The nationwide statistical analysis of each disease of classical myeloproliferative neoplasm (MPN) in Korea has not been reported yet. To this end, we have analyzed incidence rates, survival rates and treatment pattern of polycythemia vera (PV), primary myelofibrosis (MF) and essential thrombocythemia (ET) using Korea National Cancer Incidence Database (KNCIDB) and Health Insurance Review and Assessment Service (HIRA) database. Between 2003 and 2011, a total of 4,342 new cases of MPN were reported to the KNCIDB. ET was the most common, followed by MF and PV. The crude incidence rates for PV, MF, and ET have increased during the period, reaching 0.40, 0.15, and 0.84 per 100,000, respectively. Five-year relative survival rate of all MPN patients was 89.3%, with lowest relative survival rate with MF (53.1%). The prevalence of each disease estimated from HIRA data also increased during the study period. Notably, ET was found to be most prevalent. The prescription rate of hydroxyurea and phlebotomy to PV, MF and ET patients remained constant over the period, and the prescription rate of hydroxyurea was higher in patients with age over 60 years. This is the first Korean nationwide statistics of MPN, using central registry data. This set of data can be utilized to compare the Korean MPN status to international data and guidelines.
Humans ; Hydroxyurea ; Incidence* ; Insurance, Health ; Korea* ; Phlebotomy ; Polycythemia Vera ; Prescriptions ; Prevalence* ; Primary Myelofibrosis ; Survival Rate ; Thrombocythemia, Essential

No abstract available.
Heparin ; Parenteral Nutrition ; Thrombocytopenia

Sarcomatoid carcinoma of the lung is defined as a group of poorly differentiated non-small cell carcinomas that contain a component of sarcoma or a sarcoma-like element. Most sarcomatoid carcinomas are known to have a poor prognosis. We describe a 45-year-old female never smoker and 49-year-old female never smoker with sarcomatoid carcinomas of the lung that expressed a specific EGFR mutation: microdeletion of exon 19. Their cancers progressed rapidly, despite appropriate conventional chemotherapy. After they took the EGFR-targeted agent gefitinib, there was a dramatic reduction in tumor size. Sarcomatoid carcinoma of the lung is a rare cancer whose pathogenesis is not well understood. According to these cases, the EGFR mutation could be a driver mutation and the potential therapeutic target of EGFR-targeted agents for sarcomatoid carcinoma in lung cancer patients, especially never smokers.
Exons ; Female ; Genes, erbB-1 ; Humans ; Lung ; Lung Neoplasms ; Prognosis ; Quinazolines ; Sarcoma

Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

PURPOSE: The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients. MATERIALS AND METHODS: From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea. RESULTS: A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026). CONCLUSION: The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.
Female ; Humans ; Korea ; Patient Education as Topic ; Seoul ; Volition

PURPOSE: Exemestane has shown good efficacy and tolerability in postmenopausal women with hormone receptor-positive metastatic breast cancer. However, clinical outcomes in Korean patients have not yet been reported. METHODS: Data on 112 postmenopausal women with metastatic breast cancer were obtained retrospectively. Clinicopathological characteristics and treatment history were extracted from medical records. All patients received 25 mg exemestane daily until objective disease progression. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR=complete response+partial response+stable disease for 6 months). RESULTS: The median age of the subjects was 55 years (range, 28-76 years). Exemestane treatment resulted in a median PFS of 5.7 months (95% confidence interval [CI], 4.4-7.0 months) and median OS of 21.9 months (95% CI, 13.6-30.3 months). ORR was 6.4% and CBR was 46.4% for the 110 patients with evaluable lesions. Symptomatic visceral disease was independently associated with shorter PFS (hazard ratio, 3.611; 95% CI, 1.904-6.848; p<0.001), compared with bone-dominant disease in a multivariate analysis of PFS after adjusting for age, hormone receptor, human epidermal growth factor receptor 2, Ki-67 status, dominant metastasis site, and sensitivity to nonsteroidal aromatase inhibitor (AI) treatment. Sensitivity to previous nonsteroidal AI treatment was not associated with PFS, suggesting no cross-resistance between exemestane and nonsteroidal AIs. CONCLUSION: Exemestane was effective in postmenopausal Korean women with hormone receptor-positive metastatic breast cancer who failed previous nonsteroidal AI treatment.
Androstadienes ; Aromatase ; Aromatase Inhibitors ; Breast ; Breast Neoplasms ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Retrospective Studies

BACKGROUND/AIMS: We investigated the clinical characteristics and prognosis of elderly patients with acute lymphoblastic leukemia (ALL). METHODS: We reviewed the clinical data, laboratory findings, bone marrow findings, and cytogenetic analysis of elderly patients (> or = 60 years) with ALL, and data of an additional 101 younger adult patients (< 60 years) with ALL were reviewed for comparison. RESULTS: Twenty-six elderly patients (> or = 60 years) and 101 younger adult patients (< 60 years) with ALL were retrospectively enrolled. The median follow-up duration was 6.0 months (range, 0.4 to 113.2) in the elderly patients and 21.7 months (range, 1.0 to 122.7) in the adult patients. In total, 34.6% (9 patients) of the elderly patients and 24.8% (25 patients) of the adult patients had Philadelphia chromosome positive ALL. The overall complete remission (CR) rate was much higher in the younger than in the elderly patients (94.1% vs. 57.7%, p < 0.001). The median overall survival (OS) of the younger patients (< 60 years) was 26.3 months, whereas that of the elderly patients (> or = 60 years) was 10.3 months (p = 0.003). In the elderly patients with ALL, T cell lineage and the presence of lymphadenopathy were significant prognostic factors for OS in a univariate analysis (p = 0.033 and 0.041, respectively). CONCLUSIONS: The outcomes of Korean elderly patients with ALL were poor, and the shorter OS was mainly due to the low CR rate. T-cell lineage and the presence of lymphadenopathy were significant prognostic factors in Korean elderly patients with ALL.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Marrow Examination ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Philadelphia Chromosome ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/drug therapy/genetics/immunology/mortality ; Proportional Hazards Models ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Rate ; Time Factors ; Treatment Outcome ; Young Adult

PURPOSE: FDG PET is effective in treatment response evaluation of cancer. However, there is no standard method for quantitative evaluation of FDG PET, particularly regarding cytostatic drugs. We compared various FDG PET quantitative methods in terms of response determination.METHODS: A total of 39 refractory metastatic colorectal cancer patients who received a multikinase inhibitor treatment were included. Baseline and posttreatment FDG PET/CT scans were performed before and two cycles after treatment. Standardized uptake value (SUV) and total lesion glycolysis (TLG) values using various margin thresholds (30–70 % of maximum SUV with increment 10 %, twice mean SUV of blood pool, SUV 3.0, and SUV 4.0) were measured, with measurement target of the hottest lesion or a maximum of five hottest lesions. Treatment response by the PERCIST criteria was also determined. Predictive values of the PET indexes were evaluated in terms of the treatment response determined by the RECIST 1.1 criteria.RESULTS: The agreement rate was 38 % between response determined by the PERCIST and the RECIST criteria (κ = 0.381). When patients were classified into disease control group (PR, SD) and non-control group (PD) by the RECIST criteria, percent changes of TLG with various margin thresholds (particularly, 30–50%of maximum SUV) exhibited significant differences between the two groups, and high diagnostic power for the response by the RECIST criteria. TLG-based criteria, which used a margin threshold of 50 % of maximum SUV, exhibited a high agreement with the RECIST criteria compared with the PERCIST criteria (κ = 0.606).CONCLUSION: In metastatic colorectal cancer, FDG PET/CT could be effective for treatment response evaluation by using TLG measured by margin thresholds of 30–50%of maximum SUV. Further studies are warranted regarding the optimal cutoff values for this method.
Colorectal Neoplasms ; Cytostatic Agents ; Evaluation Studies as Topic ; Fluorodeoxyglucose F18 ; Glycolysis ; Humans ; Methods ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Response Evaluation Criteria in Solid Tumors

Purpose: Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib. Materials and Methods: In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes. Results: A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. Conclusion Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

Purpose: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. Materials and Methods: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. Results: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. Conclusion The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.