A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. @*Materials and Methods@#Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. @*Results@#After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. @*Conclusion@#Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Prospective Multicenter Feasibility Study of Laparoscopic Sentinel Basin Dissection after Endoscopic Submucosal Dissection for Early Gastric Cancer: SENORITA 2 Trial Protocol

PURPOSE: Although standard radical gastrectomy is recommended after noncurative resection of endoscopic submucosal dissection (ESD) for early gastric cancer in most cases, residual tumor and lymph node metastasis have not been identified after surgery. The aim of this study is to evaluate the feasibility of sentinel node navigation surgery after noncurative ESD. MATERIALS AND METHODS: This trial is an investigator-initiated, multicenter prospective phase II trial. Patients who underwent ESD for clinical stage T1N0M0 gastric cancer with noncurative resections were eligible. Qualified investigators who completed the prior phase III trial (SENORITA 1) are exclusively allowed to participate. In this study, 2 detection methods will be used: 1) intraoperative endoscopic submucosal injection of dual tracer, including radioisotope and indocyanine green (ICG) with sentinel basins detected using gamma-probe; 2) endoscopic injection of ICG, with sentinel basins detected using a fluorescence imaging system. Standard laparoscopic gastrectomy with lymphadenectomy will be performed. Sample size is calculated based on the inferior confidence interval of the detection rate of 95%, and the calculated accrual is 237 patients. The primary endpoint is detection rate, and the secondary endpoints are sensitivity and postoperative complications. CONCLUSIONS: This study is expected to clarify the feasibility of laparoscopic sentinel basin dissection after noncurative ESD. If the feasibility is demonstrated, a multicenter phase III trial will be initiated to compare laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy in early gastric cancer after endoscopic resection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03123042

Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS. RESULTS: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs. 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea. CONCLUSION: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

Lifestyle Risk Prediction Model for Prostate Cancer in a Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The use of prostate-specific antigen as a biomarker for prostate cancer (PC) has been controversial and is, therefore, not used by many countries in their national health screening programs. The biological characteristics of PC in East Asians including Koreans and Japanese are different from those in the Western populations. Potential lifestyle risk factors for PC were evaluated with the aim of developing a risk prediction model. MATERIALS AND METHODS: A total of 1,179,172 Korean men who were cancer free from 1996 to 1997, had taken a physical examination, and completed a lifestyle questionnaire, were enrolled in our study to predict their risk for PC for the next eight years, using the Cox proportional hazards model. The model’s performance was evaluated using the C-statistic and Hosmer–Lemeshow type chi-square statistics. RESULTS: The risk prediction model studied age, height, body mass index, glucose levels, family history of cancer, the frequency of meat consumption, alcohol consumption, smoking status, and physical activity, which were all significant risk factors in a univariate analysis. The model performed very well (C statistic, 0.887; 95% confidence interval, 0.879 to 0.895) and estimated an elevated PC risk in patients who did not consume alcohol or smoke, compared to heavy alcohol consumers (hazard ratio [HR], 0.78) and current smokers (HR, 0.73) (p < 0.001). CONCLUSION: This model can be used for identifying Korean and other East Asian men who are at a high risk for developing PC, as well as for cancer screening and developing preventive health strategies.

Survival Benefit of Perioperative Chemotherapy in Patients with Locally Advanced Gastric Cancer: a Propensity Score Matched Analysis

PURPOSE: It has been reported that the survival of patients with locally advanced gastric cancer (LAGC) is better in East Asia countries than in developed western countries; however, the prognosis of LAGC remains poor. This study aimed to evaluate the effects of perioperative chemotherapy on the long-term survival of East Asia patients with LAGC. MATERIALS AND METHODS: From October 2006 through August 2008, 43 patients with LAGC received perioperative S-1 combined with weekly docetaxel in a phase II study (neoadjuvant group). These patients were matched using propensity scores to patients who underwent surgery without neoadjuvant chemotherapy during the same period (surgery group). The surgical outcomes and long-term survivals were compared between the 2 groups. RESULTS: After matching, 43 and 86 patients were included in the neoadjuvant and surgery groups, respectively, and there was no significant difference in their baseline characteristics. Although the operating time was longer in the neoadjuvant group, there was no significant difference in postoperative complications between the 2 groups. The neoadjuvant group had a significantly higher 5-year overall survival (OS) rate (73.3% vs. 51.1%, P=0.005) and a trend towards higher 5-year progression-free survival (PFS) (62.8% vs. 49.9%, P=0.145). In the multivariate analysis, perioperative chemotherapy was an independent factor for OS, with a hazard ratio of 0.4 (P=0.005) and a marginal effect on the PFS (P=0.054). CONCLUSIONS: Perioperative chemotherapy was associated with better long-term survival without increasing postoperative complications in the setting of D2 surgery for patients with LAGC, suggesting that perioperative chemotherapy can be a therapeutic option in East Asia countries.

Effect of a Proton Pump Inhibitor on Tumor Bleeding Prevention in Unresectable Gastric Cancer Patients: a Double-Blind, Randomized, Placebo-Controlled Trial

PURPOSE: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. MATERIALS AND METHODS: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). RESULTS: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. CONCLUSIONS: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

ERCC1 Expression-Based Randomized Phase II Study of Gemcitabine/Cisplatin Versus Irinotecan/Cisplatin in Patients with Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m² on days 1 and 8, and cisplatin 75 mg/m² on day 1 every 3 weeks) or IP (irinotecan 65 mg/m² and cisplatin 30 mg/m² on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level. RESULTS: A total of 279 patients were randomly assigned to the GP (n=139) and IP (n=140) arms, among which 63% were ERCC1-positive and 268 patients were assessable for the RR. The GP and IP arms did not differ significantly with respect to the RR (29.8% vs. 27.0%, respectively; p=0.082), median progression-free survival (PFS; 4.5 months vs. 3.9 months, respectively; p=0.117), and overall survival (OS; 16.5 months vs. 16.7 months, respectively; p=0.313). When comparing the efficacy between the ERCC1-positive and ERCC1-negative groups, there was no significant difference in the RR (GP, 28.2% vs. 32.6%, respectively, p=0.509; IP, 30.2% vs. 21.6%, respectively, p=0.536), median PFS (GP, 4.6 months vs. 5.0 months, respectively, p=0.506; IP, 3.9 months vs. 3.7 months, respectively, p=0.748), or median OS (GP, 18.6 months vs. 11.9 months, respectively, p=0.070; IP, 17.5 months vs. 14.0 months, respectively, p=0.821). CONCLUSION: Immunohistochemical analysis of the ERCC1 expression level did not differentiate the efficacy of platinum-based chemotherapy in advanced NSCLC.

Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. MATERIALS AND METHODS: Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). RESULTS: Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. CONCLUSION: Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.

A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. MATERIALS AND METHODS: This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms. RESULTS: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions. CONCLUSION: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.

Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications. MATERIALS AND METHODS: We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed. RESULTS: Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2- tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2- tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2- throughout. The HR+/HER2- to TN group had significantly poorer recurrence-free survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2-showed improved comparable survival outcomes. CONCLUSION: Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.

Robotic Versus Laparoscopic Surgery for Rectal Cancer after Preoperative Chemoradiotherapy: Case-Matched Study of Short-Term Outcomes / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Robotic surgery is expected to have advantages over laparoscopic surgery; however, there are limited data regarding the feasibility of robotic surgery for rectal cancer after preoperative chemoradiotherapy (CRT). Therefore, we evaluated the short-term outcomes of robotic surgery for rectal cancer. MATERIALS AND METHODS: Thirty-three patients with cT3N0-2 rectal cancer after preoperative CRT who underwent robotic low anterior resection (R-LAR) between March 2010 and January 2012 were matched with 66 patients undergoing laparoscopic low anterior resection (L-LAR). Perioperative clinical outcomes and pathological data were compared between the two groups. RESULTS: Patient characteristics did not differ significantly different between groups. The mean operation time was 441 minutes (R-LAR) versus 277 minutes (L-LAR, p < 0.001). The open conversion rate was 6.1% in the R-LAR group and 0% in the L-LAR group (p=0.11). There were no significant differences in the time to flatus passage, length of hospital stay, and postoperative morbidity. In pathological review, the mean number of harvested lymph nodes was 22.3 in R-LAR and 21.6 in L-LAR (p=0.82). Involvement of circumferential resection margin was positive in 16.1% and 6.7%, respectively (p=0.42). Total mesorectal excision (TME) quality was complete in 97.0% in R-LAR and 91.0% in L-LAR (p=0.41). CONCLUSION: In our study, short-term outcomes of robotic surgery for rectal cancer after CRT were similar to those of laparoscopic surgery in respect to bowel function recovery, morbidity, and TME quality. Well-designed clinical trials are needed to evaluate the functional results and long-term outcomes of robotic surgery for rectal cancer.

The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study

PURPOSE: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. MATERIALS AND METHODS: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. RESULTS: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. CONCLUSIONS: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.

A Phase II Study of Weekly Paclitaxel Plus Gemcitabine as a Second-Line Therapy in Patients with Metastatic or Recurrent Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Paclitaxel (P) and gemcitabine (G) are clinically synergistic in small cell lung cancer (SCLC). We evaluated the efficacy of PG as a salvage treatment for SCLC patients whose disease progressed after a platinum-containing regimen. MATERIALS AND METHODS: Eligibility included histologically confirmed SCLC, one dimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and progressive disease after platinum-based chemotherapy. Treatment consisted of P (80 mg/m2) and G (1,000 mg/m2) on days 1 and 8 of each cycle of 21 days until disease progression. RESULTS: Thirty-three patients seen between December 2005 and February 2009 were selected into this study. Thirty patients (91%) had received irinotecan-platinum, and three had received etoposide-platinum. Sixteen patients (49%) had a treatment-free interval of less than 3 months. The overall response rate was 30.3% (29.4% in sensitive relapse and 31.3% in refractory relapse). The median time to progression was 12.0 weeks and median overall survival (OS) 31.0 weeks, with a 1-year OS rate of 30.3%. Toxicities were moderate and manageable with 18.2% grade (G) 4 neutropenia, 24.2% G3 thrombocytopenia, 6.1% G3 sensory neuropathy, and 3% G3 asthenia. One patient developed febrile neutropenia. CONCLUSION: Second-line paclitaxel and gemcitabine were well-tolerated and moderately active in SCLC patients previously treated with platinum-based chemotherapy.

Development and Validation of Osteoporosis Risk-Assessment Model for Korean Men

PURPOSE: The aim of the present study was to develop an osteoporosis risk-assessment model to identify high-risk individuals among Korean men. MATERIALS AND METHODS: The study used data from 1340 and 1110 men > or =50 years who participated in the 2009 and 2010 Korean National Health and Nutrition Examination Survey, respectively, for development and validation of an osteoporosis risk-assessment model. Osteoporosis was defined as T score < or =-2.5 at either the femoral neck or lumbar spine. Performance of the candidate models and the Osteoporosis Self-assessment Tool for Asian (OSTA) was compared with sensitivity, specificity, and area under the receiver operating characteristics curve (AUC). A net reclassification improvement was further calculated to compare the developed Korean Osteoporosis Risk-Assessment Model for Men (KORAM-M) with OSTA. RESULTS: In the development dataset, the prevalence of osteoporosis was 8.1%. KORAM-M, consisting of age and body weight, had a sensitivity of 90.8%, a specificity of 42.4%, and an AUC of 0.666 with a cut-off score of -9. In the validation dataset, similar results were shown: sensitivity 87.9%, specificity 39.7%, and AUC 0.638. Additionally, risk categorization with KORAM-M showed improved reclassification over that of OSTA up to 22.8%. CONCLUSION: KORAM-M can be simply used as a pre-screening tool to identify candidates for dual energy X-ray absorptiometry tests.

What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy? / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. MATERIALS AND METHODS: This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. RESULTS: All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. CONCLUSION: The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone.

A Study of Relationship of Atheroembolic Risk Factors with Postoperative Recovery in Renal Function after Partial Nephrectomy in Patients Staged T1-2 Renal Cell Carcinoma during Median 4-Year Follow-up / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The objective of this study is to evaluate the relationship of atheroembolic risk factors with postoperative recovery of renal function after on-clamp partial nephrectomy (PN) with warm ischemia in patients with staged T1-2 renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 234 patients from 2004 to 2012 were included, and their clinicopathologic and operative parameters, including atheroembolic risk factors were reviewed retrospectively. Renal function, as determined by estimated glomerular filtration rate (eGFR) and measurement of serum creatinine level (Cr) at each scheduled follow-up for a median four years, was compared between the high-risk (HR) group (n=49, > or = five risk factors) and the low-risk (LR) group (n=185, < five risk factors). RESULTS: Except for baseline renal function and number of risk factors for atheroembolism, differences in characteristics between groups were comparatively insignificant. At 3 months after the operation, Cr and eGFR differed significantly between the two groups (p < 0.05), but no differences were observed afterward. Significant deterioration from baseline in Cr and eGFR was observed in both groups at 1 month after the operation, with a greater change in the HR group (p < 0.05). From measurement to measurement, significantly faster deterioration in Cr and eGFR was observed in the HR group than in the LR group until 6 months after the operation (Cr: LR, 0.02 mg/dL and HR, 0.13 mg/dL; eGFR: LR, 1.50 mL/min/1.73 m2 and HR, 6.38 mL/min/1.73 m2; p < 0.05). CONCLUSION: The presence of atheroembolic risk factors may negatively influence postoperative recovery of renal function after PN in patients with localized RCC.

Stomach cancer incidence rates among Americans, Asian Americans and Native Asians from 1988 to 2011 / 한국역학회지

Stomach cancer is the second most common cancer in Eastern Asia, accounting for approximately 50% of all new cases of stomach cancer worldwide. Our objective was to compare the stomach cancer incidence rates of Asian Americans in Los Angeles with those of native Asians to assess the etiology of stomach cancer from 1988 to 2011. To examine these differences, Asian Americans (Korean, Japanese, Chinese, and Filipino Americans living in Los Angeles, California, USA) and native Asians (from Korea, Japan, China, and the Philippines) were selected for this study. Using the Cancer Incidence in Five Continents database, stomach cancer incidence rates were examined. Data from the National Cancer Registry of Korea were used for native Koreans. Between native countries, the incidence rates in Japan, China, the Philippines, and the US declined over time, but the incidence in Korea has remained constant. The incidences among Asian immigrants were lower than those among native Asians. The incidence rates of males were approximately 2 times higher than those among females in Asian countries were. The effect of immigration on stomach cancer incidence suggests that lifestyle factors are a significant determinant of stomach cancer risk. However, the incidence in Korea remains the highest of these countries.

Cross-Cultural Adaptation of the Korean Version of the Minneapolis-Manchester Quality of Life Instrument-Adolescent Form

We verified the reliability and validity of the Korean version of the Minneapolis-Manchester Quality of Life Instrument-Adolescent Form (KMMQL-AF) among Korean childhood cancer survivors. A total of 107 childhood cancer patients undergoing cancer treatment and 98 childhood cancer survivors who completed cancer treatment were recruited. To assess the internal structure of the KMMQL-AF, we performed multi-trait scaling analyses and exploratory factor analysis. Additionally, we compared each domains of the KMMQL-AF with those of the Karnofsky Performance Status Scale and the Revised Children's Manifest Anxiety Scale (RCMAS). Internal consistency of the KMMQL-AF was sufficient (Cronbach's alpha: 0.78-0.92). In multi-trait scaling analyses, the KMMQL-AF showed sufficient construct validity. The "physical functioning" domain showed moderate correlation with Karnofsky scores and the "psychological functioning" domain showed moderate-to-high correlation with the RCMAS. The KMMQL-AF discriminated between subgroups of different adolescent cancer survivors depending on treatment completion. The KMMQL-AF is a sufficiently reliable and valid instrument for measuring quality of life among Korean childhood cancer survivors.

Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001)

PURPOSE: Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer. MATERIALS AND METHODS: Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation. DISCUSSION: Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).