1,721,342 research outputs found
Tumour Infiltrating Lymphocytes and Immune-Related Genes as Predictors of Outcome in Pancreatic Adenocarcinoma
Full text linkBackground: Pancreatic Carcinoma (PC) is a lethal disease with a poor prognosis. Pancreatic Carcinoma is characterized by a desmoplastic, highly heterogeneous and immune-suppressive microenvironment that hinders antitumour immunity. The aim of this study is to investigate the correlation between PC patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.
Materials and Method: Fresh PC specimens were obtained from patients (n=12) undergoing surgical resection at the Department of Medical, Surgical & Health Sciences, Cattinara Teaching Hospital, Trieste University, between 2005 and 2015. Prognosis of primary PC patients was determined using clinical data and Kaplan-Meier curves. Overall survival (OS) was measured from the time of surgery to the time of death or the last follow up visit. A more in-depth analysis of the 12 patients revealed two groups with different disease free survival (DFS) and/or OS: six patients with an OS between 25 and 66 months were classified as “good cases”, while six with OS between 2 and 9 months or DFS between 1 and 2 months were classified as “worse cases”. Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA).
Results: Our data showed that the CD3 level was statistically higher in the good prognosis group compared to the worse prognosis group (p=0.0267). Three primary PC patients with a good prognosis and three with a worse prognosis were then chosen for mRNA analysis by PanCancer Immune Profile Panel multiplex gene expression analysis. Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37.
Conclusion: The key findings from this study, that longer-surviving PC patients had higher levels of intratumoural TILs and overexpressed five immune markers (TLR7, TNF, C1QA, FOXP3, CD37), could have two main uses. Together with an assessment of TIL levels, such an immune system gene panel constitutes a potential prognostic tool to permit a risk-based stratification of pancreatic tumour patients into personalized treatment protocols towards improving the current abysmal clinical outcome of these patients
Is there a place for bevacizumab in patients with extensive-stage small cell lung cancer?
No full textIt was estimated that small cell lung cancer (SCLC) accounts for about one Sixth of all lung cancer cases. Patients with SCLC are usually diagnosed in advanced stage of disease. Unfortunately at this stage, prognosis is very poor. Bevacizumab is a monoclonal antibody against VEGF, which inhibits the angiogenesis in malignant tumors. Although Bevacizumab has been approved for firstline use in advanced non-SCLC, the first report has been available for its use in SCLC. In this review, we summarized all available data on the use of Bev in SCLC patients. Finally, future directions are discusse
Is the Gleason score the driver for the treatment decision-making of patients with castration-resistant prostate cancer in the new era of the anti-androgenic therapies?
No full textFizazi et al. [1] showed the initial diagnostic Gleason score in patients with metastatic castration-resistant prostate cancer (mCRPC) should not be considered in the medical decision oriented to abiraterone. Based on these findings, we believe it would be important to extend the analyses carried out by Fizazi et al. to all novel anti-androgenic therapies with a pooled analysis of available trials from the literature. The studies were identified, according to the following inclusion criteria: (i) patients with mCRPC; (ii) a novel anti-androgenic therapy including the selective 17,20-lyase inhibitor orteronel; (iii) the presence of a control arm for comparison ( placebo or not); and (iv) the presence of data on overall survival (OS) and progression-free survival (PFS) according to the Gleason score. The following
exclusion criteria were used: (i) insufficient data were available to estimate the outcomes; (ii) animal studies; (iii) the size of each arm was<10 participants; and (iv) non-randomized studies. The summary estimates were generated using a fixedeffect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird method) depending on the absence or presence of heterogeneity (I2). Seven studies were included in the analysis (Table 1), Gleason score of 8 was the cut-off for the analysis. ELM-PC 4, ELM-PC 5, COU-AA-301, COU-AA-302 and PREVAIL trials reported data on hazard ratio (HR) of OS (Table 1) according to the initial Gleason score. The AFFIRM trial was excluded because it does not report data on PFS and OS according to the Gleason score. In regard to OS, a total of 6187 cases were included; 2982 cases (1654 in the experimental and 1328 in the control arm) had Gleason score <8, while 3205 cases (1797 in the experimental and 1408 in the control arm) had Gleason score ≥8 (Table 1). The analysis according to the Gleason score revealed novel anti-androgenic therapies significantly improved OS with similar extent in patients with Gleason score <8 [HR = 0.82, 95% confidence interval (CI) 0.73–0.91; P = 0.0004] compared with performance Gleason score ≥8 (HR = 0.81, 95% CI 0.73– 0.90; P < 0.00001] (Figure 1A). The fixed-effects model was used for the analysis due to the moderate heterogeneity (I2 = 46%) between the trials
Pertuzumab therapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer
No full textIn The Lancet Oncology, Josep Tabernero and colleagues 1 report the final analysis of the JACOB trial, which tested the efficacy and safety of pertuzumab (a monoclonal antibody targeting HER2 receptors) combined with
trastuzumab and chemotherapy in previously untreated patients with HER2-positive metastatic gastric or gastrooesophageal junction cancer. JACOB was the first trial to investigate a dual HER2 blockade in metastatic gastric
cancer; unfortunately, no significant improvement in overall survival was observed in the group treated with the dual-HER2 targeted combination
Re: Karim Fizazi, Kim N. Chi, Johann S. de Bono, et al. Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.02.035: Corticosteroid-associated Adverse Events in Elderly Patients
No full textLow Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cance
Re: Johann S. de Bono, Matthew R. Smith, Fred Saad, et al. Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.06.033
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Expanding treatment options for metastatic gastric cancer
No full textExpanding treatment options for metastatic gastric cance
Influence of Prior Tyrosine Kinase Inhibitor on Survival for Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab or Cabozantinib: Data from a Literature-based Meta-analysis
Full text linkThe aim of this letter is to focus on the survival of patients treated with nivolumab and cabozantinib according to prior first-line TKI. We used data from CheckMate 025 and METEOR for a subsequent subgroup analysi
Is the fatigue an adverse event of the second generation of hormonal therapy? Data from a literature-based meta-analysis
No full textNew hormonal therapies have enriched the therapeutic armamentarium for patients with castration-resistant prostate cancer (CRPC). Fatigue is one of the most common adverse events registered in phase III trials of these new drugs. The aim of this article is to perform a meta-analysis based on all available literature data focused on the risk rate (RR) of fatigue from new hormonal agent-based therapy in patients with CRPC. A total of 11,751 cases were included from 11 randomized trials. The analysis revealed that the second generation of hormonal therapies increased the RR of any-grade fatigue (RR = 1.27) and grade 3-4 fatigue (RR = 1.25). This last adverse event was always higher in a pre-chemotherapy setting. In conclusion, given the limitations of a literature-based study, rather than a meta-analysis based on individual patients' data, our study confirmed the increase in the RR for any-grade and grade 3-4 fatigue during the second generation of hormonal therapies, with particular attention being paid to grade 3-4 in the pre-chemotherapy setting of the disease
Lower urinary tract infections from external beam radiation therapy in prostate cancer: A single institution experience
No full textExternal beam radiation therapy (EMRT) is effective for the treatment of localized prostate cancer. Lower urinary tract infections (LUTIs) are considered one of the main possible adverse events related to External beam radiation therapy. Here we analyzed the incidence of LUTI during EMRT. Urinary tract infection was assumed when the findings of bacteriuria exceeded 100,000 units/mL, accompanied by specific cystitis symptoms. Among the total 540 analyzed patient, 208 (38.5%) developed a LUTI. E. coli was the main microorganism involved in LUTIs (102, 49.04%) with 8 cases of a combination between E. coli and another germ. In conclusion, a risk of urinary infections in cancer patients treated with pelvic radiotherapy was observed, in order to reduce the use of antibiotic resistance, preventive treatment with non-antibiotic agents 5 are warranted
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