Koo Foundation Sun Yat-Sen Cancer Research Articles

Therapeutic Drug Monitoring of Busulfan in Patients Undergoing Hematopoietic Cell Transplantation: A Pilot Single-Center Study in Taiwan.

Busulfan has been used as a conditioning regimen in allogeneic hematopoietic cell stem transplantation (HSCT). Owing to a large inter-individual variation in pharmacokinetics, therapeutic drug monitoring (TDM)-guided busulfan dosing is necessary to reduce graft failure and relapse rate. As there exists no TDM of busulfan administration for HCT in Taiwan, we conducted a pilot study to assess the TDM-dosing of busulfan in the Taiwanese population; Seven patients with HCT from The Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, received conditioning regimens consisting of intravenous busulfan and other chemotherapies. After the initial busulfan dose, blood samples were collected for busulfan TDM at 5 min, 1 h, 2 h, and 3 h. Busulfan was extracted and detected by performing stable-isotope dilution LC–MS/MS. Plasma busulfan concentration was quantified and used for dose adjustment. Potential adverse effects of busulfan, such as mucositis and hepatic veno-occlusive disease (VOD), were also evaluated; The LC–MS/MS method was validated with an analyte recovery of 88–99%, within-run and between-run precision of <15%, and linearity ranging from 10 to 10,000 ng/mL. Using TDM-guided busulfan dosing, dose adjustment was necessary and performed in six out of seven patients (86%) with successful engraftments in all patients (100%). Mild mucositis was observed, and VOD was diagnosed in only one patient; This single-center study in Taiwan demonstrated the importance of busulfan TDM in increasing the success rate of HCT transplantation. It is also necessary to further investigate the optimal busulfan target value in the Taiwanese population in the future.

Protein Arginine Methyltransferase 3-Induced Metabolic Reprogramming Is a Vulnerable Target of Pancreatic Cancer

Background: The biological function of protein arginine methyltransferase 3 (PRMT3) is not well known because very few physiological substrates of PRMT3 have been identified to date. Methods: The clinical significance of PRMT3 in pancreatic cancer was studied by database analysis. The PRMT3 protein level in human pancreatic tumors was detected by immunoblotting. PRMT3-associated proteins and the methylation sites on the proteins were investigated using mass spectrometry. Capillary electrophoresis time-of-flight mass spectrometry and seahorse bioscience were performed to analyze metabolic reprogramming. Combination index analysis and xenograft animal model were conducted to explore the effects of combination of inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and oxidative phosphorylation on tumor growth. Findings: We find the expression of PRMT3 is upregulated in pancreatic cancer, and its expression is associated with poor survival. We further demonstrate that GAPDH is methylated at R248 by PRMT3 in vivo. The methylation of GAPDH by PRMT3 enhances its catalytic activity while the mutation of R248 abolishes the effect. In cells, PRMT3 overexpression triggers metabolic reprogramming and enhances glycolysis and mitochondrial respiration simultaneously in a GAPDH-dependent manner. PRMT3-overexpressing cancer cells are addicted to GAPDH-mediated metabolism and sensitive to the inhibition of GAPDH and mitochondrial respiration. The combination of inhibitors of GAPDH and oxidative phosphorylation induces a synergistic inhibition on cellular growth in vitro and in vivo. Interpretation: Our results suggest PRMT3-induced metabolic reprogramming is a vulnerable target of pancreatic cancer. Funding Statement: This work was supported by the grants from the Ministry of Science and Technology (MOST-103-2314-B-037-075; MOST-104-2314-B-037-004; MOST-105-2314-B-037-001; MOST-107-2320-B-400-006-MY3 to M.-R.P. and W.-C.H. and MOST-106-2321-B-400-007 to L.-T.C.). This study was also supported by the grant from National Research Institutes (NHRI-107A1-CACO-02181811 to Y.-S.S.) and the Yen-Hsu Education Foundation to W.-C.H. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Human pancreatic tumor tissues were obtained from patients undergoing surgical resection at Koo Foundation Sun Yat-Sen Cancer Center (Taipei, Taiwan) and National Cheng Kung University Hospital (Tainan, Taiwan) under the guidelines approved by the Institution Review Board at National Health Research Institutes. Written informed consent was obtained from each patient. All animal experiments were approved by Animal Care Committee of National Health Research Institutes.

Post-Mastectomy Radiation Therapy in Stage II N1 Breast Cancer Patients Is Associated with Improved Survival with Different Sub-Type

Post-operative radiotherapy (PMRT) has shown to reduce locoregional recurrence and increase disease-free survival and overall survival in high risk breast cancer patients, in combination with chemotherapy or hormone therapy. For stage II breast cancer, PMRT was still under discussion. Current NCCN guideline recommend N1 patients to receive PMRT. This study aims to evaluate the impact of PMRT on different breast cancer subtype. Between 1990 and 2013, there were 1252 patients with Stage II breast cancer (T1-2 with one to three positive) treated by mastectomy at the Koo Foundation Sun Yat-Sen Cancer Center. We divided breast cancer into luminal (ER/PR+, HER2-), HER2 overexpressed, and triple negative subtype. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier method. The median follow up time was 80 months. In this cohort, luminal, HER2 overexpressed, triple negative subtypes accounted for 59%, 28.4%,12.6%, respectively. Among them, 765 (61%) of patients were treated with PMRT. Survival analyses revealed that PMRT was significant improved 10 years OS and DFS in all subtypes except HER2 subtype (Table 1). The absolute 10-year survival gain was 8% in luminal subtype, and 25% in triple negative subtype. Further propensity score matching results are pending.Abstract TU_4_3360; Table 1Luminal, HER2 and triple negative breast cancer with or without PMRTNRadiotherapyDFSp valueOSP valueAll765Yes82%<0.00184%0.0043487No68%78%Luminal406Yes78%0.007887%0.0089332No72%79%HER2240Yes75%0.017378%0.5696116No67%76%Triple negative119Yes80%0.001989%0.005339No56%64% Open table in a new tab PMRT improved long term DFS in women with pT1-T2/N1 breast cancer in luminal and triple negative breast cancers.

1054PD - A New Classification for Nasopharyngeal Carcinoma

Background: This study is to develop and validate a new classification for nasopharyngeal carcinoma (NPC). Methods: Fifteen hundred and twenty-eight (1528) newly diagnosed NPC patients treated between 1995 and 2010 were included in this study. Seven hundred and one patients (n = 701) were treated with 3D conformal radiotherapy (3D-RT) and 827 patients were treated with IMRT. Cox proportional hazards model was used to select the significant split node to partition patients into the different risk group. Recursive partitioning analysis derived a new classification in patients treated with 3D-RT objectively. This new staging system was then validated in patients treated with IMRT. Results: The median follow-up interval was 84.6 months (ranging 2-175 months). According to the 7th AJCC staging system, the stage I patients showed a 5-year overall survival (OS) rate of 93.0%, stage II of 94.5%, stage III of 87.5%, stage IVA of 71.5%, stage IVB of 61.3%, and stage IVC of 5.8% (p < 0.0001). In the validation group (n = 827), the Group I in new system was patients with stages of T1-3N0-1 and T1N2 (n = 364); their 5-year OS was 92.4%. The Group II was patients with stages of T2N2 and T3N2 (n = 175); thier 5-year OS was 86.0%. The Group III was patients with stages of any T4 and N3 (n = 249); their 5-year OS was 72.0%. The Group IV was patients with distant metastasis (n = 36); their 5-year OS was 17.9%. This new classification system will be compared to the 8th AJCC staging system. Conclusions: We propose a new staging system for NPC, which distributes more patients in the early stage.Table1054PD Patient Distribution According to Chinese 2008 and the 7th AJCC staging systemsStageChinese 2008 staging2010 AJCC stagingCurrent proposalStage I2.3%2.3%42.9%Stage II11.0%23.7%21.9%Stage III39.4%49.1%30.0%Stage IV47.3%24.9%5.2% Open table in a new tab Legal entity responsible for the study: None Funding: Koo Foundation Sun Yat-Sen Cancer Center Disclosure: All authors have declared no conflicts of interest.

Prevalence, risk factors, and the desire for help of distressed newly diagnosed cancer patients: A large-sample study.

Beginning in 2007, all newly diagnosed cancer patients at the Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were screened for psychosocial distress. Our social workers, as part of the psychosocial care team (PCT), have engaged in proactive outreach with patients identified as distressed. The goal of the present study was to assess the prevalence of psychosocial distress and the extent of contact between the PCT and distressed patients. Newly diagnosed patients who were treated at KF-SYSCC between 2007 and 2010 for cancer were eligible if there were at least 100 patients with the same type of cancer. Before treatment began, they were screened with the Pain Scale and the Distress Thermometer (DT) and had the option to specify a desire for help. The rates of distress were analyzed by cancer type and by probable related factors. Information regarding contact with the PCT was retrieved from computerized databases. Overall, some 5,335 cancer patients representing 12 major cancer types were included in our study. Of these, 1,771 (33.20%) were significantly distressed. By multivariate logistic regression, younger age, female gender, higher pain score, and disease stage, but not cancer type, were found to be associated with higher rates of distress. Among these distressed patients, 628 (36%) had some contact with the PCT. This Taiwanese study with a large sample size revealed a prevalence rate of psychosocial distress similar to rates found in Western countries. Contact with the PCT was established in only 36% of significantly distressed patients, despite a proactive outreach program. It is very important to have screening results made available in a timely fashion to the psycho-oncology team so that appropriate care can be offered promptly.

Laparoscopic intracorporeal stapling of the gastric tube on the basis of surface blood supply after minimally invasive esophagectomy

Background/IntroductionMinimally invasive esophagectomy is a complex operation in which creating a healthy gastric substitute is crucial. The present study evaluated a novel method of reconstructing the intracorporeal laparoscopic gastric tube on the basis of surface blood supply to the stomach. PurposeTo study the feasibility and safety of a novel method of laparoscopic gastric tube reconstruction. MethodsAfter the complete mobilization of the stomach, the stomach was intracorporeally stapled along the watershed area between the blood supplies of the lesser and greater curvatures. Subsequently, the gastric tube was pulled up to the neck for end-to-side cervical esophagogastrostomy. Perioperative data were prospectively collected for the first 20 patients who had undergone this novel laparoscopic gastric reconstruction at our institute. The descriptive statistics are reported in this paper. ResultsWe enrolled 20 patients (18 men and 2 women) with esophageal cancer who were admitted to the Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan between January 2013 and December 2013. The mean operative time was 7.10 ± 1.08 hours, and the mean operative blood loss was 118.00 ± 79.71 mL. The average length of the gastric tubes above the sternal notch was 7.65 cm (∼5.0–15.0 ± 2.40 cm); the average width of the gastric tubes was 3.74 ± 0.47 cm. No case required conversion to open surgery, and only one patient (5%) experienced a minor anastomotic leak. The overall complication rate was 45% (predominantly involving postoperative transient hoarseness), and no surgical mortality was observed in this study. ConclusionTotal laparoscopic intracorporeal gastric tube reconstruction based on anatomical characteristics of the surface blood supply to the stomach is safe and feasible.

Experiences with a simple laparoscopic gastric tube construction

BackgroundMinimally invasive esophagectomy (MIE) is a complex operation, and the detailed optimal surgical procedure has not been well described. Our aim was to evaluate use of a simple method of laparoscopic gastric tube construction as minimally invasive surgery for patients with esophageal cancer.MethodsWe performed a retrospective review of 26 consecutive patients who underwent MIE for esophageal cancer in the Koo Foundation Sun Yat-Sen Cancer Center between September 2009 and August 2011. Perioperative data and postoperative complications were statistically analyzed.ResultsThe patient group consisted of 22 men and 4 women. MIE was performed successfully in all patients. The mean operative time was 430.4 ± 60.6 minutes, and the mean estimated operative blood loss was 135.0 ± 97.8 mL. There were no cases of conversion to open surgery during the procedure. The postoperative complication rate was 53.8%, and there was no surgical mortality.ConclusionsWe recommend this novel method of total laparoscopic staplized formation of gastric tube to facilitate gastric pull-up.

Abstract P4-16-05: Benefit from Postoperative Radiotherapy for N1 Breast Cancer

Abstract Purpose: To evaluate the outcomes for patients with Stage II breast cancer and one to three positive lymph nodes after mastectomy who were treated with observation or adjuvant radiotherapy to the chest wall (CW) and regional lymphatics; and to identify a group of patients who benefit from postmastectomy radiotherapy (PMRT). Methods and Materials: The subjects were 716 patients diagnosed between 1990 and 2007 with Stage II breast cancer (one to three positive lymph nodes) treated with mastectomy at the Koo Foundation Sun Yat-Sen Cancer Center. 283 patients had undergone PMRT to the CW and regional lymphatics according to in-house treatment guideline or physician decision. Since 2003, we recommend PMRT for patients who had 2 or more risk factors; age less than 40 y/o, T2 disease, GrII/GrIII, prominent lymphovascular invasion (LVI), presence of extracapsular spreading (ECS), and negative Estrogen Receptor (ER(−)). Survival was analyzed by the Kaplan—Meier method. The survival free of isolated locoregional disease(LRR), metastasis free survival(MFS), disease free survival(DFS), and overall survival(OS) were analyzed according to the delivery of radiotherapy or not. Results: The median follow-up was 80 months. LRR, MFS, DFS and OS were significantly improved by PMRT. The 5- and 10-year LRR rate without PMRT was 89.9% and 81.6%, respectively and, with PMRT was 97.7% and 97.0% respectively (p &amp;lt;0.0001). The 5- and 10-year MFS rate without PMRT was 84.4% and 76.5%, respectively, and, with PMRT, was 90.8% and 87.2% respectively (p = 0.0153). The 5- and 10-year DFS rate without PMRT was 80.8% and 69.8%, respectively, and, with PMRT, was 89.6% and 86.1% respectively (p = 0.001). The 5- and 10-year OS rate without PMRT was 89.1% and 77.3%, respectively, and, with PMRT, was 94.6% and 86.2% respectively (p = 0.0039). 239 patients had less than 2 risk factors, their LRR, MFS and DFS did not benefit from PMRT. Conclusion: Our data suggest that adjuvant PMRT improve LRR, MFS, DFS and OS for stage II breast cancer with one to three positive lymph nodes who had 2 or more risk factors (Age less than 40 y/o, T2, GrII/GrIII, LVI, ECS, ER(−)). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-05.

P130Cas/Cyclooxygenase-2 axis in the control of mesenchymal plasticity of breast cancer cells

IntroductionIntrinsic plasticity of breast carcinoma cells allows them to undergo a transient and reversible conversion into mesenchymal cells to disseminate into distant organs, where they can re-differentiate to an epithelial-like status to form a cohesive secondary mass. The p130Cas scaffold protein is overexpressed in human ER+ and HER2+ breast cancer where it contributes to cancer progression, invasion and resistance to therapy. However, its role in regulating mesenchymal aggressive breast cancer cells remains to be determined. The aim of this study was to investigate the molecular and functional involvement of this adaptor protein in breast cancer cell plasticity.MethodsWe used silencing strategies and rescue experiments to evaluate phenotypic and biochemical changes from mesenchymal to epithelial traits in breast tumor cell lines. In the mouse A17 cell model previously related to mesenchymal cancer stem cells and basal-like breast cancer, we biochemically dissected the signaling pathways involved and performed functional in vivo tumor growth ability assays. The significance of the signaling platform was assessed in a human setting through the use of specific inhibitors in aggressive MDA-MB-231 subpopulation LM2-4175 cells. To evaluate the clinical relevance of the results, we analyzed publicly available microarray data from the Netherlands Cancer Institute and from the Koo Foundation Sun Yat-Sen Cancer Center.ResultsWe show that p130Cas silencing induces loss of mesenchymal features, by downregulating Vimentin, Snail, Slug and Twist transcriptional factors, resulting in the acquirement of epithelial-like traits. Mechanistically, p130Cas controls Cyclooxygenase-2 transcriptional expression, which in turn contributes to p130Cas-dependent maintenance of mesenchymal phenotype. This cascade of events also compromises in vivo tumor growth through inhibition of cell signaling controlling cell cycle progression. c-Src and JNK kinases are sequential players in p130Cas/ Cyclooxygenase-2 axis and their pharmacological inhibition is sufficient to downregulate Cyclooxygenase-2 leading to an epithelial phenotype. Finally, in silico microarray data analysis indicates that p130Cas and Cyclooxygenase-2 concomitant overexpression predicts poor survival and high probability of breast tumor recurrence.ConclusionsOverall, these data identify a new p130Cas/Cyclooxygenase-2 axis as a crucial element in the control of breast tumor plasticity, opening new therapeutic strategies leading to inhibition of these pathways in aggressive breast carcinoma.

Short-term results of thoracoscopic lobectomy and segmentectomy for lung cancer in koo foundation sun yat-sen cancer center.

Thoracoscopic lobectomy and segmentectomy have been demonstrated to be safe and technically feasible for curative resection of lung cancer. This minimally invasive surgery is increasingly popular and adopted by the world all over. We report our short-term results of thoracoscopic lobectomy/segmentectomy operations comparing with previous surgical approach for lung cancer resection by muscle-sparing vertical minithoracotomy in Koo Foundation Sun Yat-Sen Cancer Center. We performed a retrospective review of 317 consecutive patients who underwent lobectomy or segmentectomy either by thoracoscopic surgery (n=121) or muscle-sparing vertical mini-thoracotomy (n=195) for lung cancer in Koo Foundation Sun Yat-Sen Cancer center between Jan 2000 and Jun 2009. The operative details, postoperative complication, and length of stay were statistically analyzed. Thoracoscopic lobectomy and segmentectomy were performed successfully in 121 patients. One patient was converted to open thoracotomy during operation due to uncontrolled bleeding. There is no significant difference in age factors (p=0.763), forced expiratory volume in one second (p=0.480) or comorbidities (p=0.549) between these two groups. Thoracoscopic group had a significantly predominant percentage in women, diabetes mellitus, less smoking index and chronic obstructive pulmonary disease incidence. Patients undergoing a thoracoscopic surgery had a shorter length of stay (6.8±3.4 vs. 10.2±9.1 days, p<0.001), longer operative time (3.6±1.0 vs. 3.2±1.2 hours, p=0.004), and less blood loss (102.7±95.7 vs. 140.1±171.2 ml, p<0.029). There was no significant difference in postoperative complication rate between the two groups (18.2% vs. 23.6%, p=0.255). No surgical mortality was found in the thoracoscopic group. Our findings suggested thoracoscopic surgery for lung cancer would be as safe as muscle-sparing vertical mini-thoracotomy in lobectomy and segmentectomy.

Chemotherapy-related delayed bilateral spontaneous pneumothorax and lung fibrosis: methotrexate or cyclophosphamide, or both?

A 27-year-old man was diagnosed with pre-T-cell acute lymphoblastic leukemia in November 2004 and underwent chemotherapy by German multicenter ALL (GMALL) protocol (including vincristine, daunorubicin, L-asparaginase, prednisolone, cyclophosphamide, Ara-C, intrathecal methotrexate (MTX), high dose MTX and mitoxantrone) between December 2004 and March 2005 with complete remission. Because the patient refused autologous stem cell transplantation, he received two cycles of high dose cyclophosphamide (2 g/m) and one cycle of high dose CEP (cyclophosphamide 3 g/m ¥ 2 days, etoposide 100 mg/m ¥ 4 days and cisplatin 50 mg/m ¥ 2 days) during July to September 2005 as intensive consolidation. Afterward, maintenance chemotherapy with weekly MTX (intravenous injection 40 mg) and daily mercaptopurine 50 mg was applied for 2 years. The last cycle of MTX was completed on 10 January 2008, and his disease status was determined in complete remission. The patient began to feel dyspnea since May 2008. His chest radiograph showed bilateral spontaneous pneumothorax and fibrotic change in the bilateral hilar area (Fig. 1). His chest computed tomography showed ground-glass appearance at the bilateral upper lung field (Fig. 2), and his pulmonary function test showed severe restrictive lung disease (forced vital capacity: 1.06 L; forced expiratory volume in 1 s: 0.78 L/s). Then the patient received video-assisted thoracoscopic surgery for bilateral wedge biopsy and pleurodesis. The pathology of lung tissue showed bilateral lung fibrosis without the evidence of microorganism involvement (Fig. 3). The etiology of bilateral pneumothorax with severe lung fibrosis was thought to be related to methotrexate or cyclophosphamide. The patient then received high dose prednisolone (60 mg daily), but his condition and pulmonary function responded poorly to steroid treatment. Now the patient is waiting for lung transplantation. Correspondence Chung-Jen Huang, MD, Division of Pulmonary and Intensive Care Medicine, Koo Foundation Sun Yat-Sen Cancer Center, 125 Lih-Der Road, Pei-Tou District, Taipei, Taiwan 11259. Tel: (886) 2-2897011 ext. 1720 Fax: (886) 2-8972233 email: huang600517@yahoo.com Figure 1. Chest radiograph showed bilateral pneumothorax, perihilar fibrosis and severe volume reduction. The Clinical Respiratory Journal FORUM

Improving diagnosis of central venous catheter-related bloodstream infection by using differential time to positivity as a hospital-wide approach at a cancer hospital

Considering the difficulty of diagnosing catheter-related bloodstream infection (CRBSI), Koo Foundation Sun Yat-Sen Cancer Center uses differential time to positivity (DTP) as a hospital-wide approach to improve the diagnosis of CRBSI in febrile patients with indwelling central venous catheters (CVCs). This study describes the result of a hospital-wide use of DTP in a real practice setting. During January 2003-August 2007, 142 positive paired blood cultures from 125 patients without infection focus other than CVC were included. These were evaluated by DTP and semi-quantitative catheter culture (SQCC) to confirm the diagnosis of CRBSI, and were further divided into two groups: confirmed (either by DTP or SQCC) and non-confirmed CRBSI (neither DTP nor SQCC positive). Fifty-nine point two percent (84/142) of episodes were confirmed as CRBSI, of which DTP was positive in 83.3% (n=70). Non-confirmed CRBSI was associated with hematologic malignancy, neutropenia status, previous antibiotics exposure and a lower CVC removal rate. A hospital-wide approach of DTP was practical and feasible in improving the diagnosis of CRBSI in a real practice setting.

Study of Prostate Cancer Pathologic Features in Chinese Populations

To report the pathologic features of prostate cancer and its clinical outcome in the Chinese population in Taiwan. A total of 139 radical prostatectomy specimens removed at Koo Foundation Sun Yat-Sen Cancer Center from 1993 to 2001 were reviewed. The median patient age was 69 years. The histologic type was acinar adenocarcinoma in 137, mucinous adenocarcinoma in 1, and ductal adenocarcinoma in 1. The median tumor number in each prostate gland was 2. The main tumor location was distributed in peripheral zone (76.3%), followed by the transitional zone (15.1%). The Gleason score of the largest tumor was 2 to 4 in 1.5%, 5 to 6 in 7.9%, 7 in 48.9%, and 8 to 10 in 41.7%. Extraprostatic tumor extension, seminal vesicle invasion, and lymph node metastasis were found in 59.0%, 28.8%, and 13.7% of the patients, respectively. Of the 139 specimens, 56 (40.3%), 64 (46.1%), and 19 (13.7%) were pathologic Stage T2, T3, and T4, respectively. The clinical stage (P = 0.0059), serum prostate-specific antigen (PSA) level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.002), extraprostatic extension (P = 0.0012), seminal vesicle invasion (P <0.0001), and surgical margin status (P <0.0001) were all significant factors for disease progression on univariate analysis. On multivariate analysis, the serum PSA level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.03), seminal vesicle invasion (P = 0.02), and surgical margin status (P = 0.02) remained significant. The patients with prostate cancer cared for at the Koo Foundation Sun Yat-Sen Cancer Center were older and had greater PSA levels, a more advanced stage, higher grade tumors, and high positive surgical margin rates. Increased public awareness and implementing a PSA screening program in Taiwan are of crucial importance.

Prevertebral muscle involvement in nasopharyngeal carcinoma

The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC). Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors. Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p<0.001), locoregional recurrence (adjusted relative risk, 2.69; p<0.001), and distant metastasis (adjusted relative risk, 2.25; p<0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p=0.10). Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence.

Nasopharyngeal biopsy imprint cytology: A retrospective analysis of 191 cases

Patients with nasopharyngeal carcinoma (NPC) are common in Taiwan. To provide efficient management to patients, the surgeons often perform cytological imprints immediately after biopsies of lesions suspicious for NPC. The results of cytological assessment of imprints usually are reported within 30 min after biopsies. The patients with positive cytological results can then be arranged for further examinations during the same visit. We reviewed 191 imprints and corresponding biopsies from 187 patients during 1997-2004 at Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The cytological diagnoses were categorized into four groups: negative (62 cases), suspicious (8 cases), positive (116 cases), and inadequate specimen (5 cases). There were 18 false-negative and 1 false-positive diagnoses. All suspicious cases were positive histologically. Our results showed a sensitivity of 87.2% and a specificity of 97.8%. The accuracy was 89.8%. Therefore, nasopharyngeal imprint cytology is a sensitive and specific method for rapid diagnosis of nasopharyngeal cancer at an outpatient setting.

How aggressive should we be in patients with stage IV colorectal cancer?

The prognosis for metastatic colorectal cancer is grave. Whether to perform surgical resection or palliative treatment remains controversial for this advanced disease. In this retrospective study, we collected data from patients with Stage IV colorectal cancer to identify prognostic factors for predicting selection criteria for surgical treatment in patients with metastatic disease. A retrospective chart review was performed for patients treated from 1992 to 1999 from the Koo Foundation Sun Yat-Sen Cancer Center Tumor Registry. Seventy-four patients were identified as having Stage IV disease at the time of diagnosis. Data concerning the patients' demographics, laboratory results, operative procedure, mortality, morbidity, and survival were collected. Independent variables and survival time were analyzed by the independent t-test method. The difference was considered statistically significant at P < 0.05. Overall survival time for the patients with Stage IV colorectal cancer was 16.1 months. Survival in the curative resection group was significantly longer than that in the noncurative group (31.9 vs. 12.7; P < 0.016). The operative mortality and morbidity rates were 5.6 percent (4 of 71) and 21.1 percent (15 of 71), respectively. The two most common complications were leakage at the site of anastomosis and urinary tract infection. Based on these results, we conclude that patients older than 65 years, with metastases at multiple sites, intestinal obstruction, preoperative carcinoembryonic antigen level > or =500 ng/ml, lactate dehydrogenase > or =350 units/liter, hemoglobin <10 mg/dl, or hepatic parenchymal replacement by tumor >25 percent have poor prognosis for surgical intervention. Whether to perform primary tumor resection in patients with asymptomatic Stage IV colorectal cancer remains controversial; however, the more aggressively we perform radical resection and metastasectomy to selected patients, the more survival benefits the patients obtain.

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy

Purpose: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy. Methods and Patients: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease. Results: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69.4% ( p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% ( p = 0.0001). Conclusion: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.

Fine Needle Aspiration Cytodiagnosis of Liver Tumors

To present our experience with liver fine needle aspiration (FNA) diagnosis based on Riu's stain. We reviewed a total of 322 liver fine needle aspirates from 286 patients seen in a seven-year period from April 1990 to April 1997 at Koo Foundation Sun Yat-Sen Cancer Center, Taipei. Surgical and/or clinical follow-up was available for confirmation in 292 aspirates. The cytologic diagnosis was categorized into four groups: benign in 81 cases, suspicious in 13, malignant in 225, and inadequate specimen in 3 cases. There were 16 false negative and no false positive diagnoses. Two suspicious aspirates were negative. Our results showed a sensitivity of 93.3% and a specificity of 100% for the detection of malignancy. If suspicious cases were considered positive, the specificity decreased to 95.1%, while the sensitivity increased to 93.6%. Among 87 hepatocellular carcinomas (HCCs) in our series, correct FNA diagnosis was made in 84 cases with an accuracy of 96.6%. Out of 135 cases of non-HCCs, 1 was incorrectly diagnosed. The accuracy of identifying a liver malignancy as non-HCC was 99.3%. Cytologic features of HCC are well demonstrated by Riu's stain, with high accuracy in identifying them. Liver FNAs using Riu's stain combined with cell block study and clinicopathologic correlation can achieve very high sensitivity and specificity in the detection of hepatic malignancies.

T classification and clivus margin as risk factors for determining locoregional control by radiotherapy of nasopharyngeal carcinoma.

The purpose of this study was to determine risk factors that affect locoregional control of nasopharyngeal carcinoma (NPC) after radiotherapy. Computed tomography (CT) is utilized for radiotherapy planning and for identifying high risk anatomic areas. Between April 1990 and December 1993, 40 consecutive patients (1 in Stage I, 3 in Stage II, 5 in Stage III, and 31 in Stage IV) who had locoregional NPC were given definitive radiotherapy at the Koo Foundation Sun Yat-Sen Cancer Center in Taipei, Taiwan. All patients had individualized CT treatment planning. The dimension of each tumor as shown on the treatment planning CT were mapped on conventional simulation films. The extent of each tumor was further affirmed by magnetic resonance imaging (MRI) and the tumor map revised as necessary. The primary radiation fields were designed to include the primary tumor and potential spread areas with appropriate margins. Concurrent chemotherapy was also given to 35 patients (87.5%) who had positive cervical lymph nodes or primary tumors extending beyond the nasopharynx. By the end of December 1995, after a median follow-up of 42 months and minimal follow-up of 24 months, the locoregional control rate at 4 years was 84.8% (95% confidence interval [CI], 72.3-97.3), disease free survival 68.4% (95% CI, 52. 1-84.7), and overall survival 76.7% (95% CI, 63.4-90.0). The radiation field margin near the sphenoid sinus averaged 1.9 cm, the clivus margin 1.1 cm, the pterygoid fossa margin 2.0 cm, and the oral cavity margin 1.7 cm. Risk factor analysis revealed that T classification and the radiation field margin at the clivus were the most important factors for locoregional control of the tumor. The locoregional control rates were 92.6% (25/27) for T1-T3 patients and 76.9% (10/13) for T4 patients (P = 0.03). The locoregional control rates were 71.4% (5/7) for patients with a clivus margin < 1 cm and 90.6% (29/32) for patients with a clivus margin > or = 1 cm (P = 0.08). The excellent locoregional control observed in this series may be attributed to the concurrent chemotherapy and radiotherapy as well as meticulous treatment planning with CT and MRI. The precise delineation of the involved area with the aid of CT, which is taken while the patient is in the position for irradiation, serves to define the necessary safety margin of the radiation field. T classification and clivus margin are the most important factors in determining locoregional control of radiotherapy of NPC. The statistical trend observed in this study indicated that the clivus margin should be adequate to reduce the failure around the clivus, as all local recurrences were observed in this area.

Riu's stain and the cytologic diagnosis of thyroid fine-needle aspiration: a single cancer center experience.

Riu's stain, a Romanowsky-type stain, has been in use in Taiwan over the past 40 years. In order to determine whether it is useful for the diagnosis of thyroid disease in thyroid fine-needle aspiration, we reviewed 254 of these aspirates obtained between April 1990 and June 1996 from patients seen in Koo Foundation Sun Yat-Sen Cancer Center in Taipei. Surgical follow-up was available for confirmation in 61 aspirations. The cytologic diagnosis was categorized into four groups: benign, 174; suspicious, 30; malignant, 41): and inadequate specimen, 9. There were two false-negative and no false-positive diagnoses. Our results showed a sensitivity of 93.5% and a specificity of 100% for the detection of malignancy. If suspicious cases were considered positive, the specificity decreased to 55%, while the sensitivity increased to 95%. We conclude that Riu's stain is a reliable quick stain in the diagnosis of thyroid malignancy. Compared to Papanicolaou stain, it shortens the time needed for a cytopathologist to reach a diagnosis. Papanicolaou stain can be reserved for confirmation.