Biometrics & Biostatistics International Journal
A single-arm phase II clinical trial is usually conducted for finding an appropriate dose-level a... more A single-arm phase II clinical trial is usually conducted for finding an appropriate dose-level and testing toxicity for an experimental cancer therapy in comparison to some historical controls, and is usually the most doable trial type due to the feasibility under limited budget, patient pool and medical conditions that can be met. We considered the standard setting of a single-arm two-stage phase II clinical trial, and investigated the patterns of critical values and sample sizes at both two stages of minimax and optimal designs under different design parameters, i.e., under different response rates of control and treatment, significant level of the test, and statistical power. We provided analytic derivations to the patterns we are interested under large sample approximation, and investigated them under finite ans small sample via a numerical study by considering extensively possible design parameters over a fine grid. We finally concluded that the critical values at different st...
4045 Background: Accurate prediction of metastatic lymph node is critical to avoid unnecessary ga... more 4045 Background: Accurate prediction of metastatic lymph node is critical to avoid unnecessary gastrectomy and improve quality of life for patients with early gastric cancer. The aim of this study was to develop and validate a nomogram for prediction of lymph node metastasis in early gastric cancer patients. Methods: We reviewed the clinicopathological data of 10595 patients who underwent curative resection for early gastric cancer from 2001 to 2015 at Samsung Medical Center. This model was externally validated by 2100 patients who underwent curative resection for gastric cancer in National Cancer Center. Multivariate analysis using the Cox proportional hazard regression model was performed to develop the nomogram, and discrimination and calibration were evaluated by external validation. Overall survival, disease free survival, and recurrence free survival were compared between gastrectomy groups of 6641 patients and endoscopic dissection group of 999 patients who was performed the treatment in Samsung Medical Center for early gastric cancer by risk on nomogram to demonstrate the efficacy of nomogram. Results: Multivariate analyses revealed that age, tumor size, lymphatic invasion, depth of invasion, and histologic differentiation were significant prognostic factors for lymph node metastasis. The nomogram had good discrimination with a concordance index of 0.845 [95% confidence interval 0.832-0.858], supported by an external validation point of 0.813[95% confidence interval 0.786-0.84]. In low risk on nomogram, endoscopic dissection group had similar overall survival (P = 0.319), disease free survival (P = 0.469) and recurrence free survival (P = 0.091) compared to gastrectomy group. Conclusions: We developed and validated a nomogram predicting lymph node metastasis for early gastric cancer based on a large database. This personalized nomogram is useful to avoid unnecessary gastrectomy after endoscopic dissection resulting in improved quality of life for early gastric cancer patients.
Background: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway... more Background: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway of B-cell receptor (BCR) signaling pathway and plays a crucial role in the pathogenesis of B-cell lymphoma. However, there have been preclinical data showing PI3K/AKT pathway activation in T-cell lymphoma, with in different mechanisms from those in B-cell lymphoma. In this study, we investigated the impact of p-AKT expression on clinical outcomes of peripheral T-cell lymphoma (PTCL). Materials and methods: We analyzed 63 patients with PTCL [PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) or extranodal natural kiler T-cell lymphoma (NKTCL)]. To define the clinical implications of p-AKT expression in PTCL, we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression. Results: Based on a cutoff value of the upper limit of the third quartile (Q3) of the AU, 12 patients were classified into the high p-AKT group, while the remaining 51 patients were classified into the low p-AKT group. The overall response rate to frontline chemotherapy was significantly lower in the high p-AKT group than in the low p-AKT group (20.0% vs. 71.1%, p=0.004). The high p-AKT group showed substantially worse overall survival (OS) (median OS=2.3 vs. 25.2 months, p<0.001) and progression-free survival (PFS) (median PFS=1.6 vs. 8.8 months, p<0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT expression remained a significant independent poor prognostic factor for OS (hazard ratio (HR)=7.0; 95% confidence interval (CI)=3.0-16.6; p<0.001) and PFS (HR=6.8; 95% CI=3.0-15.2; p<0.001). Conclusion: PTCL patients with high p-AKT expression showed aggressive clinical courses with significantly worse OS and PFS and a poor chemotherapy response rate. We suggest that targeting the PI3K/AKT pathway may be a promising therapeutic strategy for PTCL.
To evaluate the natural course of subcentimeter hypervascular nodules at high risk for developing... more To evaluate the natural course of subcentimeter hypervascular nodules at high risk for developing into hepatocellular carcinomas (SHNHR) using serial magnetic resonance imaging (MRI) in patients with a history of hepatocellular carcinoma (HCC). An SHNHR was defined as a subcentimeter hypervascular nodule having typical imaging findings of HCC on gadoxetic acid-enhanced MRI and diffusion-weighted imaging. We included 39 patients with 46 SHNHRs (mean size ± standard deviation, 6.1 ± 1.6 mm; range, 3.2 - 9.0 mm). Overt HCC was defined as pathology proven HCC or a nodule larger than 1 cm with typical imaging findings of HCC. The cumulative rate and the independent predictive factors for progression to overt HCC were evaluated. The median follow-up period was 139 days (range, 64 - 392 days). The cumulative progression rate to overt HCC at 3, 6, 9, and 12 months was 13.9 %, 61.7 %, 83.2 %, and 89.9 %. The initial size of SHNHR was a significant predictor of progression to overt HCC, with an optimal cut-off value of 5.5 mm. The progression rate of SHNHR to overt HCC within 12 months was high (89.9 %) in patients with history of HCC. The initial size of SHNHR was an important predictor for progression to overt HCC. • Most SHNHRs (89.9 %) progressed to overt HCCs within 12 months. • Initial size was an important predictor for progression to overt HCCs. • The optimal cut-off value for initial nodule size was 5.5 mm.
Uterine fibroids are composed of altered collagen fibrils and represent an arrested response to i... more Uterine fibroids are composed of altered collagen fibrils and represent an arrested response to injury-initiating fibrosis. In many tissues, TSP-1 is secreted by adult macrophages and monocytes upon wounding and is involved in the activation of transforming growth factor beta. In the absence of TSP-1, the orchestrated process of wound healing is impaired. The authors obtained tissue from the edge and center of fibroids at the time of hysterectomy and compared them with adjacent myometrium. The pattern of TSP-1 and TSP-2 expression was correlated to that of COL1A1 and COL3A1. Collagen and hydroxyproline were increased in fibroids. Thrombospondin-1 was consistently underexpressed in both the edge and center of the fibroids, while COL1A1 and COL3A1 were consistently overexpressed. However, TSP-2 was inconsistently expressed. These findings lead to the conclusion that the underexpression of TSP-1 may contribute to the overall development of uterine fibroids.
Machine learning methods have been a standard approach to select features that are associated wit... more Machine learning methods have been a standard approach to select features that are associated with an outcome and build a prediction model when the number of candidate features is large. LASSO has been one of the most popular approaches to this end. LASSO approach selects features with large regression estimates, rather than based on statistical significance, associating the outcome, by imposing L1-norm penalty to overcome the high dimensionality of the candidate features. As a result, LASSO may select insignificant features while possibly missing significant ones. Furthermore, from our experience, LASSO has been found to select too many features. By selecting features that are not associated with the outcome, we may have to spend more cost to collect and manage them in the future use of a fitted prediction model. Using the combination of L1- and L2-norm penalties, elastic net (EN) tends to select more features than LASSO. The overly selected features that are not associated with th...
Biometrics & Biostatistics International Journal
A single-arm phase II clinical trial is usually conducted for finding an appropriate dose-level a... more A single-arm phase II clinical trial is usually conducted for finding an appropriate dose-level and testing toxicity for an experimental cancer therapy in comparison to some historical controls, and is usually the most doable trial type due to the feasibility under limited budget, patient pool and medical conditions that can be met. We considered the standard setting of a single-arm two-stage phase II clinical trial, and investigated the patterns of critical values and sample sizes at both two stages of minimax and optimal designs under different design parameters, i.e., under different response rates of control and treatment, significant level of the test, and statistical power. We provided analytic derivations to the patterns we are interested under large sample approximation, and investigated them under finite ans small sample via a numerical study by considering extensively possible design parameters over a fine grid. We finally concluded that the critical values at different st...
4045 Background: Accurate prediction of metastatic lymph node is critical to avoid unnecessary ga... more 4045 Background: Accurate prediction of metastatic lymph node is critical to avoid unnecessary gastrectomy and improve quality of life for patients with early gastric cancer. The aim of this study was to develop and validate a nomogram for prediction of lymph node metastasis in early gastric cancer patients. Methods: We reviewed the clinicopathological data of 10595 patients who underwent curative resection for early gastric cancer from 2001 to 2015 at Samsung Medical Center. This model was externally validated by 2100 patients who underwent curative resection for gastric cancer in National Cancer Center. Multivariate analysis using the Cox proportional hazard regression model was performed to develop the nomogram, and discrimination and calibration were evaluated by external validation. Overall survival, disease free survival, and recurrence free survival were compared between gastrectomy groups of 6641 patients and endoscopic dissection group of 999 patients who was performed the treatment in Samsung Medical Center for early gastric cancer by risk on nomogram to demonstrate the efficacy of nomogram. Results: Multivariate analyses revealed that age, tumor size, lymphatic invasion, depth of invasion, and histologic differentiation were significant prognostic factors for lymph node metastasis. The nomogram had good discrimination with a concordance index of 0.845 [95% confidence interval 0.832-0.858], supported by an external validation point of 0.813[95% confidence interval 0.786-0.84]. In low risk on nomogram, endoscopic dissection group had similar overall survival (P = 0.319), disease free survival (P = 0.469) and recurrence free survival (P = 0.091) compared to gastrectomy group. Conclusions: We developed and validated a nomogram predicting lymph node metastasis for early gastric cancer based on a large database. This personalized nomogram is useful to avoid unnecessary gastrectomy after endoscopic dissection resulting in improved quality of life for early gastric cancer patients.
Background: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway... more Background: The oncogenic PI3K/serine-threonine kinase (PI3K/AKT) pathway is a downstream pathway of B-cell receptor (BCR) signaling pathway and plays a crucial role in the pathogenesis of B-cell lymphoma. However, there have been preclinical data showing PI3K/AKT pathway activation in T-cell lymphoma, with in different mechanisms from those in B-cell lymphoma. In this study, we investigated the impact of p-AKT expression on clinical outcomes of peripheral T-cell lymphoma (PTCL). Materials and methods: We analyzed 63 patients with PTCL [PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) or extranodal natural kiler T-cell lymphoma (NKTCL)]. To define the clinical implications of p-AKT expression in PTCL, we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression. Results: Based on a cutoff value of the upper limit of the third quartile (Q3) of the AU, 12 patients were classified into the high p-AKT group, while the remaining 51 patients were classified into the low p-AKT group. The overall response rate to frontline chemotherapy was significantly lower in the high p-AKT group than in the low p-AKT group (20.0% vs. 71.1%, p=0.004). The high p-AKT group showed substantially worse overall survival (OS) (median OS=2.3 vs. 25.2 months, p<0.001) and progression-free survival (PFS) (median PFS=1.6 vs. 8.8 months, p<0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT expression remained a significant independent poor prognostic factor for OS (hazard ratio (HR)=7.0; 95% confidence interval (CI)=3.0-16.6; p<0.001) and PFS (HR=6.8; 95% CI=3.0-15.2; p<0.001). Conclusion: PTCL patients with high p-AKT expression showed aggressive clinical courses with significantly worse OS and PFS and a poor chemotherapy response rate. We suggest that targeting the PI3K/AKT pathway may be a promising therapeutic strategy for PTCL.
To evaluate the natural course of subcentimeter hypervascular nodules at high risk for developing... more To evaluate the natural course of subcentimeter hypervascular nodules at high risk for developing into hepatocellular carcinomas (SHNHR) using serial magnetic resonance imaging (MRI) in patients with a history of hepatocellular carcinoma (HCC). An SHNHR was defined as a subcentimeter hypervascular nodule having typical imaging findings of HCC on gadoxetic acid-enhanced MRI and diffusion-weighted imaging. We included 39 patients with 46 SHNHRs (mean size ± standard deviation, 6.1 ± 1.6 mm; range, 3.2 - 9.0 mm). Overt HCC was defined as pathology proven HCC or a nodule larger than 1 cm with typical imaging findings of HCC. The cumulative rate and the independent predictive factors for progression to overt HCC were evaluated. The median follow-up period was 139 days (range, 64 - 392 days). The cumulative progression rate to overt HCC at 3, 6, 9, and 12 months was 13.9 %, 61.7 %, 83.2 %, and 89.9 %. The initial size of SHNHR was a significant predictor of progression to overt HCC, with an optimal cut-off value of 5.5 mm. The progression rate of SHNHR to overt HCC within 12 months was high (89.9 %) in patients with history of HCC. The initial size of SHNHR was an important predictor for progression to overt HCC. • Most SHNHRs (89.9 %) progressed to overt HCCs within 12 months. • Initial size was an important predictor for progression to overt HCCs. • The optimal cut-off value for initial nodule size was 5.5 mm.
Uterine fibroids are composed of altered collagen fibrils and represent an arrested response to i... more Uterine fibroids are composed of altered collagen fibrils and represent an arrested response to injury-initiating fibrosis. In many tissues, TSP-1 is secreted by adult macrophages and monocytes upon wounding and is involved in the activation of transforming growth factor beta. In the absence of TSP-1, the orchestrated process of wound healing is impaired. The authors obtained tissue from the edge and center of fibroids at the time of hysterectomy and compared them with adjacent myometrium. The pattern of TSP-1 and TSP-2 expression was correlated to that of COL1A1 and COL3A1. Collagen and hydroxyproline were increased in fibroids. Thrombospondin-1 was consistently underexpressed in both the edge and center of the fibroids, while COL1A1 and COL3A1 were consistently overexpressed. However, TSP-2 was inconsistently expressed. These findings lead to the conclusion that the underexpression of TSP-1 may contribute to the overall development of uterine fibroids.
Machine learning methods have been a standard approach to select features that are associated wit... more Machine learning methods have been a standard approach to select features that are associated with an outcome and build a prediction model when the number of candidate features is large. LASSO has been one of the most popular approaches to this end. LASSO approach selects features with large regression estimates, rather than based on statistical significance, associating the outcome, by imposing L1-norm penalty to overcome the high dimensionality of the candidate features. As a result, LASSO may select insignificant features while possibly missing significant ones. Furthermore, from our experience, LASSO has been found to select too many features. By selecting features that are not associated with the outcome, we may have to spend more cost to collect and manage them in the future use of a fitted prediction model. Using the combination of L1- and L2-norm penalties, elastic net (EN) tends to select more features than LASSO. The overly selected features that are not associated with th...
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Papers by Sin-Ho Jung