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Robust Association Tests for the Replication of Genome-Wide Association Studies
Joo, Jungnam,Park, Ju-Hyun,Lee, Bora,Park, Boram,Kim, Sohee,Yoon, Kyong-Ah,Lee, Jin Soo,Geller, Nancy L. Hindawi Publishing Corporation 2015 BioMed research international Vol.2015 No.-
<P>In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimum <I>p</I> value of Pearson's Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by <I>p</I> values of the discovery and replication studies.</P>
Kim, Yeon-Joo,Kim, Joo-Young,Lim, Do Hoon,Park, Hyeon Jin,Joo, Jungnam,Sung, Ki Woong,Shin, Hyung Jin,Kim, Seung-Ki,Phi, Ji Hoon,Kim, Il Han,Park, Kyung Duk,Ahn, Seung-do,Jung, Jinhong,Ra, Young-Shin M. Nijhoff ; Kluwer Academic Publishers 2013 Journal of neuro-oncology Vol.113 No.1
<P>We analyzed the treatment outcomes of intracranial ependymomas in Korean children aged <18 years. Data for 96 patients were collected from five hospitals. Survival rates were calculated using the Kaplan-Meier method. Log-rank tests for univariate analyses and Cox regression model for multivariate analysis were conducted to identify prognostic factors for survival. The median age of the patients was 4 years (range, 0.3-17.9 years). The median follow-up was 55 months (range, 2-343 months). Age <3 years was an important factor for selecting adjuvant therapy after surgery. Among children aged <3 and 3 years, adjuvant radiotherapy (RT) was applied to 55 and 84 %, respectively, and adjuvant chemotherapy to 52 and 10 %, respectively. The 5 year local progression-free survival (LPFS), disease-free survival (DFS), and overall survival (OS) rates were 54, 52, and 79 %, respectively. Gross total resection was the most significant prognostic factor for all survival endpoints. Age 3 years and RT were significant prognostic factors for superior LPFS and DFS. However, the significance of age was lost in multivariate analysis for DFS. LPFS, DFS, and OS were superior in patients who started RT within 44 days after surgery (the median time) than in patients who started RT later in the patients aged 3 years. Postoperative RT was a strong prognostic factor for intracranial ependymomas. Our results suggest that early use of RT is an essential component of treatment, and should be considered in young children.</P>
Kim, Yeon-Joo,Park, Won,Ha, Boram,Park, Boram,Joo, Jungnam,Kim, Tae Hyun,Park, In Hae,Lee, Keun Seok,Lee, Eun Sook,Shin, Kyung Hwan,Kim, Haeyoung,Yu, Jeong Il,Choi, Doo Ho,Huh, Seung Jae,Wee, Chan Woo 대한암학회 2017 Cancer Research and Treatment Vol.49 No.4
<P><B>Purpose</B></P><P>The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. </P><P><B>Materials and Methods</B></P><P>We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. </P><P><B>Results </B></P><P>We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081).</P><P><B>Conclusion </B></P><P>PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.</P>
Kwon, Ji-Woong,Yoon, Joon Ho,Lim, Myong Cheol,Joo, Jungnam,Yoo, Heon,Shin, Sang-Hoon,Park, Sang Yoon,Lee, Sang Hyeon,Kim, Yeon-Joo,Kim, Joo-Young,Gwak, Ho-Shin Blackwell Scientific Publications 2018 International journal of gynecological cancer Vol.28 No.8
<B>Objectives</B><P>The most appropriate treatments for brain metastases from ovarian cancer have not been established mainly because of its rarity. The objective of this study was to describe clinical results of treatment and prognostic factors of patients with brain metastases from ovarian cancer treated at a single institution.</P><B>Materials and Methods</B><P>We retrieved information from the electronic medical records of 56 consecutive patients (2.8%) with brain metastases, from a total of 2008 patients with ovarian cancer. Endpoints were the pattern of treatment failure, progression-free survival, and overall survival (OS).</P><B>Results</B><P>Radiation was the most common initial treatment for brain metastases (59%), followed by surgery (23%). The median progression-free survival was 9.8 months. Radiological progression was confirmed in 20 patients: 7 had leptomeningeal carcinomatosis (37%), 8 had local recurrence, and 5 had distant recurrence. Median OS was 11.25 months, and the 1-year OS rate was 48.2%. Patients received surgery for single metastasis as initial treatment showed median OS of 24.1 months, which was significantly prolonged compared with the other patients (<I>P</I> = 0.0002). Of the 48 patients who died, 29 (60%) died of systemic disease and 7 (15%) died of central nervous system progression. Karnofsky Performance Status greater than or equal to 70, control of systemic cancer, serous histology, and surgery for brain metastases were associated with improved OS in multivariable analysis (<I>P</I> < 0.05).</P><B>Conclusions</B><P>Surgical resection for single or symptomatic brain metastases from ovarian cancer prolonged OS significantly. Multimodality treatment, including control of systemic cancer, appeared to be an important factor in prolonging OS.</P>
Jungnam Lee,Young-Joo Jin,Seung Kak Shin,Jung Hyun Kwon,Sang Gyune Kim,Young Ju Suh,Yujin Jeong,Jung Hwan Yu,Jin-Woo Lee,Oh Sang Kwon,Soon Woo Nahm,Young Seok Kim 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.2
Background/Aims: We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA). Methods: We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment. Results: The median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396– 1.232) (P=0.215) and 1.698 (1.777–2.448) (P=0.005), respectively. Conclusions: SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.
Kim, Sun Young,Joo, Jungnam,Kim, Tae Won,Hong, Yong Sang,Kim, Jeong Eun,Hwang, In Gyu,Kim, Beom Gyu,Lee, Keun-Wook,Kim, Ji-Won,Oh, Ho-Suk,Ahn, Joong Bae,Zang, Dae Young,Kim, Dae Yong,Oh, Jae Hwan,Baek Elsevier 2018 International journal of radiation oncology, biolo Vol.101 No.4
<P><B>Purpose</B></P> <P>Preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME) in locally advanced rectal cancer is the standard of care. To date, the role of consolidation chemotherapy after CRT has rarely been addressed through randomized trials. This study aimed to evaluate the efficacy of CRT followed by consolidation chemotherapy compared with CRT alone.</P> <P><B>Methods and Materials</B></P> <P>This study enrolled patients with adenocarcinoma of the rectum and cT3 or cT4 disease with any N category and no metastasis. In arm A (control arm), we planned CRT (50.4 Gy in 28 fractions) with capecitabine followed by TME. In arm B, 2 cycles of capecitabine and oxaliplatin were administered 1 week after the completion of CRT before TME (capecitabine, 1700 mg/m<SUP>2</SUP> per day from day 1 to 14, and oxaliplatin, 100 mg/m<SUP>2</SUP> on day 1, every 3 weeks). The downstaging rate (the proportion of ypT0 to ypT2 and ypN0M0) was the primary endpoint, which was to be tested with a 1-sided type I error of 15% and with 85% power.</P> <P><B>Results</B></P> <P>From September 2014 to February 2016, 110 patients (56 in arm A and 54 in arm B) were randomized and 108 (55 in arm A and 53 in arm B) started CRT. TME was conducted per protocol in 96 patients (52 in arm A and 44 in arm B). In arms A and B, downstaging was achieved in 21.2% and 36.4% (<I>P</I> = .077), respectively, and the pathologic complete response rate was 5.8% and 13.6% (<I>P</I> = .167), respectively. Grade ≥3 adverse events occurred in 3.6% of patients in arm A and 9.4% of patients in arm B during the preoperative treatment phase and in 1.9% and 9.0%, respectively, during the postoperative recovery phase.</P> <P><B>Conclusions</B></P> <P>Consolidation chemotherapy with 2 cycles of capecitabine and oxaliplatin demonstrated a marginal improvement in the downstaging rate. However, a phase 3 trial of this strategy is discouraged because of the high dropout rate and safety issues.</P>
Eom, Bang Wool,Joo, Jungnam,Kim, Young-Woo,Park, Boram,Park, Ji Yeon,Yoon, Hong Man,Lee, Jun Ho,Ryu, Keun Won Raven Press 2013 Annals of surgical oncology Vol.20 No.8
<P>Extended lymph node dissection beyond D2 in resectable gastric cancer has not shown any survival benefits. However, whether the retropancreatic (No. 13) lymph node should be dissected still remains controversial. The purpose of this study was to evaluate the effects of additional No. 13 lymph node dissection on D2 gastrectomy for gastric cancer in terms of overall survival.</P>
Gwak, Ho-Shin,Joo, Jungnam,Kim, Sohee,Yoo, Heon,Shin, Sang Hoon,Han, Ji-Youn,Kim, Heung Tae,Lee, Jin Soo,Lee, Seung Hoon Lippincott Williams Wilkins 2013 JOURNAL OF THORACIC ONCOLOGY Vol.8 No.5
<P>Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non-small-cell lung cancer.</P>
Kim, Young-Woo,Joo, Jungnam,Yoon, Hong Man,Eom, Bang Wool,Ryu, Keun Won,Choi, Il Ju,Kook, Myeong Cherl,Schuhmacher, Christoph,Siewert, Joerg Ruediger,Reim, Daniel Williams & Wilkins Co 2016 Medicine Vol.95 No.28
<P><B>Abstract</B></P><P>Several retrospective analyses on patients who underwent gastric cancer (GC) surgery revealed different survival outcomes between Eastern (Korean, Japanese) and Western (USA, Europe) countries due to potential ethnical and biological differences. This study investigates treatment outcomes between specialized institution for GC in Korea and Germany.</P><P>The prospectively documented databases of the Gastric Cancer Center of the National Cancer Center, Korea (NCCK) and the Department of Surgery of the Technische Universitaet Muenchen (TUM), Germany were screened for patients who underwent primary surgical resection for GC between 2002 and 2008. Baseline characteristics were compared using <I>χ</I><SUP>2</SUP> testing, and 2 cohorts were matched using a propensity score matching (PSM) method. Patients’ survival was estimated using Kaplan–Meier method, and multivariable Cox proportional hazard model was used for comparison.</P><P>Three thousand seven hundred ninety-five patients were included in the final analysis, 3542 from Korea and 253 from Germany. Baseline characteristics revealed statistically significant differences for age, tumor location, pT stage, grading, lymphatic vessel infiltration (LVI), comorbidities, number of dissected lymph nodes (LN), postoperative complications, lymph-node ratio stage, and application of adjuvant chemotherapy. After PSM, 171 patients in TUM were matched to NCCK patients, and baseline characteristics for both cohorts were well balanced. Patients in Korea had significantly longer survival than those in Germany both before and after PSM. When the analysis was performed for each UICC stage separately, same trend was found over all UICC stages before PSM. However, significant difference in survival was observed only for UICC I after PSM.</P><P>This analysis demonstrates different survival outcomes after surgical treatment of GC on different continents in specialized centers after balancing of baseline characteristics by PSM.</P>
Gwak, Ho-Shin,Joo, Jungnam,Shin, Sang-Hoon,Yoo, Heon,Han, Ji-Youn,Kim, Heung Tae,Yun, Tak,Ro, Jungsil,Lee, Jin Soo,Lee, Seung Hoon AlphaMed Press 2014 The oncologist Vol.19 No.10
<P><B>Background.</B></P><P>The efficacy of ventriculolumbar perfusion (VLP) chemotherapy with methotrexate (MTX) was evaluated for treatment of leptomeningeal carcinomatosis (LMC).</P><P><B>Methods.</B></P><P>The primary outcome was the response rate of increased intracranial pressure (ICP), which was available for comparison from historical data on conventional intraventricular chemotherapy. Secondary endpoints were response rates of other LMC symptoms and overall survival of patients. Artificial cerebrospinal fluid (CSF) premixed with MTX was continuously perfused intraventricularly through a preinstalled intraventricular reservoir and drained via lumbar catheter for 72 hours. The VLP was repeated twice at 3-day intervals for each cycle.</P><P><B>Results.</B></P><P>Forty-five of 65 patients had increased ICP, and 32 patients (71%) showed response after VLP chemotherapy, including 31 patients with normalization of ICP. Altered mentation improved in 7 of 21 patients (33%). Cauda equina symptoms responded in 5 of 27 patients (19%), including 4 patients who became ambulatory from a bedridden state. Median overall survival was 187 days, and the 1-year survival rate was 27%. All side effects, including nausea, vomiting, confusion, and sleep disturbance, were tolerable and transient except for two cases of CSF infection.</P><P><B>Conclusion.</B></P><P>VLP chemotherapy with MTX provided better control of increased ICP, improved symptom response, and prolonged survival at a cost of acceptable toxicity in patients with LMC.</P>