Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell
lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed
population including patients who have far more extensive and bulky disease than others.
Management of these patients continue to be a challenge; frequently, patients have both local
recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall
survival estimated between 3% and 7% for inoperable disease. The standard treatment for these
patients is concurrent chemo-radiotherapy (CRT) improving survival when compared to sequential
combination as shown in several metanalysis. Recently, immune-therapies, including checkpoint
inhibitor, such as monoclonal antibodies against programmed death receptor 1 (PD-1) and programmed
death ligand 1 (PD-L1), have shown to enhance survival compared to chemotherapy in patients with
advanced NSCLC. The integration of radiotherapy with immunotherapy is a conceptually promising
strategy and several preclinical experiments have further developed the rationale for combining them.
Radiotherapy has the capacity to overcome a lot of tumor immune escape mechanisms through the
liberation of immunogenic private antigens showing a better local control and augmenting the
immune response of systemic agents. This manuscript discusses the potential clinical interest for the
combination of radiation and immunotherapy in locally advanced NSCLC.
Keywords: Immunotherapy, radiotherapy, lung cancer, combining treatment, locally advanced, NSCLC, PD-1 inhibitors,
PD-L1 inhibitors, anti-CTLA-4.
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