Oncology最新文献

Introduction: Esophageal squamous cell carcinoma (ESCC) has one of the poorest cancer prognosis rates; there is an urgent need to develop new drug therapies and biomarkers. CD63, a tetraspanin protein and well-known exosomal marker, is implicated in cancer progression; however, the significance of CD63 expression in ESCC remains unclear. Herein, we report the significance of CD63 expression by analyzing ESCC patient samples and ESCC cell lines.

Methods: ESCC patient samples (n=86) were evaluated for CD63 expression by immunostaining; univariate and multivariate analysis using Cox proportional hazards were used to evaluate CD63 expression and clinicopathological features as prognostic factors for survival. For in vitro analysis, CD63 knockdown was performed in human ESCC cell lines (TE2 and TE15) using siRNA, and changes in proliferative potential. The gene expression change were also analyzed by microarray and gene set enrichment analysis.

Results: Overall survival was significantly worse in the CD63 high group (P=0.031, log-rank test). Five-year overall survival univariate analysis identified positive lymph nodes, pStage 3 or higher, and CD63 high expression as poor prognostic factors, while multivariate analysis showed that CD63 high expression was an independent poor prognostic factor (P=0.009, HR 2.56, 95%CI 1.269-5.167). CD63 knockdown in ESCC cell lines resulted in a phenotype of decreased proliferative potential. CD63 knockdown increased the expression of genes involved in cell adhesion and suppressed the expression of genes involved in granule secretion. CD63 also shown to affect nuclear import, protein complex localization, and ERBB-signaling pathways. In conclusion, CD63 affects gene expression in ESCC, and high tissue expression of CD63 predicts poor prognosis in ESCC patients.

Introduction: The occurrence of Gleason grade group upgrading (GGU) significantly impacts both treatment strategy development. We aim to develop an optimal predictive model to assess the risk of GGU in patients with localized prostate cancer (PCa), by comparing traditional logistic regression (LR) with seven machine learning algorithms.

Methods: A retrospective collection of clinical data was conducted on patients who underwent RP at Wuhan Central Hospital (January 2017 to December 2023, n=177) and Jiangxi Cancer Hospital (July 2019 to February 2024, n=87). The least absolute shrinkage and selection operator (LASSO) regression was employed to filter the clinical characteristics of patients. Subsequently, models were conducted using multivariate LR, along with seven diverse machine learning algorithms: eXtreme Gradient Boosting, Decision Tree, Multilayer Perceptron, Naive Bayes, k-Nearest Neighbors, Random Forest, and Support Vector Machine. By employing the receiver operating characteristic curve, accuracy, brier score, recall, calibration curve, and decision curve analysis, we compared the predictive capabilities and clinical utility of eight models to identify the optimal one.

Results: In the evaluation of eight models, the LR model demonstrated superior performance. In the modeling set, it achieved an AUC of 0.826 (95% CI: 0.808 - 0.845), accuracy of 0.765, and a brier score of 0.167. In the validation set, it kept good results with an AUC of 0.819 (95% CI: 0.758 - 0.880), accuracy of 0.725, and a brier score of 0.180. The calibration curve, brier score， and DCA also demonstrated the excellent calibration and net benefit of the LR model.

Conclusions: After conducting a comprehensive multi-model comparison, we concluded that the LR model was optimal for predicting GGU, which was confirmed by external validation. Our study also revealed percent free prostate-specific antigen density as a predictive factor for GGU, offering a novel approach for managing localized PCa patients.

Introduction: Temozolomide (TMZ) is a widely used chemotherapy agent for the treatment of malignant gliomas and other brain tumors. Despite its established therapeutic benefits, there is an ongoing need to understand better its safety profile, particularly in real-world clinical settings. This study aimed to identify critical adverse drug reactions (ADRs) associated with TMZ by utilizing the FDA Adverse Event Reporting System (FAERS) database, thereby providing valuable safety insights for clinical practice.

Methods: We utilized the reported odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean as primary algorithms for disproportionality analysis. Adverse events (AEs) were classified as ADRs only upon meeting the criteria set by all four algorithms. To ensure the accuracy of our results, we meticulously excluded any AEs deemed unrelated to TMZ.

Results: From October 2003 to September 2023, a total of 10,502,538 case reports and 9,073 cases explicitly attributed to TMZ were retrieved from the FAERS database. After applying our filters, 116 ADRs, each with a corresponding Preferred Term (PT), were identified across 18 System Organ Classes (SOCs). The identified ADRs associated with TMZ primarily involved bone marrow suppression, hepatotoxicity, and various infections, notably Pneumocystis jirovecii pneumonia. Furthermore, our analysis identified valuable ADRs not listed in the drug label, including congenital, familial, and genetic disorders at the SOC level, as well as unexpected ADRs at the PT level, such as seizures, pulmonary embolism, and sepsis.

Conclusion: This real-world pharmacovigilance study has identified significant and previously unreported ADRs associated with TMZ. Further research for validation and resolution is urgently needed to guide the clinical application of TMZ, ensuring the safety and efficacy of its use in treating brain tumors.

Introduction: In August 2018, the Japanese PMDA approved nivolumab, an immune checkpoint inhibitor, for previously treated, unresectable, advanced, or recurrent pleural mesothelioma (PM) based on the MERIT trial, a phase II study of 34 cases. However, concerns regarding limited evidence persist.

Methods: We retrospectively analyzed 83 patients with previously treated, unresectable, advanced, or recurrent malignant PM treated with nivolumab from August 2018 to May 2022. Efficacy was evaluated using overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) per modified RECIST criteria. Safety was assessed by treatment-related adverse events (TRAEs) according to CTCAE v5.0. PD-L1 expression was analyzed with the anti-PD-1 antibody (22C3).

Results: The median age was 73 years. Histological subtypes included epithelioid (60), sarcomatoid (15), biphasic (6), and unknown (2). Lines of treatment were 2nd (62), 3rd (13), and 4th or later (8). Partial response was seen in 16 patients, stable disease in 30, progressive disease in 29, and not evaluable in 8, with an ORR of 19.3% and a disease control rate of 55.4%. Median PFS and OS were 5.1 and 12.4 months, respectively. TRAEs occurred in 45 patients (54.2%), with grade ≥3 in 6 (7.2%) and one treatment-related death. PFS correlated with male gender, TRAEs, and good performance status (PS: 0-1), while OS correlated with PS.

Conclusion: Nivolumab demonstrated efficacy and safety in clinical practice, supporting its use in patients with good PS, even in later lines.

Introduction: Health-related quality of life (HRQOL) has been reported in clinical trials of pembrolizumab and avelumab treatment of locally advanced or metastatic urothelial carcinoma. However, few studies have investigated the effect of immune checkpoint inhibitors (ICIs) on HRQOL in patients with urothelial carcinoma in a real-world setting.

Methods: We included 44 patients with advanced urothelial cancer who were treated with pembrolizumab or avelumab from January 2018 to November 2023. When patients visited our hospital for treatment, we evaluated their HRQOL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care. We retrospectively reviewed the interview sheets.

Results: The median time to deterioration in global health status was 19.1 weeks. The mean scores of emotional functioning were improved in weeks 18 and 36 compared with baseline. The mean scores for fatigue and appetite loss were also improved in weeks 18 and 36.

Conclusion: ICI treatment for advanced urothelial carcinoma did not worsen HRQOL over time in a real-world setting. Tolerability of ICIs for advanced urothelial carcinoma appears good in those who received long-term treatment.

Introduction: EGFR tyrosine kinase inhibitor (TKI)-induced rash can be alleviated with tetracyclines (TCN) and topical corticosteroids (TCS), whereas drugs for acid-related disorders (DARD) can affect EGFR TKI absorption. The present study investigated the concomitant use of TCNs, TCSs, and DARDs with EGFR-TKIs in non-small cell lung cancer (NSCLC) and whether these affect patient outcomes.

Methods: We retrospectively collected data from all patients (n=1498) who had purchased for EGFR TKIs (erlotinib, gefitinib, and afatinib) in Finland between 2011-2020. Overall survival (OS) and time on treatment (ToT) were analyzed from the first EGFR TKI purchase.

Results: Early TCN purchases were registered in 298 (19.6%) patients; early TCS and DARD purchases were observed in 154 (10.1%) and 192 (12.9%) while similar percentages were detected in the EGFR mutant cohort. In the entire cohort, early purchase of TCSs and TCNs was associated with improved ToT, OS, and DARDs with inferior outcomes. In the multivariate analysis, TCSs retained their significance in ToT (HR, 0.78; 95% 0.66-0.94), TCNs in OS (HR, 0.73; 95% 0.63-0.84), and DARDs in both (HR, 1.28; 95% 1.091-1.495; HR, 1.19; 95% 1.01-1.41). In the EGFR mutant cohort, similar non-significant trends were observed for TCSs and DARDs. In the analysis according to EGFR TKI, erlotinib users had improved outcomes when early TCN or TCS purchases were registered, whereas DARDs were associated with worse outcomes among gefitinib users.

Conclusions: Among EGFR-TKI-treated NSCLCs, the use of TCN, TCS, and DARD can affect treatment outcomes that should be considered in optimal patient care.

Introduction: The prognostic differences between neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) remain unclear.

Methods: This study aims to compare the prognostic outcomes of NEC and MiNEN by analyzing the clinicopathological features of these diseases and exploring factors affecting progression after radical surgery. Additionally, we employed whole-exome sequencing to investigate the molecular mechanisms influencing the prognosis of both conditions.

Results: Among the 252 patients followed, 163 underwent surgical treatment. The median time to tumor progression was 16 months (range: 9 to 56 months). Tumor pathology type (P=0.007), lymph node metastasis (P<0.0001), and distant metastasis (P<0.0001) were identified as independent factors affecting disease progression in NEC and MiNEN patients. MiNEN patients without lymph node or distant metastasis generally had a better prognosis. First-line chemotherapy regimens did not show a significant impact on disease progression (P=0.160, mPFS: 36 vs 13 vs 23 vs 15 months). However, the EP (etoposide plus cisplatin) regimen has shown good efficacy in gastric NENs (neuroendocrine neoplasms) (P=0.048, mPFS: 45 vs 12 vs 32 vs 16 months), especially in gastric MiNENs (P=0.022, mPFS: Undefined vs 11 vs 52 vs 37 months). Further investigation into the genetic mutation differences between NECs and MiNENs revealed that among previously sequenced data, rectal NECs commonly exhibited mutations in MUC16, SPTA1, ATM, PDGFB, NF1, FAT4, AR, APC, ANTXR2, and ADGRA2. In contrast, rectal MiNENs showed common mutations in NOTCH2, ZNRF3, CARD11, TP53, OBSCN, FPR1, APC, ANGPT2, ARID1A, and AR. Mutations in ANGPT2 and OBSCN were present in two rectal MiNEN cases, while NF1 and PDGFB mutations were found in two rectal NEC cases but not in MiNENs. The JAK-STAT signaling pathway appears to be specific to rectal NECs and may be involved in tumor progression.

Conclusion: EP regimen remains the most effective chemotherapy option for neuroendocrine tumor patients. There were prognostic differences between NECs and MiNENs, as well as differences in genetic mutations and signaling pathways. This study provided new insights into the prognosis assessment and treatment strategies for NENs, particularly highlighting the importance of personalized treatments and the development of novel targeted therapies.

Introduction: The relationship between preoperative peak oxygen uptake/weight (VO2/W) and postoperative pulmonary complications (PPC) in lobectomies, including video-assisted thoracoscopic surgery, remains unclear. Traditional pulmonary function tests are often unreliable in this group, necessitating alternative predictive methods. Therefore, this study aimed to clarify the predictive value of preoperative peak VO2/W for PPC and explore factors related to PPC in lung cancer patients with chronic obstructive pulmonary disease (COPD).

Methods: This single-center retrospective cohort study included 40 patients with lung cancer complicated by COPD who underwent a preoperative cardiopulmonary exercise test between January 2017 and March 2024. Patients were divided into those with and without PPC (PPC and non-PPC groups, respectively). Clinical parameters such as surgical approach, pulmonary function, low attenuation area, and peak VO2/W were compared between the groups. The association between these parameters and PPC was analyzed using multivariate logistic regression.

Results: The preoperative % diffusing capacity of the lung for carbon monoxide (%DLCO) and peak VO2/W were significantly lower in the PPC group than in the non-PPC group (p<0.01 and p<0.001, respectively), while the ventilatory equivalent/ventilatory carbon dioxide (VE/VCO2) was significantly higher in the PPC group than in the non-PPC group (p<0.05). In the multivariate logistic analysis including the %DLCO, peak VO2/W, VE/VCO2, and forced expiratory volume in 1 second, only peak VO2/W was identified as a significant independent factor for predicting PPC. The area under the receiver operating characteristic curve of peak VO2/W to predict PPC was 0.93, with a cutoff value of 14.6 mL/min/kg, sensitivity of 78%, and specificity of 95%.

Conclusions: This study revealed that peak VO2/W was the most important parameter for predicting PPC in lung cancer patients with COPD. Incorporating cardiopulmonary exercise tests into preoperative assessments could improve risk stratification and perioperative management, potentially reducing the incidence of PPC in this high-risk population.

Introduction: The prognostic nutritional index (PNI) and D-dimer level are two useful measures for gastric cancer prognosis. As they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a PNI-D score - which combines the PNI and D-dimer level - and validate its usefulness as a prognostic marker.

Methods: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three PNI-D score groups based on the following criteria: score 2, low-PNI (≤46) and high D-dimer levels (>1.0 µg/mL); score 1, either low-PNI or high D-dimer levels; and score 0, no abnormality. We defined the PNI-D score as low (score 0 or 1) and high (score 2), respectively.

Results: The PNI-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank p < 0.0001). The 5-year overall survival rates of patients with PNI-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high-PNI-D score was an independent, statistically significant prognostic factor for poor overall (p = 0.01) survival in patients with gastric cancer.

Conclusions: The PNI-D is an independent prognostic factor for patients with gastric cancer.

Introduction: Recent reports have described the usefulness of carbon ion radiotherapy (CIRT) for inoperable sacral chordomas. However, its long-term local control rate needs to be improved. The present study identified the risk factors that affect the local relapse of sacral chordomas and the appropriate margins from the tumors.

Methods: Forty-nine patients with sacral chordoma treated with CIRT between 2011 and 2022 were retrospectively analyzed. Factors predicting the risk of local recurrence were evaluated, including age, sex, tumor size, muscle invaded with tumor, and surgery before CIRT. To determine the appropriate margin, the distance between the clinical target volume (CTV) and the out-field recurrent lesions was analyzed.

Results: The patients included 37 males and 12 females with a mean age of 67.1 years. A multivariate analysis showed that a tumor size >8 cm and invasion into the gluteus maximus muscle were significant risk factors with hazard ratios of 5.56 and 15.20 (p = 0.02 and 0.01), respectively. Out-field recurrence occurred in 13 cases, with 6, 3, and 4 relapses occurring in the muscle, bone, and both, respectively. The tumor occurred within 20 mm from the CTV in 60% of relapses in the muscles.

Conclusion: The current study presented novel findings on CIRT for sacral chordomas, although there were several limitations, such as a short follow-up period to investigate slow-growth tumors and a small number of tumor specimens owing to inoperative cases. A tumor size >8 cm and invasion into the gluteus maximus muscle were shown to be risk factors for recurrence in the treatment of sacral chordoma with CIRT. Our findings further suggest that an additional 2-cm margin from the CTV in the muscle fiber direction is recommended during CIRT.