The impact of primary tumor location in patients with metastatic colorectal cancer: a Korean Cancer Study Group CO12-04 study

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.

Clinical Significance of Peroxisome Proliferator-Activated Receptor gamma and TRAP220 in Patients with Operable Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARgamma or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARgamma and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARgamma and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARgamma positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARgamma and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARgamma and TRAP220 represents a biomarker for good prognosis in CRC patients.

A Phase II Study of Paclitaxel and Cisplatin as Salvage Therapy for Patients with Advanced or Metastatic Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the therapeutic activity and safety of paclitaxel and cisplatin combination chemotherapy in patients with advanced or metastatic gastric cancers that are unresponsive to primary chemotherapy. MATERIALS AND METHODS: Advanced or metastatic gastric cancer patients unresponsive to first line chemotherapy were entered into this trial. The treatment regimen consisted of paclitaxel, 175 mg/m(2) by 3-hour infusion on day 1, and cisplatin, 60 mg/m(2) by 1 hour infusion on day 1, with the treatment repeated every 3 weeks. RESULTS: 37 patients were entered in this study, with 32 fully evaluable for response. 4 (13%), 13 (40%) and 15 (47%) patients achieved a partial response, stable disease and progressed, respectively. The median time to progression was 4.0 months (95% CI: 2.0~6.0 months), and the median overall survival was 12.6 months (95% CI: 5.5~19.7 months), with a 1-year survival rate of 54%. Of a total of 135 cycles of chemotherapy, grades 3 and 4 hematological toxicities were neutropenia (14%) and anemia (3%). Grade > or =2 neuropathy was observed in 6 patients (17%). CONCLUSION: The combination of paclitaxel and cisplatin is an effective and tolerable salvage treatment modality for advanced gastric cancer.

Hematologic Recovery and Clinical Outcomes according to Cell Dose after HLA-matched Sibling Allogeneic Bone Marrow Transplantation

BACKGROUND: There has been changed in estimation of the stem cell content of the graft for several decades. However, there is not always correlating the transplanted cell dose with hematologic recovery, and there are few reports in human leukocyte antigen (HLA)-matched sibling allogeneic bone marrow transplantation (AlloBMT) in Korea. The purpose of this study is to report the influence of number of transplanted cell dose on hematologic recovery and the clinical outcomes in HLA-matched sibling AlloBMT. METHODS: Between June 1999 and March 2004, 31 AlloBMT from HLA-matched sibling donor was done in patients with hematologic malignancy. All patients were conditioned with busulfan and cyclophosphamide. Short course methotrexate and cyclosporine regimen was used for prophylaxis of graft-versus-host disease. We analyzed hematologic recovery time and clinical outcomes according to transplanted cell dose. RESULTS: There were 16 male and 15 female patients, with a median age of 34 years (range, 16~48). Underlying diseases were 17 acute myeloid leukemia, 4 acute lymphoblastic leukemia, 3 myelodysplastic syndrome (high-risk), and 7 chronic myelogenous leukemia. The median number of total nucleated cell (TNC), mononuclear cell (MNC) and CD34+ cell infused was 3.95x10(8)/kg (range, 1.67~7.30x10(8)/kg), 0.65x10(8)/kg (range, 0.11~2.50x10(8)/kg), and 2.32x106/kg (range, 0.35~7.45x106/kg), respectively. The median days of neutrophil and platelet engraftment (ANC>500/microliter and platelet > 20,000/L without transfusion) were 15 (range, 10~19), 16 (range, 7~37), respectively. Relationship between the rate of neutrophil engraftment and the number of infused TNC was only statistically significant (P=0.038, R2=0.328). This study showed survival benefit with the increment of CD34+ cell dose without significance statistically (P=0.082). CONCLUSION: Although the dose of the number of transplanted MNC and CD34+ cells had no influence on granulocyte or platelet recovery, the number of TNC had only a beneficial effect on neutrophil recovery. The transplanted dose of CD34+ cells, rather than those of TNC and MNC may be related with better survival.

A Case of Autoimmune Hemolytic Anemia after Fludarabine Treatment in Waldenstrom Macroglobulinemia

Waldenstrom macroglobulinemia, which is characterized by elevation of serum monoclonal IgM paraprotein, has recently been responsible for the treatment of purine analogues. Fludarabine, one of purine analogues, has been associated with autoimmune hemolytic anemia in patient with chronic lymphocytic leukemia. However, autoimmune hemolytic anemia after fludarabine treatment for Waldenstrom macroglobulinemia has not been reported. We experienced a case of autoimmune hemolytic anemia after fludarabine treatment for Waldenstrom macroglobulinemia. In this case, hemolytic anemia with positive direct Coombs' test occurred at 20 months after the first administration of fludarabine, relapsed at 5 days after re-administration. This anemia responded to steroid therapy. Autoimmune hemolytic anemia associated with fludarabine therapy can be severe and fatal, especially if a patient is re-treated with this drug after a previous episode of hemolytic anemia.

Clinical significance of chromosomal abnormality in multiple myeloma / 대한내과학회지

BACKGROUND: Multiple myeloma is a clonal B-cell malignancy manifested by the accumulation of terminally differentiated plasma cells. The disease is characterized by clinical heterogeneity, with survival ranging from a few months to more than 10 years. The purpose of this study is to evaluate the prognostic value of specific chromosomal abnormality in multiple myeloma. METHODS: We analyzed the clinical records of 40 patients who were diagnosed as multiple myeloma, between April, 1995 and August, 2004. Cytogenetic analysis was conducted by metaphase karyotype analysis. Patients were grouped into normal cytogenetic group (arm A), complete or partial deletion of chromosome 13 and hypodiploidy group (arm B) and other cytogenetic abnormality group (arm C). RESULTS: Median follow up duration was 13.1 months (range 1.5-92.1). Overall response rate to chemotherapy was 58.8% and response rate among arm A, B and C were 56.3%, 33.3% and 75%, respectively (p=0.229). The prognostic factors affecting survival were clinical stage, performance status, serum creatinine level, sex and chromosomal abnormality. The median overall survival was significantly different among arm A, B and C (34.9 months, 8.5 months and 19.8 months, respectively, p=0.0125). CONCLUSION: chromosomal abnormality, especially, complete or partial deletion of chromosome 13 and hypodiploidy at initial diagnosis is significantly associated with survival duration.

Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients. MATERIALS AND METHODS: Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on the first day plus LV 20 mg/m2 over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m2 followed by a 22-hour continuous infusion of 600 mg/m2 on days 1~2. The treatment was repeated at 2 week intervals. RESULTS: The median age of the patients was 50 years (range: 31~74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5~32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6~4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9~9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths. CONCLUSIONS: The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.