Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 175
Filter
1.
Article in English | WPRIM | ID: wpr-913817

ABSTRACT

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

2.
Article in English | WPRIM | ID: wpr-889758

ABSTRACT

Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

3.
Cancer Research and Treatment ; : 1096-1103, 2021.
Article in English | WPRIM | ID: wpr-913815

ABSTRACT

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.

4.
Blood Research ; : 285-292, 2021.
Article in English | WPRIM | ID: wpr-913725

ABSTRACT

Background@#High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL). @*Methods@#In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa-based conditioning regimen but did not undergo radiotherapy. @*Results@#The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions.Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis. @*Conclusion@#The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.

5.
Article in English | WPRIM | ID: wpr-918964

ABSTRACT

Background/Aims@#Anastomotic stricture at the esophagus and the conduit anastomosis site after the surgical resection of esophageal cancer is relatively common. This study examined whether a hypertrophic scar or keloid formation at a surgical wound is related to an anastomotic stricture. @*Methods@#From March 2007 to July 2017, 59 patients underwent curative surgery for esophageal cancer. In 38 patients, end-to-end anastomosis (EEA) of the esophagus and the conduit was performed using EEA 25 mm. A hypertrophic wound scar was defined when the width of the midline laparotomy wound scar exceeded 2 mm. The relationship between the hypertrophic scar and stricture and the other risk factors for anastomotic stricture in these 38 patients was analyzed. @*Results@#Of the 38 patients, eight patients (21.1%) had an anastomotic stricture, and a hypertrophic skin scar was observed in 14 patients (36.8%). Univariate analysis revealed lower BMI and hypertrophic scars as risk factors (p=0.032, p=0.001 respectively).Multivariate analysis revealed a hypertrophic scar as an independent risk factor for an anastomotic stricture (p=0.010, OR=27.06, 95% CI 2.19-334.40). @*Conclusions@#Hypertrophic wound scars can be a risk factor for anastomotic stricture after surgery for esophageal cancer. An earlier prediction of anastomotic stricture by detecting hypertrophic wound healing in patients undergoing esophagectomy may improve the patients’ quality of life and surgical outcomes by earlier treatments.

6.
Journal of Breast Cancer ; : 97-105, 2021.
Article in English | WPRIM | ID: wpr-898994

ABSTRACT

In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant. This subgroup analysis examined the efficacy and safety of palbociclib among Korean patients enrolled in PALOMA-3 (n = 43 [palbociclib group, n = 24; placebo group, n = 19]). In both groups, > 40% of patients were pre/perimenopausal at enrollment. The median PFS was significantly prolonged with palbociclib vs. placebo (12.3 [95% confidence interval (CI), 9.1–not estimable] vs. 5.4 months [95% CI, 1.9–9.2]; hazard ratio, 0.40 [95% CI, 0.19–0.83]; one-sided p = 0.005), and the confirmed objective response was 21.1% and 11.8%, respectively (odds ratio, 2.0 [95% CI, 0.24–24.8]). Neutropenia was the most common adverse event associated with palbociclib. Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2− ABC, regardless of menopausal status.

7.
Article in English | WPRIM | ID: wpr-897462

ABSTRACT

Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

8.
Article in Korean | WPRIM | ID: wpr-892931

ABSTRACT

An emblem is a symbolic representational image that stands for a certain organization, concept, team, or society. This study investigated the emblems of the sleep societies in South Korea and the international sleep societies in which they were registered as members. Three South Korean sleep societies were found by searching for the keyword ‘sleep’ in the Korea Citation Index. Subsequently, we identified three international societies in which the three South Korean conferences participate. The emblems can be classified according to their composition. Taegeuk patterns represent yin and yang, electroencephalography that stands for the objective indicator of sleep, and the acronym or abbreviation indicating the name of the society. All emblems in this study were combinations of pictorial images and letters. The pictorial image of the Korean Sleep Research Society is the only emblem representing an inset with Hangeul. The emblem is a medium that conveys diverse meanings beyond representation. The societies have attempted to embody the identity as well as their directions.

9.
Journal of Breast Cancer ; : 97-105, 2021.
Article in English | WPRIM | ID: wpr-891290

ABSTRACT

In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant. This subgroup analysis examined the efficacy and safety of palbociclib among Korean patients enrolled in PALOMA-3 (n = 43 [palbociclib group, n = 24; placebo group, n = 19]). In both groups, > 40% of patients were pre/perimenopausal at enrollment. The median PFS was significantly prolonged with palbociclib vs. placebo (12.3 [95% confidence interval (CI), 9.1–not estimable] vs. 5.4 months [95% CI, 1.9–9.2]; hazard ratio, 0.40 [95% CI, 0.19–0.83]; one-sided p = 0.005), and the confirmed objective response was 21.1% and 11.8%, respectively (odds ratio, 2.0 [95% CI, 0.24–24.8]). Neutropenia was the most common adverse event associated with palbociclib. Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2− ABC, regardless of menopausal status.

10.
Gut and Liver ; : 100-108, 2021.
Article in English | WPRIM | ID: wpr-874572

ABSTRACT

Background/Aims@#Astragalin (kaempferol-3-O-β-D-glucoside) is a flavonoid isolated from the leaves of persimmon or Rosa agrestis. Astragalin exhibits various anti-inflammatory properties; however, little is known about its therapeutic potential for inflammatory bowel disease (IBD). This study aims to investigate the anti-inflammatory effect of astragalin via blockade of the nuclear factor κB (NF-κB) signaling pathway in human colonic epithelial cells and a murine colitis model. @*Methods@#HCT-116 and HT-29 human colonic epithelial cells were pretreated with astragalin and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was assessed by the MTS assay. Real-time reverse transcription polymerase chain reaction was used to analyze the messenger RNA expression of the inflammatory cytokines interleukin (IL)-6 and IL-8. The effect of astragalin on the NF-κB pathway was evaluated by Western blot analysis of inhibitor of NF-κB alpha (IκBα) phosphorylation/degradation and by electrophoretic mobility shift assay. Dextran sulfate sodium (DSS)-induced acute murine colitis model was used for in vivo experiments. @*Results@#Astragalin strongly suppressed the expression of proinflammatory cytokines in human colonic epithelial cells in a dose-dependent manner. Western blot analysis showed that astragalin inhibited IκBα phosphorylation/degradation. Additionally, astragalin reduced the DNA binding ac-tivity of NF-κB. Astragalin alleviated colon shortening and improved the pathologic scores in DSSinduced acute murine colitis model. Furthermore, astragalin reduced the level of phosphorylated IκBα and decreased the production of the inflammatory cytokines IL-6, IL-8, and TNF-α in the DSS-treated colon mucosa. @*Conclusions@#Astragalin exerted an anti-inflammatory effect through NF-κB pathway inhibition and attenuated murine colitis. Astragalin is thus a potential therapeutic agent for IBD.

11.
Article in Korean | WPRIM | ID: wpr-900635

ABSTRACT

An emblem is a symbolic representational image that stands for a certain organization, concept, team, or society. This study investigated the emblems of the sleep societies in South Korea and the international sleep societies in which they were registered as members. Three South Korean sleep societies were found by searching for the keyword ‘sleep’ in the Korea Citation Index. Subsequently, we identified three international societies in which the three South Korean conferences participate. The emblems can be classified according to their composition. Taegeuk patterns represent yin and yang, electroencephalography that stands for the objective indicator of sleep, and the acronym or abbreviation indicating the name of the society. All emblems in this study were combinations of pictorial images and letters. The pictorial image of the Korean Sleep Research Society is the only emblem representing an inset with Hangeul. The emblem is a medium that conveys diverse meanings beyond representation. The societies have attempted to embody the identity as well as their directions.

12.
Article in English | WPRIM | ID: wpr-917765

ABSTRACT

Purpose@#At the end of life, communication is a key factor for good care. However, in clinical practice, it is difficult to adequately discuss end-of-life care. In order to understand and analyze how decision-making related to life-sustaining treatment (LST) is performed, the shared decision-making (SDM) behaviors of physicians were investigated. @*Methods@#A questionnaire was designed after reviewing the literature on attitudes toward SDM or decision-making related to LST. A final item was added after consulting experts. The survey was completed by internal medicine residents and hematologists/medical oncologists who treat terminal cancer patients. @*Results@#In total, 202 respondents completed the questionnaire, and 88.6% said that the decision to continue or end LST is usually a result of SDM since they believed that sufficient explanation is provided to patients and caregivers, patients and caregivers make their own decisions according to their values, and there is sufficient time for patients and caregivers to make a decision. Expected satisfaction with the decisionmaking process was the highest for caregivers (57.4%), followed by physicians (49.5%) and patients (41.1%). In total, 38.1% of respondents said that SDM was adequately practiced when making decisions related to LST. The most common reason for inadequate SDM was time pressure (89.6%). @*Conclusion@#Although most physicians answered that they practiced SDM when making decisions regarding LST, satisfactory SDM is rarely practiced in the clinical field. A model for the proper implementation of SDM is needed, and additional studies must be conducted to develop an SDM model in collaboration with other academic organizations.

13.
Article in English | WPRIM | ID: wpr-832087

ABSTRACT

Objective@#Habitual snoring is a common problem in children. We evaluated the association between a high risk for sleep-disordered breathing and attention deficit/hyperactivity symptoms. @*Methods@#Parents of 13,560 children aged 6 to 12 years responded to questionnaires including items on habitual snoring and the Korean attention deficit/hyperactivity disorder rating scale. The snoring score comprised the number of “yes” responses to habitual-snoring items, and a high risk for sleep-disordered breathing was defined as a snoring score ≥ 2. @*Results@#The odds ratio (OR) of a high risk for sleep-disordered breathing was significantly higher in boys (OR = 1.47; p < 0.001), overweight children (OR = 2.20; p < 0.001), and children with current secondhand-smoking exposure (OR = 1.38; p < 0.001). The Korean attention deficit/hyperactivity disorder rating scale score increased significantly with the snoring score (0 vs. 1, B = 1.56, p < 0.001; 0 vs. 2, B = 2.44, p< 0.001; 0 vs. 3, B = 2.48, p< 0.001; 0 vs. 4, B = 3.95; p < 0.001). @*Conclusion@#Our study confirms several risk factors of sleep-disordered breathing, namely male sex, overweight, and exposure to tobacco smoking, and found a positive association between habitual snoring and attention deficit/hyperactivity symptoms.

14.
Journal of Breast Disease ; (2): 25-36, 2020.
Article | WPRIM | ID: wpr-835616

ABSTRACT

Purpose@#Although the number of elderly patients with breast cancer is increasing as the population ages, their treatment is controversial. We evaluated the prognostic factors associated with survival in elderly breast cancer patients and assessed the impact of comorbidity on prognosis. @*Methods@#This study included 362 patients (aged ≥65 years) who underwent surgery for breast cancer in our institution between 2003 and 2014. The patients were divided into early-aged (65–74 years) and late-aged (≥75 years) groups. Comorbidity was parametrized using the Charlson comorbidity index (CCI). Kaplan–Meier analysis was used to analyze overall survival (OS) and distant metastasis-free survival (DMFS). Prognostic factors were evaluated by Cox proportional hazards regression. @*Results@#The surgical method, subtypes, stage, and oncological features were similar between early- and late-aged groups; however, smaller proportions of patients in the late-aged group received chemotherapy (12.9% vs. 45.5%) and endocrine therapy (55.3% vs. 73.3%). In multivariable analysis, the poor prognostic factors associated with DMFS and OS were high CCI, high histologic grade, and advanced stage. Chemotherapy, endocrine therapy, and radiotherapy were not significantly related to DMFS and OS. @*Conclusion@#In this study, adjuvant treatments did not affect the prognosis of elderly patients with breast cancer. To clarify the effects of adjuvant therapies in these patients, a large-scale retrospective study that considers not only tumor characteristics but also life expectancy is necessary.

15.
Article | WPRIM | ID: wpr-831350

ABSTRACT

Objective@#Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation. @*Methods@#Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells. @*Results@#Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency. @*Conclusion@#These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

16.
Cancer Research and Treatment ; : 1086-1097, 2019.
Article in English | WPRIM | ID: wpr-763171

ABSTRACT

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Therapy , Humans , Immunohistochemistry , Neoadjuvant Therapy , Platinum , Prognosis , Retrospective Studies
17.
Cancer Research and Treatment ; : 1249-1256, 2019.
Article in English | WPRIM | ID: wpr-763155

ABSTRACT

PURPOSE: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. MATERIALS AND METHODS: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). RESULTS: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). CONCLUSION: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.


Subject(s)
Area Under Curve , Asian Continental Ancestry Group , Drug Therapy , Geriatric Assessment , Humans , Mass Screening , Prospective Studies , Sensitivity and Specificity
18.
Article in English | WPRIM | ID: wpr-763143

ABSTRACT

PURPOSE: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. RESULTS: A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8). CONCLUSION: OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.


Subject(s)
Biomarkers , Carcinoma, Hepatocellular , Cohort Studies , Disease-Free Survival , Dizziness , Fatigue , Humans , Maximum Tolerated Dose , STAT3 Transcription Factor , Thrombocytopenia
20.
Journal of Breast Cancer ; : 439-452, 2019.
Article in English | WPRIM | ID: wpr-764278

ABSTRACT

PURPOSE: There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis. METHODS: A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer. CONCLUSION: Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.


Subject(s)
Biomarkers , Breast Neoplasms , Breast , Diagnosis , Estrogens , Follow-Up Studies , Humans , Neoplasm Metastasis , Prognosis , ErbB Receptors , Receptors, Progesterone
SELECTION OF CITATIONS
SEARCH DETAIL