Biomarkers in lung cancer.

Here we review the role of tissutal and circulating biomarkers in the management of lung cancer. In the past they were considerate quite ineffective tools as regards prognosis and prediction of treatment activity, nowadays instead, they are becoming a crucial key point as potential predictive issues in driving therapy, with possibly prognostic values as well

Treatment of lung microcytoma with neuroendocrine differentiation in elderly patient

We describe the case of a 80-year-old patient with lung microcytoma and comorbidity (diabetes, COPD and hypertensive cardiomiopaty). To manage the complexity of the elderly patient with comorbidity, he was evaluated by a Comprehensive Geriatric Assessment (CGA). Radiotherapy and chemotherapy were excluded because of the low Performance Status of the patient. A treatment with octerotide LAR was administered, allowing a good clinical benefit

The prognostic value of peripheral blood inflammatory indices early variation in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with nivolumab (Δ-Meet-URO analysis)

Background: Immunotherapy has improved the treatment landscape of mRCC pts and identifying biomarkers for patients’ selection is clinically needed. Inflammatory indices from peripheral blood showed a prognostic value in different tumors and therapies, including immunotherapy. These biomarkers are inexpensive and readily available in clinical practice. We aimed to assess the prognostic role of the dynamic evaluation of these indices in immunotherapy-naïve pretreated mRCC pts. Methods: The Meet-URO 15 multicentric retrospective study enrolled 571 pretreated mRCC pts receiving nivolumab. The Δ-Meet-URO was a secondary analysis on the early variation through the first four cycles of therapy compared with baseline (difference, delta - Δ) of white blood cells, platelets and inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII, platelets x NLR), their comparison with baseline values and correlation with treatment response, overall (OS) and progression-free survival (PFS). The baseline and Δ cut-offs were identified by ROC curves for OS. Results: The analysis was performed on 422 mRCC pts (74% of the entire cohort). Patients with ΔNeutrophils < 730 at 2nd, 3rd and 4th cycles were more responders (p < 0.001, p = 0.003 and p < 0.001) with longer mPFS (11 vs 6.1 months, p = 0.033) and mOS (46.9 vs 20.8 months, p = 0.046) compared to ΔNeutrophils ≥ 730. There was a significant interaction between baseline and ΔNeutrophils on PFS (p = 0.047). Pts with baseline neutrophils ≥ 4330/mm3 had longer mPFS when ΔNeutrophils < 730 (p = 0.002), whilst no difference was observed in those pts with baseline neutrophils < 4330/mm3 according to ΔNeutrophils (p = 0.46). Similar non-significant trends were observed in mOS. Patients with ΔNLR < 0.5 at 3rd and 4th cycles were more responders (p = 0.004 and p = 0.001, respectively) with doubled mPFS (12.1 vs 6.4 months, p = 0.007) and mOS (46.9 vs 21.7 months, p = 0.062) compared to ΔNLR ≥ 0.5. No significant interaction between baseline NLR and ΔNLR was observed in PFS and OS, suggesting a similar association between ΔNLR and PFS or OS, regardless of the baseline NLR cut-off of 3.2. The multivariable analyses confirmed all these results. Conclusions: The early assessment of NLR and neutrophils variations during immunotherapy for mRCC pts is a promising, affordable and non-invasive prognostic tool. Prospective and external validation analyses are warranted

The Geriatric G8 Score Is Associated with Survival Outcomes in Older Patients with Advanced Prostate Cancer in the ADHERE Prospective Study of the Meet-URO Network

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73–82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8–29.3) and OS 48.8 mo. (95% CI, 36.8–60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 (p < 0.001 and p = 0.004) and PSA decline ≥50% (p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only (p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only (p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care

Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies

The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study

Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era

Temporal Data Mining for the Assessment of the Costs Related to Diabetes Mellitus Pharmacological Treatment

Diabetes care and chronic disease management represent data-intensive contexts which allow Local Healthcare Agencies (ASL) to collect a huge amount of information. Time is often an essential component of such information, given the strong importance of the temporal evolution of the considered disease and of its treatment. In this paper we show the application of a temporal data mining technique to extract temporal association rules over an integrated repository including both administrative and clinical data related to a sample of diabetic patients. We will show how the method can be used to highlight cases and conditions which lead to the highest pharmaceutical costs. Considering the perspective of a Regional Healthcare Agency, this method could be properly exploited to assess the overall standards and quality of care, while lowering costs

Dietary inflammatory index and cancer risk in the elderly: A pooled-analysis of Italian case-control studies

OBJECTIVES: The aim of this study was to evaluate whether the association between the inflammatory potential of one's diet and cancer risk varies across age groups in a population characterized by widespread use of the Mediterranean diet. METHODS: We analyzed data from a network of case-control studies conducted in Italy between 1991 and 2014. The studies included cancers of the oral cavity (n = 509), pharynx (n = 436), nasopharynx (n = 198), larynx (n = 459), esophagus (n = 304), stomach (n = 230), colon (n = 1225), rectum (n = 728), liver (n = 184), pancreas (n = 326), breast (n = 2569), endometrium (n = 454), ovary (n = 1031), prostate (n = 1294), kidney (n = 767), and bladder (n = 690). Controls were 13 563 patients hospitalized for acute, non-neoplastic conditions. Dietary inflammatory index (DII) scores were computed based on 31 food parameters assessed using a reproducible and validated food frequency questionnaire. Odds ratios were estimated through logistic regression models adjusting for recognized confounding factors. RESULTS: The DII increased with age, with lower scores among men than women, in individuals located in northern rather than in central or southern Italy, and in controls more than in cancer cases. After adjustment for cancer-specific potential confounders, an increasing DII score was directly associated with cancer risk for all considered cancer sites, except for liver and endometrium. Although the DII level varied across age groups, no heterogeneity in cancer risk emerged for any of the considered cancer sites. CONCLUSIONS: In the Italian population, DII scores were higher in elderly than in middle-aged individuals. Although not directly affecting cancer risk, this finding may have important implications for the older population because elevated DII scores, indicating a proinflammatory diet, also have been associated with frailty

Patogenesi ed epidemiologia dei tumori associati all’infezione da virus di Epstein-Barr

The Epstein-Barr virus (EBV) is one of the most successful human viruses: it is ubiquitous worldwide, and more than 80% of people over the age of 30 show serological evidence of infection. In addition, EBV infection tends to be persistent, so that, once it has occurred, it remains for the lifetime, a feature that is common to many other herpesviral infections. EBV is strongly associated with the development of several cancers, in particular with Burkitt’s lymphoma, Hodgkin’s disease, and lymphoproliferative disorders which complicate immune suppression conditions. These EBV-associated neoplasms are characterized by peculiar geographic distributions and distinctive epidemiologic features.This review refers to recent advances in the mechanisms of EBV-induced cell transformation, and is focused on the main epidemiological aspects of virus-associated malignancies