Background: A systemic immune-inflammation index (SII) based on neutrophil (N), lymphocyte (L), and platelet (P) counts has shown a prognostic impact in several solid tumors. The aim of this study is to evaluate the prognostic role of SII in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone post docetaxel.Patients and Methods: We retrospectively reviewed consecutive mCRPC patients treated with abiraterone after docetaxel in our Institutions. X-tile 3.6.1 software, cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR) defined as N/L and platelets-to-lymphocyte ratio (PLR) as P/L. Overall survival (OS) and their 95% Confidence Intervals (95% CI) was estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of SII, PLR, and NLR on overall survival (OS) was evaluated by Cox regression analyses and on prostate-specific antigen (PSA) response rates were evaluated by binary logistic regression.Results: A total of 230 mCRPC patients treated abiraterone were included. SII ≥ 535, NLR ≥ 3 and PLR ≥ 210 were considered as elevated levels (high risk groups. The median OS was 17.3 months, 21.8 months in SII < 535 group and 14.7 months in SII ≥ 535 (p < 0.0001). At univariate analysis Eastern Cooperative Oncology Group (ECOG) performance status, previous enzalutamide, visceral metastases, SII, NLR, and PLR predicted OS. In multivariate analysis, ECOG performance status, previous enzalutamide, visceral metastases, SII, and NLR remained significant predictors of OS [hazard ratio (HR) = 5.08, p < 0.0001; HR = 2.12, p = 0.009, HR = 1.77, 95% p = 0.012; HR = 1.80, p = 0.002; and HR = 1.90, p = 0.001, respectively], whereas, PLR showed a borderline ability only (HR = 1.41, p = 0.068).Conclusion: SII and NLR might represent an early and easy prognostic marker in mCRPC patients treated with abiraterone. Further studies are needed to better define their impact and role in these patients.
Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes recruited into the renal cell carcinoma (RCC) microenvironment. In response to inflammatory stimuli, macrophages undergo M1 (classical) or M2 (alternative) activation. M1 cells produce high levels of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-12, IL-23 and IL-6, while M2 cells produce anti-inflammatory cytokines, such as IL-10, thus contributing to RCC-related immune dysfunction. The presence of extensive TAM infiltration in RCC microenvironment contributes to cancer progression and metastasis by stimulating angiogenesis, tumor growth, and cellular migration and invasion. Moreover, TAMs are involved in epithelial-mesenchymal transition of RCC cancer cells and in the development of tumor resistance to targeted agents. Interestingly, macrophage autophagy seems to play an important role in RCC. Based on this scenario, TAMs represent a promising and effective target for cancer therapy in RCC. Several strategies have been proposed to suppress TAM recruitment, to deplete their number, to switch M2 TAMs into antitumor M1 phenotype and to inhibit TAM-associated molecules. In this review, we summarize current data on the essential role of TAMs in RCC angiogenesis, invasion, impaired anti-tumor immune response and development of drug resistance, thus describing the emerging TAM-centered therapies for RCC patients.
The prognosis of patients affected by metastatic renal cell carcinoma (mRCC) has improved markedly with targeted therapies. Unfortunately, 20-25% of the patients are refractory to treatment at the first response assessment and most patients will acquire drug resistance during the treatment. Moreover, current data on the clinical activity of targeted agents in poor risk or non-clear-cell mRCC patients are inconclusive because of the absence of prospective trials. Therefore, there are still several patients in need of new therapeutic approaches to improve clinical outcomes. Kidney cancer is historically considered resistant to chemotherapy on the basis that the results of phase II trials have not always been promising. We carried out a systematic review of both monochemotherapy and polychemotherapy alone or combined with immunotherapy or targeted agents in mRCC to define the state of the art and to evaluate further clinical research fields. All retrospectives, phase I/dose finding, phase II and phase III studies on chemotherapy in mRCC, published in the literature from January 2003 to November 2012, with at least 20 patients enrolled, were evaluated. Although the results of clinical trials have often been disappointing, in selected cases of mRCC, chemotherapy may have a promising antitumor activity, particularly when there are sarcomatoid differentiation features, or in highly progressive disease where the combination of doxorubicine plus gemcitabine or capecitabine has yielded interesting results. Chemotherapy may play a role in mRCC, whereas targeted agents and immunotherapy have not yielded durable and satisfactory results; further studies are needed.
It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent.
BackgroundThe potential benefits of the introduction of electronic and mobile health (mHealth) information technologies, to support the safe delivery of intravenous chemotherapy or oral anticancer therapies, could be exponential in the context of a highly integrated computerized system.ObjectiveHere we describe a safe therapy mobile (STM) system for the safe delivery of intravenous chemotherapy, and a home monitoring system for monitoring and managing toxicity and improving adherence in patients receiving oral anticancer therapies at home.MethodsThe STM system is fully integrated with the electronic oncological patient record. After the prescription of chemotherapy, specific barcodes are automatically associated with the patient and each drug, and a bedside barcode reader checks the patient, nurse, infusion bag, and drug sequence in order to trace the entire administration process, which is then entered in the patient’s record. The usability and acceptability of the system was investigated by means of a modified questionnaire administered to nurses. The home monitoring system consists of a mobile phone or tablet diary app, which allows patients to record their state of health, the medications taken, their side effects, and a Web dashboard that allows health professionals to check the patient data and monitor toxicity and treatment adherence. A built-in rule-based alarm module notifies health care professionals of critical conditions. Initially developed for chronic patients, the system has been subsequently customized in order to monitor home treatments with capecitabine or sunitinib in cancer patients (Onco-TreC).ResultsThe STM system never failed to match the patient/nurse/drug sequence association correctly, and proved to be accurate and reliable in tracing and recording the entire administration process. The questionnaires revealed that the users were generally satisfied and had a positive perception of the system’s usefulness and ease of use, and the quality of their working lives. The pilot studies with the home monitoring system with 43 chronic patients have shown that the approach is reliable and useful for clinicians and patients, but it is also necessary to pay attention to the expectations that mHealth solutions may raise in users. The Onco-TreC version has been successfully laboratory tested, and is now ready for validation.ConclusionsThe STM and Onco-TreC systems are fully integrated with our complex and composite information system, which guarantees privacy, security, interoperability, and real-time communications between patients and health professionals. They need to be validated in order to confirm their positive contribution to the safer administration of anticancer drugs.
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