Transarterial Yttrium-90 Radioembolization Treatment of Patients with Liver-Dominant Metastatic Renal Cell Carcinoma

Purpose

To evaluate safety and efficacy of transarterial hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC).

肾细胞癌免疫治疗的研究进展

肾细胞癌（renal cell carcinoma, RCC）是成年男性常见的恶性肿瘤, 其发病率和死亡率排名均较前。免疫治疗能够激活机体免疫系统产生对肿瘤的反应使疾病稳定,但高剂量不良反应限制了其在临床的广泛应用。而靶向药物的兴起让肾癌患者治疗方式向靶向治疗转变。随着对肾癌临床治疗方式的不断深入研究,发现单纯的免疫或靶向治疗难以得到令人满意的疗效。因此有学者提出肾细胞癌的治疗应该向免疫联合靶向治疗方向转变。本文旨在对当前肾细胞癌相关免疫治疗的临床研究作一综述,以期为临床肾细胞癌的免疫治疗提供一定的理论依据。     

Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma

Renal cell carcinoma (RCC) is a highly malignant and often fatal disease of the kidney. Chmp1A is a member of the Endosomal Sorting Complex Required for Transport (ESCRT-III) family, and plays a role in the cytoplasm in sorting proteins to the multivesicular body (MVB). Chmp1A functions as a tumor suppressor gene and has been reported in pancreatic tumor cells. Here, we examined the expression level of Chmp1A in human RCC tissues and renal tumor cells by real-time quantitative RT-PCR and western blot. We found that the expression level of Chmp1A is significantly lower in RCC tissues and renal tumor cells compared with adjacent non-tumorous tissues and normal renal cells. Additionally, inhibition of Chmp1A expression by shRNA induced tumor formation in normal renal cells. However, inhibition of Chmp1A did not significantly affect tumor cell proliferation in vitro and tumor progression in vivo. Interestingly, overexpression of Chmp1A using a eukaryotic plasmid inhibited the proliferation of renal tumor cells in vitro and the growth of renal tumor in vivo. Thus, our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells and may be a useful target for treatment of RCC.     

年龄和环境对肾细胞癌临床病理特征的影响

目的探讨不同年龄和生活环境的肾细胞癌的临床病理特征。方法回顾性分析256例肾细胞癌患者的年龄、临床症状、临床分期、淋巴结转移、远处转移、病理特征等方面资料,比较〈40岁组、40～60岁组和〉60岁组间及农村和城市间的临床及病理特征。结果①在肾细胞癌中透明细胞癌的所占比例随年龄增长而增加,三组间两两比较差异有统计学意义（P=0.01）;嫌色细胞癌和集合管癌的所占比例则随年龄增长逐渐减少,三组间两两比较差异有统计学意义（P=0.047）;肾细胞癌病理类型与环境无关。②40～60岁组中无症状肾细胞癌所占比例均高于〈40岁组与〉60岁组,且与〈40岁组比较有显著性差异（P=0.02）;Ⅲ期肾细胞癌在40～60岁组中的比例明显低于〈40岁组（P=0.04）和〉60岁组（P=0.059）,且前者差异有统计学意义;农村肾细胞癌患者中Ⅰ期肾癌比例低于城市组（P=0.0001）,而Ⅲ期肾细胞癌（P=0.0007）和Ⅳ期肾细胞癌（P〈0.0001）比例显著高于城市。③40～60岁组肾细胞癌患者淋巴结转移比例低于〈40岁组（P=0.028）和〉60岁组（P=0.035）,差异有统计学意义;农村肾细胞癌患者淋巴结转移（P〈0.0001）和远处转移（P=0.002）的比例也显著高于城市。结论不同年龄段肾细胞癌的临床及病理特征存在差异,农村和城市间病理特征没有差异而临床特征有差别;加强肾细胞癌的早期诊断和早期治疗应重视中年人（40～60岁）和农村人群,不可忽视年轻人群（〈40岁）、老年人群（〉60岁）。     

Improving the accuracy of pre-operative survival prediction in renal cell carcinoma with C-reactive protein

Background:

Validated objective biomarkers are needed for patients with renal cell carcinoma (RCC) to guide patient management and define high-risk populations for follow-up or for therapeutic purposes.

Methods:

Patients undergoing nephrectomy for RCC (n=286 all stages, 84% with conventional clear cell type) were included with a median duration follow-up of 5 years. The prognostic significance of pre-operative haematological and biochemical variables, including C-reactive protein (CRP) values were examined and whether they added additional information to a recently published pre-operative scoring system was determined.

Results:

C-reactive protein was the most significant predictor of overall survival (OS; χ²=50.9, P<0.001). Five-year OS for patients with CRP⩽15 mg l⁻¹ vs >15 mg l⁻¹ was 72% (95% CI 65–78%) and 33% (95% CI 23–44%), respectively. Similar results were seen for cancer-specific survival (CSS) and disease-free survival. On multivariate analysis, CRP remained highly significant for CSS (χ²=17.3, P<0.0001) and OS (χ²=9.8, P<0.002), in addition to other pre-operative variables including log of neutrophil/lymphocyte ratio, red blood cell count and white cell count. C-reactive protein was significant in addition to the pre-operative nomogram score (χ²=12.5, P=0.0004 for OS, χ²=16.2, P=0.0001 for CSS and χ²=8.6, P=0.003 for DFS) and was still significant when other pre-operative variables were included.

Conclusion:

C-reactive protein and other haematological and biochemical variables have independent prognostic significance in RCC and may enhance pre-operative scoring systems.     

Cabozantinib for the treatment of kidney cancer

Introduction: Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy.

Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator. Cabozantinib also showed activity in the front line setting in RCC within the CABOSUN trial. The study randomized untreated metastatic RCC patients to either cabozantinib or sunitinib and the former showed improved progression free survival which was the primary endpoint. The future holds promise for indications in other malignancies, given the preliminary efficacy and unique mechanism of action of cabozantinib.

In this review we address the mechanism of action, pharmacodynamics and pharmacokinetics of cabozantinib, and also review the development pathway of this agent in the treatment of advanced renal cell carcinoma. The potential benefit in specific patient populations, such as poor risk patients and bone metastases subgroups is also discussed.

Expert commentary: The clinical applications of cabozantinib will be addressed within the context of the current competitive therapeutic landscape of RCC.     

Nonoperable Recurrent Renal Cell Carcinoma: Management with Embolization and CT-Guided RF Ablation

We report the case of a 59-year-old male who underwent embolization and computed-tomography-guided radiofrequency ablation of a recurrent renal cell carcinoma that developed after radical nephrectomy in contiguity to the inferior vena cava. The alternative of a new operation was rejected because of the proximity of the tumor to the vessel and percutaneous approach seemed to be the better solution.     

Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma

Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs.In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities.We identified TP53 gene alterations in primary tumors, metastases and xenografts.Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived.Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC.Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC.