Treatment Of Renal Cell Cancer Research Articles

Using three-dimensional model-based tumour volume change to predict the symptom improvement in patients with renal cell cancer

In our recent study, we explored the efficacy of three-dimensional (3D) measurement of tumor volume in predicting the improvement of quality of life (QoL) in patients suffering from renal cell cancer (RCC), who were treated with axitinib and anti-PD-L1 antibodies. This study encompassed 18 RCC patients, including 10 men and 8 women, with an average age of 56.83 ± 9.94 years. By utilizing 3D Slicer software, we analyzed pre- and post-treatment CT scans to assess changes in tumor volume. Patients' QoL was evaluated through the FKSI–DRS questionnaire. Our findings revealed that 3D models for all patients were successfully created, and there was a moderate agreement between treatment response classifications based on RECIST 1.1 criteria and volumetric analysis (kappa = 0.556, p = 0.001). Notably, nine patients reported a clinically meaningful improvement in QoL following the treatment. Interestingly, the change in tumor volume as indicated by the 3D model showed a higher area under the curve in predicting QoL improvement compared to the change in diameter measured by CT, although this difference was not statistically significant (z = 0.593, p = 0.553). Furthermore, a multivariable analysis identified the change in tumor volume based on the 3D model as an independent predictor of QoL improvement (odds ratio = 1.073, 95% CI 1.002–1.149, p = 0.045).In conclusion, our study suggests that the change in tumor volume measured by a 3D model may be a more effective predictor of symptom improvement in RCC patients than traditional CT-based diameter measurements. This offers a novel approach for assessing treatment response and patient well-being, presenting a significant advancement in the field of RCC treatment.

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.

Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC.

TIGIT may Serve as a Potential Target for the Immunotherapy of Renal Cell Carcinoma.

This study aims to explore whether TIGIT is an effective target for the immunotherapy of renal cell cancer (RCC) with PD-1 as a positive control. The expression of TIGIT and PD-1 in RCC and peripheral blood mononuclear cells (PBMC) and the correlation between TIGIT and PD-1 are evaluated. The expression of TIGIT and PD-1 is inhibited, and then the proliferation, apoptosis, and migration are assessed. TIGIT expression is positively related to the expression of PDCD1, BTLA, ICOS, and FOXP3 (p<0.05). TIGIT expression in the PBMC, TIL, RCC, and adjacent normal tissues is higher than PD-1 expression. Blocking the TIGIT and PD-1 signaling pathways significantly inhibits the proliferation, migration, and invasion of RCC cells and promotes their apoptosis. These effects are more evident in TIGIT inhibitors than in PD-1 inhibitors. TIGIT inhibitor mainly regulates the expression of differential genes to achieve the reconstruction of immune killing and restore the killing effect on the RCC, and its mechanism by which TIGIT functions overlap that of PD-1 inhibitor. TIGIT may become a target for the immunotherapy of RCC, and there is a theoretical basis for the combination of TIGIT inhibitors and PD-1 inhibitors for the treatment of RCC.

Effect of adherent perinephric fat on outcomes of nephron-sparing treatment of renal cell cancer

Introduction. Nephrometric scales have been developed to determine the appropriate surgical tactics and to predict intraoperative values more accurately, considering the characteristics of the renal tumour. However, there is a need to assess the perinephric fat. The Mayo Adhesive Probability (MAP) scale aims to identify adherent perinephric fat (APF) or 'complex' paranephric fat preoperatively.Objective. To evaluate the effect of APF on intraoperative and functional outcomes of patients with renal cell cancer (RCC) who underwent laparoscopic partial nephrectomy.Materials &amp; methods. We analysed 118 patients with localised RCC who underwent laparoscopic partial nephrectomy. At the preoperative stage, according to the results of contract-enhanced msCT, the presence of APF was assessed using the MAP scale. At the same time, the thickness of the posterior perinephric fat was measured and the grade of its twisting was assessed. As a result, the patients were divided into two groups: group 1 MAP 0 – 2 pts (no APF) 34 patients and group 2 MAP 3 – 5 pts (presence of APF) 84 patients. In each group, the following indicators were assessed: stage according to the TNM classification, mean age and BMI, average nephrometry score according to the R.E.N.A.L. system, glomerular filtration rate (GFR).Results. The median surgery time for group 1 patients was 115.0 [92.5; 142.5] min, for group 2 — 130.0 [101.3; 180.0] min. The median warm ischemia time in patients in group 1 was 15 [0; 20] min, in group 2 — 12 [0; 18] min. The median blood loss in the groups 1 and 2 was 50 [15; 100] and 50 [0; 100] ml, respectively. The mean GFR on the first day after surgery was 63.34 ± 18.40 ml/min/1.73 m2 in group 1 and 55.09 ± 16.01 ml/min/1.73 m2 in group 2. Openings of the pyelocalyceal system were observed in 8 (23.53%) and 23 (27.38%) patients in groups 1 and 2, respectively. A positive surgical margin was detected one patient in group 1 and two in group 2. Early postoperative complications in group 1 were four patients and group 2 — 15 patients.Conclusion. The presence of APF and its severity can be effectively assessed using the MAP score, which is promising, but is limited only to the prognostic of APF without correlation with nephrometric scales that assess tumour anatomy parameters. However, the issue of developing a unified assessment system that includes APF and kidney morphometry is currently open, and the definition of APF is still subjective and requires an objective analysis to obtain more accurate outcomes.

Expert recommendation on image-guided irreversible electroporation ablation treatment for renal carcinoma (2023 edition)

Irreversible electroporation ablation therapy can destroy tumor cells while retaining the integrity of the important surrounding physiological structures. It is suitable for patients with renal cell carcinoma who cannot be surgically resected or who do not want surgical resection, and can ensure the best postoperative renal function to the greatest extent, and has advantages that other thermal ablation treatments do not have. However, since irreversible electroporation therapy has high requirements for electrode needles and parameter settings, improper operation will directly affect the prognosis of patients. In order to improve the level of comprehensive treatment of renal cell cancer and standardize the operation technique of irreversible electroporation for renal cell carcinoma, the Committee of interventional minimally invasive therapy of the Chinese Medical Education Association took the lead in formulating the Expert Recommendation on image-guided irreversible electroporation ablation for Renal Cancer (2022 edition). The article introduces in detail the indications, contraindications, perioperative preparation, basic principles of operation, complications and related management and follow-up of irreversible electroporation for renal cell carcinoma, in order to provide reference for clinical practice.

Access to treatment among patients with advanced kidney cancer in Mexico.

130 Background: The socioeconomic status of patients diagnosed with metastatic renal cell carcinoma (mRCC) in developing countries could in many cases limit their access to the best available therapeutic options. We aimed to describe the clinical characteristics and access to treatment of Mexican patients with mRCC. Methods: We performed a retrospective analysis of all patients with a histopathologically confirmed diagnosis of renal cell carcinoma who were treated at an oncology referral center in Northeast Mexico over a 5-year period. Results: We included 233 patients in the analysis, of whom 63% were men. The mean age at diagnosis was 58.2 years; 87% of the tumors were histopathologically classified as clear cell carcinoma. Regarding laterality, 54% of the tumors originated from the right kidney. The distribution of cases by clinical stage (CS) was as follows: CS I 15%, CS II 8%, CS III 17%, CS IV 60%. All of the included patients had government health insurance coverage; however, specific treatment for renal cell cancer was not included in this coverage. In terms of access to first-line systemic management in the 139 patients with advanced kidney cancer who were candidates for treatment, 29% received treatment with a single-drug tyrosine kinase inhibitor (TKI), 4% were treated with combined or single-drug immunotherapy (IO), and 12% were treated with TKI combined with IO. All but one patient who was treated with a single drug or a combination of IO received these drugs in the context of a clinical trial. Fifty-five percent of patients with advanced disease did not have access to standard first-line therapy. The rate of loss to medical follow-up was 69% of cases. Conclusions: Despite the proven oncological benefit of the latest generation of therapies based on IO/IO or IO/TKI for mRCC, access to first-line standard management is still poor in our country, even with single agent TKI. Public health programs should be implemented to expand therapeutic options for this group of patients.

Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS).

Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20–50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10−8–7.5 × 10−3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.

Non-Wilms' renal tumors in children: experience with 139 cases treated at a single center

BackgroundPediatric non-Wilms renal tumors (NWRTs), which comprise a small proportion of renal tumors, are a heterogeneous group of neoplasms with variable malignant potential, mortality, and response to treatment. We performed this study to determine the clinical characteristics, management and prognosis of children with Pediatric NWRTs.MethodsMedical records of all patients (n = 139) treated for NWRTs over a 12-year period (2008.01–2019.10) at a single center were reviewed retrospectively.ResultsThe histopathological groups of NWRTs included malignant rhabdoid tumor of the kidney (MRTK) (n: 30, 21.6%), renal cell cancer (RCC) (n: 26,18.7%), clear cell sarcoma of the kidney (CCSK) (n: 24,17.3%), congenital mesoblastic nephroma (CMN) (n: 21,15.1%), cystic nephroma (CN) (n: 16,11.5%), metanephric tumors (n: 12, 8.6%), renal angiomyoliporma (RAML) (n: 3, 2.2%), renal primitive neuroectodermal tumor (n: 2, 1.4%), renal hemangioma (n: 2, 1.4%), inflammatory myofibroblastic tumor (n: 2, 1.4%), ossifying renal tumor of infancy (ORTI) (n: 1, 0.7%). The distribution of all malignant NWRTs, including MRTK, CCSK, RCC and PNET, according to stage was as follows: stages I (n = 26), II (n = 16), III (n = 29), and IV (n = 11). The summary table shows the treatment offered to children with NWRTs. A total of 123 children were followed up for an average of 42 months. Sixteen children were lost to follow-up. Tumor-free survival was observed in 94 children. One patient who suffered from RCC is currently receiving targeted therapy and survives with the tumor. Twenty-eight children (22.8%) died.ConclusionsPediatric NWRTs comprise 19.1% of all renal tumors in our single center. Most NWRTs can readily be distinguished using a range of immunohistochemical markers. Molecular genetic profiling has allowed much progress in the understanding of this group of tumors, making diagnosis and classification less difficult. The mainstay treatment of malignant NWRTs, including MRTK, CCSK, RCC and PNET, is comprehensive treatment. The mainstay treatment of benign NWRTs, including RAML, CN, ORTI, CMN, metanephric tumors, and renal hemangioma, is surgical resection alone and when the tumor diameter is smaller than 7 cm and the tumor locates in one pole, NSS can be performed.

An Evaluation of Cabozantinib for the Treatment of Renal Cell Carcinoma: Focus on Patient Selection and Perspectives.

Cabozantinib is an oral tyrosine kinase inhibitor (TKI) with activity against several receptors involved in the angiogenesis pathway, including vascular endothelial growth factor receptor (VEGFR), c-MET and AXL. The antiangiogenic properties of cabozantinib led to its use as a monotherapy for the treatment of metastatic renal cell cancer (RCC), and quickly resulted in this treatment becoming part of the standard of care for these tumors. Since the advent of immune checkpoint inhibitors (ICIs), new standards of care have emerged in first-line settings, involving dual ICI or ICI–VEGF-TKI (including ICI–cabozantinib) combination treatments, and leading to a more complex algorithm of care. Cabozantinib remains an option in second-line settings and is still a first-line standard of care treatment in cases where the use of ICIs is contraindicated. This review focuses on the selection of patients who may benefit most from cabozantinib therapy, including those with bone and brain metastases and those with a non-clear cell RCC histology. The need to consider disease-related symptoms, comorbidities, age, drug interactions and biomarker analyses in the choice of therapeutic strategy is also highlighted. Finally, the perspectives for the use of cabozantinib in RCC treatment are discussed.

Long-term oncological results of surgical treatment of localized renal tumors

Objective: to analyze the long-term oncological results of surgical treatment of patients with stage cT1-сТ2аN0M0 renal cell cancer.Materials and methods. The analysis included 326 patients who underwent partial nephrectomy (PN) in 210 (64.42 %) and radical nephrectomy (RN) - in 116 (35.58 %). Stage cT1a tumors were found in 129 (39.57 %), cT1b - in 149 (45.71 %), cT2a - in 48 (14.72 %) cases. PN and RN for cT1a was performed in 113 (53.81 %) and 16 (13.79 %), for cT1b -in 86 (40.95 %) and 63 (54.31 %), for cT2a - in 11 (5.24 %) and 37 (31.90 %) patients. We used open approach in 5 (1.53 %), laparoscopic in 148 (45.26 %) and robotic in 173 (53.21 %). The median follow-up was 49.9 [26.0; 81.4] months.Results. In the group of patients with stage cT1a disease, 4 recurrences of the tumor process were revealed (3 local recurrences after PN and 1 after RN). Seven deaths were recorded (4 after PR and 3 after RN). Two deaths occurred due to the progression of kidney cancer (1 after PN and 1 after RN). 5-year disease-free survival after PN and RN was 95.93 ± 2.32 % versus 92.31 ± 7.39 % (p &gt;0.05); 5-year overall survival - 96.48 ± 2.08 % versus 85.56 ± 9.65 % (p &gt;0.05); 5-year cancer-specific survival - 98.33 ± 1.65 % versus 92.25 ± 6.5 % (p &gt;0.05).In the group of patients with stage cT1b disease, 12 recurrences were revealed (5 after PN and 7 after RN). 14 deaths were recorded (4 after PN and 10 after RN). Four deaths were related to the development of kidney cancer (all after RN). 5-year disease-free survival after PN and RN was 92.97 ± 3.1 % versus 86.99 ± 4.64 % (p &gt;0.05); 5-year overall survival -95.1 ± 2.78 % versus 88.63 ± 4.4 % (p &gt;0.05); 5-year cancer-specific survival - 100 % versus 94.1 ± 3.33 % (p &gt;0,05).There were no recurrences of the oncological process or deaths after PN in the group of patients with the stage of cT2a disease during four years of follow-up. After RN six recurrences of the oncological process, four deaths (3 of them due to the progression of kidney cancer) were recorded. Thus, the disease-free survival at was 80.57 ± 7.15 %; overall survival - 90.28 ± 5.34 %; cancer-specific survival - 93.63 ± 4.37 %.Conclusion. PN is the priority treatment for renal cell cancer. Oncological results of nephron-sparing surgery are superior to the results of RN, however, these differences are not reliable and require a longer study.

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma.

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.

Abstract 1363: Exposure-toxicity analysis of cabozantinib in patients with salivary gland cancer and renal cell cancer

Abstract Background Cabozantinib is approved for treatment of renal cell cancer (RCC) in a starting dose of 60 mg. However, in the registration studies dose reductions were needed in 46-62% of patients due to toxicity. Improved clinical efficacy of cabozantinib was observed in RCC patients with an average exposure of &amp;gt; 750 ug/L. Data about cabozantinib pharmacokinetics in patients routinely treated with this drug is scarce, while treatment is challenging due to toxicity. Therefore, we explored the cabozantinib exposure in patients with two different tumour types in our clinic. Methods Clinical data and cabozantinib trough concentrations (Cmin) were collected from all patients treated with cabozantinib with at least one measured Cmin at steady state in our clinic between Jan 2018 - Aug 2020. We included salivary gland cancer (SGC) patients treated in a phase II study and RCC patients from our outpatient clinic. Geometric mean (GM) Cmin at the start dose, at 40 mg and at best tolerated dose (BTD) were compared between the two tumour types. Results In total 47 patients were included. All patients with SGC (n=22) started with 60 mg, while 13 of 25 patients with RCC started with 40 mg. GM Cmin level at the start dose was 1350 µg/L (95% CI 1182-1781) vs. 689 µg/L (95% CI 576-823) (P&amp;lt;.001) for patients with SGC and RCC, respectively. When dose-normalized to 40 mg, SGC patients had a significantly higher cabozantinib exposure compared to RCC patients (GM Cmin 968 µg/L (95% CI 788-1188) vs. 676 µg/L (95% CI 571-799)(P=.007). A higher cabozantinib GM Cmin level was observed in female compared to male patients. Dose reductions due to toxicity were needed in 91% and 60% of patients with SGC and RCC, respectively. Median BTD was 25 mg for SGC patients and 40 mg for RCC patients. GM Cmin at BTD were comparable between the SGC group and the RCC group, i.e. 692 µg/L (95% CI 582-822) vs. 576 µg/L (95% CI 493-673) (P=.1), respectively. At BTD, 64% of SGC patients and 80% of RCC patients had an exposure below the proposed target of &amp;gt;750 ug/L. Conclusion Unexpectedly, cabozantinib levels were significantly higher in patients with SGC compared to those with RCC at the dose of 40 mg. However, cabozantinib levels at BTD were comparable between patients with SGC and RCC. At BTD, the majority of patients did not reach the target of &amp;gt;750 µg/L. For most patients with RCC, the cabozantinib level at BTD corresponded to a dose of 40 mg. Therefore, 40 mg instead of 60 mg as a starting dose followed by dose-adjustment based on exposure and tolerability may be preferred in patients with RCC. Although cabozantinib is not registered for SGC, an even lower starting dose of 20 mg/day may be required in these patients based on cabozantinib levels at BTD. Future studies should focus on identifying an optimal and tolerable exposure-response target value for cabozantinib and elucidate factors that contribute to the differences in exposure, in order to individualise and improve treatment. Citation Format: Stefanie D. Krens, Wim van Boxtel, Maike J. Uijen, Frank G. Jansman, Ingrid M. Desar, Sasja F. Mulder, Carla M. van Herpen, Nielka P. van Erp. Exposure-toxicity analysis of cabozantinib in patients with salivary gland cancer and renal cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1363.

Predicting changes in glomerular filtration rate in patients with kidney cancer using a mathematical model.

Chronic renal failure is one of the most challenging complications after the completed surgical treatment for renal cell cancer. In 2016, a grading system of tumorous renal involvement was developed, referred to as NCIU nephrometry. However, the systematic parameter to reflect the functional status of the functional renal parenchyma is defined by tumor volume only, with no regard for spatial disposition of the segment(s) where the tumor is located. Our research team decided to improve the NCIU nephrometry system by developing and testing a modified formula for calculation of creatinine clearance, which makes allowance for spatial disposition of tumor within the kidney. We performed numerical computations and analysis of changes in functional status of renal parenchyma depending on coordinate-based spatial location of the tumor in order to augment the existing NCIU nephrometry scale; Matlab, a specialized software package was used as a principal instrument to calculate the number of nephrons and functional renal parenchyma depending on the coordinate-based position of the mass center of the tumor and tumor volume. This model was shown to create a feasible opportunity to increase the percentage of organ-sparing procedures for renal cell cancer and to reduce the incidence/progression of chronic renal failure in these patients.

Magnetic-core-based silibinin nanopolymeric carriers for the treatment of renal cell cancer

AimsSilibinin offers potential anticancer effect with less aqueous solubility and high permeability. The present study aimed to develop biocompatible magnetic-core-based nanopolymeric carriers of poly (D, l-lactide-co-glycolic) acid (PLGA) encapsulated silibinin for the sustained release action on renal cancerous cell. Main methodsThe synthesized iron oxide nanoparticles were prepared by precipitation method via encapsulation of silibinin in PLGA network using double emulsion method. The nanoparticle formulations were characterized for morphological, physicochemical properties (HRTEM, FTIR, Raman Spectroscopy and VSM), in vitro drug release and cytotoxicity study on kidney cancer cells (A-498). The safety of magnetic-core-based silibinin nanopolymeric carriers was conducted by i.v. administration at a dose of 50 mg/kg in mice. Key findingsThe mean particle size, zeta potential and % encapsulation efficiency of magnetic-core-based silibinin nanopolymeric carriers were found to be 285.9 ± 0.28 nm, −14.71 ± 0.15 mV and 84.76 ± 1.29%, respectively. The saturation magnetization of magnetic core and optimized nanoparticles were reported as 36.35 emu/g and 12.78 emu/g, respectively. HRTEM analyses revealed the spherical shapes of the particles with uniform size distribution. The in vitro release profile of silibinin from the nanoparticles exhibited a sustained delivery for 15 days and displayed better cytotoxicity against human kidney cancer cells (A-498) than silibinin. In vivo study showed the safety of magnetic-core-based silibinin nanopolymeric carriers in mice. SignificanceThe magnetic-core-based silibinin nanopolymeric carriers will act as a potential carrier for targeted transportation of actives in cancer therapy.

From oxygen sensing to angiogenesis: Targeting the hypoxia signaling pathway in metastatic kidney cancer.

This article summarizes examples of current and emerging therapies that target the hypoxia and angiogenesis signaling pathways in the clear cell type of renal cell cancer (RCC), with an emphasis on the hypoxia signaling pathway. Mammalian cells transduce signals of decreased oxygen to hypoxia inducible factor (HIF), an intracellular heterodimer that mediates the adaptation of normal and tumor cells to oxygen deprivation. HIF is frequently overexpressed in cancer cells and is involved in the transcriptional activation of many genes essential for cell invasion, migration, survival, and angiogenesis (including vascular endothelial growth factor [VEGF]). Moreover, HIF confers resistance to cytotoxic chemotherapy and radiation therapy and is associated with poor prognosis in patients with cancer. Blocking the activity of HIF inhibits the expression of VEGF and oncogenic pathways, resulting in the inhibition of tumor growth. Interestingly, activation of oncogenes and/or inactivation of tumor suppressor genes (eg, the gene encoding von Hippel-Lindau [VHL] tumor suppressor protein) can activate tumorigenesis even with normal levels of oxygen, providing support for the notion that the HIF-VHL-VEGF axis is amenable to targeted therapies for the treatment of RCC. This article highlights the current understanding of the hypoxia signaling pathway and its relevance to RCC development. Pharmacologic agents targeting the hypoxia and angiogenesis signaling pathways are discussed. Development of novel therapeutic agents that target the hypoxia and angiogenesis signaling pathways holds promise in the management of metastatic clear cell RCC.

Renal Cancer with Tumor Thrombus of the Inferior Vena Cava and the Right Atrium

ntroduction. A distinctive feature of kidney cancer is a frequent, compared with other tumors, spread of the tumor through the venous collectors (in the renal and inferior vena cava up to the right atrium), along the path of least resistance to invasive growth.The aim of the study was to present a clinical case of radical treatment of kidney cancer involving extensive IVC thrombosis.Materials and methods. The study describes a clinical case of radical treatment of patient M. with kidney cancer involving extensive IVC thrombosis, extending to the right atrium (written informed consent for patient information and images to be published was obtained prior to the study). During preoperative examination, the patient was diagnosed with renal cell carcinoma with non-occlusive hypervascular tumor thrombus of the renal vein, the inferior vena cava and the right atrium based on the findings of ultrasound examination (transabdominal and transthoracic, and transesophageal), multislice computed tomography (MSCT) and magnetic resonance imaging (MRI).Results and discussion. Surgical treatment remains the main method of treatment of renal cell cancer, moreover, the inferior vena cava thrombosis cannot serve as a cause for refusing surgical treatment. The thrombus spreading along the venous collectors is an important factor in determining the tactics of surgical treatment. The length of the tumor thrombus, as well as the degree of its fixation and ingrowth into the vein wall is of great significance for planning surgical techniques and predicting clinical outcomes. Based on various methods of radiological examination, patient M. was diagnosed with cancer of the right kidney, 3 stage T3cNxM0, IVC tumor thrombus, paraneoplastic syndrome (hyperthermia), right-sided nephrectomy with aortocaval lymphadenectomy, thrombectomy from the IVC, vascular isolation of the liver, resection of the IVC, thrombectomy from the right atrium combined with cardiopulmonary bypass.Conclusion. Despite the technical complexity of nephrectomy with thrombectomy from the IVC, especially in the presence of a massive supradiaphragmatic thrombus, these interventions have no alternatives if a radical treatment is to be achieved. Step-by-step support using radiological methods of investigation is an important aspect of patients preparation; this allowing determining the exact volume of the damage and non-invasively assessing clinical outcomes of surgical treatment.

SC218 - Angiovac device in the treatment of renal cell cancer with cavo-athrial neoplastic thrombus

SC218 - Angiovac device in the treatment of renal cell cancer with cavo-athrial neoplastic thrombus

Surgical treatment of patients with renal cell cancer complicated by specific (tumor) and non-specific thrombosis of the inferior Vena cava

Among malignant neoplasms, kidney cancer occupies one of the first places in terms of the growth rate of incidence in Russia. Despite the possibilities of modern diagnostic research methods, the number of patients with common forms of the disease does not decrease. In 5–10% of cases, renal cell carcinoma is complicated by the formation of a tumor clot in the inferior Vena cava (VCI), which requires volume surgery — nephrectomy with thrombectomy, which is the only effective treatment option for this group of patients. Previously, the results of treatment of locally advanced kidney cancer were unsatisfactory due to the high incidence of complications and mortality after extended surgical interventions. However, improving the operation technique requires a re-evaluation of previous representations. Performing a nephrectomy with a VCI thrombectomy is not an easy task and is often associated not only with technical difficulties due to the need for mobilization, control and resection of the inferior Vena cava, but also with the risk of intra — and postoperative complications. The most difficult task is the choice of surgical tactics for descending non-tumor hemorrhagic thrombosis. As a result of long-term tumor obstruction, organized blood clots that are soldered to the intima of the vessel often spread to the common iliac veins and, as a rule, are technically impossible to remove. If the VCI is preserved, a residual hemorrhagic blood clot in the area of its confluence is a potential source of pulmonary embolism (PE), for the prevention of which mechanical plication is used. This maneuver does not lead to the development of clinically significant chronic venous insufficiency of the lower extremities (CVI NC), postoperative VCI or PE thrombosis. Despite the technical complexity of the operation and the difficult course of the postoperative period, surgical treatment of renal cell cancer complicated by tumor thrombosis is certainly justified. This article presents a clinical case of surgical treatment of a patient with renal cell cancer complicated by massive specific (tumor) and non-specific thrombosis in the presence of reduced parenchymalexcretory function of the contralateral kidney and severe cardiac pathology. Goal: to share experience and demonstrate the results of successful surgical treatment of renal cell carcinoma.

Epigenetic Approaches to the Treatment of Renal Cell Cancer

Epigenetic Approaches to the Treatment of Renal Cell Cancer

Abstract A02: Detection of circulating cell-free DNA in renal cancer using renal cancer-specific DNA mutations and methylation changes

Abstract Renal cell cancer (RCC) is the most deadly of urologic malignancies. It is a very invasive and chemoresistant disease that is often treated by surgical resection as it also responds poorly to radiotherapy. Importantly, more than 30% of RCCs recur or metastasize following treatment and in the cases believed to be curable by nephrectomy, distant metastasis can develop even 10 years post-surgery. There is therefore a significant focus on tissue-based biomarkers from the primary kidney tumors to help predict which patients are likely to recur, though there are no biomarkers used in routine clinical practice. Over recent years, much research has aimed at the utilization of blood-based biomarkers, mainly circulating cell-free DNA (cfDNA), as a method of noninvasive disease diagnosis and monitoring. cfDNA is detected through the identification of tumor-specific cfDNA mutations, although cfDNA methylation may be a more specific biomarker as many CpG sites can be tested in parallel. We have collected tumor tissue and pre- and post-surgery blood samples from renal cancer patients and generated exome sequencing and EPIC array data of 20 tumors with matched blood samples to detect tumor-specific DNA mutations and methylation patterns. We have identified well-known driver mutations in renal cancer in VHL in 11 tumors at 0.12-0.51 variant allele fraction (VAF); PBRM1 in 8 tumors at 0.12-0.45 VAF; BAP-1 in 2 tumors at 0.45 and 0.3 VAF; and SETD2 at 0.39 VAF; KDM5C at 0.27 VAF, and CTNNA2 at 0.2 VAF in one out of 20 patients. We aim to validate these changes using droplet digital PCR (ddPCR) in tumor and circulating tumor DNA (ctDNA) pre- and post-surgery. We next plan to combine the result of the exome sequencing with EPIC array data as well in house-developed cfDNA profiles based on publicly available tissue and individual cell type DNA methylation data. This approach will allow us to select the best mutation and methylation diagnostic and prognostic markers to aid the monitoring of early disease and relapse as well as the treatment of renal cell cancer. Citation Format: Martyna J. Adamowicz, John Thomson, Sophie J. Warlow, Utsa Patra, Helen Thain, Sophie Marion de Proce, Alexander Laird, Timothy J. Aitman. Detection of circulating cell-free DNA in renal cancer using renal cancer-specific DNA mutations and methylation changes [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A02.