Safety, efficacy, and patient-perceived satisfaction of peripherally inserted central catheters in terminally ill cancer patients: a prospective multicenter observational study.

PURPOSE: The purpose of this study was to investigate the safety, efficacy, and subjective satisfaction of peripherally inserted central catheters (PICCs) in terminally ill cancer patients. METHODS: All PICCs were inserted by an interventional radiologist with radiological guidance. We monitored the occurrence of PICC-related complication and evaluated the patient-perceived satisfaction for PICC using semi-structured questionnaire. RESULTS: A total of 36 terminally ill cancer patients underwent PICC. Three patients had 2 PICC insertions; hence, finally 39 episodes during 829 PICC days were analyzed. All procedures were completed without any procedure-related complication. The median catheter life span was 19.0 days (95 % CI, 14.1-23.9). Thirty-four cases maintained the PICC until the intended time, while the other 5 cases (12.8 %; 6.1/1000 PICC days) were premature PICC removals. Totally 10 complications (25.6 %; 12.3/1000 PICC days) were reported including premature removals (n = 5), trivial bleedings (n = 3), and thrombophlebitis (n = 2). Patients reported that the procedure was not distressing (42 %), a little distressing (36 %), or distressing (21 %). Of 30 patients who had preserved cognitive function at fifth day, most patients (n = 25, 83 %) reported more comfort although the other 5 patients reported no change (n = 3) or less comfort (n = 2). CONCLUSIONS: PICCs were safely inserted and showed favorable maintenance rate with acceptable complications. Additionally, most of the patients felt that parenteral access became much comfortable after PICC insertion. When considering the characteristics of terminally ill cancer patients, poor general condition and a limited period of survival, PICC could be a safe and effective method for intravenous access.

Inhibition of EGFR induces a c-MET-driven stem cell population in glioblastoma.

Glioblastoma multiforme (GBM) is the most lethal form of primary brain tumors, characterized by highly invasive and aggressive tumors that are resistant to all current therapeutic options. GBMs are highly heterogeneous in nature and contain a small but highly tumorigenic and self-renewing population of stem or initiating cells (glioblastoma stem cells or GSCs). GSCs have been shown to contribute to tumor propagation and resistance to current therapeutic modalities. Recent studies of human GBMs have elucidated the genetic alterations common in these tumors, but much remains unknown about specific signaling pathways that regulate GSCs. Here we identify a distinct fraction of cells in a genetically engineered mouse model of EGFR-driven GBM that respond to anti-EGFR therapy by inducing high levels of c-MET expression. The MET-positive cells displayed clonogenic potential and long-term self-renewal ability in vitro and are capable of differentiating into multiple lineages. The MET-positive GBM cells are resistant to radiation and highly tumorigenic in vivo. Activation of MET signaling led to an increase in expression of the stemness transcriptional regulators Oct4, Nanog, and Klf4. Pharmacological inhibition of MET activity in GSCs prevented the activation of Oct4, Nanog, and Klf4 and potently abrogated stemness. Finally, the MET expressing cells were preferentially localized in perivascular regions of mouse tumors consistent with their function as GSCs. Together, our findings indicate that EGFR inhibition in GBM induces MET activation in GSCs, which is a functional requisite for GSCs activity and thus represents a promising therapeutic target.

Clinicopathological features and prognostic significance of HER2 expression in gastric cancer.

BACKGROUND: HER2 positivity is reported to be <20% in gastric cancer. Clinicopathological characteristics will be helpful to understand the biological features of HER2-positive gastric cancer. METHODS: A total of 813 gastric cancer patients who underwent HER2 testing between January 2005 and December 2010 were included in this study. RESULTS: Ninety-five (11.7%) patients had HER2-positive gastric cancer. Elevated serum carcinoembryonic antigen (CEA) concentration [odds ratio (OR), 5.629; p < 0.001] and differentiated histology (OR, 3.717; p = 0.002) were significant predictive factors for HER2 positivity in localized disease. For recurrent or metastatic disease, elevated serum CEA concentration (OR, 2.545; p < 0.001), differentiated histology (OR, 3.299; p < 0.001), pulmonary metastasis (OR, 3.321; p = 0.001), and distant lymph node metastasis (OR, 2.286; p = 0.002) were significant predictive factors. Median disease-free survival (DFS) was shorter in HER2-positive patients than in others, especially in stage I or II disease (24.7 vs. 49.2 months; p < 0.001). Among HER2-negative patients with stage II diseases, patients who received adjuvant chemotherapy had longer DFS than others (42.2 vs. 30.7 months; p = 0.025). CONCLUSIONS: Clinicopathological factors may be useful in predicting the HER2 positivity of gastric cancer. Further studies are needed to understand the molecular basis of HER2-positive gastric cancer.

Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea-experience from 110 patients.

We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.

Clinical features and treatment outcome of primary systemic light-chain amyloidosis in Korea: results of multicenter analysis.

Primary systemic light-chain (AL) amyloidosis a disorder characterized by accumulation of monoclonal light chains as aggregated amyloid fibrils in tissues of multiple organs to cause organ dysfunction and death (Kyle and Gertz, Semin Hematol 1995;32:45-59; Merlini and Bellotti, N Engl J Med 2003;349:583-596). Although there are quite a number of data regarding clinical features and treatment outcomes of AL amyloidosis, most of them are from western countries except for a couple of reports from Japan (Kyle and Gertz, Semin Hematol 1995;32:45-59; Yamazaki et al., Clin Exp Nephrol 2009;13:522-525; Goodman et al., Br J Haematol 2006;134:417-425; Michael et al., Clin Lymphoma Myeloma Leuk 2010;10:56-61; Palladini et al., Blood 2004;103:2936-2938). Considering the effect of ethnic difference on the clinical course and outcomes of AL amyloidosis, the analysis of Asian patients may help better understanding of this disease entity. Therefore, we conducted retrospective analysis of clinical features and treatment outcomes of 84 newly diagnosed AL amyloidosis patients in six referral centers in Korea between 1995 and 2010.

Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum.

OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma. METHODS: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity. CONCLUSIONS: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.

Clinical presentation of carcinoma of unknown primary: 14 years of experience.

A carcinoma of unknown primary (CUP) is a histologically confirmed metastatic cancer without a definitive primary site after performing a detailed medical examination. The purpose of the study was to classify unfavorable CUPs into more reliable disease entities, which reflect the clinical course. We reviewed the medical records of patients diagnosed with a CUP between January 1995 and March 2008. Patients were classified into a conventional favorable-risk group and a newly proposed unfavorable-risk group according to the clinicopathologic features. Five hundred eighty-six patients were diagnosed with CUPs. Fifty-six (9.6%) patients were classified in the conventional favorable-risk group, and 486 (82.9%) patients were classified in the unfavorable-risk group. We further classified the 486 patients into six subgroups with an unfavorable risk, while excluding 29 patients (5.0%) who were not classifiable. The overall survival of the conventional favorable-risk group was 47.0 months (95% CI, 11.1~82.9 months), which was significantly longer than that of any subgroup of the newly proposed unfavorable-risk group (P < 0.001). Patients with squamous cell carcinoma in the abdominopelvic cavity showed similar overall survival with unfavorable-risk group (P = 0.484). Women with non-papillary malignant ascites had a survival in between the favorable and unfavorable groups (P < 0.001). The newly proposed unfavorable-risk group may assist in classifying CUP patients with an unfavorable risk in a clinically more meaningful way. Squamous cell carcinoma in the abdominopelvic cavity should be considered in the unfavorable-risk group and women with non-papillary malignant ascites in an intermediate-risk group. Further studies with molecular profiling would help in classifying and treating patients with CUPs and an unfavorable risk.

EGFRvIII tumorigenicity requires PDGFRA co-signaling and reveals therapeutic vulnerabilities in glioblastoma.

Focal amplification of epidermal growth factor receptor (EGFR) and its ligand-independent, constitutively active EGFRvIII mutant form are prominent oncogenic drivers in glioblastoma (GBM). The EGFRvIII gene rearrangement is considered to be an initiating event in the etiology of GBM, however, the mechanistic details of how EGFRvIII drives cellular transformation and tumor maintenance remain unclear. Here, we report that EGFRvIII demonstrates a reliance on PDGFRA co-stimulatory signaling during the tumorigenic process in a genetically engineered autochthonous GBM model. This dependency exposes liabilities that were leveraged using kinase inhibitors treatments in EGFRvIII-expressing GBM patient-derived xenografts (PDXs), where simultaneous pharmacological inhibition of EGFRvIII and PDGFRA kinase activities is necessary for anti-tumor efficacy. Our work establishes that EGFRvIII-positive tumors have unexplored vulnerabilities to targeted agents concomitant to the EGFR kinase inhibitor repertoire.

Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study.

BACKGROUND: We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. METHODS: Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria. RESULTS: Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n=39, 30.2%) which was followed by nasal cavity (n=30, 23.3%), genitourinary (n=21, 16.3%), oral cavity (n=14, 10.9%), upper gastrointestinal tract (n=6, 4.7%) and maxillary sinus (n=5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age>50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P=.04). CONCLUSION: Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.

Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype.

BACKGROUND: We analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype. METHODS: A retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status. RESULTS: Of the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001). CONCLUSIONS: The response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.

Definitive chemoradiation therapy with capecitabine in locally advanced pancreatic cancer.

We evaluated safety and efficacy of concurrent chemoradiotherapy (CCRT) with capecitabine in patients with locally advanced pancreatic cancer (LAPC). Between January 2004 and January 2008, 39 patients with LAPC treated with capecitabine CCRT were reviewed. Capecitabine was administered at 850 mg/m twice daily every day with 5 days per week radiotherapy (1.8 Gy fractions) over the 5 weeks. Thirty-seven (94.8%) patients completed CCRT. Of the 36 evaluable patients, 15 (41.7%) and 13 (36.1%) patients achieved partial response and stable disease, and eight (28.6%) among them received gemcitabine-based post-CCRT chemotherapy without dose reduction or delay. The overall survival was 14.3 months [95% confidence interval (CI): 10.6-17.9 months]. Median progression-free survival was 11.1 months for all patients, and 7.9 months for those patients who had not received post-CCRT chemotherapy. Eight patients (21.6%) had severe grade 3 toxicities, seven (18.9%) with gastrointestinal toxicity, and one (2.7%) with hematologic toxicity. Prognostic factors for survival were serum albumin (P = 0.014; relative risk: 3.4; 95% CI: 1.4-9.7), and adjuvant gemcitabine treatment (P=0.005; relative risk: 3.5; 95% CI: 1.2-10.6). Combined therapy with capecitabine CCRT was well tolerated and seems to be a promising regimen, in terms of response, survival, and adverse effects.

Effect of education on preference of parenteral nutrition for patients in palliative care unit: quantitative and qualitative study with an anthropological approach.

BACKGROUND: Patients and their family have resistance in withholding parenteral nutrition (PN) when patient become unable to intake food in the end-of-life. We aimed to investigate whether the preference for PN is changed after receiving an individual education about the risk and benefit of PN. Additionally, we focused on the preferences of patients and their family and why they prefer it about the nutritional support in the end of life. METHODS: This is prospective study. Patients are eligible if they cannot tolerate oral intake and enteral feeding and have Palliative Performance Scale (PPS) ≤50% due to progressive cancer. After informed consent, investigators educated patients and family for an hour using the handouts. Then, patients decided if they will receive PN. Quality of life (QOL) was checked by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C15-PAL) weekly during 3 weeks. Symptoms related to fluid overloading or dehydration was surveyed weekly also. A social anthropologist participated as an observer or interviewer during whole process of this study. RESULTS: After education, 12 patients (80%) chose to keep receiving PN and 3 patients (20%) changed their decision from PN to minimal hydration among the 15 patients. More calories were administered to patients who chosen PN (median 1,042.2 vs. 324.3 Kcal/day, P<0.001) for initial 7 days. Overall survival, scores of QLQ-C15-PAL, and symptoms were not different with or without PN. According to the anthropologist, medical staffs regard PN as complex medical treatments, while patients and family recognize it as meal rather than medicine. CONCLUSIONS: Most patients and family prefer to receive PN despite its potential harm and marginal benefit. An in-depth discussion about prognosis and aim of care must be preceded before a decision whether to receive PN can be made.

Glioblastoma-Derived Extracellular Vesicles Facilitate Transformation of Astrocytes via Reprogramming Oncogenic Metabolism.

Glioblastoma (GBM) may arise from astrocytes through a multistep process involving a progressive accumulation of mutations. We explored whether GBM-derived extracellular vesicles (EVs) may facilitate neoplastic transformation and malignant growth of astrocytes. We utilized conditioned media (CM) of cultured glioma cells, its sequential filtration, diverse cell-based assays, RNA sequencing, and metabolic assays to compare the effects of EV-containing and EV-depleted CM. GBM EVs facilitated the neoplastic growth of pre-transformed astrocytes but not normal human or mouse astrocytes. They induced proliferation, self-renewal, and colony formation of pre-transformed astrocytes and enhanced astrocytoma growth in a mouse allograft model. GBM EVs appear to reprogram astrocyte metabolism by inducing a shift in gene expression that may be partly associated with EV-mediated transfer of full-length mRNAs encoding ribosomal proteins, oxidative phosphorylation, and glycolytic factors. Our study suggests an EV/extracellular RNA (exRNA)-mediated mechanism that contributes to astrocyte transformation via metabolic reprograming and implicates horizontal mRNA transfer.

Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer patients who received platinum-containing chemotherapy.

The aim of this study was to evaluate the role of platinum-containing chemotherapy for metastatic triple-negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression-free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane-platinum chemotherapy as the first- or second-line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum-containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor-2 (HER2) receptor status received taxane-platinum regimen as the first- or second-line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p = 0.037) and overall survival (OS) (21 vs. 56 months, p = 0.030) differed significantly between patients with TNBC and non-TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum-containing chemotherapy, patients with TNBC had a shorter OS than patients with non-TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted.

Clinical significance of a serum CA15-3 surge and the usefulness of CA15-3 kinetics in monitoring chemotherapy response in patients with metastatic breast cancer.

One hundred and twenty-two patients in whom the CA 15-3 level showed either a decline (92 patients) or an acute surge followed by a decline (30 patients) after chemotherapy were included. The clinical characteristics between the two groups and the CA 15-3 kinetics using receiver operating characteristic curves were analyzed. Patients with a surge had a significantly higher risk of disease progression than patients without a surge (P = 0.004; odds ratio 2.62; 95% CI 1.45-4.72). The clinicopathologic characteristics were significantly different between the two groups with respect to the distribution of ER, PR, and HER2 status, relapse-free survival, and the severity and extent of the involved organs. For patients with a surge, a CA 15-3 slope threshold > -0.0038 was chosen with a sensitivity of 80.0% and a specificity of 80.4%. The area under the curve was 0.847 (95% CI 0.771-0.906; P = 0.0001). A significant correlation between PFS and CA 15-3 slope was shown with Cox-regression modeling (P = 0.036; hazard ratio [HR], 2.1; 95% CI 1.01-4.14).These kinetics may serve as a good predictive marker of treatment response and response duration.

Comparison of survival in advanced non-small cell lung cancer patients in the pre- and post-gefitinib eras.

BACKGROUND: The aim of this study was to analyze the survival difference between advanced non-small cell lung cancer (NSCLC) patients in the pre-gefitinib and post-gefitinib eras in Korea. PATIENTS AND METHODS: 830 patients with advanced/metastatic or recurrent NSCLC who received palliative chemotherapy were retrospectively reviewed. Using a matched-pair case-control study design, 334 pairs from the pre-gefitinib era (January 1999 to December 2001) and the post-gefitinib era (January 2002 to December 2005) were matched by age, sex and histology. RESULTS: The median overall survival from the date of first administration of palliative chemotherapy was significantly longer in the post-gefitinib era (11.5 vs. 19.3 months, p< 0.001). Multivariate analysis showed that gefitinib was associated with longer overall survival (hazard ratio 0.58, p< 0.001) as were never having been a smoker, adenocarcinoma histology, good performance, stage IIIB, >or=3 prior episodes of chemotherapy, platinum-based chemotherapy and previous docetaxel or pemetrexed treatment. Patients in the post-gefitinib era showed significantly longer overall survival in almost all subgroups. Gefitinib treatment was of significantly greater benefit in patients with adenocarcinoma than in those with non-adenocarcinoma (test for interaction p< 0.001). CONCLUSION: These results indicate a significant improvement of survival in advanced NSCLC patients treated with gefitinib in Korea.

Liposarcoma: exploration of clinical prognostic factors for risk based stratification of therapy.

BACKGROUND: Prognosis and optimal treatment strategies of liposarcoma have not been fully defined. The purpose of this study is to define the distinctive clinical features of liposarcomas by assessing prognostic factors. METHODS: Between January 1995 and May 2008, 94 liposarcoma patients who underwent surgical resection with curative intent were reviewed. RESULTS: Fifty patients (53.2%) presented with well differentiated, 22 (23.4%) myxoid, 15 (16.0%) dedifferentiated, 5 (5.3%) round cell, and 2 (2.1%) pleomorphic histology. With the median 14 cm sized of tumor burden, about half of the cases were located in the retroperitoneum (46.8%). Seventy two (76.6%) patients remained alive with 78.1%, and 67.5% of the 5- and 10-year overall survival (OS) rates, respectively. Low grade liposarcoma (well differentiated and myxoid) had a significantly prolonged OS and disease free survival (DFS) with adjuvant radiotherapy when compared with those without adjuvant radiotherapy (5-year OS, 100% vs 66.3%, P = 0.03; 1-year DFS, 92.9% vs 50.0%, respectively, P = 0.04). Independent prognostic factors for OS were histologic variant (P = 0.001; HR, 5.1; 95% CI, 2.0 - 12.9), and margin status (P = 0.005; HR, 4.1; 95% CI, 1.6-10.5). We identified three different risk groups: group 1 (n = 66), no adverse factors; group 2, one or two adverse factors (n = 28). The 5-year OS rate for group 1, and 2 were 91.9%, 45.5%, respectively. CONCLUSION: The histologic subtype, and margin status were independently associated with OS, and adjuvant radiotherapy seems to confer survival benefit in low grade tumors. Our prognostic model for primary liposarcoma demonstrated distinct three groups of patients with good prognostic discrimination.

A retrospective analysis of second-line chemotherapy in patients with advanced gastric cancer.

BACKGROUND: Because treatment of advanced gastric cancer (AGC) patients after failure with first-line chemotherapy remains controversial, we performed this retrospective analysis based on the data obtained from 1455 patients registered in a first-line treatment cohort with respect to receiving or not receiving subsequent chemotherapy. METHODS: The decision for administering second-line chemotherapy was, in most cases, at the discretion of the physician. Seven-hundred twenty-five (50%) received second-line chemotherapy after first-line failure. Univariate and multivariate analyses were performed on the recognized baseline parameters for survival. RESULTS: At the time of initiating second-line chemotherapy, the patients' median age was 56 years (range, 22 to 86) and 139 (19%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. Seven (1%) complete and 108 (15%) partial responses to second-line chemotherapy were observed for an overall response rate of 16% (95% confidence interval [CI], 13 to 19%). The median progression-free and overall survivals, calculated from the start of second-line chemotherapy, were 2.9 months (95% CI, 2.6 to 3.3) and 6.7 months (95% CI, 5.8 to 7.5), respectively. Multivariate analysis revealed that low baseline hemoglobin level (hazard ratio [HR], 0.74; 95% CI 0.61-0.90) and a poor performance status (HR, 0.66; 95% CI, 0.52-0.83) were independent negative prognostic factors for overall survival. CONCLUSION: Performance status, along with baseline hemoglobin level, could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy for AGC.

Treatment outcome of adult patients with Burkitt lymphoma: results using the LMB protocol in Korea.

Burkitt lymphoma (BL) is a rare subtype of adult non-Hodgkin lymphoma, so studies on the outcome of adult BL, especially in Asian patients, are scarce. We report our results using the LMB protocol on Korean adult BL patients. Thirty-eight newly diagnosed BL patients were treated with the LMB protocol; 29 males and nine females with a median age of 47 years (range 18-70) were analyzed, and 14 (36.8%) patients had central nervous system or bone marrow involvement. After the induction phase, 28 patients achieved complete response (CR, 73.7%) and five showed partial response (PR, 13.2%). Among those achieving CR, only four showed relapse. All of the non-CR patients died, including five PR and one with progressive disease. The other four patients died because of infection after the first course of induction. The progression-free and overall estimated survival at 5 years was 74.99% and 68.10%, respectively. Of the 12 patients who died, the median survival was 4.43 months (95% confidence interval 1.43-7.43 months). Thus, most deaths occurred shortly after diagnosis, and four patients older than 58 years died after the first induction cycle. Most early deaths were caused by treatment-related morbidity and failure to achieve complete response. B symptoms, advanced age, bone marrow involvement, and St. Jude/Murphy stage IV classification were significantly associated with poor overall survival. In conclusion, the LMB protocol was effective for Korean adult BL patients. However, considering the high incidence of treatment-related deaths and the poor outcome of non-CR patients, risk-adapted modification of the induction phase is warranted.

Characterization of monoclonal antibodies against the nonstructural 5A protein of hepatitis C virus.

The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) is a multifunctional protein that leads to pleiotropic responses, in part by regulating cell growth and cellular signaling pathways. Here, we produced monoclonal antibodies (mAbs) directed against the HCV NS5A protein. The N-terminal epitope was mapped to amino acids 60-80 of the NS5A protein, and the epitope in the middle region was mapped to amino acids 221-236. Because these epitopes overlap with binding regions of human vesicle-associated membrane-protein-associated protein (hVAP)-B and TNF-receptor-associated factor 2 (TRAF2), respectively, we investigated these mAbs for their potential capacity to inhibit viral and cellular interactions. We found that NS5A and hVAP-B interaction was abolished by mAb E5D3, and NS5A and TRAF2 interaction was inhibited by mAb C6D4. Since hVAP-B is necessary for HCV replication and TRAF2 is the major transducer in TNF signaling cascades, these data may provide further insights into the mechanisms underlying HCV replication and viral modulation of host signal transduction.