- Email: [email protected]
217 LONG-TERM FOLLOW-UP AFTER RADIOFREQUENCY ABLATION (RFA) FOR SMALL HEPATOCELLULAR CARCINOMA (HCC)
POSTERS 215 A PHASE II OPEN LABEL TRIAL EVALUATING SAFETY AND EFFICACY OF A TELOMERASE PEPTIDE VACCINATION IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA T.F. Greten1 , A. Forner2 , F. Korangy1 , G. N’Kontchou3 , N. Barget3 , C. Ayuso2 , L. Ormandy4 , M. Manns1 , M. Beaugrand3 , J. Bruix2 . 1 Hannover Medical School, Hannover, Germany; 2 BCLC Group, Liver Unit, Barcelona, Spain; 3 Hopital Jean Verdier, Bondy, France; 4 Hannover Medical School, Halle, Germany E-mail: [email protected] Background: The sole effective option for patients with advanced HCC is sorafenib and there is major need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. Methods: 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day −3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results: None of the patients had a complete or partial response to treatment, 17 patients (45.9 %) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+ CD25+ Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions: Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration: NCT00444782. 216 OXALIPLATIN-ASSOCIATED VASCULAR LIVER INJURY IN METASTATIC COLORECTAL CANCER: PATHOLOGIC EXAMINATION LIMITED TO SINUSOIDAL DILATION MISSES THE MAJORITY OF PARENCHYMAL INJURIES M. Guindi1 , P. Ryan2 , S. Nanji3 , A. Pollett2 , M. Moore4 , C.-A. Moulton5 , S. Gallinger5 . 1 Laboratory Medicine Program, University Health Network, 2 Dept of Pathology, Mount Sinai Hospital, 3 Division of Hepatopancreatobiliary Surgical Oncology, University of Toronto, 4 Division of Medical Oncology, 5 Division of Hepatopancreatobiliary Surgical Oncology, University Health Network, Toronto, ON, Canada E-mail: [email protected] Background and Aims: The use of newer chemotherapeutic agents prior to resection of colorectal cancer liver metastases has been with linked with parenchymal liver injury, in particular preoperative irinotecan and oxaliplatin with chemotherapyassociated steatohepatitis (CASH) and vascular parenchymal injury, respectively. In a retrospective analysis we assessed cases from 2002–2007 seen in a single centre and correlated pathologic findings of fatty disease or vascular injury with chemotherapy use. Methods: Pathologic features were scored semi-quantitatively and included: steatosis and steatohepatitis; sinusoidal dilatation; hepatic and portal vein loss; nodular regenerative hyperplasia (NRH); hepatocyte plate disruption; and parenchymal extinction lesion (PEL). A combined vascular injury (CVI) score was also determined. S92
Results: Moderate and severe fatty injury was uncommon with steatohepatitis detected in 8 cases (2.4%), 7 of whom did not receive chemotherapy. Multivariate analysis showed steatosis greater than 33% and steatohepatitis were independently associated with Body Mass Index of 30 or more (p < 0.001) but not chemotherapy. Vascular injuries were detected in 117 cases, were significantly associated with oxaliplatin, and the combined assessment of vascular features (a CVI score of 3 or more) was more strongly associated with oxaliplatin (p = 0.0004) than any one feature in isolation, including grade 2 or 3 diffuse sinusoidal dilation which was seen in 18 cases with vascular injury. Conclusion: No significant association was demonstrated in this series between the use of newer chemotherapeutic agents and CASH, but vascular injury is frequently seen in resection specimens and pathologic examination limited to assessment of sinusoidal dilation misses the majority of these. Semiquantitative measurement enables reproducible assessment of vascular injuries, allows comparison between studies, and may help inform future treatment decisions in patients with limited hepatic reserve. 217 LONG-TERM FOLLOW-UP AFTER RADIOFREQUENCY ABLATION (RFA) FOR SMALL HEPATOCELLULAR CARCINOMA (HCC) K. Hosoda1 , A. Yagawa2 , M. Hanawa1 , Y. Minai1 , S. Kobayashi1 , T. Yasumura2 , T. Ozawa2 , R. Iida1 , Social Insurance Yamanashi Hospital. 1 Internal Medicine, 2 Surgery, Social Insurance Yamanashi Hospital, Kofu, Japan E-mail: [email protected] Background: The long-term survival data following treatment of HCC using RFA are lacking. The aim of study was to examine the long-term survival outcome after RFA for small HCC retrospectively. Patients and Methods: Between June 1999 and November 2009, a consecutive series of 213 patients who have HCC ≤3 cm in size and also ≤3 tumors in number underwent RFA and followed at Social Insurance Yamanashi Hospital. RFA was performed percutaneously with ultrasound guidance using Radio Therapeutics RF 2000 generator system. To determine parameters at the time of the RFA that might predict survival, a number of variables such as age, gender, etiology, number of tumors, size of the maximum tumor, clinical stage, presence of cirrhosis, Child–Pugh classification, and presence of previous treatment were analyzed. Other 53 patients with HCC ≤3 cm in size and also ≤3 tumors in number underwent surgical resection between June 1991 and June 2008. Patients were stratified based on Japan Integrated Stage score (JIS score) and survival outcome of those who underwent RFA and surgical resection were compared. Kaplan–Meier survival analyses were applied. Comparisons between groups were performed using the log-rank test. Results: There was no treatment-related mortality. Five patients (2.3%) had major complications. All of these patients had recovered by conservative treatment. Local tumor recurrence developed in 27 of 499 tumors (5.4%). Factors that had significant effect on survival outcome after RFA were Child–Pugh classification, presence of cirrhosis and previous treatment. The cumulative survival rates at 1, 3, 5, 7and 10 years were 96.4%, 80.1%, 59.2%, 41.7% and 33.0% for patients who underwent RFA as the initial treatment and 93.8%, 72.4%, 55.0%, 43.1% and 33.5% for patients who underwent surgical resection, respectively. There were no significant differences between two groups statistically, and even when stratified according to JIS score, there were no significant differences between two groups. Conclusion: Treatment with RFA has shown significant long-term survival results comparable to surgical resection for the treatment of small HCC. RFA could be an effective first-line treatment for patients with small HCC in Japan.
Journal of Hepatology 2010 vol. 52 | S59–S182
Results: Moderate and severe fatty injury was uncommon with steatohepatitis detected in 8 cases (2.4%), 7 of whom did not receive chemotherapy. Multivariate analysis showed steatosis greater than 33% and steatohepatitis were independently associated with Body Mass Index of 30 or more (p < 0.001) but not chemotherapy. Vascular injuries were detected in 117 cases, were significantly associated with oxaliplatin, and the combined assessment of vascular features (a CVI score of 3 or more) was more strongly associated with oxaliplatin (p = 0.0004) than any one feature in isolation, including grade 2 or 3 diffuse sinusoidal dilation which was seen in 18 cases with vascular injury. Conclusion: No significant association was demonstrated in this series between the use of newer chemotherapeutic agents and CASH, but vascular injury is frequently seen in resection specimens and pathologic examination limited to assessment of sinusoidal dilation misses the majority of these. Semiquantitative measurement enables reproducible assessment of vascular injuries, allows comparison between studies, and may help inform future treatment decisions in patients with limited hepatic reserve. 217 LONG-TERM FOLLOW-UP AFTER RADIOFREQUENCY ABLATION (RFA) FOR SMALL HEPATOCELLULAR CARCINOMA (HCC) K. Hosoda1 , A. Yagawa2 , M. Hanawa1 , Y. Minai1 , S. Kobayashi1 , T. Yasumura2 , T. Ozawa2 , R. Iida1 , Social Insurance Yamanashi Hospital. 1 Internal Medicine, 2 Surgery, Social Insurance Yamanashi Hospital, Kofu, Japan E-mail: [email protected] Background: The long-term survival data following treatment of HCC using RFA are lacking. The aim of study was to examine the long-term survival outcome after RFA for small HCC retrospectively. Patients and Methods: Between June 1999 and November 2009, a consecutive series of 213 patients who have HCC ≤3 cm in size and also ≤3 tumors in number underwent RFA and followed at Social Insurance Yamanashi Hospital. RFA was performed percutaneously with ultrasound guidance using Radio Therapeutics RF 2000 generator system. To determine parameters at the time of the RFA that might predict survival, a number of variables such as age, gender, etiology, number of tumors, size of the maximum tumor, clinical stage, presence of cirrhosis, Child–Pugh classification, and presence of previous treatment were analyzed. Other 53 patients with HCC ≤3 cm in size and also ≤3 tumors in number underwent surgical resection between June 1991 and June 2008. Patients were stratified based on Japan Integrated Stage score (JIS score) and survival outcome of those who underwent RFA and surgical resection were compared. Kaplan–Meier survival analyses were applied. Comparisons between groups were performed using the log-rank test. Results: There was no treatment-related mortality. Five patients (2.3%) had major complications. All of these patients had recovered by conservative treatment. Local tumor recurrence developed in 27 of 499 tumors (5.4%). Factors that had significant effect on survival outcome after RFA were Child–Pugh classification, presence of cirrhosis and previous treatment. The cumulative survival rates at 1, 3, 5, 7and 10 years were 96.4%, 80.1%, 59.2%, 41.7% and 33.0% for patients who underwent RFA as the initial treatment and 93.8%, 72.4%, 55.0%, 43.1% and 33.5% for patients who underwent surgical resection, respectively. There were no significant differences between two groups statistically, and even when stratified according to JIS score, there were no significant differences between two groups. Conclusion: Treatment with RFA has shown significant long-term survival results comparable to surgical resection for the treatment of small HCC. RFA could be an effective first-line treatment for patients with small HCC in Japan.
Journal of Hepatology 2010 vol. 52 | S59–S182