Background: About 30% of new non-small cell lung cancer (NSCLC) cases are diagnosed at a locally advanced stage, which includes a highly heterogeneous group of patients with a wide spectrum of treatment options. The management of stage III NSCLC involves a multidisciplinary team, adequate staging, and a careful patient selection for surgery or radiation therapy integrated with systemic treatment. Methods: This is a single-center observational retrospective and prospective study including a consecutive series of stage III NSCLC patients who were referred to the Veneto Institute of Oncology and University Hospital of Padova (Italy) between 2012 and 2021. We described clinico-pathological characteristics, therapeutic pathways, and treatment responses in terms of radiological response in the entire study population and in terms of pathological response in patients who underwent surgery after induction therapy. Furthermore, we analysed survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS). Results: A total of 301 patients were included. The majority of patients received surgical multimodality treatment (n = 223, 74.1%), while the remaining patients (n = 78, 25.9%) underwent definitive CRT followed or not by durvalumab as consolidation therapy. At data cut-off, 188 patients (62.5%) relapsed and the median RFS (mRFS) of the entire population was 18.2 months (95% CI: 15.83–20.57). At the time of analyses 140 patients (46.5%) were alive and the median OS (mOS) was 44.7 months (95% CI: 38.4–51.0). A statistically significant difference both in mRFS (p = 0.002) and in mOS (p < 0.001) was observed according to the therapeutic pathway in the entire population, and selecting patients treated after 2018, a significant difference in mRFS (p = 0.006) and mOS (p < 0.001) was observed according to treatment modality. Furthermore, considering only patients diagnosed with stage IIIB-C (N = 131, 43.5%), there were significant differences both in mRFS (p = 0.047) and in mOS (p = 0.022) as per the treatment algorithm. The mRFS of the unresectable population was 16.3 months (95% CI: 11.48–21.12), with a significant difference among subgroups (p = 0.030) in favour of patients who underwent the PACIFIC-regimen; while the mOS was 46.5 months (95% CI: 26.46–66.65), with a significant difference between two subgroups (p = 0.003) in favour of consolidation immunotherapy. Conclusions: Our work provides insights into the management and the survival outcomes of stage III NSCLC over about 10 years. We found that the choice of radical treatment impacts on outcome, thus suggesting the importance of appropriate staging at diagnosis, patient selection, and of the multidisciplinary approach in the decision-making process. Our results confirmed that the PACIFIC trial and the following introduction of durvalumab as consolidation treatment may be considered as a turning point for several improvements in the diagnostic-therapeutic pathway of stage III NSCLC patients.

The human immunodeficiency virus (HIV) infection continues to be a social and public health problem. Thanks to more and more effective antiretroviral therapy (ART), nowadays HIV-positive patients live longer, thus increasing their probability to acquire other diseases, malignancies primarily. Senescence along with immune-system impairment, HIV-related habits and other oncogenic virus co-infections increase the cancer risk of people living with HIV (PLWH); in the next future non-AIDS-defining cancers will prevail, lung cancer (LC) in particular. Tumor in PLWH might own peculiar predictive and/or prognostic features, and antineoplastic agents’ activity might be subverted by drug-drug interactions (DDIs) due to concurrent ART. Moreover, PLWH immune properties and comorbidities might influence both the response and tolerability of oncologic treatments. The therapeutic algorithm of LC, rapidly and continuously changed in the last years, should be fitted in the context of a special patient population like PLWH. This is quite challenging, also because HIV-positive patients have been often excluded from participation to clinical trials, so that levels of evidence about systemic treatments are lower than evidence in HIV-uninfected individuals. With this review, we depicted the epidemiology, pathogenesis, clinical-pathological characteristics and implications for LC care in PLWH, offering a valid focus about this topic to clinicians.

The global immuno-oncology pipeline has grown progressively in recent years, leading cancer immunotherapy to become one of the main issues of the healthcare industry. Despite their success in the treatment of several malignancies, immune checkpoint inhibitors (ICIs) perform poorly in others. Again, ICIs action depends on such a multitude of clinico-pathological features, that the attempt to predict responders/long-responders with ad-hoc built immunograms revealed to be quite complex. In this landscape, the role of nuclear medicine might be crucial, with first interesting evidences coming from small case series and pre-clinical studies. Positron-emission tomography (PET) techniques provide functional information having a predictive and/or prognostic value in patients treated with ICIs or adoptive T-cell therapy. Recently, a characterization of the tumor immune microenvironment (TiME) pattern itself has been shown to be feasible through the use of different radioactive tracers or image algorithms, thus adding knowledge about tumor heterogeneity. Finally, nuclear medicine exams permit an early detection of immune-related adverse events (irAEs), with on-going clinical trials investigating their correlation with patients’ outcome. This review depicts the recent advances in molecular imaging both in terms of non-invasive diagnosis of TiME properties and benefit prediction from immunotherapeutic agents.

Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.