The 5-year OS and PFS rates in randomly assigned patients with resectable stage III non-small-cell lung cancer were excellent with both treatments. Both are acceptable strategies for this good-prognosis group.

Purpose Pemetrexed-based chemotherapy represents the standard of care in firstline-treatment of advanced malignant pleural mesothelioma (MPM). However, there are no established predictors of clinical benefit. Pemetrexed inhibits multiple enzymes involved in pyrimidine and purine synthesis, but the main target is thymidylate synthase (TS). Following cellular uptake pemetrexed is converted into more effective polyglutamated forms by folylpoly-γ-glutamate synthetase (FPGS). We hypothesized that FPGS and TS protein expression is associated with clinical outcome following pemetrexed-based chemotherapy. Patients and Methods Pretreatment tumor samples from 84 patients with histologically confirmed MPM, who received pemetrexed combined with platinum (79/84) or single-agent pemetrexed (5/84) as firstline treatment, were retrospectively analyzed. FPGS and TS protein expression was semiquantitatively assessed by using the H-Scoring system (range: 0–300). H-scores were correlated with radiological response according to modified RECIST, progression-free survival (PFS) and overall survival (OS). Results Median H-score of the entire cohort was 230 for FPGS (range: 100–300), and 210 for TS (range: 100–300). High FPGS protein expression was significantly associated with longer PFS (PCOX=0.0337), better objective tumor response (PR vs. SD + PD; PKW=0.003), and improved disease control rate (PR + SD vs. PD; PKW=0.0208), but not with OS. In addition, high TS protein expression was associated with PD under pemetrexed-based therapy (P=0.0383), and shorter OS (PCOX=0.0071), but no association with PFS was observed. Conclusion FPGS and TS expression were associated with clinical response and outcome to pemetrexed-based firstline chemotherapy in MPM. Prospective evaluation of FGPS and TS expression and their prognostic/predictive power in MPM patients is warranted.

Background:Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both βIII- and βV-tubulins are expressed by cancer cells and may lead to resistance against TBAs.Methods:Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of βIII- and βV-tubulin was morphometrically quantified.Results:Median pre-treatment H-score for βIII-tubulin was 110 (range: 0–290), and 160 for βV-tubulin (range: 0–290). Low βIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high βV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high βV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy.Conclusion:Expression of βV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of βIII-tubulin. Prospective evaluation of βIII/βV-tubulin expression in NSCLC is warranted.