Treatment Of Renal Cell Carcinoma Research Articles

Differential immunohistochemical expression of Galectin-1 and Galectin-3 in renal cell carcinoma

Background Renal cell carcinoma (RCC) is a heterogeneous cancer with many histological and molecular subtypes. Many new potential diagnostic, prognostic, and predictive biomarkers are still emerging. RCC treatment approaches are plentiful, including surgical resection, ablation, and active surveillance as well as immunotherapy. However, many cases are nonresponsive to such modalities and others experience recurrence or metastatic disease. Accordingly, the research work nowadays is concerned with looking for new targeted therapy biomarkers to treat RCC. Galectin-1 and Galectin-3 are the proposed biomarkers for this issue. Aim and methods This work aims to review the expression of Galectin-1 and Galectin-3 immune markers among the main histological subtypes of RCC and their correlation with clinicopathological parameters. To carry out this work, 60 cases of RCC were included in this study: 36 clear RCC, 16 papillary RCC I and II, and eight cases chromophobe RCC. Results Galectin-1 was highly expressed in 42 out of 60 cases, while Galectin-3 was highly expressed in only 13 cases. There was a statistically significant association between Galectin-1 and Galectin-3 expression and the histological subtype being expressed more in chromophobe subtype rather than others. There was a statistically significant inverse association between Galectin-1 expression and lymphovascular invasion as well as Galectin-3 expression and tumor necrosis and hemorrhage. There was no statistically significant association between Galectin-1 and 3 and the remaining clinicopathological parameters. Conclusion Galectin-1 and Galectin-3 could be used as potential diagnostic markers for chromophobe RCC as they are highly expressed in this subtype in comparison to others and can be used as targeted biomarkers for RCC therapy in the future. Galectin-3 has an anti-necrotic role and this could lead to chemotherapy resistance.

A future directions of renal cell carcinoma treatment: combination of immune checkpoint inhibition and carbon ion radiotherapy.

Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC.

Emerging Antibody-Drug Conjugate Therapies and Targets for Metastatic Renal Cell Carcinoma

Background: Approximately 30% of renal cell carcinoma (RCC) cases present with de novo metastatic disease, while 20% to 30% of those with localized disease will develop metastases following surgical resection. Various drug classes have been investigated to treat RCC, including cytokine-based therapies, small molecule Vascular Endothelial Growth Factor (VEGF) tyrosine kinase inhibitors (TKIs) and antibody-based therapies. Up to 58% of patients fail to respond to primary immune checkpoint inhibitor (ICI) therapy, and nearly all initial responders experience disease progression due to the development of secondary resistance. Consequently, novel treatment options are being investigated. Objective: Review the rapidly evolving ADC therapeutic landscape in metastatic RCC including recent trials, emerging ADCs targets, and future directions for ADCs in the treatment of advanced RCC. Methods: Literature review using the MEDLINE database on important trials and presentations from the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) conferences. Key words used included “renal cell carcinoma,” “RCC,” “metastatic RCC,” “advanced RCC,” “antibody-based therapies,” “immunotherapy,” “clinical trials,” and “emerging drugs.” Specifically for review of ADCs in RCC, the following search string was used with additional review of bibliographies from retrieved papers: “((antibody drug conjugate) OR (antibody-dependent cellular cytotoxicity) OR (chimeric antigen receptor)) AND ((kidney cancer) OR (renal cell carcinoma))”. Results: Several promising targets including MMP14, EGFR, MCT4, CA9, MET, CDH13, B7-H3, and PSMA were identified with relevant preclinical and clinical studies reviewed. Conclusions: While ADCs therapeutics have not shown benefit to date for renal cell carcinoma, there are ample promising candidates and targets for future research.

A novel two-stage approach to the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome.

To present the early results of a new technique for the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome. The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse-string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. Three of five patients presented with clinical Budd-Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. While we continue to compile longer-term data for a larger follow-up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery.

Cancer Immunotherapy with Lipid Nanoparticles Loaded with a Stimulator of Interferon Genes Agonist against Renal Tumor Lung Metastasis.

Metastatic renal cell carcinoma (RCC) has a poor prognosis, and the major organ of metastasis is the lung. Immunotherapy with immune checkpoint inhibitors (ICIs) is the first-line therapy, but the response rates are low. Thus, the development of a more effective immunotherapy against metastatic RCC would be highly desirable. We previously demonstrated how a stimulator of an interferon gene (STING) agonist-loaded lipid nanoparticles (STING-LNPs) significantly activates natural killer (NK) cells and induces an antitumor effect against cases of melanoma lung metastasis that have shown ICI resistance. In this study, we evaluated the potential of using STING-LNPs in the treatment of lung metastatic RCC (Renca). An intravenous injection of STING-LNPs drastically decreased the amount of Renca tumor colonies. In contrast, monotherapies using ICIs showed no antitumor effect, and even a combination of ICI and STING-LNP therapies failed to enhance the antitumor effects. The main effector cells would be NK cells, and the activation of NK cells by the STING-LNPs may avoid the increased expression of immune checkpoint molecules. These findings provide useful insights into the development of an effective immunotherapy against metastatic RCC.

Nephrotoxicity Associated with Contemporary Renal Cell Carcinoma Regimens: A Systematic Review and Meta-Analysis

Background: The nephrotoxicity profile of contemporary first-line regimens for treatment of metastatic renal cell carcinoma (mRCC) has not been systematically studied in published clinical trials. Objective: To assess the rates of nephrotoxic events of contemporary first-line regimens for treatment of mRCC in comparison to vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) mono-therapy. Methods: We performed a systematic search of the literature looking for randomized clinical trials that contemplated National Comprehensive Cancer Network (NCCN) recommended first-line regimens for treating mRCC in which the control arm was a VEGF-TKI. Selected trials could either include an experimental arm of immune checkpoint inhibitor (ICI) plus VEGF-TKI combination or ICI-ICI combination. Nephrotoxic events were defined as proteinuria, hypertension, blood creatinine increase, acute kidney failure or nephritis, which were all described separately. Results: Five studies satisfied our inclusion criteria. Combination of ICI with VEGF-TKI showed a statistically significant higher degree of proteinuria compared to VEGF-TKI alone. There was no statistically significant difference in rates of hypertension between ICI-TKI and VEGF-TKI alone, but VEGF-TKI alone was statistically significantly more associated with hypertension than immunotherapy alone. Other renal toxicities, such as an increase in creatinine, acute kidney injury (AKI) and nephritis, were uncommon and not consistently reported in each trial. Conclusions: Contemporary regimens for first-line treatment of mRCC are associated with a higher grade of proteinuria than VEGF-TKI alone, while VEGF-TKI is more associated with hypertension than an ICI-ICI combination. Description of many renal toxicities across the studies reported have been diverse and a standardized definition across clinical trials would be helpful to reliably interpret the data regarding nephrotoxicity in the setting of treatment of renal cell carcinoma.

Current status and future perspective of immunotherapy for renal cell carcinoma.

In the last decade, the standard treatment for advanced renal cell carcinoma (RCC) has evolved, mainly driven by the development and approval of immune checkpoint inhibitors (ICIs). Currently, ICI monotherapy and ICI-based combinations with tyrosine kinase inhibitors and targeted therapies against mammalian target of rapamycin or vascular endothelial growth factor have become new standard treatments for first-line and subsequent-line therapies. ICIs play an important role as an adjuvant postoperative therapy, and this field is the subject of active research. Furthermore, ongoing randomized controlled trials are investigating the clinical value of more intense treatments by combining multiple effective treatments for RCC. Additionally, novel biomarkers for prognosis have been investigated. This study reviews the current evidence on immunotherapy as a treatment for RCC patients, randomized controlled trials, and ongoing studies including RCC patients and recent findings, and discusses future perspectives.

Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab

Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.

The Diagnosis and Treatment Approach for Oligo-Recurrent and Oligo-Progressive Renal Cell Carcinoma.

One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed "oligo-recurrent" disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as "oligo-progression", can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials.

Effect of FRAIL Nursing on Rehabilitation Quality and Nutritional Status in Elderly Patients with Renal Cell Carcinoma

Renal cell carcinoma is a common malignancy of the urinary system. Surgery can save renal cell carcinoma patients’ lives, but concerns associated with their quality of life are a major clinical concern. Herein, we have analyzed the value of fatigue, resistance, aerobic, illness, and lost nursing, commonly known as FRAIL nursing, on the improvement in rehabilitation quality and nutritional status of renal cell carcinoma patients. The results show that compared with renal cell carcinoma patients in the control group receiving routine care, patients who received fatigue, resistance, aerobic, illness, and lost nursing had significantly shortened postoperative rehabilitation time, reduced incidence of postoperative complications, and enhanced nursing compliance and quality of life. Also, the nutritional status and immune function of renal cell carcinoma patients were significantly improved after fatigue, resistance, aerobic, illness, and lost nursing, demonstrating its high application value in clinical treatment of renal cell carcinoma.

Convolutional Neural Network Model for Segmentation and Classification of Clear Cell Renal Cell Carcinoma Based on Multiphase CT Images.

(1) Background: Computed tomography (CT) imaging challenges in diagnosing renal cell carcinoma (RCC) include distinguishing malignant from benign tissues and determining the likely subtype. The goal is to show the algorithm's ability to improve renal cell carcinoma identification and treatment, improving patient outcomes. (2) Methods: This study uses the European Deep-Health toolkit's Convolutional Neural Network with ECVL, (European Computer Vision Library), and EDDL, (European Distributed Deep Learning Library). Image segmentation utilized U-net architecture and classification with resnet101. The model's clinical efficiency was assessed utilizing kidney, tumor, Dice score, and renal cell carcinoma categorization quality. (3) Results: The raw dataset contains 457 healthy right kidneys, 456 healthy left kidneys, 76 pathological right kidneys, and 84 pathological left kidneys. Preparing raw data for analysis was crucial to algorithm implementation. Kidney segmentation performance was 0.84, and tumor segmentation mean Dice score was 0.675 for the suggested model. Renal cell carcinoma classification was 0.885 accurate. (4) Conclusion and key findings: The present study focused on analyzing data from both healthy patients and diseased renal patients, with a particular emphasis on data processing. The method achieved a kidney segmentation accuracy of 0.84 and mean Dice scores of 0.675 for tumor segmentation. The system performed well in classifying renal cell carcinoma, achieving an accuracy of 0.885, results which indicates that the technique has the potential to improve the diagnosis of kidney pathology.

Results of stereotactic radiation therapy in treatment of patients with T1N0M0 kidney cancer

Background. Currently, the main treatment for T1N0M0 kidney cancer is surgery, mainly in the amount of kidney resection. However, not all patients can be operated on, and most often due to the severity of comorbidity, some patients refuse surgery. In such cases, it becomes necessary to search for an acceptable operation of an alternative method of treatment. Such requirements can be met by stereotactic radiotherapy (SBRT), being a non-invasive method of treating renal cell carcinoma.Purpose. To determine overall survival (OS), local control, and renal toxicity after treatment of T1N0M0 renal cell carcinoma (RCC) with stereotactic radiotherapy.Material and methods. Since 2011 to 2022 in the Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine, 50 patients with verified RCC underwent SBRT up to 30–45 Grey in three fractions using the CyberKnife. The mean age of the patients was 69.8 years. Primary tumor was diagnosed in 44 cases, recurrence after previous surgical treatment in 6 cases, including one patient with recurrence of cancer of both kidneys. The average tumor volume was 29.1 cm3 .Results. Median overall survival was not reached as most patients were alive at the time of the study. Indicators of 1-, 3- and 5-year OS are 94.8%, 87.3% and 75.1%, respectively. In 74.5% of cases, according to the RECIST 1.1 criteria, stabilization of the process was recorded 6 months after STLT, in 21.6% of cases – a partial response, in 3.9% – progression of the process. One-year local control – 98%. Renal toxicity occurred in 26% of patients 6 months after radiation therapy, but within a year, kidney function was restored in these patients.Conclusions. Stereotactic radiation therapy T1N0M0 of kidney cancer in SOD = 30–45 Grey allows to stabilize the tumor process with sufficiently high results of overall survival and local control with low renal toxicity, respectively, can be used in the treatment of inoperable patients with localized renal cell carcinoma.

Theranostic Lipid Nanoparticles for Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is a common urological malignancy and represents a leading threat to healthcare. Recent years have seen a series of progresses in the early diagnosis and management of RCC. Theranostic lipid nanoparticles (LNPs) are increasingly becoming one of the focuses in this field, because of their suitability for tumor targeting and multimodal therapy. LNPs can be precisely fabricated with desirable chemical compositions and biomedical properties, which closely match the physiological characteristics and clinical needs of RCC. Herein, a comprehensive review of theranostic LNPs is presented, emphasizing the generic tool nature of LNPs in developing advanced micro-nano biomaterials. It begins with a brief overview of the compositions and formation mechanism of LNPs, followed with an introduction to kidney-targeting approaches, such as passive, active, and stimulus responsive targeting. With examples provided, a series of modification strategies for enhancing the tumor targeting and functionality of LNPs are discussed. Thereafter, research advances on applications of these LNPs for RCC including bioimaging, liquid biopsy, drug delivery, physical therapy, and gene therapy are summarized and discussed from an interdisciplinary perspective. The final part highlights the milestone achievements of translation medicine, current challenges as well as future development directions of LNPs for the diagnosis and treatment of RCC.

LONG TERM OUTCOME OF LAPAROSCOPIC RADICAL NEPHRECTOMY FOR PATHOLOGICAL T1, T2 RENAL CELL CANCER AT VIET DUC HOSPITAL

Background: To evaluation of the long term outcome of laparoscopic radical nephrectomy for pathological T1, T2 renal cell cancer at Viet Duc Hospital. Methods: We retrospectively identified 73 patients who underwent RN between 2015 and 2022. We divided patients into three groups based on tumour size: <4 cm, 4– 7 cm, >7 cm. Clinical and paraclinical characteristics include age, gender, back pain, tumor size, tumor location, disease stage on computed tomography scans, histopathological results, postoperative outcomes and complications, postoperative survival time, and accumulated survival time. Results: the average age was 53.52 ± 12.17 years. CT scans classified renal cell carcinoma stages preoperatively according to IUAC 2009: 53.4% were stage T1a, 42.4% were stage T1b, 2.8% were stage T2a, and 1.4% were stage T2b, 2 patients experienced infection at the trocar site used for kidney extraction, 4 patients developed postoperative fever, and 1 patient had postoperative bleeding requiring a blood transfusion. One patient underwent emergency open surgery immediately after discharge due to bleeding through the drainage. The postoperative complication rate according to the Clavien-Dindo classification was 11% (8 patients). The results show that 63 patients are still alive, 5 patients have passed away due to the disease, and 5 patients have died from other causes such as traffic accidents, cardiovascular diseases, and cerebral vascular accidents. The average follow-up time is 46.7±26.5 months. The cumulative survival rates at 3, 4, 5, 6, and 7 years after radical nephrectomy for the treatment of renal cell carcinoma were 100%, 97.6%, 94.8%, 90.9%, and 83.3%, respectively. The average additional survival time after surgery was 84.11 ± 1.80 months. Conclusions: Laparoscopic radical nephrectomy for early-stage renal cell carcinoma (T1 and T2) demonstrates high surgical safety and absolute efficacy in oncology.

Abstract B024: KO-2806, a next-generation farnesyltransferase inhibitor, potentiates the antitumor activity of cabozantinib in clear cell renal cell carcinoma models

Abstract Conventional treatments for advanced clear cell renal cell carcinoma (ccRCC) include tyrosine kinase inhibitors (TKI) that target angiogenesis, a critical element for ccRCC tumor growth and survival. Cabozantinib, a TKI that inhibits VEGFR, AXL, and MET, is an approved therapy in advanced RCC. However, cabozantinib has limited therapeutic benefit; for example, patients with prior VEGFR TKI therapy had an overall response rate of 21% and median progression-free survival of 7.4 months. Thus, there is an urgent need to identify combination drug partners that can improve the depth and/or durability of clinical responses to cabozantinib. Here, we present preclinical evidence that supports combining the farnesyltransferase inhibitor (FTI), KO-2806, with cabozantinib in ccRCC. KO-2806 is a next-generation farnesyltransferase inhibitor with increased potency and improved pharmacokinetic properties relative to earlier FTI drug candidates and is poised to enter a first-in-human clinical trial. We demonstrate that addition of KO-2806 enhanced tumor growth inhibition of cabozantinib in multiple ccRCC cell line- and patient-derived xenograft models, resulting in either tumor stasis or regression. Immunohistochemical analysis of angiogenic markers in 786-O tumors revealed that, consistent with its mechanism of action, cabozantinib significantly reduced angiogenesis, an effect that was deepened by KO-2806. In support of this, cell viability experiments performed in primary human endothelial cells showed that the combination of KO-2806 and cabozantinib was more effective in reducing cell viability than cabozantinib alone. In addition, we investigated the mechanism underlying the improved response of tumors with the KO-2806-cabozantinib combination by analyzing the major growth signaling pathways in 786-O tumors. Cabozantinib alone reduced both MAPK and PI3K/AKT/mTOR signaling, but addition of KO-2806 resulted in enhanced inhibition of mTOR signaling and increased cell cycle arrest compared to either agent alone. We hypothesize that exposure to anti-angiogenic TKIs render ccRCC tumors more hypoxic, and thus more reliant on compensatory, oncogenic mechanisms like mTOR signaling that allow them to adapt to a nutrient- and oxygen-deprived environment. Mechanistically, KO-2806 potently inhibits the farnesylation, and hence the activity, of the farnesylation-dependent protein RHEB, a positive regulator of mTOR, suggesting that the improved anti-tumor efficacy of the combination may arise through RHEB inhibition in this model. Further in vitro and in vivo studies are underway to establish the scope and mechanistic underpinnings of the effects of the KO-2806-cabozantinib combination and strengthen the therapeutic rationale for the investigation of this approach in the treatment of patients with ccRCC. Citation Format: Jovylyn Gatchalian, Linda Kessler, Hetika Patel, Stacia Chan, Francis Burrows, Shivani Malik. KO-2806, a next-generation farnesyltransferase inhibitor, potentiates the antitumor activity of cabozantinib in clear cell renal cell carcinoma models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B024.

Abstract IA012: REGN10597: A PD-1-targeted, receptor-masked wild type IL-2 with improved therapeutic window for cancer immunotherapy

Abstract Recombinant IL-2 has been used for the treatment of metastatic melanoma and renal cell carcinoma, and induced complete, durable tumor regression in some patients. ​However, its broader use in cancer immunotherapy has been limited by severe toxicity. Here, we describe the development of REGN10597, a PD-1-targeted, receptor-masked IL-2 immunocytokine with attenuated systemic IL-2 activity but maintained capacity to engage endogenous IL-2Ra on PD-1+ T cells. We will share preclinical data on in vitro characterization as well as in vivo efficacy and toxicity studies of REGN10597. Citation Format: Jiaxi Wu, Nicolin Bloch, Aaron Chang, Ramandeep Bhavsar, Qingqing Wang, Supriya Patel, Vidur Garg, Hassan Shakil, Michael Amatulli, Drew Dudgeon, Yuetian Yan, Shunhai Wang, Willy Ramos, Pamela Krueger, Kristin Vazzana, Alison Crawford, Jacqueline Idun, Corinne Decker, David DiLillo, Samira Chandwani, Tammy Huang, Jessica Kirshner, Chungguang Guo, Lynn Macdonald, Erica Ullman, Aynur Hermann, William Olson, Samuel Davis, John Lin, Eric Smith, Tong Zhang. REGN10597: A PD-1-targeted, receptor-masked wild type IL-2 with improved therapeutic window for cancer immunotherapy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr IA012.

LA INMUNOTERAPIA EN EL MANEJO DEL CÁNCER RENAL METASTÁSICO: EN TRATAMIENTO CON INHIBIDORES DE CHECKPOINT PD-L1 Y/O ANTI-CTLA-4. A

Renal cell carcinoma (RCC) represents approximately 15%, presenting as advanced or metastatic, where surgery is not curative. The prognosis of patients with advanced or metastatic CRC can vary from a few months to a few years, depending on the clinical, pathological and radiological characteristics of the disease. Currently, anti-monoclonals are being used, which is based on immunotherapy-based as checkpoint inhibitors in the initial systemic therapy of advanced treatment of clear cell RCC. This research presents a clinical case where immunotherapy plays a role through the use of anti-monoclonals for the approach of a male patient with metastatic kidney disease who presents a clinical response after surgical treatment and immunotherapy for two years without evidence of oncological disease to date.

Prognostic significance of annexin A2 and tumor associated macrophages (TAMs) in metastatic renal cell carcinoma and their relation to Sunitinib resistance

ABSTRACT Sunitinib, an antiangiogenic tyrosine kinase inhibitor, is the main treatment for metastatic renal cell carcinoma (mRCC). Development of resistance is a major obstacle against therapy success. The aim of this study was to assess annexin A2 and CD163+ tumor associated macrophages (TAMs) immunohistochemical expression in 50 mRCC cases as regard to patients’ prognosis and Sunitinib response. Also, to assess the correlation between annexin A2 and TAMs expression. High annexin A2 expression and TAMs density were associated with serum calcium level (P = 0.024 and 0.037, respectively), larger tumor size (P < 0.001), high tumor grade (P = 0.014 and <0.001, respectively), and the presence of tumor necrosis (P < 0.001). High annexin A2 and TAMs expressions were related to shorter patients’ overall survival (P = 0.009 and 0.001, respectively) and progression-free survival (P = 0.003 and 0.001, respectively). Annexin A2 was correlated with TAMs density (r = 0.890). Annexin A2 and TAMs are associated with poor prognostic parameters in mRCC patients, including high nuclear grade, increased tumor size, and the presence of tumor necrosis, together with shorter patients’ survivals and poor response to Sunitinib. Annexin A2 expression is correlated with TAMs density suggesting immunomodulatory role of annexin A2.

PBRM1 mutation and WDR72 expression as potential combinatorial biomarker for predicting the response to Nivolumab in patients with ccRCC: a tumor marker prognostic study.

Immune checkpoint therapy (ICT) provides a new idea for the treatment of advanced clear cell renal cell carcinoma (ccRCC), which can bring significant benefits to patients. However, the clinical application of ICT is limited because of the lack of predictive biomarkers to select potential responders. This study aims to propose a new biomarker to predict the response to Nivolumab in patients with ccRCC. The genes that significantly improve the prognosis of ccRCC were retrieved from The Cancer Genome Atlas (TCGA) database. The genomic and clinical data were from patients that had been registered in prospective clinical trials (CheckMate 009, CheckMate 010 and CheckMate 025). TCGA, Gene Expression Omnibus (GEO), and The Human Protein Atlas database were used to analyze the gene and protein expression of WD repeat-containing protein 72 (WDR72) in ccRCC. Gene Ontology (GO) & The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to dig relevant mechanisms of WDR72. Single sample gene set enrichment analysis (ssGSEA) was conducted to evaluate the role of WDR72 in immune infiltration. Cell proliferation assay, FAO and ATP quantification were used to explore and verify the molecular mechanisms. The expression of WDR72, FOXP3, CD8, and CPT1A was examined by IHC in 20 advanced ccRCC tissue samples at the Urology Department of our hospital. The MethSurv was used to identify PBRM1 and WDR72 gene methylation and its effect on prognosis of ccRCC. WDR72 is the most significant gene for improving overall survival (OS) in ccRCC. In all three checkmates, OS and progression free survival (PFS) were found to be significantly higher in WDR72 high expression group than that in WDR72 low expression group (P=0.040 and P=0.012, respectively), and similar conclusions could be drawn from the PBRM1-mutation (MUT) compared with the PBRM1-wildtype (WT) (P=0.007 and P=0.006, respectively). What's more, high expression of WDR72 plus PBRM1-MUT as a combinatorial biomarker showed improved OS (HR=0.388, P=0.0026) and PFS (HR=0.39, P=0.0066) compared to low expression of WDR72 plus PBRM1-WT. Functional enrichment analysis showed that WDR72 was closely positively related to fatty acid degradation and fatty acid beta oxidation pathway in ccRCC. In vitro experiments showed that high expression of WDR72 can promote fatty acids oxidation and inhibit the proliferation of ccRCC cells. Immune analysis revealed that WDR72 high expression was associated with decreased infiltration of Treg cells and low ssGSEA score of check-point. IHC results showed that WDR72 was negatively correlated with FOXP3 expression (r=-0.506, P=0.023) and positively correlated with CPT1A expression (r=0.529, P=0.017). The present study indicated that high expression of WDR72 may indicate a good prognosis of patients treated with Nivolumab and WDR72 expression combined with PBRM1 mutation could be more persuasive to predict the response for ICT in ccRCC patients.

Pancreatic metastasis of renal cell carcinoma: case report

Pancreatic metastases account for 2% of pancreatic malignancies and are rare. Metastases to the pancreas originate from many organ systems in the body but occur more frequently from the lung, breast, kidney, and gastrointestinal tract. It may occur years after the treatment of the primary tumor. Symptoms such as abdominal pain, weight loss, and jaundice are present at presentation, but it can also be detected on radiologic imaging without any symptoms. In this article, we present a case of RCC metastasis to the pancreas detected 16 years after renal cell carcinoma (RCC) treatment that was found to be incidental and detected by EUS FNAB.