Renal cell carcinoma (RCC) comprises a highly heterogeneous group of kidney tumours built upon distinct genetic- and epigenetic-driven mechanisms and molecular pathways. Therefore, responsiveness to treatment is considerably variable across patients, adding an extra layer of complexity to the already challenging therapeutic decision process. The last decade brought an unprecedented shift in the medical approach to advanced or metastatic RCC; in fact, immunotherapy-based combinations have significantly transformed the therapeutic arsenal and clinical outcomes of these patients. These strategies were quickly adopted by international guidelines committees as the new standards of care. However, this enhanced efficacy comes at the expense of tolerability, with a predictable negative impact on patients’ quality of life. Moreover, subgroup and post hoc analyses of the major clinical trials have shown that not all patients benefit equally from these innovative approaches. In this context, a group of experts on kidney cancer met and discussed the state of the art in the field, with a special emphasis on the appropriateness of using monotherapy with an anti-angiogenesis tyrosine kinase inhibitor (TKI) to treat specific subgroups of patients with RCC. This article reviews the main topics that were considered to be pertinent for that discussion and establishes the profile of patients for whom TKI monotherapy remains a sensible frontline option by avoiding overtreatment and an unnecessary exposure to treatment-related toxicity.

Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies. This paper will review the current evidence of immunotherapy in advanced gastric cancer.

A 10-year review of primary major salivary gland cancers Andreia Cruz1, Helena Magalhães2, Filipa Ferreira Pereira1, José Dinis1 and Cláudia Vieira

Localized prostate cancer is a heterogeneous entity, and new biomarkers are required for risk stratification. This study aimed to characterize tumor-infiltrating lymphocytes (TILs) in localized prostate cancer and assess their potential prognostic markers. Radical prostatectomy specimens were analyzed to determine infiltration levels of CD4+, CD8+, T cells, and B cells (characterized by CD20+ cells) in the tumor tissue using immunohistochemistry and the recommendations of the International TILs Working Group 2014. The clinical endpoint was biochemical recurrence (BCR), and the study sample was divided into two cohorts (cohort 1: without BCR; cohort 2: with BCR). Prognostic markers were assessed using Kaplan-Meier and univariate/multivariate Cox regression analysis using SPSS version 25 (IBM Corp., Armonk, NY, USA). We included 96 patients in this study. BCR occurred in 51% of the patients. Normal TILs infiltration was found in most of the patients (41/31, 87%/63%). T CD4+ infiltration was statistically superior in cohort 2. This enrichment was associated with BCR (p < 0.05; log-rank test). After adjustment for routine clinical variables and Gleason grade groups (grade group ≤2 and grade group ≥3), it remained an independent prognostic variable of early BCR (p < 0.05; multivariate Cox regression). This study showed that immune cell infiltration appears to be an important prognostic variable for early recurrence in localized prostate cancer.

Gastric cancer is the fifth most common cancer worldwide and its incidence is rising. Surgery is the only curative strategy and its association with perioperative chemotherapy is now standard treatment for most resectable tumors. Despite treatment advances, disease relapse is high, even in early stages, and continued improvement in curative treatment is imperative. With deeper knowledge of gastric cancer heterogeneity, molecular subtypes, and the tumor immune microenvironment, new standard treatment strategies may emerge in the near future. This paper provides a comprehensive review of the current treatment landscape in resectable gastric cancer and future perspectives for the next decade regarding new agents such as targeted therapies, immunotherapy, antibody–drug conjugates, and the combination of multiple treatment modalities.

Diabetes mellitus (DM) predicts ominous outcomes in acute pulmonary embolism (PE). The influence of gender on the prognostic impact of DM in PE is unknown. We did a retrospective analysis of a cohort of patients hospitalized with PE between 2006 and 2013. The exclusion criteria were age <18, non-pulmonary veins thromboembolism, recurrent PE, chronic thromboembolic pulmonary hypertension, no radiologic confirmation of PE, and active neoplasia. The primary endpoint was all-cause mortality. The follow-up was from diagnosis until October 2017. We assessed the prognostic impact of DM using a multivariate Cox regression analysis. The analysis was stratified according to gender. The interaction between gender and DM in the outcome of patients with PE was tested. We studied 577 PE patients (median age 65 years, 36.9% men, 19.8% diabetic). The genders were similar regarding the prevalence of DM, the extension and location of PE, and the thrombolytic therapy or brain natriuretic peptide (BNP) value. Diabetics presented higher all-cause mortality (Hazard ratio (HR) = 2.33 (95% confidence Interval (CI) 1.513.61)) when compared with non-diabetics. However, when analysis was stratified according to gender, DM was independently associated with a worse prognosis only in women (HR = 2.31 (95% CI 1.453.65)), while in men the HR was 1.10 (95% CI 0.592.04). The interaction between gender and DM was significant (p = 0.04). Gender influences the prognostic impact of DM in acute PE. Diabetic women with PE have twice the long-term mortality risk, while DM is not mortality-associated in men.