Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma.

Mutational processes giving rise to lung adenocarcinomas (LADCs) in non-smokers remain elusive. We analyzed 138 LADC whole genomes, including 83 cases with minimal contribution of smoking-associated mutational signature. Genomic rearrangements were not correlated with smoking-associated mutations and frequently served as driver events of smoking-signature-low LADCs.

Harmonization of Busulfan Plasma Exposure Unit (BPEU): A Community-Initiated Consensus Statement.

Busulfan therapeutic drug monitoring (TDM) is often used to achieve target plasma exposures. Variability in busulfan plasma exposure units (BPEU) is a potential source for misinterpretation of publications and protocols and is a barrier to data capture by hematopoietic cell transplantation (HCT) registry databases. We sought to harmonize to a single BPEU for international use.

Preclinical Modeling of Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutations.

Introduction: NSCLC with EGFR exon 20 insertion mutations is the third most common type of EGFR-mutant NSCLC and is resistant to EGFR tyrosine kinase inhibitors (TKIs). This study was conducted to evaluate the efficacies of first- to third-generation EGFR TKIs against NSCLC cells harboring EGFR exon 20 insertion mutations.

Methods: We developed seven EGFR exon 20 insertion-mutant Ba/F3 models and one patient-derived NSCLC (SNU-3173) of subtypes A763insFQEA, V769insASV, D770insSVD, D770insNPG, P772insPR, H773insH, H773insNPH, and H773insAH.

Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015.

Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center.

NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors.

Background: Treatment with tyrosine kinase inhibitors (TKIs) has improved the outcomes for patients with non-small cell lung cancer (NSCLC) harboring targetable driver mutations. However, acquired resistance to TKIs invariably develops within approximately 1 year of treatment by various mechanisms, including gatekeeper mutations, alternative pathway activation and histological transformations. Because immunotherapy is an option for patients with drug-resistant cancers, we generated several TKI-resistant NSCLC cell lines in vitro, and then evaluated the cytotoxicity of NK92-CD16 cells to these resistant cells.

Pemetrexed in the Treatment of Leptomeningeal Metastasis in Patients With EGFR-mutant Lung Cancer.

Introduction: Leptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC.

Patients And Methods: We retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016.

Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma.

Purpose: Lymphopenia in patients with glioblastoma (GBM) is related to treatment as well as disease progression. This retrospective study investigated the prevalence, influencing factors, recoverability, and clinical significance of lymphopenia in GBM patients treated with concomitant chemoradiotherapy (CCRT).

Patients And Methods: A total of 219 patients with newly diagnosed GBM who had received at least 3 cycles of adjuvant temozolomide (TMZ) followed by CCRT with TMZ were enrolled.

Late Recurrence of Wilms Tumor After 17 Years: A Case Report.

Wilms tumor is the most common renal malignancy in children. Most of Wilms tumor recurrences occur within 2 years of the first diagnosis. Relapse after 5 years after the first diagnosis is called "late recurrence" and is rare in Wilms tumor.

Electromagnetic navigation bronchoscopic dye marking for localization of small subsolid nodules: Retrospective observational study.

Thoracoscopic resection of small subsolid nodules is challenging and requires preoperative localization. We investigated the efficacy, safety, and factors affecting accuracy in localizing pulmonary nodules with electromagnetic navigation bronchoscopy (ENB)-guided dye marking.Patients with small subsolid nodule(s) who underwent thoracoscopic resection after ENB-guided dye marking were retrospectively reviewed.

Acute Kidney Injury in Pediatric Cancer Patients.

Objective: To analyze the incidence of acute kidney injury (AKI) in the first year after cancer diagnosis in children and to evaluate the short-term and long-term effects on renal function and proteinuria.

Study Design: Retrospective review of medical records was done on children who were diagnosed and treated for cancer at Seoul National University Hospital between 2004 and 2013. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria.

Validation of treatment outcomes according to revised severity criteria from European Society for Blood and Marrow Transplantation (EBMT) for sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD).

Traditional severity criteria of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) were determined retrospectively but found inappropriate for therapeutic decisions. Data of 203 patients with SOS/VOD were collected according to the modified Seattle diagnostic criteria and were analyzed for validation of the revised severity criteria recently proposed from European Society for Blood and Marrow Transplantation (EBMT). According to the traditional severity criteria, none of the patients were mild grade, while 63.

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study.

Background: NUT carcinoma is a rare aggressive disease caused by fusion, and upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC-targeting agents against patient-derived NUT carcinoma cell lines.

Materials And Methods: Thirteen patients with NUT carcinoma were evaluated for p53, C-MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD-L1) by immunohistochemistry.

Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

Background & Aims: Genome-wide association studies (GWASs) have associated approximately 50 loci with risk of colorectal cancer (CRC)-nearly one third of these loci were initially associated with CRC in studies conducted in East Asian populations. We conducted a GWAS of East Asians to identify CRC risk loci and evaluate the generalizability of findings from GWASs of European populations to Asian populations.

Methods: We analyzed genetic data from 22,775 patients with CRC (cases) and 47,731 individuals without cancer (controls) from 14 studies in the Asia Colorectal Cancer Consortium.

Intracranial Ewing sarcoma with whole genome study.

Introduction: Ewing sarcoma (ES) as a primary intracranial tumor is very rare. Recently, CNS embryonal tumors with ES-like genomic change have been reported. Patients and methods We report a case of intracranial Ewing sarcoma in a 13-year-old girl who complained of headache and migraine.

Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor.

Characterizing the molecular immune subtype and micro-environment of lung cancer is necessary to understand immunogenic interactions between infiltrating immune and stromal cells, and how tumor cells overcome immune checkpoint blockades. This study seeks to identify computational methodologies for subtyping gene expression-based tumor-immune micro-environment interactions, which differentiate non-small cell lung cancer (NSCLC) into immune-defective and immune-competent subtypes. Here, 101 lung squamous cell carcinomas (LUSCs) and 87 lung adenocarcinomas (LUADs) tumor samples have been analyzed.

A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma.

Lessons Learned: Pazopanib shows a modest efficacy in metastatic alveolar soft part sarcoma.Clinical outcomes were comparable to those in previous studies using antiangiogenic drugs.Further prospective studies evaluating the benefit of pazopanib in alveolar soft part sarcoma with a larger sample are warranted to validate results.

Brainstem astroblastoma with MN1 translocation.

Astroblastoma is a rare glial neoplasm that occurs mostly in the cerebral hemisphere of children, adolescents and young adults. Although astroblastic perivascular pseudorosettes are unique histopathology of this neoplasm, diagnosis is usually challenging. Recently, it was discovered that the meningioma 1 gene (MN1)-altered pediatric central nervous system high-grade neuroepithelial tumors are actually astroblastomas.

Effect of dose rate on pulmonary toxicity in patients with hematolymphoid malignancies undergoing total body irradiation.

Background: This study evaluated the effect of radiation dose rate in patients with hematolymphoid malignancies undergoing myeloablative conditioning with total body irradiation (TBI), for hematopoietic stem cell transplantation.

Methods: The incidence of pulmonary toxicity (PT) and treatment efficacy were compared between the conventional (≥ 6 cGy/min) and reduced dose rate (< 6 cGy/min). Seventy-seven patients receiving once-daily TBI between 2000 and 2016 were reviewed.

Radiologic evaluation of pulmonary injury following carmustine- and cyclophosphamide-based preparative regimen for autologous peripheral blood stem cell transplantation in children.

Background: Toxicity of carmustine and cyclophosphamide can cause pulmonary injury after hematopoietic stem cell transplantation.

Objective: To evaluate the radiologic findings of pulmonary injuries following carmustine- and cyclophosphamide-based preparative regimens in children.

Materials And Methods: From 2010 to 2014, 35 children received carmustine- and cyclophosphamide-based preparative regimens.

Overexpression of endoplasmic reticulum stress-related proteins, XBP1s and GRP78, predicts poor prognosis in pulmonary adenocarcinoma.

Objectives: Endoplasmic reticulum (ER) stress is associated with tumor development and progression via pro-tumorigenic and anti-tumorigenic effects. However, the clinicopathological implications of the ER stress pathway in non-small cell lung cancer remain unclear. Therefore, we sought to address these issues in this study.

Favorable Outcome of Post-Transplantation Cyclophosphamide Haploidentical Peripheral Blood Stem Cell Transplantation with Targeted Busulfan-Based Myeloablative Conditioning Using Intensive Pharmacokinetic Monitoring in Pediatric Patients.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PTCy) was performed previously in adults using a nonmyeloablative conditioning regimen and bone marrow as a graft source. In an effort to reduce relapse rates, myeloablative conditioning regimens with higher intensities are now used. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing in children for effective myeloablation and to reduce toxicity.

Successful Treatment of Pediatric Epstein-Barr Virus-positive Aggressive Natural Killer-Cell Leukemia.

Epstein-Barr virus (EBV)-positive aggressive natural killer-cell leukemia (ANKL) is a rare malignancy of mature natural killer cells, with a very poor survival rate. Patients have a rapidly declining clinical course and a poor prognosis, with a median survival of only a few months. Herein, we describe a 16-year-old boy who was diagnosed with EBV-positive ANKL and successfully treated using combination chemotherapy and a subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT).

The prognostic effect of the epidermal growth factor receptor gene mutation on recurrence dynamics of lung adenocarcinoma.

Objectives: The prognostic effects of epidermal growth factor receptor (EGFR) gene mutation on lung adenocarcinoma recurrence have not been well established. The relationship between EGFR gene mutation and recurrence dynamics of lung adenocarcinoma was investigated.

Methods: A total of 527 patients with complete resection for adenocarcinoma were reviewed retrospectively.

Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical centre.

Objectives: To validate the performances of two prediction models (Brock and Lee models) for the differentiation of minimally invasive adenocarcinoma (MIA) and invasive pulmonary adenocarcinoma (IPA) from preinvasive lesions among subsolid nodules (SSNs).

Design: A retrospective cohort study.

Setting: A tertiary university hospital in South Korea.