Predictors of Tumor Response and of Radiation Therapy Side Effects in Patients With Gastrointestinal Cancers

Background:

- Gastrointestinal (GI) carcinomas represent one of the most commonly diagnosed
malignancies in the United States.

- A sensitive and specific marker of tumor persistence or recurrence would permit a more
accurate determination of the appropriateness of adjuvant therapy in patients with no
clinical evidence of disease following curative resection and allow the diagnosis of
recurrences at earlier stages that may be amenable to curative salvage therapies.

- A biomarker detectable shortly after treatment or in the early stages of chronic
radiation toxicity may allow the identification of patients at risk and early
intervention.

Objectives:

- Our primary objective is to determine if patient specific tumor markers in stool, urine,
or serum can be reliably detected prior to treatment and followed after treatment to
monitor the extent of residual disease.

- A second objective is to evaluate the predictive value of potential markers of chronic
gastrointestinal injury after radiotherapy.

Eligibility:

- Age greater than or equal to 18 years

- Histologically confirmed carcinoma of the gastrointestinal tract (esophagus, stomach,
pancreas, rectum)

- Planned to receive radiotherapy to the site of the gastrointestinal malignancy on an NCI
protocol

Design:

- This protocol provides a means of acquiring tissue, serum, urine, and stool samples from
patients who will receive radiation therapy as part of their treatment for
gastrointestinal malignancies.

- Patients treated with radiation therapy on NCI treatment protocols will be asked to
provide samples prior to any local or systemic therapy as well as before, during and
after their radiation treatment.

- These samples will be tested for the presence of tumor specific DNA mutations and
aberrant methylation patterns determined to be present in each patient s tumor by
screening of initial biopsy or surgical material.

- Tumor markers specific to each patient, such as tumor specific DNA mutations or aberrant
DNA methylation, may provide an individualized method to evaluate disease status and
determine prognosis after therapy. Additionally, a number of stool and serum markers
will be explored as early indicators of acute and eventual chronic gastrointestinal
injury in patients receiving radiotherapy to the abdomen.

- INCLUSION CRITERIA:

- Age greater than or equal to 18 years.

- Histologically confirmed carcinoma of the gastrointestinal tract (esophagus, stomach,
pancreas, bile duct, rectum).

- Treatment plan includes radiotherapy to the site of the gastrointestinal malignancy on
an NCI protocol.

- Paraffin embedded tumor tissue from biopsy or surgery adequate in amount to perform
PCR and methylation specific PCR or willingness to undergo rebiopsy.

EXCLUSION CRITERIA:

- Inability to provide informed consent.

- Patients who have a history of prior therapeutic radiation.

- Patients with evidence of distant metastases on initial staging evaluation.

- Patients with other cancers excluding non-melanomatous skin cancers or carcinoma in
situ.

- History of inflammatory bowel disease.

- History of collagen vascular disease or disease of altered collagen metabolism (end
stage renal disease or hepatic fibrosis due to chronic hepatitis).

- History of hypersensitivity to radiation or a history of a disease which results in
mucosal or other hypersensitivity to radiation (Ataxia-Telengiectasia, Bloom s
Syndrome, Human Immunodeficiency Virus, Fanconi anemia, nevoid basal cell carcinoma
syndrome, Li-Fraumeni syndrome, and Nijmegen breakage syndrome).

- Inability to return for follow-up visits.

- Patients who have previously received or are currently receiving MDX-101 (ipilimumab).

- Diagnosis of HIV, Hepatits B, or Hepatits C.