Evaluation of RAS mutational status through BEAMing assay to monitor disease progression of metastatic colorectal cancer: a case report.

Since the introduction of antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies (moAbs), the treatment of metastatic colorectal cancer (mCRC) has become crucially dependent on the mutation profile of the tumour over the last two decades. Recently, rechallenge strategy with cetuximab-based chemotherapy has demonstrated to be active in a subgroup of patients whose tumour maintained wild-type RAS and RAF status. In this setting, liquid biopsy may replace tissue sample for the identification of specific subgroups of pretreated patients that may benefit from the reintroduction of anti-EGFR moAbs. In November 2014, a 64-year-old man with IVB stage BRAF, KRAS and NRAS wild-type mCRC was admitted in our hospital. He received FOLFIRI cetuximab as first-line treatment with deep and long-lasting partial response (PR), followed by cetuximab maintenance therapy until January 2016. At the time of disease progression, FOLFIRI cetuximab regimen was reintroduced resulting in stabilization of disease and he continued with capecitabine cetuximab therapy until disease progression in October 2016. Then, the patient consecutively received FOLFOX bevacizumab, TAS-102, regorafenib and FOLFIRI followed by de Gramont maintenance treatment. Finally, he was retreated with FOLFIRI cetuximab with disease progression within 3 months and died in May 2019. During his clinical course, liquid biopsy detected two mutations: one in KRAS Cd.12 and one in NRAS Cd. 61. The longitudinal assessment of RAS status offers considerable advantages in order to avoid side effects and economic costs for ineffective treatment choices. Liquid biopsy could help better monitor the disease and provide molecularly guided treatments.

Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective.

Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAbs) or a multi-target vascular endothelial growth factor-(VEGF) tyrosine kinase inhibitor (TKI). In this paper, we review the main evidence on the use of Immune Checkpoint Inhibitors (ICIs) for RCC treatment from the first demonstration of activity of a nivolumab single agent in a phase I trial to the novel combination strategies (anti-PD-1 plus anti-CTLA4 or anti-PD-1 plus TKI). In addition, we discuss the use of anti-PD-1/PD-L1 agents in patients with non-clear cells and rare histological subtype RCC. Then, we critically examine the current findings in biomarkers that have been proposed to be prognostic or predictive to the response of immunotherapy including immune gene expression signature, B7-H1 expression, PBRM1 loss of function, PD-L1 expression, frame shift indel count, mutations in bromodomain-containing genes in patients with MiT family translocation RCC (tRCC), high expression of the T-effector gene signature, and a high myeloid inflammation gene expression pattern. To date, a single biomarker as a predictor of response has not been established. Since the dynamic behavior of the immune response and the different impact of ICI treatment on patients with specific RCC subtypes, the integration of multiple biomarkers and further validation in clinical trials are needed.

Bone Metastases in Renal Cell Carcinoma: Impact of Immunotherapy on Survival.

Background/Aim: We performed a multicenter retrospective observational study to investigate the impact of immune checkpoint inhibitors (ICIs) on the survival of patients with bone metastases (BMs) from renal cell cancer (RCC). Patients and Methods: A total of 98 patients with metastatic RCC (mRCC) treated with ICIs were retrospectively enrolled. All patients received standard treatments with nivolumab alone or in combination with ipilimumab from December 2015 to March 2022. The primary endpoint was median overall survival (OS). Results: Forty-three patients (44%) had radiological evidence of BMs. No statistically significant difference in OS was reported between the BM population and the entire population (p=0.254). Conclusion: Our study suggests some degree of ICI activity to treat patients with BMs from RCC, historically associated with a poorer prognosis.

Robotic approach with neoadjuvant chemotherapy in adult Wilms' tumor: A feasibility study report and a systematic review of the literature.

Objective: The incidence of Wilms' tumor (WT) among adult individuals accounts for less than 1% of kidney cancer cases, with a prognosis usually less favorable when compared to younger individuals and an overall survival rate of 70% for the adult patients versus 90% for the pediatric cases. The diagnosis and treatment of WT are complex in the preoperative setting; neoadjuvant chemotherapy (NAC) or robotic surgery has rarely been described. This study aimed to review the literature of robotic surgery in WT and report the first adult WT management using both NAC and robotic strategy. Methods: We reported a case of WT managed in a multidisciplinary setting. Furthermore, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations, a systematic review of the literature until August 2020 of WT treated with a robotic approach was carried out. Results: A 33-year-old female had a diagnosis of WT. She was scheduled to NAC, and according to the clinical and radiological response to a robotic radical nephrectomy with aortic lymph nodes dissection, she was managed with no intraoperative rupture, a favorable surgical outcome, and a follow-up of 25 months, which did not show any recurrence. The systematic review identified a total number of 230 cases of minimally invasive surgery reported in the literature for WT. Of these, approximately 15 patients were carried out using robotic surgery in adolescents while none in adults. Moreover, NAC has not been administered before minimally invasive surgery in adults up until now. Conclusion: WT is a rare condition in adults with only a few cases treated with either NAC or minimally invasive approach so far. The advantage of NAC followed by the robotic approach could lead to favorable outcomes in this complex scenario. Notwithstanding, additional cases of adult WT need to be identified and investigated to improve the oncological outcome.

Immune checkpoint inhibitor-induced neurologic toxicity: a case report and literature review.

Immune checkpoint inhibitors (ICIs) are approved for the treatment of head and neck carcinoma. They have significantly improved survival in these patients but may cause immune-related adverse events (irAEs), some of which may be serious. The report presents a rare case of a neurologic adverse event associated with programmed death-1 inhibitor monotherapy. Neurologic irAEs (NirAEs) can occur in various and atypical forms, be potentially disabling and occur at various times during and after treatment. Prompt identification and drug withdrawal are essential to improve outcomes. A high dose of systemic corticosteroid has been recommended for the management of NirAEs, although optimal immunomodulatory treatment is still debated.

Current recommendations for head and neck squamous cell carcinoma treatments have been significantly modified after the introduction of immunotherapy. Indeed, immune checkpoint inhibitors (ICIs) are now recommended in localized and metastatic disease. Programmed death ligand-1 (PD-L1)-positive tumors can be treated with immunotherapy in the first and second lines regardless of PD-L1 expression. By increasing immune system activity, ICIs can have adverse effects. In most cases, these can be treated with the interruption of treatment and/or supportive therapy, which can include the administration of immunosuppressants. This report describes a case of suspected a neurologic adverse event characterized by trouble with balance and double vision in a person with head and neck cancer treated with nivolumab. This was adverse event was by pausing therapy and low-dose steroid treatment, leading to complete reduction of symptoms. Unfortunately, the laboratory and instrumental investigations could not determine an exact diagnosis or the area of neurological damage.

Darolutamide in hormone-sensitive and castration-resistant prostate cancer.

Introduction: Important changes in the treatment of prostate cancer have taken place in recent years. Non-metastatic castration-resistant prostate cancer (nmCRPC) has been clinically delineated. In this setting, three drugs have been approved in high-risk disease: apalutamide, enzalutamide and darolutamide.Areas covered:This manuscript aims to profile darolutamide, its clinical development, pharmacologic properties, efficacy and safety. We presented the results of published clinical studies, but we also investigated ongoing ones.Expert opinion: An indirect comparison with the other two aforementioned drugs emerged. While the clinical efficacy is comparable, the toxicity profile is different for darolutamide, resulting in greater tolerance. We must wait for the results of the trials that study darolutamide in hormone-sensitive disease, both in the metastatic phase and in the localized phase. Clinical experience will also be important to determine ever more personalized treatments for patients.

Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives.

Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease. This review investigates the current state and future perspectives of immunotherapy in BC, focusing on the rationale and results of combining immunotherapy with other therapeutic strategies.

Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study.

BACKGROUND: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. METHODS: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. RESULTS: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. CONCLUSION: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.