Adjuvant Tyrosine Kinase Inhibitors in Treatment of Renal Cell Carcinoma: A Meta-Analysis of Available Clinical Trials

Although tyrosine kinase inhibitors (TKIs) are widely used in the metastatic setting, they have shown more limited effectiveness in the adjuvant setting. Despite multiple clinical trials, there has been no improvement in overall survival (OS) with the use of these agents as adjuvant therapy, and conflicting data on disease-free survival (DFS). We carried out a meta-analysis of available phase III randomized clinical trials on adjuvant TKIs in clear-cell renal cell carcinoma (RCC). Primary end points of our study were the effect of adjuvant TKIs on OS and DFS in the overall population. Furthermore, we investigated if use of adjuvant TKIs resulted in improved DFS among patients with different risk of tumor relapse. Higher-risk patients were patients with 1 or more of the following features: positive nodes (N+), T4 tumors and T3 tumors, with higher Fuhrman grades (3-4). We adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to carry out our study. In the overall population, the pooled hazard ratio (HR) of OS and DFS was 0.89 (95% confidence interval [CI], 0.76-1.04) and 0.84 (95% CI, 0.76-0.93), respectively. In the low- and high-risk populations, the pooled DFS HR was 0.98 (95% CI, 0.82-1.17) and 0.85 (95% CI, 0.75-0.97), respectively. Adjuvant use of TKIs do not appear to provide a statistically significant OS benefit. However, a benefit in DFS has been observed in overall and high-risk populations, suggesting that better selection of patients might be important for the evaluation of adjuvant therapies in RCC.     

Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: A histologic dichotomy

Background

Treatment failures in stage IIIC endometrial carcinoma (EC) are predominantly due to occult extrapelvic metastases (EPM). The impact of chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs G3EC.

Methods

All surgical-stage IIIC EC cases from January 1, 1999, through December 31, 2008, from Mayo Clinic were included. Patient-, disease-, and treatment-specific risk factors were assessed for association with overall survival, cause-specific survival, and extrapelvic disease-free survival (DFS) using Cox proportional hazards regression.

Results

109 cases met criteria, with 92 (84%) having systematic lymphadenectomy (> 10 pelvic and > 5 paraaortic lymph nodes resected). In patients with documented recurrence sites, occult EPM accounted for 88%. Among G1/2EC cases (n = 48), the sole independent predictor of extrapelvic DFS was grade 2 histology (hazard ratio [HR], 0.28; 95% CI, 0.08–0.91; P = .03) while receipt of adjuvant chemotherapy approached significance (HR 0.13; 95% CI, 0.02, 1.01; P = .0511). The 5-year extrapelvic DFS with and without adjuvant chemotherapy was 93% and 54%, respectively (log-rank, P = .02). Among G3EC (n = 61), the sole independent predictor of extrapelvic DFS was lymphovascular space involvement (HR, 2.63; 95% CI, 1.16–5.97; P = .02). Adjuvant chemotherapy did not affect occult EPM in G3EC; the 5-year extrapelvic DFS for G3EC with and without adjuvant chemotherapy was 43% and 42%, respectively (log-rank, P = .91).

Conclusions

Chemotherapy improves extrapelvic DFS for stage IIIC G1/2EC but not stage IIIC G3EC. Future efforts should focus on prospectively assessing the impact of chemotherapy on DFS in G3EC and developing innovative phase I and II trials of novel systemic therapies for advanced G3EC.     

HPV感染对口咽癌无病生存期影响的Meta分析

目的 综合评价人乳头状瘤病毒（HPV）感染与口咽癌无病生存期（disease-free survival,DFS）的关联。方法 检索中国知网、维普、万方、PubMed等数据库,全面收集研究HPV感染与口咽癌无病生存期关系的文献,设定纳入和排除标准,评价文献质量,检验异质性,计算合并风险比（HR）及其95%可信区间（95%CI）,评估发表偏倚。结果 纳入文献16篇,口咽癌病例共2 512例,其中HPV阳性1 210例,HPV阳性率48.17%,HPV阴性1 302例。与HPV阴性相比,HPV感染的口咽癌病例复发或转移风险较低（合并HR: 0.371, 95%CI: 0.231~0.511）,其中HPV-16型感染对口咽癌DFS的合并HR为0.248, 95%CI: 0.132~0.365;HPV阳性且p16蛋白表达对口咽癌DFS有保护作用（合并HR:0.281, 95%CI: 0.137~0.424)。结论 HPV感染对口咽癌无病生存期可能有保护作用。     

PD-L1及TGF-β在非小细胞肺癌中的表达及其临床意义

目的 探讨在非小细胞肺癌(NSCLC)中PD-L1及TGF-β表达水平,及其与NSCLC临床病理参数和术后无病生存期(DFS)的关系.方法 收集81例NSCLC标本,采用免疫组化方法检测术后肿瘤组织中PD-L1、PD-1、Foxp3+和TGF-β蛋白的表达水平.结果 81例患者中PD-L1阳性表达为46例(56.8%),阴性表达35例(43.2%).TGF-β阳性36例(44.4%),阴性45例(55.6%).PD-1阳性33例(40.7%),阴性48例(59.3%);Foxp3+阳性44例(54.3%),阴性37例(45.7%).NSCLC中PD-L1蛋白表达与各临床病理参数无明显相关性.单因素分析发现T分期、TGF-β表达、PD-L1表达影响.SCLC术后DFS,具有统计学差异(P<0.05),多因素分析发现T分期、TGF-β表达、PD-L1表达是影响NSCLC术后DFS的独立因素(P<0.05).PD-L1阳性表达组术后DFS为(21.000±1.429)个月,阴性表达组为(14.500±1.615)个月,两组有统计学差异(χ2=6.930,P=0.008).TGF-β阳性组PFS为(14.500±0.813)个月,阴性组为(21.000±1.639)个月,两组有统计学差异(χ2=8.71,P=0.003).结论 非小细胞肺癌中PD-L1及TGF-β蛋白是预测NSCLC术后DFS的重要指标,且PD-L1表达越高预示术后DFS越长,而TGF-β则表达越高,预示术后DFS越短.     

乳腺癌组织中COX-2、TRX-1表达及其预后意义

目的：应用免疫组化法,检测COX-2、TRX-1在乳腺癌组织中表达,探讨COX-2、TRX-1表达与乳腺癌临床病理特征及预后因素的关系。方法：122例乳腺癌组织石蜡标本制作成乳腺癌组织芯片。免疫组化sP法检测COX-2、TRX-1表达。所有患者均接受规范性手术、术后辅助化疗及放疗,激素受体阳性病人接受5年的内分泌治疗。从手术日期到复发转移或随访截止日期（2008年7月）确定为患者无病生有溯。共有45例复发嘲多病例。结果：122例乳腺癌组织中COX-2、TRX-1均呈高表达,分别为58．2％、54．1％,且二者表达呈正相关（r=0．286,P=0．001）;COX-2表达与临床分期（r=0．193,P=0．033）、肿块大小（r=0．192,P=0．034）及淋巴结转移（r=0．186,P=0．040）呈正相关,TRX-1表达与临床分期（r=0．206,P=0．023）、肿块大小（r=0．236,P=0．009）呈正相关,与淋巴结转移（r=0．175,P=0．054）不相关。COX-2或TRX-1表达与无病生存期呈负相关（P=0．027,P=0．046）;COX-2和TRX-1共表达与无病生存期呈负相关（P=0．017）。结论：乳腺癌组织中COX-2、TRX-1均呈高表达,两者与乳腺癌患者预后密切相关;COX-2、TRX-1表达呈正相关,推测乳腺癌组织中TRX-1可能参与COX-2调节。     

Adjuvant therapy in renal cell carcinoma: is it the right strategy to inhibit VEGF?

Despite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outcomes when used ad adjuvant treatments. In this study, we performed a meta-analysis of 5 randomized clinical trials to assess the impact of tyrosine kinase inhibitors (TKIs) targeting angiogenesis after surgery: ASSURE, S-TRAC, PROTECT, ATLAS, SORCE. Among the 6,531 patients assessed, we confirmed the lack of efficacy of adjuvant treatments in terms of disease-free survival (DFS) (pooled-HR 0.93, 95% CI, 0.84–1.02, P=0.16) and overall survival (OS) (pooled-HR 0.98, 95% CI, 0.88–1.09, P=0.54). To the best of our knowledge, we still ignore why some treatments active in the metastatic setting do not show similar efficacy as adjuvant treatment. Exploring possible reasons of this apparently conflicting results is important as it may offer new insights that should be evaluated in next generation adjuvant trials. Immune checkpoint inhibitors (ICIs) have reported significant results—as monotherapy or in combinations with other anticancer agents—in metastatic setting, and the results of trials evaluating these agents in the adjuvant setting are awaited.     

Perioperative blood transfusion is not an independent predictor for worse outcomes in retroperitoneal sarcoma surgery

BackgroundSurgery for retroperitoneal soft tissue sarcoma (RPS) is technically challenging, often requiring perioperative red blood cell transfusion (PBT). In other cancers, controversy exists regarding the association of PBT and oncologic outcomes. No study has assessed this association in primary RPS, or identified factors associated with PBT.MethodsData was collected on all resected primary RPS between 2006 and 2020 at The Ottawa Hospital (Canada) and University Hospital Birmingham (United Kingdom). ‘PBT’ denotes transfusion given one week before surgery until discharge. Multivariable regression (MVA) identified clinicopathologic factors associated with PBT and assessed PBT association with oncologic outcomes. Surgical complexity was measured using resected organ score (ROS) and patterns of resection.Results192 patients were included with 98 (50.8%) receiving PBT. Median follow-up was 38.2 months. High tumour grade (OR 2.20, P = 0.048), preoperative anemia (OR 2.78, P = 0.020), blood loss >1000 mL (OR 4.89, P = 0.004) and ROS >2 (OR 2.29, P = 0.026) were associated with PBT on MVA. A direct linear relationship was observed between higher ROS and increasing units of PBT (β = 0.586, P = 0.038). Increasingly complex patterns of resection were associated with increasing odds of PBT. PBT was associated with severe post-operative complications (P = 0.008) on MVA. Univariable association between PBT and 5-year disease-free or overall survival was lost upon MVA.ConclusionsSurgical complexity and high tumour grade are potentially related to PBT. Oncologic outcomes are not predicted by PBT but are better explained by tumour grade which subsequently may increase surgical complexity. Strategies to reduce PBT should be considered in primary RPS patients.     

Propensity-matched comparison of video-assisted thoracoscopic with thoracotomy lobectomy for locally advanced non–small cell lung cancer

Objective

We evaluated whether video-assisted thoracoscopic lobectomy for locally advanced non–small cell lung cancer could be performed safely and with acceptable long-term outcomes by our improved technique and compared with standard thoracotomy lobectomy in a well-balanced population.