A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities.

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, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. CONCLUSION: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.

Feasibility of CYFRA 21-1 as a serum biomarker for the detection of colorectal adenoma and advanced colorectal adenoma in people over the age of 45.

BACKGROUND: Colon adenoma (CA) is a premalignant lesion of colorectal cancer, and its early removal is closely associated with more prolonged survival in the general population. In this study, we aimed to evaluate the relationship between diverse biologic markers and a newly diagnosed CA and to predict the clinical possibility of cytokeratin-19 soluble in serum fragment (CYFRA 21-1) as a screening tool in asymptomatic adults aged over 45 years. METHODS: Four hundred and seventy-nine patients with a histologically confirmed CA or benign colon polyp (BCP), 76 patients with only benign colorectal diseases and 223 negative controls with no CA or BCP detected on colonofibroscopy were investigated. Multiple tumor markers and biochemical markers were simultaneously checked by radioimmunoassay and enzyme immunoassay. RESULTS: The CYFRA 21-1 alone showed significant stepwise contrastive potential among the three groups (P<.001). Based on the receiver operating characteristic (ROC) analysis, Area under the curve (AUC) for CYFRA 21-1, with a value of 0.732 (95% confidence interval, 0.656-0.809, P<.001) for differentiating between negative controls and patients with advanced colon adenoma, was comparatively the highest among all analyzed factors. The sensitivity of CYFRA 21-1 was significantly higher than that of the other tumor markers in the diagnosis of CA and advanced CA, respectively (P<.001). CONCLUSIONS: Considering the results of our study, CYFRA 21-1 showed a significant diagnostic performance and significant stepwise comparative potential in differentiating patients with CA from benign controls. CYFRA 21-1 could be a simple and effective screening test for the diagnosis of CA.

Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. METHODS: The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/ rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). RESULTS: The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P <0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. CONCLUSION: This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

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.

Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer.

BACKGROUNDS: Cisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers. METHODS: In 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS). RESULTS: The median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin level CONCLUSION: All of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.

Metastatic lymph node in gastric cancer; is it a real distant metastasis?

BACKGROUND: Currently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients. METHODS: Among data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection. RESULTS: In 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival. CONCLUSION: In this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.

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.

Comparative effectiveness of palliative chemotherapy versus neoadjuvant chemotherapy followed by radical cystectomy versus cystectomy followed by adjuvant chemotherapy versus cystectomy for regional node-positive bladder cancer: A retrospective analysis: KCSG GU 17-03.

The regional lymph node-positive bladder cancer was classified as stage IV in the AJCC 7th edition but was changed to stage IIIB in the 8th edition, revised in 2018. Among the various studies involving immune checkpoint inhibitors, groups that had only lymph node metastasis showed better outcomes than those with distant metastasis. Therefore, it is necessary to rethink the treatment strategy for lymph node-positive bladder cancer. The aim of this study was to compare the treatment outcomes of chemotherapy, surgery, and combination therapy in patients with lymph node-positive bladder cancer. From 1 January 2010 to 31 December 2015, patients with bladder cancer presenting local lymph node metastasis at the time of diagnosis were treated with a single treatment strategy, with either radical cystectomy or chemotherapy or with a combined strategy using both. Treatment outcomes were retrospectively analyzed on the basis of clinical indices and survival time. Out of 230 patients with bladder cancer, 44 (19.1%) were treated with palliative chemotherapy, 30 (13.0%) with neoadjuvant chemotherapy followed by cystectomy, 129 (56.1%) with cystectomy followed by adjuvant chemotherapy, and 27 (11.7%) with cystectomy alone. Median survival among all groups was 30.4 months. For each group, median overall survival was 19.3, 49.1, 42.6, and 11.2 months, respectively. This study represents an advancement in understanding the impact of clinical treatment patterns of lymph node-positive bladder cancer through comparison of survival data of patients treated with different therapeutic strategies. Combined treatment resulted in better outcomes than did single treatments.

A multicenter, retrospective analysis of elderly patients with acute myeloid leukemia who were treated with decitabine.

Decitabine is widely accepted as the treatment options for elderly acute myeloid leukemia (AML) patients. However, the efficacy has yet been assessed in Asian population. We retrospectively analyzed the outcomes of 80 Korean elderly AML patients who were treated with decitabine. The median age was 74 years (range, 64 to 86 years) and 6 (7.5%), 48 (60.0%), and 25 (31.3%) patients were categorized to favorable, intermediate, and poor risk group, respectively. The median OS was 10.2 months (95% CI 5.0-15.4). Given that decitabine treatment demonstrated improved clinical outcomes, it could be considered as one of the first-line treatment for Korean elderly AML patients.

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study.

BACKGROUND: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods. RESULTS: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. CONCLUSION: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

Relationship Between Dual Time Point FDG PET/CT and Clinical Prognostic Indexes in Patients with High Grade Lymphoma: a Pilot Study.

PURPOSE: This study investigated the correlative relationship between metabolic parameters estimated from dual time point 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) positron emission tomography/computerized tomography (PET/CT) and the clinical tools predicting the outcome of a lymphoma. We also measured metabolic and volumetric alterations between early and delayed 18F-FDG PET/CT in patients with high grade lymphoma (HGL). METHODS: The samples were 122 lymph nodes and extralymphatic lesions from 26 patients diagnosed with HGL. All patients were applied to the International Prognostic Index (IPI), Ann Arbor stage, and revised IPI as clinical prognostic parameters. 18F-FDG dual time point PET/CT (DTPFP) consisted of an early scan 1 h after 18F-FDG injection and a delayed scan 2 h after the early scan. Based on an analysis of DTPFP, we estimated the standardized uptake value (SUV) of tumors from the early and delayed scans, retention index (RI) representing the percentage change between early and delayed SUV, and metabolic volume different index (MVDI) calculated using metabolic tumor volumes (MTV). RESULTS: RImax showed a multiple positive correlative relationship with stage and IPI in lesion-by-lesion analysis (p < 0.01). In the case of IPI, the high risk group exhibited higher RImax than the low risk group (p = 0.004). In the case of revised IPI, the RImax of the low risk group were significantly lower than the intermediate and high risk groups, respectively (p < 0.01). The MVDIs of the best outcome group were decreased in comparison to the moderate outcome group (p = 0.029). There was a significant negative correlative relationship between RImax and MVDI, and the inclinations for decreased MVDIs were slightly associated with increased RIs. CONCLUSIONS: RImax extracted from DTPFP had a significant relationship to extranodal involvement, staging, IPI, and revised IPI. MVDI showed significant negative correlation with RImax. Further large scale studies are warranted to support and extend these preliminary results.

Stage IV advanced diffuse large B-cell lymphoma in human immunodeficiency virus infection with achieving cure by using highly active antiretroviral therapy alone: a case report.

After the introduction of highly active antiretroviral therapy (HAART), there has been a decrease in the incidence of lymphoma among the HIV-infected population and also significantly improved survival rates. We describe a remarkable case of an HIV-infected patient with advanced stage IV diffuse large B-cell lymphoma (DLBCL), completely regressed with the use of HAART alone. He remained disease-free for 6 years and he achieved cure without chemotherapy. Although several cases of low-grade lymphoma with complete regression were reported, we could not find any case of stage IV high-grade malignant lymphoma with HAART alone in complete remission for over 5 years from our review of the literature. This unique case shows the importance of HAART in improving survival and achieving cure in HIV-high-grade malignant lymphoma.

Intrinsic resistance to sunitinib in patients with metastatic renal cell carcinoma.

AIM: Although targeting angiogenesis with vascular endothelial growth factor receptor (VEGFR) inhibitors has demonstrated efficacy in the treatment of renal cell carcinoma, primary, intrinsic resistance to the VEGFR inhibitor sunitinib is not fully understood in a subset of metastatic RCC (mRCC) patients. METHODS: Between 2008 and 2012, a total of 134 patients with mRCC were treated with first-line sunitinib at one of six tertiary centers. Patients in whom progressive disease was the best response were classified as the intrinsic resistance group. Univariate and multivariate analyses were performed on the recognized baseline parameters. RESULTS: Among 134 patients, 33 (25%) intrinsically resistant to sunitinib were identified. Multivariate logistic regression analyses revealed that the number of metastatic sites (OR = 3.6) and neutrophilia (OR = 7.4) were independently associated with development of intrinsic resistance. There were significant differences with regard to overall survival (P = 0.001) and progression-free survival (P < 0.0001) between the patients with and without intrinsic resistance. CONCLUSIONS: Intrinsic resistance to first-line sunitinib treatment is associated with a dismal prognosis in mRCC patients. Patients with known high-risk factors (poor performance, neutrophilia, elevated lactate dehydrogenase) and multiple metastatic sites including the liver may experience a limited benefit from sunitinib. Greater understanding of the underlying mechanism and molecular biomarkers for detecting intrinsically resistant disease is needed.

A Retrospective Analysis for Patients with HER2-Positive Gastric Cancer Who Were Treated with Trastuzumab-Based Chemotherapy: In the Perspectives of Ethnicity and Histology.

PURPOSE: While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. MATERIALS AND METHODS: Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. RESULTS: A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025). CONCLUSION: While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.

Mitomycin-C and capecitabine as third-line chemotherapy in patients with advanced colorectal cancer: a phase II study.

PURPOSE: The aim of this study was to investigate the therapeutic value and safety of third-line treatment with mitomycin-C (MMC) and capecitabine (Xeloda) in patients with advanced colorectal cancer pretreated with combination regimens including 5-fluorouracil (5-FU), folinic acid (FA) and irinotecan (CPT-11) or 5-FU, FA and oxaliplatin (L-OHP). PATIENTS AND METHODS: A total of 21 patients (M/F 16/5, median age 60.0 years) with advanced colorectal cancer, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP, were accrued to this study. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous MMC 7 mg/m(2) on therapeutic day 1 plus oral capecitabine 1000 mg/m(2) twice daily on days 1-14, was initiated. After rest for 7 days, capecitabine 1000 mg/m(2) twice daily was administered on days 22-35 followed by 7 days rest. Treatment courses were repeated every 6 weeks unless there was evidence of progressive disease, unacceptable toxicity or patient refusal of treatment. RESULTS: All the patients were assessable for toxicity and 19 for response. The median number cycles of chemotherapy was two (range one to four). Only 1 patient (4.8%) had a partial response, 4 patients (19.0%) had stable disease, and 14 patients (66.7%) progressed. The median follow-up period was 7.3 months and median time to progression was 2.6 months. The median overall survival was 6.8 months. No toxic deaths occurred. Toxicities of third-line treatment were mild and manageable. As NCI/NIH common toxicity criteria, grade 3/4 anemia, neutropenia and thrombocytopenia occurred in two, one and one patients, respectively. CONCLUSION: Our findings suggest that the combination of MMC and capecitabine in patients with advanced colorectal cancer pretreated with combination regimens including 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP is safe. However, this regimen had a poor response rate and no definitive contribution to increasing patients' overall survival time. Further evaluation of other salvage regimens seems to be warranted.

Microarray Gene-expression Profiling Analysis Comparing PCNSL and Non-CNS Diffuse Large B-Cell Lymphoma.

AIM: The purpose of the present study was to compare microarray gene-expression profiling data between primary central nervous system (CNS) lymphoma and non-CNS lymphomas. MATERIALS AND METHODS: We performed whole-genomic cDNA-mediated annealing, selection and ligation assay with 177 formalin-fixed paraffin-embedded tumor samples. RESULTS: We identified 20 differentially expressed genes out of which 5 were predominantly expressed in CNS DLBCL compared to non-CNS DLBCL (C16orf59, SLC16A9, HPDL, SPP1, and MAG). SLC16A9 may be involved in aerobic glycolysis of malignant tumors. The alteration in gene expression of SPP1 in primary CNS lymphoma is involved in biological activity, such as CNS tropism, B-cell migration, proliferation, and aggressive clinical behavior. MAG may be an important adhesion molecule that contributes to perineural cancer invasion. CONCLUSION: Genomic differences between CNS and non-CNS DLBCL exist and the most prominent genes are SPP1 and MAG. SPP1 may play a key role in CNS tropism of primary CNS lymphoma.

Retrospective analysis of extra-gastrointestinal stromal tumors.

AIM: To investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors (EGISTs) in South Korea. METHODS: A total of 51 patients with an EGIST were identified. The clinicopathologic features, including sex, age, location, tumor size, histology, mitotic rate, immunohistochemical features, genetic status and survival data, were analyzed. RESULTS: The median age was 55 years (range: 29-80 years), and male:female ratio was 1:1.04. The most common site was in the mesentery (n = 15) followed by the retroperitoneum (n = 13) and omentum (n = 8). The median tumor size was 9.0 cm (range: 2.6-30.0 cm) and the median mitotic rate was 5.0/50HPF. (1/50 - 185/50). KIT was analyzed in 16, which revealed 10 cases with wild-type KIT and 6 cases with an exon 11 mutation. Among 51 patients, 31 patients had undergone surgery, and 10 had unresectable disease and had taken palliative imatinib, which resulted in 22.7 mo of progression-free survival. Of the patients who had undergone surgery, 18 did not take adjuvant imatinib, and 8 of these were categorized as "high risk" according to the risk criteria. However, the relapse-free survival was not different (P = 0.157) between two groups. CONCLUSION: Because the biologic behaviors of GISTs differ according to the location of the tumor, a more stratified strategy is required for managing EGISTs including incorporation of molecular features.