Trial Information

The Gene Expression Studies of Tumor Microenvironments and Their Roles in Tumor Progression

In the first part of the proposal, we will determine the cellular responses to various
microenvironmental factors (such as lactosis, acidosis, hypoxia, glucose deprivation) in
cultured epithelial cells (commercially obtained) making use of DNA microarray analysis.
From the analysis of these microarray assays, we will obtain the gene signatures reflecting
how cells respond to these environments stresses. These gene signatures will be used to
analyze and annotate the gene expression patterns in the tumor samples and whether
hyperthermia will affect the physiological parameters and the corresponding gene signatures.

In the second part of the proposal, we will work with Dr. Dewhirst to perform gene
expression study of cervical cancer samples from a phase III, multicenter, randomized
clinical trial (IRB 4516-05-2R2). The subjects will de-identified and we will not obtain
directly the PHI of the subjects in this trial. Subjects will be randomized to
chemoradiotherapy alone or chemoradiotherapy + hyperthermia. For subjects randomized to
hyperthermia, heat treatments will be administered concurrently with chemotherapy once
weekly during the course of external beam radiation. In the hyperthermia suite, catheters
will be placed in the cervical os, vagina and rectum for internal temperature monitoring.
Hyperthermia will be given externally to the pelvis and abdomen using the BSD Sigma 60
,Sigma Eye or Sigma Ellipse systems. Initial power will be limited to less than 1500 watts
with phase and amplitude adjusted for equal surface electric fields in each quadrant of the
applicator. Heating will continue for 60 minutes after average cervical os or interstitial
temperatures of 40°C have been achieved, or for a maximum total duration of 90 minutes,
whichever is longest. The bolus temperature will be 37° at initiation of power and will be
reduced as necessary for patient comfort and/or to help maintain oral temperature of 38.5C.
Power will also be reduced or treatment will be stopped at the patient request, or due to
intractable pain, nausea or vomiting, if normal tissue temperature rises to 44°C, pulse >
160, BP > 180/100 or < 90/50, altered mental status, or systemic temperature > 38.5°C.

A. The research materials will include the tumor biopsy obtained before and after HT
treatments to be used for gene expression studies as well as for the IHC and ISH studies to
the findings from our microarray analysis. We will also obtain the information on the tumor
physiological parameters information measured in these tumors.

B. The data of the tumor physiological parameters measured and the response to treatments
and other clinical outcomes of these patients will also be acquired.

C. Only the physicians taking care of the patients will have access to the patient
identifies and other Protected Health Information (PHI). All information will be
de-identified and remain anonymous during the studies.

D. The specimens will be collected when the patients undergo medical care for their
respective diseases. No new materials or data will need to be collected specifically for
this proposal. These biopsies and physiological measurements are included in the original
proposed clinical trials.