Stereotactic Body Radiation Therapy With Sequential S-1 for Patients With Locally Advanced Pancreatic Cancer and Poor Medical Conditions --a Phase II Clinical Trial
Phase: NA
Conditions: Pancreatic Cancer
Sponsor: Changhai Hospital

Official title: Stereotactic body radiation therapy with sequential S-1 for patients with 
locally advanced pancreatic cancer and poor medical conditions --a phase II clinical 
trial (SILAPANC trial) 
NCT number: NCT02704143 
Document state: 9th May 2020 
 
1. Participants and eligibility 
To be eligible for inclusion in the SILAPANC trial, all patients with clinical suspicion 
for pancreatic cancer, as presented in the imaging studies, were required to receive 
pathological examinations. If deemed necessary, further high-quality dedicated imaging 
of the pancreas should be performed before patients are enrolled into the study and 
undergo any study-related procedures. Biopsies were performed with fine needle 
aspiration via endoscopic ultrasound by experienced gastroenterologists. Specimen 
sections would be evaluated by two independent pathologists. After confirmed 
diagnosis of locally advanced pancreatic cancer by pathological examinations, patients 
should have the willingness and ability to provide an informed consent and comply with 
subsequent treatment plans, tests and other study procedures.  
The following inclusion and exclusion criteria would be employed to preserve high 
internal validity and reduce risks of SBRT or S-1-induced adverse effects.  
Inclusion criteria: 
1. Unresectable without metastasis: 
(a) Pancreatic head/uncinate process: 

(i) Solid tumor contact with the superior mesenteric artery >180°; 
   
(ii) Solid tumor contact with the celiac axis >180°; 
 (iii) Solid tumor contact with the first jejunal superior mesenteric artery branch; 
(iv) Unreconstructible superior mesenteric vein/portal vein due to involvement 
or occlusion (can be due to tumor or bland thrombus); 
(v) Contact with most proximal draining jejunal branch into the superior 
mesenteric vein. 
(b) Pancreatic body/tail: 
   
 (i) Solid tumor contact of >180° with the superior mesenteric artery branch; 
 
 (ii) Solid tumor contact with the celiac axis and aortic involvement; 
 (iii) Unreconstructible superior mesenteric vein/portal vein to tumor 
involvement or occlusion (can be due to tumor or bland thrombus). 
2. Without any other treatment before SBRT. 
3. A life expectancy of >3months. 
4. ECOG: 2 or 3 points. 
5. Age of more than 18 years old. 
6. Blood routine examination: Absolute neutrophil count (ANC) ≥ 1.5 ×109 cells/L, 
leukocyte count≥ 3.5 ×109 cells/L, platelets ≥ 70×109 cells/L, hemoglobin ≥ 8.0 g/dl. 
7. Liver and kidney function tests: Albumin > 2.5 g/dL, total bilirubin < 3 mg/dL, 
creatinine < 2.0 mg/dL, AST <2.5 × ULN (Upper Limit of Normal) (0-64 U/L), 
ALT<2.5 × ULN (0-64 U/L). 
8. INR < 2 (0.9-1.1). 

9. Ability of the research subject or authorized legal representative to understand and 
the willingness to sign a written informed consent document. 
 
Exclusion criteria: 
1. Prior surgery, chemotherapy or radiation for the pancreatic cancer. 
2. Evidences of metastatic disease such as nodal or distant metastases by abdomen CT 
and chest CT or FDG PET-CT. 
3. Contraindication to receiving radiotherapy. 
4. ECOG: 0-1 point. 
5. Age<18 
6. Abnormal results of blood routine examinations, liver and kidney function and 
coagulation tests. 
7. Patients with active inflammatory bowel diseases or peptic ulcer. 
8. Gastrointestinal bleeding or perforation within 6 months. 
9. Heart failure: NYHA III-IV. 
10. Women who are pregnant. 
11. Participation in another clinical treatment trial while on study. 
12. Patients in whom fiducial implantation was not possible. 
13. Inability of the research subject or authorized legal representative to understand and 
the willingness to sign a written informed consent document. 
Due to better diagnostic yield, safety and the potential lower risk of peritoneal seeding, 
endoscopic ultrasound-guided fine-needle aspiration is preferred for all patients 

suspected of pancreatic cancer. 
 
2. Doses of S-1 
The doses of S-1 are calculated by the body surface. Hence, patients will receive S-1 
orally, twice daily, at a dose of 80 mg/m2 for 28 days, followed by a 14-day interval, 
which would repeat for 6 cycles. It was initiated one month after SBRT. 
 
3. CT simulation for treatment planning 
Each patient should fast for at least eight hours before the simulation. Vacuum bags are 
customized with patients in the supine position, according to the patient’s body shape 
for immobilization during Cyberknife. SBRT is delivered via Cyberknife, an image-
guided frameless stereotactic robotic radiosurgery system (Accuray Corporation, 
Sunnyvale CA), that consists of a linear accelerator mounted on a robot arm with six 
degrees of freedom. In this system, the confluence of a large number of non-isocentric 
pencil beams permits the treatment of irregularly shaped target volumes with rapid dose 
falloffs. Cyberknife tracking system automatically compensates for the alignment offset 
and patient motions by adjusting the treatment isocenter. In addition, a CT based 
treatment planning system is used at our institution. Then, plain CT and an enhanced 
pancreatic parenchymal CT are performed for radiation treatment planning and target 
delineations. CT images are acquired under breath hold (preferably end-expiratory). 
Pretreatment diagnostic imaging would be co-registered to the simulation CT in cases 
where the patient is unable to tolerate intravenous contrast. The scan range includes the 

whole pancreas, at least 10 cm above and below the tumor. Spiral CT is performed with 
a slice thickness of 1.5 mm, and images are reconstructed in slices of 1.5 mm at most. 
Intravenous contrast enhancement is performed with an injection of 80-100 ml of 
iodixanol, a flow rate of 2.5 ml/sec, and a delay of 45-55 seconds; as acquired for the 
pancreatic parenchymal phase. 
 
4. Registration and tracking 
The co-registrations of biphasic CT images are based on fiducials and anatomical 
(spinal) fusion. Before CT simulation, fiducials should be implanted using endoscopic 
ultrasound or CT guidance. This is pivotal for treatment planning and delivery. CT 
simulation will be performed 7-10 days after fiducial placement. This time interval is 
required to avoid early fiducial marker displacement or migration. In order to improve 
the accuracy of the treatment planning, the recommended number of implanted 
fiducials is preferably close to 3-5. As a result, given that fiducials could simulate the 
spatial location and displacement of the tumor, which is attributable to respiration, 
motion tracking should be performed by means of the correlation with these seeds; and 
fiducial markers render the Synchrony system equipped in Cyberknife feasible. This 
allows for respiratory motion tracking during irradiation. Nevertheless, patients with 
high risk of bleeding, abdominal infection, pancreatitis or pancreatic fistula are 
contradictory to several fiducial implants. Hence, one fiducial plus X-sight spine and 
Synchrony Tracking technique would be alternatively used. Before treatment, direct 
digital radiography images of the spine would be applied to detect 6-D errors; and this 

would be subsequently corrected for X-sight spine tracking on the patient’s positioning. 
This would enable fiducial tracking during treatment. 
 
5. Treatment planning and target delineation 
After CT simulation, CT images are transferred to the workstation where the target 
volumes are contoured by an attending radiation oncologist. Gross tumor volume (GTV) 
is delineated as a radiographically evident gross disease by contrast CT acquired from 
the portal-venous phase. At the discretion of the physician, clinical target volume (CTV) 
encompassing areas of the potential subclinical disease spread is also designated. In 
most cases, the CTV equals GTV. A 2-5 mm expansion margin is included to determine 
the planning target volume (PTV). When the tumor is adjacent to critical organs, the 
expansion of CTV should be avoided. Therefore, an individualized treatment plan 
would be developed based on tumor geometries and locations. Ninety percent of PTV 
should be covered by the prescription dose. The prescription isodose line is limited to 
70-75%, which would restrict the tumor Dmax. If dose level violates the constraint of 
SBRT, the patient would be considered as ineligible for this trial. The prescribed dose 
of PTV varies from 35-40Gy/5f with a single dose of 7-9Gy. In particular, these doses 
would be reduced if the tumor is approximately one-third or more of the duodenum or 
stomach circumference, or if the tumor abuts the bowel in only one area, as determined 
by the relationship of the tumor to the duodenum in axial, coronal and sagittal planes 
in CT scans, or the space between the tumor and the bowel wall is <3 mm. Normal 
tissue constraints are according to the American Association of Physicists in Medicine 

guidelines in TG-101.  
 
6. Follow-up 
Patients are re-evaluated after Cyberknife every one month for the first three months, 
every 2-3 months for the next two years, and every six months for a total three years. 
Remissions of symptoms and radiation-related toxicities would be assessed. In addition, 
they would undergo laboratory tests, physical examinations, analysis of quality of life, 
and imaging studies every month within the first three months. Subsequent 
examinations in later follow-ups are the same.  
 
7. Statistical analysis 
All outcomes would be analyzed based on intention-to-treat principle. Continuous and 
categorical data were expressed as median (interquartile range, IQR) and n (%), 
respectively. Overall survival and progression free survival are calculated via the 
Kaplan-Meier method compared by the log-rank test. A two-sided α of less than 0.05 
was considered statistically significant. Statistical testing is performed using SPSS 
version 20.0 (IBM Corp, Armonk, NY, USA).