Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b)

Background: Immune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO. Methods: 287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan–Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model. Results: 246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9–5.7) vs 3.7 months (95%CI 1.9–5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15; p = 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6–24.1) vs 13 months (95%CI 7.7–18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755; p = 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958). Conclusions: IO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice

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

The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis

Background: Treatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors. Methods: By a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs. Results: The analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p &lt; 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction &lt;0.001), higher baseline IR values (NLR: p = 0.012, SII: p = 0.003, PLR: p = 0.003), increasing NLR and systemic immune-inflammatory index (SII) (i.e., NLR x platelets) Δ (p for interaction time-group = 0.0053 and 0.0435, respectively) were associated with disease progression. OS and PFS were significantly shorter in patients with baseline lower lymphocytes (p &lt; 0.001 for both) and higher platelets (p = 0.004 and p &lt; 0.001, respectively) alongside early neutrophils Δ (p = 0.046 and p = 0.033, respectively). Early neutrophils and NLR Δ were independent prognostic factors for both OS (p = 0.014 and p = 0.011, respectively) and PFS (p = 0.023 and p = 0.001, respectively), alongside baseline NLR (p &lt; 0.001 for both) and other known prognostic variables. Conclusions: Early neutrophils and NLR Δ may represent new dynamic prognostic factors with clinical utility for on-treatment decisions

IMPACT OF DIFFERENT DOSING STRATEGIES OF NIVOLUMAB IN PATIENTS WITH SOLID TUMORS: ITALIAN SINGLE CENTER ANALYSIS

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Prognostic role of neuroendocrine differentiation in prostate cancer, putting together the pieces of the puzzle

Neuroendocrine (NE) differentiation is a common feature in prostate cancer (PC). The clinical significance of this phenomenon is controversial; however preclinical and clinical data are in favor of an association with poor prognosis and early onset of a castrate resistant status. NE PC cells do not proliferate, but they can stimulate the proliferation of the exocrine component through the production of paracrine growth factors. The same paracrine signals may favor the outgrowth of castrate adapted tumors through androgen receptor dependent or independent mechanisms. Noteworthy, NE differentiation in PC is not a stable phenotype, being stimulated by several agents including androgen deprivation therapy, radiation therapy, and chemotherapy. The proportion of NE positive PC, therefore, is destined to increase during the natural history of the disease. This may complicate the assessment of the prognostic significance of this phenomenon. The majority of clinical studies have shown a significant correlation between NE differentiation and disease prognosis, confirming the preclinical rationale. In conclusion the NE phenotype is a prognostic parameter in PC. Whether this phenomenon is a pure prognostic factor or whether it can influence the prognosis by favoring the onset of a castrate resistance status is a matter of future research. © 2010 Berruti et al

Fungal deterioration of medieval wall fresco determined by analysing small fragments containing copper.

A medieval fresco at the Chapel of the Holy nail, Siena was analysed to determine microbiological causes of deterioration of the painted surface or fresco micro-layer. Fragments of fresco a few mm wide were sampled under sterile conditions and some were incubated in mineral medium to isolate microbial species growing on endogenous carbon sources. Quiescent spores of fungi were detected. After 18 h fungal hyphae grew from turgid spores and pH dropped from 5.5 to 5.0, suggesting organic acid production during growth. Light microscopy (LM) and transmission electron microscopy (TEM) were used to study the ultrastructure of the fungi. Molecular studies involving sequencing 18S rDNA led to identification of Penicillium crysogenum. Element concentrations in the painted layer were analysed by scanning electron microscopy (SEM) with energy dispersive X-ray microanalysis of the fresco micro-layer before and after incubation of fragments. The main finding was that total carbon decreased from 26% to 13% while copper increased from 5% to 28%. The high concentration of copper and the acid pH inhibiting bacterial proliferation, indicated P. crysogenum as the main agent of deterioration. Hypotheses are formulated with regard to the high concentrations of copper useful for conservation of fresco substrates. © 2005 Elsevier Ltd. All rights reserved