Topic: March 2012 Society of Surgical Oncology Poster Presentations
Here is a synopsis of the poster presentations that pertain to our specific cancer. I have taken photos of each poster, and if anyone would like me to email them, please let me know. With an email, I can forward on the detailed data, i.e. graphs, pie charts, scans, etc. or upload to a doc and email the link.
Remember that this is very technical jargon. It is posted as it was found on the presentation materials.
In further postings I will attempt to attach all links for detailed info.
Thank you much!
Phase 2 Trial Results for Sunitinib and Transarterial Chemoembolization (TACE) in Inoperable Hepatocellular Carcinoma. (HCC)
Y.V. Wu, C.M. Tomaszewski, G.J. Fetterly, B. Kuvshinoff, A. Groman, N.W. Wilkinson, N.I. Khushalani, R.V. Iyer.
Roswell Park Cancer Institute, Buffalo, NY.
Hepatocellular cancer (HCC) is rapidly fatal vascular endothelial growth factor driven cancer. Both TACE and targeted anti-angiogenic therapies have been shown to improve outcomes in patients with inoperable HCC. High intratumoral pressure and vasucal permeability limits delivery of chemo during TACE. High VEGF expression correlates with poor response to TACE and neo angiogenesis occurs after TACE that promotes tumor growth and progression. Sunitinib, a potent inhibitor of VEGF driven antiogenesis, and vascular permeability may allow better delivery of TACE, and prevent neoangiogenesis after TACE.
Sunitinib is an oral small molecule tyrosine kinase inhibitor of VEGFR 1, 2, 3, PDGF alpha and beta, Flt3, KIT, CSF 1R and RET. Binding of sunitinib to VEGFRs has been correlated with decrease in the spliced variant of soluble VEGFR2 and circulating monocyte numbers, we examined these markers and correlated them with sunitinib pharmacokinetics (PK) and other clinical outcomes in this prospective trial.
To estimate the Progression Free Survival (PFS) in patients with advanced inoperable HCC.
To estimate the Overall Survival (OS), radiological response rate (RR) by RECIST, quality of Life using the FACT-HEP scale and toxicity of all pts on study.
Correlation of clinical outcomes with functional imaging response assessed by DCE-MRI (Ktrans, AUC 90, % necrotic tumor), sunitinib PK, soluble VEGFR2 levels and monocyte numbers.
1. Patients with histologically or biochemically confirmed HCC that is inoperable and involves 50% or less of the liver parenchyma.
2. Child Pugh Class A or B cirrhosis
3. ECOG performance status 0 or 1.
4. Adequate hematologic, hepatic and renal parameters (Platelets equal to or greater than 100K, Bilirubin less than or equal to 2mg/dl)
5. Written informed consent.
1. Impedence to hepatopedal flow/ other contraindication to TACE.
2. Known allergy to the study drug, iodinated contrast, or doxorubicin.
3. Prior liver transplant.
4. Prolonged Qtc
5. Other uncontrolled comorbid illness.
Design: This is a single arm, multicenter phase II trial. A total of 37 eligible patients will be enrolled.
Treatment: Cycle 1-Sunitinib 37.5mg PO QD days 1-7 followed by TACE with doxorubicin in lipiodol on day 8, continued sunitinib 37.5mg PO QD day 15-36 followed by 2 weeks off. Cycle 2 onwards- sunitinib 4 weeks on and 2 weeks off, with dose escalation to 50 mg in pts without any grade 3 toxicities in Cycle 1.
Assessments: Radiographic response (RECIST) was assessed by CT scans Q 6 weeks and QOL questionnaires (FACET Hep) were filled at baseline and before each new cycle. In patients who consented for additional imaging (optional), DCE MRI was performed at baseline, day 8 (after 7 days of sunitinib), day 10 (48 hrs post TACE) and then day 36 (after sunitinib + TACE cycle 1). Blood samples for sunitinib PK, soluble VEGFR2 and monocytes were obtained in all patients at the same timepoints as DCE-MRI imaging.
Statistics: Statistical analysis will be performed by the Kaplan-Meier method, log-rank test, Cox proportional hazards model and the Wilcoxon rank sum test.
Sixteen of the planned 37 pts were accrued between April 2007 and January 2011. The study was closed when sunitinib failed to show superiority to sorafenib in a large Phase 3 trial. Patient characteristics are summarized in Table 1.
Median PFS was 8 mo (95% CL 4.3-9.3) and OS was 14.9 mo (95% Cl 6.3-27.1) with a median follow up of 12.8 months, and 5 patients still alive. Responses by RECIST criteria were 2 PR, 11 SD and 3 clinical deteriorations; clinical benefit rate was 81%. Median number of cycles on study was 3 (range 1-7). Dose delays and dose reductions occurred in 13 and 3 patients respectively. Reasons for discontinuation therapy were toxicity (7), progression of disease (7) and withdrawal of consent (2).
Toxicities: Eleven pts (69%) had grade 3/4 toxicities attributable to sunitnib. Of the 57 total events, the most frequent (n=5 or more) were thrombocytopenia (10), amylase/lipase increase (9), lymphopenia (7) and fatigue (6).
DCE-MRI: Eight pts consented for the optional DCE- MRIs at baseline., day8, 10 and 36. Median Ktrans change was -20% (95%Cl - 37% to 0%) after 7 days of sunitinib and a 7% further decrease was seen after TACE and sunitinib.
A decrease in viable tumor at same timepoints was 3% (day 8) and 15 % (day 36) respectively.
Sunitinib PK: Steady-state sunitinib concentrations ranged from 20-150 ng/ml, which were above the IC50 values of 15 and 10 ng/m; for modulation of K trans and SUC90.
Soluble VEGFR2 and circulating monocytes:Median plasma sVEGFR2 was 8 ng/ml and decreased by 16% on day 9 and 40& on day 36 sVEGR2 levels increased with Ktrans and AUC90. Median monocyte counts were 0.4 x 10 x9/L before and decreased by 50% on day 36 after TACE.
Quality of Life: QOL data are being analyzed.
This is the first study of sunitinib and TACE in HCC. Encouraging PFS and OS was seen with acceptable toxicity. Our studies show a relationship between sunitinib concentration and following markers: Ktrans, AUC90, SVEGR2 and monocytes: additional marker decrease was seen post TACE.
ROSWELL PARK CANCER INSTITUTE
Significance of CEACAM6 Expression in Cholangiocarcinoma
F.G. Rocha, J. Torres, N. Katabi, M. Gonen, R.P. DeMatteo, Y. Fong, M.I. D'Angelica, P.J. Allen, D.S. Klimstra, W.R. Jarnagin. 1. Virginia Mason Medical Center, Seattle, WA: 2. Memorial Sloan-Kettering Cancer Center New York, NY.
Background: The entire biliary tree is at risk for malignant change, but little is known about differences in molecular pathogenesis with respect to anatomic site. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in pancreatic adenocarcinoma and associated with poor prognosis. This study examines CEACAM6 expression in the entire spectrum of cholangiocarcinoma and its relationship to outcome.
Methods: Tissue microarrays containing triplicate cores of paraffin-embedded surgical specimens from patients with cholangiocarcinoma (hilar, intrahepatic, distal) and control tissue were probed for CEACAM6 immunohistochemistry. Clinical, pathologic and survival data were analyzed and correlated with CEACAM6 expression. Survival was estimated using the Kaplan-Meier method and compared with log rank tests.
Results: One hundred twenty cases of cholangiocarcinoma from 1992-2000) were assembled in the tissue microarray. Strong CEACAM6 signal was present in 30/60 (50%0 of hilar tumors, 7/45 (16%) of intrahepatic tumors, 15 (47%) of distal tumors, and none of the control tissues. Overall median survical and follow-up were 36.4 months and 98.2 months, respectively. CEACAM6 staiing did not correlate with sex, grade of differentiation, positive lymph nodes, vasuclar invasion or metastases but was associated with age >65 (p<0.05) and higher T stage (p<0.05). After R0 resection, CEACAM6 expression was associated with disease-specific survival (DSS) only in the subset of patients with intrahepatic cholangiocarcinoma (median DSS 78 months for negative and 16 months for positive, p<0.000 . Vascular invasion was the sole independent predictor or survival on multivariate proportional hazards regression (HR=1.742[1.048-2.895 95%Cl], p<0.0323).
* Vascular invasion is an independent predictor of survival in patients with biliary tract cancers
* CEACAM6 expression may be determinant of poor outcome in intrahepatic cholangiocarcinoma
* These patients should be considered for adjuvant therapy following R0 resection
Are We Justified in Excluding Patients with Combined Hepatocellular-Cholangiocarcinoma from Transplantation?
R.T. Groeschl, S.G. Pappas, K.K. Christians, S. Tsai, E.J. Quebbeman, T.C. Gamblin, K.K. Turaga. Medical College of Wisconsin, Milwaukee, WI.
Although transplantation has demonstrated survival benefit for patients with hepatoceullular carcinoma [HCC], there is limited data to support or refute transplantation for combined hepatocellular-cholangiocarcinoma [cHCC-CC].
We hypothesized that patients with cHCC-CC had a poorer overall survival than patients with HCC after liver transplantation [LT]. we also examined the outcomes of partial hepatectomy [PH] for patients with HCC and cHCC-CC.
Patients with localized HCC and cHCC-CC who underwent either LT of PH were identified using the Surveillance, Epidemiology and End Results [SEER] database (1973-2007). cHCC case data from the United Network for Organ Sharing [UNOS] was used as a control.
Overall survival [OS] was analyzed with Kaplan-Meier curves, and Cox proportional hazards models were used to study potential prognostic factors.
We included 3378 patients with HCC of cHCC-CC from the SEER database (table 1).
Patients undergoing LT for HCC had a significantly greater survival benefit at 3 years as compared to patients transplanted for cHCC-CC (78% vs 48%, p = 0.01 Table 2).
The number of cHCC-CC diagnoses annually from the SEER and UNOS datasets are shown in Figure 1.
OS for cHCC-CC patients by treatment type is shown in Figure 2.
Clinical characteristics and OS of the control cohort of 65 cHCC-CC patients from UNOS is shown in Table3.
In a multivariable model controlling for age and gender, LT for cHCC-CC was associated with a significantly greater hazard of death when compared to LT for HCC (hazard ration: 2.5, 95% Cl: 1.2-5.1, p = 0.01).
Patients with cHCC-CC had poorer overall survival than patients with HCC after transplantation.
Both transplant and resection offered similar survival benefit for patients with cHCC-CC. In an era of organ shortage, this supports liver resection as a viable treatment option for these patients.
Further research is needed to address the comparative benefits of systemic and liver-directed therapies for patients with cHCC-CC.