The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs.

BACKGROUND: Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC). METHODS: Patients with mccRCC undergoing standard first line treatment were enrolled. Blood (12 ml) was drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) was performed on cfDNA using the Oncomine Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy findings. RESULTS: A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/µl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.008, respectively). cfDNA amount was also correlated with best response (p = 0.006). Additional cfDNA cut-points divided patients into short, intermediate and long responders, with PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p < 0.001). PFS resulted to be significantly shorter in carriers of mutant TP53 compared to not carriers (p = 0.04). Patients with high cfDNA levels and mutant TP53 have the worst PFS, while patients with low cfDNA amounts and no mutations in TP53 displayed the longest PFS (p = 0.004). CONCLUSIONS: The present study demonstrates that cfDNA and TP53 are potential predictive biomarkers of response in mccRCC to be further explored in larger and/or prospective studies.

Dedifferentiated liposarcoma: when eribulin can make the difference.

We describe the case of a male subject affected by retroperitoneal advanced, anthracycline-pretreated liposarcoma, who experienced a long, beneficial clinical effect from eribulin treatment. In March 2013, a left, paraortic, retroperitoneal mass was surgically removed and diagnosed as Mdm2-positive dedifferentiated liposarcoma. In June 2015, a CT scan revealed disease progression and first-line epirubicin/ifosfamide treatment was started, followed by epirubicin in monotherapy. In January 2017, following a new disease progression, the patient started a second-line eribulin treatment that went on for about 1 year with no major adverse events. The CT scans performed every 3-4 months showed stable disease. After 13 months of treatment, a CT scan revealed disease progression and 10 days later, the patient died of bowel perforation and peritonitis.

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC.

This corrects the article DOI: 10.1038/bjc.2017.85.

First-Line Treatments and Management of Metastatic Renal Cell Carcinoma Patients: An Italian Interdisciplinary Uro-Oncologic Group Algorithm.

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformations in recent years. The introduction of novel combination therapies involving tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors has resulted in improved oncological outcomes compared to traditional TKI monotherapy. In this evolving paradigm, the pivotal role of the multidisciplinary tumor board is underscored, particularly in shaping the therapeutic trajectory for patients eligible for locoregional interventions like cytoreductive nephrectomy and metastasectomy. In cases where systemic treatment is deemed appropriate, the absence of direct comparisons among the various combination therapies complicates the selection of a first-line approach. The clinician is faced with the challenge of making decisions based on patient-specific factors such as performance status, risk classification according to the International Metastatic Renal Cell Carcinoma Database Consortium, comorbidities, and disease characteristics, including the number and location of metastases and tumor histology. Considering these concerns, we propose, as a member of a Tuscany Interdisciplinary Uro-Oncologic Group, an algorithm to streamline the decision-making process for mRCC patients, offering guidance to clinicians in their day-to-day clinical practice.

Front-Line Therapeutic Strategy in Metastatic Hormone Sensitive Prostate Cancer: An Updated Therapeutic Algorithm.

Prostate carcinoma (PC), the second most diagnosed cancer globally, saw approximately 1,414,000 new cases in 2020, with 17% being de novo metastatic. In these cases, the 5-year relative survival rate is 32%. Metastatic hormone-sensitive prostate cancer (mHSPC) includes those with metastatic disease at initial diagnosis or after initial therapy without long-term androgen deprivation therapy (ADT), eventually progressing to castration-resistant prostate cancer (CRPC). The established therapeutic principle of ADT has persisted for 80 years, with luteinizing hormone-releasing hormone (LHRH) agonists like leuprorelin being commonly used. LHRH antagonists, such as degarelix, have also emerged. Recent advances in mHSPC treatment involve combination strategies with drugs proven effective in CRPC, considering prognostic factors like disease volume and presentation. This review outlines pivotal trials leading to drug approvals in mHSPC and proposes a treatment decision algorithm for the same, based on statement from the Tuscan Interdisciplinary Uro-Oncological Group. A multidisciplinary approach is crucial to tailor treatment intensity and weigh risks and benefits effectively.

BL-MOL-AR Project, Preliminary Results about Liquid Biopsy: Molecular Approach Experience and Research Activity in Oncological Settings.

Background Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring.

Some Concerns from a Radiological Point of View. Comment on Huang et al. Outcomes of Conversion Surgery for Metastatic Gastric Cancer Compared with In-Front Surgery Plus Palliative Chemotherapy or In-Front Surgery Alone. J. Pers. Med. 2022, 12, 555.

We read, with great interest, the article by Huang Ruo-Yi and colleagues entitled "Outcomes of Conversion Surgery for Metastatic Gastric Cancer Compared with In-Front Surgery Plus Palliative Chemotherapy or In-Front Surgery Alone", published on 1 April 2022 [...].

Predicting the spread of COVID-19 in Italy using machine learning: Do socio-economic factors matter?

We exploit the provincial variability of COVID-19 cases registered in Italy to select the territorial predictors of the pandemic. Absent an established theoretical diffusion model, we apply machine learning to isolate, among 77 potential predictors, those that minimize the out-of-sample prediction error. We first estimate the model considering cumulative cases registered before the containment measures displayed their effects (i.e. at the peak of the epidemic in March 2020), then cases registered between the peak date and when containment measures were relaxed in early June. In the first estimate, the results highlight the dominance of factors related to the intensity and interactions of economic activities. In the second, the relevance of these variables is highly reduced, suggesting mitigation of the pandemic following the lockdown of the economy. Finally, by considering cases at onset of the "second wave", we confirm that the territorial distribution of the epidemic is associated with economic factors.

Clinical and economic effect of administration of red blood product transfusions in an outpatient supportive care cancer service.

Patients with cancer may develop disease- or treatment-associated anemia, requiring red blood product transfusions. In Italy, transfusions are usually administered in a day hospital service or in inpatient wards. Since 2013, a dedicated supportive care service for outpatients has been implemented in Pisa, where red blood product transfusions are administered. The present study evaluated the patients that received red blood product transfusions at the dedicated supportive care service for outpatients in 2016. The clinical features of patients were analyzed, and the procedural cost was evaluated by comparing its administration with a hypothetical scenario in which transfusions were provided via day hospital services or inpatient wards. The results revealed that the dedicated supportive care service for outpatients avoided the hospitalization of patients, allowing them to receive prompt and timely transfusions, with a rapid resolution of symptoms. Avoiding hospitalization was also estimated to decrease transfusion-associated costs by €48,805-177,805.

Effectiveness of Multi-Prognostic Index in older patients with advanced malignancies treated with immunotherapy.

BACKGROUND: Older adults with cancer are less likely to be offered treatment for cost-benefit concern. The Multi-Prognostic Index (MPI) has been validated in various clinical settings for survival estimation. We aimed to evaluate MPI as a screening tool for older adults with cancer eligible to receive immunotherapy. PATIENTS AND METHODS: Older adults with advanced or metastatic cancer, admitted to the Oncology Day Hospital of the University Hospital of Pisa from January 2017 to May 2018, eligible to receive immunotherapy were prospectively enrolled. In addition to routine oncological evaluation, each patient received a comprehensive geriatric assessment with MPI calculation. Overall survival (Cox-adjusted curve) was stratified by tertiles of MPI score. Drug toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03: June 14, 2010). RESULTS: Seventy-nine patients [26.6% women, mean age (±SD) 74.0 ±â€¯6.1 years] were enrolled with the following diagnosis: melanoma (51.9%), non-small cell lung cancer (25.3%), renal cell cancer (12.7%), urothelial cancer (8.9%) and Merkel cell carcinoma (1.2%). Median follow-up was 7 months (range 1-35). The patients' survival rate resulted progressively longer proceeding from the first to the third MPI tertile [HR 1.76 (0.49-6.31) Vs 2nd tertile, p < 0.05; HR 5.33 (1.68-16.89) Vs 3rd tertile, p < 0.01]. CONCLUSIONS: MPI score is an effective tool for the stratification of older patients with cancer eligible for immunotherapy with checkpoint inhibitors. Further studies are required to achieve conclusive remarks on MPI usefulness in different underlying tumor types.

CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone.

BACKGROUND: Abiraterone became a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between the single nucleotide polymorphism (SNP) c.-362T>C in the CYP17A1 gene, and clinical outcome in mCRPC patients treated with abiraterone. PATIENTS AND METHODS: mCRPC patients candidate to receive abiraterone were enrolled in the present retrospective pharmacogenetic study. Based on a literature selection, CYP17A1 rs2486758 (c.-362T > C) was selected and analysed by real-time PCR on genomic DNA extracted from whole blood. Univariate analysis was performed to test the association between the SNP and treatment-related clinical outcomes. RESULTS: Sixty mCRPC patients were enrolled in the present study. Patients carrying the mutant CYP17A1 c.-362CT/CC genotypes showed a shorter median progression-free survival (PFS) and prostate-specific antigen-PFS (PSA-PFS) compared to patients carrying the TT genotype (10.7 vs 14.2 months and 8 vs 16 months, respectively; p = 0.04). No association between the selected SNP and the overall survival was found. CONCLUSIONS: These findings suggest an association between CYP17A1 c.-362T>C polymorphism and poorer clinical outcome with abiraterone for mCRPC patients. However, further validations on larger cohort of patients are needed to confirm its role as a predictive biomarker for abiraterone resistance.

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. METHODS: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options. RESULTS: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. CONCLUSION: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.