Min-Young Lee

Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the Revised European-American Lymphoma (REAL) classification

The aim of this study was to analyse the clinical characteristics and prognostic factors of peripheral T-cell lymphomas (PTCLs) according to the Revised European-American Lymphoma (REAL) classification. From 1994 to 1999, 78 patients were diagnosed with PTCLs, excluding cutaneous T-cell lymphomas and T-cell chronic lymphocytic leukaemia. The distribution of the histological subgroups were: PTCL unspecified (PTCL-U), 40%; angiocentric lymphoma, 32%; anaplastic large cell lymphoma (ALCL), 17%; angioimmunoblastic T-cell lymphoma (AILD), 6%; intestinal T-cell lymphoma, 3%; and panniculitic T-cell lymphoma, 3%. Patients with angiocentric lymphoma presented with favourable prognostic factors, whereas those with AILD presented with unfavourable prognostic factors. Most patients were treated with doxorubicin-containing combination chemotherapy (with or without radiation therapy). The overall complete remission rate was 61.2% (95% Confidence Interval (CI): 48.5-72.8%) and the 5-year probability of failure-free survival was 33.5%. Median survival of all patients was 45 months (range 0-64+ months) and the 5-year probability of survival was 36.2%. In the multivariate analysis, only the International Prognosis Index (IPI) was an independent prognostic factor for overall survival (P<0.01). Taken together, the proportion of angiocentric lymphoma in this study was higher than that in the studies of Western countries. PTCL responds poorly to treatment with low survival rates and the IPI is a useful prognostic factor for PTCL.

Capecitabine monotherapy in patients with anthracycline-and taxane-pretreated metastatic breast cancer

The selection of chemotherapeutic regimens is challenging for metastatic breast cancer (MBC) patients whose diseases have failed to respond to anthracyline and taxane. Capecitabine has advantages of oral administration and favorable toxicity profiles. This study was conducted to evaluate the efficacy of capecitabine and to identify the subgroup of patients who would potentially have benefit from capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC. Female patients with MBC who had been previously treated with anthracycline and taxane received oral capecitabine 2500 mg/m2 divided in two doses daily for 2 wk with 1-wk rest period. Between September, 1999, and December, 2002, a total of 38 patients were enrolled. Among the 36 evaluable patients, one patient achieved a complete response (CR), 9 patients had partial responses (PRs), and 13 patients had stable diseases (SDs). Response rate was 26% [95% confidence interval (CI), 12–40%] and the tumor control rate (TCR, CR+PR+SD) was 61% (95% CI, 45–77%). The median follow-up duration was 27.8 mo. The median duration of response was 8.9 mo, the median time to progression was 4.6 mo, and the median overall survival was 18.1 mo. The major toxicities were hand-foot syndrome, diarrhea, and emesis. There was no treatment-related death. The predictors of better overall survival were positivity of hormone receptor, disease-free survival longer than 1 yr, non-refractoriness to anthracycline, and fewer number (≤3) of involved organs. Capecitabine monotherapy is effective and well tolerated for MBC patients who had previously been treated with anthracycline and taxane. The TCR could predict overall survival as well as the objective respose in this study, suggesting a possible role of TCR as a surrogate marker for survival in MBC patients on salvage chemotherapy. The patients who have relatively slow growing tumor and less tumor burden could have benefit from capecitabine monotherapy following anthracycline- and taxane-based chemotherapy.

Hepatitis B reactivation in multiple myeloma patients with resolved hepatitis B undergoing chemotherapy.

Despite increasing reports of hepatitis B virus (HBV) reactivation in multiple myeloma (MM), HBV reactivation in patients with resolved hepatitis B [hepatitis B surface antigen (HBsAg)‐negative/anti‐hepatitis B core antigen antibody (anti‐HBc)‐positive] is still poorly characterized. The aim of this study was to clarify its frequency and risk factors.

The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors

Introduction: A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant non–small-cell lung cancer (NSCLC). Methods: Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib). Results: The BIM deletion polymorphism was present in 15.6% (32 of 205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were younger than 65 years (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar objective response rates (91 vs. 84%, p = 0.585). Progression-free survival and overall survival did not differ significantly between patients with and without the BIM deletion polymorphism (median progression-free survival 12 vs. 11 months, p = 0.160; median overall survival 31 vs. 30 months, p = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including Eastern Cooperative Oncology Group performance status 0–1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients. Conclusions: It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.

The impact of KRAS mutations on prognosis in surgically resected colorectal cancer patients with liver and lung metastases: a retrospective analysis

BackgroundKRAS mutations are common in colorectal cancer (CRC). The role of KRAS mutation status as a prognostic factor remains controversial, and most large population-based cohorts usually consist of patients with non-metastatic CRC. We evaluated the impact of KRAS mutations on the time to recurrence (TTR) and overall survival (OS) in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.MethodsPatients who underwent curative resection for primary and synchronous metastases were retrospectively collected in a single institution during a 6xa0year period between January 2008 and June 2014. Patients with positive surgical margins, those with known BRAF mutation, or those with an unknown KRAS mutation status were excluded, and a total of 82 cases were identified. The pathological and clinical features were evaluated. Patients’ outcome with KRAS mutation status for TTR and OS were investigated by univariate and multivariate analysis.ResultsKRAS mutations were identified in 37.8xa0% of the patients and not associated with TTR or OS between KRAS wild type and KRAS mutation cohorts (log-rank pu2009=u20090.425 for TTR; log-rank pu2009=u20090.137 for OS). When patients were further subdivided into three groups according to mutation subtype (wild-type vs. KRAS codon 12 mutation vs. KRAS codon 13 mutation) or amino acid missense mutation type (Gu2009>u2009A vs. Gu2009>u2009T vs. Gu2009>u2009C), there were no significant differences in TTR or OS. Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (pu2009=u20090.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung.ConclusionsKRAS mutation was not associated with TTR or OS in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.

Regorafenib as Salvage Treatment in Korean Patients with Refractory Metastatic Colorectal Cancer

Purpose Regorafenib, an oral multi-targeted tyrosine kinase inhibitor, is considered the new standard of care in patients with chemotherapy-refractory colorectal cancers (CRCs). However, there are no data on this drug in Korean patients. Materials and Methods We evaluated patients who received oral regorafenib 160 mg once daily during the first 3 weeks of each 4-week cycle between August 2013 and September 2013. All patients had previously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agents such as cetuximab or bevacizumab. Results Thirty-two patients were enrolled (median age, 57 years; male:female ratio, 20:12; Eastern Cooperative Oncology Group performance status [0-1:2], 31:1; colon:rectum, 21:11). The overall response rate was 3.1% and the disease control rate was 50.0% (95% confidence interval [CI]) with one partial response and 15 patients with stable disease. The median progression-free survival was 4.2 months (95% CI, 3.1 to 5.2 months) and the median overall survival has not yet been reached. The most common adverse events of grade two or higher related to regorafenib were hand-foot skin reaction (25%), mucositis (19%), abdominal pain (9%), and liver function test (LFT) abnormalities (9%). Grade 3 or 4 toxicities included LFT abnormalities (9%), abdominal pain (9%), rash (6%), anemia (3%), leukopenia (3%), neutropenic fever (3%), and fatigue (3%). There was no treatment-related death. Conclusion Regorafenib appears to have promising activity and tolerable toxicity profiles in Korean patients with refractory CRC, consistent with the CORRECT trial findings.

Clinicopathological Features and Prognostic Factors Affecting Survival Outcomes in Isolated Locoregional Recurrence of Breast Cancer: Single-Institutional Series

Purpose The purpose of this study was to investigate the clinicopathologic features and prognostic factors affecting outcome in patients with isolated locoregional recurrence of breast cancer (ILRR). Methods We retrospectively analyzed the medical records of 104 patients who were diagnosed with ILRR and underwent curative surgery from January 2000 to December 2010 at Samsung Medical Center. Results Among 104 patients, 43 (41%) underwent total mastectomy and 61 (59%) underwent breast-conserving surgery for primary breast cancer. The median time from initial operation to ILRR was 35.7 months (4.5–132.3 months). After diagnosis of ILRR, 45 (43%) patients were treated with mastectomy, 41 (39%) with excision of recurred lesion, and 18 (17%) with node dissection. During a median follow-up of 8.9 years, the 5-year overall survival was 77% and 5-year distant metastasis-free survival (DMFS) was 54%. On multivariate analysis, younger age (< 35 years), higher stage, early onset of elapse (≤ 24 months), lymph node recurrences, and subtype of triple negative breast cancer (TNBC) were found to be independently associated with DMFS. Patients in the no chemotherapy group showed a longer DMFS after surgery for ILRR than those treated with chemotherapy (median 101.5 vs. 48.0 months, p = 0.072) but without statistical significance. Conclusion Our analysis showed that younger age (< 35 years), higher stage, early onset of relapse (≤ 24 months), lymph node recurrence, and subtype of TNBC are the worst prognostic factors for ILRR.

Biocompatible and Biodegradable Fe3+–Melanoidin Chelate as a Potentially Safe Contrast Agent for Liver MRI

Currently, most MRI probes available for clinical use contain gadolinium, which is a high-risk paramagnetic metal that can cause severe side effects (e.g., nephrogenic systemic fibrosis). To limit such side effects and improve diagnostic efficacy, we developed a novel biocompatible MRI contrast agent using glucose, glycine, and paramagnetic iron ion. Glucose and glycine were polymerized into melanoidin by the nonenzymatic Maillard reaction, and Fe3+ was chelated stably with the melanoidin during polymerization. The Fe3+-melanoidin chelate had biocompatibility, biodegradability, and unique contrast effects on both T1- and T2-weighted MRI, depending on the pH and oxidative environments. The administration of the Fe3+-melanoidin chelate to a mouse model of liver cancer showed highly enhanced liver-to-tumor contrasts on both T1- and T2-weighted MRI.

Efficacy and feasibility of autologous stem cell transplantation in patients with diffuse large B-cell lymphoma with secondary central nervous system involvement

Secondary central nervous system (CNS) involvement is a fatal complication of diffuse large B-cell lymphoma (DLBCL). We evaluated the efficacy and feasibility of high-dose chemotherapy containing busulfan and thiotepa followed by autologous stem cell transplantation (HDC-ASCT) in DLBCL with secondary CNS involvement. Thirty-one patients with secondary CNS involvement including CNS involvement at diagnosis (nxa0=xa09), isolated CNS relapse (nxa0=xa014), and CNS involvement with systemic disease progression or relapse (nxa0=xa08) were selected and analyzed from our prospective cohorts. Of these, 12 patients, including seven with isolated CNS relapse, successfully completed HDC-ASCT without engraftment failure or transplantation-related mortality. After ASCT, six patients were alive; however, three patients experienced post-transplantation relapse. With a median follow-up of 29xa0months after secondary CNS involvement, the median overall survival of 31 patients was 9 months (95xa0% CI 5–12xa0months). The survival outcomes of patients who had undergone HDC-ASCT were significantly better than those of patients who did not (pxa0<xa00.01). Accordingly, patients with isolated CNS relapse tended to have a longer survival outcome than other cases. Our results suggest that HDC-ASCT may provide survival benefits in DLBCL patients with secondary CNS involvement, especially in case of isolated CNS relapse.