Chi Hoon Maeng

The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC)

We evaluated whether ribonucleotide reductase regulatory subunit M1 (RRM1) protein expression by immunohistochemistry (IHC) is a predictor of survival and response in gemcitabine-treated, advanced non-small cell lung cancer (NSCLC). We retrospectively collected 40 formalin-fixed, paraffin-embedded NSCLC tissues to investigate the protein expression of RRM1 by IHC with a purified rabbit anti-human RRM1 polyclonal antibody (ProteinTech Group, Chicago, IL, USA). RRM1 expression was positive in 14 (35%) and negative in 26 (65%) cases. Ten (25%) patients were treated as first-line and 30 (75%) patients as second-line. The median age was 61 years and M/F was 31/9. Stage IIIB/IV was 7/33 and adenocarcinoma/squamous cell carcinoma/other cell type was 20/16/4. Other characteristics, including age, gender, stage, cell type and first/second-line were not statistically different in the RRM-positive and RRM-negative groups. The overall survival of RRM1-positive groups was significantly shorter than RRM-negative groups (5.1 months vs. 12.9 months, p = 0.022). The response rates of 38 out of 40 patients were assessable. Disease control rate (PR+SD) of the RRM1-positive groups was significantly lower than that of RRM1-negative groups (23% vs. 56%, p = 0.053). In patients with gemcitabine-treated advanced NSCLC, patients with RRM1-positive tumors had worse overall survival and disease control than patients with RRM1-negative tumors.

Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication.

Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.

A Case of Organizing Pneumonia Associated with Rituximab

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody used to treat CD20-positive B-cell non-Hodgkins lymphoma (NHL). Although most of the adverse effects associated with rituximab are usually reversible and temporary infusion-related reactions, including fever, chills, flushing and skin reactions, there are several reports of pulmonary events after long-term administration of rituximab. We present a case of asymptomatic nodular organizing pneumonia occurring during rituximab-based chemotherapy in a patient with non-Hodgkins lymphoma.

The Prognostic 97 Chemoresponse Gene Signature in Ovarian Cancer

Patient diagnosis and care would be significantly improved by understanding the mechanisms underlying platinum and taxane resistance in ovarian cancer. Here, we aim to establish a gene signature that can identify molecular pathways/transcription factors involved in ovarian cancer progression, poor clinical outcome, and chemotherapy resistance. To validate the robustness of the gene signature, a meta-analysis approach was applied to 1,020 patients from 7 datasets. A 97-gene signature was identified as an independent predictor of patient survival in association with other clinicopathological factors in univariate [hazard ratio (HR): 3.0, 95% Confidence Interval (CI) 1.66–5.44, p = 2.7E-4] and multivariate [HR: 2.88, 95% CI 1.57–5.2, p = 0.001] analyses. Subset analyses demonstrated that the signature could predict patients who would attain complete or partial remission or no-response to first-line chemotherapy. Pathway analyses revealed that the signature was regulated by HIF1α and TP53 and included nine HIF1α-regulated genes, which were highly expressed in non-responders and partial remission patients than in complete remission patients. We present the 97-gene signature as an accurate prognostic predictor of overall survival and chemoresponse. Our signature also provides information on potential candidate target genes for future treatment efforts in ovarian cancer.

The Role of Prophylactic Cranial Irradiation in Patients With Extensive Stage Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Introduction: The role of prophylactic cranial irradiation (PCI) is controversial in patients with extensive stage small cell lung cancer. The aim of this study was to determine the impact of PCI in these patients. Methods: We performed a systematic review and meta‐analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. A systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Central Register. The primary outcome was overall survival (OS). Results: We identified five studies comprising 984 patients, of whom 448 received PCI and 536 did not receive PCI. In pooled estimates, PCI did not statistically improve OS compared with controls (hazard ratio [HR] = 0.82; 95% confidence interval [CI]: 0.60–1.11; I2 = 77%; p = 0.19). However, the PCI group had a significant advantage in 1‐year survival compared to the no‐PCI group (37.1% versus 27.1%; risk ratio = 0.87; 95% CI: 0.80–0.95; I2 = 47%; p = 0.002), and the pooled estimates indicated that progression‐free survival and the risk of brain metastasis were associated with significant benefit in the PCI group (HR = 0.83; 95% CI: 0.70–0.98; I2 = 22%; p = 0.03; and HR = 0.34; 95% CI: 0.23–0.50; I2 = 0%; p < 0.001, respectively). Conclusions: Our findings suggest that PCI in patients with extensive stage small cell lung cancer may lead to a significant benefit in 1‐year survival, progression‐free survival, and the risk of brain metastasis, despite the lack of a significant advantage in OS.

Thyroid Cancer and T Lymphoblastic Leukemia in Crohn Disease: A Case Report and Literature Review

The effectiveness of the tumor necrosis-α (TNF-α) blockade has changed the treatment of several chronic inflammatory diseases, including inflammatory bowel disease; however, this treatment also has disadvantages. The use of immunosuppressants in combination with infliximab has been associated with greater risk of developing malignant neoplasms. Herein, we report the case of a 33-year-old ethnic Korean man with Crohn disease (CD) who developed papillary thyroid carcinoma (PTC) and, subsequently, T-cell acute lymphoblastic leukemia (ALL) after approximately 16.0 years of immunosuppressant therapy and 5.5 years of infliximab therapy. To our knowledge, this is the first case described in the literature of 2 different malignant neoplasms, 1 of hematologic origin and the other involving the solid organs, in a patient with CD. Through a systematic literature review, we found 28 cases of acute leukemia in adult patients with CD, of whom 22 had myeloid leukemia and 6 had lymphoid leukemia. Half of the patients with ALL underwent TNF-α-blocker therapy in combination with thiopurines.

Crohn's disease and smoldering multiple myeloma: a case report and literature review

Crohns disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD.

962PCLINICAL OUTCOME OF UPFRONT HIGH DOSE CHEMOTHERAPY PLUS TOTAL BODY IRRADIATION WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS ASSOCIATED WITH T-CELL LYMPHOMA

ABSTRACT Aim: T-cell lymphoma is characterized by aggressiveness and poor response to conventional chemotherapy. Athough high-dose chemotherapy plus total body irradiation with autologous stem cell transplantation (HD TBI-ASCT) has been introduced to improve clinical outcomes, significant benefit has not been established yet. Furthermore, the role of TBI in this setting is not proven either. We report data of upfront HD TBI-ASCT for patients associated with T-cell lymphoma. Methods: We collected clinical data of patients who were treated with upfront HD TBI-ASCT for T-cell lymphoma from January 2004 to December 2013 at Samsung Medical Center, Korea. Total 42 patients were analyzed retrospectively. All patients received etoposide and cyclophosphamide plus TBI (900 cGy for 3 days) as conditioning regimen. The clinical data includes age, sex, histological subtypes, IPI score, types of induction chemotherapy and response, pre-ASCT status, recurrence or death. Results: Most common histological subtype was natural killer/T-cell lymphoma, nasal type. Median hospitalized period was 17 days. Median recovery time of neutrophil and platelet was 10 and 11 days, respectively. 5-year survival rate was 57.5%. Median relapse-free survival of the patients was 2.1 years and median overall survival was 2.2 years suggesting very aggressive and refractory disease after relapse. Initial complete response to induction chemotherapy was related to better OS (not reached vs 6.0 months) (p = 0.009) even if RFS failed to show statistical significant difference (p = 0.081). Pre-ASCT PET response (CR vs non-CR) showed strong prognostic impact for Relapse-free survival (not reached vs 6.0 months) and overall survival (not reached vs 9.6 months) (p Conclusions: Upfront HD TBI-ASCT is tolerable and effective treatment strategy and might improve RFS and OS in selected patients. Disclosure: All authors have declared no conflicts of interest.

All-Trans Retinoic Acid–Induced Myositis and Retinoic Acid Syndrome in Microgranular-Variant Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML). All-trans retinoic acid (ATRA) is an effective drug in the treatment of APL by promoting the terminal differentiation of leukemic cells into phenotypically mature myeloid cells. The microgranular-variant APL counts for a quarter of APL and is similar to monocytic origin leukemia. The microgranular-variant type has no effect on APL treatment. ATRA is related with some serious side effects such as Sweet’s syndrome and retinoic acid syndrome (RAS). Histologic characteristics of RAS are seen in capillary leakage and infiltration of organs by mature myeloid cells. ATRA-induced myositis is rarely described in adults and rare in children with APL. There have been increasing reports of ATRA-induced myositis, with its frequent association with RAS and Sweet’s syndrome. We report a patient with ATRA-induced myositis and RAS in microgranular variant APL and review the previously reported cases in the literature of ATRA-induced myositis. * APL : acute promyelocytic leukemia; ATRA : all-trans retinoic acid; RAS : retinoic acid syndrome; FISH : fluorescence in situ hybridization; MRI : magnetic resonance imaging; CK : creatine kinase; ICU : intensive care unit; CT : computed tomography; WBC : white blood cell