[Show abstract][Hide abstract] ABSTRACT: Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of patients who are candidate to radical prostatectomy.
We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival.
389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small.
Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.
[Show abstract][Hide abstract] ABSTRACT: Background:
Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression.
To investigate the prognostic role of PD-L1 expression in patients affected by renal cell carcinoma (RCC).
MEDLINE/PubMed, the Cochrane Library, and ASCO University were searched for studies investigating the prognostic role of PD-L1 expression in RCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
Six studies and 1323 cases were included in the final analysis. PD-L1 was expressed in 24.2 % of clear cell tumors compared to 10.9 % of non-clear cell tumors (p = 0.002). In the overall population, a higher level of PD-L1 expression increased the risk of death by 81 % (HR; 1.81, 95 % CI 1.31-2.49; p < 0.001). When the analysis was restricted to cases evaluated by immunohistochemistry alone, the higher expression of PD-L1 more than doubled the risk of death (HR; 2.05, 95 % CI 1.38-3.05; p < 0.001). In clear cell histology, higher PD-L1 expression increased the risk of death by 53 % (HR; 1.53, 95 % CI 1.27-1.84; p < 0.001), while in metastatic patients, the evaluation of PD-L1 expression on primary tumors revealed that it retains its prognostic role (HR; 1.45, 95 % CI 1.08-1.93; p = 0.01).
Significant heterogeneity has been identified among the included studies. As a consequence, cautious interpretation of the results is recommended.
This meta-analysis indicates that a higher level of PD-L1 expression is a negative prognostic factor in RCC. Its validation as an independent prognostic factor compared to other traditionally used clinical parameters in localized or advanced disease is recommended.
[Show abstract][Hide abstract] ABSTRACT: Background: The primary analysis of ASPECCT (NCT01001377; Sponsor: Amgen Inc.) demonstrated that pmab was non-inferior to cmab for overall survival (OS) in chemorefractory WT KRAS mCRC. Skin toxicity is the most common adverse event associated with EGFR inhibitors and prior studies with pmab or cmab suggested skin toxicity was associated with better outcome. Here we report skin toxicity and the relationship between severity and survival in patients treated with pmab versus cmab in ASPECCT.
Materials and Methods: Patients were randomized 1:1 to receive pmab 6mg/kg Q2W or cmab 400mg/m2 followed by 250mg/m2 QW. The primary endpoint was OS assessed for non-inferiority. Secondary endpoints included progression free survival (PFS) and safety. A retrospective analysis was conducted to evaluate the effect of skin toxicity severity (worst grade ≤1 versus worst grade 2–4) on efficacy (OS and PFS) from the primary analysis data of ASPECCT. Hazard ratios (HR) were estimated using a stratified Cox proportional hazards model. Skin toxicity was defined as any treatment emergent skin-related adverse event.
Results: 496 patients were treated with pmab versus 503 with cmab. The incidence of worst grade skin toxicity by any grade (1–4), grade ≤1, and grade 2–4 was similar between arms: 87%, 47%, and 53%, respectively. Worst grade 3–4 skin toxicity was 12.5% in the pmab arm and 9.5% in the cmab arm. Median time to first event (any grade) was 10 days (range, 1 to 236) in the pmab arm and 11 days (range, 1 to 367) in the cmab arm. Median time to resolution after the last dose was 37 days in the pmab arm and 35 days in the cmab arm. Demographics and baseline characteristics were generally balanced between patients with worst grade 2–4 and worst grade ≤1 skin toxicity with the following exceptions: a higher percentage of patients with worst grade 2–4 skin toxicity were white, male, or Western (9% to 11% higher in either arm) and had ECOG performance status of 0 (11%, pmab arm only). Patients with worst grade 2–4 skin toxicity had longer median OS and PFS in both arms (Table).
Conclusions: Consistent with previous anti-EGFR therapy analyses, this study demonstrates that higher grade skin toxicity (worst grade 2–4) is associated with better survival outcome compared to no or low grade (worst grade ≤1) in patients with WT KRAS mCRC treated with pmab or cmab.
worst grade 2–4
N=263 Skin toxicity
worst grade ≤1
N=233 Skin toxicity
worst grade 2–4
N=266 Skin toxicity
worst grade ≤1
Median OS, months (95%CI) 14.2 (12.6–15.5) 7.1 (6.0–8.2) 12.6 (10.9–14.0) 8.3 (6.8–9.3)
HR (95%CI) 0.45 (0.37–0.56) 0.58 (0.48–0.71)
Median PFS, months (95%CI) 5.1 (4.9–6.4) 2.9 (1.9–3.0) 4.9 (4.8–5.0) 3.0 (3.0–3.1)
HR (95%CI) 0.46 (0.38–0.56) 0.65 (0.54–0.78)
[Show abstract][Hide abstract] ABSTRACT: Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib.Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤vs.> upper normal rate).A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021).After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012).LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.
[Show abstract][Hide abstract] ABSTRACT: We assessed the impact on survival of angiogenesis and inflammation-related factors, particularly LDH serum levels, platelet, neutrophil and lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR), in metastatic colorectal cancer patients receiving regorafenib monotherapy.
LDH serum levels, neutrophil, lymphocyte and platelet counts were collected at the start of regorafenib monotherapy. Cut-off values were calculated by ROC curve analysis. Survival analyses were performed by Kaplan-Meier method, and multivariate analysis by Cox method.
A total of 208 patients were eligible for analysis. Among factors who were related with worse overall survival and who maintained their role at the multivariate analysis, high platelet count (Exp(b):1.4963, 95% CI:1.0130-2.2103, p = 0.0439) and high neutrophil/lymphocyte ratio (Exp(b):1.6963, 95% CI:1.0757-2.6751, p = 0.0237) were those who more deeply were related to worse overall survival. High lymphocyte count (Exp(b):0.4527, 95% CI:0.2801-0.7316, p = 0.0013) was correlated with improved overall survival.
High neutrophil, high platelet, low lymphocyte count and/or high NLR may represent negative prognostic factors in patients receiving regorafenib monotherapy. It is advisable that these factors are taken into account in the design of subsequent trials in colorectal cancer patients receiving this drug.
[Show abstract][Hide abstract] ABSTRACT: In recent years, the treatment of metastatic colorectal cancer (mCRC) has evolved significantly with the increase of new therapeutic options, leading to an improved median survival for these patients. In particular, the identification of molecular targets in tumor cells has led to the introduction of biological drugs for the treatment of mCRC. Panitumumab is a fully human monoclonal antibody that binds the EGF receptor of tumor cells and inhibits downstream cell signaling with antitumor effect on inhibition of tumor growth. Its use has been approved by randomized clinical trials as monotherapy in chemorefractory patients or combined with chemotherapy in the treatment of RAS wild-type mCRC, where it demonstrated a significant improvement in survival and response rate. The purpose of this review is to analyze the use and efficacy profile of panitumumab, particularly focusing on recently reported data on its use, and future perspectives in patients with mCRC.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, short overall survival and few chemotherapeutic choices. Micro-RNAs (miRNAs) are non-coding, single-stranded RNAs of around 22 nucleotides involved in the pathogenic mechanisms of carcinogenesis and metastasis. They have been studied in many tumors in order to identify potential diagnostic, prognostic or therapeutic targets. In the current literature, many studies have analyzed the role of miRNAs in PDAC. In fact, the absence of appropriate biomarkers, the difficultly of early detection of this tumor, and the lack of effective chemotherapy in patients with unresectable disease have focused attention on miRNAs as new, interesting advance in this malignancy.In this review we analyzed the role of miRNAs in PDAC in order to understand the mechanisms of action and the difference between the onco-miRNA and the tumor suppressor miRNA. We also reviewed all the data related to the use of these molecules as predictive as well as prognostic biomarkers in the course of the disease.Finally, the possible therapeutic use of miRNAs or anti-miRNAs in PDAC is also discussed.In conclusion, although there is still no clinical application for these molecules in PDAC, it is our opinion that the preclinical evidence of the role of specific miRNAs in carcinogenesis, the possibility of using miRNAs as diagnostic or prognostic biomarkers, and their potential therapeutic role, warrant future studies in PDAC.
[Show abstract][Hide abstract] ABSTRACT: Several novel recurrent mutations of histone modifying and chromatin remodeling genes have been identified in renal cell carcinoma. These mutations cause loss of function of several genes located in close proximity to VHL and include PBRM1, BAP1 and SETD2. PBRM1 encodes for BAF180, a component of the SWI/SNF chromatin remodeling complex, and is inactivated in, on average, 36% of clear cell renal cell carcinoma (ccRCC). Mutations of BAP1 encode for the histone deubiquitinase BRCA1 associated protein-1, and are present in 10% of ccRCCs. They are largely mutually exclusive with PBRM1 mutations. Mutations to SETD2, a histone methyltransferase, occur in 10% of ccRCC. BAP1- or SETD2-mutated ccRCCs have been associated with poor overall survival, while PBRM1 mutations seem to identify a favorable group of ccRCC tumors. This review describes the roles of PBRM1, BAP1 and SETD2 in the development and progression of ccRCC and their potential for future personalized approaches.
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Aims: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations.
Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival.
MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors.
KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets.
[Show abstract][Hide abstract] ABSTRACT: The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Rosen Shingle Creek, Orlando, FL, USA, 26-28 February 2015 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium was held in Orlando (FL, USA), from 26 to 28 February 2015. This meeting was focused on 'Integrating Biology into patient-centric care' and represented an attractive opportunity for oncology professionals with a special interest in the diagnosis and treatment of genitourinary tumors. The identification and validation of biomarkers for tumor response had been the focus of several researchers at the symposium, together with the development of novel targeted agents. This report is a summary of the highlights on kidney and prostate tumors presented at the 2015 ASCO Genitourinary Cancers Symposium by various investigators.
[Show abstract][Hide abstract] ABSTRACT: Cancer is a disease that has far-reaching consequences for patients and their families. The present study targets unmet caregiver needs so that better support can be provided and planned for.
The first phase of the study was to conduct a survey designed to explore basic needs (medical and nursing information, psychological support, social welfare). The survey also investigated the caregiver's personal details (age, sex, degree of kinship). The survey was distributed to caregivers coming to the day hospitals of the 4 oncology departments involved in the study.
A total of 137 relatives of cancer patients completed the survey. Among the explored needs, the most recurrent was the availability of a doctor who provides full information on the treatment choices. A further important request was for consistency between the information provided by doctors and that provided by other health-care workers, with specific reference to a patient-centered approach that can be easily and fully understood, available therapeutic options especially at home, and prognosis.
The study showed that the need for exhaustive and simple information provided by a referral physician is still an unmet need in the Internet age.
[Show abstract][Hide abstract] ABSTRACT: HER family receptors play a key role in tumor progression in several malignancies, such as colorectal, lung or breast cancer. The aims of this study were to investigate expression of HER-1, HER-2 and HER-3 in pancreatic cancer (PC) samples and evaluate the association between HER-family receptor expression and patients' clinical outcomes.
Tissue samples from 91 PC patients were subjected to immunohistochemical staining to assess the expression of HER-1, HER-2 and HER-3. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+ or 3+ were assigned to each sample based on the intensity of staining for HER receptors. Scores of 2+ or 3+ were defined as positive staining.
HER-1 overexpression was observed in 41 out of 91 samples (45.1%), while HER-2 was not overexpressed in any of the analyzed samples. HER-3 was overexpressed in 37 samples (40.7%) and was found to be associated with advanced TNM stage. In particular, HER-3 was overexpressed in 12 out of 16 stage IV patients (75%) compared with only 33.3% of stage I-III patients (p = 0.02). Among 79 patients with available survival data, the 6 patients with strong HER-3 expression (score 3+) had a shorter survival compared with remaining patients (median overall survival 6.9 months vs. 12.3 months, respectively).
HER-1 and HER-3 were found to be expressed in a significant proportion of PC patients. Strong HER-3 expression represents an indicator of poor prognosis in PC patients, being associated with advanced stage and shorter survival.
The International journal of biological markers 06/2015; 30(3). DOI:10.5301/jbm.5000157 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Although epidermal growth factor receptor (EGFR) inhibitors have progressively become a relevant therapeutic arm in the treatment of patients with advanced colorectal cancer, the responses achieved are not durable and resistance invariably occurs. The advances in sequencing technology have allowed not only a more profound molecular tumor characterization but also the identification of the different molecular pathways involved in drug resistance and disease progression. These biological improvements have encouraged researchers to design clinical studies testing novel target therapies.
After discussing the results of key Phase III randomized trials and providing commentary on the most promising novel agents (Sym004, MM-151, GA201 and MEHD7945A), the authors present the future steps ahead toward a real tailored treatment.
EGFR inhibitors are highly effective in the advanced disease setting. Although the negative predictive role of RAS and possibly BRAF mutations has already been established, more comprehensive efforts are needed to optimize the use of these drugs. At the same time, understanding the underlying biology will help basic scientists to develop new compounds able to overcome both primary and acquired resistance and help clinical researchers to test novel drugs within adequately designed trials whose results eventually are expected to reshape the overall treatment strategy.