Purpose of review: Malignant pleural mesothelioma (MPM) is a rare, but aggressive tumor with still poor prognosis. In this article, we focus on recent developments in the management of MPM including diagnosis, staging, biomarkers, and treatment strategies. Recent findings: Molecular markers such as programmed death-ligand 1 (PDL-1), Breast Cancer gene 1-associated protein gene, and cyclin-dependent kinase inhibitor 2A (CDKN2A) have prognostic impact and should be considered for assessment in patient samples. In addition to histological subtype and tumor pattern, tumor volumetry plays an increasing important role in staging, assessment of treatment response, and prediction of survival. Several new blood-based biomarkers have been recently reported including peripheral blood DNA methylation, microRNAs, fibulin, and high-mobility group box 1, but have not been established in clinical routine use yet. Regarding treatment, targeted therapies, immunotherapy, and vaccination are considered as new promising strategies. Moreover, extended pleurectomy/decortication is favored over extrapleural pneumonectomy (EPP) and intensity-modulated radiotherapy represents a possible approach in combination with EPP and pleurectomy/decortication. Intracavitary treatment options are promising and deserve further investigations. Summary: Overall, there has not been a real breakthrough in the treatment of MPM. Further research and clinical trials are needed to evaluate outcome and to identify new potential treatment candidates.

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV.

Small cell lung cancer (SCLC) is a devastating disease, which owns the poorest prognosis of all different types of lung cancer. There has been only modest progress in its treatment over the last decades, and 5-year survival rates still are as low as 5%–7%.1 Main reasons for these disappointing results are the early and rapid spread of the tumour and the high recurrence rate after initial response to chemotherapy. Both these features of SCLC have at the same time been used as strong arguments against the use of surgery as part of any treatment algorithm. However, over the last two decades, we have seen major improvements in diagnosis, precision of staging and development of more sophisticated multimodality-based treatment strategies, which have changed the therapeutic standards in many fields of oncology. It therefore seems to be timely and appropriate to also rediscuss the treatment algorithm for SCLC, especially with regard to a potential contribution of surgery for limited-stage SCLC. Although surgery was in fact the treatment of choice in patients who were diagnosed at an early limited-stage of SCLC, many decades ago, chemotherapy and radiation therapy soon became the only accepted treatment modalities, mainly based on the findings of three randomised studies which, seen from today’s perspective, did all not fulfil modern quality requirements. In 1973, the medical research council trial2 compared surgery and radiotherapy for the primary treatment of SCLC. Patients treated in the surgery group had a significantly inferior mean survival (199 vs 300 days, p=0.04) compared with the radiotherapy group. However, the study …

Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1–FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1–4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1–4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not sufficient to predict FGFR inhibitor response in MPM cell lines.