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Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I–III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4 %) patients were stage I, and 682 (59.6 %) were stage II or III. In addition, 701 (61.2 %) patients were HR positive, 239 (20.9 %) were HER2 positive, and 205 (20.9 %) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0–25 %) was 99 %. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83 %, respectively (P value =

Necrotizing sialometaplasia (NS) is a self-limiting, benign, ischemic, inflammatory disease that is most often described in the submandibular glands of dogs, with clinical and histologic features that resemble malignancy. Unilateral swelling of the parotid salivary gland in a 7-year-old Cocker Spaniel dog was diagnosed as NS. The dog also had otitis externa on the same side as the parotid gland lesions. The main histologic features were included lobular necrosis of salivary tissue; fibrinoid necrosis of some arteries; marked squamous metaplasia of duct and/or acinar epithelium, with intercellular bridge formation; preservation of salivary lobular morphology; and variable inflammation and fibrosis. Etiologic factors for NS in both humans and animals remain obscure.

A comparison of the volatile profiles between Korean and Japanese Shiranui cold-pressed peel oil was performed by GC and GC-MS. Limonene was the most abundant in the Japanese (91.8%) and Korean (86.4%) oil. Alcohols accounted for 1.8% in the Korean oil, and 0.2% in the Japanese oil, in which the respective linalool levels were 1.2% and 0.1%. The level of aldehydes was also higher in the Korean oil (1.6%) than in the Japanese oil (0.7%).

BACKGROUND Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. METHODS A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. RESULTS The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p

Primary TNBCs are treated as if they were a single disease entity, yet it is clear they do not behave as a single entity in response to current therapies. Recently, we reported that statins might have a potential benefit for TNBCs associated with ets-1 overexpression. The aim of this study is to investigate the role of PTEN loss in the effects of statin on TNBC cells. In addition, we analyze the relationship between AKT downstream pathways and the effects of statin on TNBC cells. We investigated the effect of a statin on TNBC cells and analyzed the association of PI3K pathways using various TNBC cells in terms of PTEN loss and AKT pathways. Simvastatin treatments resulted in decreased cell viabilities in various TNBC cell lines. Compared with PTEN wild-type TNBC cells, PTEN mutant-type TNBC cells showed a decreased response to simvastatin. Expressions of phosphorylated Akt and total Akt showed an inverse relationship with PTEN expression. The TNBC cell lines, which showed increased expression of p-Akt, appeared to attenuate the expression of p-Akt by PTEN loss in simvastatin-treated TNBC cells. The Akt inhibitor, LY294002, augmented the effect of simvastatin on PTEN wild-type TNBC cells. Simvastatin induces inhibition of TNBC cells via PI3K pathway activation.

This study aims to evaluate the impact of chemotherapy-induced alopecia (CIA) distress on body image, psychosocial well-being, and depression among breast cancer patients.A cross-sectional survey was conducted at the breast cancer advocacy events held at 16 hospitals in Korea. Alopecia distress was assessed using the 'Chemotherapy-Induced Alopecia Distress Scale', body image and psychosocial well-being were measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and breast specific module (BR23), and depression was measured using the Center for Epidemiological Studies Depression scale. Means of outcomes were compared between low and high CIA distress groups. Univariable and multivariable linear regression models were used to analyze the relationship between the CIA distress and body image, psychosocial well-being, and depression.One hundred sixty-eight breast cancer patients participated in the study; the mean age was 48.4 (SD = 8.4) years, and 55.3% of the patients experienced higher distress from alopecia. In fully adjusted models, the high distress group was more likely to have a poorer body image than the low distress group (35.2 vs. 62.0; p 0.001). Distressed patients were also more likely to report lower emotional (55.3 vs. 76.9; p 0.001), role (58.6 vs. 72.0; p 0.001), and social functioning (51.3 vs. 70.9; p 0.001). The high distress group was also more likely to have depression compared with the low distress group (19.6 vs. 14.8; p 0.001).Chemotherapy-induced alopecia distress was negatively associated with body image, psychosocial well-being, and depression in women with breast cancer. It is necessary to develop specific interventions to minimize distress due to alopecia for women with breast cancer.

Background Paclitaxel and gemcitabine (PG) combination chemotherapy is effective as a maintenance chemotherapeutic regimen in metastatic breast cancer (MBC) patients because it increases progression-free survival (PFS), which increases overall survival (OS). The primary purpose of our study was to investigate the association between genetic polymorphisms in the genes involved in PG pathways and clinical outcomes in MBC patients treated with PG chemotherapy. Methods A total of 324 MBC patients were enrolled in this prospective multicenter trial of PG as the first-line chemotherapy. Eighty-five of the 324 patients from two institutes were available for analysis of single nucleotide polymorphisms (SNPs). Germline DNA was extracted from peripheral blood mononuclear cells. Thirty-eight SNPs in 15 candidate genes selected from pathways that may influence the metabolism and transport of, or sensitivity, to PG were analysed. Results The median PFS and OS of all 324 patients were 8.7 months (95% confidence interval [CI]: 7.5–9.6 months) and 26.9 months (95% CI: 23.6–30.1 months), respectively. An SNP in SLC28A3 (rs7867504, C/T) was associated with OS (CC or CT versus TT: 37 versus 21 months, p = 0.027, hazard ratio [HR] 2.6, 95% CI: 1.1–6.3). SLC29A1 GA haplotype had a significantly shorter OS ( p = 0.030, HR 3.391, 95% CI: 1.13–10.19). RRM1 (ribonucleotide reductase large subunit M1) SNP (rs9937), and haplotypes ATAA and ATGA were significantly associated with neurotoxicity. Conclusion Genetic polymorphisms in SLC28A3, SLC29A1 and RRM1 can influence the clinical outcome of MBC patients treated with PG chemotherapy. Further studies on the functional mechanisms relating to these germline polymorphisms in these genes are warranted.

The aims of the present study were to investigate how breast cancer (BC) subtypes and treatment affect time to brain metastasis (TTBM). We retrospectively investigated 189 consecutive patients who were diagnosed with brain metastasis (BM) from BC between 2000 and 2009 at Samsung Medical Center. We analyzed TTBM from initial diagnosis of metastatic BC according to subtypes and trastzumab (T) administration before BM diagnosis. The median age of 189 BM patients from BC was 48 years. We divided TTBM into four groups considering BC subtypes and treatment; HR-positive/HER2-negative (n=45), HER2-positive with T before BM development (n=47), HER2-positive without T before BM development (n=39), and TNBC (n=58). The median TTBMs for each group were 17.5 months, 13.7 months, 5.8 months, and 2.9 months, respectively (p

Breast cancers (BC) in younger, premenopausal patients (YBC) tend to be more aggressive with worse prognosis, higher chance of relapse and poorer response to endocrine therapies compared to breast cancers in older patients (OBC). The proportion of YBC (age ? 40) among BC in East Asia is estimated to be 16-32%, significantly higher than the 7% reported in Western countries. Genomic and molecular characterizations have deepened our understanding of breast cancer biology in areas ranging from intrinsic subtypes to treatment responses, however, the molecular bases of Asian YBC remains poorly characterized. We have performed whole-exome sequencing (WES), whole-transcriptome sequencing (WTS) and high coverage targeted sequencing on tumor and matched normal samples from 133 Korean BC patients consisting of 74 YBC cases (age ? 40). We further performed immunohistochemistry (IHC) analyses to characterize tumor-infiltrating lymphocytes (TILs) in 46 tumors using four markers (CD45, CD4, CD8 and CD163). We found that BRCA1/2 germline deleterious mutations are enriched in YBC and the ER+/HER2- subtype, indicating that Asian ER+ YBC has a significant germline contribution. MutSig analysis4 identified ARID1A as a significantly mutated gene, implicating chromatin modeling as a cancer driver in Asian BC. Differential expression analyses suggested that Asian YBC differ in energy metabolism and are more active in protein synthesis than OBC tumors, whereas OBC is more proliferative than YBC. Using gene expression signatures representing distinct immune cell types and immunohistochemistry, we classified our cohort into four subtypes of varying TIL activities: high, medium, low and quiet. The majority of immunogenic cases with high TIL levels lie in ER+ or HER2+ subtypes although higher proportion is seen in TNBC. Moreover, YBC tumors appear to harbor lower levels of TIL activities than OBC, suggesting that younger patients may be less likely to benefit from immunomodulatory therapies than older patients. To our knowledge, this is the first large-scale multi-omics study of Asian breast cancer and would significantly contribute to the compendium of molecular data available for young, premenopausal breast cancer. While the major landmarks in the molecular and immune landscape of Asian BC look similar to that of the predominantly Caucasian BC cohorts, we have identified a number of distinguishing characteristics pointing to distinctive oncogenic mechanisms underlying Asian BC. Citation Format: Yeon Hee Park, Ying Ding, Soonweng Cho, Soo-Hyeon Lee, Hae Hyun Jung, Woosung Chung, Jinho Kim, Woong-Yang Park, Eric Powell, Pamela Vizcarra, Shibing Deng, Se Kyung Lee, Seok Won Kim, Jeong Eon Lee, Ji-Yeon Kim, Jin Seok Ahn, Young-Hyuck Im, Seok Jin Nam, Zhengyan Kan. Multi-omics and immuno-oncology profiling of an Asian breast cancer cohort enriched in young and premenopausal patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-325.

Background: In Asia, large-scale studies on anti-HER2 treatment in HER2-positive breast cancer patients with brain metastases are limited. We studied the treatment patterns of these patients in Asia to evaluate the impact of anti-HER2 treatment on the time to occurrence of brain metastases (TTBM) and survival after brain metastasis (BM). Methods: A retrospective study of HER2-positive breast cancer patients diagnosed with BM between January 2006 and December 2008 in six Asian countries was conducted. Demographics, tumour characteristics, treatment details, and events dates were collected from medical records. Results: Data from 280 patients were analysed. Before BM, 63% received anti-HER2 treatment. These patients had significantly longer TTBM than those without anti-HER2 treatment (median 33 vs 19 months; P

Among proteases, matrix metalloproteinases (MMPs) have been of significant interest because they are considered as one of the promising biomarkers in association with cancer metastasis, inflammation and other degenerative diseases. Many attempts based on the optical sensing have been made to analyze the activity of MMPs, but most of them require an expensive fluorescence readout and a labor-intensive process. To circumvent this issue, we demonstrated a simple colorimetric detection of protease activity by using carboxy gold nanoparticles (AuNPs) and histidine-containing peptides via metal-affinity coordination. Due to their higher surface-to-volume ratio, the nanometer size of AuNPs enables the surface ligands to function like a chelator, providing greater affinity with metal ions, even in the absence of chelators. With no additional modification by multidentate ligands, the carboxy AuNPs were easily aggregated and changed in color (from reddish-brown to violet) after adding peptide substrates with hexahistidine at both ends and metal ions, whereas the presence of proteases in solution prevented NP aggregation by cleaving the peptides, thereby retaining the original color of the AuNPs. When the extinction ratio (E(520)/E(700)) of the AuNP solution was measured as a function of matrix metalloproteinase concentration in a single reaction, there was good linearity from as low as 3 nM to 52 nM. This approach is anticipated to be useful in designing other diagnostic nanosensors.

The aims of the study were to identify a subpopulation more likely to be at greater risk of recurrence in small T1b-c node-negative hormone receptor (HR)-positive breast cancer, and which would benefit from adjuvant chemotherapy. Clinico-pathologic characteristics and clinical outcomes of 538 postoperative HR-positive T1b-cN0 breast cancer patients were retrospectively analyzed. High Ki67 index and a young age (35 years) were identified as independent risk factors for relapse (p0.0001 and 0.015, respectively). A nomogram based on Cox-regression model showed an area under the curve (AUC) of 0.73 in the training set. The validation set showed a good discrimination with an AUC of 0.65. In patients with high nomogram scores (≥ 100, n = 24, 4.5%) who had high Ki67 index with more than 75%, or young age (35 years) and a Ki67 index50%, the relapse-free survival curve of patients who had received anthracycline-containing adjuvant chemotherapy showed a better outcome than those who had not (p = 0.029). Ki67 index and age are valuable surrogate markers to predict recurrence and as indicators of tumors that could benefit from adjuvant chemotherapy in small T1b-c node-negative HR-positive breast cancer.

Paraneoplastic pemphigus is an autoimmune blistering and erosive mucocutaneous syndrome associated with underlying neoplasm. It is primarily associated with lymphoproliferative disorders, and uncommonly with malignancies of epithelial origin. We report on a case of a 68-year-old male who presented with whole body bullous and erosive skin lesions. Findings on upper gastrointestinal endoscopy and skin biopsy revealed esophageal squamous cell carcinoma and paraneoplastic pemphigus. Palliative chemotherapy and systemic glucocorticoid were started, however, the patient died of overwhelming sepsis on the ninth day of chemotherapy. This case demonstrates that paraneoplastic pemphigus can occur in esophageal squamous cell carcinoma and could be a cause of morbidity.

Leptomeningeal metastasis (LM) usually occurs late during the course of breast cancer. The aim of this study was to characterize the clinical features and outcomes of LM based on breast cancer subtypes in conjunction with brain parenchymal metastases. A retrospective study was performed of breast cancer patients with LM, who received palliative management at Samsung Medical Center between 1995 and 2008. Among the 272 metastatic breast cancer patients with central nervous system (CNS) involvement, 68 patients with LM were identified. The median age was 46 years (range, 24–72 years). The median survival duration from LM to death (LM-OS) was 4.5 months (range, 0.2–26.4 months). Patients surviving for 12 or more months were rarer among triple negative (TN) patients compared to other subtypes (21.7% for HR + ve vs. 27.8% for HER2 + ve vs. 72.7% for TN, P = 0.217). Death caused by CNS involvement appeared to be much more common in TN than in other subtypes (0% for HR + ve vs. 36% for HER2 + ve vs. 64% for TN, P = 0.060). Median survival time from distant metastasis was significantly different among the three groups (28.3 vs. 29.1 vs. 11.8 months, P < 0.0001). However, median survival time from LM did not differ (4.1 vs. 5.9 vs. 3.8 months, P = 0.226). Characteristic manifestations and treatment outcomes of LM may be affected by the unique biology of breast cancer intrinsic subtypes. The different roles of active combined treatment modalities including both systemic chemotherapy and local treatment modalities should be considered to improve outcomes.

The aim of this study was to investigate the prognostic role of insulin-like growth factor-1 receptor (IGF-1R) and IGF binding protein-3 (IGFBP-3) in patients with squamous cell carcinoma of the head and neck (SCCHN). The clinical data of 131 SCCHN patients who had undergone surgical resection were retrospectively reviewed, and their intratumoral expression of IGF-1R and IGFBP-3 was evaluated by immunohistochemistry. Thirty-six cases (27.5%) experienced tumor recurrence during the median follow-up period of 53.7months (95% CI, 19.0-90.7months). IGF-1R-positivity and IGFBP-3-positivity were observed in 96 (73.3%) and 70 cases (53.4%), respectively. IGFBP-3-positivity was associated with shorter time to progression (TTP) by univariate (P=0.03) and multivariate analyses (95% CI, 0.23-0.91), whereas IGF-1R itself failed to show its prognostic relevance. However, it was revealed that the prognostic role of IGFBP-3 expression was dependent on IGF-1R expression in the analysis of four subgroups classified according to IGF-1R and IGFBP-3 expression: the IGF-1R-positive/IGFBP-3-positive subgroup was the best prognostic group, while the IGF-1R-negative/IGFBP-3-positive subgroup was the worst in terms of TTP (P=0.017). In conclusion, it is suggested that IGFBP-3 expression, in a state of co-expression with IGF-1R, can predict poor prognosis in SCCHN patients.

Activation of epidermal growth factor receptor (EGFR)-induced signaling pathways has been correlated with tumor progression, invasion and metastasis in a variety of cancers including breast carcinoma, but the underlying mechanism is not well understood. Matrix metalloproteinases (MMPs) have been implicated in cancer invasion and metastasis for their extracellular matrix (ECM)-proteolytic activity. However, the correlation of EGFR pathway with MMP expression in breast cancer has not been established. The aim of this study was to elucidate the interaction between EGFR ligands and their signaling pathway and MMP expression which might be closely related with breast cancer pathogenesis. We investigated the effect of EGF ligands on the MMP1 expression in SK-BR3 cell lines using RT-PCR, Western blot, ELISA and EMSA. Treatments with EGFR ligands, EGF and TGF-α enhanced MMP1 expression at the level of both transcription and translation in SK-BR3 breast cancer cells. EGF and TGF-α treatment resulted in phosphorylation of EGFR, and consequent activation of ERK1/2 pathway. Tyrosine kinase inhibitors of HER family, erlotinib, lapatinib and canertinib suppressed EGF-ligands mediated MMP1 overexpression. The specific MEK inhibitor, U0126, significantly blocks EGF and TGF-α-mediated ERK1/2 activation and subsequent MMP1 induction in SK-BR3 cells. Inhibition of the Akt pathway with LY294002 paradoxically augmented MMP1 expression by reciprocal activation of ERK1/2 pathway. These data suggest that invasive potential of SK-BR3 cell would be affected by these drugs by suppression of EGFR ligands-induced MMP1 expression.

Purpose Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC). Patients and methods Patients with locally advanced, metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations (female, adenocarcinoma histology, and never-smoker) were eligible. Results A total of 96 (48 per arm) patients were randomly assigned to gefitinib- or erlotinib-arm, respectively. Baseline characteristics were well-balanced between the two arms. The response rates (RR) were 47.9% in the gefitinib arm and 39.6% in the erlotinib arm. Median PFS was 4.9months (95% CI, 1.3–8.5) in the gefitinib arm and 3.1months (95% CI, 0.0–6.4) in the erlotinib arm. The most common grade 3/4 toxicity was skin rash. Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm (RR (%) 47.9 vs. 39.6, p =0.269; median survival (months) 4.9 vs. 3.1, p =0.336). There was no significant difference in QOL between the two arms. Conclusion Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC. We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population.

Purpose The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis. Materials and Methods Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases. Results The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077). Conclusion Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'

Epidermal growth factor receptor (EGFR) mutations are associated with sensitivity to gefitinib or erlotinib in non-small cell lung cancer (NSCLC). We investigated the relationships between the two most common types of somatic EGFR mutations, exon 19 deletions and L858R mutations, and clinical outcomes of Korean NSCLC patients after treatment with gefitinib or erlotinib. In Korean patients with NSCLC, EGFR exon 19 deletions and EGFR L858R mutation were identified from tumor specimens obtained before treatment with gefitinib or erlotinib. The response rates, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. A total of 77 patients with either an exon 19 deletion (n = 58) or L858R mutation (n = 19) were treated with gefitinib or erlotinib. The overall response rate was 69%. Patients with an exon 19 deletion had a significantly longer PFS compared with patients with L858R mutation (9.5 vs. 7.7 months; P = 0.029). The L858R mutation was independently associated with a shorter PFS compared with an exon 19 deletion, even after adjusting for other clinical factors (hazard ratio 2.72; 95% CI 1.38–5.38). However, there were no significant differences in response rate (71 vs. 63%) and OS (21.4 vs. 30.7 months) between subjects with exon 19 deletions and L858R mutations, respectively. In Korean NSCLC patients, EGFR exon 19 deletions are associated with longer PFS compared with EGFR L858R mutations. These observations need to be confirmed by large-scale studies of patients.

BackgroundProspective studies have implied that maintenance therapy for non-small cell lung cancer (NSCLC) has its effect by giving active drugs earlier to patients who otherwise die without receiving second-line therapy. The purpose of this study was to select patients with NSCLC who could most benefit from maintenance therapy, by evaluating which patients would be less likely to receive second-line therapy.MethodsClinicopathologic data of patients with advanced NSCLC who received four cycles of first-line chemotherapy followed by time-off therapy and eventual disease progression or death were reviewed retrospectively. Patients were grouped into ones with first-line therapy only or ones with more than first-line therapy. Clinical characteristics between the two groups were compared.ResultsA total of 271 patients were eligible for analysis, and 39 patients (14.4%) received only first-line therapy. Patients significantly more likely to receive only first-line therapy had performance status of two or three after first-line therapy, large volume of initial target lesions (sum of long diameters ≥70 mm), or smaller decrease in target lesions (decrease

Insulin-like growth factor receptor-1 (IGFR-1) is a cellular membrane receptor which is overexpressed in many tumors and seems to play a critical role in anti-apoptosis. The insulin-like growth factor binding protein-3 (IGFBP-3) is known as a growth suppressor in multiple signaling pathways. The aim of this study was to determine IGFR-1 and IGFBP-3 expression in small-cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. We analyzed IGFR-1 and IGFBP-3 expression in 194 SCLC tissues by immunohistochemical staining. Correlative analyses between IGFR-1 and IGFBP-3 expression in SCLC and clinicopathologic factors were performed. A total of 117 patients had extensive disease (ED) (60.3%) and 77 had limited disease (39.7%). With the median follow-up duration of 49.5 months (24-82 months), the median progression-free survival (PFS) and overall survival (OS) were 7.2 months [95% confidence interval (CI): 6.4-8.0 months] and 14.4 months (95% CI: 12.7-16 months), respectively. IGFR-1 expression was observed in 154 of the 190 tumor tissues, whereas there was no IGFBP-3 expression. Multivariate analysis showed that stage (p0.001), response rate (p0.001), and lactate dehydrogenase (LDH) levels (p0.001) were the independent prognostic factors for PFS, and age (p = 0.014), LDH level (p0.001), and stage (p0.001) for OS. The IGFR-1 positivity was not associated with PFS or OS in the entire cohort. Subgroup analysis revealed that OS was significantly longer in patients with IGFR-1-positive tissue than IGFR-1-negative tissue in SCLC-ED (p = 0.034). These results suggest that IGFR-1 expression may be useful as a prognostic marker in patients with SCLC-ED.

On the basis of inhibitory activity of truncated cyclopentenyl cytosine against S-adenosylhomocysteine hydrolase (SAH), its fluorocyclopentenyl pyrimidine derivatives were efficiently synthesized from D-ribose via electrophilic fluorination as a key step. The final nucleosides were evaluated for SAH inhibitory activity, among which the uracil derivative 9 showed significant inhibitory activity (IC50 = 8.53 μM). They were also evaluated for cytotoxic effects in several human cancer cell lines such as fibro sarcoma, stomach cancer, leukemia, and colon cancer, but they did not show any cytotoxic effects up to 100 μM, indicating that 4′-hydroxymethyl groups are essential for the anticancer activity.

BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) play a key role in the downstream pathway of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer and promote cell proliferation, invasion, and angiogenesis. The clinical significance of phosphorylated STAT3 (pSTAT3), EGFR, p53, and vascular endothelial growth factor receptor 1 (VEGFR-1) expression in patients with completely resected lung adenocarcinoma was evaluated to determine the effects of pSTAT3 in tumor angiogenesis and proliferation. METHODS: The expressions of pSTAT3, EGFR, p53, and VEGFR-1 were evaluated by immunohistochemical staining of tissue microarrays from 162 samples of resected lung adenocarcinoma. RESULTS: The median age of the 162 patients was 62 years, the median disease-free survival was 41.7 months, and the median OS (OS) was 80.2 months. Expression of pSTAT3, EGFR, p53, and VEGFR-1 was detected in 51.2%, 71%, 35.2%, and 35.2% of the samples, respectively. pSTAT3 expression was correlated significantly with VEGFR-1 expression (P = .025). The coexpression of pSTAT3 and VEGFR-1 was correlated with increased lymph node involvement (P = .021) and a trend toward a short OS (P = .085). In multivariate analysis, the expression levels of p53 and VEGFR-1 were identified as independent prognostic factors that affected OS. CONCLUSIONS: The results of this study suggested that pSTAT3 and VEGFR-1 expression may play roles in the tumor progression and angiogenesis of lung adenocarcinoma. Further studies are needed, however, to uncover the detailed mechanisms that underlie the roles of these proteins in lung adenocarcinoma. Cancer 2010. © 2010 American Cancer Society.

The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer. Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER− patients were analyzed. This analysis was evaluated by the validation patients’ cohort of our institute prospectively. Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER− group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER− patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER− patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p

When monitoring vital sign, cables between medical sensors and monitoring system make a patient uncomfortable. Furthermore, it gets worse in case of a steady monitoring is needed. Recently researches, therefore, are actively underway to integrate a wireless sensor network into vital sign monitoring devices. However, the measured data from the sensor can't be transmitted if a patient moves out of the transmission range since the receiving and transmitting range of the measured date is limited within a specific range. In order to clear out this sort of problem, this research suggests the Bridge Transmission Method that can deliver data between nodes via other devices even if the medical sensor device went out of transmission range for a gateway. Experiments have been carried out by materializing a bridge transmission module on sensor nodes to verify effectiveness of our suggesting transmission method, and ten experiments having transmitted 1,000 packets by case showed 98.4% of success in receiving

Introduction: For the identification of the patients who most likely benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), molecular assays are considered to be of paramount importance. Given the heterogeneity of NSCLC at the molecular level, this study was conducted to determine the discrepancy in EGFR mutations between primary tumors and the corresponding lymph node metastasis. Patients and Methods: Surgically resected 101 paired primary NSCLC and metastatic lymph nodes were evaluated for the EGFR mutations by direct DNA sequencing and heteroduplex analysis. Results: EGFR mutation was detected in 29.7% (30 of 101) of the primary tumors and in 27.7% of lymph node metastases (28 of 101) by either direct sequencing or heteroduplex analysis, respectively. By direct sequencing, 12 cases (11.9%) showed discordance in EGFR mutations between primary tumors and metastasis. In 11 cases, EGFR mutations were detected only in the primary tumor, whereas 1 case only in lymph node metastases. By heteroduplex analysis, 17 cases (16.8%) were discordant. Ten cases were primary tumor positive and lymph node negative, whereas seven cases were lymph node positive and primary tumor negative. Conclusions: A considerable proportion of NSCLC showed discrepancy in EGFR mutations between primary tumors and metastatic lymph nodes, suggesting tumor heterogeneity at the molecular level during the process of metastasis.

Background The optimal treatment for non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastasis is still controversial. This study aimed to analyze the outcome for various treatment modalities including chemotherapy only, upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in NSCLC patients with asymptomatic brain metastases. Methods We retrospectively reviewed the medical records of patients with histopathologically proven NSCLC and synchronous asymptomatic brain metastasis between January 2003 and December 2007. Results From the database, 741 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between January 2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were identified to have synchronous brain metastasis without associated symptoms. Of the 129 patients included in the analysis, 78 (57.8%) patients received systemic chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24 (17.8%) patients received upfront SRS and chemotherapy. There was no significant difference in overall survival among three groups (systemic chemotherapy alone, 13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT followed by chemotherapy, 17.7 months, respectively; P = 0.86). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7 months; P = 0.01) or chemotherapy alone (29.3 months versus 14.6 months; P = 0.04). Conclusion This study suggested a potential role of systemic chemotherapy alone or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal treatment modality, however, needs to be defined in prospective trials for this subset of patients.

We conducted a prospective phase II trial of IrOx in patients with advanced non-small cell lung cancer to evaluate the efficacy and toxicity.Patients with histologically or cytologically proven non-small cell lung cancer (NSCLC), agedor =18 years, Eastern Cooperative Oncology Group performance status 0-1, at stage IIIB (pleural effusion)/IV or with recurrent disease not suitable for primary surgical treatment, with no palliative chemotherapy or radiotherapy to the chest or immunotherapy or biologic therapy, the presence of measurable disease by RECIST, and who had given signed written informed consent, were eligible. Treatment consisted of irinotecan 65 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 1, repeated every 3 weeks.A total of 18 patients were enrolled in June and August 2007, the median age was 59 years (47-73). In total, 71 cycles were administered with a median of 4 cycles per patient (range, 1-6 cycles) and 18 patients were evaluable for treatment response. An independent review of tumor responses gave an overall response rate of 27.7% (CR: 0, PR: 5/18; 95% CI, 7-48.4%) by intent-to-treat analysis. The median overall survival of all patients was 14 months and the median time-to-progression was 4.2 months (95% CI, 1.959-6.441). The most common grade 3/4 toxicities were diarrhea (7% of all cycles) and neutropenia (5.6% of all cycles). Grade 3 peripheral neuropathy occurred in one patient and one patient died due to sepsis.This study suggests that IrOx combination therapy has moderate activity with a tolerable toxicity profile. However, it was not warranted to evaluate further this regimen as first-line treatment for patients with advanced or metastatic NSCLC using the current dosages and schedule.

The human epidermal growth factor receptor-2 (HER2) plays an important role in breast cancer. Enhanced Ets-1 activity has recently been shown to be associated with breast cancer pathogenesis. To test the role of Ets-1 in breast cancer cells in relation to the expression of HER2 and MMP-1, we transiently overexpressed Ets-1 and/or HER2 in MCF-7 breast cancer cells and comprehensively searched for genes related to HER2 and Ets-1 using cDNA microarray analysis. The expression of matrix metalloproteinase (MMP) genes was enhanced by the overexpression of HER2/Ets-1. We analyzed the relationship between HER2-induced MMP-1 expression and the transcription factor Ets-1, which has significant activity in breast cancer pathogenesis. Our results demonstrate that HER2-induced MMP-1 expression is positively regulated by Ets-1 in breast cancer cells. This study confirms that Ets-1 is a downstream effector of oncogenic HER2, associated with MMP-1.

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, ≥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.

This study assessed the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with non-Hodgkin's lymphoma in a highly HBV-endemic area. The prevalence of either HBV or HCV infection in 235 patients with non-Hodgkin's lymphoma was compared with that of an age- and sex-matched hospital control group of 235 patients. The prevalence of HBV infection was higher in B-cell non-Hodgkin's lymphoma (15.5%) than control (8.1%), but the prevalence of HCV infection in the non-Hodgkin's lymphoma patients (2.1%) and control group (3%) was similar. HBV prevalence increased significantly with age in the B-cell non-Hodgkin's lymphoma patients. The presence of HBV proteins and DNA in lymphoma tissues and peripheral blood mononuclear cells (PBMCs) from HBV-infected non-Hodgkin's lymphoma patients was also investigated using immunohistochemistry and PCR. HBV DNA was frequently detected in PBMCs from HBV-infected non-Hodgkin's lymphoma patients, but HBV antigens were not. Therefore, HBV infection, but not HCV infection, was associated with B-cell non-Hodgkin's lymphoma in Korea, suggesting a possible role for HBV in the development of non-Hodgkin's lymphoma.

We conducted this study to analyze clinicopathologic features and treatment outcomes for various treatment modalities in breast cancer patients with brain metastases.Retrospective analysis was performed using medical records of patients who were diagnosed with metastatic brain tumors from breast cancer. The treatment modalities applied included whole-brain radiotherapy (WBRT), surgical resection, stereotactic radiosurgery (SRS) and systemic treatments such as chemotherapy and endocrine therapy.Among 125 female breast cancer patients with brain metastases, 87.2% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. The median overall survival (OS) was 6.6 months (95% CI 3.9-9.2). A multivariate analysis using the Cox-regression test identified three risk factors; poor PS (P = 0.023), HER2 positivity (P = 0.013), and no additional systemic treatment (P = 0.006). Those patients who had no risk factors showed outstanding outcome (median OS 49 months). On the contrary, the patients who had all risk factors (poor PS with HER2 positive and did not receive additional systemic chemotherapy) showed dismal prognosis (median OS 2 months).Our new classification according to the suggested risk factors for patients with metastatic brain tumor from breast cancer reflects particular characteristics of each subset of the patients with good prognostic capacity.

Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6–9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.

We assessed the quality of life (QOL) at least one year after sequential chemoradiotherapy for the treatment of localized gastric diffuse large B-cell lymphoma (DLBCL). We used the EORTC Quality of Life Questionnaire for Stomach Cancer (EORTC QLQ-STO22). Among the 45 patients available at the one-year follow-up after radiation therapy, 40 patients completed the EORTC QLQ-STO22 questionnaire. Their median age was 54.5 (range, 20-70 years). Social functioning was most adversely affected among the respondents with a score of 59, whereas other functions and the global scales were preserved above a score of 70 by linearly transformed values. Fatigue, the financial impact and specific emotional problems such as "thinking about their illness" (STO-ANX) and "worry about weight loss or future health" (STO-BI) were persistently bothersome for some patients. Other stomach-related symptoms such as dysphagia, pain, or reflux were negligible at 1 year after treatment. Therefore, this organ-preserving combined approach was effective for the maintenance of the QOL and minimization of stomach abnormalities in patients with gastric lymphoma.

Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6–9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.

Intestinal marginal zone B-cell lymphoma of the MALT type (I-MZL) is a relatively uncommon form of lymphoma. Twenty-seven patients with histologically-confirmed I-MZL were analyzed. The patients initially presented with abdominal pain (62.9%), and diarrhea (22.2%). The most common involved site was the ileo-caecal area (40.7%). Musshoff's stage I(E), II(E)1, II(E)2, III(E) and IV were present in 44%, 15%, 11%, 7.4% and 22% respectively. Sixty-three percent were in the low-risk group according to the Follicular Lymphoma International Prognostic Index. Complete response and partial response were achieved in 82% and 4% patients. The estimated 5-year overall survival (OS) and progression-free survival (PFS) rates were 86% and 54%. Stage > or = II(E)2 was determined to be a poor prognostic factor for PFS and OS. I-MZL commonly manifests in an early-stage, low-risk state and tends to respond well to local and systemic treatment with favorable prognosis. I-MZL tends to be an indolent disease - characterized by prolonged survival with frequent relapses, similarly to other site MZLs.

The therapeutic strategy for relapsed or refractory patients with diffuse large B-cell lymphoma (DLBL) remains challenging yet. Salvage therapy has been tried for these patients according to their clinical status. We studied ICD (irinotecan, cisplatin and dexamethasone) regimen as salvage chemotherapy for DLBL patients previously treated with RCHOP.Between February 2005 and May 2006, 15 patients were treated prospectively with ICD chemotherapy; irinotecan 65 mg/m(2)/day on days 1 and 8, cisplatin 30 mg/m(2)/day on days 1 and 8, and dexamethasone 40 mg/day on days 1-2 and 8-9. This schedule was planned to repeat every 3 weeks until disease progression, severe toxicity or stem cell transplantation.Of the 14 patients evaluable for response, 3 patients achieved CR, 7 patients PR, with 1 SD and 3 PD; overall response rate 71% (10/14; 95% confidence interval, 47-95%). The median progression free survival (PFS) and event free survival (EFS) were 113 (range 21-493+) and 77 (range 21-324+) days, respectively. The median overall survival was 267 (range 31-493+) days. Grade 3/4 neutropenia and grade 3 neutropenic fever were observed in 67% (22/33) and 18% (6/33) of cycles, respectively. There were 20% of grade 3/4 nausea and diarrhea observed.The ICD regimen with current schedule showed high response rate for DLBL patients previously treated with RCHOP. But the high incidence of neutropenia led to delay of subsequent cycles causing dose intensity reduced, which seems to be related with short PFS and EFS.

Purpose: The aim of the study was to determine the effect of EBV-encoded RNA-1 in situ hybridization (EBER-1 ISH) in bone marrow specimens on survival outcome in patients with clinical stage I/II natural killer/T-cell lymphoma. Experimental Design: We systematically did EBER-1 ISH on 182 archival bone marrow tissues from 91 patients who were diagnosed of stage I/II natural killer/T-cell lymphoma and analyzed the correlation between bone marrow EBER-1 ISH status and survival. We defined minimal bone marrow involvement and definite bone marrow involvement to distinguish the subgroups who revealed EBV-positive cells from normal marrow by EBER-1 ISH from those who showed typical neoplastic cells in bone marrow biopsies. Results: In total, 17 of the 91 (18.7%) patients showed positivity for EBER-1 ISH at least in one of the bilateral bone marrow biopsies with 14 minimal bone marrow involvements and 3 definite bone marrow involvements. Patients with positive bone marrow EBER-1 ISH showed significantly poorer overall survival than those who were negative for bone marrow EBER-1 ISH (median survival, 16.1 months versus not reached; P = 0.045). Conclusion: Considering a high proportion of stage I/II patients (15.4%) with minimal in bone marrow specimens, bone marrow EBER-1 ISH should be routinely done in all patients with localized disease for more accurate staging.

Summary Interleukin-10 (IL-10) is one of the cytokines implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) in which it acts as auto/paracrine growth factor for lymphoma growth. T-cell non-Hodgkin lymphoma (NHL) is a heterogeneous disease, the biological basis of which is not fully understood. Some evidence suggests that IL-10 might be associated with the progression of T-cell NHLs and that IL-10 may be involved in a rescue effect, protecting T cells from apoptotic cell death associated with upregulated bcl-2 expression. The current study evaluated the impact of IL-10 gene (IL10) polymorphism on the response to chemotherapy and survival in T-cell NHL. IL10 polymorphisms were determined in 108 patients with T-cell NHL. The response to chemotherapy was not dependent on IL10 polymorphism, while survival differed significantly according to IL10 polymorphism. The group with ATA haplotype showed superior overall survival (61·2 ± 5·9% vs. 21·2 ± 11·7%, P = 0·001) and failure-free survival (35·0 ± 5·7% vs. 13·2 ± 8·7%, P = 0·001) compared to those without ATA haplotype. The ATA haplotype was identified as a favourable prognostic factor compared to non-ATA haplotype (P = 0·037, hazard ratio 2·1), together with international prognostic index (IPI) in a multivariate model for overall survival. In conclusion, IL10 polymorphism may affect the survival of T-cell NHL patients.

e12031 Background: EMBRACE/Study305 demonstrated the efficacy of eribulin for the treatment of advanced breast cancer after two-to-five lines of chemotherapy. Only 1% of patients were from Asia Pac...

e12596 Background: Metastatic breast cancer (MBC) remains a devastating and largely incurable disease. Over the past decade, clinical trials with new therapeutic agents with or without molecular ta...

Background: The incidence of breast cancer (BC) has been rapidly increasing in many countries in the last decades. In contrast to Western countries, approximately 50% of BC patients in Eastern countries are premenopausal, with hormone receptor-positive (HR+) disease, or luminal subtype by molecular classification. Benefit from the most recent advances in endocrine treatments for patients with HR+ BC is currently confined to postmenopausal women. For premenopausal metastatic BC (MBC) tamoxifen and/or ovary ablation/suppression remain the recommended first-line therapies for metastatic disease through category 2 evidence, calling for further clinical investigations. In the context of growing evidence of the role of PI3K/AKT/mTOR pathway inhibition in enhancing and extending the benefit of endocrine therapies in HR+ MBC pre-clinical and clinical models, the B-YOND study is a phase II, three-arm randomized trial aimed at exploring the PI3K inhibitors buparlisib and BYL719 in combination with tamoxifen in the context of ovarian suppression in premenopausal patients with MBC. Design & Objectives: Premenopausal women with HR+/HER2-negative locally advanced or MBC who a) are newly diagnosed or b) recurred during or after adjuvant treatment with tamoxifen monotherapy, and received no endocrine treatment in the metastatic setting, will be randomized to receive tamoxifen plus goserelin (control arm, Arm 3) or the same combination with buparlisib (Arm 2) or BYL719 (Arm 1) until progression. Stratification based on previous treatment with tamoxifen and presence of liver and/or lung metastasis will be applied. Primary objective is the efficacy comparison of Arm 1 vs Arm 3 and Arm 2 vs Arm 3 in terms of 9-month progression free survival (PFS) rate. Secondary objectives include additional efficacy evaluations (median PFS, overall response rate, clinical benefit), safety and tolerability, quality of life, and pharmacokinetics. Statistical Methods: Based on previous reports, the estimated proportion of patients who are alive without progression at 9 months is 50% for the control arm (P0=0.50), and we hypothesize that this proportion is 75% for both experimental arms (P1=0.75). Using a two-sided 0.05 level of significance for both the comparisons [Arm 1 vs Arm 3; Arm 2 vs Arm 3], with an overall type-I error not greater than 0.10, with 80% power, the estimated patient numbers needed is 58 patients for each arm. With an assumption that approximately 10% patients will be lost to follow-up, a total of 192 patients will need to be randomized to the three treatment arms in 1:1:1 ratio. Accrual This study will be open for recruitment in Taiwan, South Korea, China, Hong Kong and Thailand and potentially extended to additional Eastern countries. Enrollment started in May 2014 and will last for an estimated period of 18 months. Citation Format: Yen-Shen Lu, Yeon Hee Park, Zhimin Shao, Roberta Valenti. The B-YOND study: A phase II three-arm randomized trial of the combination of tamoxifen plus goserelin acetate with BYL719 or buparlisib (BKM120) in premenopausal patients with hormone receptor-positive/HER2-negative locally advanced or metastatic breast [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-11.

The present study aimed to evaluate the clinicopathologic features and treatment outcomes of patients with primary thyroid lymphoma (PTL). The patients included 14 women and four men with a median age of 50 years (range 31 – 82 years). Thirteen cases involved the thyroid alone (stage IE) and five cases involved the regional lymph nodes (stage IIE). Histopathologic studies revealed marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in 13 patients and diffuse large B-cell lymphoma (DLBCL) in three patients. The other two patients showed features of both MALT and DLBCL. Surgery and chemotherapy with or without radiotherapy were performed. All patients achieved complete remission. All 18 patients were alive with a median follow-up period of 55 months. The prognosis of patients with primary thyroid lymphoma appears to be favourable.

We conducted a retrospective analysis to evaluate the Musshoff staging system for high-grade primary gastric lymphoma (HG-PGL), particularly in those patients with stages IE and IIE localized diseases. One hundred twenty-six patients presented with stage IE or IIE diseases were retrospectively reclassified on the basis of a pretreatment CT examination as to whether there was lymph node involvement. A positive M1 node (by AJCC staging system) on pretreatment CT scanning was associated with poor clinical outcome for localized stage I or II patients.

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count (500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.

We conducted a retrospective analysis to investigate the natural history and the clinical outcome after treatment of primary gastric lymphoma of T-cell origin. Seventeen cases of T-cell origin among 444 primary gastric lymphoma patients were analyzed. The median age of the 14 male and 3 female patients was 49 years (range 22-76 years). The median progression-free survival (PFS) and overall survival (OS) were only 10 months (95% CI; 0-20 months), and 12 months (95% CI; 4-21 months), respectively. This study showed that the incidence of this subtype of T-cell gastric lymphoma was very rare, and had poor prognosis.