According to the most recent statistics provided by Cancer Research UK, lung cancer is the third most common cancer in the UK, with around 49 000 new cases in the UK every year which account for 13% of all new cancer cases.

As with most cancers survival rates depend on the stage at diagnosis, which occurs at stage 4 more than any other stage and where the 5-year survival rate is only 4.3%. The most common type of lung cancer is non-small cell lung cancer (NSCLC). Therapy for stage 4 patients is aimed at controlling the cancer for as long as possible and helping to reduce symptoms. Therapy can involve targeted cancer drugs, chemotherapy, immunotherapy as well as a combination of chemotherapy and immunotherapy.

(Adobe Stock.com)

The choice of therapy depends on the mutational landscape of the individual patient’s disease; for example, presence or absence of disease driver mutations in epidermal growth factor receptor (EGFR) or ALK tyrosine kinase receptor (ALK) genes and the programmed death ligand-1 (PD-L1) tumour proportion score (TPS). Immunotherapy with pembrolizumab (an anti-PD-L1 antibody) alone (in patients with metastatic NSCLC with PD-L1 TPS ≥ 50%) or in combination with chemotherapy (regardless of tumour PD-L1 expression) is providing much improved 5-year overall survival rates compared to patients treated with platinum-based chemotherapy. There is also some data that suggest that thyroid transcription factor 1 (TTF-1) expression affects the efficacy of therapy. Expression of TTF-1 is restricted to epithelial cells of the thyroid and lung, and is, therefore, a useful immunohistochemical marker for the diagnosis of tumours of thyroid or lung origin. Also, TTF-1 expression is used in the decision-making process for chemotherapy in lung cancer patients, as it is a positive prognostic factor for the use of pemetrexed or docetaxel. In a recent study Uhlenbruch et al. analysed the effect of expression of TTF-1 in tumour cells on progression-free survival (PFS) of patients with stage 4 lung cancer being treated with chemo-/immunotherapy (CIT) or immunotherapy with a checkpoint inhibitor (CPI). The study compared four groups of patients: groups 1 and 2 (patients with CPI with and without TTF-1 expression) and groups 3 and 4 (patients with CIT with and without TTF-1 expression) and found that PFS was better in both of groups 1 and 3 (i.e. with TTF-1 expression). Additionally, they found that PFS was significantly affected by antimicrobial treatment one month before the lung cancer treatment in patients with CPI but not in patients with CIT. As the study involved a relatively small number of patients, further validation is needed, but the data suggest that TTF-1 expression could be a useful predictive factor for the use of chemotherapy in combination with PD-L1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor therapy.

Read the research

Effect of TTF-1 expression on progression free survival of immunotherapy and chemo-/immunotherapy in patients with non-small cell lung cancer. Uhlenbruch M, Krüger S. J Cancer Res Clin Oncol 2024;150(8):394
(https://link.springer.com/article/10.1007/s00432-024-05916-x).