Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable.

The precise etiology of multiple myeloma remains elusive, but both genetic and environmental factors have been suggested to contribute to disease risk. Several occupational categories and toxic agents have been implicated as potentially causative, yet findings from the literature are inconsistent. The aim of this review was to summarize and critically comment on the accumulated epidemiological evidence, across published meta-analyses, about the association between occupational exposure and risk of multiple myeloma. Overall, results from eleven meta-epidemiological studies underscore a significantly increased risk for firefighters, hairdressers, and employees exposed to engine exhaust, whereas farming and methylene chloride exposure have been non-significantly correlated with the disease. Further epidemiological studies are of utmost importance whilst emphasis should be placed on occupational hazard surveillance, as such studies will obtain a more accurate picture of disease occurrence in working populations, and will enable both the implementation of preventive actions and the evaluation of their effectiveness.

Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.

Biliary tract cancer, and intrahepatic cholangiocarcinoma (iCC) in particular, represents a rather uncommon, highly aggressive malignancy with unfavorable prognosis. Therapeutic options remain scarce, with platinum-based chemotherapy is being considered as the gold standard for the management of advanced disease. Comprehensive molecular profiling of tumor tissue biopsies, utilizing multi-omics approaches, enabled the identification of iCC’s intratumor heterogeneity and paved the way for the introduction of novel targeted therapies under the scope of precision medicine. Yet, the unmet need for optimal care of patients with chemo-refractory disease or without targetable mutations still exists. Immunotherapy has provided a paradigm shift in cancer care over the past decade. Currently, immunotherapeutic strategies for the management of iCC are under intense research. Intrinsic factors of the tumor, including programmed death-ligand 1 (PD-L1) expression and mismatch repair (MMR) status, are simply the tip of the proverbial iceberg with regard to resistance to immunotherapy. Acknowledging the significance of the tumor microenvironment (TME) in both cancer growth and drug response, we broadly discuss about its diverse immune components. We further review the emerging role of immunotherapy in this rare disease, summarizing the results of completed and ongoing phase I–III clinical trials, expounding current challenges and future directions.

Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.

We herein investigated the detection frequency and clinical relevance of circulating tumor cells (CTCs) in chemotherapy-naïve stage IIIB/IV non-small cell lung cancer (NSCLC), by using the CellSearch and real-time CEACAM5mRNA assays. Blood samples from 43 patients were obtained at different time points during first-line chemotherapy. CellSearch revealed the detection of ≥1 CTCs in 41.9%, 40.9%, and 16.7% of patients at baseline, post-1st, and post-2nd treatment cycle, respectively, and of ≥5 CTCs in 11.6%, 9.1%, and 5.6%, respectively. CEACAM5mRNA+ CTCs were detected in 29.3% and 16% of patients pre- and post-treatment, respectively. The positivity concordance between the two assays was 2.2%. CTC-detection by CellSearch (≥5 CTCs: p = 0.004), CEACAM5mRNA (p = 0.010), or by any assay (p = 0.000) was associated with disease progression. Reduced survival was demonstrated for patients harboring ≥5 CTCs (progression-free survival; PFS: p = 0.000; overall survival; OS: p = 0.009), CEACAM5mRNA+ CTCs (PFS: p = 0.043; OS: p = 0.039), and CTCs by any assay (PFS: p = 0.005; OS: p = 0.006, respectively). CTC-detection by any assay independently predicted for increased risk of relapse (hazard ratio; HR: 3.496; p = 0.001) and death (HR: 2.866; p = 0.008). CellSearch-positivity either pre-, post-1st, or post-2nd cycle, was predictive for shorter PFS (p = 0.036) compared to negativity in all time points. Persistent CEACAM5mRNA-positivity pre- and post-treatment was associated with reduced PFS (p = 0.036) and OS (p = 0.026). In conclusion, CTC detection and monitoring using the CellSearch and CEACAM5mRNA assays provides valuable and complementary clinical information for chemo-naïve advanced or metastatic NSCLC.