Cervical Cancer
Conditions
Keywords
cervical squamous cell carcinoma, stage IIB cervical cancer, stage III cervical cancer, stage IV cervical cancer, stage IVA cervical cancer, stage IB cervical cancer, stage IIA cervical cancer
Brief summary
RATIONALE: Diagnostic procedures, such as 64Cu-labeled diacetyl-bis\[N4-methylthiosemicarbazone\] (copper Cu 64-ATSM) PET/CT scans, may help doctors predict how patients will respond to treatment. PURPOSE: This phase II trial is studying how well copper Cu 64-ATSM PET/CT scans work in predicting disease progression in patients undergoing standard of care treatment with cisplatin and radiation therapy (external beam and brachytherapy) per National Comprehensive Cancer Network (NCCN) guidelines for newly-diagnosed stage IB, stage II, stage III, or stage IVA cervical cancer via the Federation of Gynecology and Obstetrics (FIGO) staging systems.
Detailed description
OBJECTIVES: Primary * To define the role of pre-therapy \^64Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) (copper Cu 64-ATSM) in predicting prognosis and determining the behavior of an invasive squamous cell cervical cancer in patients with newly-diagnosed stage IB2-IVA cervical squamous cell carcinoma. * To determine whether higher copper Cu 64-ATSM uptake is associated with lower progression-free survival of these patients after chemoradiotherapy. Secondary * To determine if higher copper Cu 64-ATSM uptake is associated with lower overall survival of these patients. * To determine if higher copper Cu 64-ATSM uptake is associated with earlier primary cervical tumor recurrence and a higher rate of development of distant metastatic disease in these patients. * To determine if higher copper Cu 64-ATSM uptake is associated with a lower frequency of complete metabolic response on 2-Deoxy-2-\[18F\]fluoroglucose (FDG) -PET/CT scan performed 3 months after completion of radiotherapy and chemotherapy. * To estimate the accuracy of copper Cu 64-ATSM uptake as a predictor of progression-free survival, overall survival, primary tumor recurrence, and future development of distant metastatic disease in these patients. * To evaluate the performance of copper Cu 64-ATSM uptake as a predictor of lymph node metastasis at study entry. * To evaluate whether copper Cu 64-ATSM uptake correlates with tumor volume at study entry. * To examine the relationship between tumor uptake of copper Cu 64-ATSM and other markers of tumor hypoxia, including Vascular endothelial growth factor (VEGF) , Glucose transporter 1 (GLUT1), Carbonic anhydrase IX (CA9/CA IX), and Osteopontin (OPN). * To compare the predictive ability of pre-therapy copper Cu 64-ATSM-PET to that of post-therapy FDG-PET/CT scan. * To assess whether pre-therapy FDG-PET/CT findings are predictive of progression-free survival. OUTLINE: This is a multicenter study. Patients receive copper Cu 64-ATSM IV and undergo PET/CT scan over 30 minutes 30-40 minutes later. Within 4 weeks after copper Cu 64-ATSM-PET/CT scan, patients begin planned concurrent standard of care chemoradiotherapy comprising 6 weeks of radiotherapy (external beam and brachytherapy)and weekly cisplatin administration per NCCN guidelines. Patients then undergo FDG-PET/CT scan 3 months after completion of chemoradiotherapy. Tissue samples from previously collected cervical biopsy (obtained for diagnosis) are used for detecting hypoxic markers by immunohistochemistry analysis. After completion of study intervention, patients are followed for every 3 months for 2 years and then every 6 months for 1 year.
Sponsors
National Cancer Institute (NCI)
American College of Radiology Imaging Network
American College of Radiology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary invasive cervical squamous cell carcinoma * Newly diagnosed disease * Stage IB2 - IVA disease based on FIGO staging system * Plan to receive standard of care treatment with concurrent cisplatin and radiation therapy (external beam and brachytherapy) per NCCN guidelines * Must be scheduled to receive 6 weekly courses of cisplatin * Meets 1 of the following criteria: * Pelvic nodal (or no nodal) disease only by FDG-PET/CT scan within 4 weeks of enrollment * Para-aortic nodal metastasis by FDG-PET/CT scan within 4 weeks of enrollment, and patient will undergo radiotherapy to para-aortic nodes * FDG-PET/CT scan at baseline if not meeting any of the above criteria * No stage IVB disease (distant metastases or supraclavicular metastasis) confirmed by FDG-PET/CT scan * No recurrent invasive carcinoma of the uterine cervix regardless of previous treatment * No know metastases to lungs, supraclavicular lymph nodes, or other organs outside of the pelvis or abdominal lymph nodes at time of diagnosis PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to lie flat for the duration of the PET/CT scan * No septicemia or severe infection * No uncontrolled or poorly controlled diabetes * No circumstances that would prevent completion of imaging studies or required clinical follow-up * No other prior or concurrent invasive malignancies, with the exception of non-melanoma skin cancer, within the past 5 years PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior pelvic or abdominal lymphadenectomy * No prior pelvic radiation therapy * No previous cancer treatment contraindicates this protocol therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy | every 3 months for first 2 years and every 6 months during year 3, up to 3 years | Progression-free survival (PFS) evaluated every 3 months for first 2 years and every 6 months during year 3 to determine PFS at 3years. Cu64-ATSM Uptake measured within 14 days of baseline Uptake is a measure of activity within a tumor 1. the maximum standardized uptake value (SUVmax = tracer uptake in ROI / (injected activity / patient weight)) 2. Tumor-to-Muscle uptake ratio (T/M, An FDG-PET/CT-guided circular region of interest of 1.0-1.5 cm in diameter is drawn around the most intense region of the primary tumor to calculate the maximum uptake within the region. In addition, regions of interest are drawn on bilateral gluteal muscle groups on at least 3 slices, and the mean uptake is calculated. The T/M is the ratio of these measurements.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Copper Cu 64-ATSM T/M Uptake and Overall Survival | every 3 months for first 2 years and every 6 months during year 3, up to 3 years | To determine if higher 64Cu-ATSM uptake on PET/CT is associated with lower Overall survival (OS) T/M Uptake measured within 14 days of baseline; Overall survival (OS) is measured every 3 months for first 2 years and every 6 months during year 3,until time of death or 3 years from baseline. |
| Relationship Between Copper Cu 64-ATSM Uptake and Complete Metabolic Response | 3 months after completion of chemoradiation | Complete metabolic response determined by FDG PET/CT performed 3 months after completion of chemoradiation By definition, metabolic response (as defined by NCI Concept ID: C3897320. https://www.ncbi.nlm.nih.gov/medgen/856914) is the disappearance of metabolic tumor activity in target and non-target lesions, marked by a decrease in tumor standardized uptake value to the level of surrounding normal tissue (tumor uptake/normal uptake = \ 1) |
| Primary Tumor Recurrence | every 3 months for first 2 years and every 6 months during year 3, up to 3 years | To determine if higher 64Cu ATSM uptake is associated with earlier primary cervical tumor recurrence images were taken every 3 months for first 2 years and every 6 months during year 3, up to 3 years and evaluated for primary cervical tumor recurrence |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Carbonic anhydrase IX (CA-IX) markers using the Percentage of Tumor Cells Staining Score: 0=\<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=\>66% tumor cells. |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia | baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with CA-IX markers using the Staining Intensity Score: 0=No staining; 1=Weak staining; and 2=Moderate to strong staining. |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | Baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with CA-IX markers using the Composite Score (range 0-6): Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2). |
| Lymph Node Metastasis at Baseline | Two weeks | Lymph nodes were evaluated at 5 locations: Pelvic, Common Iliac, Para Aortic, Mediastinal, and Supraclavicular This outcome looks at the Association of Ratio of Tissue to Muscle (T/M) uptake with Lymph Node Metastases at Baseline |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Staining Intensity Score: as a Marker of Tumor Hypoxia | baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Vascular endothelial growth factor (VEGF) markers using the Staining Intensity Score: 0=No staining; 1=Weak staining; and 2=Moderate to strong staining. |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | Baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Vascular endothelial growth factor (VEGF) markers using the Composite Score (range 0-6): Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2). |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Glucose transporter 1 (GLUT1) markers using the Percentage of Tumor Cells Staining Score: 0=\<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=\>66% tumor cells. |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia | baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with GLUT-1 markers using the Staining Intensity Score: 0=No staining; 1=Weak staining; and 2=Moderate to strong staining. |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | Baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Glucose transporter 1 (GLUT1) markers using the Composite Score (range 0-6): Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2). |
| Relationship Between Copper Cu 64-ATSM Uptake and Development of Distant Metastasis | every 3 months for first 2 years and every 6 months during year 3, up to 3 years | Existence of distant metastasis was evaluated every 3 months for first 2 years and every 6 months during year 3 Copper Cu 64-ATSM Uptake (T/M) measured within 14 days of baseline; |
| Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | baseline | The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with VEGF markers using the Percentage of Tumor Cells Staining Score: 0=\<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=\>66% tumor cells. |
Countries
United States
Participant flow
Recruitment details
Study funding source changed (from National Cancer Institutes to American College of Radiology Imaging Network foundation) after accrual of 28 individuals
Participants by arm
| Arm | Count |
|---|---|
| Copper ATSM pre-therapy pelvic 64Cu-ATSM-PET/CT with Pre- and post- therapy FDG PET/CT
64Cu-ATSM
FDG | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ATSM imaging not complete or inadequate | 3 |
| Overall Study | Ineligible | 4 |
| Overall Study | Tx not per protocol | 1 |
| Overall Study | Tx prior to ATSM | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Copper ATSM |
|---|---|
| Age, Continuous | 51.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| FIGO stage IB2 | 15 Participants |
| FIGO stage IIA | 5 Participants |
| FIGO stage IIB | 21 Participants |
| FIGO stage III | 1 Participants |
| FIGO stage IIIA | 2 Participants |
| FIGO stage IIIB | 12 Participants |
| FIGO stage IVA | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 39 Participants |
| Sex: Female, Male Female | 59 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 59 |
| other Total, other adverse events | 0 / 59 |
| serious Total, serious adverse events | 0 / 59 |
Outcome results
Primary
Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy
Progression-free survival (PFS) evaluated every 3 months for first 2 years and every 6 months during year 3 to determine PFS at 3years. Cu64-ATSM Uptake measured within 14 days of baseline Uptake is a measure of activity within a tumor 1. the maximum standardized uptake value (SUVmax = tracer uptake in ROI / (injected activity / patient weight)) 2. Tumor-to-Muscle uptake ratio (T/M, An FDG-PET/CT-guided circular region of interest of 1.0-1.5 cm in diameter is drawn around the most intense region of the primary tumor to calculate the maximum uptake within the region. In addition, regions of interest are drawn on bilateral gluteal muscle groups on at least 3 slices, and the mean uptake is calculated. The T/M is the ratio of these measurements.)
Time frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Population: As a fully paired analysis, all participants were evaluated in each group. 21 participants progressed by year 3 and 38 participants were progression free at year 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy | Progression within 3 years | 4.4 ratio | Standard Deviation 1.3 |
| 64 CU-ATSM SUVmax @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy | No progression within 3 years | 4.2 ratio | Standard Deviation 1.3 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy | Progression within 3 years | 8.2 ratio | Standard Deviation 4.1 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake in the Primary Tumor and Progression-free Survival 3 Years After Chemoradiotherapy | No progression within 3 years | 8.0 ratio | Standard Deviation 3.1 |
Secondary
Copper Cu 64-ATSM T/M Uptake and Overall Survival
To determine if higher 64Cu-ATSM uptake on PET/CT is associated with lower Overall survival (OS) T/M Uptake measured within 14 days of baseline; Overall survival (OS) is measured every 3 months for first 2 years and every 6 months during year 3,until time of death or 3 years from baseline.
Time frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Population: Participants were divided into two groups by whether their T/M Ratio fell at or above vs. below the observed median of 7.3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Copper Cu 64-ATSM T/M Uptake and Overall Survival | 773.5 days |
| 64 CU-ATSM T/M Ratio @ Baseline | Copper Cu 64-ATSM T/M Uptake and Overall Survival | 786.0 days |
Comparison: Participants were divided into two groups by whether their T/M Ratio fell at or above vs. below the observed median of 7.3 and the the median survival was compared between the 2 groups.p-value: 0.4883Wilcoxon (Mann-Whitney)
Secondary
Lymph Node Metastasis at Baseline
Lymph nodes were evaluated at 5 locations: Pelvic, Common Iliac, Para Aortic, Mediastinal, and Supraclavicular This outcome looks at the Association of Ratio of Tissue to Muscle (T/M) uptake with Lymph Node Metastases at Baseline
Time frame: Two weeks
Population: one patient's scan could not evaluated for any lymph nodes, and three others could be evaluated only for pelvic lymph nodes.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Common Iliac | Positive Nodes | 14 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Pelvic | Positive Nodes | 31 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Pelvic | Negative Nodes | 27 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Common Iliac | Negative Nodes | 41 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Para Aortic | Positive Nodes | 7 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Para Aortic | Negative Nodes | 48 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Mediastinal | Positive Nodes | 0 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Mediastinal | Negative Nodes | 55 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Supraclavicular | Positive Nodes | 0 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Lymph Node Metastasis at Baseline | Supraclavicular | Negative Nodes | 55 Participants |
Comparison: Logistic Regression Evaluating Tissue to Muscle (T/M) uptake Ratio as a Predictor of COMMON ILIAC Lymph Node Metastases at Baselinep-value: 0.9684Regression, Logistic
Comparison: Logistic Regression Evaluating Tissue to Muscle (T/M) uptake Ratio as a Predictor of Para Aortic Lymph Node Metastases at Baselinep-value: 0.7327Regression, Logistic
Comparison: Logistic Regression Evaluating Tissue to Muscle (T/M) uptake ratio as a Predictor of PELVIC Lymph Node Metastases at Baselinep-value: 0.5291Regression, Logistic
Secondary
Primary Tumor Recurrence
To determine if higher 64Cu ATSM uptake is associated with earlier primary cervical tumor recurrence images were taken every 3 months for first 2 years and every 6 months during year 3, up to 3 years and evaluated for primary cervical tumor recurrence
Time frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Population: Two participants were off study before the follow up period began (one death and one withdrawal) and were not assessed for disease status - thus only 57 of the 59 participants were evaluated for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Primary Tumor Recurrence | 773.5 days |
| 64 CU-ATSM T/M Ratio @ Baseline | Primary Tumor Recurrence | 797.0 days |
Comparison: Participants were divided into two groups: those at or above the median for T/M Ratio (7.3) vs. those below, and the time to primary tumor recurrence was compared between the 2 goups.p-value: 0.309Wilcoxon (Mann-Whitney)
Secondary
Relationship Between Copper Cu 64-ATSM Uptake and Complete Metabolic Response
Complete metabolic response determined by FDG PET/CT performed 3 months after completion of chemoradiation By definition, metabolic response (as defined by NCI Concept ID: C3897320. https://www.ncbi.nlm.nih.gov/medgen/856914) is the disappearance of metabolic tumor activity in target and non-target lesions, marked by a decrease in tumor standardized uptake value to the level of surrounding normal tissue (tumor uptake/normal uptake = \ 1)
Time frame: 3 months after completion of chemoradiation
Population: 52 observations were used for this analysis. 7 participants did not have FDG PET data available for analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake and Complete Metabolic Response | Complete metabolic response | 23 Participants |
| 64 CU-ATSM SUVmax @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake and Complete Metabolic Response | Partial response or progressive disease | 29 Participants |
Comparison: Logistic Regression Modeling Complete Metabolic Response by T/M Ratiop-value: 0.1924Regression, Logistic
Secondary
Relationship Between Copper Cu 64-ATSM Uptake and Development of Distant Metastasis
Existence of distant metastasis was evaluated every 3 months for first 2 years and every 6 months during year 3 Copper Cu 64-ATSM Uptake (T/M) measured within 14 days of baseline;
Time frame: every 3 months for first 2 years and every 6 months during year 3, up to 3 years
Population: Participants were divided into two groups by whether their T/M Ratio fell at or above vs. below the observed median of 7.3 and the median time (days) was calculated for the development of new distant metastases.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake and Development of Distant Metastasis | 725.5 days |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship Between Copper Cu 64-ATSM Uptake and Development of Distant Metastasis | 786.0 days |
Comparison: Participants were divided into two groups by whether their T/M Ratio fell at or above vs. below the observed median of 7.3 and the time to observe new distant metastases was compared between the groupsp-value: 0.4981Wilcoxon (Mann-Whitney)
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with CA-IX markers using the Composite Score (range 0-6): Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2).
Time frame: Baseline
Population: No cases had a composite score of 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | 7.58 ratio | Standard Deviation 2.87 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | 5.82 ratio | Standard Deviation 1.99 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | 8.04 ratio | Standard Deviation 3.44 |
| >66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | 6.50 ratio | — |
| Composite Score: 4 | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | 10.60 ratio | Standard Deviation 5.54 |
| Composite Score: 6 | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Composite Score as a Marker of Tumor Hypoxia | 8.20 ratio | — |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with CA-IX markers using the Staining Intensity Score: 0=No staining; 1=Weak staining; and 2=Moderate to strong staining.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia | 7.58 ratio | Standard Deviation 2.87 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia | 6.20 ratio | Standard Deviation 2.56 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and CA-IX Staining Intensity Score: as a Marker of Tumor Hypoxia | 9.40 ratio | Standard Deviation 4.37 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Carbonic anhydrase IX (CA-IX) markers using the Percentage of Tumor Cells Staining Score: 0=\<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=\>66% tumor cells.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 7.58 ratio | Standard Deviation 2.87 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 7.57 ratio | Standard Deviation 3.17 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 9.40 ratio | Standard Deviation 5.26 |
| >66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Carbonic Anhydrase IX (CA-IX) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 7.35 ratio | Standard Deviation 1.2 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Glucose transporter 1 (GLUT1) markers using the Composite Score (range 0-6): Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2).
Time frame: Baseline
Population: No cases had a composite score of 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | 9.70 ratio | Standard Deviation 0.42 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | 6.55 ratio | Standard Deviation 0.07 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | 6.89 ratio | Standard Deviation 1.84 |
| >66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | 5.40 ratio | — |
| Composite Score: 4 | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | 8.93 ratio | Standard Deviation 4.5 |
| Composite Score: 6 | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Composite Score as a Marker of Tumor Hypoxia | 7.58 ratio | Standard Deviation 3.56 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Glucose transporter 1 (GLUT1) markers using the Percentage of Tumor Cells Staining Score: 0=\<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=\>66% tumor cells.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 9.70 ratio | Standard Deviation 0.42 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 6.01 ratio | Standard Deviation 1.08 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 8.83 ratio | Standard Deviation 4.22 |
| >66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 7.46 ratio | Standard Deviation 3.49 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with GLUT-1 markers using the Staining Intensity Score: 0=No staining; 1=Weak staining; and 2=Moderate to strong staining.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia | 9.70 ratio | Standard Deviation 0.42 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia | 7.15 ratio | Standard Deviation 1.47 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Glucose Transporter 1 (GLUT1) Staining Intensity Score: as a Marker of Tumor Hypoxia | 8.11 ratio | Standard Deviation 4.01 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Vascular endothelial growth factor (VEGF) markers using the Composite Score (range 0-6): Computed by using the coded values of Percentage of Tumor Cells Staining Score (0-3) multiplied by the coded value of Staining Intensity Score (0-2).
Time frame: Baseline
Population: No cases had a composite score of 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | 6.98 ratio | Standard Deviation 2.54 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | 4.44 ratio | Standard Deviation 1.22 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | 8.79 ratio | Standard Deviation 3.67 |
| >66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | 6.59 ratio | Standard Deviation 1.83 |
| Composite Score: 4 | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | 8.48 ratio | Standard Deviation 4.11 |
| Composite Score: 6 | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Composite Score as a Marker of Tumor Hypoxia | 11.76 ratio | Standard Deviation 6.13 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Staining Intensity Score: as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with Vascular endothelial growth factor (VEGF) markers using the Staining Intensity Score: 0=No staining; 1=Weak staining; and 2=Moderate to strong staining.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Staining Intensity Score: as a Marker of Tumor Hypoxia | 6.98 ratio | Standard Deviation 2.54 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Staining Intensity Score: as a Marker of Tumor Hypoxia | 7.50 ratio | Standard Deviation 3.17 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and Vascular Endothelial Growth Factor (VEGF) Staining Intensity Score: as a Marker of Tumor Hypoxia | 10.22 ratio | Standard Deviation 4.93 |
Secondary
Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia
The Ratio of Tissue to Muscle (T/M) agent uptake measured at baseline was used as a predictor of Hypoxia Tumor Hypoxia was assessed with VEGF markers using the Percentage of Tumor Cells Staining Score: 0=\<1% tumor cells; 1=1 33% tumor cells; 2=34 66% tumor cells; and 3=\>66% tumor cells.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 64 CU-ATSM SUVmax @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 6.98 ratio | Standard Deviation 2.54 |
| 64 CU-ATSM T/M Ratio @ Baseline | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 7.57 ratio | Standard Deviation 4.57 |
| 34-66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 8.51 ratio | Standard Deviation 3.65 |
| >66% Tumor Cells | Relationship of Copper Cu 64-ATSM Uptake T/M Ratio and VEGF Percentage of Tumor Cells Staining Score as a Marker of Tumor Hypoxia | 8.44 ratio | Standard Deviation 4.5 |