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Increased Vitamin C Intake Is Associated With Decreased Pancreatic Cancer Risk. 维生素 C 摄入量的增加与胰腺癌风险的降低有关。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1854
Maria Pereira, Matthew Cardeiro, Lexi Frankel, Bryan Greenfield, Kazuaki Takabe, Omar M Rashid

Background: Patients with pancreatic cancer have an unfavorable 5-year survival rate of approximately 3% due to diagnosis occurring at advanced stages. Prior research has proposed vitamin C may have a therapeutic and preventative role in pancreatic cancer.

Methods: A Health Insurance Portability and Accountability Act (HIPAA) compliant national database was utilized to assess pancreatic cancer risk in patients with or without a history of vitamin C intake. The International Classification of Diseases (ICD) codes were used, specifically the International Classification of Diseases, 10th Edition (ICD-10) and International Classification of Diseases, Nineth Edition (ICD-9), between January 2010 and December 2020. Patients were matched, and statistical analyses were implemented. Chi-squared, logistic regression, and odds ratio were used to test for significance and to estimate relative risk.

Results: A total of 83,941 patients were identified as utilizing prescribed vitamin C. Subsequent matching by Charlson Comorbidity Index (CCI) score and age resulted in two groups of 50,384 patients. The incidence of pancreatic cancer was 243 (0.48%) in the group with a history of vitamin C intake compared to 442 (0.88%) in the control group. The difference was statistically significant by P < 3.174 × 10-14 with an odds ratio of 0.548 (95% confidence interval (CI): 0.468 - 0.641). Overall, patients without vitamin C prescription had an increased prevalence of pancreatic cancer throughout all ages and regions of the United States when compared to those with a vitamin C prescription. In addition, healthcare costs were higher in total for the control group when compared to the experimental group.

Conclusions: This retrospective cohort study found a statistically significant correlation between vitamin C and subsequent incidence of pancreatic cancer. Further studies are recommended to explore vitamin C's redox and cofactor activity in the context of preventing and possibly treating pancreatic cancer, as well as consider pancreatic cancer lifestyle risk factors such as smoking.

背景:胰腺癌患者由于确诊时已是晚期,5 年生存率约为 3%。先前的研究认为维生素 C 对胰腺癌有治疗和预防作用:方法:利用一个符合《健康保险可携性和责任法案》(HIPAA)的国家数据库,对有或无维生素 C 摄入史的患者的胰腺癌风险进行评估。数据库使用了国际疾病分类(ICD)代码,特别是 2010 年 1 月至 2020 年 12 月期间的第 10 版国际疾病分类(ICD-10)和第 9 版国际疾病分类(ICD-9)。对患者进行配对,并进行统计分析。采用卡方、逻辑回归和几率比来检验显著性和估计相对风险:根据夏尔森综合症指数(Charlson Comorbidity Index,CCI)评分和年龄进行匹配后,得出两组共 50,384 名患者。有维生素 C 摄入史的一组胰腺癌发病率为 243 例(0.48%),而对照组为 442 例(0.88%)。差异具有统计学意义(P < 3.174 × 10-14),几率比为 0.548(95% 置信区间(CI):0.468 - 0.641)。总体而言,与有维生素 C 处方的患者相比,没有维生素 C 处方的患者在美国各年龄段和各地区的胰腺癌发病率都有所上升。此外,与实验组相比,对照组的医疗费用总额更高:这项回顾性队列研究发现,维生素 C 与胰腺癌的后续发病率之间存在统计学意义上的显著相关性。建议进一步研究维生素 C 在预防和治疗胰腺癌方面的氧化还原和辅助因子活性,并考虑胰腺癌的生活方式风险因素,如吸烟。
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引用次数: 0
Comparison of Outcomes Between Partial and Radical Laparoscopic Nephrectomy for Localized Renal Tumors Larger Than Four Centimeters: A Systematic Review and Meta-Analysis. 局部和根治性腹腔镜肾切除术治疗大于四厘米的局部肾肿瘤的疗效比较:系统回顾与元分析》。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1866
Bao Nan Dong, Jie Song, Wen Li Yang, Hui Zhan, Ting Luan, Jian Song Wang

Background: Earlier studies have juxtaposed different laparoscopic methods for treating renal tumors; however, extensive evidence with a particular focus on large kidney tumors remains lacking. The objective of this meta-analysis was to assess the perioperative outcomes, kidney performance, and cancer-related results of laparoscopic partial nephrectomy (LPN) versus laparoscopic radical nephrectomy (LRN) for treating extensive, localized, non-metastatic kidney tumors (cT1b-cT2N0M0).

Methods: We systematically searched multiple databases from database inception until December 2023 for relevant studies. Selected data were analyzed with the Cochrane Collaboration's Review Manager 5.4 software using a random-effects model. Outcomes were expressed as odds ratios and weighted mean differences with 95% confidence intervals, considering a P value of < 0.05 as significant.

Results: Data from nine studies encompassing 1,303 patients (529 LPN, 774 LRN) revealed that LPN was associated with lengthier surgeries and increased blood loss compared to LRN. While LPN exhibited higher postoperative complication rates, the disparity did not reach statistical significance. LPN led to improved postoperative renal function, manifesting as a reduced estimated glomerular filtration rate (eGFR) decline and fewer incidents of new chronic kidney disease cases. Both groups demonstrated comparable tumor recurrence and overall mortality rates, but LPN exhibited significantly lower cancer-specific mortality rates.

Conclusions: LPN, despite longer operative times and greater intraoperative blood loss, was found to be superior to LRN in preserving postoperative renal function. Oncologically, LPN and LRN have comparable overall mortality rates, but LPN showed a significant advantage in terms of lower cancer-specific mortality rates.

背景:早期的研究将不同的腹腔镜方法并列用于治疗肾脏肿瘤;然而,特别是针对大型肾脏肿瘤的大量证据仍然缺乏。本荟萃分析的目的是评估腹腔镜肾部分切除术(LPN)与腹腔镜根治性肾切除术(LRN)治疗广泛、局部、非转移性肾肿瘤(cT1b-cT2N0M0)的围术期结果、肾脏表现和癌症相关结果:我们系统地检索了从数据库开始到 2023 年 12 月的多个数据库中的相关研究。采用随机效应模型,使用 Cochrane Collaboration 的 Review Manager 5.4 软件对所选数据进行分析。研究结果以几率比和加权平均差表示,95% 为置信区间,以 P 值小于 0.05 为显著:九项研究共涉及 1303 名患者(529 名 LPN,774 名 LRN),研究数据显示,与 LRN 相比,LPN 的手术时间更长,失血量更多。虽然 LPN 的术后并发症发生率较高,但其差异未达到统计学意义。LPN 术后肾功能有所改善,表现为估计肾小球滤过率(eGFR)下降和新发慢性肾病病例减少。两组的肿瘤复发率和总死亡率相当,但LPN的癌症特异性死亡率明显较低:结论:尽管LPN手术时间更长、术中失血更多,但在保护术后肾功能方面却优于LRN。从肿瘤学角度看,LPN 和 LRN 的总死亡率相当,但 LPN 在降低癌症特异性死亡率方面具有显著优势。
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引用次数: 0
Use of Period Analysis to Timely Assess Five-Year Relative Survival for the Patients With Bone Cancer. 利用周期分析及时评估骨癌患者的五年相对生存率
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1875
Xian Kuan Xie, Xiao Jiao Zhao, Run Hua Li, Yong Ran Cheng, Xin Bing, Jun Yang, Liang You Wang, Hui Jun Zhu, Tian Hui Chen, Jin Fei Chen

Background: While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China.

Methods: Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Five-year relative survival (RS) of bone cancer patients was calculated by period analysis for overall and the stratification. We further predicted 5-year RS during upcoming 2019 - 2023 using a model-based period analysis and survival data during 2004 - 2018.

Results: Overall, 5-year RS for patients with bone cancer during 2014 - 2018 reached 46.6%, being 40.8% for male and 51.0% for female. Five-year RS declined along with aging, decreasing from 58.9% for age < 45 years to 41.5% for age > 60 years, while 5-year RS for urban area was higher compared to rural area (59.1% vs. 44.3%). The 5-year RS during upcoming 2019 - 2023 reached 48.3%. We found a clear upward trend in 5-year RS during 2004 - 2023 for overall and the stratification by sex, age at diagnosis, and region.

Conclusions: We found that, for first time in China using period analysis, most up-to-date 5-year RS for patients with bone cancer reached 46.6% during 2014 - 2018, and is projected to reach 48.3% for the period 2019 - 2023, which has important implications for timely evaluation on early detection and prognosis level of treatment for patients with bone cancer in Eastern China.

背景:及时评估骨癌患者的长期生存率对于评价骨癌的早期发现和预后治疗水平至关重要,但这些数据在中国却非常缺乏。我们旨在及时、准确地评估华东地区骨癌患者的长期生存情况:方法:纳入华东地区台州市四个具有高质量数据的癌症登记处 2004-2018 年期间确诊的骨癌患者。骨癌患者的五年相对生存率(RS)是通过总体和分层的周期分析计算得出的。我们利用基于模型的时期分析和 2004 - 2018 年间的生存数据,进一步预测了 2019 - 2023 年间的 5 年相对生存率:结果:总体而言,2014-2018年间骨癌患者的5年RS达到46.6%,其中男性为40.8%,女性为51.0%。随着年龄的增长,5年生存率有所下降,从年龄小于45岁的58.9%降至年龄大于60岁的41.5%,而城市地区的5年生存率高于农村地区(59.1%对44.3%)。在即将到来的 2019-2023 年期间,5 年 RS 达到 48.3%。我们发现,2004-2023年期间,总体5年期RS以及按性别、诊断年龄和地区划分的5年期RS呈明显上升趋势:我们发现,在中国首次采用周期分析法,骨癌患者的最新5年RS在2014-2018年期间达到46.6%,预计2019-2023年期间将达到48.3%,这对及时评估华东地区骨癌患者的早期发现和预后治疗水平具有重要意义。
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引用次数: 0
Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs. 开发三阴性乳腺癌抗体药物共轭物的机遇与挑战:多样化的选择和不断变化的需求。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1853
Qi Tang, Hui Li, Xin Tong Zhao, Ze Ying Li, Chun Xiao Ma, Shao Qiang Zhou, De Dian Chen

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

三阴性乳腺癌(TNBC)是一种高度异质性的乳腺癌亚型,具有侵袭性表型、高复发率和预后差等特点。抗体药物共轭物(ADC)是一种单克隆抗体,其细胞毒性载荷由连接体连接。作为一种靶向抗癌药物,ADC 正受到越来越多的关注。在转移性乳腺癌(包括 TNBC)患者中,新出现的 ADC 药物(如 sacituzumab govitecan 和 trastuzumab deruxtecan)的临床研究进展迅速。鉴于其卓越的临床疗效和良好的耐受性,Sacituzumab govitecan于2020年获得了美国FDA的加速批准,用于治疗晚期转移性TNBC。本综述讨论 TNBC 的治疗现状和挑战,重点是 TNBC 和转移性乳腺癌的 ADC 开发和临床试验现状。我们还总结了针对 TNBC 患者的 ADC 开发的临床经验和未来探索方向。
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引用次数: 0
Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging. 磁共振成像上模仿骨肉瘤的表皮生长因子受体突变肺腺癌股骨近端转移瘤
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1888
Chang Jun Chen, Jun Feng Yin, Hao Xuan Zhang, Qing Wei Ma, Xin Zhao, Meng Chen, Da Yong Peng

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.

肺癌的侵袭性常常伴随着骨转移的高发病率;然而,与其他恶性肿瘤相比,肺癌引起的股骨近端转移并不常见。在本报告中,我们介绍了一名 53 岁亚洲男性的病例,他因左大腿和背部疼痛而就诊。磁共振成像显示左大腿处有严重的骨质破坏,邻近的软组织肿块也受累,成像结果与骨肉瘤相似。随后的骨活检确诊为表皮生长因子受体(EGFR)突变的肺腺癌并发骨转移。患者在服用奥希替尼后获得了生存,并接受了股骨转移手术,而没有接受肺癌姑息手术。因此,在怀疑患有骨肉瘤的患者中,应将表皮生长因子受体(EGFR)突变的肺腺癌引起的股骨近端转移作为鉴别诊断。本文介绍了表皮生长因子受体(EGFR)突变肺腺癌股骨近端转移的影像学检查结果,并讨论了其治疗方法。
{"title":"Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.","authors":"Chang Jun Chen, Jun Feng Yin, Hao Xuan Zhang, Qing Wei Ma, Xin Zhao, Meng Chen, Da Yong Peng","doi":"10.14740/wjon1888","DOIUrl":"10.14740/wjon1888","url":null,"abstract":"<p><p>The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (<i>EGFR</i>)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from <i>EGFR</i>-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from <i>EGFR</i>-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Results of Stereotactic Body Radiotherapy With CyberKnife-M6 for Primary and Metastatic Lung Cancer. 使用 CyberKnife-M6 进行立体定向体放射治疗原发性和转移性肺癌的结果。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1865
Sureyya Sarihan, Sema Gozcu Tunc, Zenciye Kiray Irem, Arda Kahraman, Gokhan Ocakoglu

Background: The aim of the study was to evaluate the efficacy of stereotactic body radiotherapy (SBRT) using the CyberKnife-M6 (CK-M6) with lung optimized treatment (LOT) module in patients with primary lung cancer and lung metastases.

Methods: Forty-two lesions from 35 patients were treated between 2019 and 2022. Four-dimensional computed tomography images were obtained when the patients were in a free breathing modality. Tracking modality was selected prospectively according to the visibility of the target. The median prescribed dose was 48 Gy in four fractions (fx) (28 - 55 Gy/1- 7 fx). The median age was 68 years (47 - 82 years), and 43% of cases were adenocarcinoma. The median lesion size was 15 mm (6 - 36 mm).

Results: Complete, partial and stable responses were obtained as 26%, 62%, and 9.5% at a median of 2 months (1 - 6 months), and 35.5%, 47.5% and 5% at the 12th month evaluation, respectively. Grade 3 and higher toxicity was not observed in any case. The mean and 2-year overall survival (OS) was 31.5 months and 54%, and the local recurrence-free survival (LRFS) was 29.6 months and 51%, respectively. In univariate analysis, target lesion type, complete response (CR), and higher esophagus maximum dose were favorable factors for OS and LRFS (P < 0.05). The CR at 12th month evaluation remained significant in multivariate analysis in terms of OS (hazard ratio = 8.602, 95% confidence interval: 1.05 - 70.01; P = 0.044).

Conclusions: A mean LRFS of 29.6 months and OS of 31.5 months were obtained in patients with primary and metastatic lung cancer. With a median treatment time of 25 min, motion-managed strategy with CK-M6-LOT-based SBRT is an effective, safe, and comfortable treatment method for lung cancer.

研究背景该研究旨在评估使用带有肺优化治疗(LOT)模块的CyberKnife-M6(CK-M6)立体定向体放射治疗(SBRT)对原发性肺癌和肺转移患者的疗效:在2019年至2022年期间,对35名患者的42个病灶进行了治疗。患者在自由呼吸模式下获得四维计算机断层扫描图像。追踪方式根据靶点的可见度进行前瞻性选择。处方剂量中位数为48 Gy,分四次进行(28 - 55 Gy/1- 7 fx)。中位年龄为68岁(47 - 82岁),43%的病例为腺癌。中位病灶大小为 15 毫米(6 - 36 毫米):在中位 2 个月(1 - 6 个月)和第 12 个月的评估中,完全、部分和稳定应答的比例分别为 26%、62% 和 9.5%,而在第 12 个月的评估中,完全、部分和稳定应答的比例分别为 35.5%、47.5% 和 5%。所有病例均未出现 3 级及以上毒性。平均2年总生存期(OS)分别为31.5个月和54%,无局部复发生存期(LRFS)分别为29.6个月和51%。在单变量分析中,靶病灶类型、完全反应(CR)和较高的食管最大剂量是影响OS和LRFS的有利因素(P < 0.05)。在多变量分析中,第12个月评估时的CR对OS仍有显著影响(危险比=8.602,95%置信区间:1.05 - 70.01;P=0.044):原发性和转移性肺癌患者的平均长生存期为29.6个月,生存期为31.5个月。中位治疗时间为25分钟,基于CK-M6-LOT的SBRT运动管理策略是一种有效、安全、舒适的肺癌治疗方法。
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引用次数: 0
Significance and Possible Biological Mechanism for CLDN8 Downregulation in Kidney Renal Clear Cell Carcinoma Tissues. 肾脏透明细胞癌组织中 CLDN8 下调的意义和可能的生物学机制
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1869
Han Chu Ji, Jian Di Li, Guan Lan Zhang, Zhi Guang Huang, Ji Wen Cheng, Sheng Hua Li, Chun Yan Zhao, Yu Xing Tang, Kai Qin, You Liang Ma, Yu Long, Gang Chen, Bin Qin

Background: The clinical role of claudin 8 (CLDN8) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of CLDN8 underlying KIRC were determined.

Methods: High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the CLDN8. In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of CLDN8. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of CLDN8. Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC.

Results: A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). CLDN8 downregulation was also confirmed at the single-cell level. Knocking out CLDN8 stimulated KIRC cell proliferation. Lower CLDN8 expression was correlated with worse overall survival of KIRC patients (hazard ratio of CLDN8 downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with CLDN8 co-expressed genes were centered on carbon metabolism obstruction, with key hub genes ACADM, ACO2, NDUFS1, PDHB, SDHD, SUCLA2, SUCLG1, and SUCLG2.

Conclusions: CLDN8 is downregulated in KIRC and is considered a potential tumor suppressor. CLDN8 deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.

背景:Claudin 8(CLDN8)在肾透明细胞癌(KIRC)中的临床作用仍未明确。方法:从 GEO、ArrayExpress、SRA 和 TCGA 数据库中收集 KIRC 的高通量数据集,以确定 CLDN8 的 mRNA 表达水平。为了检测CLDN8蛋白的表达,还进行了内部组织微阵列和免疫化学研究。使用Stata v16.0生成了接收者操作特征曲线(SROC)和标准化平均差(SMD)森林图。为进一步证明CLDN8的表达水平,还进行了单细胞分析。为评估 CLDN8 对生长的影响,进行了聚类规律性间隔短回文重复敲除筛选分析。利用 Metascape 数据库进行了功能富集分析。此外,还进行了单样本基因组富集分析,以探讨免疫细胞在KIRC中的浸润情况:本研究共纳入了 17 个 mRNA 数据集,包括 1,060 个 KIRC 样本和 452 个非癌症对照样本。此外,还使用内部免疫组化方法分析了 105 例 KIRC 和 16 例非 KIRC 组织。综合SMD为-5.25(95%置信区间(CI):-6.13至-4.37),CLDN8下调产生的SROC曲线下面积(AUC)接近1.00(95% CI:0.99 - 1.00)。CLDN8 下调也在单细胞水平上得到了证实。敲除 CLDN8 会刺激 KIRC 细胞增殖。较低的CLDN8表达与KIRC患者较差的总生存率相关(CLDN8下调的危险比=1.69,95% CI:1.2 - 2.4)。与CLDN8共表达基因相关的功能通路以碳代谢障碍为中心,关键枢纽基因为ACADM、ACO2、NDUFS1、PDHB、SDHD、SUCLA2、SUCLG1和SUCLG2:CLDN8在KIRC中下调,被认为是潜在的肿瘤抑制因子。CLDN8缺乏可能与代谢功能障碍一起促进KIRC的发生和发展。
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引用次数: 0
Risk Stratification Tools to Aid Decisions on Adjuvant Chemotherapy Usage in Resected Soft Tissue Sarcomas: A Ten-Year Review of an Irish Sarcoma Center Experience. 风险分层工具用于辅助已切除软组织肉瘤的辅助化疗决策:爱尔兰肉瘤中心十年经验回顾。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-17 DOI: 10.14740/wjon1863
Catherine S Weadick, Caitriona Goggin, Rachel J Keogh, Jake F Murphy, Linda Feeley, Michael W Bennett, Seamus O'Reilly, H Paul Redmond, Jason Kelly, Deirdre O'Mahony, Sinead Noonan, A James P Clover, Richard M Bambury

Background: Soft tissue sarcoma (STS) is comprised of approximately 80 subtypes, with an incidence of 4 - 5 per 100,000 annually in Europe. The National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of neoadjuvant/adjuvant chemotherapy in tumors at high risk of recurrence based on the American Joint Committee on Cancer (AJCC) staging. Alternatively, the Sarculator is a risk prediction tool that has identified a threshold of risk, above which chemotherapy may provide an overall survival (OS) benefit. Using this nomogram, patients with a 10-year predicted OS < 60% are classified as high risk and should be considered for chemotherapy. The aim of this study was to assess the prognostic accuracy of these two risk prediction methods in an Irish population.

Methods: All newly diagnosed patients with resected STS discussed in the STS tumor board in Cork University Hospital between January 2012 and December 2021 were identified. Clinicopathological data were collected. Risk assessment using AJCC and Sarculator nomogram was performed on all patients with an extremity/trunk sarcoma. The OS was calculated including Kaplan-Meier method for time to event analysis.

Results: In total, 200 STS patients were reviewed, of whom 134 had truncal or extremity tumors. Sarculator score was calculated for 60 of these (well differentiated liposarcomas, desmoid tumors and dermatofibrosarcoma protuberans were excluded). Using the Sarculator nomogram to calculate 10-year predicted OS, 19 patients were categorized as high risk and 41 were categorized as low risk. Using AJCC staging, 25 patients were categorized as high risk and 35 as low risk. The 5-year OS rate in the Sarculator high-risk group was 60.2%, compared with 87.1% in the low-risk group (P = 0.009). The 5-year OS rate in the AJCC high-risk group was 67.6%, compared with 86.3% in the low-risk group (P = 0.083).

Conclusions: Our cohort is representative of the broad histological subtypes expected. In our population, Sarculator score results correlate with international outcomes and higher scores were associated with increased mortality. The Sarculator was more predictive of clinical outcome than AJCC staging, and its use would lower the proportion of patients being considered for adjuvant chemotherapy thereby sparing toxicity, which is important in the setting of uncertain clinical benefit.

背景:软组织肉瘤(STS)包括约 80 种亚型,在欧洲的发病率为每年每 10 万人中 4-5 例。美国国家综合癌症网络(NCCN)指南建议,根据美国癌症联合委员会(AJCC)的分期,复发风险高的肿瘤应考虑新辅助/辅助化疗。另外,Sarculator 是一种风险预测工具,它确定了一个风险阈值,超过该阈值,化疗可能会带来总生存期(OS)的获益。使用该提名图,10年预测OS<60%的患者被归类为高风险患者,应考虑接受化疗。本研究旨在评估这两种风险预测方法在爱尔兰人群中的预后准确性:方法:确定科克大学医院 STS 肿瘤委员会在 2012 年 1 月至 2021 年 12 月期间讨论的所有新诊断的 STS 切除患者。收集临床病理数据。使用 AJCC 和 Sarculator 提名图对所有肢体/躯干肉瘤患者进行风险评估。采用 Kaplan-Meier 法对事件发生时间进行分析,计算 OS:结果:共对200例STS患者进行了复查,其中134例为躯干或四肢肿瘤。对其中的 60 例进行了 Sarculator 评分(不包括分化良好的脂肪肉瘤、类苔藓瘤和原发性皮纤维肉瘤)。使用 Sarculator 提名图计算 10 年预测 OS,19 例患者被归类为高风险,41 例被归类为低风险。使用AJCC分期,25名患者被归为高风险,35名被归为低风险。Sarculator 高风险组的 5 年 OS 率为 60.2%,而低风险组为 87.1%(P = 0.009)。AJCC高风险组的5年OS率为67.6%,低风险组为86.3%(P = 0.083):结论:我们的队列在广泛的组织学亚型中具有代表性。在我们的人群中,Sarculator评分结果与国际结果相关,评分越高,死亡率越高。Sarculator 比 AJCC 分期更能预测临床结果,使用 Sarculator 可以降低考虑辅助化疗的患者比例,从而减轻毒性,这在临床疗效不确定的情况下非常重要。
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引用次数: 0
Cancer Screening in Renal Transplant Recipients: Real-World Data. 肾移植受者的癌症筛查:真实世界数据。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.14740/wjon1822
Mohammad Hassan Al-Thnaibat, Sundus Yahya Nser, Yasmeen Jamal Alabdallat, Maysoun Hajir

Background: Multiple international guidelines have endorsed cancer screening in renal transplant patients. This study aimed to describe a series of patients with post-transplant cancer and to report physicians' adherence to cancer screening guidelines.

Methods: This is a retrospective study of cancer patients who had a history of renal transplant. Charts of patients who were treated at our institution between 2012 and 2023 were reviewed, patients' clinical data were collected.

Results: Thirty-nine patients were identified. The most common types of cancer were lymphoma (n = 9, 23%), squamous cell carcinoma (SCC) of the skin (n = 8, 20.5%), and breast (n = 6, 15.4%). The median age at diagnosis was 56.5 years (range: 16.9 - 70.2), family history of malignancy was depicted in 18 (46.2%) cases. Chart review and patients' questionnaire revealed that increased risk of malignancy was discussed in seven (18%) out of 39 recipients (P < 0.001) at time of transplant, and only three (7.7%, P < 0.001) patients were on post-transplant age-matched cancer screening.

Conclusions: The increased risk of malignancy is a serious post-transplant complication. Lymphoma and non-melanoma skin cancer were the most common cancers. Most patients were not offered routine cancer screening; it is important to raise awareness among nephrologists and caregivers regarding the risk of post-transplant malignancy.

背景:多个国际指南都认可对肾移植患者进行癌症筛查。本研究旨在描述一系列移植后癌症患者的情况,并报告医生对癌症筛查指南的遵守情况:这是一项针对有肾移植史的癌症患者的回顾性研究。方法:这是一项回顾性研究,研究对象为2012年至2023年期间在我院接受治疗的癌症患者:结果:共发现 39 例患者。最常见的癌症类型为淋巴瘤(9例,23%)、皮肤鳞状细胞癌(8例,20.5%)和乳腺癌(6例,15.4%)。确诊时的中位年龄为 56.5 岁(16.9 - 70.2 岁),18 例(46.2%)患者有恶性肿瘤家族史。病历回顾和患者问卷调查显示,39名受者中有7人(18%)在移植时讨论过恶性肿瘤风险增加的问题(P<0.001),只有3人(7.7%,P<0.001)在移植后接受了年龄匹配的癌症筛查:结论:恶性肿瘤风险的增加是移植后的一个严重并发症。淋巴瘤和非黑色素瘤皮肤癌是最常见的癌症。大多数患者没有接受常规癌症筛查;提高肾脏科医生和护理人员对移植后恶性肿瘤风险的认识非常重要。
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引用次数: 0
Untapped Potential of Poly(ADP-Ribose) Polymerase Inhibitors: Lessons Learned From the Real-World Clinical Homologous Recombination Repair Mutation Testing. 多聚(ADP-核糖)聚合酶抑制剂尚未开发的潜力:从现实世界的临床同源重组修复突变检测中汲取的教训。
IF 2.1 Q3 ONCOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-11 DOI: 10.14740/wjon1820
Alexandra Lebedeva, Egor Veselovsky, Alexandra Kavun, Ekaterina Belova, Tatiana Grigoreva, Pavel Orlov, Anna Subbotovskaya, Maksim Shipunov, Oleg Mashkov, Fanil Bilalov, Peter Shatalov, Andrey Kaprin, Peter Shegai, Zhan Diuzhev, Ochir Migiaev, Natalya Vytnova, Vladislav Mileyko, Maxim Ivanov

Background: Testing for homologous recombination deficiency (HRD) mutations is pivotal to assess individual risk, to proact preventive measures in healthy carriers and to tailor treatments for cancer patients. Increasing prominence of poly(ADP-ribose) polymerase (PARP) inhibitors with remarkable impact on molecular-selected patient survival across diverse nosologies, ingrains testing for BRCA genes and beyond in clinical practice. Nevertheless, testing strategies remain a question of debate. While several pathogenic BRCA1/2 gene variants have been described as founder pathogenic mutations frequently found in patients from Russia, other homologous recombination repair (HRR) genes have not been sufficiently explored. In this study, we present real-world data of routine HRR gene testing in Russia.

Methods: We evaluated clinical and sequencing data from cancer patients who had germline/somatic next-generation sequencing (NGS) HRR gene testing in Russia (BRCA1/2/ATM/CHEK2, or 15 HRR genes). The primary objectives of this study were to evaluate the frequency of BRCA1/2 and non-BRCA gene mutations in real-world unselected patients from Russia, and to determine whether testing beyond BRCA1/2 is feasible.

Results: Data of 2,032 patients were collected from February 2021 to February 2023. Most had breast (n = 715, 35.2%), ovarian (n = 259, 12.7%), pancreatic (n = 85, 4.2%), or prostate cancer (n = 58, 2.9%). We observed 586 variants of uncertain significance (VUS) and 372 deleterious variants (DVs) across 487 patients, with 17.6% HRR-mutation positivity. HRR testing identified 120 (11.8%) BRCA1/2-positive, and 172 (16.9%) HRR-positive patients. With 51 DVs identified in 242 formalin-fixed paraffin-embedded (FFPE), testing for variant origin clarification was required in one case (0.4%). Most BRCA1/2 germline variants were DV (121 DVs, 26 VUS); in non-BRCA1/2 genes, VUS were ubiquitous (53 DVs, 132 VUS). In silico prediction identified additional 4.9% HRR and 1.2% BRCA1/2/ATM/CHEK2 mutation patients.

Conclusions: Our study represents one of the first reports about the incidence of DV and VUS in HRR genes, including genes beyond BRCA1/2, identified in cancer patients from Russia, assessed by NGS. In silico predictions of the observed HRR gene variants suggest that non-BRCA gene testing is likely to result in higher frequency of patients who are candidates for PARP inhibitor therapy. Continuing sequencing efforts should clarify interpretation of frequently observed non-BRCA VUS.

背景:同源重组缺陷(HRD)基因突变检测是评估个体风险、对健康携带者采取预防措施以及为癌症患者量身定制治疗方案的关键。多聚(ADP-核糖)聚合酶(PARP)抑制剂的作用日益突出,对不同病种的分子选择患者的存活率产生了显著影响,这使得 BRCA 基因及其他基因的检测在临床实践中根深蒂固。然而,检测策略仍是一个争论不休的问题。虽然有几种致病性 BRCA1/2 基因变异已被描述为俄罗斯患者中经常发现的创始致病性突变,但其他同源重组修复(HRR)基因尚未得到充分探讨。在本研究中,我们展示了俄罗斯常规 HRR 基因检测的真实数据:我们评估了在俄罗斯进行种系/体细胞下一代测序(NGS)HRR 基因检测(BRCA1/2/ATM/CHEK2 或 15 个 HRR 基因)的癌症患者的临床和测序数据。本研究的主要目的是评估俄罗斯真实世界中未入选患者的 BRCA1/2 和非 BRCA 基因突变频率,并确定 BRCA1/2 之外的检测是否可行:从 2021 年 2 月到 2023 年 2 月,共收集了 2032 名患者的数据。大多数患者患有乳腺癌(715 人,35.2%)、卵巢癌(259 人,12.7%)、胰腺癌(85 人,4.2%)或前列腺癌(58 人,2.9%)。我们在487名患者中观察到了586个意义不确定的变异(VUS)和372个有害变异(DV),其中17.6%为HRR突变阳性。HRR 检测发现了 120 例(11.8%)BRCA1/2 阳性患者和 172 例(16.9%)HRR 阳性患者。在 242 例福尔马林固定石蜡包埋(FFPE)患者中发现了 51 个 DV,其中一例患者(0.4%)需要进行变异来源鉴定。大多数 BRCA1/2 基因变异为 DV(121 个 DV,26 个 VUS);在非 BRCA1/2 基因中,VUS 无处不在(53 个 DV,132 个 VUS)。硅预测发现了另外4.9%的HRR和1.2%的BRCA1/2/ATM/CHEK2突变患者:我们的研究是通过 NGS 评估俄罗斯癌症患者 HRR 基因(包括 BRCA1/2 以外的基因)中 DV 和 VUS 发生率的首批报告之一。对观察到的 HRR 基因变异进行硅学预测表明,非 BRCA 基因检测可能会导致更多患者接受 PARP 抑制剂治疗。持续的测序工作应能澄清对经常观察到的非 BRCA VUS 的解释。
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引用次数: 0
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World Journal of Oncology
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