EPR Tumor Oximetry With CE India Ink
EPR Tumor Oximetry With CE India Ink
It has been well established that malignant tumors tend to have low levels of oxygen and that
 tumors with very low levels of oxygen are more resistant to radiotherapy and other
 treatments, such as chemotherapy and immunotherapy. Previous attempts to improve response to
 therapy by increasing the oxygen level of tissues have had disappointing results and
 collectively have not led to changing clinical practice. Without a method to measure oxygen
 levels in tumors or the ability to monitor over time whether tumors are responding to methods
 to increase oxygen during therapy, clinician's reluctance to use oxygen therapy in usual
 practice is not surprising.

 The hypothesis underlying this research is that repeated measurements of tissue oxygen levels
 can be used to optimize cancer therapy, including combined therapy, and to minimize normal
 tissue side effects or complications. Because studies have found that tumors vary both in
 their initial levels of oxygen and exhibit changing patterns during growth and treatment, we
 propose to monitor oxygen levels in tumors and their responsiveness to hyperoxygenation
 procedures. Such knowledge about oxygen levels in tumor tissues and their responsiveness to
 hyper-oxygenation could potentially be used to select subjects for particular types of
 treatment, or otherwise to adjust routine care for patients known to have hypoxic but
 unresponsive tumors in order to improve their outcomes.

 The overall objectives of this study are to establish the clinical feasibility and efficacy
 of using in vivo electron paramagnetic resonance (EPR) oximetry-a technique related to
 magnetic resonance imaging (MRI)-to obtain direct and repeated measurements of clinically
 useful information about tumor tissue oxygenation in specific groups of subjects with the
 same types of tumors, and to establish the clinical feasibility and efficacy of using
 inhalation of enriched oxygen to gain additional clinically useful information about
 responsiveness of tumors to hyper-oxygenation. Two devices are used: a paramagnetic charcoal
 suspension (Carlo Erba India ink) and in vivo EPR oximetry to assess oxygen levels. The ink
 is injected and becomes permanent in the tissue at the site of injection unless removed;
 thereafter, the in vivo oximetry measurements are noninvasive and can be repeated
 indefinitely.
The study design uses consecutively enrolled patients. Patients can participate as long as
 they are willing, fit the criteria for being assigned to a cohort, and the India ink spot
 remains measurable by EPR. Patients whose ink spot is resected during usual care and who do
 not have or are not willing to obtain additional injections will be withdrawn. Otherwise,
 patients can be re-measured using the previously injected ink at any time during the course
 of the study.

 The study is split into four cohorts, with a minimum of 1-5 patients expected to be enrolled
 annually in each cohort, and a total of approximately 10 subjects expected for each cohort.
 The cohorts are defined by the type of tumor and by scenarios when our measurements will be
 made relative to the patient's standard therapies: 1) intraoral tumors with planned resection
 and adjuvant radiation therapy; 2) cutaneous malignant tumors receiving surgical resection
 only, receiving radiation therapy only, or receiving both surgical resection and adjuvant
 radiation therapy; 3) breast tumor receiving radiation therapy following surgery; and 4)
 other tumors receiving radiation therapy. The diagnosis for patients in all cases assumes
 that an eligible tumor (or the postsurgical area receiving radiation) occurs within
 approximately one-half centimeter of the surface, as determined by physical exam or imaging
 if available. All potentially eligible subjects are approached by their treating physician;
 those who agree to be contacted and are subsequently consented are assigned to the cohort for
 which they qualify. There is no randomization and no stratification within the cohorts.

 Our interest in in situ tumor oxygenation relates to the clinical need to measure oxygen in
 tumors prior to therapy, to understand tumor oxygen dynamics over the course of therapy, and
 to assess the effectiveness of oxygen modulation therapy during treatment. Our interest in
 the postsurgical radiation field relates to the clinical need to understand whether the
 temporal dynamics of oxygen within the postsurgical radiation field has the potential to
 enhance the effectiveness of adjuvant therapies, and to understand how changes in short and
 long term oxygenation within the postsurgical radiation field may facilitate diminishment of
 late side effects from surgery and/or radiotherapy.

 Following enrollment in the study, each subject will receive an initial placement of one or
 more geographically separate injections of India ink into the tissue of interest (i.e., tumor
 and/or tumor bed and/or adjacent tissue) using the established procedures for the injection
 of the ink. The subject is expected to agree to periodic measurements of all injection sites
 (unless the ink injection has been surgically removed); the subject will be told to expect
 six or more visits for measurements during treatment, but must agree to have at least one
 measurement per injection site. Each measurement will typically consist of 3 ten minute
 consecutive periods during which the subject initially breathes room air, then 100% oxygen
 delivered through a non-rebreather face mask followed by a period breathing room air.

 Patients will be evaluated during clinical and oximetry appointments with respect to the
 presence of any adverse events.
Inclusion Criteria:

 1. Subject must be capable of giving informed consent or has an acceptable surrogate
 capable of giving consent on behalf of the subject.

 2. Subject has an eligible tumor that is within 5 mm of the surface (either skin or
 mucosa) or has had a tumor removed with a tumor bed that is within 5 mm of the
 surface.

 1. Eligible tumors types:

 -  Intraoral tumors: squamous cell carcinoma (SCC), melanoma;

 -  Primary cutaneous tumors (including, but not limited to): SCC, basal cell
 carcinoma (BCC,) melanoma;

 -  Breast malignancies post surgery;

 -  Other tumors: any tumor within 5 mm of the surface and with planned
 radiation therapy.

 Exclusion Criteria:

 1. Previous adverse reaction to a charcoal product e.g., a local hypersensitive response
 from a black tattoo or from ingestion of activated charcoal

 2. Previous adverse reaction to the suspending agent

 3. Subject has a pacemaker that is not known to be MRI compatible

 4. Subject has a non-removable implant or device with metal that is not known to be MRI
 compatible

 5. Subject is pregnant or has a likelihood for becoming pregnant during the basic study
 timeframe.

 Note: There is no known harm to the woman or her fetus from participating; this is
 precautionary only.