A 17-Gene Expression Signature for Early Identification of Poor Prognosis in Clear Cell Renal Cell Carcinoma

: The Identification of reliable Biomarkers able to predict the outcome after nephrectomy of patients with clear cell renal cell carcinoma (ccRCC) is an unmet need. The gene expression analysis in tumor tissues represents a promising tool for better stratification of ccRCC subtypes and patients' evaluation. Methods: In our study we retrospectively analyzed using Next-Generation expression analysis (NanoString), the expression of a gene panel in tumor tissue from 46 consecutive patients treated with nephrectomy for non-metastatic ccRCC at two Italian Oncological Centres. Significant differences in expression levels of selected genes was sought. Additionally, we performed a univariate and a multivariate analysis on overall survival according to Cox regression model. Results: A 17-gene expression signature of patients with a recurrence-free survival (RFS) < 1 year (unfavorable genomic signature (UGS)) and of patients with a RFS > 5 years (favorable genomic signature (FGS)) was identified and resulted in being significantly correlated with overall survival of the patients included in this analysis (HR 51.37, p < 0.0001). Conclusions: The identified Genomic Signatures may serve as potential biomarkers for prognosis prediction of non-metastatic RCC and could drive both follow-up and treatment personalization in RCC management

Competitividad internacional en fresa y frutos rojos de España

[EN] This article examines the situation of the strawberry and red fruits in Spain, and competitiveness maps are presented in the strawberry, raspberry and blueberry. It is observed as is has last of a monoculture (Strawberry) to a greater diversification varietal (Blueberry, raspberry and BlackBerry). Huelva continues being the province leader in Spain both in production as marketing and is consolidated year to year. Strawberry’s main markets are Germany, France, United Kingdom; or raspberry is the United Kingdom, France and Netherlands; and blueberries is United Kingdom, Germany and the Netherlands. These products face four challenges: diversification, quality, labor and water. They are generally a sector very competitive and with good prospects for the future.[ES] En este artículo novedoso se estudia la situación de la fresa y los frutos rojos en España, y se presentan los mapas de competitividad en fresa, frambuesa y arándanos. Se observa como se ha pasado de un monocultivo (fresa) a una mayor diversificación varietal (arándano, frambuesa y mora). Huelva sigue siendo la provincia líder en España tanto en producción como comercialización y se consolida año a año. Los principales mercados de la fresa son Alemania, Francia, Reino Unido; para la frambuesa es Reino Unido, Francia y Países Bajos; y en arándanos es Reino Unido, Alemania y Países Bajos. Estos productos se enfrentan a cuatro retos; diversificación, calidad, mano de obra y el agua. En general son sectores muy competitivos y con buenas perspectivas para el futuro.Peer reviewe

Castration resistance prostate cancer: what is in the pipeline?

To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely update on new pharmacological treatments

Clinical Outcome of Third-Line Pazopanib in a Patient with Metastatic Renal Cell Carcinoma

Background. Renal cell carcinoma accounts for about 2-3% of all malignant tumors. The prevalence of brain metastases from RCC is less than 20% of cases. Traditionally, whole brain radiotherapy as well as the latest stereotactic radiosurgery improves both survival and local tumor control. These treatments also allow stabilization of clinical symptomatology. However, validated treatment guidelines for RCC patients with brain metastases are not yet available on account of the frequent exclusion of such patients from clinical trials. Moreover, limited data about the sequential use of three therapies, changing the class of agent, have been published up to now. Case Report. We report the case of a patient with metastatic RCC who developed disease progression after sunitinib and everolimus as first-line and second-line therapy, respectively. Thus, he underwent a multimodality treatment with pazopanib, as third-line therapy, to control systemic disease and radiosurgery directed on the new brain metastasis. To date, the patient is still receiving pazopanib, with progression-free survival and overall survival of 43 and 103 months, respectively. Conclusion. In a context characterized by different emerging options, with no general consensus on the optimal treatment strategy, the use of pazopanib in pretreated patients could be a suitable choice

Heterogeneity of PD-L1 expression and relationship with biology of NSCLC

Immunotherapy with monoclonal antibodies against programmed cell death (PD-1), such as nivolumab and pembrolizumab, has significantly improved the survival of patients with metastatic non-small cell lung cancer (NSCLC). In order to determine the subset of patients that can benefit most from these therapies, biomarkers such as programmed death ligand-1 (PD-L1) have been proposed. However, the predictive and prognostic role of the use of PD-L1 is controversial. Anti-PD-L1 immunohistochemistry may not represent the actual status of the tumour because of individual variability and tumour heterogeneity. Additionally, there may be analytical variability due to the use of different assays and antibodies to detect PD-L1. Moreover PD-L1 expression is also regulated by oncogenic drivers in NSCLC, such as epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4 (EML4) fusion with anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS). Preclinical studies have shown the potential role of targeted therapy in immune escape mechanisms in NSCLC cells. This review summarizes current literature data on the heterogeneity of PD-L1 expression and the relationship with such factors and with clinicopathological features of NSCLC

Multimodality treatment of brain metastases from renal cell carcinoma in the era of targeted therapy

In patients with renal cancer, brain metastasis is associated with poor survival and high morbidity. Poor life expectancy is often associated with widespread extracranial metastases. In such patients, a multidisciplinary approach is paramount. Brain metastases-specific therapies may include surgery, radiosurgery, conventional radiation and targeted therapies (TT) or a combination of these treatments. Some factors are important prognostically when choosing the best strategy: performance status, the number, size and location of brain metastases, the extension of systemic metastases and a well-controlled primary tumour. Failure of chemical therapy has always been attributed to an intact blood-brain barrier and acquired drug resistance by renal cancer cells. Recent studies have demonstrated objective responses with TT in a variety of cancer types, including renal cancer. In most cases, these agents have been used in combination and in conjunction with whole-brain radiation therapy and radiosurgery. Local control appears to be better with the combined method if the patient has a good performance status and may improve overall survival. This review summarizes current literature data on multidisciplinary approach in the management of renal brain metastasis with radiation, surgery and TT with an emphasis on potential better outcomes with a combination of current treatment methods

Molecular basis of drug resistance and insights for new treatment approaches in mCRPC

Inhibiting androgen receptor (AR) signaling with androgen deprivation therapy (ADT) represents the mainstay of therapy for advanced and metastatic prostate cancer. However, about 20-60% of patients receiving first-line treatment for prostate cancer will relapse, evolving in a more aggressive and lethal form of the disease, the castrationresistant prostate cancer (CRPC), despite the use of ADT. Multiple approved systemic therapies able to prolong survival of patients with metastatic CRPC (mCRPC) exist, but almost invariably, patients treated with these drugs develop primary or acquired resistance. Multiple factors are involved in CRPC treatment resistance and elucidating the mechanisms of action of these factors is a key question and an active area of research. Due to such a complex scenario, treatment personalization is necessary to improve treatment effectiveness and reduce relapse rates in CRPC. In this review, current evidence about the major mechanisms of resistance to the available prostate cancer treatments were examined by introducing insights on new and future therapeutic approaches

The impact of locoregional treatments for metastatic castration resistant prostate cancer on disease progression. real life experience from a multicenter cohort

Background: Available data on medical treatment of metastatic castration resistant prostate cancer (mCRPC) support the use of more than one therapy line to delay chemotherapy. We evaluate in a longitudinal real life multicenter cohort, the oncological outcome of mCRPC patients treated with Abiraterone Acetate (AA) and Enzalutamide (EZ) in a chemo-naïve setting, who received locoregional treatments for subsequent development of oligorecurrent disease. Methods: We prospectively collected data on chemo-naïve mCRPC patients, who received either AA or EZ as first or second line treatment between Oct-2012 and Nov-2020 at 5 centers. High-volume disease at mCRPC onset was defined as bulky positive nodes (≥5 cm) or more than 6 bone metastases. Survival probabilities were computed at 12, 24, 48 and 60 months after treatment start. The impact of loco-regional treatments on progression free survival (PFS) were assessed with the Kaplan-Meier method and the log-rank test was applied. Results: Overall, 117 chemo-naive mCRPC patients received a first line therapy. Fifty-seven (48.7%) patients received AA and 60 (51.3%) received EZ. Eight (6.7%) patients underwent salvage chemotherapy after first line failure. Overall, 28 patients shifted to a second line therapy. Two-yr progression-free, cancer-specific and overall survival probabilities were 65.5%, 82.2% and 78.4% respectively. Since diagnosis of mCRPC, oligo progression occurred in 25 patients who received stereotactic radiation therapy (23/25, 92%) focused on metastasis (4 nodal sites and 19 bones) or salvage lymph node dissection (2/25, 8%). At Kaplan-Meier analysis, patients with low volume disease displayed higher PFS probabilities (log rank p = 0.009) and in this subgroup of patients loco-regional treatments had a significant impact on PFS (p = 0.048), while it was negligible in the whole cohort and in patients with high volume disease (p = 0.6 and p = 0.75). Conclusions: Low-volume mCRPC patients are exposed to improved PFS and seem to benefit from locoregional treatments