Renal cell carcinoma and viral infections: A dangerous relationship?

: Virus-related cancers in humans are widely recognized, but in the case of renal cancer, the link with the world of viruses is not clearly established in humans, despite being known in animal biology. In the present review, we aimed to explore the literature on renal cell carcinoma (RCC) for a possible role of viruses in human RCC tumorigenesis and immune homeostasis, hypothesizing the contribution of viruses to the immunogenicity of this tumor. A scientific literature search was conducted using the PubMed, Web of Science, and Google Scholar databases with the keywords "virus" or "viruses" or "viral infection" matched with ("AND") "renal cell carcinoma" or "kidney cancer" or "renal cancer" or "renal carcinoma" or "renal tumor" or "RCC". The retrieved findings evidenced two main aspects testifying to the relationship between RCC and viruses: The presence of viruses within the tumor, especially in non-clear cell RCC cases, and RCC occurrence in cases with pre-existing chronic viral infections. Some retrieved translational and clinical data suggest the possible contribution of viruses, particularly Epstein-Barr virus, to the marked immunogenicity of sarcomatoid RCC. In addition, it was revealed the possible role of endogenous retrovirus reactivation in RCC oncogenesis, introducing new fascinating hypotheses about this tumor's immunogenicity and likeliness of response to immune checkpoint inhibitors

Prognostic and predictive molecular biomarkers in metastatic renal cell carcinoma patients treated with immune checkpoint inhibitors: a systematic review

: Introduction: In recent years, the treatment landscape of metastatic renal cell carcinoma (mRCC) has been improved using immune-checkpoint inhibitors (ICI). Nevertheless, the number of patients experiencing clinical benefit from immunotherapy is still limited, while others obtain more benefit from tyrosine kinase inhibitors (TKI). The identification of prognostic and predictive factors would be crucial to better select patients most likely to benefit from immunotherapy among the other potentially available therapeutic options.Areas covered: This systematic review summarizes the current knowledge (2010-2019) on molecular prognostic and predictive biomarkers, assessed in peripheral blood and/or from tumor tissue, in mRCC patients treated with ICI.Expert opinion: Among all the biomarkers analyzed, PD-L1 expression on tumor tissue is the most studied. It has an unfavorable prognostic role for patients treated with TKI, which seems to be overcome by ICI-based combinations. Nevertheless, no clear predictive role of immunotherapy efficacy has been observed for PD-L1 in mRCC. Emerging evidence regarding pro-angiogenic or pro-immunogenic genomic and transcriptomic signatures suggests a potential predictive role in patients treated with ICI-based combinations. The rationale for TKI-ICI combinations is based on tumor microenvironment and genomic background, which represent the target of these two main therapeutic options for mRCC

Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer

SIMPLE SUMMARY: Several strategies have demonstrated the ability to improve the survival of patients with both metastatic and nonmetastatic prostate cancer. The old backbone of androgen-deprivation monotherapy has been disrupted in the hormone-sensitive setting, and several options have been introduced for the management of the castration-resistant disease. However, no optimal sequencing is still defined, and few randomized comparisons are currently available to identify the approach that maximizes the long-term benefit for these patients. This comprehensive review aims at resuming the current evidence on this topic to help physicians during the treatment choice for patients with advanced prostate cancer. ABSTRACT: The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177–PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN)

The right immune-modulation at the right time: thymosin α1 for prevention of severe COVID-19 in cancer patients

We presented the rationale for the use of thymosin alpha1 as prophylaxis of severe COVID-19 in cancer patients undergoing active treatment, constituting the background for the PROTHYMOS study, a prospective, multicenter, open-label, Phase II randomized study, currently in its start-up phase(Eudract no.2020-006020-13). We aim to offer new hope for this incurable disease, especially to frail patient population, such as patients with cancer. The hypothesis of an effective prophylactic approach to COVID-19 would have immediate clinical relevance, especially given the lack of curative approaches. Moreover, in the 'COVID-19 vaccine race era' both clinical and biological results coming from the PROTHYMOS trials could even support the rationale for future combinatorial approaches, trying to rise vaccine efficacy in frail individuals

Treatment Outcome of metastatic lesions from renal cell carcinoma underGoing Extra-cranial stereotactic body radioTHERapy: The together retrospective study

Abstract Objectives stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients. Methods all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion. Results 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions ( Conclusions consistently with the previous literature, our findings support the use of SBRT in selected mRCC patients

Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

Background Nivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC. Methods In this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression-free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated. Results After progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13 months (95% CI: 4-NR) in actively treated patients and 3 months (95% CI: 2–4) in BSC patients (p = 0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p = 0.03), with no significant differences in PFS (5 and 3 months, 95% CI: 1–6 vs. 2–5; p = 0.6) and OS (12 and 4 months, 95% CI: 3-NR vs. 2-NR; p = 0.2). Conclusion After treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. Conclusion: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy

Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential

Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall survival and quick time to treatment response. Its safety profile is acceptable and its discontinuation rate, due to toxicity, is similar to those of other TKIs. It is still not clear if the effectiveness of this drug is justified by its wide spectrum of multikinase activity, extended to the MET and AXL kinases, or by the simple maintenance of a ‘vascular endothelial growth factor receptor pressure’ after another previous TKI. Early-phase studies are currently ongoing to investigate the potential activity and safety of cabozantinib in association with immunotherapy, albeit with the risk of an overly toxic combination. Thus, future opportunities to improve the clinical use of this drug will probably be represented by a smart treatment sequence