1237 Proton therapy for hepatocellular carcinoma: largest reported U.S. experience to date

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AASLD ABSTRACTS

1236 PROGNOSTIC EVALUATION OF HEPATOCELLULAR CARICNOMA: A COMPARATIVE ANALYSIS OF FOUR DIFFERENT STAGING SYSTEMS IN ANTI-HCV PATIENTS WITH LIVER CIRRHOSIS. ~ doardo Giannini, Federica Botta,

Paola Romagnoli, Federica Malfa~', Alessandra Fumagalli, ~ manuela Testa, ~ lena Podesth, Bruno Chiarbonello, Simone Polegato, Roberto Testa, Gastroenterology Unit and Postgraduate School of Gastroenterology, Genoa, Italy Background: Accuracy of HCC staging is an important clinical issue, since epidemiological studies have foreseen an increase in the incidence of HCC in the near future, and this trend will mostly affect hepatitis C virus (HCV) positive cirrhotic patients. Okuda staging system is historically considered the most widely used staging system for HCC. Aim: To compare the discriminatory capability and survival predictive power of newly proposed HCC prognostic system such as the Cancer of the Liver Italian Program (CLIP) score, the Groupe d'Etude et de Traitement du Carcinome H6patocellulaire (GRETCH) m o d e l and the Barcelona Clinic Liver Cancer (BCLC) staging system to the that of the Okuda staging system in a group of anti-HCV positive cirrhotic patients with HCC seen at a single centre. Methods: CLIP score, Okuda stage, GRETCH model, and BCLC stages were retrospectively computed in 81 anti-HCV positive cirrhotic patients with HCC. We evaluated the ability of these methods to assess survival prognosis and treatment allocation. Moreover, we assessed their i n d e p e n d e n t contribution to the prognostic model. Univariate survival curves were estimated using the Kaplan-Meier method and compared by using the Logrank (Mantel-Cox) test. Akaike's Information Criteria (AIC) was calculated in order to find the best model. Results: After a median follow-up of 18 months, 51 patients had died, and overall median survival was 18 months. All the staging systems significantly discriminated patients' prognosis and treatment allocation. However, both the CLIP and the BCLC scores allowed for improved prognostic definition of the patients' prognosis, especially in the long-term. (Table 1). Moreover, the CLIP score had better discriminatory ability as compared to both the Okuda staging system or GRETCH model. Noteworthy, this result was not due to the higher number of categories in the CLIP score (AIC analysis). Conclusions: We observed that all the recently proposed scoring systems for HCC are able to establish the prognosis of anti-HCV positive HCC patients, and most importantly that the results obtained in large, or multi-centre studies can be reproduced in cohorts seen at smaller or single centres in common clinical practice. The CLIP score and the BCLC staging classification showed similar characterization of the patients' prognosis, and performed better than the Okuda staging system, especially in long-term prognostic assessment. Tabfe:~:

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Disclosures: Federica Botta - No relationships to disclose Bruno Chiarbonello - No relationships to disclose Alessandra Fumagalli - No relationships to disclose

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HEPATOLOGY, October 2003

Edoardo Giannini - No relationships to disclose Federica Malfatti - No relationships to disclose Elena Podesta - No relationships to disclose Simone Polegato - No relationships to disclose Paola Romagnoli - No relationships to disclose Emanuela Testa - No relationships to disclose Roberto Testa - No relationships to disclose

1237 PROTON THERAPY FOR HEPATOCELLULAR CARCINOMA: LARGEST REPORTED U.S. EXPERIENCE TO DATE. Donald J

Hillebrand, David A Bush, Ke-Qin Hu, PaR" Radovich, Jerry D Slater, James A Slater, Loma Linda University Medical Center, Loma Linda, CA BACKGROUND: Proton Therapy is a safe, effective and welltolerated treatment option for localized hepatocellular carcinoma (HCC) as demonstrated in small series from both the U.S. and Japan. AIMS: This report details the largest presented series of U.S. patients followed prospectively while undergoing Proton Therapy for treatment of localized HCC. METHODS: From May 1998 to March 2003 a total of 50 patients with HCC have b e e n treated with Proton Therapy receiving 15 daily 4.2 Gy fractions over a 3 week period for a total of 63 Gy to the radiographic extent of the tumor(s) and a surrounding 1-2 cm margin of non-neoplastic liver. Monitoring after treatment included clinical evaluations, laboratory testing of liver and kidney function and serum AFP, in addition to every 3 months CT scans and bone scintigraphy. RESULTS: Included in this series are 32 males (64%) and 18 females (36%) with ages 64±11.4 years (range 44-86 years). Cirrhosis (median and mean Child-Turcotte-Pugh scores 7.0 and 7.2±1.7, respectively with Child-Pugh class A-19, class B-22, and class C-2) was present in 43 (86%) patients. Bridging fibrosis was present in an additional 2 (4%) patients. HCC was diagnosed histologically in 24 (48%) or by radiographic and/or serum AFP criteria in 26 (52%). Single tumors were present in 46 (92%) patients while 3 (6%) patients had 2 lesions and I patient (2%) had 3 lesions. Tumor sizes ranged from 1.3-10.7 cm, including median and mean sizes 4.5 cm and 5.2±2.6 cm, respectively. American Liver Tumor Study Group staging revealed 4 stage I (8%), 21 stage II (42%), and 25 stage III (50%) tumors. Median pretreatment serum AFP value was 70.5 ng/mL (range 2.5-185,520 ng/mL) including 18 (36%) patients with AFP values above 200 ng/mL. Proton Therapy was well tolerated. Treatment related morbidities included anorexia, nausea, abdominal discomfort, and erythema of the skin overlying the port of entry of the proton beam. Radiation-induced liver disease developed in less than 10% of patients. In 35 patients with serum AFP levels determined pretreatment and at 3 months following Proton Therapy there was a significant dramatic decrease (896.5±2660.2 vs 52.6±104.2 ng/mL, p<0.05). Tumor progression occurred at a median of 276 days in those 12 (24%) patients with demonstrated tumor progression following Proton Therapy. Overall survival is 52% at a median follow up of 541 days following completion of treatment. Actuarial survival at 3 months, 1 year, 2 years, 3 years, and 4 years is 86.0%, 75.0%, 44.4%, 36.4% and 17.9%, respectively. Survival varied among patients with stage TI+T2 compared to T3 tumors (3 months, I year, 2 years, and 3 years survival of 88.0%, 80.0%, 56.3%, and 25.0% vs 84.0%, 54.2%, 40.0%, and 31.6%, repectively). Among all patients with T1 and T2 tumors 15/20 (75%) patients continued to meet tumor-related eligibility criteria for liver transplantation at I year following treatment. Patients with T1 and T2 tumors with I year disease progression-free survival had significantly smaller tumors than patients that died or had tumor progression (3.0±1.4 cm with range 1.3-5.0 cm vs 4.1±0.7 cm with range 3.0-5.0 cm, p<0.05). A total of 9 patients have undergone definitive liver transplantation after local tumor control by Proton Therapy. Following Proton Therapy of ALTSG stage I (2), II (5), and III (2) disease including a mean tumor size of 3.6±1.5 cm (range 1.4-5.7 cm) these patients underwent liver transplantation after a median additional waiting period of 321 days. Overall post transplant survival is 88.9% (8/9) and there has b e e n no recurrence of HCC at a median follow up post transplant of 779.5 days.

HEPATOLOGY, Vol. 38, No. 4, Suppl. 1, 2003

AASLD ABSTRACTS

Conclusion: Proton T h e r a p y of localized H C C is a safe, welltolerated a n d effective t r e a t m e n t option even in elderly patients with locally a d v a n c e d t u m o r s a n d u n d e r l y i n g cirrhosis. The combination of Proton T h e r a p y for local t u m o r control followed b y liver t r a n s p l a n t a t i o n can result in l o n g - t e r m disease-free survival. Disclosures: David A Bush - N o relationships to disclose Donald J Hillebrand - N o relationships to disclose Ke-Qin H u - N o relationships to disclose Patti Radovich - N o relationships to disclose James A Slater - No relationships to disclose Jerry D Slater - No relationships to disclose

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1238 E X P A N D I N G THE SELECTION CRITERIA FOR T R A N S P L A N T PATIENTS WITH HEPATOCELLULAR C A R C I N O M A : A W O R D OF CAUTION. Bashar A Aqel, Mayo

Clinic, Jacksonville, FL; Gregory Gores, Mayo Clinic, Rochester, MN; Jeffery Steers, Mayo Clinic, Jacksonville, FL; Charles Rosen, Mayo Clinic, Rochester, MN; Victor Machicao, Denise Harnois, Mayo Clinic, Jacksonville, FL Background: Liver t r a n s p l a n t a t i o n (LT) is t h e t r e a t m e n t of choice for hepatocellular carcinoma (HCC) in the setting of liver cirrhosis. A p p r o p r i a t e p a t i e n t selection has a major i m p a c t o n p a t i e n t survival. The Milan criteria (single lesion ~ 5cm, ~ 3 lesions with total d i a m e t e r ~ 9cm) are t h e s t a n d a r d u s e d b y m o s t centers. Some centers are advocating e x p a n s i o n of t h e selection criteria (UCSF criteria: Single lesion ~ 6.5cm, ~ 3 lesions with total d i a m e t e r ~ 8cm). Aim: 1. To describe t h e o u t c o m e of LT in patients with H C C b a s e d on t u m o r size 2. To define predictors of t u m o r recurrence. Methods: Longitudinal cohort study of all patients u n d e r g o i n g LT for HCC at Mayo Clinic (Jacksonville & Rochester) b e t w e e n 1/9812/01. Pre-LT radiological data were r e v i e w e d o n all patients. Results: During the s t u d y period, 101 patients u n d e r w e n t OLT for HCC. HCC was d i a g n o s e d pre-LT in 86 patients. Fifteen patients with incidental t u m o r s on explant were e x c l u d e d from t h e analysis. Pre-LT protocol c h e m o e m b o l i z a t i o n was p e r f o r m e d in 82 patients, alcohol ablation in 2 patients a n d no t r e a t m e n t in 2 patients. All t r a n s p l a n t s were p e r f o r m e d using the piggyback technique. Based on pre-LT t u m o r description, patients were div i d e d according to the Milan and UCSF criteria. Patients w h o m e t the Milan criteria h a d significantly better t h r e e - y e a r p a t i e n t survival (p-0.006) a n d t u m o r free survival (p-0.002) after t r a n s p l a n tation w h e n c o m p a r e d with t h o s e w h o did not (figure-I). Patients t r a n s p l a n t e d outside t h e Milan criteria b u t still within UCSF criteria ( n - 1 3 ) h a d significantly poorer survival rates (p-0.004) w h e n c o m p a r e d to patients t r a n s p l a n t e d within Milan criteria (n-57)(Figure-2). T u m o r r e c u r r e n c e was s e e n in 10/29 (34.5%) of patients w h o did not m e e t Milan criteria, b u t only 8/57 (14%) w h o did m e e t t h e s a m e criteria. U s i n g Cox p r o p o r t i o n a l - h a z a r d s model, t h e following factors w e r e statistically significant predictors of t u m o r recurrence (table 1). Conclusions: E x p a n d i n g t u m o r selection criteria b e y o n d Milan criteria is associated with significant risk of t u m o r recurrence. Pre-LT AFP >100 ng/mL, vascular invasion, a n d residual viable t u m o r on explant are strong predictors of t u m o r recurrence.

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iiiiiiiiiiiiiiiiiiiii ~i~ iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii~ ~ iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii ~ii~iiiiiiiiiiiiiiiii~i3 iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii ~i~ iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii ~.si iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii ~i.c, iiiiii iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii ~!~!ii~%!~i~~i!~ii~~!~i~i~ ! ~ i i •iiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii Disclosures: Bashar A Aqel - No relationships to disclose Gregory Gores - N o relationships to disclose Denise Harnois - N o relationships to disclose Victor Machicao - No relationships to disclose Charles Rosen - No relationships to disclose Jeffery Steers - N o relationships to disclose