The purpose of this study was to evaluate the efficacy and toxicity of the postoperative radiotherapy in patients with incompletely resected NSCLC, and to investigate whether the histological subtype is a prognostic factor.

Forty-one incompletely resected NSCLC patients who underwent postoperative radiotherapy were retrospectively analyzed. The microscopic residual tumor (R1 group) was recognized in 23 patients, and the macroscopic residual tumor (R2 group) in 18.

The postoperative pathological stages were I (n = 3), II (n = 8), IIIA (n = 17), and IIIB (n = 13). The histology included squamous cell carcinoma (n = 23), adenocarcinoma (n = 14) or other types (n = 4). The first site of disease progression was distant metastases alone for 3 (13%) of 23 with squamous cell carcinoma, and for 9 (64%) of 14 with adenocarcinoma (p < 0.01). The 5-year overall, local control, disease-free, and distant metastasis-free survival rates were 56%, 63%, 37% and 49%. Univariate analyses showed that squamous cell carcinoma histology, N0-1 stage and the R1 group were significant predictors for better disease-free and distant metastasis-free survival. Multivariate showed that squamous cell carcinoma and N0-1 stage were significant predictors for better distant metastasis-free survival. Toxicity was generally mild; Grade 3 toxicities occurred in 3 patients (neutropenia, radiation pneumonia and esophageal stenosis), and no acute and late toxicities of Grade 4 to 5 were observed. In conclusion, postoperative radiotherapy for incompletely resected NSCLC could achieve a relatively high local control rate without severe toxicity.

However, different treatment strategies for non-squamous cell carcinoma should be considered, because of the higher risk for the distant metastases.

Erlotinib-an oral tyrosine kinase inhibitor (tki) of the epidermal growth factor receptor (egfr)-has commonly been used as a therapeutic option in metastatic non-small-cell lung cancer (nsclc) patients in the second- or third-line treatment setting. A mutation in the EGFR gene (EGFR M+) confers an increased response to this class of drugs. In the first-line setting, use of tkis is restricted to patients having a mutation.

The importance of this biomarker has been questioned in subsequent treatment lines.Here, we report a case showing a positive response to erlotinib treatment in the second-line setting. The patient, an elderly male smoker with stage iv nsclc, had a tumour that was EGFR mutation-negative (wild-type EGFR).

Based on this clinical case, we discuss the controversy concerning the need for, and impact of, testing for EGFR mutation after first-line treatment.

PURPOSE: Platinum-based regimens represent the standard first-line treatment for non-small-cell lung cancer (nsclc). However, newer data have established a role for pemetrexed in the treatment of this disease. Such data suggest that histology represents a determining factor in the selection of treatment.

METHODS: We undertook a systematic review of the literature for randomized controlled trials that compared the efficacy of pemetrexed with that of other treatments in advanced nsclc. Data and study quality were assessed according to published guidelines.

RESULTS: We identified five trials that compared pemetrexed with other treatments or with placebo. Overall survival for patients treated with pemetrexed was superior to that with other treatments: hazard ratio (hr): 0.89; 95% confidence interval (ci): 0.80 to 0.99. The survival benefit was limited to patients with non-squamous histology: hr: 0.82; 95% ci: 0.73 to 0.91. Pemetrexed was inferior to other chemotherapy options in patients with squamous histology: hr: 1.19; 95% ci: 0.99 to 1.43.

CONCLUSIONS: Compared with other chemotherapy agents, pemetrexed is more effective for the treatment of nsclc in patients with non-squamous histology.

The tumor genome is commonly aberrant as a consequence of mutagenic insult and incomplete DNA repair. DNA repair as a therapeutic target has recently received considerable attention owing to the promise of drugs that target tumor-specific DNA-repair enzymes and potentiate conventional cytotoxic therapy through mechanism-based approaches, such as synthetic lethality.

Treatment for non-small-cell lung cancer (NSCLC) consists mainly of platinum-based chemotherapy regimens and improvements are urgently needed. Optimizing treatment according to tumor status for DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, could predict response to platinum, taxanes and gemcitabine-based therapies, respectively, and might improve substantially the response of individual patients' tumors.

Finally, recent data on germline variation in DNA-repair genes may also be informative. Here, we discuss how a molecular and functional DNA-repair classification of NSCLC may aid clinical decision making and improve patient outcome.