Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Purpose: We aimed to investigate the feasibility of four criteria on oligometastasis (OM) concerning clear survival benefits of local therapy (LT) during tyrosine kinase inhibitor (TKI) treatment in non–small cell lung cancer (NSCLC). Materials and Methods: This single-center, retrospective study included patients with advanced NSCLC who received LT because of OM during TKI treatment at Asan Medical Center from January 2011 to December 2020. At the application of LT OM was classified according to four criteria: TNM, European Organization for Research and Treatment of Cancer Lung Cancer Group (EORTC-LCG), National Comprehensive Network (NCCN), and ORGAN. We compared survival outcomes between patients with and without OM. Results: The median overall survival of the 117 patients included in the analysis was 70.8 months (95% confidence interval [CI], 56.6 to 85.1). The patients with OM meeting all four criteria (hazard ratio [HR] with 95% CI of TNM criteria 0.24 with 0.10-0.57; p=0.001, EORTC-LCG criteria 0.34 with 0.17-0.67; p=0.002, NCCN criteria 0.41 with 0.20-0.86; p=0.018 and ORGAN criteria 0.33 with 0.18-0.60; p < 0.001) had significantly longer survival compared with patients who did not after adjusting for confounding factors. Furthermore, increasing the number of extra-thoracic metastatic organs to two or more were independent predictive factors for worse survival outcomes (2 organs: HR, 3.51; 95% CI, 1.01 to 12.14; p=0.048; 3 organs: HR, 4.31; 95% CI, 0.94 to 19.73; p=0.060; 4 organs: HR, 24.47; 95% CI, 5.08 to 117.80; p < 0.001). Conclusion Patients with OM defined by all four criteria showed prognostic benefits from LT during TKI therapy.

Purpose: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. Materials and Methods: Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. Results: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. Conclusion Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Purpose: Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261). Materials and Methods: Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR). Results: In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%). Conclusion Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.
Anemia ; Arm ; Cisplatin* ; Diarrhea ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Etoposide* ; Humans ; Lung Neoplasms ; Male ; Nausea ; Small Cell Lung Carcinoma*

Objectives Medical knowledge extraction (MKE) plays a key role in natural language processing (NLP) research in electronic medical records (EMR), which are the important digital carriers for recording medical activities of patients. Named entity recognition (NER) and medical relation extraction (MRE) are two basic tasks of MKE. This study aims to improve the recognition accuracy of these two tasks by exploring deep learning methods. Methods This study discussed and built two application scenes of bidirectional long short-term memory combined conditional random field (BiLSTM-CRF) model for NER and MRE tasks. In the data preprocessing of both tasks, a GloVe word embedding model was used to vectorize words. In the NER task, a sequence labeling strategy was used to classify each word tag by the joint probability distribution through the CRF layer. In the MRE task, the medical entity relation category was predicted by transforming the classification problem of a single entity into a sequence classification problem and linking the feature combinations between entities also through the CRF layer. Results Through the validation on the I2B2 2010 public dataset, the BiLSTM-CRF models built in this study got much better results than the baseline methods in the two tasks, where the F1-measure was up to 0.88 in NER task and 0.78 in MRE task. Moreover, the model converged faster and avoided problems such as overfitting. Conclusion This study proved the good performance of deep learning on medical knowledge extraction. It also verified the feasibility of the BiLSTM-CRF model in different application scenarios, laying the foundation for the subsequent work in the EMR field.

OBJECTIVETo investigate the relationship between acute graft-versus-host disease and graft composition in patients with aplastic anemia(AA) after haploidentical hematopoietic stem cell transplantation.

METHODSFifty-seven cases of AA after haploidentical hematopoietic stem cell transplantation were retrospectively analyzed. All the patients were divided into 2 groups according to whether presence or absence grade Ⅱ-Ⅳ aGVHD, the relationship between aGVHD and graft composition was analyzed by comparing the differences of graft components between the 2 groups.

RESULTSFourteen out of 57 patients had grade Ⅱ-Ⅳ aGVHD and the other 43 did not have grade Ⅱ-Ⅳ aGVHD. The mononuclear cells, CD3, CD4, CD8, NK cells, NKT cells, B cells and Treg cells were not significantly different between the 2 groups (P>0.05), the CD34 cell count in the patients with grade Ⅱ-Ⅳ aGVHD was 3.85（1.73-10.61）×10/kg, which was significantly lower than that without grade Ⅱ-ⅣaGVHD: 6.31（2.98-19.35）×10/kg (P<0.05).

CONCLUSIONSThe incidence of grade Ⅱ-Ⅳ aGVHD may be related with CD34 cell count in AA after haploidentical hematopoietic stem cell transplantation..

STUDY DESIGN: Literature review. OBJECTIVES: To propose possible mechanisms of osteoporotic back pain and its management with antiosteoporotic drugs. SUMMARY OF LITERATURE REVIEW: No general conclusion has yet been reached regarding whether osteoporosis without fractures can cause pain. Instead, only treatments for back pain without osteoporotic spine fractures have been reviewed in the previous literature. Although key studies of antiosteoporotic drugs have not investigated their analgesic efficacy, plausible mechanisms have been suggested. MATERIALS AND METHODS: The analgesic effects of antiosteoporotic agents available in Korea were reviewed. RESULTS: Rather than the long-term use of conventional analgesics or narcotics, antiosteoporotic drugs would be more beneficial because they can enhance bone strength and have fewer side effects. Both anabolic and antiresorptive agents available in Korea have been proven to have an analgesic effect against osteoporotic back pain, with or without fractures. Anabolic agents depend on skeletal effects. Among antiresorptive agents, bisphosphonates have both skeletal and extraskeletal mechanisms for analgesia. Calcitonin and selective estrogen receptor modulators mostly depend on extraskeletal effects. The order of analgesic strength for osteoporotic back pain is teriparatide > bisphosphonate > calcitonin. This implies that the analgesic effect of antiosteoporotic drugs primarily depends on their skeletal effects rather than on their extraskeletal effects. Moreover, because non-fracture osteoporotic pain has been recognized only in the spine, where fractures can occur without a sensible injury, pain may arise from undiscovered spine fractures. CONCLUSIONS: Antiosteoporotic drugs ameliorate osteoporotic back pain. Their analgesic strength is proportional to their fracture prevention efficacy.
Anabolic Agents ; Analgesia ; Analgesics ; Back Pain ; Bone Density Conservation Agents ; Calcitonin ; Diphosphonates ; Korea ; Narcotics ; Osteoporosis ; Selective Estrogen Receptor Modulators ; Spine ; Teriparatide

STUDY DESIGN: Retrospective case-control study. PURPOSE: To examine the hypothesis that the misuse of thrombin-containing local hemostatics (TCLH) increases the risk of postoperative spinal epidural hematoma (POSEH). OVERVIEW OF LITERATURE: Many studies have focused on hypocoagulability as a risk factor for POSEH. However, there are no prior reports on the increased risk of POSEH in hypercoagulable states. METHODS: Posterior instrumented lumbar spine surgery cases over 2 consecutive years were divided into two groups: a study group (98 patients in whom TCLH was used) and a control group (176 patients in whom TCLH was not used). The excess TCLH matrix that was not associated with blood clot was not removed from the patients in the study group. The senior author decided whether to use TCLH or not. Suction drains were used in all patients. The demographics, coagulation-related factors, and intraoperative factors of the patients in the two groups were analyzed. The development of POSEH was compared between the two groups. RESULTS: The two groups were homogenous in demographics (age and sex), coagulation-related factors (platelet count, prothrombin time, activated partial thromboplastin time, and platelet function analysis), and surgical factors (total blood loss, operation time, blood loss/10 minutes, number of fusion segments, posterolateral fusion/posterior lumbar interbody fusion, and virgin or revision surgery). POSEH developed more frequently in the patients in the study group than in those in the control group (14/98 patients, 14.3% vs. 3/176 patients, 1.7%, respectively; p=0.001; odds ratio, 17.1). CONCLUSIONS: TCLH causes blood clot not only at the edge of damaged vessels but also at the site of extravascular blood. Excess TCLH matrix not associated with blood clot at the epidural space can enhance POSEH development because early clotted hematomas do not drain through suction drains.
Blood Platelets ; Case-Control Studies ; Demography ; Epidural Space ; Hematoma ; Hematoma, Epidural, Spinal* ; Hemostatics* ; Humans ; Odds Ratio ; Partial Thromboplastin Time ; Prothrombin Time ; Retrospective Studies ; Risk Factors ; Spine ; Suction