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influence of liver irradiation on the pharmacokinetics (PK)
of sorafenib using rats as an experimental model.
Material and Methods
Free-moving rat model was used in the current study.
Image-guided RT with 2 Gy was delivered to the whole
liver of Sprague-Dawley rats. The rats were feeding with
sorafenib at 40 mg/kg after RT 1 hour (concurrent model)
or post RT 24 hours (sequential model) for the plasma
system. The experimental animals were randomized to the
sham RT (0 Gy with sorafnib), concurrent group and
sequential group, respectively. The PK of sorafenib in the
plasma system was calculated. Each group’s data was
collected from six to eight rats
Results
Compared to the sham-irradiated controls, the area under
the concentration versus time curve (AUC) of sorafenib (40
mg/kg) was increased by 132% in concurrent group (719
versus 1669 min*ug/mL, p = 0.046). In contrast, the AUC
of sorafenib was decreased by 59% in sequential group (719
versus 297 min*ug/mL, p = 0.036). Compared with the
concurrent and sequential group, there was a statistically
significant difference between both groups (1669 vs 297
min*ug/mL, p = 0.012). There were no differences at Tmax
and Cmax between groups.
Conclusion
A whole liver RT modulates the systemic PK of sorafenib
of the rats. Interestingly, the AUC of sorafenib is increased
at concurrent with RT and decreased in sequential model.
The RT-PK phenomena are not only noted in chemotherapy
agents but also in target therapy drug. The RT-PK
phenomena are worth further investigation.
PO-0685 The value of postoperative adjuvant therapy
for pT2-3 esophageal cancer treated by radical
resection
S. Zhu
1
, L. Shuguang
2
, L. Youmei
2
, S. Wenbin
3
, L. Juan
2
,
L. Zhukun
2
, S. Jingwei
2
, L. Teng
2
1
Fourth Hospital of Hebei Medical University,
Department Radiation Oncology, Sijiazhuang- Hebei,
China
2
Fourth Hospital of Hebei Medical University,
Department of Radiation Oncology, Shijiazhuang, China
3
Fourth Hospital of Hebei Medical University,
Department of RadiationOncology, Shijiazhuang, China
Purpose or Objective
The aim of this study was to analyze failure modalities and
evaluate efficacy of postoperative treatment of pT
2-3
N
0
M
0
esophageal squamous cell carcinoma. The endpoint was to
find an efficient way of postoperative adjuvant therapy
for this type esophageal cancer.
Material and Methods
The clinical data of 702 patients with pT
2-3
N
0
M
0
esophageal
squamous cell carcinoma who received radical resection
in our hospital from 2007 to 2010 were retrospectively
analyzed. Male 482, female 220, median age 60 years. All
did not receive any preoperative treatment, were
performed with curative esophagectomy included removal
of primary tumor and draining lymph nodes, and 343 cases
surgical alone. Postoperative adjuvant chemotherapy 279
cases, four courses with an interval of 4 weeks with 80
mg/m2 of cisplatin on day 1and 600 mg/m2/day of 5-
fluorouracil given by continuous intravenous infusion on
day1-4. Postoperative prophylactic radiotherapy alone 40
cases with 50.4-59.4Gy of external beam radiation at 1.8-
2.0Gy per fraction, and postoperative chemoradiotherapy
40 cases. Analysis of prognostic survival was determined
by Kaplan-Meier method and checked by the log-rank test.
Cox proportional hazard model was used for multivariate
analysis.
Results
The overall failure rate of all patients was 48.4%, and
surgical alone 54.8%, postoperative chemotherapy alone
42.7%, radiotherapy alone 42.5% and chemoradiotherapy
40.0% (χ
2
=11.021,P=0.012). The local regional failure rate
of all patients was 37.5%, and surgical alone 41.7%,
postoperative chemotherapy alone 35.5%, radiotherapy
alone
27.5%
and
chemoradiotherapy
25.0%
(χ
2
=7.430,P=0.059). In 343 cases surgical alone, the
overall failure rate 58.5% and the local regional failure
rate 46.2% of stage T
3
was significantly higher than T
2
stage
42.4% (χ
2
=11.235,P=0.001) and 33.1% (χ
2
=5.524,P=0.019).
The local regional failure rate 68.0% of thoracic-upper
carcinoma was higher than that of thoracic-middle or-
lower 35.7%(χ
2
=17.101,P=0.001). Compared with surgery
alone, postoperative chemotherapy, radiotherapy and
chemoradiotherapy all improved the 5-year local control
rate.
Postoperative
chemotherapy
and
chemoradiotherapy significantly increased 5-year PFS
(P=0.001, 0.024),and 5-year OS rates (P=0.001, 0.025).
Multivariate analysis revealed that the location, stage of
pathology, postoperative adjuvant therapy were
independently prognostic factors.
Conclusion
The failure rate was high with pT
2-3
N
0
M
0
thoracic
esophageal squamous carcinoma after radical
esophagectomy alone. Postoperative adjuvant therapy
could obviously improve local control, postoperative
chemotherapy and chemoradiotherapy could improve PFS
and OS.
PO-0686 Perfusion imaging of colorectal liver
metastases treated with bevacizumab and SBRT
H. Chung
1
, J. Detsky
1
, P. Munoz-Schuffenegger
1
, L.
Milot
1
, W. Chu
1
, C. MacDonald
1
, Y. Ko
1
1
Odette Cancer Centre - Sunnybrook Health Science,
Radiation Oncology, North York- Toronto, Canada
Purpose or Objective
SBRT is an accepted alternative to surgical resection of
liver metastases from colorectal cancer (CRC). The
addition of bevacizumab holds promise as a radiosensitizer
and is an active agent in metastatic CRC. There is
increasing interest in the use of imaging biomarkers as a
method to evaluate and predict response to treatment.
Dynamic contrast-enhanced CT (DCE-CT) measures
perfusion parameters and has been used to evaluate
primary CRC tumors and liver metastases. Contrast-
enhanced ultrasound (CEUS) is another method using a
microbubble contrast agent to characterize vascular
properties of liver lesions. The purpose of this prospective
study was to evaluate the temporal evolution of perfusion
parameters in CRC liver metastases treated with SBRT and
bevacizumab.
Material and Methods
Patients with 1 – 3 liver metastases from CRC were
prospectively enrolled in this trial. Bevacizumab was
administered for 2 doses 2 weeks apart, with the second
dose within 48 hours of starting SBRT. SBRT was delivered
in 5 fractions. Functional imaging including DCE-CT and
CEUS were performed at three time points: at baseline,
just prior to SBRT, and within 7 days post-SBRT. DCE-CT
output parameters were permeability surface area (PSA),
blood volume (BV), and blood flow (BF). CEUS images were
used to calculate a quantitative perfusion index (PI).
Patients were then followed with physical and imaging
assessments every three months.
Results
The trial enrolled 11 patients, with 1 dropout. Six patients
had a complete set of DCE-CT images (one patient had 2
of 3 scans). Of the 7 evaluable patients, 3, 3 and 1 had
evidence of local, distant and simultaneous failure,
respectively. Mean PSA and BV decreased in 5 of 6 patients
from baseline to post-bevacizumab (-17% ± 37%, p=0.22
and -25% ± 33%, p=0.1 respectively), while BF was not
affected. BF and PSA was reduced in all 7 patients pre to
post-SBRT (-47% ± 22%, p=0.07 and -40% ± 21%, p=0.18,
respectively) while BV remained stable (0.4% ± 22%,
p=0.8). CEUS was attempted in 10 patients but adequate
image acquisition was only technically feasible in 4. CEUS
PI significantly decreased from baseline to post-