BackgroundReceptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG.Materials and MethodsWe examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival.ResultsMicroarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that “RANK-negative” and “RANK-positive” patients had a SDFS of 105.7 months (95% CI: 73.9–124.4) and 58.9 months (95% CI: 34.7–68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029).ConclusionsThis is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.
Purpose: Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy.Experimental Design: A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil-to-lymphocyte ratio (NLR) ! 3, systemic immune inflammation index (SII) ! 1,375, and platelet-tolymphocyte ratio (PLR) ! 232. Patients were classified as high BMI (!25 kg/m 2 ) versus normal BMI (<25 kg/m 2 ).Results: Among 313 evaluable patients, 235 (75.1%) were male, and median age was 65 years (range, 40-84 years), with 105 (33.69%) !70 years. In univariate analysis, age, performance status, BMI, SII, NLR, and PLR were able to predict outcome. In multivariate analyses, SII !1,375, BMI <25 kg/m 2 , and age !70 years independently predicted overall survival [OS; HR ¼ 2.96, 95% confidence interval (CI), 2.05-4.27; HR ¼ 1.59, 95% CI, 1.10-2.30; and HR ¼ 1.65, 95% CI, 1.07-2.55, respectively). A patient with both SII !1,375 and BMI <25 kg/m 2 was estimated to have much worse OS (HR, 3.37; 95% CI, 2.29-4.95; P <0.0001) than a patient with neither or only one risk factor. SII changes at 3 months predicted OS (P <0.0001).Conclusions: Normal BMI combined with inflammation tripled the risk of death, suggesting that these biomarkers are critical prognostic factors for OS in patients with RCC treated with nivolumab.Four groups of SII changes: (i) low-low (baseline SII < 1,375 and follow-up SII < 1,375); (ii) low-high (baseline SII < 1,375 and follow-up SII ! 1,375); (iii) high-low (baseline SII ! 1,375 and follow-up SII < 1,375); and (iv) high-high (baseline SII ! 1,375 and follow-up SII ! 1,375).De Giorgi et al.
word count: 244. Abstract:The novel severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) pandemic is a global health problem, which started to affect China by the end of year 2019. In Europe, Italy has faced this novel disease entity (named COVID-19) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits, and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during pandemic. Acknowledgments:We thank all the CIPOMO members for participating in the present survey, thereby making this work possible to be shared in the oncologists' community.Fundings: no funding was obtained for the present investigation.
To evaluate diagnostic performance of endorectal magnetic resonance (eMR) for diagnosing local recurrence of prostate cancer (PC) in patients with previous radical prostatectomy (RP) and to assess whether contrast-enhanced (CE)-eMR improved diagnostic accuracy in comparison to unenhanced study. Unenhanced eMR data of 72 male patients (mean of total PSA: 1.23 +/- 1.3 ng/ml) with previous RP were interpreted retrospectively and classified either as normal or suspicious for local recurrence. All eMR examinations were re-evaluated also on CE-eMR 4 months after the first reading. Images were acquired on a 1.5-T system. These data were compared to the standard of reference for local recurrence: prostatectomy bed biopsy results; choline positron emission tomography results; PSA reduction or increase after pelvic radiotherapy; PSA modification during active surveillance. Sensitivity, specificity, predictive positive value, negative predictive value and accuracy were 61.4%, 82.1%, 84.4%, 57.5% and 69.4% for unenhanced eMR and 84.1%, 89.3%, 92.5%, 78.1% and 86.1% for CE-eMR. A statistically significant difference was found between accuracy and sensitivity of the two evaluations (chi(2) = 5.33; p = 0.02 and chi(2) = 9.00; p = 0.0027). EMR had great accuracy for visualizing local recurrence of PC after RP. CE-eMR improved diagnostic performance in comparison with T2-weighted imaging alone.
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