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1.  The influence of the treatment response on the impact of resection margin status after preoperative chemoradiotherapy in locally advanced rectal cancer 
BMC Cancer  2013;13:576.
Background
Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated.
Methods
Total of 403 patients with rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM or less than 1 cm for DRM, 151 cases with locally advanced rectal cancer were included as a study cohort. All patients underwent conventionally fractionated radiation with radiation dose over 50 Gy and concurrent chemotherapy with 5-fluorouracil or capecitabine. Postoperative chemotherapy was administered to 142 patients (94.0%). Median follow-up duration was 43.1 months.
Results
The 5-year overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) rates, and locoregional control rates (LRC) were 84.5%, 72.8%, 74.2%, and 86.3%, respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference in a maximally selected rank method. In univariate analysis, CRM of 1.5 mm was significantly related with worse clinical outcomes, whereas DRM of 7 mm was not. In multivariate analysis, CRM of 1.5 mm, and ypN were prognosticators for all studied endpoints. However, CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging, which was found in 16.5% and 40.5% among studied patients, respectively. In contrast, poor responders demonstrated a significant difference according to the CRM status for all studied end-points.
Conclusions
Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was only prominent for poor responders in subgroup analysis. Postoperative treatment strategy may be individualized based on this finding. However, findings from this study need to be validated with larger cohort.
doi:10.1186/1471-2407-13-576
PMCID: PMC3938897  PMID: 24304825
Rectal cancer; Preoperative chemoradiotherapy; Resection margin; Treatment response
2.  Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy 
BMC Cancer  2011;11:452.
Background
This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy.
Methods
Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response.
Results
The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008).
Conclusions
The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype.
Trial Registration
ClinicalTrials.gov: NCT01396655
doi:10.1186/1471-2407-11-452
PMCID: PMC3224348  PMID: 22011459
FDG PET; breast cancer; neoadjuvant chemotherapy; molecular phenotype
3.  Diagnostic performance of contrast enhanced CT and 18F-FDG PET/CT in suspicious recurrence of biliary tract cancer after curative resection 
BMC Cancer  2011;11:188.
Background
Because of the late clinical presentation of biliary tract cancer (BTC), only 10% of patients are eligible for curative surgery. Even among those patients who have undergone curative surgery, most patients develop recurrent cancer. This study is to determine the clinical role of 18F-FDG PET/CT during post-operative surveillance of suspected recurrent BTC based on symptoms, laboratory findings and contrast-enhanced CT (ceCT) findings.
Methods
We consecutively enrolled 50 patients with BTC who underwent curative surgery. An 18F-FDG PET/CT was obtained for assessment of recurrence based on clinical suspicion during post-operative surveillance. The final confirmation of recurrence was determined pathologically or clinically. When a pathologic confirmation was impossible or inconclusive, a clinical confirmation was used by radiologic correlation with subsequent follow-up ceCT at a minimum of 3-month intervals. Diagnostic efficacy was evaluated by comparing the results of ceCT and 18F-FDG PET/CT with the final diagnosis.
Results
Among the 50 patients, 34(68%) were confirmed to have a recurrence. PET/CT showed higher sensitivity (88% vs. 76%, p = 0.16) and accuracy (82% vs. 66%, p = 0.11) for recurrence compared to ceCT, even though the difference was not significant. The positive (86% vs. 74%, p = 0.72) and negative predictive values for recurrence (73% vs. 47%, p = 0.55) were not significantly different between PET/CT and ceCT. However, an additional PET/CT on ceCT significantly improved the sensitivity than did a ceCT alone (94% [32/34] for PET/CT on ceCT vs. 76% [26/34] for ceCT alone, p = 0.03) without increasing the specificity, positive predictive value, and negative predictive value.
Conclusions
18F-FDG PET/CT alone is not more sensitive or specific than ceCT in the detection of recurrent BTC after curative surgery. These results do not reach statistical significance, probably due to the low number of patients. However, an additional 18F-FDG PET/CT on ceCT significantly improves the sensitivity of detecting recurrences.
doi:10.1186/1471-2407-11-188
PMCID: PMC3120804  PMID: 21599995
18F-FDG PET/CT; biliary tract cancer; surveillance; recurrence
4.  Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less 
BMC Cancer  2010;10:557.
Background
Whether a systemic adjuvant treatment is needed is an area of controversy in patients with node-negative early breast cancer with tumor size of ≤1 cm, including T1mic.
Methods
We performed a retrospective analysis of clinical and pathology data of all consecutive patients with node-negative T1mic, T1a, and T1b invasive ductal carcinoma who received surgery between Jan 2000 and Dec 2006. The recurrence free survival (RFS) and risk factors for recurrence were identified.
Results
Out of 3889 patients diagnosed with breast cancer, 375 patients were enrolled (T1mic:120, T1a:93, T1b:162). Median age at diagnosis was 49. After a median follow up of 60.8 months, 12 patients developed recurrences (T1mic:4 (3.3%), T1a:2 (2.2%), T1b:6 (3.7%)), with a five-year cumulative RFS rate of 97.2%. Distant recurrence was identified in three patients. Age younger than 35 years (HR 4.91; 95% CI 1.014-23.763, p = 0.048) and triple negative disease (HR 4.93; 95% CI 1.312-18.519, p = 0.018) were significantly associated with a higher rate of recurrence. HER2 overexpression, Ki-67, and p53 status did not affect RFS.
Conclusions
Prognosis of node-negative breast cancer with T1mic, T1a and T1b is excellent, but patients under 35 years of age or with triple negative disease have a relatively high risk of recurrence.
doi:10.1186/1471-2407-10-557
PMCID: PMC2966467  PMID: 20946688
5.  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.
Background
Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few.
Methods
We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed.
Results
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).
Conclusions
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.
doi:10.1186/1471-2407-10-448
PMCID: PMC2936327  PMID: 20731845
6.  Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: Which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study 
BMC Cancer  2009;9:345.
Background
There is currently no standard adjuvant therapy for patients with curatively resected extrahepatic biliary tract cancer (EHBTC). The aim of this study was to analyze the clinical features and outcomes between patients undergoing adjuvant concurrent chemoradiation therapy (CCRT) alone and those undergoing CCRT followed by adjuvant chemotherapy after curative resection.
Methods
We included 120 patients with EHBTC who underwent radical resection and then received adjuvant CCRT with or without further adjuvant chemotherapy between 2000 and 2006 at Seoul National University Hospital.
Results
Out of 120 patients, 30 received CCRT alone, and 90 received CCRT followed by adjuvant chemotherapy. Baseline characteristics were comparable between the two groups. Three-year disease-free survival (DFS) rates for CCRT alone and CCRT followed by adjuvant chemotherapy were 26.6% and 45.2% (p = 0.04), respectively, and 3-year overall survival (OS) rates were 30.8% and 62.6% (p < 0.01), respectively. CCRT followed by adjuvant chemotherapy showed longer survival than did CCRT alone, especially in R1 resection (microscopically positive margins) or negative lymph node.
Conclusion
Adjuvant CCRT followed by adjuvant chemotherapy prolonged DFS and OS, compared with CCRT alone in patients with curatively resected EHBTC. Adjuvant chemotherapy deserves to consider after adjuvant CCRT. In the future, a randomized prospective study will be needed, with the objective of investigating the role of adjuvant chemotherapy.
doi:10.1186/1471-2407-9-345
PMCID: PMC2761944  PMID: 19781103
7.  The role of PET/CT in detection of gastric cancer recurrence 
BMC Cancer  2009;9:73.
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1471-2407-9-73
PMCID: PMC2651906  PMID: 19250554
8.  Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study 
BMC Cancer  2008;8:374.
Background
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.
Methods
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).
Results
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.
Conclusion
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.
doi:10.1186/1471-2407-8-374
PMCID: PMC2615782  PMID: 19091129
9.  The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer 
BMC Cancer  2008;8:307.
Background
Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer.
Methods
Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated.
Results
Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS.
Conclusion
TN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer.
doi:10.1186/1471-2407-8-307
PMCID: PMC2577689  PMID: 18947390
10.  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.
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1471-2407-8-148
PMCID: PMC2442115  PMID: 18505590
11.  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.
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1471-2407-7-203
PMCID: PMC2217558  PMID: 17976237
12.  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.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-2407-7-63
PMCID: PMC1863427  PMID: 17430582

Results 1-12 (12)