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The imaging features of four patients with metastasis to the iliopsoas are presented with emphasis on the ultrasound, CT and MRI appearances. In patients with a known primary tumour, the possibility of iliopsoas metastasis, although uncommon should be considered.

Background Health-related quality-of-life (HRQOL) assessment with EORTC QLQ-C30 was prognostic for overall survival (OS) in patients with advance-stage hepatocellular carcinoma (HCC), but no data existed for early-stage patients. The HCC-specific QLQ-HCC18 has not been evaluated for prognostic value in HCC patients. Utilization of raw HRQOL data in clinical setting has been impractical and non-meaningful. Therefore we developed index scores of QLQ-C30 and QLQ-HCC18 in an attempt to enable clinical utilization of these HRQOL measurements. This study investigates the prognostic significance of QLQ-C30, QLQ-HCC18 and C30/HCC18 index-scores in patients with newly diagnosed HCC which encompasses all stages. Methods From 2007–2011, 517 patients were prospectively recruited. HRQOL was assessed at diagnosis using QLQ-C30 and QLQ-HCC18; C30 and HCC18 index-scores were calculated from raw HRQOL data. Cox regression was performed using continuous, dichotomized QLQ-C30 and QLQ-HCC18 variables, or index-scores, together with clinical factors to identify independent factors for OS. Various multivariate models were validated with c-index and bootstrapping for 1000 replications. Results Four hundred and seventy two patients had complete HRQOL data. Their median OS was 8.6 months. In multivariate analysis, independent prognostic HRQOL variables for OS were QLQ-C30 pain (HR 1.346 [1.092–1.661], p = 0.0055), QLQ-C30 physical functioning (HR 0.652 [0.495–0.860], p = 0.0024); QLQ-HCC18 pain (HR 1.382 [1.089–1.754], p = 0.0077) and QLQ-HCC18 fatigue (HR 1.441 [1.132–1.833], p = 0.0030). C30 index-score (HR 2.143 [1.616–2.841], p

Cumulative evidences demonstrate that epigenetic deregulations, in particular histone acetylation, play important roles in the pathogenesis and progression of hepatocellular carcinoma (HCC). Preclinical studies have shown that HDAC inhibitors are active in HCC by inducing acetylation of histones and demethylation of tumour suppressor genes, as well as leading to apoptosis. From 2008 to 2011, our group has led a multi-centered phase I/II clinical trial on the use of an HDAC inhibitor, belinostat, for HCC with the support of the National Cancer Institute and the Cancer Therapeutics Research Group. In the clinical trial, patients with advanced HCC and available histological tissues were recruited. They were treated with intravenous injection of single-agent belinostat every 3 weeks. In the phase I portion, the drug could be escalated to the maximal dose level without significant toxicity. In the phase II portion, amongst a heavily pre-treated population of advanced HCC, belinostat was associated with disease control rate of 47.6% including one case of partial response. The treatment was well tolerated with common toxicities including fatigue and injection site reaction. Toxicities of ≥ grade 3 occurred in fewer than 5% of patients. In exploratory studies, the protein expression of HR23B, a potential predictive biomarker identified by genome-wide-loss-of function screen, in histological samples of HCC was associated with the rate of stable disease (p < 0.05). Our group is currently testing the combination of HDAC inhibitors with various targeted agent. Further results will be updated in the lecture.

4073 Background: Axitinib is a potent and specific inhibitor of VEGFRs. Elevation of VEGF level in plasma and tumor is frequently observed after TACE treatment for HCC. We hypothesize that combinin...

4069 Background: Although the use of taxanes has produced encouraging response rates in patients with advanced local or metastatic gastric cancer, outcomes remain unsatisfactory. Patupilone (EPO906; epothilone B), a novel microtubule stabilizer, has demonstrated anti-tumor activity against a broad range of tumors in vitro and in animal models. The present trial evaluated the efficacy of patupilone in patients with locally advanced or metastatic gastric cancer. Methods: Patients with confirmed gastric adenocarcinoma (defined by RECIST) received patupilone 2.5 mg/m2/wk by single 5- to 7-minute IV infusion for 3 weeks, followed by 1 week off (4-week cycle). Additional inclusion criteria: WHO performance status ≤2, age ≥18 years, life expectancy ≥3 months, and no major hematologic, renal, or hepatic impairment. The primary objective of this open-label, single-arm, 2-stage, multicenter study was to determine the objective response rate (using RECIST) of treatment with patupilone in this population. Results: All 22 patients enrolled were evaluable. Mean age was 61.1 years, 63.6% were men, and 72.7% were oriental. Of 18 patients (81.8%) who completed the study, 10 (45.5%) had disease progression and 8 (36.4%) died from the disease; of 4 discontinuations, 3 were due to adverse events (AEs) and 1 to abnormal alkaline phosphatase. Overall response: 2 patients had partial responses, 6 disease stabilization, 12 disease progression, and 2 unknown. The duration of response in the 2 partial responders was 176 and 113+ days, with the latter censored at 113 days. The most frequently reported AEs were diarrhea (n = 18), nausea (n = 14), vomiting (n = 13), abdominal pain (n = 10), and fatigue (n = 10). Of these AEs, 9 were grade 3 (4 diarrhea, 3 vomiting, 1 nausea, and 1 fatigue) and 2 were grade 4 (1 nausea and 1 vomiting). Grade 4 AEs also included 1 gastric outlet obstruction and 1 dehydration. Conclusions: Patupilone resulted in an overall tumor response/disease stabilization rate of 36.4%, was well tolerated, and may prove to be a viable alternative to taxane treatment in advanced local/metastatic gastric cancer. [Table: see text]

LBA101 Background: Overexpression of PD-L1 in HCC has a poor prognosis. Safety and preliminary antitumor efficacy of nivolumab, a fully human IgG4 monoclonal antibody PD-1 inhibitor, was evaluated in a multiple ascending-dose, phase I/II study in patients (pts) with HCC. Methods: Pts with histologically confirmed advanced HCC with Child-Pugh (CP) score ≤ B7 and progressive disease (PD) on, intolerant of, or refusing sorafenib were enrolled. Dose escalation occurred in parallel cohorts based on etiology: no active hepatitis virus infection or virus-infected HCC pts. Pts received nivolumab 0.1 – 10 mg/kg intravenously for up to two years. The primary endpoint was safety. Secondary endpoints included antitumor activity using mRECIST criteria, pharmacokinetics, and immunogenicity. Results: The study has enrolled 41 pts with a CP score of 5 (n = 35) or 6 (n = 6), ECOG score of 0 (n = 26) or 1 (n = 15), 73% with extrahepatic metastasis and/or portal vein invasion, and 77% with prior sorafenib use. Eighteen pts remain on study, and 23 discontinued treatment due to PD (n = 17), complete response (CR; n = 2), drug-related adverse events (AEs; n = 2) and non-drug–related AEs (n = 2). Drug-related AEs of any grade occurred in 29 pts (71%; 17% grade 3/4), with ≥ 10% of pts experiencing aspartate aminotransferase (AST) increase and rash (each 17%), alanine aminotransferase(ALT) and lipase increase (each 15%), and amylase increase (12%). Grade 3 and 4 AEs ≥ 5% were AST increase (12%), ALT increase (10%) and lipase increase (5%). A dose-limiting toxicity occurred in an uninfected pt at 10 mg/kg; no maximum tolerated dose was defined in any cohort. Response was evaluable in 39 pts: 2 CR (5%) and 7 partial responses (PR; 18%). Response duration was 14–17+ months for CR, < 1–8+ months for PR, and 1.5–17+ months for stable disease (SD). Overall survival (OS) rate at 6 months is 72%. Conclusions: Nivolumab has a manageable AE profile and produced durable responses across all dose levels and HCC cohorts, with a favorable 6-month OS rate. Updated safety, antitumor activity, and biomarker data will be presented. Clinical trial information: NCT01658878. [Table: see text]

e15048 Background: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). Preliminary studies on mTOR inhibitors such as temsirolimus show promising results but there is limited data on the dose limiting toxicities (DLTs) in chronic liver disease, a co-morbidities commonly occurring in HCC pts. This phase I study aims to determine DLTs and maximum tolerated dose (MTD) of temsirolimus in advanced HCC. Methods: Patient (Pt) eligibilitie criteria include unresectable disease, ECOG 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, additional pts to make up to 10 patients were treated at this dose to further define toxicity. The study has been registered in ClinicalTrials.gov (NCT00321594). Results: 19 pts were entered; level I (n=3), level II (n=10), and level III (n=6). 2 of the 6 pts in level 3 developed DLT; 1 developed grade 3 syncope and 1 had treatment delay for >2 weeks due to prolonged neutropenia. In cycle 1, grade 3/4/5 toxicities included: raised ALP 2/0/0, oral mucositis 2/0/0, neutropenia 1/0/0, syncope 1/0/0, dehydration 1/0/0 and dysphagia 1/0/0. A total of 77 cycles were administered; overall grade 3/4/5 toxicities: raised ALT 2/0/0, raised ALP 2/0/0, raised bilirubin 2/0/0, cough 1/0/0, dehydration 1/0/0, dysphagia 1/0/0, dyspnea 1/0/0, abdominal distension 1/0/0, anemia 1/0/0, hemorrhoids 1/0/0, hyperglycemia 1/0/0, hypokalemia 2/0/0, hyponatremia 1/0/0, infection 5/0/0 (1 dental, 2 pulmonary, upper airway 2), oral mucositis 2/0/0, neutropenia 1/0/0, thrombocytopenia 2/0/0, pleural effusion 1/0/0, pneumonitis 1/0/0, syncope 1/0/0. Clinical benefit rate (PR, CR or SD ≥12 weeks) was 36.8% (7 of 19 pts had confirmed SD). Conclusions: At the MTD of 25 mg weekly every 3 weeks, temsirolimus is well tolerated with no DLTs. Clinical trial information: NCT00321594.

4139 Background: HCC is a common cause of cancer morbidity and mortality. For patients (pts) who are not candidate of curative surgery, chemotherapy (CT) is one of the main treatments but response has been poor due to drug resistance. In this study, using the pre-CT tumor biopsies of HCC pts who were entered into our recently reported phase III prospective randomized CT study (J Natl Cancer Inst 2005; 97(7): 536–539), we aimed to correlate selected biomarkers with CT responsiveness and survival. Methods: 188 HCC pts were entered into the CT study. They were separately consented for the present correlative study. CT response was based on WHO criteria. For the purpose of this study, pts were categorized into CT-‘responsive’ group (those who obtained clinical benefits and achieved CR, PR or SD) and CT-‘non-responsive’ group (those who developed PD). Immunohistochemical staining for Ki67, topo IIa, MRP1, p53 and p-gp were performed on the pre-CT tumor biopsies; findings of which were analyzed with conventional clinical variables to identify factors that influenced CT response and survival. Results: 149 pts had pre-CT tumor biopsies available and were thus included in the present analysis, 1 pt was not assessable for response; there were 75 pts in the CT-‘responsive’ group (23 PR and 52 SD) and 73 pts in the CT-‘non-responsive’ group. The overall median survival was 7.9 months. Using multivariate analysis, predictors of response to CT were Ki67 positivity (p = 0.0427; OR = 0.475), MRP1 positivity (p = 0.0323; OR = 0.429), age (p = 0.0027; OR = 1.056) and albumin level (p = 0.0130; OR = 1.108). Predictors of survival included Ki67 positivity (p = 0.0097; HR = 1.662), topo IIa positivity (p = 0.0358; HR = 1.566), total bilirubilin level (p = 0.0006; HR = 1.039) and ALT level (p = 0.0092; HR = 1.005). Conclusions: In addition to conventional factors, Ki67 and MRP1 positivity are predictors of response to CT, while Ki67 and topo IIa positivity are predictors of survival. The present study demonstrates that immunohistochemical staining of biomarkers can be instrumental in highlighting genes in the drug-resistant phenomenon of HCC. Acknowledgements: This study has been supported by the Direct Grant of Chinese University of Hong Kong, project no. 2041124. No significant financial relationships to disclose.

5608 Background: Brain metastasis (mets) from nasopharyngeal carcinoma (NPC) is a controversial entity. Only 2 cases had ever been reported and no cohort study performed. Methods: We reviewed the clinical follow-up of a cohort of 1124 NPC cases first seen in our institute from 1993 to 2000, and identified 3 cases with intracranial mets on follow-up. All 3 patients received whole brain radiation therapy (WBRT) for the brain mets. Results: Case #1: A 45-year-old man presented with Stage T1N2M0 disease in 1996. In 2001, disease recurred in the neck and was inoperable. Static disease was achieved with chemotherapy. 1 year later, he experienced vertigo. Contrast CT brain revealed enhancing cystic lesions in both cerebellums. Histology of the lesion revealed metastatic undifferentiated carcinoma, staining positive for Epstein-Barr virus-encoded RNA (EBER). He received WBRT and remained alive at the most recent follow-up, which was 1 year after the diagnosis of brain mets. Case #2: A 51-year-old man presented wi...

8157 Background: CHM is a common complimentary and alternative medicine used by both East and West cancer patients for reduction of chemotherapy-induced toxicity. A double-blind placebo-control ran...

e15513 Background: HCC is a common cause of morbidity and mortality. CT has been one of the treatments offered to patients (pts) who are not candidate of curative surgery. Treatment of HCC could be complicated by underlying CLD. In this study, we aimed to assess pre-CT severity of CLD on treatment outcome of HCC pts who were entered into our previously reported phase III prospective randomized CT study (J Natl Cancer Inst 2005). Methods: The severity of CLD for each pt was arbitrary assessed by adopting the Child-Pugh's classification. Patients’ characteristics were compared. Treatment outcomes in terms of responses, survival and treatment-related toxicities (NCI CTC) were compared. Results: 160 were Child's A; 28 were Child's B. Proportion of pts with cirrhosis (45% vs 71%, P=0.01) and pre-CT bilirubin level (11 vs. 15 umol/l, p=0.02) were significantly higher, while age (52 vs 45 yrs, p=0.05) and albumin level (35 vs 30 g/l, p No significant financial relationships to disclose.