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Purpose:To study the dynamic changes in plasma Epstein–Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC).Experimental Design:We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS).Results:We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation.Conclusions:Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.

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Purpose: Current immunomagnetic enrichment method can only detect general epithelial antigens of circulating tumor cells (CTC). Further characterization of the CTCs to provide specific information on the tumor type is not possible. We attempted to overcome this drawback by developing the methodology for using a gastrointestinal-specific anti-cytokeratin (CK) 20 antibody to detect CTCs in colorectal cancer patients' blood.Experimental Design: The protocol was validated using a colorectal cancer SW480 cell line. The clinical significance of findings in colorectal cancer was investigated by detecting CK20-positive CTCs (pCTC) in patients with colorectal cancer, other common cancers, colorectal adenoma, benign colorectal diseases, and normal subjects. Moreover, the malignant nature of CK20 pCTCs was examined by comparing chromosome 17 aberration patterns with those from the corresponding primary tumors.Results: The assay successfully showed CK20-positive SW480 cells. When applied in patient samples, the detection rates were 62% (132 colorectal cancer patients; median number = 11 CTCs), 0% (120 patients with other common cancers), 6% (50 colorectal adenoma patients), 0% (120 patients with benign colorectal diseases), and 0% (40 normal subjects). Furthermore, statistical analysis showed that CK20 pCTC numbers were associated with tumor-node-metastasis stage and lymph node status. Using the median CK20 pCTC numbers as the cutoff points, stratified groups of colorectal cancer patients had significant differences in their recurrence, metastasis, and survival. Finally, chromosome 17 aneusomy in 90% of colorectal cancer patients with CK20 pCTCs matched with those from the primary tumors.Conclusions: Detection of CK20 pCTCs using the new protocol could generate clinically important information for colorectal cancer patients.

Supplementary Tables S1-S3 from Clinical Significance of Cytokeratin 20-Positive Circulating Tumor Cells Detected by a Refined Immunomagnetic Enrichment Assay in Colorectal Cancer Patients

To compare transarterial chemoembolization (TACE), transarterial radioembolization using Yttrium-90 (TARE), and transarterial ethanol ablation (TEA) for huge hepatocellular carcinoma (HCC) in treatment responses and long-term survival outcomes.In this retrospective study approved by institutional committee, inclusion criteria were tumour ≥ 10 cm, newly diagnosed, treatment naïve, Child A, Performance Score 0 or 1, no venous invasion or extrahepatic disease on contrast-enhanced CT or MRI. There were 107 patients (Supportive Care [SC] 17, TACE 54, TARE 17, TEA 19). Survival outcomes of SC and TACE were compared (TACE selected as benchmark for transarterial treatments). Tumour response and overall survival (OS) of the three groups were compared.OS of TACE (vs. SC) was significantly longer (9.9 [5.9, 24.1] months versus 2.8 [1.5, 10.2], p = 0.001). Complete response of TEA was significantly better (TEA 10/19 [52.6%] versus TARE 2/17 [12.5%], p = 0.013, versus TACE 9/54 [16.7%], p = 0.002). OS of TEA (vs. TACE) was significantly longer (21.6 [12, 41] months versus 9.9 [5.9, 24.1], p = 0.014, hazard ratio 0.6 (0.3, 1). OS of TEA (vs. TARE) was longer (21.6 [12, 41] months versus 11.9 [7, 28.7], p = 0.082, hazard ratio 0.6 (0.3, 1.3) in favour of TEA).In patients with huge HCC, transarterial treatment as represented by TACE had a survival benefit over supportive care. In this retrospective analysis, TEA was associated with better tumour response and survival outcome as compared to TACE or TARE; therefore, transarterial treatment could be useful for prolonging patient survival, and TEA could be a preferred option.

We focus on the emerging data from randomized clinical trials for optimal integration of induction, concurrent, and/or adjuvant chemotherapy with intensity-modulated radiotherapy in locally advanced nasopharyngeal carcinoma (NPC), and the use of plasma Epstein-Barr virus (EBV) DNA for risk stratification.Several phase 3 trials have shown that induction chemotherapy followed by concurrent chemoradiation (CRT) improved overall survival or disease-free survival when compared to CRT alone in stage III/IV NPC who is at high risk of distant metastases. The benefit of adjuvant chemotherapy following CRT when compared to CRT alone is uncertain. There are increasing clinical data supporting the use of plasma EBV DNA for risk stratification. There are growing clinical data supporting the integration of immune checkpoint inhibitors into the induction, concurrent, and/or adjuvant/maintenance phase of treatment in locally advanced NPC.Concurrent chemoradiation remains the standard treatment backbone in locally advanced NPC. There is level 1 evidence for induction chemotherapy followed by CRT in stage III/IV NPC. There is increasing evidence against the indiscriminate use of adjuvant chemotherapy following CRT. With the increasing treatment intensification, future treatment algorithm in NPC should incorporate plasma EBV DNA and other biomarkers for risk stratification and treatment selection.

In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients' prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received 'prophylactic lamivudine' prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.

Hepatitis B virus (HBV) reactivation is a well-described complication in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. As chemotherapy is used increasingly in cancer patients, HBV reactivation during cytotoxic treatment may become a more common problem. In lymphoma patients, the incidence of chronic HBV infection has been reported to be 26%, of whom 47% developed HBV reactivation during chemotherapy. However, corresponding data for patients with other malignancies undergoing cytotoxic chemotherapy are not known. In this prospective study, hepatitis B surface antigen (HBsAg) was determined in 626 consecutive cancer patients who received cytotoxic chemotherapy over a 12-month period. Seventy-eight patients (12%) were found to be HBsAg positive. Thirty-four (44%) developed raised alanine transaminase during their course of chemotherapy. In these 34 patients, hepatitis was attributed to HBV reactivation in 15 patients (44%), chronic active HBV infection in 1 patient (3%), hepatitis C infection in 1 patient (3%), malignant hepatic infiltration in 2 patients (6%), and the use of hepatotoxic chemotherapeutic agents in 11 patients (32%). The causes of hepatitis were unknown in 4 patients (12%). HBV reactivation was more likely to develop in patients who were male, younger age, HBeAg seropositive, and those with lymphoma. Presence of malignant hepatic infiltration, baseline pre-treatment alanine transaminase, total bilirubin, and HBV DNA levels did not correlate with the development of HBV reactivation. Of the 15 patients who developed HBV reactivation, antiviral therapy with lamivudine was available and used in 9. There was no HBV-related mortality during chemotherapy. It is concluded that in patients with chronic HBV infection under chemotherapy, HBV reactivation occurs in nearly 20% of them and accounts for 44% of hepatitis cases. The risk factors identified include male sex, younger age, HBeAg seropositive, and the diagnosis of lymphoma. In HBV endemic areas, patients with risk factors for HBV reactivation should be identified prior to receiving cytotoxic treatment and monitored closely. The potential benefit of lamivudine requires further confirmation.

BACKGROUND Chemotherapy containing anthracycline is the standard initial treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International Prognostic Index (IPI) is widely accepted as the standard tool for determining the prognosis of patients with this disease. However, the data on which the IPI was based primarily came from studies conducted in Western countries. It may not be directly applicable to Asian populations, in which the incidence of primary extranodal lymphoma (PENL) is known to be high. METHODS The authors conducted a retrospective study of 218 patients with aggressive NHL who were treated with chemotherapy. They analyzed the distribution of stage and pathology, prognostic factors, toxicity, and treatment outcome. The IPI was then applied and its ability to identify distinct prognostic groups tested. RESULTS Eighty-six patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation, bulk of disease, and histologic confirmation at an extranodal site). The most common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar ring (18.9%). The complete response rate of PENL patients to chemotherapy containing anthracycline was 52%, as compared with 64% of the LNL group. The 5-year survival rates for patients with LNL and PENL were 57.4% and 52.1%, respectively. The toxicity in the two patient groups was similar. Four of the prognostic factors in the IPI–age, serum LDH, performance status, and disease stage–predicted significantly different survival for PENL and LNL patients. However, the number of extranodal sites involved was not a significant predictive variable in PENL. CONCLUSIONS The IPI was applicable to this Chinese population in which the incidence of PENL was high, although the number of extranodal sites did not achieve statistical significance as a risk factor. A proposal for modification was made. Chemotherapy containing anthracycline was an effective treatment for both PENL and LNL patients. Cancer 1998;82:2439-2448. © 1998 American Cancer Society.

Docetaxel is a commonly-used anti-cancer chemotherapeutic agent given its efficacy in a large variety of solid tumors. It is associated with various adverse effects one of which is nail toxicity. We report a case of severe onycholysis as a result of treatment with docetaxel in a patient who suffered from metastatic nasopharyngeal carcinoma. The case report will be followed by a discussion on the possible mechanism and preventive strategies for taxane-induced nail toxicity.

HCC is a common cause of morbidity and mortality. For patients who are not candidates for curative surgery, systemic chemotherapy is one of the standard treatments. In parts of China and the Far East, over 80% of HCC patients have chronic HBV infection. In this study, we aimed to assess the relationship between pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection status was determined prior to chemotherapy in 188 patients, 170 of whom had evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody–positive). Of these, 125 had pretreatment HBV DNA levels determined via real-time PCR. Virological data were analyzed using conventional clinical variables to identify factors that influenced survival. Multivariate analysis revealed that high total bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 μM increase; 95% CI 1.015–1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606–30.129), and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076–2.531) affected survival significantly. Exploratory analysis revealed that high levels of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis during chemotherapy. Conclusion: For HCC patients with HBV chronic infection/exposure, a high viral load prior to treatment is an adverse factor for survival and may be associated with a higher incidence of severe hepatitis during chemotherapy. Future strategies to improve the prognosis of HCC patients undergoing chemotherapy should consider supportive therapy that incorporates antiviral therapies to reduce HBV viral load. (HEPATOLOGY 2007;45:1382–1389.)

To evaluate the applicability of the University of California Los Angeles Integrated Staging System (UISS) in predicting the prognosis of Chinese patients with localized renal cell carcinoma after radical nephrectomy, with reference to that reported by Patard et al in an international multicenter study (J Clin Oncol 2004, 22:3316-3322).One hundred and twenty-eight Chinese patients with localized renal cell carcinoma were stratified into low risk (LR), intermediate risk (IR) and high risk (HR) groups according to the UISS, based on the TMN staging and Fuhrman grading of the tumor and the Eastern Cooperative Oncology Group performance status of the patients. The survival curves of each risk group were then calculated.The number of patients in the LR, IR and HR was 24 (18.8%), 94 (73.4%) and 10 (7.8%) respectively. The estimated 2-year survival rates were 100%, 89.9% and 100% for the LR, IR and HR groups respectively. Whereas the estimated 5-year survival rates were 93.3%, 72.4% and 80% for the LR, IR and HR groups respectively. The LR and IR patients had comparable 2-year and 5-year estimated survival rates with those reported by Patard et al. However, the estimated survival rate for HR patients was better than that reported.UISS provided a valuable tool in predicting the survival of Chinese patients with localized renal cell carcinoma of LR and IR groups, as reported in other international centers. Further large scale study may be needed to confirm the applicability in HR population.

Background: Patients with unresectable hepatocellular carcinoma (HCC) have a dismal prognosis. The objective of this study was to evaluate whether patient-reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument is predictive of survival for these patients. Materials and methods: Two hundred and thirty-three patients with unresectable HCC (mainly hepatitis B-associated) who were recruited into two separate randomized phase III clinical studies, based on palliative chemotherapy and palliative hormonal therapy, respectively, gave consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and clinical variables at the time of study entry were analyzed to identify factors that influenced survival by applying multivariate analysis. Independent prognostic factors for survival were studied by Cox regression analysis. Results: Median survival of the 233 patients was 5.5 months (95% CI 4.2–6.5 months). Significant independent predictors of shorter survival were advanced Okuda staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR = 1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10 point increase = 1.070). Patients who were entered into the chemotherapy trial (P = 0.0002; HR = 0.503), those who scored better in the physical functioning domain (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were associated with longer survival. Conclusions: In the studied HCC population, patient-reported baseline QoL provides additional prognostic information that supplements traditional clinical factors, and is a new prognostic marker for survival for patients with unresectable HCC.

Background: Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma (HCC), but the response rate is low (

Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in southern China and South East Asia. Epidermal growth factor receptor (EGFR) has been proposed as a new target for anticancer therapy. EGFR was over-expressed in 85% of NPC tissues and was associated with poor prognosis.EGFR protein expression in four NPC cell lines, CNE-2, HONE-1, HK1 and C666-1, was examined by Western immunoblotting. The antitumor effect of cetuximab was studied in the cell lines, either alone or in combination with cisplatin or paclitaxel.EGFR protein expression was highest in the HK1 cell line, moderate in CNE-2 and HONE-1, and lowest in C666-1. Single agent cetuximab demonstrated significant antitumor effect in the HK1 and HONE-1 cell lines, but minimal activity in CNE-2 and C666-1 cells. When cetuximab was combined with cisplatin or paclitaxel in the HK1 and HONE-1 cell lines, an additive enhancement of cytotoxic drug activity was demonstrated.Cetuximab demonstrated single agent activity selectively in NPC cell lines with moderate to high EGFR protein expression. Cetuximab could also additively enhance the antitumor effects of cisplatin or paclitaxel in these NPC cell lines. These results support the rationale of combining cetuximab with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC. Future studies should aim at defining the predictive markers for response to cetuximab in order to select the responsive tumor for the correctly targeted agents.

Breast cancer is a rapidly increasing problem in many developing countries, and cytotoxic chemotherapy is now an integral part of its management. In several developing countries, the carriage of hepatitis B virus (HBV) in cancer patients may be as high as 12%, and such patients are at risk of developing fatal HBV reactivation during chemotherapy. HBV reactivation is well recognized in patients with hematological malignancies, but limited data are available on patients with other, more common, cancers, such as breast cancer. Recent data have suggested that increased viral replication, an indication of HBV reactivation, may precede clinical hepatitis. In the absence of serial HBV DNA monitoring, HBV reactivation during chemotherapy may have been underestimated. In this prospective study, breast cancer patients who were hepatitis B surface antigen (HBsAg) seropositive were followed up during chemotherapy. The main objectives were to determine the incidence of HBV reactivation in breast cancer patients undergoing conventional chemotherapy; to investigate whether "serial HBV DNA monitoring" improves the accuracy of diagnosing HBV reactivation when compared with previous schema that only measured HBV DNA at the time of clinical hepatitis ("conventional monitoring"); and to assess the clinical consequences as a result of developing the condition. The secondary objective was to identify risk factors associated with this condition. Over an 18-month period, 41 patients were studied. Ten developed HBV reactivation by conventional monitoring criteria, but with serial HBV DNA monitoring, seven additional patients were diagnosed when increased HBV DNA levels were detected before, but not concomitant with, clinical hepatitis. Thus, a total of 17 patients (41%) developed HBV reactivation. Premature termination of chemotherapy or delay in treatment schedules occurred in 71% of the patients who developed viral reactivation, as compared with 33% in those who did not develop the condition (P = 0.019). No risk factors associated with the development of HBV reactivation could be identified. Serial monitoring of HBV DNA, in addition to liver function, increases the sensitivity of diagnosing of HBV reactivation, and helps explain some cases that would otherwise be labeled as "cryptogenic hepatitis," for which concomitant HBV DNA measured at the time of hepatitis was undetectable. The present study highlights the importance of monitoring HBsAg-seropositive patients who are receiving chemotherapy for common solid tumors such as breast cancer.

A cohort of 85 Chinese breast cancer patients who received adjuvant chemotherapy with doxorubicin and cyclophosphamide was found to have a significantly higher incidence of grade 3 (n=44, 52%) and grade 4 (n=21, 25%) neutropenia when compared with an historic Western cohort. Also noted was a higher incidence of hepatotoxicity (n=8, 9%). When compared to Caucasian patients, the higher myelotoxicity in our patients may be related to ethnic variation in susceptibility to chemotherapy-related toxicity, lower body mass index with higher percentage of body fat composition, and the popular practice of concurrent alternative medicine during chemotherapy. The higher incidence of hepatoxicity was possibly associated with endemic chronic hepatitis B infection in this geographical area.

The TT virus (TTV), a member of a family of human viruses related to the circoviridae viruses, was associated initially with acute and chronic liver diseases. TTV consists of a single-stranded, circular DNA genome of 3.8 kilobases (kb) and at least three open reading frames (ORFs). The objective of the present study was to determine whether or not TTV replicated in peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs). DNA was extracted from the PBMCs or BMCs of 153 cancer patients and from the PBMCs of 50 healthy blood donors (the controls). By using a single round of polymerase chain reaction (PCR), TTV was detected in 98.6% (141 of 143) of the PBMCs and in 90% (9 of 10) of the BMCs from cancer patients. TTV DNA was detected in significantly fewer control subjects at 86% (43 of 50; P

Aim: TACE is associated with an upregulation of VEGF leading to revascularization. Axitinib is a potent and selective inhibitor of VEGFR1, 2 and 3. We hypothesized that the addition of axitinib to TACE has synergistic activity by abolishing the VEGF driven signal after TACE. To prove this concept, we designed a phase II study to evaluate the efficacy and safety of the combination for treatment of inoperable HCC. Methods: This is an investigator-initiated phase II single-arm study. The target sample size is 50. Key eligibility criteria include confirmed diagnosis of inoperable HCC; Child's A liver function; ECOG PS 0-2; absence of prior systemic nor TACE treatment; the absence of main portal vein thrombosis or distant metastases. Treatment consists of 8 weekly cycle of axitinib 5mg twice daily. In each cycle, TACE is administered at 5th week when there is radiologically viable tumour and absence of ≥grade 3 toxicity from axitinib. Axitinib is withheld 24h before each TACE, and resumed 24h after TACE when patients (pts) have preserved liver function. Reassessment imaging is done every 8 weeks. In the 1st year, each pt is treated with a maximum number of 6 cycles of TACE. Pt is put on maintenance axitinib alone if there is no PD after 1 year. Results: Total 50 pts have been accrued. Baseline characteristics: BCLC stage B 38; C 12. Median age 62.1years. At the time of data cutoff on 17 Apr 2014, the median follow-up was 1.32 years. 27 pts have PD, and the median TTP is 10.4 months (95% CI = 5.43-13.72). The median OS is 15.9 months (95% CI = 12.9-not reached). Amongst 42 evaluable pts, the response rate (mRECIST) is 48.8% (7 CR; 14 PR) and the disease control rate is 88.4% (21 CR/PR and 16 SD). Amongst the responders, 3 pts underwent hepatectomy after shrinkage of tumour, and surgical specimen showed extensive tumour necrosis; 2 pts just had portal vein embolization to induce left lobe hypertrophy, and is currently wait-listed for hepatectomy. Total 5 pts could proceed to the axitinib maintenance phase. Common ≥grade 3 toxicity events from axitinib include hypertension (20%), hand foot skin reaction (10%), fatigue (4%) and hyperbilirubinaemia (4%). The toxicity of TACE is not worsened by axitinib. Conclusions: Combination of axitinib and TACE is associated with high tumour response rate and efficacy in unresectable HCC. Further evaluation with randomized study is indicated. (NCT01352728) Disclosure: S.L. Chan: received research funding from Pfizer. All other authors have declared no conflicts of interest.

TT virus (TTV) is a recently described circular DNA virus of about 3.8 kb, which is related to the circoviridae viruses. It is commonly detected in healthy subjects and no association with any specific disease has been established. TTV was initially thought to be hepatotropic, but subsequent reports have shown that it is detectable in other tissues, including kidney, prostate, mammary gland, brain, bone marrow, and peripheral blood mononuclear cells. Plasma samples from cancer patients and healthy subjects were tested for the presence or absence of TTV by heminested polymerase chain reaction (PCR). We also developed a quantitative competitive PCR (QC-PCR) assay for TTV that permits accurate measurement of TTV DNA load. Using this assay, the TTV genome load in peripheral blood mononuclear cells (PBMCs) of healthy control subjects (n = 50) and patients with various types of cancer (n = 148), including breast cancer, non-Hodgkin's lymphoma, colon cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and other cancers, was measured. TTV DNA was detected in 69 of 100 plasma samples (69%) of cancer patients tested and in 39 of 100 plasma samples (39%) randomly selected from 1000 plasma samples of blood donors (p0.05). TTV DNA was detectable in the PBMCs of 99% of the cancer patients and 86% of the controls. However, the median virus load was more than 100-fold higher in the cancer patients (3599 copies/100,000 cells) than among the controls (30 copies/100,000 cells; p0.0001). There was no significant difference in TTV load among the different cancer types. Using a cutoff value of250 copies per 100,000 PBMCs, 93.2% of cancer patients were "positive" compared to only 4% of healthy control subjects. Almost all the cancer patients have TTV infection and their TTV genome load in PBMCs is significantly higher than that in control subjects. It remains to be elucidated whether such findings are specific to cancer patients or occur in all seriously ill subjects.

4591 Background: Prognosis of patients with HBV-related chronic liver disease and hepatocellular carcinoma (HCC) depends on both extent of tumor involvement and functional hepatic reserve. The Chin...

15081 Background: Hepatocellular carcinoma (HCC) is a common cause of cancer morbidity and mortality. It is a highly aggressive tumor with 90% presenting with unresectable disease, resulting in a median survival of 3–6 months. Inhibitors of histone deacetylase (HDAC) have been demonstrated in HCC cell lines and xenografts to induce apoptosis and tumor regression, and have anti-proliferative, anti-metastatic and anti-invasive effects. Belinostat (N-hydroxy-3-[phenylsulphamoylphenyl] acryl amide) is a novel, low molecular weight, HDAC inhibitor. The Cancer Therapeutic Research Group (CTRG) is conducting a phase I/II study of belinostat as the first line therapy for pts with unresectable HCC. The phase I study aims to determine dose limiting toxicity (DLT) and maximum tolerated dose (MTD). Methods: Patient eligibilities include histologically or cytologically confirmed unresectable HCC, ECOG = 2, adequate hematologic, renal and hepatic functions. The dose of belinostat was started at 600 mg/m2/day i.v. on day 1–5 every 3 weeks; with increment of 300 mg/m2/day up to 1200 mg/m2/day. Dose limiting toxicities (DLT) are defined as grade 4 hematological toxicity or grade 3 or 4 nonhematological toxicity during cycle 1 (according to NCI CTC v3), or treatment delay >2 weeks. The MTD is defined as the dose below which ≥ 2 of 3 or ≥ 2 of 6 patients experiencing DLT. After determination of the MTD, 3 additional patients will be treated at this dose to further define toxicity. Results: From June-December 2006, 12 pts were entered; 3 were treated at level I (600 mg/m2/day), 3 at level 2 (900 mg/m2/day), and 6 at level 3 (1200 mg/m2/day). There were no DLTs on level 1, 2 or 3. Therefore, the MTD of belinostat was not reached. Overall toxicities were WBC gr. 0/1/2/3/4: 12/0/0/0/0, ANC gr. 0/1/2/3/4: 12/0/0/0/0; Hb gr. 0/1/2/3/4: 4/7/0/1/0; platelet gr. 0/1/2/3/4: 8/4/0/0/0; lethargy gr. 0/1/2/3: 12/0/0/0/0, phlebitis gr. 0/1/2/3: 10/0/2/0; Cough gr. 0/1/2/3: 9/0/3/0; Nausea gr. 0/1/2/3: 7/3/2/0 and vomiting gr. 0/1/2/3: 9/3/0/0. Conclusions: At the maximum dose of 1200 mg/m2/day (level 3), MTD has not been reached. Belinostat is very well tolerated. Phase II study will be started at dose level 1200 mg/m2/day. Sponsor: The Division of Cancer Treatment and Diagnosis, National Cancer Institute, USA. No significant financial relationships to disclose.

20026 Background: In order to obtain a good prognostic model for HCC, clinical data alone may not be adequate. DNA microarray technology has enabled quantification of thousands of genes in a single assay but it has the inborn drawback of high background noise. In order to deal with the problem of information overflow, we developed multivariate dependencies approach using CGH to guide the initial modeling process. This approach takes into account the multivariate nature and potential interaction among the genes during the prognostic modeling process. Methods: The study includes 165 patients with CGH data containing 858 regions/bands. The clinical outcome is survival at 1.72 years. Potential prognostic factors include CGH regions, albumin, ALT, bilirubin, AFP, ascites, alkaline phosphatase (ALP), tumor size, and encephalopathy. We used a blocked wavelet-shrinkage principal component analysis (BWSPCA) to reduce the dimension of CGH data with respect to clinical outcome and followed by logistic regression. We compared the BWSPCA with PCA alone, supervised PCA (Bair et al. 2004), and supervised BWSPCA. Results: Among the 165 patients, 133 (80%) were male, average age of 54.8 years, 78 (47%) stage I-II and 75 (45%) ECOG 0–2. PCA alone and supervised PCA models failed to identify significant CGH regions. BWSPCA model includes tumor size (p = 0.005), albumin (p = 0.047), ALP (p = 0.025), Chr.6q25.1 (p = 0.031), Chr.12q24.32 (p = 0.012), Chr.Xq28 (p = 0.035). Supervised BWSPCA approach includes tumor size (p = 0.016), ALP (p = 0.002), Chr.12q24.11 (p = 0.047). The area under the receiver operating curve (ROC) for the BWSPCA model was 0.78 with a sensitivity and specificity about 0.8 and 0.6 respectively. Conclusions: PCA alone is not effective in identifying CGH regions as prognostic factors. Supervised learning approach did not improve the results. The BWSPCA method identified a number of significant CGH regions associated with survival outcome for HCC patients. These results would be verified in future study. This method will be extended and applied to develop prognostic models using both CGH and DNA microarray data. Acknowledgement: This study is funded by the Research Grant Council of Hong Kong #CUHK4469/03M. No significant financial relationships to disclose.

Natural killer T-cell lymphoma (NKTL) of the nasopharyngeal regions is an aggressive tumor of dismal prognosis. We describe in a 19-year-old female, a primary gingival NKTL diagnosed by morphology, immunohistochemistry, and EBV-encoded RNAs, associated with the longest reported survival despite relapses in the nasal cavity.