Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). Conclusion This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Objective: To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. Methods: This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. Results: The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p ＜ 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71−100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p＜ 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p＜ 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p ＜ 0.001; McNemar-Bowker test). Conclusion Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Purpose: Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed. Materials and Methods: Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety. Results: Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia. Conclusion Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Background/Aims: The alcoholic hepatitis histologic score (AHHS) is a recently developed clinical model for predicting short-term mortality in Caucasian patients with alcoholic hepatitis (AH). The AHHS has not been extensively validated in other ethnic populations. This study validated the AHHS in a Korean patient cohort. Methods: We conducted a pro-spective cohort study of hospitalized Korean patients with AH between January 2010 and August 2017. Histopatho-logical findings were assessed to determine the AHHS in all study subjects. Histopathological risk factors were examined by Cox regression analysis to predict overall survival (OS).Kaplan-Meier curves were plotted to assess the diagnostic performance of the AHHS. Results: We recruited a total of 107 patients with biopsy-proven AH. None of the individual AHHS components were associated with 3-month mortality.However, the bilirubinostasis type and fibrosis severity were significantly associated with AH mortality beyond 6 months (all p<0.05, except fibrosis severity for 6-month mortality) and OS (all p<0.05). The modified AHHS classification as a binary variable (<5 vs ≥5) was also associated with OS (haz-ard ratio, 2.88; 95% confidence interval [CI], 1.50 to 5.56;p=0.002), and had higher predictive performance for OS (concordance index [C-index], 0.634; 95% CI, 0.561 to 0.707) than the original AHHS classification (mild vs moderate vs severe: C-index, 0.577; 95% CI, 0.498 to 0.656). This differ-ence was statistically significant (p=0.045). Conclusions In this prospective Korean AH cohort, the modified AHHS was significantly associated with OS. Therefore, the AHHS might be a useful histological prognosticator for long-term progno-sis in patients with nonsevere AH.

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) developed recommendations for the optimal use of radiofrequency ablation for thyroid tumors in 2012. As new meaningful evidences have accumulated, KSThR decided to revise the guidelines. The revised guideline is based on a comprehensive analysis of the current literature and expert consensus.
Advisory Committees ; Catheter Ablation* ; Consensus ; Humans ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography

PURPOSE: Pregnancy-associated breast cancer (PABC) is rare, and its cause and prognosis are not well known. Additionally, treatment is limited with respect to the risk to the fetus. The purpose of this study was to investigate the characteristics and treatment trends of PABC and the survival rate according to the treatment. METHODS: In the Korean Breast Cancer Society Registry database, women younger than 50 years and who were diagnosed with breast cancer from 1996 to 2015 were included. PABC was defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. RESULTS: We examined 411 patients with PABC and 83,381 patients with non-PABC. Over time, the proportions of patients undergoing breast-conserving surgery and sentinel lymph node biopsy increased, and neoadjuvant chemotherapy and radiation therapy administration rates also increased. In the past, the overall survival of patients with PABC was poorer than that of patients with non-PABC, but there was no difference in overall survival rates in more recent years. There was no difference in overall survival rates between patients who received neoadjuvant chemotherapy (hazard ratio [HR], 1.28; 95% confidence interval [CI], 0.66–2.49; p=0.459), but PABC conferred poorer prognosis than non-PABC in patients receiving adjuvant chemotherapy (HR, 1.63; 95% CI, 1.27–2.08; p < 0.001). CONCLUSION: There was no difference in the prognosis between patients with PABC and those with non-PABC receiving neoadjuvant chemotherapy. The increase in neoadjuvant chemotherapy according to current treatment guidelines is expected to improve the survival rate of patients with PABC.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Drug Therapy* ; Female ; Fetus ; Humans ; Mastectomy, Segmental ; Pregnancy ; Prognosis* ; Sentinel Lymph Node Biopsy ; Survival Rate

Hepatocellular carcinoma (HCC) is the 2nd most common cause of cancer related death in Korea and well-known malignancy with poor prognosis. Sorafenib is the first-line molecular targeted agent in patients with extra-hepatic spread of HCC. However, complete response is extremely rare in patients treated with sorafenib and the disease control rate is only 43%. We report a 53-year-old man with advanced HCC with pulmonary metastasis who showed complete response by cytotoxic chemotherapy with doxorubicin and cisplatin with relatively tolerable adverse effects after failure of treatment with sorafenib.
Carcinoma, Hepatocellular* ; Cisplatin ; Doxorubicin ; Drug Therapy* ; Humans ; Korea ; Middle Aged ; Neoplasm Metastasis* ; Prognosis

PURPOSE: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. MATERIALS AND METHODS: The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. RESULTS: KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. CONCLUSION: KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.
Aneuploidy ; Animals ; Breast Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Fluorescent Antibody Technique ; Heterografts ; In Vitro Techniques ; Mice ; Microtubules ; Mitosis* ; src-Family Kinases* ; Triple Negative Breast Neoplasms ; Tubulin ; Wound Healing

PURPOSE: This study aimed to evaluate the efficacy and safety of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy beyond standard treatment for anthracycline- and taxane-pretreated metastatic breast cancer (MBC). METHODS: We consecutively enrolled 158 MBC patients who underwent CMF chemotherapy in a palliative setting at two academic hospitals in Korea between 2002 and 2016. RESULTS: The median age of the 158 enrolled patients was 51 years (range, 30–77 years). The enrolled patients were treated with a median of 5 lines of systemic treatment (range, 2–11) before CMF therapy, and the median time from diagnosis of MBC to CMF administration was 36.0 months (range, 7.1–146.7 months). The median number of cycles of CMF treatment was 3 (range, 1–19), and the relative dose intensity was 90.4%. The toxicity profile was mild, with an observed 3.1% of grade 2 and 5.0% of grade 3/4 neutropenia. Among 147 patients (93.0%) whose response to CMF was evaluated, the response rate was 10.9% (16/147), with complete response (CR) in one and partial response (PR) in 15. In addition, the disease control rate (calculated as CR+PR+stable disease) was 44.2% (65/147). The median progression-free survival and overall survival were 3.1 months (95% confidence interval [CI], 2.7–3.6) and 9.4 months (95% CI, 7.1–11.6), respectively. CONCLUSION: CMF therapy is effective and tolerable as salvage treatment for heavily pretreated MBC.
Breast Neoplasms* ; Breast* ; Cyclophosphamide* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Fluorouracil* ; Humans ; Korea ; Methotrexate* ; Neutropenia ; Palliative Care* ; Retrospective Studies* ; Salvage Therapy

PURPOSE: Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. MATERIALS AND METHODS: This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. RESULTS: The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. CONCLUSION: Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.
Administration, Oral ; Breast Neoplasms* ; Breast* ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Korea* ; Multivariate Analysis ; Retrospective Studies