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ABSTRACT: OBJECTIVES: Neuroendocrine tumor originates from several sites. This study was conducted to reveal the differences in clinical course of neuroendocrine tumors by the origin. METHODS: We reviewed data of patients diagnosed with neuroendocrine tumor between January 1996 and July 2007. RESULTS: A total of 371 patients were enrolled [pancreas 60, gastrointestinal (GI) tract 210, lung 35, other sites 46, unknown primary sites 20]. The primary tumor site correlated with the stage (P=0.000) and grade (P=0.000). At diagnosis, metastasis was observed in 28.3%, 6.7%, and 2.9% of the cases in pancreatic, GI, and pulmonary neuroendocrine tumors, respectively. Grade 3 neuroendocrine tumor was observed in 7.7%, 0.5%, and 0.0% in pancreatic, GI, and pulmonary neuroendocrine tumors. Overall survival was 116.0 months (95% confidence interval, 86.9-145.1). Overall survival was 116.0 months in pancreatic neuroendocrine tumor, not reached in GI neuroendocrine tumor and 120.0 months in pulmonary neuroendocrine tumor (P=0.024). The recurrence rate was 18.0%. It was 20.9%, 11.9%, and 2.9% in pancreatic, GI, and pulmonary neuroendocrine tumors (P=0.062). In multivariate analysis, stage, grade, and age were prognostic for overall survival (OS). Stage, grade, and sex were prognostic for disease-free survival. CONCLUSIONS: Neuroendocrine tumors from the pancreas, GI tract, and lung showed different clinical characteristics.
American journal of clinical oncology 06/2011; · 2.21 Impact Factor
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ABSTRACT: OBJECTIVES: To compare the treatment outcome of surgery alone with that of surgery followed by adjuvant chemoradiotherapy (CRT) for duodenal cancer. METHODS: Between January 1991 and December 2002, 24 patients with duodenal cancer underwent pancreaticoduodenectomy. There were 14 males and 10 females, and median age was 61 years (range, 33-75). Nine patients received adjuvant CRT, and 15 did not. Postoperative radiotherapy was delivered up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m/d) was given on days 1 to 3 of each split course. Median follow-up period was 32 months (range, 5-170). RESULTS: Nodal stage and stage group were more advanced in CRT (+) group (P=0.0894 and 0.0361, respectively). However, other patient and tumor characteristics were similar in each group. Five-year overall survival rates of CRT (-) and CRT (+) group were 47% and 30%, respectively (P=0.3799). Five-year locoregional relapse-free survival rates of CRT (-) and CRT (+) group were 64% and 80%, respectively (P=0.4188). On multivariate analysis, patients treated with adjuvant CRT had better locoregional relapse-free survival with borderline significance (P=0.0750). No patient suffered grade 3 or higher toxicity during CRT. CONCLUSIONS: Adjuvant CRT is feasible and may enhance locoregional control in advanced-staged duodenal cancer after curative resection.
American journal of clinical oncology 06/2011; · 2.21 Impact Factor
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Junshik Hong,
Sae-Won Han,
Hye Seon Ham,
Tae-Yong Kim,
In Sil Choi,
Byung-Su Kim,
Do-Youn Oh, Seock-Ah Im,
Gyeong Hoon Kang,
Yung-Jue Bang,
Tae-You Kim
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ABSTRACT: To evaluate the efficacy and safety of S-1 in combination with oxaliplatin in a biweekly schedule as first-line treatment in metastatic colorectal cancer and the association between genetic polymorphisms and treatment outcomes.
Eligibility included age 18-75 years, at least one measurable lesion, no prior chemotherapy except adjuvant chemotherapy, and Eastern Cooperative Oncology Group Performance Status (PS) 0-2. S-1 40 mg/m(2) b.i.d. on days 1-7 with 85 mg/m(2) of oxaliplatin on day 1 was repeated every 2 weeks. Genomic DNA from whole blood was analyzed for 15 single-nucleotide polymorphisms (SNPs) among 8 genes.
Fifty-two patients (median age 63 years, range 37-74) were enrolled: 37 men and 15 women; 44 with a PS of 0 and 8 with a PS of 1; and 41 with initially metastatic cancer and 11 with relapsed disease. Among 51 evaluable patients, objective response rate was 47.1% [95% confidence interval (CI) 32.9-61.2]. Median follow-up duration was 17.1 months (range 3.9-28.2 months). Median progression-free survival (PFS) was 6.4 months (95% CI 4.8-8.1), and median overall survival had not been reached yet. Reported grade 3 toxicities were neutropenia (7.7%), thrombocytopenia (5.8%), sensory neuropathy (7.7%) and diarrhea (1.9%). There was no grade 4 toxicity or neutropenic fever. Patients with A/G or G/G genotype in GSTP1 Ile105Val SNP had longer PFS than patients with A/A (median 8.3 vs. 6.1 months, P = 0.04).
Biweekly S-1 with oxaliplatin is effective and has improved tolerability and convenience compared to other fluoropyrimidine with oxaliplatin combinations. GSTP1 Ile105Val SNP is associated with treatment outcomes.
Cancer Chemotherapy and Pharmacology 06/2011; 67(6):1323-31. · 2.83 Impact Factor
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Seock-Ah Im,
Jin Won Kim,
Jin-Soo Kim,
Min A Kim,
Bruce Jordan,
Marlene Pickl,
Sae-Won Han,
Do-Youn Oh,
Hyuk Joon Lee,
Tae-You Kim,
Woo Ho Kim,
Han-Kwang Yang,
Yung-Jue Bang
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ABSTRACT: Despite recent advances in chemotherapy, the prognosis for patients with advanced gastric cancer (GC) or gastroesophageal junction cancer remains poor. Human epidermal growth factor receptor 2 (HER2) is a novel target for biologic therapy in metastatic GC. We analyzed the association between HER2 overexpression and the clinicopathologic characteristics of advanced GC. Formalin-fixed, paraffin-embedded tumor samples were collected from patients with stage III or to IV (M(0)) GC who subsequently underwent curative surgery followed by adjuvant chemotherapy with 5-fluorouracil and cisplatin. All the samples were analyzed for HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization. Of 142 samples analyzed, 7.1% scored IHC 2+ and 8.6% scored IHC 3+, whereas 9.3% were HER2-amplified. Of HER2-amplified cases, 76.9% (10/13) scored IHC 3+, showing the correlation between HER2 amplification and overexpression (P=0.01). HER2 IHC 3+ cases were more common in the intestinal-type tumors compared with diffuse-type tumors (16.7% vs. 5.1%, respectively; P=0.049), and a nonsignificant trend was observed using fluorescence in situ hybridization (14.3% vs. 9.2%, respectively; P=0.399). HER2 gene amplification was more frequent in stage IV (M(0)) than stage III disease (15.4% vs. 4.0%, respectively; P=0.037). Interestingly, HER2-amplified disease was more common than nonamplified disease in patients with nodal stage 3 tumors (76.9% vs. 38.6%, respectively; P=0.009); a similar pattern was observed using IHC. HER2 overexpression correlated with nodal stage, and a lymph node ratio greater than 0.5 was more common in HER2-amplified tumors than HER2-nonamplified tumors (69.2% vs. 43.3%, respectively; P=0.086). These findings suggest that further investigations of adjuvant therapy with HER2-targeted therapy for advanced GC are warranted.
Diagnostic molecular pathology: the American journal of surgical pathology, part B 06/2011; 20(2):94-100. · 1.58 Impact Factor
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ABSTRACT: Gastric hepatoid adenocarcinoma (HAC) is a special type of gastric cancer that morphologically mimics hepatocellular carcinoma. In this study, we performed an evaluation of clinicopathologic characteristics, treatment outcome, and prognosis in patients with gastric HAC.
We consecutively enrolled patients with pathologically proven gastric HAC at Seoul National University Hospital between January 1996 and December 2008 and conducted a retrospective review. Among 15,253 patients with gastric cancer, 26 patients (0.17%) were diagnosed as gastric HAC.
Among 26 patients, 22 were male and the median age was 63. Stage at diagnosis was stage IB in 3 patients, stage II in 6 patients, stage III in 7 patients, and stage IV in 10 patients. Eight patients out of 18 patients with stage IB, II, III, and IV relapsed after curative surgery. Relapse-free survival for these patients was 16.67 months. The most common metastatic site was intraabdominal lymph nodes (n = 9), followed by the liver (n = 8). Thirteen patients received palliative chemotherapy. The most commonly used regimen was a combination of fluoropyrimidine and platinum. Partial response was observed in one patient and stable disease in 5 patients. Median overall survival and progression free survival of these patients were 8.03 (95% CI: 6.59-9.47) and 3.47 months (95% CI: 0.65-6.29), respectively.
Gastric HAC is a very rare but unique type of stomach cancer. Early detection of this type of cancer is of critical importance to patient prognosis. Additional studies to reveal the biology of this tumor are warranted.
BMC Gastroenterology 05/2011; 11:56. · 2.42 Impact Factor
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ABSTRACT: Hepatitis B virus (HBV) reactivation is a serious clinical problem in HBV carriers undergoing chemotherapy. The clinical course of HBV reactivation can be separated into 2 phases: 1) an increase in HBV replication and 2) hepatic injury. Patients with resolved HBV infections (negative for hepatitis B surface antigen [HBsAg], and positive for both hepatitis B core antibody [anti-HBc] and/or hepatitis B surface antibody) can experience HBV reactivation, and Western guidelines recommend that not only HBsAg but also anti-HBc be screened before initiation of chemotherapy or immunosuppressive therapy. Several meta-analyses have repeatedly confirmed the prophylactic role of lamivudine in preventing HBV reactivation. In conclusion, screening for HBV is required before chemotherapy, and prophylactic antiviral therapy can reduce not only the incidence of HBV reactivation but also HBV-related morbidity and mortality.
Journal of the National Comprehensive Cancer Network: JNCCN 05/2011; 9(5):465-77. · 4.41 Impact Factor
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Bhumsuk Keam, Seock-Ah Im,
Kyung-Hun Lee,
Sae-Won Han,
Do-Youn Oh,
Jee Hyun Kim,
Se-Hoon Lee,
Wonshik Han,
Dong-Wan Kim,
Tae-You Kim,
In Ae Park,
Dong-Young Noh,
Dae Seog Heo,
Yung-Jue Bang
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ABSTRACT: Triple negative breast cancer (TNBC) has a poorer survival, despite a higher response rate to neoadjuvant chemotherapy. The purpose of this study was to identify the predictive or prognostic value of Ki-67 among patients with TNBC treated with neoadjuvant chemotherapy, and the role of Ki-67 in further classification of TNBC.
A total of 105 TNBC patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were included in the present study. Pathologic complete response (pCR) rate, relapse-free survival (RFS), and overall survival (OS) were compared according to the level of Ki-67.
pCR was observed in 13.3% of patients. TNBC with high Ki-67 expression (≥ 10%) showed a higher pCR rate to neoadjuvant chemotherapy than TNBC with low Ki-67 expression. None of the low Ki-67 group achieved pCR (18.2% in the high Ki-67 group vs. 0.0% in the low Ki-67 group, P = 0.019). However, a high Ki-67 expression was significantly associated with poor RFS and OS in TNBC, despite a higher pCR rate (P = 0.005, P = 0.019, respectively). In multivariate analysis, high Ki-67 was an independent prognostic factor for RFS in TNBC (hazard ratio = 7.82, P = 0.002). The high Ki-67 group showed a similar pattern of recurrence with overall TNBC, whereas the low Ki-67 group demonstrated a relatively constant hazard rate for relapse.
TNBC with high Ki-67 was associated with a more aggressive clinical feature despite a higher pCR rate. High proliferation index Ki-67 can be used for further classification of TNBC into two subtypes with different responses and prognosis.
Breast cancer research: BCR 03/2011; 13(2):R22. · 5.24 Impact Factor
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Hyun-Jin Nam,
Hwang-Phill Kim,
Young-Kwang Yoon,
Hyung-Seok Hur,
Sang-Hyun Song,
Maeng-Sup Kim,
Gwan-Sun Lee,
Sae-Won Han, Seock-Ah Im,
Tae-You Kim,
Do-Youn Oh,
Yung-Jue Bang
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ABSTRACT: Trastuzumab, a HER2 directed treatment has shown clinical benefit in HER2 amplified gastric cancer. This study demonstrated the potent antitumor activity of HM781-36B, a quinazoline-based irreversible pan-HER inhibitor, in HER2 amplified gastric cancer cells (SNU216 and N87) in vitro and in vivo. HM781-36B inhibited phosphorylation of HER family and downstream signaling molecules, and induced apoptosis and G1 arrest. Furthermore, HM781-36B exerted synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells. Therefore, HM781-36B may be useful for the treatment of HER2 amplified gastric cancer alone or in combination with chemotherapeutic agents.
Cancer letters 03/2011; 302(2):155-65. · 4.86 Impact Factor
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Jin Won Kim,
Yongjun Cha,
Su-Jung Kim,
Sae-Won Han,
Do-Youn Oh,
Se-Hoon Lee,
Dong-Wan Kim, Seock-Ah Im,
Tae-You Kim,
Dae Seog Heo,
Yung-Jue Bang
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ABSTRACT: The study aims to determine whether or not oral mucositis (OM) during active chemotherapy in patients with solid tumors is representative of the patient's quality of life (QOL) and the suffering from adverse effects.
From October 2007 to September 2008, we prospectively enrolled 344 consecutive patients with solid tumors who initiated a new chemotherapy regimen. OM, other adverse effects, and the QOL were surveyed by face-to-face interviews and patient diaries.
OM developed during 175 of 633 cycles (27.7%). Forty-five percent of the patients experienced OM during two cycles of chemotherapy. The QOL in patients with OM was significantly lower than patients without OM, as evaluated by the Functional Assessment of Cancer Therapy-General (70.26 ± 15.36 and 75.09 ± 13.12, respectively; p < 0.001). Specifically, the physical and emotional well-being was lower in patients with OM compared with patients without OM. Moreover, other adverse effects were more frequent in chemotherapy cycles with OM compared with chemotherapy cycles without OM (amount of food intake, activity, nausea, vomiting, fever, myalgias, and sensory neuropathy; p < 0.001, p = 0.008, p < 0.001, p = 0.001, p = 0.002, p < 0.001, and p < 0.001, respectively).
OM represents poor QOL and is a basic symptom of symptom clusters in patients with solid tumors receiving active chemotherapy.
Supportive Care in Cancer 03/2011; 20(2):395-403. · 2.09 Impact Factor
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ABSTRACT: Recent studies have shown that the human epidermal growth factor receptor 2 status of a metastatic site may differ from that of the primary site. This difference may influence patient prognosis and response to therapy.
We conducted a retrospective study using immunohistochemistry and/or fluorescent in situ hybridization to compare human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancers.
Fifty-six patients were included in this study. Conversion from hormone receptor positive in the primary tumor to hormone receptor negative in the metastasis occurred in 12 patients (21.4%), and hormone receptor negative to hormone receptor positive conversion occurred in two patients (3.6%). Human epidermal growth factor receptor 2 status was discordant between primary and metastatic lesions in seven patients (12.5%). All of the five patients who converted from human epidermal growth factor receptor 2 negative status to human epidermal growth factor receptor positive received trastuzumab-based chemotherapy. Overall response rate and median progression-free survival for concordant human epidermal growth factor receptor 2 positive patients were 69.2% and 16.9 months, whereas that of patients with positive conversion of human epidermal growth factor receptor 2 were 40.0% and 7.6 months, respectively (overall response rate; P = 0.169 and progression-free survival; P = 0.004).
Discordance in human epidermal growth factor receptor 2 and hormone receptor status between primary and metastatic tumors was observed, which led to altered treatment decisions. Evaluation of human epidermal growth factor receptor 2 and hormone receptor in metastatic tumors should be considered in patients with breast cancer.
Japanese Journal of Clinical Oncology 03/2011; 41(5):593-9. · 1.78 Impact Factor
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ABSTRACT: Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability of key regulators of cell survival and is an emerging target of cancer therapy. NVP-AUY922, a novel and potent inhibitor of HSP90, was evaluated against gastric cancer cell lines. NVP-AUY922 significantly inhibited the proliferation of all tested gastric cancer cell lines with 50% inhibitory concentration in the range of 2-40 nM and potently induced the degradation of growth factor receptors and other client proteins including HER-2, Akt and thymidylate synthase. HSP70 was induced by NVP-AUY922 and its binding with client proteins led to their proteasomal degradation. Moreover, the combination of NVP-AUY922 with cytotoxic chemotherapeutic agents such as 5-fluorouracil and oxaliplatin created a synergistic effect. Taken together, these preclinical data demonstrate the potent activity of NVP-AUY922 against gastric cancer cells and offer a rationale for clinical development of the agent alone or in combination with other chemotherapeutic drugs to effectively treat gastric cancer.
Cancer Science 03/2011; 102(7):1388-95. · 3.33 Impact Factor
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ABSTRACT: To analyze the outcome of adjuvant chemoradiotherapy for patients with extrahepatic bile duct (EHBD) cancer, and to identify the prognostic factors for these patients.
Between January 1995 and December 2002, 86 patients with adenocarcinoma of EHBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 59 male and 27 female patients, and median age was 59 years (range, 34 to 73 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/d) was given on day 1 to 3 of each split course. The median follow-up period was 83 months for survivors.
Forty-eight patients failed the treatment: locoregional recurrence in 20, distant metastasis in 38, and both locoregional and distant relapses in 10 patients. Five-year locoregional relapse-free survival rate was 70.3%. On multivariate analysis, resection margin status was the only significant prognosticator (P=0.0299). Five-year distant metastasis-free survival rate was 53.6%. Three or more involved lymph nodes had an adverse impact on distant metastasis-free survival (P=0.0334). Five-year overall survival rate was 44.7%, and poorly differentiated tumor was associated with inferior overall survival (P=0.0297).
Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival in patients with EHBD cancer. Resection margin status, number of involved lymph nodes, and histologic differentiation are associated with locoregional relapse, distant metastasis, and overall survival, respectively. Distant metastasis was the major pattern of failure, possibly due to the increased locoregional control by use of adjuvant chemoradiotherapy. Intensification of systemic treatment is warranted.
American journal of clinical oncology 02/2011; 35(2):136-40. · 2.21 Impact Factor
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Hyeyoung Kim,
Wonshik Han,
Hyeong-Gon Moon,
Junwon Min,
Soo-Kyung Ahn,
Tae-You Kim, Seock-Ah Im,
Do-Youn Oh,
Sae-Won Han,
Eui Kyu Chie,
Sung Whan Ha,
Dong-Young Noh
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ABSTRACT: Little is known about the benefits of preoperative staging chest computed tomography (CT) in patients with asymptomatic breast cancer. We therefore investigated the clinical value of preoperative chest CT in detecting lung and liver metastases by retrospectively reviewing the records of 1,703 patients who underwent preoperative chest CT in a single institution between January 2006 and June 2009. Abnormal CT findings, including suspected metastases and indeterminate nodules in the lung or liver, were found in 266 patients (15.6%). Among these, 26 patients (1.5% of all patients and 9.8% of patients with abnormal CT findings) had true metastases, including 17 in the lungs, 3 in the liver, and 6 in both. True metastases were detected in 1 (0.2%), 0 (0%), and 24 (6.0%) patients with stage I, II, and III disease, respectively. The sensitivity, specificity, and positive predictive value of chest CT were 100, 89.1, and 11.3%, respectively, for lung metastasis and 100, 97.6, and 18.4%, respectively, for liver metastasis. All true metastatic lung lesions were all small-sized nodules, ranging from 0.2 to 1.5 cm in largest diameter, and could not be detected on chest X-rays. In conclusion, our results demonstrate the lack of usefulness of routine preoperative chest CT in detecting asymptomatic liver and lung metastasis in patients with early breast cancer. Chest CT, however, upstaged 6.0% of stage III patients to stage IV.
Breast Cancer Research and Treatment 02/2011; 126(3):637-41. · 4.43 Impact Factor
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Jin-Soo Kim,
Min-A Kim,
Do-Youn Oh,
Se-Hoon Lee,
Dong-Wan Kim, Seock-Ah Im,
Woo Ho Kim,
Han-Kwang Yang,
Dae Seog Heo,
Yung-Jue Bang,
Kuhn-Uk Lee,
Tae-You Kim,
Tae-Min Kim,
Noe Kyung Kim,
Kuk-Jin Choe
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ABSTRACT: The aim of this study is to evaluate the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin in gastric cancer patients and to assess prognostic factors affecting relapse and survival.
We retrospectively reviewed the data of 153 patients with Stage III-IV (M0) gastric cancer. The patients were given adjuvant 5-fluorouracil/cisplatin chemotherapy after curative gastric resection with D2 dissection from November 1995 to November 2003. Chemotherapy consisted of cisplatin (60 mg/m(2) as 15 min i.v. infusion) and 5-fluorouracil (1200 mg/m(2) as 12 h continuous i.v. infusion for 4 days) in every 21 days up to six cycles.
During a median follow-up period of 72.9 months (range: 2.0-135.0 months), a total of 105 patients relapsed (locoregional 19.0% vs. systemic 81.0%). The median disease-free survival and overall survival were 19.8 and 32.2 months, respectively. Univariate analysis revealed T stage, TNM stage and lymph node ratio as prognostic factors for survival (P = 0.002, <0.0001 and <0.0001, respectively). After stepwise selection of the factors, multivariate analysis confirmed the impact of the lymph node ratio and T stage on overall survival and disease-free survival.
In patients with Stage III-IV (M0) gastric cancer, adjuvant 5-fluorouracil/cisplatin chemotherapy was tolerable, but did not seem to confer survival advantage. And the lymph node ratio was found as an independent prognostic factor in this population. This evidence suggests that the clinical trial using more active chemotherapeutic agents is mandatory.
Japanese Journal of Clinical Oncology 02/2011; 41(2):245-52. · 1.78 Impact Factor
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ABSTRACT: In gemcitabine-pretreated pancreatic cancer, salvage chemotherapy has not been established, and the prognostic factors are not completely known. The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) in patients with gemcitabine-pretreated pancreatic cancer and to elucidate the prognostic factors.
Study eligibility was as follows: (1) 18-75 years of age; (2) relapse within 6 months after adjuvant gemcitabine-based chemotherapy (GBC) or previously treated with palliative GBC; and (3) an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. iFAM consisted of a 5-FU (800 mg/m(2)) infusion over 10 h on days 1-5, doxorubicin (30 mg/m(2)) on day 1, and mitomycin-C (8 mg/m(2)) on day 1 every 4 weeks.
Sixty patients were enrolled. The responses to iFAM included a partial response in 6 patients (10.0%) and stable disease in 8 patients (13.3%). The median progression-free survival (PFS) and overall survival (OS) were 2.4 months (95% confidence interval [CI], 2.0-2.8 months) and 6.1 months (95% CI, 4.2-8.0 months), respectively. The 6- and 12-month survival rates were 50.4 and 26.4%, respectively. Grade 3/4 hematologic toxicities included neutropenia (3.3%) and thrombocytopenia (3.3%). The ECOG PS was a significant prognostic factor for PFS (P < 0.001) and OS (P = 0.022). An elevated CA 19-9 at the time of initiating iFAM (P = 0.011) was a poor prognostic factor for OS.
iFAM is an effective and well-tolerated in patients with gemcitabine-pretreated pancreatic cancer, even patients with an ECOG PS of 2. ECOG PS and CA 19-9 were shown to be significant prognostic factors in this salvage setting.
Cancer Chemotherapy and Pharmacology 02/2011; 68(4):1017-26. · 2.83 Impact Factor
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ABSTRACT: To retrospectively evaluate the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in helping to distinguish between lesions with and without residual ductal carcinoma in situ (DCIS) in patients showing no residual invasive cancer after preoperative chemotherapy.
DCE-MR images of 46 consecutive breast cancer patients (mean age, 47 years; range, 30-69 years) with no residual invasive cancer (15 had residual DCIS and 31 had no residual DCIS) following preoperative chemotherapy and surgery were blindly reviewed and categorized by two radiologists in consensus. Thereafter, DCE-MRI findings that could be helpful in distinguishing lesions with and without residual DCIS were analyzed.
When any enhancement was present, 93% (14 of 15) sensitivity and 35% (11 of 31) specificity for the detection of residual DCIS on post-chemotherapy MRI were achieved. Although 65% (20 of 31) of lesions without residual cancer had some enhancing findings, the lesion to fibroglandular signal intensity ratio showed 86.7% (13 of 15) sensitivity and 83.9% (26 of 31) specificity with an Az value of 0.854 (95% confidence interval: 0.718, 0.940) when a cut-off point of a ratio of 1.34 was used.
DCE-MRI has the potential in distinguishing between lesions with and without residual DCIS in patients showing no invasive cancer after preoperative chemotherapy.
European journal of radiology 02/2011; 81(4):737-43. · 2.65 Impact Factor
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ABSTRACT: The aim of this study was to determine the expression of molecular markers in metastatic colorectal cancer (mCRC) and the concordance between primary tumor and metastasis. We also aimed to determine the relationship between molecular markers and clinical outcomes of cetuximab-containing chemotherapy.
Seventy-five mCRC patients who received cetuximab-containing chemotherapy between 2000 and 2008 were consecutively enrolled. EGFR, p-EGFR, PTEN, and IGF-1R expression by immunohistochemistry, DNA sequencing for EGFR, KRAS, BRAF, and PI3 KCA, and EGFR amplification by FISH were done.
The positive expression of EGFR, p-EGFR, PTEN, and IGF-1R was determined in 45 (64.3%), 9 (14.8%), 35 (50.7%), and 10 patients (16.1%), respectively. EGFR gene amplification or high polysomy was detected in 10 patients (17.6%). KRAS mutation and BRAF mutation were detected in 19 patients (27.5%) and five patients (7.0%), respectively. Among tested biomarkers, only the EGFR intron 1 CA repeat polymorphism and BRAF mutation showed concordance (kappa = 0.600, P = 0.003; and kappa = 0.692, P = 0.001, respectively) between primary tumor and paired metastasis. Skin rash was a strong predictive marker for response rate, PFS, and OS. In KRAS mutant tumors, PTEN expression was associated with a longer PFS. BRAF mutation was related to poor outcome in KRAS wild-type tumors.
BRAF mutations and EGFR intron 1 CA repeat polymorphisms were concordant between primary tumors and paired metastases. In KRAS mutant tumors, PTEN expression was a predictive marker for favorable outcomes. In KRAS wild type, BRAF mutation was strong predictive markers for poor outcomes.
Cancer Chemotherapy and Pharmacology 02/2011; 68(4):1045-55. · 2.83 Impact Factor
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Bhumsuk Keam, Seock-Ah Im,
Youngil Koh,
Sae-Won Han,
Do-Youn Oh,
Nariya Cho,
Jee Hyun Kim,
Wonshik Han,
Keon Wook Kang,
Woo Kyung Moon,
Tae-You Kim,
In Ae Park,
Dong-Young Noh,
June-Key Chung,
Yung-Jue Bang
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ABSTRACT: 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.
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.
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).
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.
BMC Cancer 01/2011; 11:452. · 3.01 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
BMC Cancer 01/2011; 11:188. · 3.01 Impact Factor
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ABSTRACT: To evaluate the effect of age at diagnosis on the treatment outcome after breast conservative therapy (BCT), retrospective analysis was done for 378 patients undergoing BCT for early breast cancer. Patients were divided into two groups according to their age: 'younger' (<40years, n=108) and 'older' (≥40years, n=270). Multivariate analysis was performed on the variables including tumor characteristics, the use of systemic therapy, and age to assess risk factors for local-regional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival rates (OS). The median follow-up duration was 94months. The 8-year LRRFS, DMFS, and OS for younger and older groups were 88.1% and 96.5% (p=0.0022); 85.7% and 93.7% (p=0.0310); 89.2% and 95.9% (p=0.0205), respectively. On multivariate analysis, younger age was the only significant predictor of poor LRRFS (p=0.0022). Younger age and ER negativity showed borderline significance for DMFS (p=0.0828 and 0.0618, respectively). Younger age had trend toward inferior OS (p=0.0702). In conclusion, age younger than 40years was associated with inferior LRRFS in early breast cancer patients treated with BCT. There was also a trend for inferior DMFS and OS in younger patients. Age at diagnosis should be considered for individualized patient management.
The Breast Journal 01/2011; 17(1):75-8. · 1.64 Impact Factor
