Respiratory-gated Stereotactic Body Radiation Therapy for Adenocarcinoma of the Pancreas or Periampullary Region

Patients will receive 5 fractions of 5 gray (Gy) or 6.6 Gy delivered over a five-day period
based on whether or not they have received prior radiation therapy to the pancreatic region.
Treatment may be delivered over 2 weeks, provided that the patient receives at least 2
fractions per week. Initial patient positioning will be based on volumetric kV (cone-beam
computerized tomography) imaging with shifts to bony anatomy as appropriate. Orthogonal kV/MV
or kV/kV projection imaging will be used to verify the location of the fiducials prior to
delivery of the first treatment beam. A secondary shift based on the location of fiducials
may be utilized, as indicated by the position of the fiducials. For free-breathing
treatments, kV fluoroscopic images should be obtained to confirm the anticipated position of
these fiducials during the entire respiratory cycle. Active monitoring of treatment delivery
accuracy will be accomplished using kV and/or MV projection imaging, either immediately
before or during all (or a subset of) treatment fields. Patient-specific dosimetric quality
assurance (QA) will be performed as per standard practice in the Department of Radiation
Oncology, Indiana University School of Medicine.

Inclusion Criteria

- Age >18 years.

- Karnofsky Performance Status >70%

- Histologically confirmed adenocarcinoma of the pancreas or ampulla of Vater; at least
the majority of the histopathologic specimen must be identified as adenocarcinoma as
opposed to another histologic subtype. In patients with a diagnosis of recurrent
disease (based on radiographic progression and/or rising CA19-9 levels) and a history
of a biopsy-proven adenocarcinoma of the pancreas or the ampulla of Vater, repeat
biopsy of the recurrence site is not required for participation of the trial.

- Pancreatic or periampullary tumors must be less than 8.0 cm in greatest axial
dimension at the time of treatment planning.

- Patients who have been treated with any combination of surgical resection and
neoadjuvant/adjuvant conventional chemoradiation therapy for resectable disease or
conventional chemoradiation as definitive treatment for unresectable or borderline
resectable disease are eligible for the study, provided that at least 180 days have
elapsed since completing any previous radiation treatment. Patients who have been
receiving continued chemotherapy following their initial radiation treatment are
eligible regardless of when the most recent chemotherapy was received. Those patients
who have received prior radiation therapy will constitute Cohort A and will receive
stereotactic body radiation (SBRT) as 5 gray (Gy) x 5.

- Patients who have not previously undergone radiation therapy can have a history of
treatment with either chemotherapy (for unresectable/borderline resectable disease) or
any combination of surgery and chemotherapy (for resectable disease). Patients with no
history of prior radiation treatment will constitute Cohort B and will receive SBRT as
6.6 Gy x 5. Please note that patients must have received at least two cycles of
chemotherapy (with selection of drugs at the discretion of the treating oncologist)
before SBRT treatment on protocol.

- Acceptable organ and marrow function as defined below (within 2 weeks prior to
radiotherapy):

- Leukocytes >3,000/μL

- Absolute neutrophil count >1,500μL

- Platelets >100,000/μL

- Total Bilirubin ≤1.5x institutional upper limit of normal

- Aspartate transaminase (AST(SGOT))/Alanine transaminase (ALT(SGPT)) <2.5x
institutional upper limit of normal

- Creatinine ≤ institutional upper limit of normal OR creatinine clearance >60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal

- Ability to understand and the willingness to sign a written informed consent document.

- Life expectancy > 3 months.

- Radio-opaque markers must be present within the tumor bed. In patients who have
undergone surgical resection, radio-opaque surgical clips within the tumor bed can be
used as fiducials. Patients without surgical clips in the tumor bed must be able to
have fiducials placed endoscopically, laparoscopically, or through a CT- or
ultrasound-guided technique. If not, the tumor must be posterior and adjacent to the
aorta, and treatment will only be permitted at the discretion of the Principal
Investigator.

Exclusion Criteria

- Age < 18 years.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (or infections requiring systemic antibiotic treatment), active upper GI
ulceration or hemorrhage, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.

- Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder
cancer, early stage prostate cancer, or carcinoma in situ of the cervix. Patients with
a previous non-pancreatic, non-periampullary malignancy without evidence of disease
for > 5 years will be allowed to enter the trial.

- Pregnant and breastfeeding women are excluded as are women of child-bearing potential
who are unwilling or unable to use an acceptable method of birth control (hormonal or
barrier method of birth control; abstinence) to avoid pregnancy for the duration of
the study. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

- Women who are not post-menopausal (as defined in Appendix III) and have a positive
urine or serum pregnancy test or refuse to take a pregnancy test.

- Patients with a life expectancy of < 3 months.

- Patients with metastatic disease.

- Patients with evidence of gross tumor invasion into the lumen of the stomach or small
bowel are not eligible; if imaging suggests luminal invasion of tumor, this must be
ruled out endoscopically before the patient can be enrolled on study.