Prognostic Impact of DNA Repair Protein Expression in Non-Small Cell Lung Cancers Treated with Platinum-Based Chemotherapy and Subsequent Curative Lung Resection.

OBJECTIVE: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. METHODS: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy. RESULTS: SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers. CONCLUSION: Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer.

Characteristics and outcomes of ALK+ non-small cell lung cancer patients in Korea.

AIM: This study aimed to describe characteristics, treatment patterns and survival among Korean patients diagnosed with locally advanced or metastatic anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC). METHODS: A retrospective patient chart review was conducted in major cancer centers in Korea in 2014-2015. Participating physicians reviewed patient charts and reported characteristics, treatment patterns, clinician-defined progression-free survival (PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC patients. PFS and OS were estimated using Kaplan-Meier analysis. RESULTS: Physicians reported on 55 ALK+ NSCLC patients. Median age at locally advanced or metastatic NSCLC diagnosis was 60 years. Most patients (82%) received initial chemotherapy; 13% received an ALK inhibitor in the first line; 62% received an ALK inhibitor by the end of follow-up. Of the 30 patients who received crizotinib, 83% discontinued and 13% died during crizotinib therapy. Median PFS on crizotinib was 6.7 months. Of those who discontinued, 32% switched to chemotherapy, 16% switched to a different ALK inhibitor and 52% received no further therapy. After discontinuing crizotinib, median OS was 6.0 months overall, and 3.4 months among patients who did not receive a second-generation ALK inhibitor. CONCLUSION: In this study of locally advanced or metastatic ALK+ NSCLC patients in Korea, roughly one-third did not receive an ALK inhibitor. Among patients who discontinued crizotinib, over half received no further antineoplastic therapy and OS was poor, particularly among patients without second-generation ALK inhibitor use. These findings suggest a need for greater access to effective treatments following crizotinib discontinuation for ALK+ NSCLC patients in Korea.

A Unique Case of Erdheim-Chester Disease with Axial Skeleton, Lymph Node, and Bone Marrow Involvement.

Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis with bone and organ involvement. A 76-year-old man presented with low back pain and a history of visits for exertional dyspnea. We diagnosed him with anemia of chronic disease, cytopenia related to chronic illness, chronic renal failure due to hypertension, and hypothyroidism. However, we could not determine a definite cause or explanation for the cytopenia. Multiple osteosclerotic axial skeleton lesions and axillary lymph node enlargement were detected by computed tomography. Bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. This report describes an unusual presentation of Erdheim-Chester disease involving the bone marrow, axial skeleton, and lymph nodes.

The prognostic significance of elevated levels of serum ferritin before chemotherapy in patients with non-Hodgkin lymphoma.

BACKGROUND: Elevated levels of serum ferritin have been documented to be an adverse prognostic factor in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation. The purpose of this study was to estimate the correlation between elevated levels of serum ferritin and survival outcomes in patients with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: A total of 267 patients who were newly diagnosed with NHL and who received chemotherapy between September 1999 and April 2012 were retrospectively analyzed. RESULTS: In multivariate analysis, other chemotherapy regimens excluding CHOP-like chemotherapy regimens (cyclophosphamide, adriamycin, vincristine, prednisolone) and RCHOP (rituximab plus CHOP), a high level of ß2-microglobulin, a high-intermediate/high risk according to the international prognostic index (IPI), and elevated levels of serum ferritin were all significant independent prognostic factors for 5-year progression-free survival rates. RCHOP and other chemotherapy regimens, a high level of ß2-microglobulin, a high-intermediate/high IPI risk, and high levels of serum ferritin were significant independent prognostic factors for 5-year overall survival rates. CONCLUSION: Elevated levels of serum ferritin of 500 ng/mL or more as well as the use of chemotherapy regimens besides CHOP-like or RCHOP, a high-intermediate/high risk IPI, and a high level of beta2-microglobulin in NHL may be an important marker for predicting poor survival outcomes.