Introduction and Aim: Stage III Non-Small Cell Lung Cancer (NSCLC) has a poor prognosis, with median survival ranging from 9 to 34 months. The PACIFIC trial demonstrated that durvalumab after platinum-based chemoradiotherapy (CRT) improves overall survival (OS) and progression-free survival (PFS). This review evaluates real-world evidence (RWE) on durvalumab’s efficacy and safety, focusing on patient characteristics, prognostic factors, treatment protocols, and outcomes beyond progression. Materials and Methods: A literature search of PubMed, Embase, and Google Scholar identified 49 observational studies published from January 2017 to August 2024 on unresectable stage III NSCLC. Clinical trials, early-stage disease, and alternative treatments were excluded. Results: Compared to the PACIFIC trial, real-world patients were older, had poorer ECOG performance (≥2), and more comorbidities like COPD. Despite this, durvalumab provided consistent survival benefits. Positive prognostic factors included non-squamous histology, high PD-L1 expression, and timely durvalumab initiation (≤42 days post-CRT). Most radiotherapy regimens mirrored PACIFIC (54–66 Gy). Concomitant CRT was used in 90% of cases, with sequential CRT for frail patients. Chemotherapy regimens varied. Immune-mediated pneumonitis was a major adverse event, with incidence rates between 15% and 100%. Severe cases led to treatment discontinuation, impacting survival. Treatment beyond progression remains uncertain, with limited benefits from immunotherapy rechallenge. Conclusions: RWE supports durvalumab’s efficacy, emphasizing the need for personalized treatment strategies and further research to improve long-term outcomes.

The therapeutic management of melanoma brain metastases has undergone a profound revolution during recent decades. Optimal integration of systemic therapies with local treatments seems to represent the strategy to pursue in order to maximize clinical outcomes, stressing the need for real multidisciplinary care in this setting of patients. However, the current approach in the clinics does not necessarily reflect what the current guidelines state, and several pending issues are present, from the ideal therapeutic sequence between stereotactic radiosurgery (SRS) and drug administration to the current role of surgery and whole brain radiotherapy (WBRT), all of which need to be addressed. This narrative review aims to provide practical help for navigating the current controversies, with an eye towards possible future advancements in the field, which could help to obtain a comprehensive molecular characterization of the tumor and a more personalized patient-centered therapeutic approach.

Melanoma brain metastases (MBM) remain a major therapeutic challenge, requiring a multidisciplinary approach integrating systemic and local therapies. The advent of immune checkpoint inhibitors and targeted therapies has markedly improved patients’ survival, with the combination of ipilimumab and nivolumab now considered as first-line systemic treatment for patients with asymptomatic MBM. Radiotherapy plays a crucial role, with stereotactic radiosurgery (SRS) now preferred over whole-brain radiotherapy (WBRT), due to its efficacy and lower risk of neurocognitive impairment. Retrospective data support a potential synergy between systemic therapy and SRS and emerging clinical evidence suggests that this combined approach may offer enhanced disease control and could become the standard of care. Key unresolved questions include the ideal sequencing of SRS with systemic treatments, the optimal radiation dose to balance efficacy and neuroprotection, and the identification of predictive biomarkers to refine patient selection. Emerging research focuses on tumor microenvironment interactions and novel radiosensitizers to enhance therapeutic outcomes. Furthermore, artificial intelligence-driven models integrating radiomics, radiogenomics, and metabolomics hold promise for advancing precision medicine in MBM management. Ongoing prospective clinical trials are crucial to establishing standardized treatment guidelines, ensuring a personalized, patient-centered approach that optimizes survival while preserving quality of life.

Prostate cancer (PCa) is the second most common cancer in men, and it is frequently diagnosed at an advanced stage of the disease. Androgen Deprivation Therapy (ADT) has traditionally represented the backbone of therapy for high-risk, recurrent, and metastatic disease; however, in the last ten years a new group of molecules known as androgen receptor pathway inhibitors (ARPIs) have been demonstrated to improve outcomes in metastatic patients when added to ADT. Developed and validated originally in the setting of castration-resistant disease, ARPIs have been implemented progressively earlier in the natural history of PCa, involving patients who have never received ADT before or that are still responsive to this treatment. Considering the strong evidence for treatment intensification in patients with high-risk features, with this review we aim to provide a complete overview of the current indications for the use of ARPIs through all the stages of castration-sensitive prostate cancer (CSPC).

Stage III non-small cell lung cancer (NSCLC) is a variable entity, encompassing bulky primary tumors, nodal involvement or both. Multidisciplinary evaluation is essential to discuss multiple treatm...

Background: The standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is represented by concomitant chemo-radiotherapy followed by consolidation with durvalumab that ensures a 5-year survival of 46%. However, the risk of radiotherapy-induced pneumonia (RIP) is almost 10–15%. Complete cardiological examination is also usually performed during the cardiopulmonary pre-treatment evaluation and pulmonary function testing is one of the most used tool to predict the risk of RIP development. Aim: The aim of this study is to investigate the impact of Tc-99 macroaggregated albumin (MAA) lung perfusion scan with single photon emission-computed tomography/computed tomography (SPECT/CT) in the preliminary assessment of lung functions and its potential role for the optimization of the radiotherapy treatment planning. Methods: Descriptive and statistical analysis were performed on eight patients affected by unresectable stage III LA-NSCLC treated with chemo-radiotherapy. Before starting radiotherapy, patients underwent lung perfusion SPECT/CT. The SPECT/CT images were firstly co-registered with the simulation CT scan ones, then a specific region of interest (ROI) of lung volumes was created to represent the areas with a perfusion of at least 20% 40%, 60% and 80% of maximum perfusion, respectively. Finally, optimization of the standard treatment plan was performed with the aim of preserving the better perfused lung volumes. The dosimetric correlations of both plans were made comparing pulmonary V20 and V5, mean pulmonary, esophagus and heart dose. Results: From the DVH comparative analysis of the two treatment plans (standard one versus SPECT optimized one) obtained for each patient, the data confirmed an equal coverage of the target volume while respecting all lungs, heart and esophagus dose constraints. At the same time, SPECT-optimized plans allowed to reduce the average dose to the better perfused lung volumes. Conclusions: Lung perfusion scintigraphy could be considered a preliminary assessment tool to explore lung functions and stratify the risk of RIP development. SPECT/TC may also be proposed as a dose painting tool to optimize radiotherapy treatment plans. Only prospective analysis will be enable us to confirm the real reduction of RIP risk in lung areas with an optimal perfusion.