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1.  Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy 
BMC Cancer  2010;10:448.
Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few.
We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed.
A total of 103 patients were evaluated. Twenty-six patients (25.2%) had pancreatic NET, 27 (26.2%) had gastrointestinal NET, 2 (1.9%) had lung NET, 28 (27.2%) had NET from other sites, and 20 (19.4%) had NET from unknown origin. The liver was the most common metastatic site (68.9%). Thirty-four patients had grade 1 disease, 1 (1.0%) had grade 2 disease, 15 (14.6%) had grade 3 disease, 9 (8.7%) had large cell disease, and 7 (6.8%) had small cell disease.
Sixty-six patients received systemic treatment (interferon, somatostatin analogues or chemotherapy), 64 patients received local treatment (TACE, radiofrequency ablation, metastasectomy, etc.). Thirty-six patients received both systemic and local treatments.
Median overall survival (OS) was 29.0 months (95% confidence interval, 25.0-33.0) in the103 patients. OS was significantly influenced by grade (p = .001). OS was 43.0, 23.0, and 29.0 months in patients who received local treatment only, systemic treatment only, and both treatments, respectively (p = .245). The median time-to-progression (TTP) was 6.0 months. Overall response rate was 34.0% and disease-control rate was 64.2%. TTP was influenced by the presence of liver metastasis (p = .011).
OS of metastatic/recurrent NET was different according to tumor grade. TTP was different according to metastasis site. Therefore, development of optimal treatment strategy based on the characteristics of NET is warranted.
PMCID: PMC2936327  PMID: 20731845
2.  Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy 
BMC Cancer  2009;9:450.
We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas.
A total of 133 patients with anaplastic astrocytoma (AA, n = 56), anaplastic oligodendroglioma (AO, n = 67), or anaplastic oligoastrocytoma (AOA, n = 10) were included in the study. These patients were treated with either radiotherapy alone or radiotherapy followed by PCV chemotherapy after surgery. Five prognostic factors, including histological subsets, age, performance status, extent of resection, and treatment modality were incorporated into the RPA. The final nodes of RPA were grouped according to their survival times, and the Kaplan-Meier graphs are presented as the final set of prognostic groups.
Four risk groups were defined based on the clinical prognostic factors excluding age, and split variables were all incorporated into the RPA. Survival analysis showed significant differences in mean survival between the different groups: 163.4 months (95% CI: 144.9-182.0), 109.5 months (86.7-132.4), 66.6 months (50.8-82.4), and 27.7 months (16.3-39.0), respectively, from the lowest to the highest risk group (p = 0.00).
The present study shows that RPA grouping with clinical prognostic factors can successfully predict the survival of patients with WHO grade III glioma.
PMCID: PMC2806410  PMID: 20017960
3.  The role of PET/CT in detection of gastric cancer recurrence 
BMC Cancer  2009;9:73.
In the course of surveillance of gastric cancer recurrence after curative resection, contrast CT scan is used in general. However, new findings from CT scan are not always confirmatory for the recurrence. In this case, we usually use short-term follow up strategy or therapeutic intervention with clinical decision. Recently, the use of fusion Positron Emission Tomography/Computed Tomography (PET/CT) is increasing. The purpose of this study is to evaluate the efficacy and usefulness of PET/CT for detecting recurrence of gastric cancer after curative resection.
Fifty two patients who received curative resection of gastric cancer and had undergone PET/CT and contrast CT for surveillance of recurrence until Dec 2006 in Seoul National University Hospital were analyzed retrospectively. Recurrence of gastric cancer was validated by histologic confirmation (n = 17) or serial contrast CT follow up with at least 5 month interval (n = 35). McNemar's test and Fisher's exact test were used to evaluate sensitivity and specificity of PET/CT and contrast CT.
Of 52 patients, 38 patients were confirmed as recurrence. The sensitivity was 68.4% (26/38) for PET/CT and 89.4% (34/38) for contrast CT (p = 0.057). The specificity was 71.4% (10/14) and 64.2% (9/14), respectively (p = 1.0). In terms of the recurred sites, the sensitivity and specificity of PET/CT were similar to those of contrast CT in all sites except peritoneum. Contrast CT was more sensitive than PET/CT (p = 0.039) for detecting peritoneal seeding. Additional PET/CT on contrast CT showed no further increase of positive predictive value regardless of sites. Among 13 patients whose image findings between two methods were discordant and tissue confirmation was difficult, the treatment decision was made in 7 patients based on PET/CT, showing the final diagnostic accuracy of 42.8% (3/7).
PET/CT was as sensitive and specific as contrast CT in detection of recurred gastric cancer except peritoneal seeding. However, additional PET/CT on contrast CT did not increase diagnostic accuracy in detection of recurred gastric cancer. Further studies are warranted to validate the role of PET/CT in detection of gastric cancer recurrence.
PMCID: PMC2651906  PMID: 19250554
4.  Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study 
BMC Cancer  2008;8:374.
There is no standard palliative chemotherapy regimen in biliary tract cancers (BTC). Fluoropyrimidine or gemcitabine, with or without platinum, are most frequently used. We conducted this study to clarify the efficacy of palliative chemotherapy in BTC.
Patients with unresectable BTC treated with palliative chemotherapy between Oct 2001 and Aug 2006 at Seoul National University Hospital were reviewed retrospectively. Histologically confirmed cases of intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater carcinoma were enrolled. We analyzed the efficacy of regimens: gemcitabine (G) versus fluoropyrimidine (F) and with or without platinum (P).
A total of 243 patients were enrolled. 159 patients (65%) were male and the median age of the patients was 60 years (range 26–81). Intrahepatic cholangiocarcinoma, gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater carcinoma were 92, 72, 58, and 21 cases, respectively. The median progression free survival (PFS) was 4.3 months (95% CI, 3.7–4.9) and median overall survival (OS) was 8.7 months (95% CI, 7.4–10.0). Ninety-nine patients received G-based chemotherapy (94 GP, 5 G alone), and 144 patients received F-based chemotherapy (83 FP, 61 F alone). The response rate (RR), disease control rate (DCR), PFS and OS of G-based chemotherapy versus F-based chemotherapy were 16.7% vs. 19.5% (P = 0.591), 52.8% vs. 58.9% (P = 0.372), 4.0 months vs. 4.3 months (P = 0.816), and 7.8 months vs. 9.1 months (P = 0.848), respectively. Sixty-six patients received F or G without P, and 177 patients received F or G with P. The RR, DCR, PFS and OS of chemotherapy without P versus chemotherapy including P were 12.7% vs. 20.6% (P = 0.169), 46.0% vs. 60.6% (P = 0.049), 3.3 months vs. 4.4 months (P = 0.887), and 10.6 months vs. 8.1 months (P = 0.257), respectively.
In unresectable BTC, F-based and G-based chemotherapy showed similar efficacy in terms of RR, DCR, PFS and OS. The benefit of adding P to F or G was not significant except for DCR. Further prospective studies which define the efficacy of various chemotherapeutic regimens in BTC are warranted.
PMCID: PMC2615782  PMID: 19091129
5.  Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker 
BMC Cancer  2008;8:148.
The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.
Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2). Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.
The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3'UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038). The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p = 0.032).
Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.
PMCID: PMC2442115  PMID: 18505590
6.  Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer 
BMC Cancer  2007;7:203.
Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.
A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.
Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative vs. 62.2% in non-triple negative, p = 0.012) and pathologic complete RR (17.0% in triple negative vs. 3.1% in non-triple negative, p = 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (p < 0.001, p = 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, p = 0.044).
Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.
PMCID: PMC2217558  PMID: 17976237
7.  Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy 
BMC Cancer  2007;7:63.
Bcl-2 is positively regulated by hormonal receptor pathways in breast cancer. A study was conducted to assess the prognostic significances of clinico-pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of relapse in breast cancer patients who had received the identical adjuvant therapy at a single institution.
A cohort of 151 curatively resected stage III breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more positive lymph nodes and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic characteristics including disease-free survival (DFS) and overall survival (OS). Patients with positive ER and/or PR expression received 5 years of tamoxifen following AC/T. The protein expressions of biomarkers were assessed immunohistochemically.
The median follow-up duration was 36 months, and 37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001) significantly affected the recurrences. However, the type of surgery, the histology, histologic grade, the presence of endolymphatic emboli, and a close resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly associated with a prolonged DFS. Furthermore, multivariate analysis identified 10 or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR 2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as independent indicators of poorer DFS. In addition, bcl-2 expression was found to be significantly correlated with the expressions of ER and PR, and inversely correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2 expression had a significantly longer DFS than those without, even in the ER (+) subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2.
Bcl-2 is an independent prognostic factor of DFS in curatively resected stage III breast cancer patients and appears to be a useful prognostic factor in combination with c-erbB2 and the number of involved lymph nodes.
PMCID: PMC1863427  PMID: 17430582

Results 1-7 (7)