[F-18] Fluorothymidine PET/CT Imaging for Pelvic Cancers

Study Overview
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Brief Summary
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[F-18] Fluorothymidine PET imaging will be used to create a radiation therapy treatment plan to avoid active bone marrow in the pelvis. This will be done to evaluate if sparing bone marrow will help maintain blood counts. This would impact chemotherapy administration.

Detailed Description
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Overall survival of pelvic cancer patients depends on control of systemic disease. If local radiation therapy depletes bone marrow function to such an extent that systemic therapies must be withheld, chances of metastatic failure increase significantly. This may be more significant for this group of patients because approximately one third of adult bone marrow is located in the pelvic region. Strategies to minimize toxicities would benefit a range of pelvic cancer patients including gynecologic, anal, rectal, and prostate. New chemoradiation combinations improve outcomes for these disease sites, but come at the cost of higher levels of toxicity. As many as 40% of cervical cancer patients miss at least one chemotherapy cycle due to hematologic toxicity and 36% of anal cancer patients experience grade 3 or 4 hematologic toxicity when undergoing chemoradiation therapy. A clinical trial of concurrent chemoradiation therapy for rectal cancer was terminated due to toxicity, including hematologic toxicities. Concurrent chemoradiation therapy shows promise for advanced stage prostate cancers, but it also increases grade 3 and 4 toxicities. To successfully limit hematologic toxicities for pelvic cancers, it is extremely advantageous to avoid irradiating the highly proliferative compartments of the pelvic bone marrow. However, the complex structure of the pelvis makes it difficult to assess the efficacy of radiation therapy (RT) planning strategies to avoid areas critical to hematopoiesis. Uptake of [18F]fluorothymidine imaged with positron emission tomography (FLT PET/CT) can be an accurate and sensitive tool for identifying and monitoring the effects of chemoradiation on proliferative pelvic bone marrow. Clinically validating the utility of FLT PET/CT imaging for identifying active bone marrow in the design of bone marrow sparing RT-plans and the important bone marrow assessment time points would provide a method to reduce acute and chronic hematologic toxicities for pelvic cancer patients.

Official Title
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Improving Pelvic Cancer Patient Chemoradiotherapy Outcomes With FLT PET Imaging

Conditions
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Uterine Cervical Neoplasms, Endometrial Neoplasms, Anus Neoplasms, Rectal Neoplasms, Prostatic Neoplasms

Intervention / Treatment
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* Drug: fluorothymidine F 18


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and willingness to sign a written informed consent document. Recommended to undergo pelvic irradiation with concurrent chemotherapy. At least 18 years of age. Pediatrics would be best served by a protocol designed for their specific needs. Karnofsky Performance Status of at least 60% at time of screening. Life expectancy of greater than 6 months. Subject must have normal organ and marrow function (as defined below) within 30 days of study enrollment: leukocytes at least 3,000 / µL absolute neutrophil count of at least 1500 / µL platelets of at least 100,000 / µL creatinine equal to or less than the upper limit of normal not pregnant (as applicable) Exclusion Criteria: history of allergic reactions attributed to compounds of similar chemical or biologic composition to FLT an oncology research protocol requiring full pelvic radiation (i.e., 4 field box technique) uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. subjects taking nucleoside analog medications such as those used as antiretroviral agents.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluorothymidine F 18 PET/CT<br>Fluorothymidine F 18 (FLT) PET/CT imaging ordered pre-radiation therapy, during weeks 1 and 2 of radiation therapy, and then at 1 month and 12 months after radiation therapy. The FLT PET/CT imaging ordered pre-radiation therapy is used for bone marrow sparing IMRT radiation therapy. | Drug: fluorothymidine F 18<br>* A patient-specific bone marrow map will be designed from the pre-therapy FLT PET/CT imaging. A highly conformal radiation plan will be designed to spare active bone marrow.<br>* Other names: [F-18] Fluorothymidine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Difference From Baseline IMRT Plan (%) | The difference in volume of bone marrow receiving radiation using a bone-marrow-sparing radiation plan compared to a standard radiation plan (IMRT), expressed as a percentage. Both plans are patient-specific. Bone-marrow is identified using the baseline FLT PET/CT obtained pre-imaging. Active bone marrow is considered to have an uptake value (SUV) of 2, 3, or 4. The standard IMRT plan was created using the criteria of the National Cancer Institute's Radiation Therapy Oncology Group study RTOG-0418. Radiation doses evaluated are 5 Gray, 10 Gray, 20 Gray, and 30 Gray. The change in dose to tumor is also provided. A negative value indicates that more bone marrow or tissue was spared using the bone-marrow sparing plan. | Baseline (pre-treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy Compliance | The number of participants who had chemotherapy withheld at least once for low blood counts. | At 24 months | 
| Number of Participants With Standardized Toxicity Severity Grades for White Blood Cell Counts | White blood cell counts measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured weekly during combined chemotherapy and radiation therapy treatment and then once at 30 day follow-up and at 1 year follow-up | baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment | 
| Number of Participants With Standardized Toxicity Severity Grades for Decreased Platelet Counts. | Platelet cell counts measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured once weekly during combined chemotherapy and radiation therapy, then once at 30 day follow-up, and once at 1 year follow-up | baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment | 
| Number of Participants With Standardized Toxicity Severity Grades for Decreased Absolute Neutrophil Counts (ANCs) | Absolute neutrophil counts (ANCs) measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured once weekly during combined chemotherapy and radiation therapy, then once at 30 day follow-up, and once at 1 year follow-up | baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment | 
| Number of Participants With Standardized Toxicity Severity Grades for Decreased Lymphocyte Counts. | Lymphocyte counts measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured once weekly during combined chemotherapy and radiation therapy, then once at 30 day follow-up, and once at 1 year follow-up | baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy, Positron-Emission Tomography and Computed Tomography, chemotherapy, bone marrow