Search

Aims: We performed a meta-analysis to assess the relative risk (RR) of all-grade and grade 3–4 hypertransaminasemia in studies comparing immune-based combinations with sunitinib in treatment-naive patients with advanced renal cell carcinoma. Materials & methods: Outcomes of interest included all-grade and grade 3–4 hypertransaminasemia measured as RRs and 95% confidence intervals (CIs). Results: RRs for all-grade hypertransaminasemia were 1.73 (95% CI: 1.25–2.4) and 1.63 (95% CI: 1.25–2.12) in patients receiving immunocombinations and sunitinib, respectively. The pooled RRs for grade 3–4 hypertransaminasemia were 3.24 and 3.04 in patients treated with immunocombinations or sunitinib. Conclusion: Immune-based combinations were associated with higher hypertransaminasemia risk. Physicians should pay attention to these common but overlooked events. Careful monitoring of tolerability remains a crucial need.

The reactivation of telomerase represents a key moment in the carcinogenesis process. Mutations in the central promoter region of the telomerase reverse transcriptase (TERT) gene cause telomerase reactivation in approximately 90% of solid tumors. In some of these, its prognostic and predictive role in response to treatments has already been demonstrated, in others (such as tumors of the genitourinary tract like urothelial carcinoma) data are controversial and the research is still ongoing. In the future, TERT promoter mutations and telomerase activity could have diagnostic, prognostic, and therapeutic applications in many types of cancer.We performed a review the literature with the aim of describing the current evidence on the prognostic and predictive role ofWe described the role of

Introduction: Bone metastases are the most frequent site of secondary localization of prostate cancer (PCa) and are present in about 90% of cases of advanced disease. Consequently, an adequate management of bone involvement is of pivotal importance in the therapeutic approach and skeletal-related events (SREs) need to be closely monitored and promptly assessed and treated. Bone targeting agents (BTAs), consisting in bisphosphonates and denosumab, are an essential part of the treatment of metastatic prostate cancer that accompanies systemic treatments throughout the most part of the history of the disease. Activity and safety of bone targeting agents: These treatments are correlated to better outcomes in terms of reduction of SREs and, in metastatic castration resistant setting, of increased overall survival (OS), but several important adverse events have to be managed and prevented. Of these, osteonecrosis of the jaw (ONJ) is extremely invalidating and should be managed with a special attention. Discussion: The role of BTAs in prostate cancer is pivotal throughout many stages of the disease, but several toxicities should be quickly recognized and treated. We aim at recollecting evidence on clinical benefit of BTAs, common and specific toxicities, and explore the pathophysiology and clinical aspects of osteonecrosis of the jaw. We present a review of the literature to report the role of the different types of bone targeting agents in the management of prostate cancer with bone metastases with a particular focus on common toxicities and ONJ to recollect current evidences on the activity of these compounds and the correct management of their adverse events.

Background Positron emission tomography (PET) with 18-fluorodeoxyglucose (18FDG) has proven to be highly sensitive in early assessment of tumor response in GIST, especially in cases where there is doubt, or when early prediction of the response could be clinically useful for patient management. As widely known, kinase mutations have an undoubtful predictive value for sensitivity to imatinib and the inclusion of KIT and PDGFRa mutational analysis in the diagnostic work-up of all GIST is now considered as standard practice.Case presentation Herein we detailed described a case of an exon 11 KIT mutated-metastatic GIST patient, who presented an unexpected metabolic progression at the early 18FDG-PET evaluation after one month of first line imatinib, unconfirmed at the liver biopsy performed near after, which has conversely shown a complete pathological response.Conclusions This report aims to be aware of the existence of this metabolic pseudoprogression in GIST at the beginning of imatinib therapy, in order to avoid early treatment discontinuation. Therefore, an early metabolic progression during a molecular-targeted therapy always deserves to be evaluated in the context of the disease molecular profiling and in case of discordant finding between functional imaging and molecular background, a short-term longitudinal control should be suggested.

In recent years, the advances in the knowledge on the molecular characteristics of prostate cancer is allowing to explore novel treatment scenarios. Furthermore, technological discoveries are widening diagnostic and treatment weapons at the clinician disposal. Among these, great relevance is being gained by PARP inhibitors and radiometabolic approaches. The result is that DNA repair genes need to be altered in a high percentage of patients with metastatic prostate cancer, making these patients optimal candidates for PARP inhibitors. These compounds have already been proved to be active in pretreated patients and are currently being investigated in other settings. Radiometabolic approaches combine specific prostate cancer cell ligands to radioactive particles, thus allowing to deliver cytotoxic radiations in cancer cells. Among these, radium-223 and lutetium-177 have shown promising activity in metastatic pretreated prostate cancer patients and further studies are ongoing to expand the applications of this therapeutic approach. In addition, nuclear medicine techniques also have an important diagnostic role in prostate cancer. Herein, we report the state of the art on the knowledge on PARP inhibitors and radiometabolic approaches in advanced prostate cancer and present ongoing clinical trials that will hopefully expand these two treatment fields.

Urothelial carcinoma (UC) is a frequently diagnosed tumor and an important cause of cancer deaths worldwide. Until a few years ago, despite the unquestioned role of platinum-based chemotherapy, therapeutic choices beyond the first line were limited and related to unsatisfactory outcomes. Metastatic UC has always been associated with a poor prognosis, with overall survival only slightly above a year. In the recent past, huge progress has been made in our understanding of the molecular and genomic disease characteristics, to enable stratification of patients in terms of prognosis and treatment responses. Unfortunately, we still do not have the perfect combination of clinical biomarkers to tailor the optimal treatment for each patient, despite making several efforts in this direction. The therapeutic arsenal has been augmented by immune checkpoint inhibitors (ICIs), which nowadays represent the backbone of the second-line setting. Equally revolutionary was the FDA's approval of erdafitinib, a potent fibroblast growth factor receptor (FGFR) inhibitor, the use of which is reserved for patients whose tumor harbors specific FGF pathway alterations. Recently, the therapeutic landscape of metastatic UC has been enhanced by the introduction of novel compounds, consisting of antibody-drug conjugates (ADCs). Enfortumab vedotin is an antibody targeting nectin-4, a cell adhesion molecule highly expressed in UC, conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent. Sacituzumab govitecan is a humanized monoclonal antibody targeting Trop-2, a transmembrane glycoprotein, conjugated to the active metabolite of irinotecan. These two compounds have received accelerated approval by the FDA in patients pretreated with platinum-based chemotherapy and immunotherapy. Several ongoing trials are investigating the role of ICIs combined with chemotherapy, antiangiogenic drugs, or other ICIs, as well as the efficacy of PARP inhibitors and target therapies, hoping to provide information for some important unmet needs. In this review, we aim to evaluate the current potential treatment options after first-line chemotherapy.

Background: High-grade neuroendocrine carcinoma (NEC) is a rare and aggressive variant of bladder cancer. Considering its rarity, its therapeutic management is challenging and not standardized. Methods: We analyzed data extracted from the Surveillance, Epidemiology, and End Results (SEER) registry to evaluate prognostic factors for high-grade NEC of the bladder. Results: We extracted data on 1134 patients: 77.6% were small cell NEC, 14.6% were NEC, 5.5% were mixed neuro-endocrine non-neuroendocrine neoplasia, and 2.3% were large cell NEC. The stage at diagnosis was localized for 45% of patients, lymph nodal disease (N+M0) for 9.2% of patients, and metastatic disease for 26.1% of patients. The median overall survival (OS) was 12 months. Multivariate analysis detected that factors associated with worse OS were age being >72 years old (HR 1.94), lymph nodal involvement (HR 2.01), metastatic disease (HR 2.04), and the size of the primary tumor being >44.5 mm (HR 1.80). In the N0M0 populations, the size of the primary tumor being

Background: An acceptable risk-benefit ratio may encourage the prescription of immune checkpoint inhibitors (ICI) near the late stage of life. The lung immune prognostic index (LIPI) was validated in advanced non-small cell lung cancer (NSCLC) patients treated with ICIs. The palliative prognostic (PaP) score without clinical prediction of survival (PaPwCPS) predicts early mortality probability in terminal cancer patients. Methods: We performed a retrospective study including 182 deceased advanced NSCLC patients, treated with single-agent ICI at our Institution. Two prognostic categories of high and low mortality risk were identified through ROC curve analysis for PaPwCPS and LIPI scores. Results: Most were >65 years of age (68.3%) and received second-line ICI (61.2%). A total of 29 (15.9%) and 131 (72.0%) patients died within 30 and 90 days from treatment start, respectively. A total of 81 patients (44.5%) received ICI during the last month of life. Baseline PaPwCPS and LIPI scores were assessable for 78 patients. The AUC of ROC curves was significantly increased for PaPwCPS as compared with LIPI score for both 30-day and 90-day mortality. A high PaPwCPS score was associated in multivariate analysis with increased 30-day (HR 2.69, p = 0.037) and 90-day (HR 4.01, p < 0.001) mortality risk. A high LIPI score was associated with increased 90-day mortality risk (p < 0.001). Conclusion: We found a tendency towards ICI prescription near the late stage of life. The PaPwCPS score was a reliable predictor of 30- and 90-day mortality.

Background: Adjuvant treatment has always been a cornerstone in the therapeutic approach of many cancers, considering its role in reducing the risk of relapse and, in some cases, increasing overall survival. Adjuvant immune checkpoint inhibitors have been tested in different malignancies. Methods: We performed a meta-analysis aimed to explore the impact of adjuvant PD-1 and PD-L1 inhibitors on relapse-free survival (RFS) in cancer patients enrolled in randomized controlled clinical trials. We retrieved all phase III trials published from 15 June 2008 to 15 May 2022, evaluating PD-1/PD-L1 inhibitors monotherapy as an adjuvant treatment by searching on EMBASE, Cochrane Library, and PubMed/ Medline, and international oncological meetings’ abstracts. The outcome of interest was RFS. We also performed subgroup analyses focused on age and gender. Results: Overall, 8 studies, involving more than 6000 patients, were included in the analysis. The pooled results highlighted that the use of adjuvant PD-1/PD-L1 inhibitors may reduce the risk of relapse compared to control treatments (hazard ratio, 0.72; 95% confidence intervals, 0.67–0.78). In addition, the subgroup analyses observed that this benefit was consistent in different patient populations, including male, female, younger, and older patients. Conclusions: Adjuvant anti-PD-1/PD-L1 treatment is associated with an increased RFS in the overall population and in subgroups divided according to age and gender.

The therapeutic scenario of urothelial carcinoma is constantly expanding with the widening of the knowledge on molecular characteristics, thus claiming for the need of prognostic and predictive factors to guide treatment strategy. TERT promoter mutation is one of the most frequent genomic alterations in urothelial carcinoma and could present several implications, from diagnostic to prognostic or potentially even predictive.We performed a single-center retrospective analysis on patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor as second line of therapy to assess the status of the TERT promoter and the potential implication of its mutation on survival outcomes.We analyzed tissue samples from 11 patients with a next-generation sequencing multi-gene panel. The most frequently altered genes were TP53 (54.5%, n = 6) and TERT promoter (36.3%, n = 4). Other mutations found were BRAF, SMAD4, PIK3CA / PDGRFA. The only type of detected TERT promoter mutation was the c 0.124 CT (n = 4/4, 100%). Of the 4 TERT mutated patients, 2 presented a co-mutation of TP53. Patients with TERT promoter mutation treated with immunotherapy presented a low median overall survival (16.5 months) and progression-free survival (3.8 months).Our hypothesis-generating analysis suggests that the presence of TERT promoter mutation could have a negative prognostic value and should be further evaluated in wider cohorts.

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.

Renal cell carcinoma (RCC) scenario has radically changed with the advent of immunotherapy; in this setting, the identification of predictive and prognostic factors represents an urgent clinical need to evaluate which patients are the best candidate for an immunotherapy approach. The aim of our study was to analyze the association between nivolumab in pretreated patients with metastatic RCC and clinicopathological features, metastatic sites, and clinical outcomes. A total of 37 patients treated between January 2017 and April 2020 in our institution were retrospectively evaluated. All patients received nivolumab as second- or later-line of therapy after progression on previous tyrosine kinase inhibitors. The primary outcomes were overall survival (OS) from immunotherapy start and OS from first-line start. Univariate analysis was performed through the log-rank test and a Cox regression proportional hazards model was employed in multivariable analysis. Of the 12 variables analyzed, 4 were significantly associated with prognoses at multivariate analysis. Cox proportional hazard ratio models confirmed that International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk group, liver metastases at diagnosis, and central nervous system (CNS) metastases at diagnosis were associated with worse OS with an estimated hazard ratio of 4.76 [95% confidence interval (CI), 2.05-19.8] for liver metastases and 2.27 (95% CI, 1.13-28.9) for CNS metastases. Pancreatic metastases at diagnosis were correlated to a better prognosis with an estimated hazard ratio of 0.15 (95% CI, 0.02-0.38). IMDC risk group, liver metastases at diagnosis, and CNS metastases at diagnosis may identify a population of patients treated with immunotherapy in second- or later-line associated with worse prognosis.