Comparison of I-124 PET/CT for the Diagnosis of Thyroid Cancer

PRIMARY OBJECTIVES:

1\) Agreement between 1-124 PET and 1-123/1-131 SPECT.

SECONDARY OBJECTIVES:

1. Sensitivity and specificity of I-124 PET to detect metastatic thyroid cancer compared to composite standard.

2. Reclassification rate of I-124 PET compared to I-123 SPECT.

3. Inter-reader variability for I-124 PET and I-123 SPECT.

4. Safety of I-124 PET.

5. Participant level detection rate for I-124 in the overall population.

6. Participant level detection rate for I-124 in participants who have negative I-123 SPECT.

7. Comparison of lesion detection between I-124 PET and 24 hour I-123 SPECT.

8. Comparison of lesion detection between I-124 PET and post-treatment I-131 SPECT.

EXPLORATORY OBJECTIVES:

1\. Ability to predict lesion absorbed dose using I-124 PET/CT.

OUTLINE:

All participants will have a single PET/CT scan after administration of I-124 and will be followed for up to 3-5 days by phone for evaluation of adverse events. A subset of participants being evaluated for dosimetry will be imaged up to two additional times over five days after administration. Data from other scans for comparison will be obtained from the participant's medical record.

Primary Outcome Measures

1. Proportion of agreement between I-124 PET and I-123/I-131 SPECT (participant)
   Participant-level agreement between I-124 PET and the combination of I-123/I-131 SPECT will be measured. A participant will be classified as showing agreement only if all six regions demonstrate agreement; disagreement in one or more regions will result in a classification of disagreement. Positive percent agreement (PPA) and negative percent agreement (NPA) will be reported with corresponding 95% confidence intervals.
2. Number of agreement between 1-124 PET and 1-123/1-131 SPECT (region)
   Region-level agreement between 1-124 PET and the combination of 1-123/1-131 SPECT will be determined by Individual reader and through a consensus read. A region is in agreement if I-124 PET and I-123/I-131 SPECT results align, either as true positive (both positive) or true negative (both negative). Disagreement occurs when the results diverge, categorized as false positive (I-124 PET positive, but I-123/I-131 SPECT negative) or false negative (I-124 PET negative, but I-123/I-131 SPECT positive).

Secondary Outcome Measures

1. Overall specificity of I-124 PET for detection of metastatic thyroid cancer (participant)
   Specificity of I-124 is defined as the proportion of lesions that will be characterized as negative on I-124 PET when compared to the composite truth standard across participants. The composite truth standard is determined by a panel of highly qualified physicians and researchers and will be used to determine true positive (TP), false positive (FP), true negative (TN) and false negative (FN) by participant: o TP: I-124 PET read as positive for tumor, and composite truth standard determined to have tumor. o FP: I-124 PET read as positive for tumor, and composite truth standard determined to not contain tumor. o TN: I-124 PET read as negative for tumor, and composite truth standard determined to not contain tumor. o FN: I-124 PET read as negative for tumor, and composite truth standard determined to contain tumor. Specificity ranges from 0 to 100%, with higher values indicating a better ability for the scan to detect healthy individuals
2. Overall specificity of I-124 PET for detection of metastatic thyroid cancer (region)
   Specificity of I-124 is defined as the proportion of lesions that will be characterized as negative on I-124 PET when compared to the composite truth standard by region. The composite truth standard is determined by a panel of highly qualified physicians and researchers and will be used to determine true positive (TP), false positive (FP), true negative (TN) and false negative (FN) by region: o TP: I-124 PET read as positive for tumor, and composite truth standard determined to have tumor. o FP: I-124 PET read as positive for tumor, and composite truth standard determined to not contain tumor. o TN: I-124 PET read as negative for tumor, and composite truth standard determined to not contain tumor. o FN: I-124 PET read as negative for tumor, and composite truth standard determined to contain tumor. Specificity ranges from 0 to 100%, with higher values indicating a better ability for the scan to detect healthy individuals
3. Overall sensitivity of I-124 PET for detection of metastatic thyroid cancer (participant)
   Sensitivity of I-124 is defined as the proportion of lesions that will be characterized as positive on I-124 PET when compared to the composite truth standard on a participant level. The composite truth standard is determined by a panel of highly qualified physicians and researchers and will be used to determine true positive (TP), false positive (FP), true negative (TN) and false negative (FN) across participants: o TP: I-124 PET read as positive for tumor, and composite truth standard determined to have tumor. o FP: I-124 PET read as positive for tumor, and composite truth standard determined to not contain tumor. o TN: I-124 PET read as negative for tumor, and composite truth standard determined to not contain tumor. o FN: I-124 PET read as negative for tumor, and composite truth standard determined to contain tumor. Sensitivity ranges from 0 to 100%, with higher values indicating a more sensitive scan.
4. Overall sensitivity of I-124 PET for detection of metastatic thyroid cancer (region)
   Sensitivity of I-124 is defined as the proportion of lesions that will be characterized as positive on I-124 PET when compared to the composite truth standard by region. The composite truth standard is determined by a panel of highly qualified physicians and researchers and will be used to determine true positive (TP), false positive (FP), true negative (TN) and false negative (FN) by region: o TP: I-124 PET read as positive for tumor, and composite truth standard determined to have tumor. o FP: I-124 PET read as positive for tumor, and composite truth standard determined to not contain tumor. o TN: I-124 PET read as negative for tumor, and composite truth standard determined to not contain tumor. o FN: I-124 PET read as negative for tumor, and composite truth standard determined to contain tumor. Sensitivity ranges from 0 to 100%, with higher values indicating a more sensitive scan.
5. Reclassification Rate
   Reclassification rate is defined as the proportion of participants what will be characterized as metastatic on I-124 Positron Emission Tomography (PET) that are characterized as localized or nodal only disease on a non-investigational, usual care I-123 Single-photon emission computed tomography (SPECT).
6. Proportion of participants with treatment-related adverse events
   Proportion of participants with treatment-related adverse events, as classified and graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0). Results will be reported separately for adults and pediatric participants.
7. Proportion of participants with positive I-124 PET in the overall population
   The participant level detection rate will be assessed by calculating the number of participants interpreted as having a positive I-124 PET divided by the total number of participants with a scan evaluated by a reader.
8. Proportion of participants with positive I-124 PET in participants who have negative I-123 SPECT
   In the subset of participants where the consensus read of the I-123 imaging study was negative, then the participant level detection rate for this population will be determined. The detection rate will be assessed by calculating the number of participants interpreted as having a positive I-124 PET divided by the total number of participants with a negative I-123 SPECT scan evaluated by a reader.
9. Mean of total number of lesions characterized as positive on I-124 PET and 24 hour I-123 SPECT
   The mean total number of lesions detected for each participant using I-124 and I-123 taken within 24 hours (with a maximum of 10 lesions per region) will be reported along with the variance.
10. Mean of total number of lesions characterized as positive on both I-124 PET and 7-day post I-131
    The mean total number of lesions detected for each participant using I-124 and I-131 taken within 7 days (with a maximum of 10 lesions per region) will be reported along with the variance.
11. Inter-reader reliability (IRR) for I-124 PET (region)
    Three blinded readers will interpret the non-investigational, usual care I-123 imaging and the I-124 imaging by region. A Cohen's Kappa will be used to measure the inter-reader variability for I-124 and I-123 separately. Kappa statistics range from -1 to 1 with higher values correspond to higher inter-rater reliability.
12. Inter-reader reliability (IRR) for I-124 PET (participant)
    Three blinded readers will interpret the non-investigational, usual care I-123 imaging and the I-124 imaging per participants. A Cohen's Kappa will be used to measure the inter-reader variability for I-124 and I-123 separately. Kappa statistics range from -1 to 1 with higher values correspond to higher inter-rater reliability.
13. Intra-reader reliability (Intra-RR) for I-124 PET (participant)
    Three blinded readers will interpret fifteen I-124 imaging studies a second time with a minimum 6 week washout period. A Cohen's Kappa will be used to measure the intra-reader variability for I-124. Kappa statistics range from -1 to 1 with higher values corresponding to higher intra-rater reliability.
14. Biodistribution of I-124 measured by standardized uptake value (SUV) in tumor and target organs
    SUV will be measured in tumor and target organs by PET imaging to characterize the biodistribution of I-124. SUV measurements will be descriptively reported for adults and pediatrics separately to compare biodistribution between these age groups.