Long-term response to sunitinib: everolimus treatment in metastatic clear cell renal cell carcinoma.

AIM: The study aim was to evaluate progression-free survival (PFS) and overall survival (OS) in patients with metastatic clear cell renal cell carcinoma on sunitinib (SU) and SU-everolimus treatment. PATIENTS & METHODS: After 7 years of enrollment and 9 years of follow-up, 193 consecutively presenting patients (151 men and 42 women) were treated. RESULTS: A total of 157 patients (81.3%) died and 36 patients (18.7%) survived. Median PFS in 193 SU-treated patients was 14.7 months and OS was 28.8 months. Median PFS was 13.98 months and median OS was 26.67 months in 175 patients treated with SU only or on SU-everolimus. CONCLUSION: The development of SU-induced hypothyroidism, hypertension, neutropenia and edema was a significant predictive and prognostic factor.

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function.

The introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack of official guidelines and the exclusion of patients with reduced kidney function from the clinical trials of recently approved drugs complicate the issue even further. Early detection and correct management of renal toxic effects are crucial to preserve kidney function and ensure the optimal administration of life-prolonging therapies. This review presents detailed information on the renal toxicities of three groups of drugs commonly used in renal cell carcinoma treatment: tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and immune checkpoint inhibitors. We outline the incidence and underlying mechanisms of renal adverse effects with a focus on patients on renal replacement therapy, as well as present suggestions for their management.

Ice-cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the most frequent adverse events of high-dose conditioning chemotherapy with melphalan prior to autologous hematopoietic stem cell transplantation (AHSCT). It significantly reduces the patients' quality of life. One of the preventive strategies for OM is cryotherapy. We retrospectively analyzed whether commercially available ice-cream could prevent OM during the melphalan infusion. We retrospectively analyzed 74 patients after AHSCT to see whether there is any correlation between OM and cryotherapy (ice-cream), melphalan dose (140 mg/m2 or 200 mg/m2). The incidence of OM in our study inversely correlated with cryotherapy in the form of ice-cream. Out of 74 patients receiving conditioning chemotherapy with high-dose melphalan, 52 received cryotherapy. Fifteen patients in the cryotherapy group (28.84%) developed OM, whereas 13 patients (59.09%) developed it in the group without cryotherapy. In a multiple linear regression test cryotherapy remained a significant protective factor against OM (p = 0.02) We have also seen the relationship between melphalan dose with OM (p < 0.005). Cryotherapy in the form of ice-cream is associated with a lower rate of OM and, therefore, could potentially be used as a cost-effective, less burdensome, and easy to implement method in prevention of oral mucositis.

TP53 in Biology and Treatment of Osteosarcoma.

The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate which are more common and describe their role in in vitro and animal models. We also describe animal models with TP53 dysfunction, which provide a good platform for testing the potential therapeutic approaches. Finally, we have indicated a whole range of pharmacological compounds that modulate the action of p53, stabilize its mutated versions or lead to its degradation, cause silencing or, on the contrary, induce the expression of its functional version in genetic therapy. Although many of the described therapies are at the preclinical testing stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future.

Attitudes of Patients with Cancer towards Vaccinations-Results of Online Survey with Special Focus on the Vaccination against COVID-19.

Recently developed COVID-19 vaccines significantly reduce the risk of severe coronavirus disease, which is essential in the particularly vulnerable cancer patient population. There is a growing anti-vaccine concern that may affect the success of the fight against the SARS-CoV2 pandemic. To evaluate opinions and attitudes toward vaccination, we conducted an anonymous online survey among Polish patients diagnosed with cancer. We analyzed how socio-demographic factors, type of cancer, comorbidities, previous influenza vaccinations, and information sources affect the general willingness and opinions about vaccinations, emphasizing vaccination against COVID-19. Six hundred thirty-five patients (80.2% female) participated in the study. A positive attitude towards vaccination was presented by 73.7%, neutral by 17.8%, while negative by 8.5%. Willingness to get vaccinated was declared by 60.3%, 23.5% were unwilling, and 16.2% were undecided. Significant predictors of willingness were education, marital status, active anti-cancer treatment, previous influenza vaccination, and positive attitude towards vaccinations. Patients with cancer have concerns regarding safety, effectiveness, and the process of development of the COVID-19 vaccine. Overall, patients with cancer present positive attitudes towards COVID-19 vaccination but required sufficient information on its efficacy and side effects.

Choosing The Right Animal Model for Renal Cancer Research.

The increase in the life expectancy of patients with renal cell carcinoma (RCC) in the last decade is due to changes that have occurred in the area of preclinical studies. Understanding cancer pathophysiology and the emergence of new therapeutic options, including immunotherapy, would not be possible without proper research. Before new approaches to disease treatment are developed and introduced into clinical practice they must be preceded by preclinical tests, in which animal studies play a significant role. This review describes the progress in animal model development in kidney cancer research starting from the oldest syngeneic or chemically-induced models, through genetically modified mice, finally to xenograft, especially patient-derived, avatar and humanized mouse models. As there are a number of subtypes of RCC, our aim is to help to choose the right animal model for a particular kidney cancer subtype. The data on genetic backgrounds, biochemical parameters, histology, different stages of carcinogenesis and metastasis in various animal models of RCC as well as their translational relevance are summarized. Moreover, we shed some light on imaging methods, which can help define tumor microstructure, assist in the analysis of its metabolic changes and track metastasis development.

Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.

Papillary renal cell carcinoma (pRCC) is the second most common renal cell carcinoma (RCC) subtype and accounts for 10-15% of all RCCs. Despite clinical need, few pharmacogenomics studies in pRCC have been performed. Moreover, current research fails to adequately include pRCC laboratory models, such as the ACHN or Caki-2 pRCC cell lines. The molecular mechanisms involved in pRCC development and drug resistance are more diverse than in clear-cell RCC, in which inactivation of VHL occurs in the majority of tumours. Drug resistance to multiple therapies in pRCC occurs via genetic alteration (such as mutations resulting in abnormal receptor tyrosine kinase activation or RALBP1 inhibition), dysregulation of signalling pathways (such as GSK3ß-EIF4EBP1, PI3K-AKT and the MAPK or interleukin signalling pathways), deregulation of cellular processes (such as resistance to apoptosis or epithelial-to-mesenchymal transition) and interactions between the cell and its environment (for example, through activation of matrix metalloproteinases). Improved understanding of resistance mechanisms will facilitate drug discovery and provide new effective therapies. Further studies on novel resistance biomarkers are needed to improve patient prognosis and stratification as well as drug development.

Metastatic Tumor Burden and Loci as Predictors of First Line Sunitinib Treatment Efficacy in Patients with Renal Cell Carcinoma.

The aim of this study was to investigate the prognostic impact of baseline tumor burden and loci on the efficacy of first line renal cancer treatment with sunitinib. Baseline and on-treatment CT scans were evaluated. Both the Kaplan-Meier and Weibull modelling survival estimators have been used to describe sunitinib treatment response. Logistic regression was used to confirm associations between tumor site, burden and survival. Additionally, analysis of the metastases co-occurrence was conducted using the Bayesian inference on treated and external validation cohorts. 100 patients with metastatic clear cell renal cell carcinoma were treated with sunitinib in this study. Presence of metastases in the abdominal region (HR = 3.93), and the number of brain metastases correlate with shorter PFS, while the presence of thoracic metastases (HR = 0.47) with longer PFS. Localization of metastases in the abdominal region significantly impacts risk of metastases development in other locations including bone and brain metastases. Biology of metastases, in particular their localization, requires further molecular and clinical investigation.