-
Yoojoo Lim, Bhumsuk Keam,
Youngil Koh,
Tae Min Kim,
Se-Hoon Lee,
J Hun Hah,
Tack-Kyun Kwon,
Dong-Wan Kim,
Hong-Gyun Wu,
Myung-Whun Sung,
Dae Seog Heo,
Kwang Hyun Kim
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: The purpose of this study was to evaluate the efficacy of radiation-based locoregional therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients who did not respond to induction chemotherapy (IC). STUDY DESIGN: Outcomes after radiation-based locoregional therapy were retrospectively analyzed. RESULTS: Among a total of 208 patients treated with IC, 46 (22.1%) did not respond. After IC, patients were treated with radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or surgery with or without postoperative RT. Among the 46 nonresponders, 17 (37.8%) patients underwent surgery and 28 (62.2%) were treated with RT or CCRT. Responses to subsequent RT or CCRT for 26 evaluable patients were as follows: complete response=7 (26.9%), partial response=9 (34.6%), stable disease=4 (15.4%), and progressive disease=6 (23.1%). CONCLUSION: A significant proportion of LA-HNSCC patients who did not respond to IC can benefit from subsequent RT or CCRT.
Oral surgery, oral medicine, oral pathology and oral radiology. 04/2013;
-
Bhumsuk Keam,
Seock-Ah Im,
Yoojoo Lim,
Sae-Won Han,
Hyeong-Gon Moon,
Do-Youn Oh,
Nariya Cho,
Se-Hoon Lee,
Wonshik Han,
Woo Kyung Moon,
Dong-Wan Kim,
Tae-You Kim,
In Ae Park,
Dong-Young Noh
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: Recently, the American Joint Committee on Cancer (AJCC) 7th edition proposed new response criteria for neoadjuvant chemotherapy (NAC) in breast cancer. The purpose of this study was to evaluate the clinical usefulness of AJCC response criteria. METHODS: A total of 398 consecutive stage II or III breast cancer patients who received NAC were enrolled in this study. AJCC response criteria were as follows: (1) complete response (CR)-absence of invasive carcinoma in the breast and node; (2) partial response (PR)-decrease in either or both T or N stage; (3) no response (NR)-no change or increase in either or both T or N stage. RESULTS: Complete response, PR, and NR by AJCC criteria were 9.8, 59.3, and 30.7 %, respectively. Among the 398 patients, 337 patients were available for both paired pre- and post- breast MRI and chest CT. AJCC response criteria were significantly associated with RECIST criteria (P < 0.001). AJCC response was significantly associated with relapse-free survival (RFS) and overall survival (OS). The 5-year RFS rates were 89.6 % in CR, 74.1 % in PR, and 62.6 % in NR (P = 0.002). The 5-year OS rates were 97.4 % in CR, 88.6 % in PR, and 78.3 % in NR (P = 0.012). When adjusting potential prognostic factors, AJCC response was independently associated with RFS and OS. CONCLUSIONS: AJCC response criteria for NAC in breast cancer have clinical usefulness in evaluating response of NAC, as well as predicting survival. AJCC response criteria can discriminate among patient subgroups with respect to survival.
Annals of Surgical Oncology 03/2013; · 4.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Culturing natural killer (NK) cells from patients with advanced cancer is difficult and has restricted the generation of sufficient cell numbers for autologous adoptive NK-cell therapy. The aim of this study was to establish a novel method for ex vivo NK-cell expansion from patients with cancer.
NK cells (CD3(-)CD56(+)) were isolated from peripheral blood mononuclear cells from healthy volunteers and cancer patients, and NK(-) fractions were used as feeder cells. Purified NK cells were co-cultured with feeder cells in AIM-V medium (Invitrogen, Carlsbad, CA, USA) supplemented with 5% human serum and 1000 units/mL human interleukin-2.
NK cells co-cultured with feeder cells from healthy volunteers (feeder-HV) expanded more than NK cells co-cultured with feeder cells from cancer patients (feeder-CP). During the 14-day culture period, NK cells from patients with advanced cancer co-cultivated with feeder-HV expanded on average 300-fold. NK cells co-cultivated with feeder-CP expanded on average 169.4-fold. Cultures grown in the presence of feeder-HV contained 93.8 ± 7.0% (mean ± standard deviation; n = 6) CD3(-)CD56(+) NK cells, and cultures grown in the presence of feeder-CP contained 83.6 ± 15.9% CD3(-)CD56(+) NK cells. Feeder-HV caused a relative increase in CD3(+)CD4(+) T cells, whereas feeder-CP did not induce changes. Interleukin-15, a cytokine that induces NK-cell proliferation, was detected in the culture supernatants of feeder-HV but not in those of feeder-CP.
Feeder cells obtained from healthy volunteers have the potential to expand and activate NK cells from patients with advanced cancer. The novel NK-cell expansion method described here provides a technique for acquiring the large numbers of highly active NK cells from patients with cancer for autologous adoptive immunotherapy.
Cytotherapy 02/2013; 15(2):231-241.e1. · 3.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND:: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is markedly sensitive to the ALK inhibitor crizotinib. However, acquired resistance to crizotinib is inevitable through several mechanisms. Therefore, this study was conducted to identify genetic alterations associated with crizotinib resistance. METHODS:: Tumor samples were derived from seven ALK-positive NSCLC patients who showed acquired resistance to crizotinib, and these patients were analyzed for ALK, EGFR, and KRAS mutations and ALK and EGFR gene amplifications. In vitro cytotoxicity of crizotinib and ALK downstream signals were compared between crizotinib-naive and -resistant NSCLC cells. RESULTS:: After a median duration of 6 months (range, 4-12 months), seven ALK-positive NSCLC patients developed acquired resistance to crizotinib. Three patients harbored secondary ALK mutations, including one patient with both mutations: L1196M (n = 2) and G1269A (n = 2). Of note, one patient displayed ALK gene copy number gain (4.1-fold increase compared with the pre-crizotinib specimen) and EGFR L858R mutation with high polysomy. The amphiregulin concentration was high in the supernatant fluid from five patients with malignant pleural effusion (116.4-18934.0 pg/ml). SNU-2535 cells derived from a patient who harbored the G1269 mutation were resistant to crizotinib treatment similar to H3122 CR1 cells. L1196M and G1269A mutant clones were less sensitive to crizotinib and ALK downstream signals were ineffectively suppressed in these clones. CONCLUSIONS:: Genetic changes associated with crizotinib resistance are heterogeneous in ALK-rearranged NSCLC patients who respond to crizotinib and subsequently develop resistance.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2013; · 4.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Although activating epidermal growth factor receptor (EGFR) mutations are excellent predictors of gefitinib outcome in non-small-cell lung cancer (NSCLC), most patients become resistant to gefitinib. Despite our knowledge of the molecular basis of acquired resistance, clinical predictors have not been well elucidated. This study was undertaken to evaluate predictors of clinical outcome in patients with NSCLC and with EGFR mutations treated with gefitinib. PATIENTS AND METHODS: A total of 170 patients with NSCLC and with EGFR mutations received gefitinib as a first-line (n = 50) and a second-line or more (n = 120) treatment at Seoul National University Hospital. Treatment outcomes were compared between groups based on clinicopathologic factors, such as treatment line, metastatic site, and mutation subtype. RESULTS: Survival outcomes were similar between first-line and second-line or greater gefitinib treatment (overall response rate, 2P = .832; progression-free survival [PFS], 2P = .373; and overall survival [OS], 2P = .290). When the number of metastatic sites was at least 3, significantly reduced survival was observed (median PFS 8.5 vs. 14.0 months, 2P < .001; median OS 21.4 vs. 25.6 months, 2P = .002). In addition, the presence of at least 3 organs with metastases was an independent predictor of PFS (hazard ratio [HR] 1.97 [95% CI, 1.37-2.85]; 2P < .001) and OS (HR 2.00 [95% CI, 1.18-3.39]; 2P = .010). Patients who failed to respond to gefitinib within 6 months of treatment had more lymph node metastases and more sites of metastasis than those who responded later. CONCLUSIONS: Tumor burden, expressed as the number of metastatic sites, is predictive of inferior survival in patients with NSCLC and with activating EGFR mutations who are treated with gefitinib.
Clinical Lung Cancer 01/2013; · 2.94 Impact Factor
-
Tae Min Kim,
Jin Chul Paeng,
In Kook Chun, Bhumsuk Keam,
Yoon Kyung Jeon,
Se-Hoon Lee,
Dong-Wan Kim,
Dong Soo Lee,
Chul Woo Kim,
June-Key Chung,
Il Han Kim,
Dae Seog Heo
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: This study was undertaken to evaluate the prognostic value of quantitative metabolic parameters in [(18) F]2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) for diffuse large B cell lymphoma (DLBCL). METHODS: A total of 140 DLBCL patients underwent FDG-PET scans before rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy. The maximal standardized uptake value (SUV(max) ) and total lesion glycolysis (TLG) were calculated, with the margin thresholds as 25%, 50%, and 75% of SUV(max) of all lesions. Treatment outcomes were compared between groups according to metabolic parameters and the International Prognostic Index (IPI). RESULTS: After a median follow-up of 28.5 months (range, 5-81 months), the 2-year progression-free survival (PFS) and overall survival (OS) were 83% and 87%, respectively. Among metabolic parameters, TLG at the threshold of 50% (TLG(50) ) was significantly associated with treatment outcomes. High TLG(50) values (>415.5) were associated with reduced survivals compared with low TLG(50) values (≤415.5) (2-year PFS of 73% versus 92%, P = .007; and 2-year OS of 81% versus 93%, P = .031). High IPI score (≥3) significantly reduced OS (2-year OS of 79% versus 90%, P = .049). Ann Arbor stage III/IV adversely affected PFS (P = .013). However, high IPI score and Ann Arbor stage of III/V did not significantly shorten PFS (P = .200) and OS (P = .921), respectively. High TLG(50) values independently predicted survivals by multivariate analysis (hazard ratio = 4.4; 95% confidence interval = 1.5-13.1; P = .008 for PFS and hazard ratio = 3.1; 95% confidence interval = 1.0-9.6; P = .049 for OS). CONCLUSIONS: Combined assessment of volume and metabolism (ie, TLG) is predictive of survivals in DLBCL patients who are treated with R-CHOP. Cancer 2012. © 2012 American Cancer Society.
Cancer 12/2012; · 4.77 Impact Factor
-
Tae Ryool Koo,
Hong-Gyun Wu,
J Hun Hah,
Myung-Whun Sung,
Kwang-Hyun Kim, Bhumsuk Keam,
Tae Min Kim,
Se-Hoon Lee,
Dong-Wan Kim,
Dae-Seog Heo,
Charn Il Park
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to analyze treatment outcome of radiotherapy (RT) in patients with stage III-IV tonsil cancer managed by surgery followed by postoperative RT (SRT) and definitive chemoradiotherapy (CRT), and to thereby evaluate the most feasible treatment modality.
Of 124 patients, 67 underwent CRT, and 57 underwent SRT. We compared survival and complication rates in both groups.
The median follow-up time was 57 months (range, 19 to 255 months) for surviving patients. At five years, locoregional progression-free survival (LRPFS) and overall survival (OS) were 88% and 80%, respectively. No significant difference in LRPFS (p=0.491) and OS (p=0.177) was observed between CRT and SRT. In multivariate analysis, old age and higher T stage showed a significant association with poor LRPFS, PFS, and OS; higher N stage showed an association with poor PFS and a trend of poor LRPFS, while no association with OS was observed; treatment modality (CRT and SRT) showed no association with LRFPS, PFS, and OS. Grade 3 or higher mucositis was observed in 12 patients (21%) in the SRT group, and 25 patients (37%) in the CRT group.
Definitive CRT and SRT have similar treatment outcomes for patients with stage III-IV tonsil cancer. Although acute complication rate appears to be higher in the CRT group, it should be noted that not all data on complications were included in this retrospective study. To determine the most feasible treatment modality, not only mucositis and xerostomia, but also emotional aspect and quality of life, should be considered.
Cancer Research and Treatment 12/2012; 44(4):227-34.
-
Kyung-Hun Lee, Bhumsuk Keam,
Seock-Ah Im,
Tae-Yong Kim,
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
[show abstract]
[hide abstract]
ABSTRACT: The effects of body mass index on pathologic complete response and survival have not been reported in Korean patients with breast cancer. The purpose of this study was to evaluate the predictive or prognostic value of obesity in breast cancer receiving neoadjuvant chemotherapy.
A total of 438 stage II or III breast cancer patients treated with neoadjuvant chemotherapy were enrolled and analyzed retrospectively.
In the study, 319 patients (72.8%) were normal weight, 100 patients (22.8%) were overweight, and 19 patients (4.3%) were obese. Baseline clinicopathologic characteristics were not different among the groups, except for age. There were no differences in pathologic complete response rate between the groups (9.7% in normal weight, 10.0% in overweight, 5.3% in obese; p=0.804). Neither overweight nor obese patients showed a significant difference in relapse-free survival compared to normal weight patients (p=0.523 and p=0.931, respectively). Also, no significant difference in overall survival (p=0.520 and p=0.864, respectively) was observed.
Obesity or higher body mass index was not significantly associated with pathologic complete response and survival in Korean patients with breast cancer who received neoadjuvant chemotherapy. Our results suggest that the prognostic impact of body mass index is different from that of Western patients.
Journal of Breast Cancer 12/2012; 15(4):427-33. · 0.32 Impact Factor
-
Hyun Jung Lee,
Dae Young Kim, Bhumsuk Keam,
Jeong Hoon Lee,
Sae-Won Han,
Do-Youn Oh,
Jung Hwan Yoon,
Tae-You Kim,
Yu Jung Kim,
Keun Wook Lee,
Jin-Wook Kim,
Sook-Hyang Jeong,
Jong Seok Lee,
Jee Hyun Kim,
Seock-Ah Im
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: This study aimed to assess the efficacy of lamivudine prophylaxis on hepatic complications in HBsAg-positive patients with breast cancer undergoing adjuvant chemotherapy and to describe the temporal trend in HBV surveillance and prophylaxis during the last decade. METHODS: Patients with stage I-III curatively resected invasive breast cancer who received adjuvant and/or neoadjuvant chemotherapy between 2000 and 2009 were eligible for this study. Patients with positive HBsAg and normal liver function were enrolled. Hepatotoxicity, defined as alanine aminotransferase (ALT) ≥100 IU/ml, and HBV reactivation were compared according to lamivudine prophylaxis. Annual trends in HBV surveillance and use of lamivudine prophylaxis were also reviewed. RESULTS: One hundred sixty-five HBsAg-positive patients with breast cancer were enrolled. After the year 2004, surveillance of HBV infection status and use of lamivudine prophylaxis increased significantly (2.5 vs. 57.6 %, P < 0.001). Seventy-three (44.2 %) patients received lamivudine prophylaxis and 92 (55.8 %) patients did not. The incidence of hepatotoxicity was significantly lower in the group receiving prophylaxis (2.7 vs. 14.1 %, P = 0.011) with fewer premature terminations of planned adjuvant chemotherapy (0 vs. 10.9 %, P = 0.004) in the prophylaxis group. Among the patients for whom the baseline HBV DNA titer was available, the HBV reactivation rate was lower, albeit not significantly, in the prophylaxis group (0 %) compared with the no prophylaxis group (20 %) (P = 0.104). Lamivudine-withdrawal hepatitis was not detected; however, one case of breakthrough HBV reactivation during lamivudine treatment was observed in this study. CONCLUSIONS: Over the past decade, there has been an increase in the awareness of HBV reactivation and in the use of lamivudine during cytotoxic chemotherapy. Lamivudine prophylaxis reduced hepatic complications during adjuvant chemotherapy in patients with breast cancer. Lamivudine prophylaxis should be considered in HBsAg-positive patients with breast cancer who are candidates for adjuvant chemotherapy.
Breast Cancer 10/2012; · 1.36 Impact Factor
-
Hyeong-Gon Moon,
Seock-Ah Im,
Wonshik Han,
Do-Youn Oh,
Sae-Won Han, Bhumsuk Keam,
In Ae Park,
Jung Min Chang,
Woo Kyung Moon,
Nariya Cho,
Dong-Young Noh
[show abstract]
[hide abstract]
ABSTRACT: Estrogen receptor (ER) expression status is an independent factor predicting response to neoadjuvant systemic treatment (NST). In the current study, we aimed to investigate the characteristics of NST response and benefits of extended NST cycles according to ER expression status. We investigated the outcomes of different durations of anthracycline-taxane-based NST in 377 operable breast cancer patients treated between Aug 2008 and June 2011. In 89 patients, the serial radiologic tumor response was assessed with either ultrasonography or computed tomography. Ninety-six patients (25.5 %) received extended cycles of anthracycline-taxane-based NST (6-8 cycles) and 281 patients (74.5 %) received 3-4 cycles of NST. Treatment with extended cycles of NST led to a significant increase in the pCR rate in ER-positive tumors only (2.1-11.7 %, p = 0.008 for ER-positive tumors and 20.0-19.4 %, p = 0.941 for ER-negative tumors). Serial assessment of radiologic tumor size during extended NST therapy revealed continuous shrinkage of ER-positive tumors during the chemotherapy cycles, while ER-negative tumors mainly achieved size reduction during the first 3-4 cycles with no significant additional tumor shrinkage during the extended cycles of NST. In this study, we report a distinct pattern of response to NST according to ER expression status in breast cancer. Our observation generates the hypothesis that the optimal duration of NST can be tailored to the molecular phenotypes of tumors.
Breast Cancer Research and Treatment 07/2012; 134(3):1133-40. · 4.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: Although surrogate decision-making in cancer patients is well-known, few studies investigating the prevalence of surrogate decision-making over time have been reported. The objectives of this study were to investigate the level of surrogate decision-making in advanced cancer patients over time and the impact of demographic and clinical variables on surrogate decision-making. METHODS: The level of surrogate decision-making was measured in 572 consecutive cancer patients who died between January 1 and December 31, 2009. We reviewed 8,639 informed consent forms of these patients, calculated the proportion of decisions made by a surrogate (PDS) for each patient, and analyzed the association of PDS with demographic and clinical variables. RESULTS: Surrogates completed 40.3 % of all consent forms. The prevalence of surrogate decision-making was higher in the end-of-life period (death <7 days, OR = 29.05; reference, >365 days). Surrogates signed consent forms more frequently for do-not-resuscitate directives, intensive care unit admission, emergency hemodialysis, surgery and invasive interventions compared with chemotherapy, radiotherapy, and diagnostic tests (OR = 3.88, P < 0.001). Patients of older age (P = 0.036) and those with a shorter duration of management (P < 0.001) were independently associated with greater PDS. CONCLUSIONS: Surrogate decision-making was frequently observed among Korean cancer patients in this study, especially when the patient's death was imminent, and for decisions related to end-of-life care. Surrogates were also frequently involved in decisions for elderly or rapidly deteriorating patients. Healthcare professionals should consider the significant role of familial surrogates in the end-of-life period; comprehensive approaches are needed to preserve the best interest of the patients.
Supportive Care in Cancer 05/2012; · 2.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are important predictive markers for the response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Whether EGFR mutations can also predict the clinical outcomes in NSCLC patients receiving chemotherapy has not yet been established.
We included 217 locally advanced/metastatic NSCLC cases in our study cohort. Each patient had received platinum doublet chemotherapy as a first line treatment, and had been screened for an EGFR mutation.
The subject cohort comprised 80 EGFR wild type and 137 EGFR-mutated lung cancer patients. Gemcitabine-based and taxane-based regimens were administered in 131 (60.4%) and 86 (39.6%) cases, respectively. Among the patients with a wild type EGFR, there was no significant difference in the response rate (RR), disease control rate (DCR), or progression-free survival (PFS) between gemcitabine-based and taxane-based therapies. Among the patients with EGFR mutations, no difference in RR was observed between gemcitabine-based and taxane-based treatments. On the other hand, the DCR and PFS associated with taxane-based therapy were superior when compared with the gemcitabine-based treatments. When we analyzed patients with an EGFR exon 19 deletion, the PFS of the taxane treated cases was better than that of the gemcitabine treated cases (5.3 months vs 3.7 months, P=0.012).
Our current data indicate that lung cancer patients with EGFR-mutations had longer PFS with taxane than gemcitabine when receiving a platinum-based doublet regimen. The predictive meaning of EGFR mutations for cytotoxic chemotherapy should be further investigated.
Lung cancer (Amsterdam, Netherlands) 04/2012; 77(2):433-7. · 3.14 Impact Factor
-
Bhumsuk Keam,
Seock-Ah Im,
Hee-Jun Kim,
Do-Youn Oh,
Jee Hyun Kim,
Se-Hoon Lee,
Eui Kyu Chie,
Wonshik Han,
Dong-Wan Kim,
Nariya Cho,
Woo Kyung Moon,
Tae-You Kim,
In Ae Park,
Dong-Young Noh,
Dae Seog Heo,
Sung Whan Ha,
Yung-Jue Bang
[show abstract]
[hide abstract]
ABSTRACT: Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify
the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant
chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy
were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative
surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional
cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant
chemotherapy when indicated. Results The median follow-up duration was 28.9months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The
mean nodal ratio was 0.29 (range, 0–1.0; nodal ratio≤0.25, 121 [59.0%] vs.>0.25, 84 [41.0%]). Relapse free survival (RFS)
of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR)=2.701, P=0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR=4.109, P=0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P=0.166, P=0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR=4.246,
P<0.001; HR=7.764, P <0.001). Conclusion Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy.
Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting.
Breast Cancer Research and Treatment 04/2012; 116(1):153-160. · 4.43 Impact Factor
-
Jin Won Kim,
Seock-Ah Im,
Miso Kim,
Yongjun Cha,
Kyung-Hun Lee, Bhumsuk Keam,
Min A Kim,
Sae-Won Han,
Do-Youn Oh,
Tae-You Kim,
Woo Ho Kim,
Yung-Jue Bang
[show abstract]
[hide abstract]
ABSTRACT: We aimed to clarify the prognostic significance of HER2 positivity in advanced gastric cancer.
The cohort included patients with initially metastatic or recurrent gastric cancer treated with first-line modified FOLFOX-6. The HER2 status was analyzed according to modified scoring criteria specific for gastric cancer.
HER2 positivity was shown in 10 out of 114 patients (9.0%). The median time-to-progression (TTP) (4.3 months, 95% confidence interval (CI)=3.6-4.9) and the overall survival (OS) (7.5 months, 95% CI=6.1-8.8) of patients with HER2-positive gastric cancer tended to be shorter than the median TTP (5.9 months, 95% CI=4.5-7.2) and OS (10.8 months, 95% CI=9.2-12.3) of those with HER2-negative gastric cancer (TTP, p=0.177; OS, p=0.068). Particularly in the subgroup of patients without diffuse-type histology, HER2-positive gastric cancer had a worse TTP than those with HER2-negative gastric cancer (p=0.024). In multivariate analysis of this subgroup, HER2 positivity and ECOG performance status of 2 were associated with shorter TTP (hazard ratio (HR)=2.926, p=0.014; HR=2.489, p=0.035, respectively).
HER2-positive gastric cancer seems to confer poorer prognosis, particularly in patients without diffuse-type tumor, treated with modified FOLFOX-6.
Anticancer research 04/2012; 32(4):1547-53. · 1.73 Impact Factor
-
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
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The purpose of this study was to determine the usefulness of sequential FDG PET/CTs for prediction of axillary lymph node (ALN) status after neoadjuvant chemotherapy (NAC). METHODS: Seventy-seven stage II or III breast cancer patients who received 3 cycles of neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for early metabolic response prediction. RESULTS: Patients with pN0 had significantly lower post-NAC ALN standard uptake value (SUV) than those who were pN+ (1.22 ± 1.46 in pN0 vs. 2.13 ± 1.99 in pN+, P = 0.017). Post-NAC ALN size on CT also differed according to pathologic ALN status (6.3 mm in pN0 vs. 11.1 mm in pN+, P = 0.014). When serial FDG PET/CT and chest CT were used, patients with an SUV > 1.5 and post-NAC ALN size ≥10 mm on CT did not achieve pN0 (specificity 100% and positive predictive value 100%). CONCLUSIONS: The serial FDG PET/CT after NAC could predict the pathologic status of ALN before surgery in stage II/III breast cancer. Our findings suggest that the combined use of serial FDG PET/CTs and chest CT might provide better information regarding ALN before surgery.
Breast Cancer 02/2012; · 1.36 Impact Factor
-
Hee-Jun Kim,
Seock-Ah Im, Bhumsuk Keam,
Yu-Jung Kim,
Sae-Won Han,
Tae Min Kim,
Do-Youn Oh,
Jee Hyun Kim,
Se-Hoon Lee,
Eui Kyu Chie,
Wonshik Han,
Dong-Wan Kim,
Tae-You Kim,
Dong-Young Noh,
Dae Seog Heo,
In Ae Park,
Yung-Jue Bang,
Sung Whan Ha
[show abstract]
[hide abstract]
ABSTRACT: Central nerve system (CNS) metastases are a feared complication of breast cancer and are associated with poor prognosis. The purpose of this study is to investigate the clinical characteristics of CNS metastases and to clarify the prognostic factors after CNS metastases in breast cancer at a single institution over a long time period. We retrospectively reviewed the medical records of breast cancer patients diagnosed at Seoul National University Hospital from 1981 to 2009 and identified the patients who experienced CNS metastases. We collected the data, including demographics, clinico-pathologic characteristics, dates of diagnosis of original breast cancer and subsequent metastases, and date of death, and correlated the findings with the clinical outcome. A total of 400 patients were identified, of whom 17 (4.3%) were diagnosed with CNS metastases and primary breast cancer concurrently and 383 (95.7%) experienced CNS metastases subsequent to the diagnosis of primary breast cancer. Further, 318 patients (79.5%) had only brain parenchymal metastases, 30 (7.5%) had only leptomeningeal metastases, and 52 (13%) had both. After the diagnosis of CNS metastasis, 170 patients (42.5%) received systemic chemotherapy (CTx) and 143 (35.8%) received CTx after whole brain radiation therapy (WBRT). The patients with good performance status (PS), initial CNS metastasis as recurrence, absence of extracranial metastases, non-visceral extracranial metastases, longer interval from the date of primary breast cancer to the date of CNS metastasis, and CTx after WBRT and gamma-knife surgery (GKS), had better outcomes in univariate analyses. In multivariate analysis, good PS, systemic CTx after WBRT, GKS, and longer interval to CNS metastasis, were independent prognostic factors for overall survival after CNS metastases. Our results suggest that appropriate palliative systemic therapy after WBRT or GKS, and adequate palliative treatment via combined modalities are helpful for breast cancer patients, even after the detection of CNS metastases.
Journal of Neuro-Oncology 09/2011; 106(2):303-13. · 3.21 Impact Factor
-
Bhumsuk Keam,
Seock-Ah Im,
Sohee Park,
Byung-Ho Nam,
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
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to combine clinical pathologic variables that are associated with pathologic completer response (pCR) and relapse-free survival (RFS) after neoadjuvant chemotherapy into prediction nomograms.
A total of 370 stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We developed the nomograms using logistic regression model for pCR and Cox proportional hazard regression model for RFS.
The nomogram for pCR based on initial tumor size, estrogen receptor (ER), human epidermal growth factor receptor 2, and Ki67 had good discrimination performance (AUROC = 0.830). Multivariate Cox model identified age less than 35, initial clinical stage, pathologic stage, ER, Ki67 as prognostic factors, and the nomogram for RFS was developed based on these covariates. The concordance index for the second nomogram was 0.781, and calibration was also good.
We developed nomograms based on clinical and pathologic characteristics to predict the probability of pCR and RFS for patients receiving neoadjuvant docetaxel/doxorubicin chemotherapy.
Journal of Cancer Research and Clinical Oncology 06/2011; 137(9):1301-8. · 2.56 Impact Factor
-
[show abstract]
[hide abstract]
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
-
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
[show abstract]
[hide abstract]
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
-
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
[show abstract]
[hide abstract]
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
