Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

The prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic targeted therapy. However, it is still unclear which biological processes underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans aggregated into diagnostic scores correlated with ccRCC prognosis.Thirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous (Low vs. High) or a continuous variable in a multivariate survival analysis.The survival difference between High vs. Low-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3% vs. 100%, p = 310-4 and 2-year OS rate = 73.3% vs. 100%, p = 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60% vs. 84%, p = 0.0591 and 2-year OS rate = 66.7% vs. 90%, p = 0.0206). In multivariate analysis, the urine biomarker score was an independent predictor of PFS (HR: 4.62, 95% CI: 1.66 to 12.83, p = 0.003) and OS (HR: 10.13, 95% CI: 1.80 to 57.04, p = 0.009).This is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted

Prognostic and predictive role of miRNAs, CTCs AND AR-V7+ CTCs expression in advanced prostate cancer treated with new hormonal agents: a feasibility study

Background. Circulating tumor cells (CTC) counts of 5 or more/7.5 mL predict shorter survival in men with mCRPC. Moreover, the presence of androgen receptor splice variant-7 mRNA (AR-V7) in CTCs is thought to play a relevant role in the development of primary or acquired resistance to enzalutamide or abiraterone. MiRNAs, small endogenous mRNA, have been identified as associated to the presence and aggressiveness of prostate cancer and for instance, overexpression of some miRNAs contributes to resistance to docetaxel and cabazitaxel. We developed a new immunofluorescence-based assay for AR-V7 expression in CTCs and tested its prognostic association with PFS and OS. Co-primary aims are to investigate AR-V7 with a new integrated assay and to study role of miRNAs in mCRPC patients treated with abiraterone or enzalutamide, and to study the relationship between AR-V7 expression, CTCs, and miRNAs with PFS or OS. Methods. We performed a single-centre, observational, prospective trial enrolling patients with mCRPC candidate to receive enzalutamide or abiraterone. CTC samples have been collected at baseline, after 1 month and every three months thereafter until progression or at 12 months without progression. CTCs have been enumerated with CellSearch System. We integrated the standard assay with a monoclonal antibody able to recognize the AR-V7 protein. Slides created from pts’ samples underwent automated immunofluorescent staining and AR-V7+ CTCs were enumerated. MiRNAs have been evaluated at the same time point. Results. Since Sep 2016, 31 patients have been enrolled. We compared CTC counts between standard assay and the integrated assay and found no statistical differences in the mean total CTC number ± SD (Wilcoxon Signed Rank test, p= 0.313). 4 Sixteen out of 28 evaluable patients (57%) had 1 or more CTCs at baseline, 9 pts (32%) had more than 5 CTCs/7.5 ml, and 4 pts (14.3%) were AR-V7+ before any exposure to abiraterone or enzalutamide. After a median follow-up time of 8.1 months, 6 patients have progressed and 4 have died. No association has been found between CTCs ≥ 5/7.5 mL and survival. The presence of at least one AR-V7+ CTC at baseline did not correlate with PSA response, but had a weak association with shorter PFS (log-rank test, p = 0.055) and a statistically significant impact (p = 0.02) on OS. MiRNA failed in this analysis to correlate with survival outcome. Conclusion. We developed a new integrated assay for detecting AR-V7+ CTCs, based on an automated platform that permits serial sampling with low inter- and intra-test variability. The clinical utility of this test in anticipating the resistance to abiraterone or enzalutamide is under study

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 (< 730) groups. SII was associated with objective response, p < 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 < 730, p < 0.0001. The median OS was 43.6 months (95% CI 35.3–52.1) in patients with SII < 730, and 13.5 months (95% CI 9.8–18.5) in those with SII ? 730, p < 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

The Role of Fast and Deep PSA Response in Castration-sensitive Prostate Cancer

Background: Outcomes of castration-sensitive prostate cancer (CSPC) have improved owing to new therapies and early treatment, previously reserved for castration-resistant disease (CRPC). Prostatic-specific antigen (PSA) remains the most used marker to follow-up patients under treatment, but only limited data are available about the prognostic role of its changes over time and the impact of response to subsequent therapies. This analysis aims to assess the prognostic role of the magnitude and velocity of PSA response in CSPC and describe how this may affect the outcome to subsequent treatment outcomes in CRPC. Patients and methods: A retrospective analysis was performed on patients with de novo CSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. PSA response (PSA50), defined as a decrease > 50% compared to baseline, PSA velocity (PSAv), defined as any decrease in PSA levels over time and the deep and fast PSA response (4mPSA50), defined as the PSA response reached within the threshold of 4 months from the beginning of androgen deprivation therapy (ADT) have been evaluated for their impact on survival. Survivals were estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional-hazard models, stratified according to baseline characteristics, were used to estimate hazard ratios for overall survival (OS). Results: A totals of 94.4% of patients had PSA50, which was correlated to longer OS compared to patients without PSA50 (56.0 vs. 14.8 months; p<0.001). The median PSAv was 6.9 (ng/dl)/month, which was predictive for longer OS: Each decrease of 1 (ng/dl)/month was able to improve OS by 0.2% (HR=0.998, 95%CI=0.997-1.000; p=0.008). A total of 47.9% of patients reached 4mPSA50, with a median OS and progression-free survival (PFS) to ADT-based therapy of 101.0 and 23.4 months compared to 41.9 and 11.0 months for those who did not (p<0.001), respectively. The independent prognostic role of 4mPSA50 was retained even when evaluated in multivariable analysis adjusted for other baseline characteristics and early docetaxel for CSPC. In CRPC, 4mPSA50 evaluated during CSPC retains its prognostic role even if it does not predict a different outcome between patients treated with abiraterone/enzalutamide or taxanes. Conclusion: Achieving a deep and fast PSA response correlates with a better outcome in patients with de novo mCSPC, also positively influencing the prognosis of the subsequent first-line therapy for CRPC disease

Risk factors behind the increase of early-onset cancer in Italian adolescents and young adults: An investigation from the Italian AYA Working group

: The incidence of early-onset cancers in adolescents and young adults (AYA) has been increasing worldwide since the 1990s. In Italy, a significant increased rate of 1.6 % per year has been reported for early-onset cancers among females between 2008 and 2016. This is mainly attributable to melanoma, thyroid, breast and endometrial cancer. The aim of our work was to describe temporal trends of the main established lifestyle risk factors (tobacco use, alcohol consumption, obesity, physical inactivity, dietary westernization and reproductive factors) over the last 20 years in the Italian AYA population. Available data on behavioural risk factors, individual and household daily life have been obtained and elaborated from PASSI, ISTAT and Eurostat reports. Lowering age of smoking initiation, an increase in alcohol drinkers among young females, and an obesity and overweight epidemic, particularly among children and adolescents as a result of physical inactivity and dietary habits, may be contributing factors behind this cancer epidemic, especially among females. In-depth investigations are needed to understand the exact role of each contributing factor, the effects of exposure to nicotine-containing products and environmental factors such as endocrine disruptors that could play a role in this phenomenon

Communication in oncology between health care providers, patients, the scietntific community, and the media: recommendations from the Italian Association of Medical Oncology (AIOM)

Aim: To identify barriers between health and communication in oncology in order to promote the best possible practice. The areas of communication to be focused on are communication directly with the patient, communication within the scientific community, and communication with the media. Material and methods: A working group including eminent experts from the national mass media, healthcare system, and patients' advocacy has been established on behalf of the Italian Association of Medical Oncology (AIOM), with the aim of developing suitable recommendations for the best communication in oncology. A literature search has been conducted selecting primary studies related to the best practices applied to communication in oncology. Subsequent to having identified the most representative statements, through a consensus conference using the RAND/University of California Los Angeles modified Delphi method, the panel evaluated the relevance of each statement to support useful strategies to develop effective communication between oncologist physicians and patients, communication within the scientific community, and communication with media outlets, including social media. Results: A total of 292 statements have been extracted from 100 articles. Following an evaluation of relevance, it was found that among the 142 statements achieving the highest scores, 30 of these have been considered of particular interest by the panel. Conclusions: This consensus and the arising document represent an attempt to strengthen the strategic alliance between key figures in communication, identifying high-impact recommendations for the management of communication in oncology with respect to patients, the wider scientific community, and the media

Ethical issues in communication in a tertiary oncology center: exploratory survey

BackgroundDespite evidence of its importance, communication in oncology remains a critical challenge, especially in case of bad news. The doctor-patient relationship is often strained by time limitations, emotional challenges, and cultural or ethical dilemmas surrounding end-of-life discussions. This study examines barriers to effective communication at the Veneto Institute of Oncology (IOV), focusing on time constraints and emotional difficulties in clinical practice. It aims to identify factors hindering timely and effective discussions on bad news and end-of-life issues, the primary participants in such conversations, and reasons for delays in addressing sensitive topics.Materials and methodsAn anonymous questionnaire was completed by 43 attending physicians from Oncology and Haemato-oncology departments at the IOV, with 69.8% of the respondents being women. The majority of the respondents were under 40 years of age. Data on demographics, roles, and communication practices were analysed to identify behavioral patterns.ResultsMost respondents (65.1%) prioritized communicating bad news to patients rather than caregivers. Time constraints were the most reported barrier (40%), followed by emotional distress, fear of demotivating patients, and insufficient training. Despite challenges, 76.7% felt confident in shared decision-making with patients.ConclusionThe study highlights the need for structured communication training and better resources to address time and emotional barriers, to enhance patient autonomy and to reinforce doctor-patient relationships in end-of-life care

Prognostic value of normal sodium levels in patients with metastatic renal cell carcinoma receiving tyrosine kinase inhibitors

Background: Although serum sodium concentration, particularly hyponatremia, has been shown to be a prognostic marker of survival in metastatic renal cell carcinoma (mRCC), the impact of normal sodium levels has not been investigated. Herein, we investigate the influence of normonatremia in mRCC patients treated with tyrosine kinase inhibitors (TKIs). Materials and methods: For this retrospective study, the clinical and biochemical data of patients treated with first-line TKIs for mRCC were available from seven Italian cancer centers. We collected natremia levels at baseline and first evaluation after treatment excluding patients with sodium levels outside the normal range (<135 or >145 mEq/L). The remaining patients were subdivided into two groups according to the median sodium value: natremia patients with <140 mEq/L (n = 132) and baseline natremia patients with ≥140 mEq/L (n = 185). Subsequently, we analyzed the impact of sodium levels on response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). PFS and OS were estimated through the Kaplan–Meier method, and differences between groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were applied to evaluate the prognostic factors for PFS and OS. Results: Of the 368 patients, 317 were included in the analysis, 73.1% were men, and the median age was 67 years (range 36–89). When comparing patients with baseline natremia ≥140 mEq/L (n = 185) to patients with natremia <140 mEq/L (n = 132), the PFS was 15 vs. 10 months (p < 0.01) and the OS was 63 vs. 36 months, respectively (p = 0.02). On the first evaluation, patients with serum sodium ≥140 mEq/L had longer PFS (15 vs. 10 months, p < 0.01) and OS (70 vs. 32 months, p < 0.01) than patients with levels <140 mEq/L. Moreover, clinical outcomes showed a significant improvement in patients with natremia ≥140 mEq/L compared with patients with levels <140 mEq/L both at baseline and first evaluation: PFS was 19 vs. 11 months (p < 0.01) and OS was 70 vs. 36 months (p < 0.01), respectively. Conclusions: To the best of our knowledge, this is the first study to investigate the impact of normonatremia in mRCC. We found that serum sodium levels <140 mEq/L at baseline and first assessment are independently associated with worse PFS and OS in mRCC patients treated with TKIs in the first-line setting

Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib

Background: The addition of neutrophil-to-lymphocyte ratio (NLR) and bone metastases to the International Metastatic RCC Database Consortium (IMDC) score (by the Meet-URO score) has been shown to better stratify pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. This study aimed to validate the Meet-URO score in patients receiving cabozantinib to assess its predictivity and prognostic role. Methods: A multicenter retrospective analysis evaluated mRCC patients receiving ⩾second-line cabozantinib. NLR, IMDC score and bone metastases were assessed before the start of cabozantinib. The primary endpoint was overall survival (OS). Harrell's c-index was calculated to compare the accuracy of the prediction of the two scores. Results: Overall, 174 mRCC patients received cabozantinib as second and third line (51.7% and 48.3%, respectively) with a median follow-up of 6.8 months. A shorter median overall survival (mOS) was observed for the IMDC poor-risk group, NLR ⩾3.2 and the presence of bone metastases, while the IMDC intermediate-risk group had a similar mOS to the favourable-risk one. Applying the Meet-URO score, three risk groups were identified: group 1 (55.2% of patients) with a score of 0-3, group 2 (38.5%) with a score of 4-8 and group 3 (6.3%) with a score of 9. Compared to group 1 (mOS: 39.4 months), a statistically significant worse mOS was observed in group 2 (11.2 months) and group 3 (3.2 months) patients, respectively. The Meet-URO c-index score was 0.640, showing a higher discriminative ability than the IMDC score (c-index: 0.568). Conclusion: This analysis showed that the Meet-URO score provides a more accurate prognostic stratification than the IMDC score in mRCC patients treated with ⩾second-line cabozantinib besides nivolumab. Moreover, it is an easy-to-use tool with no additional costs for clinical practice (web-calculator is available at: https://proviso.shinyapps.io/Meet-URO15_score/). Future investigations will include the application of the Meet-URO score to the first-line immunotherapy-based combination therapies