Role of docetaxel in the treatment of advanced gastric carcinoma

With a median survival of 9-11 months, advanced gastric cancer represents one of the most aggressive neoplastic disease in western Countries. Radical surgery is considered the cornerstone for any curative procedure, however only a relatively small proportion of resected cases can be considered cured after surgery. In the last few years research data suggested that advanced gastric cancer can be classified into 2 distinct clinical categories: locally advanced (nonmetastatic, non resectable) and metastatic. While the therapeutic goal in the metastatic setting is palliation and survival improvement, in locally advanced cases one of the main goals of the treatment should be response with the aim to make resectable what was unresectable. The introduction of docetaxel for the treatment of advanced gastric cancer represented then a crucial step forward for the cure of this disease with an improvement in both survival and response rate. In this article we reviewed past and ongoing trials using docetaxel in gastric cancer with the aim to delineate a possible effective strategy for the treatment of this tumou

Development of a patient-centered aggregate score to predict survival after lung resection for non–small cell lung cancer

ObjectiveThe objective of this analysis was to develop a survival aggregate score (SAS), including objective and subjective patient-based parameters, and assess its prognostic role after major anatomic resection for non–small cell lung cancer.MethodsA total of 245 patients underwent major lung resections for non–small cell lung cancer with preoperative evaluation of quality of life (Short-Form 36v2 survey) and complete follow-up. The Cox multivariable regression and bootstrap analyses were used to identify prognostic factors of overall servival, which were weighted to construct the scoring system and summed to generate the SAS.ResultsCox regression analysis showed that the factors negatively associated with overall survival and used to construct the score were 36-item short-form health survey physical component summary score less than 50 (hazard ratio [HR], 1.7; P = .008), aged older than 70 years (HR, 1.9; P = .002), and carbon monoxide lung diffusion capacity less than 70% (HR, 1.7; P = .01). Patients were grouped into 4 risk classes according to their SAS. The 5-year overall survival was 78% in class SAS0, 59% in class SAS1, 42% in class SAS2, and 14% in class SAS3 (log-rank test, P < .0001). SAS maintained its association with overall survival in patients with stages pT1 (log-rank test, P = .01), pT2 (log-rank test, P = .02), or pT3-4 (log-rank test, P = .001), and in those with stages pN0 (log-rank test, P = .0005) or pN1-2 (log-rank test, P = .02). The 5-year cancer-specific survival was 83% in class SAS0, 71% in class SAS1, 63% in class SAS2, and 17% in class SAS3 (log-rank test, P < .0001).ConclusionsThis system may be used to refine stratification of prognosis for clinical and research purposes

Panitumumab: the evidence for its use in the treatment of metastatic colorectal cancer

Panitumumab is the first fully human monoclonal antibody to Epidermal Growth Factor Receptor (EGFR) to enter clinical trials for the treatment of solid tumors. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal (CRC). Preclinical and clinical studies have established a role for panitumumab in metastatic colorectal cancer (mCRC) refractory to multiple chemotherapeutic regimens. Based on these encouraging findings, panitumumab was approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing mCRC refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The improvement in progression free survival (PFS) and response rate (RR) produced by panitumumab monotherapy was significantly greater in patients with non mutated (wild-type) K-RAS than in those with mutant K-RAS. Therefore implementing routine K-RAS screening and limiting the use of EGFR inhibitors to patients with wild-type K-RAS appears the better strategy for select only the patients who could benefit from the therapy with panitumumab and also may have the potential for cost savings. The purpose of this review was to evaluate the patient-related, disease-related and economic-related evidence for the use of panitumumab in the treatment of metastatic colorectal cancer in clinical practice

High CTLA-4 expression correlates with poor prognosis in thymoma patients

Thymomas, tumors that arise from epithelial cells of the thymus gland, are the most common neoplasms of the anterior mediastinum, with an incidence rate of approximately 2.5 per million/year. Cytotoxic T Lymphocyte Antigen 4 (CTLA-4 or CD152) exerts inhibitory activity on T cells, and since its oncogenic role in the progression of different types of tumors, it has emerged as a potential therapeutic target in cancer patients. In this study, we assessed the expression of CTLA-4 both at mRNA and protein levels in paraffin embedded-tissues from patients with thymomas. Furthermore, we evaluated the relationship between CTLA-4 expression and the clinical-pathologic characteristics and prognosis in patients with thymomas. Sixty-eight patients with median age corresponding to 62 years were included in this analysis. Thymomas were classified accordingly to the WHO and Masaoka-Koga for histochemical analysis and for prognostic significance. A statistical difference was found between CTLA-4 mRNA levels in human normal thymus compared with thymoma specimens. CTLA-4 expression was statistically found to progressively increase in A, B1, B2, AB and it was maximal in B3 thymomas. According to Masaoka-Koga pathological classification, CTLA-4 expression was lower in I, IIA and IIB, and higher in invasive III and IV stages. By confocal microscopy analysis we identified the expression of CTLA-4 both in tumor cells and in CD45+ tumor-infiltrating leukocytes, mainly in B3 and AB thymomas. Finally, CTLA-4 overexpression significantly correlates with reduced overall survival in thymoma patients and in atypical thymoma subgroup, suggesting that it represents a negative prognostic factor

PD-1 blockade therapy in renal cell carcinoma: current studies and future promises

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC. In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway

Regulation of Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT, and NOTCH by Long Non-Coding RNAs in Pancreatic Cancer

Rapidly evolving and ever-increasing knowledge of the molecular pathophysiology of pancreatic cancer has leveraged our understanding altogether to a next level. Compared to the exciting ground-breaking discoveries related to underlying mechanisms of pancreatic cancer onset and progression, however, there had been relatively few advances in the therapeutic options available for the treatment. Since the discovery of the DNA structure as a helix which replicates semi-conservatively to pass the genetic material to the progeny, there has been conceptual refinement and continuous addition of missing pieces to complete the landscape of central dogma. Starting from transcription to translation, modern era has witnessed non-coding RNA discovery and central role of these versatile regulators in onset and progression of pancreatic cancer. Long non-coding RNAs (lncRNAs) have been shown to act as competitive endogenous RNAs through sequestration and competitive binding to myriad of microRNAs in different cancers. In this article, we set spotlight on emerging evidence of regulation of different signaling pathways (Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT and NOTCH) by lncRNAs. Conceptual refinements have enabled us to understand how lncRNAs play central role in post-translational modifications of various proteins and how lncRNAs work with epigenetic-associated machinery to transcriptionally regulate gene network in pancreatic cancer

Seroprevalence of SARS-CoV-2–Specific Antibodies in Cancer Patients Undergoing Active Systemic Treatment: A Single-Center Experience from the Marche Region, Italy

none13noSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in cancer patients may vary widely dependent on the geographic area and this has significant implications for oncological care. The aim of this observational, prospective study was to assess the seroprevalence of SARS-CoV-2 IgM/IgG antibodies in solid cancer patients referred to the academic institution of the Marche Region, Italy, between 1 July and 26 October 2020 and to determine the accuracy of the rapid serological test. After performing 3767 GCCOV-402a rapid serological tests on a total of 949 patients, seroconversion was initially observed in 13 patients (1.4%). Ten (77% of the total positive) were IgG-positive, 1 (8%) were IgM-positive and 2 (15%) IgM-positive/IgG-positive. However, only 7 out of 13 were confirmed as positive at the reference serological test (true positives), thus seroprevalence after cross-checking was 0.7%. No false negatives were reported. The kappa value of the consistency analysis was 0.71. Due to rapid serological test high false positive rate, its role in assessing seroconversion rate is limited, and the standard serological tests should remain the gold standard. However, as rapid test negative predictive value is high, GCCOV-402a may instead be useful to monitor patient immunity over time, thus helping to assist ongoing vaccination programsopenCantini, Luca; Bastianelli, Lucia; Lupi, Alessio; Pinterpe, Giada; Pecci, Federica; Belletti, Giovanni; Stoico, Rosa; Vitarelli, Francesca; Moretti, Marco; Onori, Nicoletta; Giampieri, Riccardo; Rocchi, Marco Bruno Luigi; Berardi, RossanaCantini, Luca; Bastianelli, Lucia; Lupi, Alessio; Pinterpe, Giada; Pecci, Federica; Belletti, Giovanni; Stoico, Rosa; Vitarelli, Francesca; Moretti, Marco; Onori, Nicoletta; Giampieri, Riccardo; Rocchi, Marco Bruno Luigi; Berardi, Rossan

Systemic immune-inflammation index predicts the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib.

Background: In this retrospective analysis, we explored the prognostic and predictive value of the systemic immune-inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, at baseline and changes at week 6 during first-line sunitinib in patients with metastatic renal cell cancer (RCC).Results: Patients were stratified into high SII (? 730) and low SII (&lt; 730) groups. SII was associated with objective response, p &lt; 0.0001. The median PFS was 6.3 months (95% CI 5.5–8.9) in patients with SII ? 730 and 18.7 months (95% CI 14.7–22.8) in those with SII &lt; 730, p &lt; 0.0001. The median OS was 43.6 months (95% CI 35.3–52.1) in patients with SII &lt; 730, and 13.5 months (95% CI 9.8–18.5) in those with SII ? 730, p &lt; 0.0001. In multivariate analysis, performance status, IMDC score and SII were able to predict OS (HR = 3.29, HR = 1.71 and HR = 1.79, respectively).Materials and Methods: We included 335 consecutive RCC patients treated with first-line sunitinib. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion at week 6 of treatment on PFS and OS was evaluated by Cox regression analyses.Conclusions: The SII and its changes during treatment represent a powerful prognostic indicator of clinical outcome in patients with metastatic RCC

Aromatase inhibitors: the journey from the state of the art to clinical open questions

Breast cancer is a major cause of death among females. Great advances have been made in treating this disease, and aromatase inhibitors (AIs) have been recognized as the cornerstone. They are characterized by high efficacy and low toxicity. The authors reviewed the available literature and defined state-of-the-art AI management. This study was designed to assist clinicians in addressing the need to equally weigh patients’ needs and disease control rates in their everyday clinical practice. Today, AIs play a central role in the treatment of hormone receptor-positive breast cancer. In this study, an expert panel reviewed the literature on the use of AIs, discussing the evolution of their use in various aspects of breast cancer, from pre- and postmenopausal early breast cancer to metastatic breast cancer, along with their management regarding efficacy and toxicity. Given the brilliant results that have been achieved in improving survival in everyday clinical practice, clinicians need to address their concerns about therapy duration and the adverse effects they exert on bone health, the cardiovascular system, and metabolism. Currently, in addition to cancer treatment, patient engagement is crucial for improving adherence to therapy and supporting patients’ quality of life, especially in a selected subset of patients, such as those receiving an extended adjuvant or combination with targeted therapies. A description of modern technologies that contribute to this important goal is provided