Eun Kyung Hong

Gefitinib as a First-Line Therapy of Advanced or Metastatic Adenocarcinoma of the Lung in Never-Smokers

Purpose: A subset of patients with adenocarcinoma of the lung who had never smoked cigarettes showed excellent tumor responses to gefitinib therapy. To evaluate the efficacy of gefitinib as a first-line therapy in this subgroup of patients, we conducted a phase II study. Experimental Design: Eligible patients had no smoking history, stage IIIB or IV adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ functions. Treatment consisted of daily oral administration ofF 250 mg gefitinib for 28 days until disease progression. Responses were assessed after every two cycles of therapy. Results: Of 37 patients enrolled, 36 were assessed for response. Twenty-five patients (69%) had partial response, 4 (11%) had stable disease, and 7 (19%) had progressive disease. Of 10 patients with evaluable brain metastases, 7 had objective responses in both intracranial and extracranial lesions, 1 had stable disease in the brain and dramatic response in the extracranial lesions, and 2 had progressive disease in both sites. After a median follow-up of 48 weeks (range, 4-70 weeks), 26 patients had disease progression, with median progression-free survival of 33 weeks, and 9 patients died, all due to disease progression. The median survival time has not been reached yet but the estimated 1-year survival rate was 73%. Common toxicities were skin rash and mild diarrhea but there was no significant hematologic toxicity. Conclusions: Gefitinib showed very dramatic antitumor activity, even in the brain, with unprecedented survival outcome in never-smoker adenocarcinoma patients. These data support the use of gefitinib as a first-line therapy in this particular subgroup.

Survival Analysis of Intrahepatic Cholangiocarcinoma After Resection

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, but the studies for the outcome after resection of ICC are rare. The aim of this study was to elucidate outcomes and prognostic factors of ICC in patients undergoing hepatic resection.MethodsA retrospective study was conducted with a total of 63 patients who underwent surgical resection with curative intent for ICC. We performed the survival analysis with preoperative and postoperative clinicopathologic factors according to the clinical outcome.ResultsThe cumulative 1-, 3-, and 5-year survival rates were 68.2, 50.5, and 31.8%, respectively. Univariate analysis revealed that patient’s old age, high preoperative carbohydrate antigen 19-9 (CA19-9) level, major vessel invasion, T classification, lymph node metastasis, lymphatic invasion, perineural invasion, intrahepatic metastasis, and narrow resection margin were statistically significant. By multivariate analysis, patient’s old age, high preoperative CA19-9 level, lymphatic invasion, and narrow resection margin were independent dismal prognostic factors. The preoperative CA19-9 level shows a significant correlation with some histopathologic factors including major vessel invasion, bile duct invasion, and perineural invasion.ConclusionsPreoperative CA19-9 level was a valuable clinical factor for predicting histopathologic invasiveness as well as clinical outcome. An adequate resection margin was the only modifiable factor by a surgeon during hepatic resection for ICC.

Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable.

Objectives:To evaluate 3-dimensional conformal radiotherapy (3D-CRT) of unresectable hepatocellular carcinoma (HCC) patients for whom transcatheter arterial chemoembolization (TACE) was ineffective or unsuitable, and to determine whether tumor response and portal vein thrombosis (PVT) response to treatment were prognostic factors for overall survival. Methods:From July 2001 to June 2005, 70 unresectable HCC patients were treated with 3D-CRT; PVT was present in 41 patients. A daily radiation dose ranging from 2 to 3 Gy was administered using 6 or 15 MV x-rays to deliver a total dose between 44 and 54 Gy. Results:Of 70 patients, follow-up computed tomography showed that primary tumor responses were complete response (CR) in 4 (5.7%) patients, partial response (PR) in 34 (48.6%), no response (NR) in 28 (37.1%), and progressive disease (PD) in 4 (8.6%). Of 41 patients with PVT, PVT responses were CR in 4 (9.7%) patients, PR in 12 (29.3%), NR in 20 (48.8%), and PD in 5 (12.2%). The median survival times were 18.0 and 20.1 month in the primary tumor and the PVT responders (CR + PR), respectively, which were longer than the 6.8 and 7.2 months in the primary tumor and the PVT nonresponders (NR + PD), respectively. Conclusions:3D-CRT was associated with a 54.3% objective response rate for primary tumors and a 39.0% objective response rate for PVT. Both primary tumor and PVT responses were found to be prognostic factors for overall survival. The present results suggest 3D-CRT is a practical treatment option in HCC patients for whom TACE is ineffective or unsuitable.

Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and progression of tumor, including hepatocellular carcinoma (HCC), and elevated VEGF levels in serum and tissues have been known to be related with poor prognosis in patients with HCC. However, the effect of such polymorphisms of the VEGF gene on HCC prognosis has not been elucidated. In the present study, we investigated the association between VEGF gene polymorphisms and HCC patient prognosis. The study involved 416 HCC patients treated at the National Cancer Center Korea from November 2000 to December 2005. The median patient age was 57 years, and 328 patients (78.8%) were men. A total of 19 polymorphisms were analyzed, and the hazard ratios (HRs) for genotypes and haplotypes were determined in terms of risk for overall survival using Cox proportional hazard regression analysis. Of the 19 alleles, 7 showed no heterozygous allele. PHASE analysis identified a total of 36 haplotypes. The −2578 to −1498 region of the VEGF gene showed a strong linkage disequilibrium (correlation coefficient, r2 = 0.91; Lewontins D′, D′ = 0.982). The adjusted HRs were 0.67 [95% confidence interval (CI), 0.46 to 0.99] for −634CC genotype carriers and 0.57 (95% CI, 0.36 to 0.92) for homozygous haplotype 1 (Ht1: CCGAGCCC at −2578/−1203/−1190/−1179/−1154/−634/−7/+936) carriers compared with noncarriers. Conclusion: These findings suggest that VEGF polymorphisms may be significant prognostic indicators for HCC patients. (HEPATOLOGY 2007.)

Biopsy site for detecting Helicobacter pylori infection in patients with gastric cancer

Background:  Helicobacter pylori eradication is recommended in post‐gastric cancer resection, but premalignant changes may prevent the detection of H. pylori. The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients.

The Role of Gefitinib Treatment for Korean Never-Smokers with Advanced or Metastatic Adenocarcinoma of the Lung: A Prospective Study

Purpose: This prospective trial was conducted to evaluate the role of gefitinib in never-smokers with advanced or metastatic adenocarcinoma of the lung. Patients and Methods: The main inclusion criteria were stage IIIB/IV adenocarcinoma of the lung and status as a lifetime never-smoker. Patients received a 250-mg single oral daily dose of gefitinib until disease progression, unacceptable toxicity, or patient’s refusal. Tumor response was assessed after every two 4-week cycles according to the World Health Organization response criteria. Additional analyses were performed to identify predictors of response and survival. Results: Between August 2003 and March 2005, 72 Korean patients were enrolled; 55 chemotherapy naive, 17 previously treated; 6 male, 66 female; and ECOG PS 0/1/2, 24/42/4. All patients were assessed for response, toxicity, quality of life, and survival. Overall objective tumor response rate was 55.6% (95% confidence interval [CI], 43.4–67.3%). With a median follow-up of 23 months, the median survival time was 19.7 months (95% CI, 18.5–21.0 months) with a 1-year survival rate of 76.3%. The median duration of response was 6.8 months (95% CI, 4.7–9.0 months). Therapy-related improvement of symptoms and quality of life was observed within 2 to 4 weeks after the commencement of therapy in the responders. In a multivariate Cox proportional hazard model, good performance status and no prior history of chemotherapy were the two significant predictors of better survival (p = 0.005 and 0.042). Conclusion: Gefitinib showed very promising antitumor activity and survival outcome in Korean never-smokers with adenocarcinoma of the lung. It seems to be a good alternative to standard chemotherapy as a first-line therapy for this subgroup.

Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer.

The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through induction of apoptosis. To examine whether the efficacy of GC chemotherapy might be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor, we investigated the correlation between the tumor response rate and DR5 and Bcl-2 expression in a series of patients prospectively treated with GC. Thirty-four chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) received intravenously 1000 mg/m2 gemcitabine on d 1 and 8 along with 80 mg/m2 cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2 expression by immunohistochemistry. The objective response rate was 56% (19 of 34 patients). With median follow-up of 10 mo, the predicted median survival time was 12 mo (95% confidence interval [CI], 9–15 mo). Eleven (32%) and 14 (41%) NSCLC cases were found positive for DR5 and Bcl-2, respectively. The response rate was significantly higher in patients with DR5 expression than those without DR5 expression (91% vs 39%; p=0.008). Patients with Bcl-2 expression were apparently less responsive than those without Bcl-2 expression (21% vs 80%; p=0.001). DR5 and Bcl-2 expression was significantly associated with response to GC chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting the efficacy of GC.

Clinical significance of portal-superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head cancer.

Objectives The purpose of this study was to determine the significance of portal vein–superior mesenteric vein (PV-SMV) invasion on survival in patients who underwent margin-negative pancreatoduodenectomy (PD) with PV-SMV resection for pancreatic adenocarcinoma. Methods We retrospectively reviewed the records of 60 patients who underwent margin-negative PD with or without PV-SMV resection for pancreatic adenocarcinoma between August 2001 and December 2007. The depth of vessel invasion was investigated and was categorized into 3 groups: tunica adventitia, media, and intima. Clinicopathologic factors and survival were analyzed. Results Portal vein–superior mesenteric vein resection was performed on 19 patients, but only 15 patients (78.9%) had histologically true invasion and showed poorer survival (median survival, 14 vs 9 months; P < 0.05). Univariate analysis revealed that poorly differentiated tumor, lymphatic invasion, endovascular invasion, PV-SMV invasion, and invasion into the intima of PV-SMV were statistically significant. Poorly differentiated tumor and invasion into the intima of PV-SMV were significant in multivariate analysis. Conclusions Aggressive surgical resection should be attempted in cases with suspected PV-SMV invasion because 21.1% of patients had no true invasion and showed better survival than those with true invasion. However, invasion into the tunica intima may be a poor prognostic factor for survival even after margin-negative PD for pancreatic adenocarcinoma.

A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma.

Docetaxel is an active agent in advanced nonsmall‐cell lung carcinoma (NSCLC) and demonstrates preclinical and clinical synergism with capecitabine. We conducted the current Phase II study to evaluate the efficacy and safety of the docetaxel/capecitabine combination in chemotherapy‐naive patients with advanced NSCLC.

ROLE OF ADJUVANT CHEMORADIOTHERAPY FOR RESECTED EXTRAHEPATIC BILIARY TRACT CANCER

PURPOSE To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. METHODS AND MATERIALS The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. RESULTS For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p=.007; 32.1% vs. 26.1%, p=.041; 36.5% vs. 28.2%, p=.049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p<.05). CONCLUSION Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.