Background Hyperlactatemia occurs frequently in critically ill patients, and this pathologic cond... more Background Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury. Methods A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1–7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiolog...
Objective: This phase II study was designed to assess the safety and efficacy of a modified FOLFI... more Objective: This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and con-tinuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer. Methods: Patients were treated with irinotecan 150 mg/m2 on day 1 and received ldLV 20 mg/m2 followed by 5-FU 400 mg/m2 (bolus) and 5-FU 600 mg/m2 (22 h continuous infu-sion) on days 1 and 2 every 14 days. Results: A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31–70), and 55.6 % (20/36) of the patients had performance status (ECOG) of 0 or 1.The median follow-up duration was 15.5 (range 2.6–36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0 % (95 % CI 0.0–21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 ...
It remains controversial whether patients with resectable colorectal liver metastases gain a surv... more It remains controversial whether patients with resectable colorectal liver metastases gain a survival benefit from perioperative chemotherapy with bevacizumab. We found that the overall survival was improved, but it did not affect progression-free survival from our randomized clinical trial. Patients with high carcinoembryonic antigen levels or over 2 liver metastases may benefit from the overall survival of perioperative chemotherapy. Introduction: Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. Material and Methods: Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Results: The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P ¼ .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P ¼ .049). In subgroup patients with carcinoembryonic antigens (CEA) 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.
10054Background: The efficacy of the EGFR inhibitors has been demonstrated in non-small cell lung... more 10054Background: The efficacy of the EGFR inhibitors has been demonstrated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CRC). Dermatological reactions can ca...
Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients w... more Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). Materials and Methods This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. Results Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61...
Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virot... more Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec. Pexa-Vec was cytotoxic on myeloid cell lines in a dose-dependent manner, and fluorescent imaging and qPCR revealed that Pexa-Vec expression was low in RAMOS than IM-9 after 24 hrs and 48 hrs of infection. Gene expression profiles between two groups were analyzed by microarray. Genes with at least 2-fold increase or decrease in their expression were identified. A total of 660 genes were up-regulated and 776 genes were down-regulated in lymphoid cancer cell lines. The up-and down-regulated genes were categorized into 319 functional gene clusters. We identified the top 10 up-regulated genes in lymphoid cells. Among them three human genes (LEF1, STAMBPL1, and SLFN11) strongly correlated with viral replication. Up-regulation of PVRIG, LPP, CECR1, Arhgef6, IRX3, IGFBP2, CD1d were related to resistant to Pexa-Vec. In conclusion, lymphoid malignant cells are resistant to Pexa-Vec and displayed up-regulated genes associated with resistance to oncolytic viral therapy. These data provide potential targets to overcome resistance, and suggest that molecular assays may be useful in selecting patients for further clinical trials with Pexa-Vec.
Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an... more Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an adverse clinical factor. However, it has been unknown which factor would separate clinical outcomes in DLBCL patients with BMI. Recently, metabolic tumor volume (MTV) on positron emission tomography/computed tomography (PET/CT) was suggested to predict prognosis in several lymphoma types. Therefore, we investigated whether MTV would separate the outcomes in DLBCL patients with BMI. MTV on PET/CT was defined as an initial tumor burden as target lesion ≥ standard uptake value, 2.5 in 107 patients with BMI. Intramedullary (IM) MTV was defined as extent of BMI and total MTV was as whole tumor burden. 260.5 cm 3 and 601.2 cm 3 were ideal cutoff values for dividing high and low MTV status in the IM and total lymphoma lesions in Receiver Operating Curve analysis. High risk NCCN-IPI (p < 0.001, p < 0.001), bulky disease (p = 0.011, p = 0.005), concordant subtype (p = 0.025, p = 0.029), high IM MTV status (p < 0.001, p < 0.001), high total MTV status (p < 0.001, p < 0.001), and ≥2CAs in BM (p = 0.037, p = 0.033) were significantly associated with progression-free survival (PFS) and overall survival (OS) than other groups. In multivariate analysis, high risk NCCN-IPI (PFS, p = 0.006; OS, p = 0.013), concordant subtype (PFS, p = 0.005; OS, p = 0.007), and high total MTV status (PFS, p < 0.001; OS, p < 0.001) had independent clinical impacts. MTV had prognostic significances for survivals in DLBCL with BMI.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 16, 2015
Triweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the s... more Triweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the standard regimen for treatment of locally advanced nasopharyngeal carcinoma (NPC) despite a high level of concern regarding treatment-related complications. We conducted a randomized phase II study to compare weekly and triweekly cisplatin delivery during RT with respect to efficacy and toxicity profiles. Patients with locally advanced NPC (stage II-IVb) were randomly assigned to a regimen of either seven doses of cisplatin (40mg/m(2)) given once a week or three doses of cisplatin (100mg/m(2)) given every 3weeks concurrently during RT. Of 109 eligible patients, 53 were assigned to the weekly regimen and 56 to the triweekly regimen. The two groups were comparable with respect to demographic and clinical characteristics. There were no significant differences in mean RT dose (68.3Gy vs. 67.3Gy, p=0.559) and mean cisplatin dose (248.9mg/m(2)vs. 256.6mg/m(2), p=0.433) between the two regimens....
Cancer research and treatment : official journal of Korean Cancer Association, 2014
To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and reliev... more To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator's discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p…
Background and Objectives It is well known that coronary spasm can cause acute coronary syndrome ... more Background and Objectives It is well known that coronary spasm can cause acute coronary syndrome ACS , such as unstable angina or acute myocardial infarction as well as variant angina. However, the role of coronary spasm as an initial presentation in ACS is difficult to demonstrate. Therefore, we investigated the validity and safety of ergonovine echocardiography in ACS with normal coronary angiogram CAG and suspected variant angina. Meterials and Method From July 1999 to June 2000, 53 consecutive patients were enrolled in this study mean age 56 10, 44 male. The clinical manifestations of the patients included acute myocardial infarction 8 , unstable angina 17 and suspected variant angina 28. Ergonovine maleate was administered intravenously 50 g at 5 minute intervals up to total cumulative dosage 350 g with continuous echocardiographic monitoring. The positive criterion of this test was a reversible regional wall motion abnormality seen on echocardiography. Results This test was completed in all patients without major cardiac event or malignant arrhythmia. Fourteen patients 14/53, 26% showed a positive test their clinical diagnosis was AMI in 2, unstable angina in 6, and variant angina in 6. Four cases were positive without chest pain or electrocardiographic change. Conclusion Ergonovine echocardiography is a safe and useful method for the diagnosis of coronary vasospasm in ACS with normal CAG and suspected variant angina without ST segment change.
Recent reports have suggested that ergonovine stress echocardiography is a safe and accurate proc... more Recent reports have suggested that ergonovine stress echocardiography is a safe and accurate procedure for the diagnosis of coronary vasospasm. We experienced a case of heart arrest caused by ergonovine stress echocardiography. A 44 year-old female patient was referred to our emergency room for evaluation of chest pain. She had been admitted to another hospital complaining of chest pain and syncope. The finding of a coronary angiogram was normal and an ergonovine stress echocardiography was performed in order to diagnose the coronary vasospasm, which may be an etiologic mechanism in an unstable angina. After 250 g of ergonovine was administered intravenously, we suspected segmental wall motion abnormality hypokinesia of the inferior wall. An additional dose 100 g was administered to confirm the diagnosis. The patient complained of severe chest pain and dizziness. Segmental wall motion abnormalities progressed and heart arrest finally developed. She recovered following cardiopulmonary resuscitation and was discharged without complication.
Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical ... more Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. Although the optimal chemotherapeutic regimen is not yet defined, previous randomized trials have demonstrated that 5-fluorouracil (5-FU) plus cisplatin every 3 weeks and weekly cisplatin are the most popular regimens. The purpose of this study was to compare the outcomes of weekly CCRT with cisplatin and monthly CCRT with 5-FU plus cisplatin for locally advanced cervical cancer. We retrospectively reviewed data from 255 patients with FIGO stage IIB-IVA cervical cancer. Patients were classified into two CCRT groups according to the concurrent chemotherapy: weekly CCRT group, consisted of CCRT with weekly cisplatin for six cycles; and monthly CCRT group, consisted of CCRT with cisplatin and 5-FU every 4 weeks for two cycles followed by additional consolidation chemotherapy for two cycles with the same regimen. Of 255 patients, 152 (59.6%) patients received weekly CCRT and 103 (40....
The oncolytic and immunotherapeutic vaccinia virus Pexa-Vec (JX-594) induces antibody-mediated co... more The oncolytic and immunotherapeutic vaccinia virus Pexa-Vec (JX-594) induces antibody-mediated complement-dependent cancer cell cytolysis in rabbits and cancer patients, prolonging their survival.
Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid l... more Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid leukemia (CML). However, recent studies showed that the prevalence of anemia is increased with high trough imatinib level and increased doses of imatinib influence decreased proliferation of burst forming units-erythroids (BFU-Es). The aim of this study was to evaluate the continuously increased mean cell volume (MCV) level&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s correlation with cytogenetic response and the favorable outcome in early chronic phase (CP)-CML patients. Clinical importance of MCV level was evaluated to correlate with cytogenetic response and compared with Sokal score, a known excellent prognostic parameter of cytogenetic response (CCR) in 84 early CP-CML patients. The patients with early and continuously increased MCV level irrespective of anemia achieved higher CCR after 12 months of imatinib therapy than patients with non-CCR (p=0.011). When the value was compared with low Sokal score, elevated MCV was independent predictor of CCR (RR=12.925, p=0.002 vs. RR=35.445, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Furthermore, the patients with early and continuously increased MCV level had a higher probability of maintaining CCR than non-increased level (p=0.019). Increased MCV level was surrogate marker of achievement and durability to CCR for early CP-CML patients in the present study.
Background: The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and ... more Background: The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP has recently been associated with the progression of disease in many cancer types. The principal objective of this study was to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and to correlate them with disease status and prognosis. Methods: A total of 115 patients who underwent gastrectomy were enrolled in this study. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumor size, depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (6th AJCC Stage Groupings: The staging systems; Primary tumor, regional LN, metastasis). Results: Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels were correlated with invasion depth (P < 0.001, P = 0.001), LN metastasis (P < 0.001, P = 0.024) and TNM stage (P < 0.001, P < 0.001). The presence of peritoneal seeding metastasis is associated with IL-6 levels (P = 0.012). When we established the cutoff value for IL-6 level (6.77 pg/dL) by ROC curve, we noted significant differences in time to progression (TTP; P < 0.001) and overall survival (OS; P = 0.010). However, CRP evidenced no significance with regard to patients' TTP and OS levels. Serum IL-6 levels were correlated positively with CRP levels (r 2 = 0.049, P = 0.018). Conclusion: Preoperative serum IL-6 and CRP levels might be markers of tumor invasion, LN metastasis, and TNM stage. Preoperative high IL-6 levels were proposed as a poor prognostic factor for disease recurrence and overall survival in patients with gastric cancers.
PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard o... more PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year ...
Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. T... more Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4°C and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4°C, and RT was observed in 3 days in B, while viral activity was not decreased even after 4-8 weeks at 4°C and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at-20°C, 4°C, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4°C or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4°C, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.
Bong-Gun Seo, MD, Sung Yong Oh, MD, Dong Mee Lee, MD, Hyun Seung Yoo, MD, Suee Lee, MD, Seong-Geu... more Bong-Gun Seo, MD, Sung Yong Oh, MD, Dong Mee Lee, MD, Hyun Seung Yoo, MD, Suee Lee, MD, Seong-Geun Kim, MD, Sung-Hyun Kim, MD, Ph.D., Hyuk-Chan Kwon, MD, Ph.D., and Hyo-Jin Kim, MD, Ph.D. ... Department of Internal Medicine, Dong-A University College of ...
Background Hyperlactatemia occurs frequently in critically ill patients, and this pathologic cond... more Background Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury. Methods A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1–7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiolog...
Objective: This phase II study was designed to assess the safety and efficacy of a modified FOLFI... more Objective: This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and con-tinuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer. Methods: Patients were treated with irinotecan 150 mg/m2 on day 1 and received ldLV 20 mg/m2 followed by 5-FU 400 mg/m2 (bolus) and 5-FU 600 mg/m2 (22 h continuous infu-sion) on days 1 and 2 every 14 days. Results: A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31–70), and 55.6 % (20/36) of the patients had performance status (ECOG) of 0 or 1.The median follow-up duration was 15.5 (range 2.6–36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0 % (95 % CI 0.0–21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 ...
It remains controversial whether patients with resectable colorectal liver metastases gain a surv... more It remains controversial whether patients with resectable colorectal liver metastases gain a survival benefit from perioperative chemotherapy with bevacizumab. We found that the overall survival was improved, but it did not affect progression-free survival from our randomized clinical trial. Patients with high carcinoembryonic antigen levels or over 2 liver metastases may benefit from the overall survival of perioperative chemotherapy. Introduction: Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. Material and Methods: Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Results: The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P ¼ .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P ¼ .049). In subgroup patients with carcinoembryonic antigens (CEA) 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.
10054Background: The efficacy of the EGFR inhibitors has been demonstrated in non-small cell lung... more 10054Background: The efficacy of the EGFR inhibitors has been demonstrated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CRC). Dermatological reactions can ca...
Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients w... more Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). Materials and Methods This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. Results Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61...
Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virot... more Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec. Pexa-Vec was cytotoxic on myeloid cell lines in a dose-dependent manner, and fluorescent imaging and qPCR revealed that Pexa-Vec expression was low in RAMOS than IM-9 after 24 hrs and 48 hrs of infection. Gene expression profiles between two groups were analyzed by microarray. Genes with at least 2-fold increase or decrease in their expression were identified. A total of 660 genes were up-regulated and 776 genes were down-regulated in lymphoid cancer cell lines. The up-and down-regulated genes were categorized into 319 functional gene clusters. We identified the top 10 up-regulated genes in lymphoid cells. Among them three human genes (LEF1, STAMBPL1, and SLFN11) strongly correlated with viral replication. Up-regulation of PVRIG, LPP, CECR1, Arhgef6, IRX3, IGFBP2, CD1d were related to resistant to Pexa-Vec. In conclusion, lymphoid malignant cells are resistant to Pexa-Vec and displayed up-regulated genes associated with resistance to oncolytic viral therapy. These data provide potential targets to overcome resistance, and suggest that molecular assays may be useful in selecting patients for further clinical trials with Pexa-Vec.
Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an... more Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an adverse clinical factor. However, it has been unknown which factor would separate clinical outcomes in DLBCL patients with BMI. Recently, metabolic tumor volume (MTV) on positron emission tomography/computed tomography (PET/CT) was suggested to predict prognosis in several lymphoma types. Therefore, we investigated whether MTV would separate the outcomes in DLBCL patients with BMI. MTV on PET/CT was defined as an initial tumor burden as target lesion ≥ standard uptake value, 2.5 in 107 patients with BMI. Intramedullary (IM) MTV was defined as extent of BMI and total MTV was as whole tumor burden. 260.5 cm 3 and 601.2 cm 3 were ideal cutoff values for dividing high and low MTV status in the IM and total lymphoma lesions in Receiver Operating Curve analysis. High risk NCCN-IPI (p < 0.001, p < 0.001), bulky disease (p = 0.011, p = 0.005), concordant subtype (p = 0.025, p = 0.029), high IM MTV status (p < 0.001, p < 0.001), high total MTV status (p < 0.001, p < 0.001), and ≥2CAs in BM (p = 0.037, p = 0.033) were significantly associated with progression-free survival (PFS) and overall survival (OS) than other groups. In multivariate analysis, high risk NCCN-IPI (PFS, p = 0.006; OS, p = 0.013), concordant subtype (PFS, p = 0.005; OS, p = 0.007), and high total MTV status (PFS, p < 0.001; OS, p < 0.001) had independent clinical impacts. MTV had prognostic significances for survivals in DLBCL with BMI.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 16, 2015
Triweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the s... more Triweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the standard regimen for treatment of locally advanced nasopharyngeal carcinoma (NPC) despite a high level of concern regarding treatment-related complications. We conducted a randomized phase II study to compare weekly and triweekly cisplatin delivery during RT with respect to efficacy and toxicity profiles. Patients with locally advanced NPC (stage II-IVb) were randomly assigned to a regimen of either seven doses of cisplatin (40mg/m(2)) given once a week or three doses of cisplatin (100mg/m(2)) given every 3weeks concurrently during RT. Of 109 eligible patients, 53 were assigned to the weekly regimen and 56 to the triweekly regimen. The two groups were comparable with respect to demographic and clinical characteristics. There were no significant differences in mean RT dose (68.3Gy vs. 67.3Gy, p=0.559) and mean cisplatin dose (248.9mg/m(2)vs. 256.6mg/m(2), p=0.433) between the two regimens....
Cancer research and treatment : official journal of Korean Cancer Association, 2014
To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and reliev... more To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator's discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p…
Background and Objectives It is well known that coronary spasm can cause acute coronary syndrome ... more Background and Objectives It is well known that coronary spasm can cause acute coronary syndrome ACS , such as unstable angina or acute myocardial infarction as well as variant angina. However, the role of coronary spasm as an initial presentation in ACS is difficult to demonstrate. Therefore, we investigated the validity and safety of ergonovine echocardiography in ACS with normal coronary angiogram CAG and suspected variant angina. Meterials and Method From July 1999 to June 2000, 53 consecutive patients were enrolled in this study mean age 56 10, 44 male. The clinical manifestations of the patients included acute myocardial infarction 8 , unstable angina 17 and suspected variant angina 28. Ergonovine maleate was administered intravenously 50 g at 5 minute intervals up to total cumulative dosage 350 g with continuous echocardiographic monitoring. The positive criterion of this test was a reversible regional wall motion abnormality seen on echocardiography. Results This test was completed in all patients without major cardiac event or malignant arrhythmia. Fourteen patients 14/53, 26% showed a positive test their clinical diagnosis was AMI in 2, unstable angina in 6, and variant angina in 6. Four cases were positive without chest pain or electrocardiographic change. Conclusion Ergonovine echocardiography is a safe and useful method for the diagnosis of coronary vasospasm in ACS with normal CAG and suspected variant angina without ST segment change.
Recent reports have suggested that ergonovine stress echocardiography is a safe and accurate proc... more Recent reports have suggested that ergonovine stress echocardiography is a safe and accurate procedure for the diagnosis of coronary vasospasm. We experienced a case of heart arrest caused by ergonovine stress echocardiography. A 44 year-old female patient was referred to our emergency room for evaluation of chest pain. She had been admitted to another hospital complaining of chest pain and syncope. The finding of a coronary angiogram was normal and an ergonovine stress echocardiography was performed in order to diagnose the coronary vasospasm, which may be an etiologic mechanism in an unstable angina. After 250 g of ergonovine was administered intravenously, we suspected segmental wall motion abnormality hypokinesia of the inferior wall. An additional dose 100 g was administered to confirm the diagnosis. The patient complained of severe chest pain and dizziness. Segmental wall motion abnormalities progressed and heart arrest finally developed. She recovered following cardiopulmonary resuscitation and was discharged without complication.
Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical ... more Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. Although the optimal chemotherapeutic regimen is not yet defined, previous randomized trials have demonstrated that 5-fluorouracil (5-FU) plus cisplatin every 3 weeks and weekly cisplatin are the most popular regimens. The purpose of this study was to compare the outcomes of weekly CCRT with cisplatin and monthly CCRT with 5-FU plus cisplatin for locally advanced cervical cancer. We retrospectively reviewed data from 255 patients with FIGO stage IIB-IVA cervical cancer. Patients were classified into two CCRT groups according to the concurrent chemotherapy: weekly CCRT group, consisted of CCRT with weekly cisplatin for six cycles; and monthly CCRT group, consisted of CCRT with cisplatin and 5-FU every 4 weeks for two cycles followed by additional consolidation chemotherapy for two cycles with the same regimen. Of 255 patients, 152 (59.6%) patients received weekly CCRT and 103 (40....
The oncolytic and immunotherapeutic vaccinia virus Pexa-Vec (JX-594) induces antibody-mediated co... more The oncolytic and immunotherapeutic vaccinia virus Pexa-Vec (JX-594) induces antibody-mediated complement-dependent cancer cell cytolysis in rabbits and cancer patients, prolonging their survival.
Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid l... more Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid leukemia (CML). However, recent studies showed that the prevalence of anemia is increased with high trough imatinib level and increased doses of imatinib influence decreased proliferation of burst forming units-erythroids (BFU-Es). The aim of this study was to evaluate the continuously increased mean cell volume (MCV) level&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s correlation with cytogenetic response and the favorable outcome in early chronic phase (CP)-CML patients. Clinical importance of MCV level was evaluated to correlate with cytogenetic response and compared with Sokal score, a known excellent prognostic parameter of cytogenetic response (CCR) in 84 early CP-CML patients. The patients with early and continuously increased MCV level irrespective of anemia achieved higher CCR after 12 months of imatinib therapy than patients with non-CCR (p=0.011). When the value was compared with low Sokal score, elevated MCV was independent predictor of CCR (RR=12.925, p=0.002 vs. RR=35.445, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Furthermore, the patients with early and continuously increased MCV level had a higher probability of maintaining CCR than non-increased level (p=0.019). Increased MCV level was surrogate marker of achievement and durability to CCR for early CP-CML patients in the present study.
Background: The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and ... more Background: The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP has recently been associated with the progression of disease in many cancer types. The principal objective of this study was to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and to correlate them with disease status and prognosis. Methods: A total of 115 patients who underwent gastrectomy were enrolled in this study. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumor size, depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (6th AJCC Stage Groupings: The staging systems; Primary tumor, regional LN, metastasis). Results: Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels were correlated with invasion depth (P < 0.001, P = 0.001), LN metastasis (P < 0.001, P = 0.024) and TNM stage (P < 0.001, P < 0.001). The presence of peritoneal seeding metastasis is associated with IL-6 levels (P = 0.012). When we established the cutoff value for IL-6 level (6.77 pg/dL) by ROC curve, we noted significant differences in time to progression (TTP; P < 0.001) and overall survival (OS; P = 0.010). However, CRP evidenced no significance with regard to patients' TTP and OS levels. Serum IL-6 levels were correlated positively with CRP levels (r 2 = 0.049, P = 0.018). Conclusion: Preoperative serum IL-6 and CRP levels might be markers of tumor invasion, LN metastasis, and TNM stage. Preoperative high IL-6 levels were proposed as a poor prognostic factor for disease recurrence and overall survival in patients with gastric cancers.
PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard o... more PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year ...
Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. T... more Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4°C and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4°C, and RT was observed in 3 days in B, while viral activity was not decreased even after 4-8 weeks at 4°C and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at-20°C, 4°C, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4°C or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4°C, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.
Bong-Gun Seo, MD, Sung Yong Oh, MD, Dong Mee Lee, MD, Hyun Seung Yoo, MD, Suee Lee, MD, Seong-Geu... more Bong-Gun Seo, MD, Sung Yong Oh, MD, Dong Mee Lee, MD, Hyun Seung Yoo, MD, Suee Lee, MD, Seong-Geun Kim, MD, Sung-Hyun Kim, MD, Ph.D., Hyuk-Chan Kwon, MD, Ph.D., and Hyo-Jin Kim, MD, Ph.D. ... Department of Internal Medicine, Dong-A University College of ...
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