Clinical usefulness of gefitinib for non-small-cell lung cancer with a double epidermal growth factor receptor mutation.

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.

Survival of a surgical series of lung cancer patients with synchronous multiple ground-glass opacities, and the management of their residual lesions.

OBJECTIVES: We reviewed the medical record of a series of patients with synchronous multiple lung cancers (SMLC), in an attempt to identify the optimal treatment strategy for multiple ground-glass opacities (GGOs). MATERIALS AND METHODS: From 2004 to 2010, 1223 patients underwent complete resection of non-small cell lung cancer. Among these, there were 67 patients (5.5%) with SMLC with at least 1 of the nodules showing GGO appearance. SMLC was divided into the main cancer (MC) which was a main target based on its tumor size or radiological invasiveness and sub-nodules. According to consolidation/tumor ratio (CTR) on thin-section computed tomography, 67 cases were classified into GG-group (MC showing GGO-dominant lesion; CTR≤0.5) and GS-group (MC showing solid-dominant lesion; CTR>0.5). RESULTS: There were 24 patients in the GG-group (36%) and 43 patients in the GS-group (64%). Surgical resections included 11 sublobar resections (SLs), 32 lobectomies, 19 lobectomy+SLs, and 4 bilobectomies. There were 39 patients with a total of 118 unresected GGOs after the initial surgery. Among them, the frequency of growth was 8% on a per-nodule basis with the median tumor doubling time of 1373 days, and new GGOs emerged in 15 patients (23%). Multivariate analysis demonstrated that larger size of MC and the GS-group was associated with poor prognosis, whereas growth of the residual GGOs, the development of new GGOs, or whether or not all GGOs were treated did not affect survival. The 5-year OS proportions were 95.8% for the GG-group and 68.0% for the GS-group (p=0.009), and 92.4% for a MC of ≤25 mm and 53.6% for a MC of >25 mm (p=0.008). CONCLUSION: Survival of patients with multifocal GGOs is strongly affected by radiological findings of the MC. Strict surgical control for MC could be most important.

New aspects of photodynamic therapy for central type early stage lung cancer.

BACKGROUND: and Objective Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for central type early stage lung cancer (CELC). Recent advances in the ability to diagnose CELC, and in photosensitizers, as well as sophisticated clinical management, may improve the therapeutic outcome and expand the indications of PDT. MATERIALS AND METHODS: We made the search for papers on PDT for lung cancer to select the most relevant articles. Based on this review and our recent data, we discussed the best available evidence for the diagnosis, the definition of indications, photosensitizers, and clinical management with regard to PDT. RESULTS: To obtain complete response (CR) by PDT, the selection of the indications is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) have had a large impact on diagnostic bronchoscopy for CELC. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this is a good indication for PDT. The relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin, showed similar treatment outcome even for large tumors >1.0 cm in diameter. Furthermore, comprehensive management including photodynamic diagnosis before and after PDT should be effective to minimize the possibility of local recurrence after PDT. CONCLUSION: 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.