No abstract

The present guidelines of PDT for CELC were established based on the data obtained from studies in the 1980's. We postulate that comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors.

Abstract. The aim of this study was to investigate whether the pattern of epidermal growth factor receptor (EGFR) gene mutations affects sensitivity to gefitinib treatment. We investigated 44 surgically resected non-small-cell lung cancer (NSCLC) specimens obtained between 2001 and 2012 at the Tokyo Medical University Hospital. The specimens were obtained from patients treated with gefitinib as 1st-, 2nd-, or 3rd-line therapy for postoperative recurrent NSCLC. We detected EGFR mutations using the cycleave PCR technique. In addition, the specimens from non-responders were stained with antibodies against hepatocyte growth factor receptor (HGFR; MET) and hepatocyte growth factor (HGF). We assessed the progression of non-responders over a period of 2 months. Intermediate responders were considered to be patients who responded (exhibiting at least stable disease) to gefitinib therapy for 3-11 months, while long-term responders were defined as those who responded to gefitinib therapy for >12 months. The NSCLCs were histologically classified as 43 adenocarcinomas and one large-cell neuroendocrine carcinoma. One patient had an exon 18 point mutation, 23 an exon 19 deletion, 2 an exon 20 point mutation, 16 an exon 21 point mutation and 2 patients had both exon 20 and 21 point mutations. There were 4 non-responders, including the 2 patients with exon 20 mutation, 25 intermediate responders (including 10 patients under ongoing treatment) and 15 long-term responders (2 of whom are under ongoing treatment), including the 2 patients with both exon 20 and 21 mutations. Of the specimens obtained from non-responders, 3 stained with the anti-MET antibody and 1 stained with the anti-HGF antibody. Therefore, NSCLC with exon 20 mutation may respond to gefitinib treatment in the presence of an additional EGFR mutation. IntroductionSomatic mutations in the tyrosine kinase (TK) domain of epidermal growth factor receptor (EGFR) gene have been reported in patients with non-small-cell lung cancer (NSCLC). Certain mutations in the EGFR gene, such as leucine-to-arginine substitution at amino acid position 858 (L858R) in exon 21 or deletions in exon 19, are highly correlated with sensitivity to EGFR-TK inhibitors (TKIs) (1,2). The EGFR-TKIs gefitinib and erlotinib are effective in the treatment of EGFR-mutant NSCLC; however, there are also cases of EGFR-mutant NSCLCs exhibiting resistance to EGFR-TKI treatment. EGFR-TKIs have been shown to achieve a response in ~80% NSCLC patients with EGFR mutations, indicating that ~20% of NSCLC patients with EGFR mutation are unresponsive to this treatment (3).A threonine-to-methionine substitution at amino acid position 790 (T790M) in exon 20 was reportedly associated with acquired resistance to EGFR-TKIs (4,5). In addition, hepatocyte growth factor receptor (HGFR; MET) gene amplification was reportedly associated with acquired resistance to EGFR-TKIs (6), while hepatocyte growth factor (HGF)-mediated MET activation was reported as the mechanism underlying EGFR-TKI resistance in lung cancer with EGFR-act...