Putative predictors of efficacy for immune checkpoint inhibitors in non-small-cell lung cancer: facing the complexity of the immune system

Introduction: In non-small-cell lung cancer (NSCLC) the recent introduction of immunotherapy in daily clinical practice produced a wave of enthusiasm, however, this was rapidly moderated by the evidence that only some patients could experience a relevant clinical benefit. Therefore, a great effort from the scientific community has been dedicated to the identification and validation of reliable biomarkers able to drive the activity of immunotherapeutic agents.

Areas covered: This analysis aims to review the main findings about predictive biomarkers for immunotherapy in lung cancer, retracing the history of PD-L1 and focusing on a series of innovative candidates, such as mutational load, immune cell populations and microbiome.

Expert commentary: Considering the complexity of the immune system-cancer interactions, the idea of identifying a single biomarker able to drive the activity of different immunotherapeutic agents alone, borrowing the idea of targeted therapy, is likely to represent an unrealistic objective. Nevertheless, the identification of those factors either positively or negatively affecting the response is mandatory in order to recruit the appropriate patients, but also to deeply understand the mechanisms of immune response and improve the clinical benefit deriving from these agents in monotherapy or in a biologically-rationale combination.     

Expression of Met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors.

Overexpression of the hepatocyte growth factor receptor (Met/HGF receptor), a transmembrane tyrosine kinase encoded by the met proto-oncogene, has been associated with tumor progression in different human carcinomas. More recently, the Met/HGF receptor has also been described in tumor cell lines of mesenchymal origin, suggesting the existence of an autocrine loop that may contribute to the pathogenesis of sarcomas. In this study, we analyzed the expression of Met/HGF receptor by Western blotting and immunohistochemistry in frozen samples of 87 primary tumors of bone and soft tissues. Among benign tumors, overexpression was consistently found only in giant-cell tumor, a locally aggressive lesion that may also, although rarely, spread to the lung. Among malignant lesions, the presence of the Met/HGF receptor was detected in a relevant percentage of primaries and in almost all of the recurrences. The highest levels of Met/HGF receptor were found in osteosarcoma, a highly aggressive tumor that typically permeates the host bone and rapidly expands to the soft tissues. On the contrary, only low levels of Met/HGF receptor were found in chondrosarcoma, a slowly growing tumor that usually expands without massive destruction of the surrounding structures. These data indicate an association of Met/HGF expression with local aggressiveness in human mesenchymal tumors. The finding of Met/HGF receptor overexpression in all of the osteosarcomas suggests a role for the met proto-oncogene in the pathogenesis of this tumor.     

Prevalence of diabetes in Catalonia (Spain): an oral glucose tolerance test-based population study

The goal of this study was to investigate the prevalence of diabetes mellitus and impaired glucose tolerance in the adult population of Catalonia and study their association with obesity, central obesity, hypertension and smoking habit. A random sample of 3839 subjects aged 30-89 years participated in this cross-sectional study: 2214 subjects underwent a health examination with oral glucose tolerance test (OGTT) and 1625 were interviewed by phone. Diabetes prevalence (known and unknown) in the 30-89-year-old population was 10.3%, (95% CI: 9.1-11.6). In this age group, the prevalence rates of known diabetes, unknown diabetes and impaired glucose tolerance were 6.4, 3.9 and 11.9% in men and 6.9, 3.4 and 11.9% in women. The age adjusted prevalence to the world population for the 30-64-year-old age group was 6.1% (7.1% in men and 5.2% in women).The factors significantly associated with diabetes were age, obesity, hypertension and family history of diabetes. The high ratio of previously known diabetic cases to newly discovered ones, specially in the oldest age group, suggests good levels of awareness and medical services. The prevalence in Catalonia is similar to that observed in other Mediterranean countries.     

Idiopathic Thrombocytopenic purpura and Helicobacter pylori Infection

Abstract

Objective. As a minimally invasive modality, radiofrequency ablation (RFA) has been increasingly applied not only for the treatment of hepatocellular carcinoma, but also for that of colorectal liver metastasis (CLM). However, RFA for CLM has been shown to be associated with a high local recurrence rate, and no optimal treatment for RFA failure has been established yet. The aim of this study was to evaluate the feasibility and outcome of surgical resection for local recurrence after RFA. Material and methods. A retrospective study of 17 patients, who underwent surgery for local recurrence after RFA for resectable CLM, was carried out. The surgical procedures involved in the actual surgery were compared with those envisioned for the primary resection if RFA had not been selected. Results. Surgical resection for RFA recurrence was more invasive than the envisioned surgical procedure in 10 cases (58%). In addition, the proportions of cases that required technically demanding procedures among the patients receiving surgery for RFA recurrence were higher than those in envisioned operations; major hepatectomy, eight cases [47%] versus two cases [12%] (p < 0.0205); excision and/or reconstruction of the major hepatic veins, three cases [18%] versus zero case [0%] (p = 0.035); excision of diaphragm: three cases [18%] versus zero case [0%] (p = 0.035). The 1-, 3- and 5-year overall survival rates were 92%, 45% and 45%, respectively. Conclusions. Surgical resection for RFA recurrence for CLM required more invasive and technically demanding procedures. Thus, RFA for CLM should be limited to unresectable cases, and patients with resectable CLM should be thoroughly advised not to undergo RFA, but rather surgical resection.     

Is porto sinusoidal vascular disease to be actively searched in patients with portal vein thrombosis?

Porto sinusoidal vascular liver disease(PSVD) and portal vein thrombosis(PVT)are distinct vascular liver diseases characterized, respectively, by an intrahepatic and a prehepatic obstacle to the flow in the liver portal system. PVT may also occur as a complication of the natural history of PSVD, especially if a prothrombotic condition coexists. In other cases, it is associated to local and systemic pro-thrombotic conditions, even if its cause remains unknown in up to25% despite an active search. In our opinion, the presence of PSVD should be suspected in patients with PVT especially in those with PVT "sine causa" and the active search of this condition should be included in their diagnostic work-out.However, sometimes the diagnosis of pre-existing PSVD is very hard. Biopsy cannot be fully discriminant as similar histological data have been described in both conditions. Liver stiffness may help as it has been shown to be higher in PSVD than in "pure" PVT, due to the presence of sclerosis in the portal venous radicles observable in PSVD patients. Nevertheless, comparing liver stiffness between PVT and PSVD has until now been restricted to very limited series of patients. In conclusion, even if it is still totally hypothetical, our point of view may have clinical consequences, especially when deciding to perform a liver biopsy in patients with a higher liver stiffness and suspending the anticoagulation in patients with PVT and no detectable prothrombotic factors.