Long-term disease-free survivor of metastatic large-cell neuroendocrine carcinoma of the lung treated with amrubicin and irinotecan

Shinichiro Ryuge1, Shi-Xu Jiang2, Mayuko Wada1, Ken Katono1, Maiko Iwasaki1, Akira Takakura1, Sakiko Otani1, Yuka Kimura1, Tomoya Fukui1, Masanori Yokoba1, Masaru Kubota1, Masato Katagiri1, Kazusige Hayakawa3, Noriyuki Masuda11Department of Respiratory Medicine, 2Department of Pathology, 3Department of Radiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, JapanAbstract: Large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon variant of non-small cell lung cancer. Since the biological characteristics of LCNEC are similar to those of small cell lung cancer, LCNEC is usually treated with chemotherapy regimens used for small cell lung cancer. However, the outcomes are usually dismal. Here, we report a patient with LCNEC (a metastasis to the brain). After whole brain irradiation, he received a combination of amrubicin and irinotecan chemotherapy, and has been relapse-free for two years. This treatment regimen may be beneficial for patients with advanced LCNEC. Keywords: large-cell neuroendocrine carcinoma, chemotherapy, amrubicin, irinotecan, lung cance

Pneumothorax during Pazopanib Treatment in Patients with Soft-Tissue Sarcoma: Two Case Reports and a Review of the Literature

Pazopanib, a multitargeting tyrosine kinase inhibitor, has single-agent activity in patients with advanced soft-tissue sarcoma. Herein, we describe 2 cases of pneumothorax that occurred during pazopanib treatment in patients with soft-tissue sarcoma. These 2 patients had multiple lung metastases. According to previous reports and our past experience, the risk of pneumothorax may be higher in patients with multiple lung metastases. Although a causal relationship is uncertain, the risk of pneumothorax when prescribing pazopanib for these patients should be considered

Prognostic significance of nestin expression in patients with resected non-small cell lung cancer treated with platinum-based adjuvant chemotherapy; relationship between nestin expression and epithelial to mesenchymal transition related markers.

Although adjuvant platinum-based chemotherapy (AC) has been shown to improve survival of patients with completely resected stage II and stage IIIA non-small cell lung cancer (NSCLC), its effect is limited. Nestin is a class VI intermediate filament protein expressed in neural stem cells and several cancer cells including NSCLC. In the present study, we aimed to determine its prognostic significance concerning survival in NSCLC patients receiving AC.Nestin expression in cancer cells was immunohistochemically studied in 90 patients with completely resected stage II and stage IIIA NSCLC treated with AC and its association with clinicopathologic parameters, including ABCG2, E-cadherin, and vimentin expression, was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of nestin expression on survival.Nestin expression was observed in 28 of the 90 (31.1%) NSCLCs. Clinicopathologically, nestin expression was associated with loss of E-cadherin expression (P = 0.006) and vimentin positive expression (P < 0.001). In survival analysis, nestin expression was significantly associated with a poorer prognosis (P = 0.028). Multivariable analysis confirmed that nestin expression is an independent prognostic indicator in NSCLC patients receiving AC (HR = 2.56; 95% CI, 1.23-5.30, P = 0.01).The present study reveals that nestin expression is a prognostic indicator of a poorer survival probability in NSCLC patients receiving AC, although its prognostic significance still requires confirmation with larger patient populations

Representative immunohistochemical staining for MYH9 in NSCLC.

<p>A: MYH9 was strongly expressed in the membrane of tumor cells in adenocarcinoma. B: MYH9 was strongly expressed in the membrane and cytoplasm of tumor cells in squamous cell carcinoma. (original magnification: A, B ×400).</p

Characteristics of the Patients.

<p>AD = adenocarcinoma; NS = never smoker; p-TNM = pathological TNM; S = smoker</p><p>SQ = squamous cell carcinoma</p><p>*Each case was reassigned to a pathological stage on the basis of the IASLC Lung Cancer Staging Project (seventh edition).</p><p>Characteristics of the Patients.</p

Immunoprecipitation with KU-Lu-6 antibody.

<p>Lane 1: molecular weight marker, lane 2: LC-2/ad-cis lysate combined with KU-Lu-6 antibody, lane 3: LC-2/ad-cis lysate combined with protein L, lane 4: KU-Lu-6 antibody combined with protein L, lane 5: LC-2/ad-cis lysate. Lanes 3 and 4 are negative controls, and specific immunoprecipitated product with KU-Lu-6 antibody was detected in lane 2 (arrow).</p

Immunohistochemical screening of the Ku-Lu-6 antibody with AMeX-fixed LCN1-cis (A) and LCN1 (B) cells.

<p>Membranous staining was observed in LCN1-cis cells, but not in LCN1 cells. (original magnification: A, B ×400).</p

Relationships between MYH9 Expression and Clinicopathological parameters.

<p>* See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121460#pone.0121460.t001" target="_blank">Table 1</a> for explanation of abbreviations and note on asterisk.</p><p>Relationships between MYH9 Expression and Clinicopathological parameters.</p

Cumulative survival of patients with NSCLC according to MYH9 expression estimated by the Kaplan-Meier method.

<p>(A) for all patients; (B) for patients with adenocarcinoma; (C) for patients with squamous cell carcinoma, treating all other causes of death and lost to follow-up as censored cases. MYH9 expression was significantly correlated with poorer survival in resected NSCLCs.</p