Fluoroethyltyrosine for Evaluation of Intracranial Neoplasms

Sensitivity is defined as a percentage of all participants with a true positive (TP) FET PET scan result relative to participants with a positive CSOT result = [TP / (TP + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination.

Specificity is defined as percentage of all participants with a true negative (TN) FET PET scan result relative to participants with a negative CSOT result = [TN / (TN + FP)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination.

Sensitivity is defined as percentage of all participants with a true positive (TP) FET PET scan result relative to all participants with a positive histological result = [TP / (TP + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject.

Sensitivity is defined as percentage of all lesions with a true positive (TP) FET PET scan result relative to all lesions with a positive histological result = [TP / (TP + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion.

Specificity is defined as percentage of all participants with a true negative (TN) FET PET scan result relative to all participants with a negative histological result = [TN / (TN + FP)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject.

Specificity is defined as percentage of all lesions with a true negative (TN) scan result relative to all lesions with a negative histological result = [TN / (TN + FP)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion.

The positive predictive value for all participants is defined as the probability that a positive histological standard of truth result is obtained given that the result of the FET PET scan is positive and reported as a percentage across all participants = [TP / (TP + FP)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject.

The positive predictive value for all lesions is defined as the probability that a positive histological standard of truth result is obtained given that the result of the FET PET scan is positive and reported as a percentage of all lesions = [TP / (TP + FP)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion.

The negative predictive value for all participants is defined as the probability that a negative standard of truth result is obtained given that the result of the FET PET scan is negative and reported as a percentage of all participants = [TN / (TN + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject.

The negative predictive value for all lesions is defined as the probability that a negative standard of truth result is obtained given that the result of the FET PET scan is negative and reported as a percentage of all lesions = [TN / (TN + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion.

The accuracy is defined as the probability that the FET PET scan result for all participants is correct using histopathological results and reported as a percentage: Accuracy (%) = [(TP + TN) / (TP + FP + TN + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject.

The accuracy is defined as the probability that the FET PET scan result for all lesions is correct using histopathological results and reported as a percentage: Accuracy (%) = [(TP + TN) / (TP + FP + TN + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion.

The misclassification rate is defined as the probability that the FET PET scan result for all participants is not correct using histopathological results and reported as a percentage: Misclassification Rate (%) = [(FP + FN) / (TP + FP + TN + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each subject.

The misclassification rate is defined as the probability that the FET PET scan result for all lesions is not correct using histopathological results and reported as a percentage: Misclassification Rate (%) = [(FP + FN) / (TP + FP + TN + FN)] x 100. For cases with available histopathology, the histopathology standard of truth for recurrence (positive) or TRC (negative) will also be determined by the Truth Panel as an intermediate result while reviewing histopathology as part of their overall assessment of each lesion.

Sensitivity is defined as a percentage of all lesions with a true positive (TP) FET PET scan result relative to lesions with a positive CSOT result = [TP / (TP + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion.

Specificity is defined as percentage of all lesions with a true negative (TN) FET PET scan result relative to lesions with a negative CSOT result = [TN / (TN + FP)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion.

The positive predictive value is defined as the probability that a positive CSOT result is obtained given that the result of the FET PET scan is positive, PPV (%) = [TP / (TP + FP)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination.

The positive predictive value is defined as the probability that a CSOT result is obtained given that the result of the FET PET scan is positive PPV (%) = [TP / (TP + FP)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion.

The negative predictive value is defined as the probability that a negative CSOT result is obtained given that the result of the FET PET scan is negative, NPV (%) = [TN / (TN + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination.

The negative predictive value is defined as the probability that a negative CSOT result is obtained given that the result of the FET PET scan is negative, NPV (%) = [TN / (TN + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion.

The accuracy is defined as the probability that the FET PET scan result is correct, Accuracy (%) = [(TP + TN) / (TP + FP + TN + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination.

The accuracy is defined as the probability that the FET PET scan result is correct, Accuracy (%) = [(TP + TN) / (TP + FP + TN + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion.

The misclassification rate is defined as the probability that the FET PET scan result is not correct, Misclassification Rate (%) = [(FP + FN) / (TP + FP + TN + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion, and this will be considered together with the patient-level determination.

The misclassification rate is defined as the probability that the FET PET scan result is not correct, Misclassification Rate (%) = [(FP + FN) / (TP + FP + TN + FN)] x 100. The CSOT for recurrence or benign treatment-related changes (TRC) will be evaluated by a panel of physicians independent of FET images and determined based on histopathology and other clinical data. Histopathology of target lesions obtained may be reviewed for up to 6 months after imaging. Positive for recurrence on follow-up scans will be based on Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. For lesion-level standards, features of RANO will be considered. Histopathology and imaging will be primary factors used in determinations, followed by additional clinical data. From this, an overall determination will be made for each individual lesion.

Inter-reader variability will be analyzed using Fleiss' kappa statistic to determine the agreement between three independent blinded readers in assessing FET PET images as recurrence or TRC. Fleiss's kappa ranges from 0 to 1, where 0 indicates no agreement beyond chance, 1 indicates perfect agreement among all raters.

Intra-reader variability will be analyzed based on a random sample of 15 subjects whose images were re- reviewed by the same reader. The percent of agreement between the two interpretations will be computed for each reader. Cohen's kappa statistics will be used to determine the reproducibility of the assessment by individual readers when analyzing the same data repeatedly. Cohen's Kappa ranges from -1 to 1, where-1 indicates complete disagreement between raters, 0 indicates agreement no better than chance, 1 indicates complete agreement between raters.

The proportion of all participants who have reported grade 3 and above adverse events after receiving interventional scan will be recorded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.4 will be reported.