to malignant brain tumors. The AAMR decreased from 5.57 (95% CI, 5.47-5.67) per 100,000 individuals in 1999 to 5.40 (95% CI, 5.31-5.48) per 100,000 individuals in 2020, with an annual percent decrease of -0.05 (95% CI, -0.22, 0.12). Whites had the highest AAMR (6.05 [95% CI, 6.02-6.07] per 100,000 individuals), followed by Hispanics (3.70 [95% CI, 3.64-3.76]) per 100,000 individuals, blacks (3.09 [95% CI, 3.04-3.14] per 100,000 individuals), American Indians (2.82 [95% CI, 2.64-3.00] per 100,000 individuals), and Asians (2.44 [95% CI, 2.38-2.50] per 100,000 individuals). The highest AAMRs were reported in the Midwest region (5.58 [95% CI, 5.54-5.62] per 100,000 individuals) and the rural regions (5.66 [95% CI, 5.61-5.71] per 100,000 individuals).

Conclusions: Our study highlights the mortality disparity among different races, geographic regions, and urbanization levels. The findings underscore the importance of addressing the disparities in malignant brain tumors that existed among males, white individuals, and rural populations.

Introduction: Hepatocellular carcinoma (HCC) carcinogenesis is not yet fully known. Insulin-like growth factor-1 receptor (IGF-1R) can translocate to the nucleus and modulate cellular growth, possibly participating in HCC development and aggressiveness. This study aimed to evaluate the immunoexpression of IGF-1R in HCC, the cellular compartment involved, and its association with clinicopathological parameters and clinical outcomes.

Methods: Liver specimens from 111 HCC patients who underwent liver transplantation or partial surgical resections at a Brazilian referral hospital center were studied. IGF-1R expression was determined by immunohistochemistry, clinical data were collected from medical records, and pathological parameters were obtained from path review.

Results: IGF-1R nuclear expression was higher in the tumor than in the adjacent cirrhosis (p < 0.001). The odds of IGF-1R expression in the nucleus compared to the membrane are lower in the cirrhosis condition than in the tumor, suggesting an increase in the prevalence of nucleus expression relative to the membrane from cirrhosis to tumor. There was an association between IGF-1R nuclear expression in HCC and the moderate/poor grade of histologic differentiation (p < 0.001). However, long-term clinical outcomes were not associated with IGF-1R nuclear expression.

Conclusion: The data presented here suggest the role of IGF-1R in HCC progression and carcinogenesis as its expression increases in the nucleus relative to the membrane, from cirrhosis to tumor, and it was associated with a poorer differentiated tumor grade. Further research is awaited to fully understand the mechanisms underlying this association.

Introduction: Ovarian metastasis of colorectal cancer is known to have a poor prognosis. This study aimed to elucidate the characteristics of patients who underwent oophorectomy for ovarian metastasis from colorectal cancer.

Methods: This retrospective study included 16 patients who underwent oophorectomy for colorectal cancer metastasis to the ovary from January 2004 to December 2017. Improvement in patient's symptoms and pre- and postoperative changes in various nutritional and inflammatory indicators were assessed. Survival analysis and identification of prognostic factors were conducted with a median follow-up of 40.7 (5-109) months.

Results: Of 16 patients, 12 had (75%) synchronous and 4 (25%) had metachronous metastasis. Fourteen patients were symptomatic but symptoms resolved postoperatively. Thirteen patients (81.3%) had ascites and 5 (31.3%) had pleural effusion on preoperative computed tomography that disappeared after surgery in all cases. The median value of prognostic nutritional factor was significantly increased postoperatively (36.0 [preoperatively] vs. 47.5, p < 0.0001). The median (interquartile range) values for lymphocyte-C-reactive protein ratio were 715.2 (110-2,607) preoperatively and 6,095.2 (1,612.3-14,431.8) postoperatively (p = 0.0214). The median survival of the entire cohort was 60.4 months. The 3-year survival rates for R0 + R1 and R2 cases were 83% and 24% (p = 0.018), respectively. Univariate analysis showed that R2 resection and low postoperative lymphocyte-C-reactive protein ratio were associated with poor prognosis.

Conclusions: Oophorectomy for ovarian metastasis from colorectal cancers was safely performed. It improved the patients' symptoms and nutritional status and may result in improved prognosis.

Introduction: Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India, the incidence rates of CRC are especially increasing. In this study, we have focused on the distribution of the FOXO3 gene polymorphisms among the patients with CRC in North India.

Methods: A case-control study was conducted on 487 CRC patients and 487 age-matched controls. We genotyped single-nucleotide polymorphisms rs2253310 and rs4946936 through polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and PCR-single-stranded conformation polymorphism procedure followed by sequence detection.

Results: A significantly increased risk of CRC was observed for the CC genotype of the rs4946936 polymorphism compared to the TT genotype (p = 0.02; odd ratio [OR] = 1.40, confidence interval [CI] = 1.05-1.87). GT haplotype appeared to be a "risk" haplotype (OR = 1.71, 95% CI = 0.82-2.19), while as other haplotypes CC (OR = 0.83, 95% CI = 0.32-1.54), CT (OR = 0.75, 95% CI = 0.25-1.01), and GC (OR = 0.98, 95% CI = 0.88-1.14) were found to be "protective" for developing CRC.

Conclusion: This study suggests an association of increased risk of CRC with the rs4946936 polymorphism but not with the rs2253310 polymorphism.