2 Micro abstractIntra-tumor heterogeneity of epidermal growth factor receptor (EGFR) mutations in patients with mixed-type lung adenocarcinoma was analyzed according to histological patterns. Intra-tumor heterogeneity of EGFR mutations was detected in 9 of 38 tumors, and there was a significant correlation between heterogeneity of EGFR mutations and smoking history (P<0.043). Clinical Practice Points• EGFR mutations are factors predictive of response to EGFR-TKI treatment. However, lung cancer is thought to be the result of the accumulation of genetic alterations over a long course of exposure to a carcinogen, and the existence of intra-tumor heterogeneity of EGFR mutations remains unclear. Thus, the existence of intra-tumor heterogeneity was analyzed in patients with mixed-type lung adenocarcinoma according to histological patterns.• Intra-tumor heterogeneity of EGFR mutations was detected in 9 of 38 tumors, and a significant correlation between heterogeneity of EGFR 3 mutations and smoking history was found.• Response to EGFR-TKIs might be partial and insufficient in tumors having intra-tumor heterogeneity of EGFR mutations. New treatment strategies for patients with lung adenocarcinoma harboring heterogeneous EGFR mutations are needed.

Micro abstractWe compared three PCR methods (mutant-enriched PCR, PNA-LNA PCR and PCR clamp) to detect EGFR mutations in 50 patients with advanced NSCLC. Seventeen were harboring EGFR mutations, five of whom showed discrepancies between the results of different PCR methods. All five responded to gefitinib, which we consider to suggest that the discrepancies were false negatives. Clinical Practice Points• Several methods have been used to detect EGFR mutations in non-small-cell lung cancer (NSCLC): however, it is not clear which is the most suitable for use in the clinic.• We compared three PCR methods (mutant-enriched PCR, PNA-LNA PCR and PCR clamp) in 50 patients with advanced NSCLC. Seventeen of the patients were harboring EGFR mutations, five of whom showed discrepancies between the results of different PCR methods. All five patients responded to gefitinib.• We considered that all of the discrepancies might be false negatives because the patients responded to gefitinib. To clarify the reasons for the false negatives of each PCR method, and establish the clinical sensitivity and specificity of each method, a large prospective clinical trial is warranted. AbstractBackground: Epidermal growth factor receptor (EGFR) mutations are predictive of

Background We conducted a phase II trial of erlotinib in patients with

Cryptococcal pleuritis is rare in individuals with no underlying disease. We report a case of pulmonary cryptococcosis followed by pleuritis in a patient on fluconazole treatment. Biopsy of the pleura revealed a granuloma and a cryptococcal body, while PCR and sequence analysis of extracted DNA from the pleura proved the presence of Cryptococcus species, most likely C. neoformans. Voriconazole with flucytosine and drainage of the pleural effusion were effective in treating the patient.

A high D8/D2 ratio, but not elimination half-life, might be a predictor of better PFS in patients with NSCLC harboring EGFR mutations treated with gefitinib. On the other hand, long elimination half-life was related to high-grade adverse events in these patients. Clinical Trial Registration UMIN000001066.

A phase I/II study of combination chemotherapy with amrubicin and nedaplatin for patients with untreated, advanced, non-small cell lung cancer (NSCLC) was conducted. Amrubicin was given on days 1-3, with nedaplatin given on day 1. The treatment was repeated every 3 weeks. In the phase I trial, the initial amrubicin dose of 25 mg/m² was escalated in 5-mg/m² increments until the maximum tolerated dose was reached, with the dose of nedaplatin fixed at 100 mg/m². In the phase II trial, the primary endpoint was the overall response rate (ORR), assuming 20% for a standard therapy and 40% for a target therapy (α = 0.05 and β = 0.20), and the estimated required total number of patients was 35. In the phase I study, nedaplatin 100 mg/m² and amrubicin 25 mg/m² was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. Grade 3/4 neutropenia, grade 3 anemia and grade 3/4 thrombocytopenia occurred in 62.9, 11.4 and 11.4% of cycles, respectively. Febrile neutropenia occurred in 5 cycles (3.9%) and all cases were manageable. The recommended dose of this combination is well tolerated and effective in patients with advanced NSCLC.

It is widely recognized that the risk of secondary neoplasms increases as childhood cancer survivors progress through adulthood. These are mainly hematological malignancies, and recurrent chromosome translocations are commonly detected in such cases. On the other hand, while secondary epithelial malignancies have sometimes been reported, chromosome translocations in these epithelial malignancies have not. A 33-year-old man who had been diagnosed with acute lymphoblastic leukemia and treated with chemotherapy almost 20 years earlier was diagnosed with lung adenocarcinoma. After chromosomal rearrangement of echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene was detected in this adenocarcinoma, he responded to treatment with crizotinib. It was therefore concluded that this echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase gene-positive lung adenocarcinoma was a secondary epithelial malignancy.

Background: Amrubicin is active in the treatment of extensive-disease small