We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with ...advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360.NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib.
In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to ...cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy. Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment. Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response.
Background & Aims
The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular ...carcinoma (HCC).
Methods
We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of β‐catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v‐akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor‐2 (VEGFR‐2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs.
Results
Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression‐free survival (PFS) and overall survival (OS) were associated with increased pERK staining (≥ 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR‐2 staining (≥ 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR‐2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13–3.86, P = 0.019 and HR 2.28; 95% CI, 1.13–4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers.
Conclusions
Elevated tissue expression of pERK and VEGFR‐2 was predictive of poor outcome in advanced HCC treated with sorafenib.
Abstract Despite recent biological insight and therapeutic advances, the prognosis of advanced pancreatic cancer still remains poor. For more than 15 years, gemcitabine monotherapy has been the ...cornerstone of first-line treatment. Recently, prospective randomized trials have shown that novel upfront combination regimens tested in prospective randomized trials have resulted in improved patients' outcome increasing the proportion of putative candidate to second-line therapy. There is no definite standard of care after disease progression. A novel formulation in which irinotecan is encapsulated into liposomal-based nanoparticles may increase the efficacy of the drug without incrementing its toxicity. NAPOLI-1 was the first randomized trial to compare nanoliposomal irinotecan and fluorouracil-leucovorin (5-FU/LV) to 5-FU/LV alone after a gemcitabine-based chemotherapy. This review focuses on the current data for the management of second-line treatment for metastatic pancreatic adenocarcinoma, presents the most interesting ongoing clinical trials and illustrates the biologically-driven future options beyond disease progression.
Despite some notable advances in the systemic management of gastric cancer(GC), the prognosis of patients with advanced disease remains overall poor and their chance of cure is anecdotic. In a ...molecularly selected population, a median overall survival of 13.8 mo has been reached with the use of human epidermal growth factor 2(HER2) inhibitors in combination with chemotherapy, which has soon after become the standard of care for patients with HER2-overexpressing GC. Moreover, oncologists have recognized the clinical utility of conceiving cancers as a collection of different molecularlydriven entities rather than a single disease. Several molecular drivers have been identified as having crucial roles in other tumors and new molecular classifications have been recently proposed for gastric cancer as well. Not only these classifications allow the identification of different tumor subtypes with unique features, but also they serve as springboard for the development of different therapeutic strategies. Hopefully, the application of standard systemic chemotherapy, specifictargeted agents, immunotherapy or even surgery in specific cancer subgroups will help maximizing treatment outcomes and will avoid treating patients with minimal chance to respond, therefore diluting the average benefit. In this review, we aim at elucidating the aspects of GC molecular subtypes, and the possible future applications of such molecular analyses.
Introduction:
Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, ...rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set.
Methods:
This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib.
Conclusions:
Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.
HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor ...prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies.
Fingerprint Change: Not Visible, But Tangible Negri, Francesca V.; De Giorgi, Annamaria; Bozzetti, Cecilia ...
Journal of forensic sciences,
September 2017, 2017-Sep, 2017-09-00, 20170901, Letnik:
62, Številka:
5
Journal Article
Recenzirano
Hand–foot syndrome, a chemotherapy‐induced cutaneous toxicity, can cause an alteration in fingerprints causing a setback for cancer patients due to the occurrence of false rejections. A colon cancer ...patient was fingerprinted after not having been able to use fingerprint recognition devices after 6 months of adjuvant chemotherapy. The fingerprint images were digitally processed to improve fingerprint definition without altering the papillary design. No evidence of skin toxicity was present. Two months later, the situation returned to normal. The fingerprint evaluation conducted on 15 identification points highlighted the quantitative and qualitative fingerprint alteration details detected after the end of chemotherapy and 2 months later. Fingerprint alteration during chemotherapy has been reported, but to our knowledge, this particular case is the first ever reported without evident clinical signs. Alternative fingerprint identification methods as well as improved biometric identification systems are needed in case of unexpected situations.
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