Precision medicine has revolutionized the therapeutic management of cancer patients with a major impact on non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, where advances have been remarkable. Tissue biopsy, required for tumor molecular testing, has significant limitations due to the difficulty of the biopsy site or the inadequacy of the histological specimen. In this context, liquid biopsy, consisting of the analysis of tumor-released materials circulating in body fluids, such as blood, is increasingly emerging as a valuable and non-invasive biomarker for detecting circulating tumor DNA (ctDNA) carrying molecular tumor signatures. In advanced/metastatic NSCLC, liquid biopsy drives target therapy by monitoring response to treatment and identifying eventual genomic mechanisms of resistance. In addition, recent data have shown a significant ability to detect minimal residual disease in early-stage lung cancer, underlying the potential application of liquid biopsy in the adjuvant setting, in early detection of recurrence, and also in the screening field. In this article, we present a review of the currently available data about the utility and application of liquid biopsy in lung cancer, with a particular focus on the approach to different techniques of analysis for liquid biopsy and a comparison with tissue samples as well as the potential practical uses in early and advanced/metastatic NSCLC.

Background: With the approval of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for newly diagnosed, breast cancer gene (BRCA)1/2 mutated, ovarian cancer women, the assessment of BRCA1/2 tumour status will be shortly required at the time of diagnosis. Aim: To investigate the feasibility of next-generation sequencing (NGS)-based BRCA tumour test on cytological specimens from ovarian cancer ascites. Methods: We evaluated the BRCA1/2 status on neoplastic ascites and corresponding tumour tissue of 11 patients with ovarian cancer, using the NGS ‘Oncomine BRCA Research Assay’. Results: The NGS-based BRCA test on cytological samples had a success rate of 100%, with 11 of 11 concordant BRCA1/2 results between ascites and tumour tissues analyses, including two wild type samples and nine cases harbouring somatic or germline variants. Conclusion: BRCA test may be performed on ovarian cancer ascites, reproducing BRCA1/2 tumour status and representing a useful tool for clinical decision-making.

Immune checkpoint inhibitors (ICI) have become the cornerstone of treatment in renal cell carcinoma (RCC), for both metastatic disease and in an adjuvant setting. However, an adaptive resistance from cancer cells may arise during ICI treatment, therefore many studies are focusing on additional immune checkpoint inhibitor pathways. Promising targets of immunotherapeutic agents under investigation include T cell immunoglobulin and ITIM domain (TIGIT), immunoglobulin-like transcript 4 (ILT4), lymphocyte activation gene-3 (LAG-3), vaccines, T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and chimeric antigen receptor (CAR) T cells. In this review of the literature, we recollect the current knowledge of the novel treatment strategies in the field of immunotherapy that are being investigated in RCC and analyze their mechanism of action, their activity and the clinical studies that are currently underway.

Colorectal cancer (CRC) is a common tumor, and its incidence increases with age. Elderly CRC patients constitute a daily challenge for oncologists when deciding if they are worthy of active treatments and of which kind, as data from the literature are incomplete or even lacking in specific subsets. To fill this gap, we conducted a narrative review that included not only studies dedicated to the elderly but also extracted elderly groups from major clinical trials. Results in terms of harm and benefit were dissected according to frailty categories (fit, vulnerable, unfit). As it emerged, the management of elderly CRC patients should be based not on age alone, but rather on their frailty level, as assessed by Comprehensive Geriatric Assessment (CGA), which should be implemented in trials and clinical practice. Elderly patients should be treated similarly to young patients in the first and subsequent lines, without precluding the use of innovative drugs. Vulnerable elderly individuals should receive personalized schedules that focus more on symptoms and quality of life; for frail patients, supportive care alone is often a valid option.

Immune checkpoint inhibitors (ICIs) have become the standard of care in several solid tumours. Thus the action of ICIs may lead to the development of inflammatory damage in nontumoral tissues, defined as immune-related adverse events (irAEs). Scanty data describe upper gastrointestinal tract toxicity. We conducted a monocentric retrospective study, enrolling patients with advanced cancer, who developed histology-proven immune-related oesophago-gastro-duodenitis, treated with at least one cycle of ICI between January 2016 and November 2022. We identified six patients with upper gastrointestinal irAEs: four affected by metastatic melanoma (three treated with nivolumab and one with nivolumab plus ipilimumab), one by unresectable cutaneous squamous cell carcinoma (treated with cemiplimab), and one by metastatic non-small-cell lung cancer (treated with pembrolizumab). Proton pump inhibitors and oral corticosteroids have been the mainstay of the management, and thus one patient had to receive intravenous methylprednisolone with hospitalisation, fasting, and parenteral nutrition. Based on the literature and our experience, we proposed a classification of ICI-induced upper gastrointestinal toxicity, with symptom and endoscopic sign grading. Each step of severity has been also correlated with a proposed diagnosis and clinical management. During ICI treatment, upper gastrointestinal symptoms can be a red flag for developing severe oesophago-gastro-duodenal toxicity that can impact patients’ quality of life and therapeutic plan. We recommend carefully investigating these symptoms, choosing a multidisciplinary approach to decide if an oesophagogastroduodenoscopy with random biopsy is indicated. [18]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography might represent a promising complementary diagnostic tool. Steroids still represent the cornerstone of treatment, as for other irAEs.