Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer.

BACKGROUND: Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy. METHODS: This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age [young-onset vs. others], sex, histology [intestinal vs. diffuse type], prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets. RESULTS: The median patient age was 64 years (range 25-91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099). CONCLUSIONS: These ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.

Is Prophylactic Antibiotic Use Necessary Before Dental Procedures in Primary and Revision TKA? A Propensity Score-matched, Large-database Study.

BACKGROUND: The question of whether dental procedures increase the risk of periprosthetic joint infection (PJI) in patients who have undergone total joint arthroplasty (TJA) remains controversial. QUESTIONS/PURPOSES: (1) Are dental procedures associated with an increased incidence of PJI in the setting of either primary or revision TKA after controlling for relevant potentially confounding variables? (2) Is the administration of prophylactic antibiotics before dental procedures associated with any differences in this risk? (3) Which factors are associated with increased incidence of PJI after dental procedures? METHODS: This nationwide, retrospective, comparative, large-database study evaluated 591,602 patients who underwent unilateral primary or revision TKA between 2009 and 2019 using the Health Insurance Review and Assessment Service data in South Korea, in which all people in South Korea were registered and to which all medical institutions must charge any procedures they performed. The study population was divided into 530,156 patients with dental procedures and 61,446 patients without dental procedures based on whether the patients underwent a dental procedure at least 1 year after the index surgery. After propensity score matching, patients were classified into a dental (n = 182,052) and a nondental cohort (n = 61,422). The dental cohort was then divided into two groups: 66,303 patients with prophylactic antibiotics and 115,749 patients without prophylactic antibiotics based on prophylactic antibiotic use. After propensity score matching, patients were categorized into prophylactic (n = 66,277) and nonprophylactic (n = 66,277) cohorts. Propensity score matching was used to control for covariates including posttraumatic arthritis associated with PJI risk according to the dental procedure and prophylactic antibiotic use among the cohorts. After propensity score matching, the standardized mean difference was confirmed to be less than 0.1 for all variables. Kaplan-Meier survival analyses, log-rank tests, and Cox proportional hazards regression analysis was performed. RESULTS: Dental procedures were not associated with an increase in PJI risk after primary (adjusted HR 1.56 [95% CI 0.30 to 8.15]; p = 0.60) or revision TKA (adjusted HR 1.74 [95% CI 0.90 to 3.34]; p = 0.10). Additionally, use of prophylactic antibiotics was not associated with a reduced PJI risk after the index surgery, either for primary (adjusted HR 1.28 [95% CI 0.30 to 5.42]; p = 0.74) or revision TKA (adjusted HR 0.74 [95% CI 0.45 to 1.23]; p = 0.25). Although surgery type and prophylactic antibiotic use exhibited no influence on PJI occurrence after dental procedures, posttraumatic arthritis was associated with PJI. The adjusted HR for posttraumatic arthritis was 4.54 (p = 0.046). CONCLUSION: Our findings suggest that dental procedures were not associated with an increased risk of PJI for up to 2 years after the dental procedure in patients who underwent either primary or revision TKA. Based on these findings, there is insufficient rationale for the use of prophylactic antibiotics before dental procedures in patients who have undergone primary or revision TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.

A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.

Particulate matter induces arrhythmia-like cardiotoxicity in zebrafish embryos by altering the expression levels of cardiac development- and ion channel-related genes.

Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.

Associations between missing teeth and the risk of cancer in Korea: a nationwide cohort study.

BACKGROUND: Poor dental health is correlated with an increased risk of cancer. Using a nationwide population cohort database, we investigated which cancer is highly associated with poor dental health and which dental indicator mostly influences cancer risk. METHODS: This study was conducted using the National Health Checkups (NHC) and National Health Insurance System (NHIS) database in Korea. NHC in Korea includes dental examinations. We retrieved subjects who underwent NHC between 2002 and 2003 and their medical information in NHIS database was followed until December 31,2015. RESULTS: Data for 200,170 who participated in the NHC between 2002 and 2003 were analysed. During the maximum follow-up period of 13 years, 15,506 (7.75%) subjects were diagnosed with cancer. The median time to cancer diagnosis after the dental examination was 87 months (range, 51-119 months). The proportion of people with missing teeth was higher in the cancer-diagnosed group than in the non-diagnosed group (26.27% vs. 22.59%, p < 0.001). Among several dental health factors, missing teeth were significantly associated with higher cancer risk. Subjects with missing teeth showed a 12% increased cancer risk compared to those without missing teeth (odds ratio [OR] 1.12, 95% confidence interval [CI], 1.08-1.16). The risk was significantly higher, especially in lung, head and neck, pancreatic, liver, biliary, and esophageal cancers (OR 1.27 [95% CI, 1.14-1.41], 1.32 [95% CI, 1.13-1.55], 1.27 [95% CI, 1.02-1.58], 1.24 [95% CI, 1.1-1.4], 1.28 [95% CI, 1.03-1.6], 1.4 [95% CI, 1.04-1.88], respectively). CONCLUSIONS: Missing teeth were the most important dental indicator associated with cancer risk. Korean adults with missing teeth should be cautious about the risk of several cancers, particularly head and neck, lung, gastrointestinal, hepatobiliary, and pancreatic cancer.

Effect of Herpes Zoster Treatment and Sudden Sensorineural Hearing Loss Using National Health Insurance Claims Data of South Korea.

Background and objectives: Herpes zoster (HZ) is caused by the reactivation of a pre-existing latent varicella zoster virus, which is one of the viruses that causes hearing loss, and hearing loss may occur due to a systemic immune response even if it does not invade the auditory nerve. This study aimed to determine the correlation between sudden sensorineural hearing loss (SSNHL) in older adult patients who received HZ treatment. Materials and Methods: We used the cohort data of patients aged 60 years and above (n = 624,646) between 2002 and 2015 provided by the National Health Insurance Service. The patients were divided into two groups: those who were diagnosed with HZ between 2003 and 2008 (group H, n = 36,121) and those who had not been diagnosed with HZ between 2002 and 2015 (group C, n = 584,329). Results: In the main model (adjusted HR = 0.890, 95% CI = 0.839-0.944, p < 0.001) adjusted for sex, age, and income, and the full model (adjusted HR = 0.894, 95% CI = 0.843-0.949, p < 0.001) adjusted for all comorbidities, group H had a lower risk of SSNHL than group C. Conclusions: This study showed that patients who received HZ treatment had a lower incidence of SSNHL within five years after diagnosis.

The Effect of Maternal Exposure to Air Pollutants and Heavy Metals during Pregnancy on the Risk of Neurological Disorders Using the National Health Insurance Claims Data of South Korea.

The objective of this study was to evaluate the effects of high levels of maternal exposure to ambient air pollution and heavy metals on risks of autism spectrum disorder (ASD) and epilepsy using the National Health Insurance claims data of South Korea. The data of mothers and their newborns from 2016 to 2018 provided by the National Health Insurance Service were used (n = 843,134). Data on exposure to ambient air pollutants (PM2.5, CO, SO2, NO2, and O3) and heavy metals (Pb, Cd, Cr, Cu, Mn, Fe, Ni, and As) during pregnancy were matched based on the mother's National Health Insurance registration area. SO2 (OR: 2.723, 95% CI: 1.971-3.761) and Pb (OR: 1.063, 95% CI: 1.019-1.11) were more closely associated with the incidence of ASD when infants were exposed to them in the third trimester of pregnancy. Pb (OR: 1.109, 95% CI: 1.043-1.179) in the first trimester of pregnancy and Cd (OR: 2.193, 95% CI: 1.074-4.477) in the third trimester of pregnancy were associated with the incidence of epilepsy. Thus, exposure to SO2, NO2, and Pb during pregnancy could affect the development of a neurologic disorder based on the timing of exposure, suggesting a relationship with fetal development. However, further research is needed.

Prognostic effects of cytokine levels on patients treated with taxane and zoledronic acid for metastatic breast cancer in bone (BEAT-ZO) (KCSG BR 10-13).

Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-ß1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-ß1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-ß1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-ß1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.

Compartmentalized Arrays of Matrix Droplets for Quantitative Mass Spectrometry Imaging of Adsorbed Peptides.

Mass spectrometry imaging (MSI) based on matrix-assisted laser desorption/ionization (MALDI) provides information on the identification and spatial distribution of biomolecules. Quantitative analysis, however, has been challenging largely due to heterogeneity in both the size of the matrix crystals and the extraction area. In this work, we present a compartmentalized elastomeric stamp for quantitative MALDI-MSI of adsorbed peptides. Filling the compartments with matrix solution and stamping onto a planar substrate extract and concentrate analytes adsorbed in each compartment into a single analyte-matrix cocrystal over the entire stamped area. Walls between compartments help preserve spatial information on the adsorbates. The mass intensity of the cocrystals directly correlates with the surface coverage of analytes, which enables not only quantitative analysis but estimation of an equilibrium constant for the adsorption. We demonstrate via MALDI-MSI relative quantitation of peptides adsorbed along a microchannel with varying surface coverages.

Monitoring of anesthetic depth and EEG band power using phase lag entropy during propofol anesthesia.

BACKGROUND: Phase lag entropy (PLE) is a novel anesthetic depth indicator that uses four-channel electroencephalography (EEG) to measure the temporal pattern diversity in the phase relationship of frequency signals in the brain. The purpose of the study was to evaluate the anesthetic depth monitoring using PLE and to evaluate the correlation between PLE and bispectral index (BIS) values during propofol anesthesia. METHODS: In thirty-five adult patients undergoing elective surgery, anesthesia was induced with propofol using target-controlled infusion (the Schneider model). We recorded the PLE value, raw EEG, BIS value, and hemodynamic data when the target effect-site concentration (Ce) of propofol reached 2, 3, 4, 5, and 6 µg/ml before intubation and 6, 5, 4, 3, 2 µg/ml after intubation and injection of muscle relaxant. We analyzed whether PLE and raw EEG data from the PLE monitor reflected the anesthetic depth as the Ce of propofol changed, and whether PLE values were comparable to BIS values. RESULTS: PLE values were inversely correlated to changes in propofol Ce (propofol Ce from 0 to 6.0 µg/ml, r2 = - 0.83; propofol Ce from 6.0 to 2.0 µg/ml, r2 = - 0.46). In the spectral analysis of EEG acquired from the PLE monitor, the persistence spectrogram revealed a wide distribution of power at loss of consciousness (LOC) and recovery of consciousness (ROC), with a narrow distribution during unconsciousness. The power spectrogram showed the typical pattern seen in propofol anesthesia with slow alpha frequency band oscillation. The PLE value demonstrated a strong correlation with the BIS value during the change in propofol Ce from 0 to 6.0 µg/ml (r2 = 0.84). PLE and BIS values were similar at LOC (62.3 vs. 61.8) (P > 0.05), but PLE values were smaller than BIS values at ROC (64.4 vs 75.7) (P < 0.05). CONCLUSIONS: The PLE value is a useful anesthetic depth indicator, similar to the BIS value, during propofol anesthesia. Spectral analysis of EEG acquired from the PLE monitor demonstrated the typical patterns seen in propofol anesthesia. TRIAL REGISTRATION: This clinical trial was retrospectively registered at ClinicalTrials.gov at October 2017 (NCT03299621).

Identification of Polyphenol Glucuronide Conjugates in Glechoma hederacea var. longituba Hot Water Extracts by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS).

Glechoma hederacea var. longituba (GHL) is one of many herbal plants distributed worldwide and is known to contain various biologically useful antioxidant constituents. GHL has been used in folk remedies for various treatments and as favorable tea beverages. However, research on the precise analysis of ingredients in GHL extracts remains insufficient. In this study, compositional analysis has been conducted on polyphenolic ingredients in GHL hot water extracts. GHL samples collected from growing regions were incubated in hot water at 100 °C for 1 h. The polyphenolic constituents in the hot water extracts were analyzed using high performance liquid chromatography-high resolution mass spectrometry (HPLC-HR MS) and tandem mass spectrometry (HPLC-MS/MS) in negative ion mode. As a result, a total of seven compounds were identified as the major polyphenolic constituents. Interestingly, four constituents out of the identified substances were confirmed to be polyphenol glucuronide conjugates, in which glucuronidation was known to be an important metabolic process in polyphenol aglycone along with methylation and sulphation. This study can be applied for the quality control and standardization of GHL herbal samples and the monitoring of metabolic processes involved in the polyphenolic conjugates.

The correlation between conventional coagulation tests and thromboelastography in each phase of liver transplantation.

INTRODUCTION: Thromboelastography (TEG) is gaining increasing acceptance in liver transplantation (LT) with conventional coagulation tests (CCTs) such as prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (ATIII), platelet count (PLT), and fibrinogen concentration. The purpose of this study was to evaluate the clinical utility of TEG in LT and investigate the correlation between TEG and CCT values during each phase of LT. MATERIALS AND METHODS: Medical records of patients who underwent deceased donor LT at a single, university hospital between October 2010 and July 2015 were retrospectively reviewed. Blood samples were obtained at each phase of LT (pre-anhepatic, anhepatic, and neo-hepatic phase) according to our institutional LT protocol and utilized for analysis of TEG and CCTs. The Spearman correlation coefficient between TEG and CCT values were obtained. RESULTS: During the pre-anhepatic phase, the reaction time (R), PT, and aPTT did not correlate with each other, but demonstrated a negative correlation with PLT. Clot formation time (K) demonstrated a similar correlation with R and a negative correlation with fibrinogen. The maximal amplitude (MA) and α-angle (α) were positively correlated with PLT and fibrinogen and inversely correlated with aPTT. During the anhepatic phase, MA was significantly correlated with PLT and inversely correlated with aPTT; other parameters had weak or indistinct correlation. During the neo-hepatic phase, R and K were significantly correlated with aPTT and inversely correlated with PLT and fibrinogen. A correlation of MA and α with PLT, aPTT, and fibrinogen was also observed. Clot lysis at 30 minutes and estimated percent lysis were inversely correlated with levels of ATIII and fibrinogen. CONCLUSIONS: Conventional coagulation tests and TEG show particularly poor comparability during the anhepatic period of liver transplantation. TEG can be most reliable in the anhepatic phase, during which dynamic hemostatic changes occur.

Completion rate of physician orders for life-sustaining treatment for patients with metastatic or recurrent cancer: a preliminary, cross-sectional study.

BACKGROUND: "End of life" is a difficult topic of conversation in East Asian cultures, even among patients and doctors who share a good rapport. In 2016, the Hospice, Palliative Care, and Life-Sustaining Treatment Decision-Making Act, which took the form of "Physician Orders for Life-Sustaining Treatment," was introduced in South Korea. This study was conducted to investigate the completion rate of Physician Orders for Life-Sustaining Treatment in patients with advanced cancer on the active recommendation of physicians, as well as patients' general attitudes toward end-of-life care. METHODS: We conducted a preliminary, cross-sectional descriptive survey on patients with advanced cancer. A total of 101 patients with advanced solid cancer agreed to participate in the study. The primary endpoint was the rate of completion of Physician Orders for Life-Sustaining Treatment based on a doctor's suggestion. Written interviews were conducted to understand the perceptions and factors influencing patients' decisions. RESULTS: Of the 101 patients, 72 (71.3%) agreed to prepare Physician Orders for Life-Sustaining Treatment. Patients who had an educational level of high school or higher were more likely to agree to complete Physician Orders for Life-Sustaining Treatment documentation as compared to the lower educational status group. More than half of the respondents who completed Physician Orders for Life-Sustaining Treatment documentation reported that they had more than a fair understanding of "life-sustaining care" or "Physician Orders for Life-Sustaining Treatment." Participants' reasons for Physician Orders for Life-Sustaining Treatment completion were diverse. CONCLUSIONS: We found that highly educated patients, who understood the concept behind the policy well, tended to accept Physician Orders for Life-Sustaining Treatment without hesitation. Better education, information shared through the media, and conversations with health care providers might improve understanding of Physician Orders for Life-Sustaining Treatment in patients with cancer.

Incidence and risk factors for congestive heart failure in patients with early breast cancer who received anthracycline and/or trastuzumab: a big data analysis of the Korean Health Insurance Review and Assessment service database.

PURPOSE: We aimed to analyze the incidence, time to occurrence, and congestive heart failure (CHF) risk factors for early breast cancer patients treated with anthracycline (AC)-based chemotherapy and/or trastuzumab (T) therapy in Korea. METHODS: We included female patients > 19 years old from the Health Insurance Review and Assessment Service database who had no prior CHF history and had been diagnosed with early breast cancer between January 2007 and October 2016. RESULTS: We included 83,544 patients in our analysis. In terms of crude incidence for CHF, AC followed by T showed the highest incidence (6.3%). However, 3.1 and 4.2% of the patients had CHF due to AC-based chemotherapy and non-AC followed by T, respectively. The median times to occurrence of CHF were different according to adjuvant treatments, approximately 2 years (701.0 days) in the AC-based chemotherapy group vs 1 year (377.5 days) AC followed by T group. T therapy was associated with earlier development of CHF irrespective of previous chemotherapy, but late risk of CHF 1.2 years after T therapy rapidly decreased in both chemotherapy groups. Multivariate Cox regression analysis revealed that the adjusted hazard ratio for CHF was increased in the group of older patients (≥ 65 years old) who underwent AC followed by T therapy, with Charlson comorbidity index scores of ≥ 2. CONCLUSIONS: Our study showed that neo-/adjuvant chemotherapy using T irrespective of previous chemotherapy (AC or non-AC) was associated with significantly increased risk of CHF compared with AC-based chemotherapy in Korean patients with early breast cancer.

Early venous thromboembolism at the beginning of palliative chemotherapy is a poor prognostic factor in patients with metastatic pancreatic cancer: a retrospective study.

BACKGROUND: This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. METHODS: A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. RESULTS: VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (< 135 mmol/L) and high Khorana score (≥3) were strong predictive factors of early VTE (odds ratio [OR] 5.109; 95% confidence interval [95% CI] = 1.010-25.845; p = 0.049 for Khorana score, OR 10.304; 95% CI = 1.036-102.466; p = 0.047) for hyponatremia). CONCLUSIONS: Our study demonstrated that occurrence and detection of VTE in the early period of chemotherapy was the most significant VTE-related prognostic factor in patients with metastatic pancreatic cancer receiving chemotherapy. Prediction using the Khorana score and serum Na levels would be helpful in early diagnosis of VTE.

A Case Report of Primary Pericardial Malignant Mesothelioma Treated with Pemetrexed and Cisplatin.

Primary pericardial malignant mesothelioma (PPM) is a very rare malignancy, with an incidence of less than 0.002% and represents less than 5% of all mesotheliomas. The cause of pericardial mesothelioma is uncertain that differ from pleural mesothelioma which is associated with asbestos exposure. This malignancy is terribly aggressive and has very poor prognosis with less than six months of overall survival. We present a case of a 71-year-old woman who was diagnosed with cardiac tamponade caused by PPM and received chemotherapy with pemetrexed and cisplatin for six months. During two years she was alive without disease progression. To better understand the clinical, pathologic features and treatment outcome of this entity, we reviewed 23 cases described in the English literature from 2009, together with our case, provided a total of 24 cases. Based on this review, we suggest that PPM must be considered in patients who have unexplained massive pericardial effusion and recommend chemotherapy with pemetrexed and cisplatin for the better outcome of PPM.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea.

OBJECTIVE: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). METHODS: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m2 and cyclophosphamide, 600 mg/m2 every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. RESULTS: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. CONCLUSION: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress.

BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.

A Prognostic Index to Identify Patients With Intrahepatic Cholangiocarcinoma Who Could Benefit From Gemcitabine Plus Cisplatin.

Biliary tract cancer is a heterogenous group. Gemcitabine plus cisplatin has been the standard chemotherapy for advanced biliary tract cancer, but there is lack of evidence on treatment in patients with intrahepatic cholangiocarcinoma (IHC). We analyzed 29 patients with only IHC who received gemcitabine plus cisplatin between June 2010 and February 2013. The median age was 63 years (range, 40-78 years), and Eastern Cooperative Oncology Group performance status of all patients was <2. The median progression-free survival and median overall survival (OS) were 4.3 and 7.3 months, respectively. Multivariate analysis showed that platelet count (≤180 × 10 per liter), metastatic site of more than 2, and albumin level (≤3.5 g/dL) were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: zero or 1 (good prognostic group), 2 (intermediate group), or 3 (poor prognostic group). The median OS for good (n = 15), intermediate (n = 10), and poor (n = 4) prognostic group was 10.5, 6.1, and 1.6 months, respectively (P < 0.005). Relatively better prognosis of the good prognosis group comparing to other prognosis groups can be expected from the prognostic model established in this study by analyzing patients with IHC treated with gemcitabine.

Combination chemotherapy with methotrexate and vinblastine for surgically unresectable, aggressive fibromatosis.

OBJECTIVE: To elucidate the clinical benefit and safety of low-dose chemotherapy using methotrexate and vinblastine in patients (mostly adults) with progressive and/or symptomatic fibromatosis. METHODS: Patients were enrolled if they were treated with methotrexate and vinblastine chemotherapy for recurrences after surgical excision or newly diagnosed aggressive fibromatosis that was not amenable to surgical resection at the Korea University Medical Center from May 2008 to February 2016. RESULTS: Twenty-two patients were treated with this regimen, and 21 were eligible for safety and efficacy analysis. Eleven (52%) of 21 patients showed a documented partial response (PR), and 11 showed stable disease (SD) by the end of treatment. All the patients who achieved PR reported a significant reduction in pain and improvement in the function of the affected lesions. Median progression-free survival was not reached at the time of analysis. The most common adverse event was abnormalities of the liver transaminases (overall 84.2%). The most common grade 3 or higher toxicity was neutropenia (36.8%), but no febrile neutropenic event was observed. The elevated levels of transaminases were normalized by reducing the dose of methotrexate or delaying treatment. CONCLUSIONS: Low-dose chemotherapy with methotrexate and vinblastine for 1 year was effective and well tolerated by adult patients with aggressive, recurrent fibromatosis.