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Lung cancer is the second-most commonly diagnosed cancer and the leading cause of cancer death worldwide. The most common histological type is non-small-cell lung cancer, accounting for 85% of all lung cancer cases. About one out of three new cases of non-small-cell lung cancer are diagnosed at a locally advanced stage—mainly stage III—consisting of a widely heterogeneous group of patients presenting significant differences in terms of tumor volume, local diffusion, and lymph nodal involvement. Stage III NSCLC therapy is based on the pivotal role of multimodal treatment, including surgery, radiotherapy, and a wide-ranging option of systemic treatments. Radical surgery is indicated in the case of hilar lymphnodal involvement or single station mediastinal ipsilateral involvement, possibly after neoadjuvant chemotherapy; the best appropriate treatment for multistation mediastinal lymph node involvement still represents a matter of debate. Although the main scope of treatments in this setting is potentially curative, the overall survival rates are still poor, ranging from 36% to 26% and 13% in stages IIIA, IIIB, and IIIC, respectively. The aim of this article is to provide an up-to-date, comprehensive overview of the state-of-the-art treatments for stage III non-small-cell lung cancer.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with localised and locally advanced non-small cell lung cancer has not been fully elucidated. This information could help to better interpret recent and upcoming results of phase III adjuvant or neoadjuvant anti-PD-1/PD-L1 immunotherapy studies. METHODS: In a cohort of 146 patients with early or locally advanced non-small cell lung cancer treated with curative intent (by surgery or radiotherapy), we investigated the prognostic value of PD-L1 expression and its correlation with other biological and clinical features. PD-L1 expression was stratified by quartiles. Primary endpoints were overall and disease-free survival. We also analysed the prognostic impact of the presence of actionable mutations, implemented treatment modality and completion of the treatment plan. Neither type of patient received neoadjuvant or adjuvant immunotherapy or target therapy. RESULTS: Of the 146 selected patients, 32 (21.9%) presented disease progression and 15 died (10.3%) at a median follow-up of 20 months. In a univariable analysis, PD-L1 expression ≥25% was associated with significantly lower disease-free survival (hazard ratio [HR]) 1.9, 95% confidence interval [CI] 1.0–3.9, p= 0.049). PD-L1 expression ≥50% did not lead to disease-free survival or overall survival benefits (HR 1.2 and 1.1, respectively; 95% CI 0.6–2.6 and 0.3–3.4, respectively; pnot significant). In a multivariate analysis, a stage >I (HR 2.7, 95% CI 1.2–6, p = 0.012) and having an inoperable tumour (HR 3.2, 95% CI 1.4–7.4, p = 0.005) were associated with lower disease-free survival. CONCLUSION: The population of patients with early-stage non-small cell lung cancer and PD-L1 expression ≥25% who were treated with curative intent during the pre-immunotherapy era exhibited a worse prognosis. This finding provides justification for the utilisation of adjuvant immunotherapy in this subgroup of patients, based on the current evidence derived from disease-free survival outcomes. However, for patients with PD-L1 expression

# Introduction Despite recent advances in the availability of new therapeutic agents, small-cell lung cancer (SCLC) remains an aggressive disease with a poor prognosis. While immune checkpoint inhibition has revolutionized the treatment of non-small cell histologies, results in SCLC have shown overall less favorable evolution, and despite initial data from different trials showing potential for development, the lack of reliable biomarkers for patient selection is a major hindrance to their use. Most notably, programmed death-ligand 1 (PD-L1) expression does not appear to play a key role in SCLC responsiveness to immune checkpoint inhibition. While other biomarkers such as tumor mutational burden (TMB) have been suggested to be more relevant, literature data are not univocal on this subject. # Case Presentation We report here on a 58-year-old patient with metastatic PD-L1-negative SCLC treated in an advanced and symptomatic setting who obtained a complete and sustained clinical and radiological response to the combination of nivolumab and ipilimumab. We also discuss the impact of treatment-related adverse events, such as autoimmune hypothyroidism, gastroenteric toxicity and pneumonitis, on his quality of life. # Discussion This case, while it exemplifies the potential of immune checkpoint inhibition in SCLC, highlights the need for a deeper understanding of the mechanisms underlying its efficacy in order to identify patients who are more likely to benefit from treatment. PEER REVIEWED ARTICLE