An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic Breast Cancer: Korean Multi-center Phase IV Clinical Study Results / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC), who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials. MATERIALS AND METHODS: In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease. RESULTS: A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively. CONCLUSION: This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

Diagnosis of Lymphoid Malignancy by PCR for Analysis of Antigen Receptor Rearrangement after Blood Transfusion in a Dog with Acute Lymphocytic Leukemia

Acute lymphocytic leukemia (ALL) is uncommon lymphoid malignancy in dogs, and its diagnosis is challenging. A 14-year-old spayed female mixed breed dog was transferred to a veterinary medical teaching hospital for an immediate blood transfusion. The dog showed lethargy, pale mucous membranes, and a weak femoral pulse. Complete blood count revealed non-regenerative anemia and severe leukopenia with thrombocytopenia. ALL was tentatively diagnosed based on the predominance of immature lymphoblasts on blood film examination. For confirmation of lymphoid malignancy, PCR for antigen receptor rearrangement (PARR) on a peripheral blood sample and flow cytometry analysis were performed after blood transfusion. Flow cytometry analysis revealed that lymphocyte subsets were of normal composition, but PARR detected a T-cell malignancy. The dog was diagnosed with ALL and survived 1 wk after diagnosis. In conclusion, after blood transfusion, flow cytometry was not a reliable diagnostic method for an ALL dog, whereas PARR could detect lymphoid malignancy. Our results suggest that PARR should be the first-line diagnostic tool to detect canine lymphoid malignancy after a blood transfusion.

Pain Palliation in Patients with Bone Metastases Using Magnetic Resonance-Guided Focused Ultrasound with Conformal Bone System: A Preliminary Report

PURPOSE: We evaluated the safety and effectiveness of the Magnetic Resonance-guided Focused Ultrasound (MRgFUS) with the ExAblate Conformal Bone System for the palliation of painful bone metastases. MATERIALS AND METHODS: Our Institutional Review Board approved this study, and all patients gave informed consent prior to enrollment. A total of six painful metastatic bone lesions in five patients were treated using MRgFUS with the ExAblate Conformal Bone System for pain palliation. The follow-up sessions were at 3 days, 2 weeks, 1, 2, and 3 months, and 1 year after treatment. Efficacy was evaluated by the changes in visual analog scale (VAS) scores. At 3-months and 1-year follow-ups, unenhanced computed tomography and contrast-enhanced MR imaging examinations were performed. All adverse events were assessed to evaluate treatment safety. RESULTS: All patients showed significant pain relief within 2 weeks. Two patients experienced complete pain reduction that lasted for 1 year. Two other patients showed pain relief measured as VAS scores of 2 and 4 on their last follow-up. Although the remaining patient had experienced significant pain relief in two lesions, the VAS score re-increased on his last follow-up. The size of the enhancing soft tissue mass in metastatic lesions decreased, and new bone formation was seen on follow-up images. Although adverse events were not serious, non-specific leg pain and second degree skin burn were noted. CONCLUSION: MRgFUS was demonstrated to be effective palliative treatment within 2 weeks in selected patients with painful bone metastases.

Pain Palliation in Patients with Bone Metastases Using Magnetic Resonance-Guided Focused Ultrasound with Conformal Bone System: A Preliminary Report

PURPOSE: We evaluated the safety and effectiveness of the Magnetic Resonance-guided Focused Ultrasound (MRgFUS) with the ExAblate Conformal Bone System for the palliation of painful bone metastases. MATERIALS AND METHODS: Our Institutional Review Board approved this study, and all patients gave informed consent prior to enrollment. A total of six painful metastatic bone lesions in five patients were treated using MRgFUS with the ExAblate Conformal Bone System for pain palliation. The follow-up sessions were at 3 days, 2 weeks, 1, 2, and 3 months, and 1 year after treatment. Efficacy was evaluated by the changes in visual analog scale (VAS) scores. At 3-months and 1-year follow-ups, unenhanced computed tomography and contrast-enhanced MR imaging examinations were performed. All adverse events were assessed to evaluate treatment safety. RESULTS: All patients showed significant pain relief within 2 weeks. Two patients experienced complete pain reduction that lasted for 1 year. Two other patients showed pain relief measured as VAS scores of 2 and 4 on their last follow-up. Although the remaining patient had experienced significant pain relief in two lesions, the VAS score re-increased on his last follow-up. The size of the enhancing soft tissue mass in metastatic lesions decreased, and new bone formation was seen on follow-up images. Although adverse events were not serious, non-specific leg pain and second degree skin burn were noted. CONCLUSION: MRgFUS was demonstrated to be effective palliative treatment within 2 weeks in selected patients with painful bone metastases.

Predictive Value of the ERCC1 Expression for Treatment Response and Survival in Advanced Gastric Cancer Patients Receiving Cisplatin-based First-line Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy. MATERIALS AND METHODS: A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei. RESULTS: Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%). CONCLUSION: In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.

Non-healing Iatrogenic Gastric Ulcers after Endoscopic Mucosal Resection for Gastric Epithelial Neoplasia: Report of Two Cases / 대한소화기학회지

Endoscopic mucosal resection (EMR) is widely accepted as a standard treatment for early gastric cancer or gastric adenoma. However, EMR inevitably results in the formation of large iatrogenic ulcer at the resected area. Although the characteristics of EMR-induced ulceration are not fully understood, this type of ulcer is thought to heal faster and to recur less often than non-iatrogenic gastric ulcer. Current available evidences have suggested that EMR-induced ulcers heal within 2-3 months. Herein, we report two cases of non-healing persistent gastric ulcers after EMR. One is a case of gastric carcinoma which developed at the same site of previous EMR site for the low grade dysplasia. The other is a case in which persistent EMR-induced ulcer was healed in the long run after Helicobacter pylori eradication therapy.

Late Lung Parenchymal Changes on HRCT in Children with mycoplasma Pneumonia

PURPOSE: To evaluate late lung parenchymal change, as seen on high-resolution CT(HRCT) in children with mycoplasma pneumonia MATERIALS AND METHODS: Twenty-three patients [15 boys and 8 girls aged two to 13 (mean, 6) years] with mycoplasma pneumonia underwent HRCT four to 39 (mean, 10) months after initial infection. Using increased mycoplasma antibody titer(> 1:640) mycoplasma pneumonia was diagnosed, and patients were divided into two groups : high titer group (antibody titer>1: 5120), and lower titer group (<1:5120). CT scans were performed using 2mm collimation and 5-10mm interval from apex to diaphragm. In seven patients who were cooperative, both inspiratory and expiratory scans were obtained at a window width of 1600 HU and level of -700. HRCT findings of mosaic low attenuations and changes in bronchioles and bronchial walls were assessed by three radiologists and correlated with initial chest radiographic findings. RESULTS: On HRCT, 17 of 23 patients (74 %) demonstrated abnormal findings. These included mosaic attenuation of lung density alone in 11 of 17 patients (65%), mosaic attenuation associated with bronchiectasis in five ( 29 %), and bronchiectasis only in one (6 %). Mosaic attenuation was more accentuated on expiratory scans than on inspiratory. These findings were obtained in 10 of 12 high titer group and in 7 of 11 in the lower titer group. In 15 of 23 patients (65 %), involved ageas seen on HRCT exactly corresponded with initially involved areas seen on chest radiographs (CXR). Two patients in whom findings on initial CXR were normal showed mosaic attenuation on HRCT. Six patients in whom such findings were abnormal showed normal findings on HRCT, a fact which reflected their complete recovery. CONCLUSION: The most common late parenchymal change in mycoplasma pneumonia, as seen on HRCT, was mosaic attenuation of lung density followed by bronchiectasis. The latter is presumably due to bronchiolitis obliterans, a well-known complication. We believe that HRCT is very useful for the evaluation of long-term sequelae of mycoplasma pneumonia in children.