Effect of High Doses of Radiation on Bone Structure and Metabolism

Study Overview
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Brief Summary
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This study is designed to characterize the effects of high energy radiation on bone breakdown, with a specific interest in reducing the rate of sacral fractures. Although radiation is very important in managing tumors, it is related to complications such as bone fractures. In this research study, the investigators are looking to determine changes in blood markers, bone density, and bone structure following radiation and to better understand the reason for these changes.

Detailed Description
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Participants in the Surgical Arm of the study will be treated according to the schedule outlined in protocol for a combined treatment with surgery and adjuvant high dose radiotherapy. Patients in the non surgical arm of the the study will be treated according to the protocol being treated with radiotherapy alone.

Official Title
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Pilot Study of the Effect of High Doses of Radiation on Bone Metabolism and Structure in Patients Treated With Adjuvant Radiotherapy and Surgery for Sacral Tumors

Conditions
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Malignant Bone Tumors

Intervention / Treatment
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* Radiation: Radiation (Surgical Arm)
* Radiation: Radiation (Non-surgical Arm)
* Procedure: Malignant Tumor Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All laboratory tests that are a part of the eligibility criteria must be completed within 14 days prior to the date of registration. Diagnostic tests that are a part of the eligibility criteria must be performed within 30 days of the date of registration. Participants must meet the following criteria on screening examination to be eligible to participate in the study: Study participants must have histologically confirmed primary malignant bone tumor in the sacrum for which surgery and radiation or radiation alone are planned. Age 18 years or older. In children under the age of 8, tetracycline derivatives have been reported to stain tooth enamel yellow color. These considerations lead us to exclude young persons under the age of 18 from the study. Participants must have normal organ and marrow function as defined below: Total bilirubin within normal institutional limits Aspartaataminotransferase (AST) (SGOT)/ Alanine-aminotransferase (ALT) (SGPT) < 2.5 X institutional upper limit of normal Creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels about institutional normal limit The effects of tetracyclines and radiation used in computer tomography on the developing human fetus are known to be detrimental. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Participants must be able to read and understand English language and have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. Participants who have had surgery, chemotherapy, or radiotherapy of the sacrum prior to entering the study History of allergic reactions attributed to compounds of similar chemical or biologic composition to tetracyclines. Pregnant or nursing Uncontrolled inter current 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

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non Surgical-Radiation Only<br>Non-surgical candidates receive 72 up to 77.l4 Gy of radiation depending on the histology (72 Gy for osteosarcoma and chondrosarcoma and 77.4 Gy for chordoma | Radiation: Radiation (Non-surgical Arm)<br>* Non-surgical candidates receive 72 up to 77.14 Gy of radiation depending on the histology (72 Gy for osteosarcoma and chondrosarcoma and 77.4 Gy for chordoma)<br>|
| Experimental: Malignant Tumor Surgery And Radiation<br>The standard treatment includes pre-operative radiation of 50.4 Gy, followed by a recovery period of approximately 4 to 5 weeks. Surgery involves removing the malignant tumor in the sacrum in one piece, preferably with a cuff of normal tissue around the tumor. After approximately 6 weeks of recovery, the patient is treated with another 19.8 Gy up to 27 Gy of radiation postoperatively depending on the final margin status (higher for gross residual disease). If the wound is not healed or there is another medical reason to delay adjuvant radiation, then radiation may begin later. | Radiation: Radiation (Surgical Arm)<br>* For surgical candidates, the standard treatment includes pre-operative radiation of 50.4 Gy, followed by a recovery period of approximately 4 to 5 weeks. After this surgery will take place. After approximately 6 weeks of recovery, to allow the surgical incision to heal, the patient is treated with another 19.8 Gy up to 27 Gy of radiation postoperatively depending on the final margin status (higher for gross residual disease)<br>Procedure: Malignant Tumor Surgery<br>* Surgery involves removing the malignant tumor in the sacrum in one piece, preferably with a cuff of normal tissue around the tumor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Mineral Density (Tb. BMD) | Trabecular bone mineral density will be measured in mg/cm3 using volumetric Quantitative Computed Tomography (QCT) of L1, L2 and the vertebrae adjacent to the tumor. | Non-surgical arm: baseline, 3 months Surgical arm: baseline, 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum N-Telopeptide (NTX) | Indicator for Bone Formation, units reported in nmol NTX/mmol creatinine | Non-surgical arm: baseline, 3.5 weeks, 7 weeks,  5 months,  8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks,  7 months,  10 months | 
| Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) | Indicator for Bone Formation, units reported in U/L | Non-surgical arm: baseline, 3.5 weeks, 7 weeks,  5 months,  8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks,  7 months,  10 months | 
| Serum Osteocalcin (OC) | Indicator for Bone Formation, units reported in ng/mL | Non-surgical arm: baseline, 3.5 weeks, 7 weeks,  5 months,  8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks,  7 months,  10 months | 
| Serum Type 1 Procollagen N-terminal (P1NP) | Indicator for systemic metabolism that can affect bone health, units reported in pg/mL | Non-surgical arm: baseline, 3.5 weeks, 7 weeks,  5 months,  8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks,  7 months,  10 months | 
| Serum Phosphate (P) | Indicators for systemic metabolism that can affect bone health, units reported in mg/dL | Non-surgical arm: baseline, 3.5 weeks, 7 weeks,  5 months,  8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks,  7 months,  10 months | 
| Serum 25-hydroxycalciferol Vit D (25-OH VitD) | Indicators for systemic metabolism that can affect bone health, units reported in nmol/L | Non-surgical arm: baseline, 3.5 weeks, 7 weeks,  5 months,  8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks,  7 months,  10 months | 
| Mineral Apposition Rate (MAR) | Tetracycline quadruple labeling method will be used and the unit of measure will be um/day | Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and 5). These measurements will be done in batches so timeframe isn't clear. | 
| Bone Formation Rate (BFR/BS) | Tetracycline quadruple labeling method will be used and the unit of measure will be mm3/mm2/year | Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and 5). These measurements will be done in batches so timeframe isn't clear. | 
| Mineralization Lag Time (Mlt) | Tetracycline quadruple labeling method will be used and the unit of measure will be days | Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and 5). These measurements will be done in batches so timeframe isn't clear. | 
| Osteoblast Number (N.Ob/BPm) | Immunohistochemistry staining methods will be used and the unit of measure will be mm^-1 | Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5). | 
| Osteoblast Surface (Ob. S/BS) | Immunohistochemistry staining methods will be used and the unit of measure will be mm^-1 | Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5). | 
| Osteoclast Number (N.Oc/BPm) | Immunohistochemistry staining methods will be used and the unit of measure will be mm^-1 | Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5). | 
| Osteoclast Surface (Oc.S/BS) | Immunohistochemistry staining methods will be used and the unit of measure will be mm^-1 | Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant bone tumors