Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET

Brenda F. Kurland, Lanell M. Peterson, Jean H. Lee, Hannah M. Linden, Erin K. Schubert, Lisa K. Dunnwald, Jeanne Link, Kenneth Krohn, David A. Mankoff

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Heterogeneity of estrogen receptor (ER) expression may be an important predictor of breast cancer therapeutic response. 18F-fluoroestradiol PET produces in vivo quantitative measurements of regional estrogen binding in breast cancer tumors. We describe within-patient (site-to-site) and between-patient heterogeneity of lesions in patients scheduled to receive endocrine therapy. Methods: In 91 patients with a prior ER-positive biopsy, 505 lesions were analyzed for both 18F-fluoroestradiol and 18FFDG uptake and the 18F-fluoroestradiol/ 18F-FDG uptake ratio. Standardized uptake values (SUVs) were recorded for up to 16 lesions per patient, of 1.5 cm or more and visible on 18F-FDG PET or conventional staging. Linear mixed-effects regression models examined associations between PET parameters and patient or lesion characteristics and estimated variance components. A reader study of SUV measurements for 9 scans further examined sources of within-patient variability. Results: Average 18F-fluoroestradiol uptake and 18F- fluoroestradiol/ 18F-FDG ratio varied greatly across these patients, despite a history of ER-positive disease: about 37% had low or absent 18F-fluoroestradiol uptake even with marked 18F-FDG uptake. 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio measurements within patients with multiple lesions were clustered around the patient's average value in most cases. Summarizing these findings, the intraclass correlation coefficient (proportion of total variation that is between-patient) was 0.60 (95% confidence interval, 0.50-0.69) for 18F-fluoroestradiol SUV and 0.65 (95% confidence interval, 0.56-0.73) for the 18F-fluoroestradiol/ 18FFDG ratio. Some within-patient variation in PET measures (22%-44%) was attributable to interobserver variability as measured by the reader study. A subset of patients had mixed uptake, with widely disparate 18F-fluoroestradiol SUV or 18Ffluoroestradiol/ 18F-FDG ratio for lesions in the same scan. Conclusion: 18F-fluoroestradiol uptake and the 18F-fluoroestradiol/ 18F-FDG ratio varied greatly between patients but were usually consistent across lesions in the same scan. The average 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio for a limited sample of lesions appear to provide a reasonable summary of synchronous ER expression for most patients. However, imaging the entire disease burden remains important to identify the subset of patients with mixed uptake, who may be at a critical point in their disease evolution.

Original languageEnglish (US)
Pages (from-to)1541-1549
Number of pages9
JournalJournal of Nuclear Medicine
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

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Estrogen Receptors
Fluorodeoxyglucose F18
Breast Neoplasms
Confidence Intervals
Observer Variation
Estrogens

Keywords

  • F-FES PET
  • Breast cancer
  • Estrogen receptor imaging
  • Heterogeneity

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Kurland, B. F., Peterson, L. M., Lee, J. H., Linden, H. M., Schubert, E. K., Dunnwald, L. K., ... Mankoff, D. A. (2011). Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET. Journal of Nuclear Medicine, 52(10), 1541-1549. https://doi.org/10.2967/jnumed.111.091439

Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET. / Kurland, Brenda F.; Peterson, Lanell M.; Lee, Jean H.; Linden, Hannah M.; Schubert, Erin K.; Dunnwald, Lisa K.; Link, Jeanne; Krohn, Kenneth; Mankoff, David A.

In: Journal of Nuclear Medicine, Vol. 52, No. 10, 01.10.2011, p. 1541-1549.

Research output: Contribution to journalArticle

Kurland, Brenda F. ; Peterson, Lanell M. ; Lee, Jean H. ; Linden, Hannah M. ; Schubert, Erin K. ; Dunnwald, Lisa K. ; Link, Jeanne ; Krohn, Kenneth ; Mankoff, David A. / Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET. In: Journal of Nuclear Medicine. 2011 ; Vol. 52, No. 10. pp. 1541-1549.
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title = "Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET",
abstract = "Heterogeneity of estrogen receptor (ER) expression may be an important predictor of breast cancer therapeutic response. 18F-fluoroestradiol PET produces in vivo quantitative measurements of regional estrogen binding in breast cancer tumors. We describe within-patient (site-to-site) and between-patient heterogeneity of lesions in patients scheduled to receive endocrine therapy. Methods: In 91 patients with a prior ER-positive biopsy, 505 lesions were analyzed for both 18F-fluoroestradiol and 18FFDG uptake and the 18F-fluoroestradiol/ 18F-FDG uptake ratio. Standardized uptake values (SUVs) were recorded for up to 16 lesions per patient, of 1.5 cm or more and visible on 18F-FDG PET or conventional staging. Linear mixed-effects regression models examined associations between PET parameters and patient or lesion characteristics and estimated variance components. A reader study of SUV measurements for 9 scans further examined sources of within-patient variability. Results: Average 18F-fluoroestradiol uptake and 18F- fluoroestradiol/ 18F-FDG ratio varied greatly across these patients, despite a history of ER-positive disease: about 37{\%} had low or absent 18F-fluoroestradiol uptake even with marked 18F-FDG uptake. 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio measurements within patients with multiple lesions were clustered around the patient's average value in most cases. Summarizing these findings, the intraclass correlation coefficient (proportion of total variation that is between-patient) was 0.60 (95{\%} confidence interval, 0.50-0.69) for 18F-fluoroestradiol SUV and 0.65 (95{\%} confidence interval, 0.56-0.73) for the 18F-fluoroestradiol/ 18FFDG ratio. Some within-patient variation in PET measures (22{\%}-44{\%}) was attributable to interobserver variability as measured by the reader study. A subset of patients had mixed uptake, with widely disparate 18F-fluoroestradiol SUV or 18Ffluoroestradiol/ 18F-FDG ratio for lesions in the same scan. Conclusion: 18F-fluoroestradiol uptake and the 18F-fluoroestradiol/ 18F-FDG ratio varied greatly between patients but were usually consistent across lesions in the same scan. The average 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio for a limited sample of lesions appear to provide a reasonable summary of synchronous ER expression for most patients. However, imaging the entire disease burden remains important to identify the subset of patients with mixed uptake, who may be at a critical point in their disease evolution.",
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T1 - Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET

AU - Kurland, Brenda F.

AU - Peterson, Lanell M.

AU - Lee, Jean H.

AU - Linden, Hannah M.

AU - Schubert, Erin K.

AU - Dunnwald, Lisa K.

AU - Link, Jeanne

AU - Krohn, Kenneth

AU - Mankoff, David A.

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N2 - Heterogeneity of estrogen receptor (ER) expression may be an important predictor of breast cancer therapeutic response. 18F-fluoroestradiol PET produces in vivo quantitative measurements of regional estrogen binding in breast cancer tumors. We describe within-patient (site-to-site) and between-patient heterogeneity of lesions in patients scheduled to receive endocrine therapy. Methods: In 91 patients with a prior ER-positive biopsy, 505 lesions were analyzed for both 18F-fluoroestradiol and 18FFDG uptake and the 18F-fluoroestradiol/ 18F-FDG uptake ratio. Standardized uptake values (SUVs) were recorded for up to 16 lesions per patient, of 1.5 cm or more and visible on 18F-FDG PET or conventional staging. Linear mixed-effects regression models examined associations between PET parameters and patient or lesion characteristics and estimated variance components. A reader study of SUV measurements for 9 scans further examined sources of within-patient variability. Results: Average 18F-fluoroestradiol uptake and 18F- fluoroestradiol/ 18F-FDG ratio varied greatly across these patients, despite a history of ER-positive disease: about 37% had low or absent 18F-fluoroestradiol uptake even with marked 18F-FDG uptake. 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio measurements within patients with multiple lesions were clustered around the patient's average value in most cases. Summarizing these findings, the intraclass correlation coefficient (proportion of total variation that is between-patient) was 0.60 (95% confidence interval, 0.50-0.69) for 18F-fluoroestradiol SUV and 0.65 (95% confidence interval, 0.56-0.73) for the 18F-fluoroestradiol/ 18FFDG ratio. Some within-patient variation in PET measures (22%-44%) was attributable to interobserver variability as measured by the reader study. A subset of patients had mixed uptake, with widely disparate 18F-fluoroestradiol SUV or 18Ffluoroestradiol/ 18F-FDG ratio for lesions in the same scan. Conclusion: 18F-fluoroestradiol uptake and the 18F-fluoroestradiol/ 18F-FDG ratio varied greatly between patients but were usually consistent across lesions in the same scan. The average 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio for a limited sample of lesions appear to provide a reasonable summary of synchronous ER expression for most patients. However, imaging the entire disease burden remains important to identify the subset of patients with mixed uptake, who may be at a critical point in their disease evolution.

AB - Heterogeneity of estrogen receptor (ER) expression may be an important predictor of breast cancer therapeutic response. 18F-fluoroestradiol PET produces in vivo quantitative measurements of regional estrogen binding in breast cancer tumors. We describe within-patient (site-to-site) and between-patient heterogeneity of lesions in patients scheduled to receive endocrine therapy. Methods: In 91 patients with a prior ER-positive biopsy, 505 lesions were analyzed for both 18F-fluoroestradiol and 18FFDG uptake and the 18F-fluoroestradiol/ 18F-FDG uptake ratio. Standardized uptake values (SUVs) were recorded for up to 16 lesions per patient, of 1.5 cm or more and visible on 18F-FDG PET or conventional staging. Linear mixed-effects regression models examined associations between PET parameters and patient or lesion characteristics and estimated variance components. A reader study of SUV measurements for 9 scans further examined sources of within-patient variability. Results: Average 18F-fluoroestradiol uptake and 18F- fluoroestradiol/ 18F-FDG ratio varied greatly across these patients, despite a history of ER-positive disease: about 37% had low or absent 18F-fluoroestradiol uptake even with marked 18F-FDG uptake. 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio measurements within patients with multiple lesions were clustered around the patient's average value in most cases. Summarizing these findings, the intraclass correlation coefficient (proportion of total variation that is between-patient) was 0.60 (95% confidence interval, 0.50-0.69) for 18F-fluoroestradiol SUV and 0.65 (95% confidence interval, 0.56-0.73) for the 18F-fluoroestradiol/ 18FFDG ratio. Some within-patient variation in PET measures (22%-44%) was attributable to interobserver variability as measured by the reader study. A subset of patients had mixed uptake, with widely disparate 18F-fluoroestradiol SUV or 18Ffluoroestradiol/ 18F-FDG ratio for lesions in the same scan. Conclusion: 18F-fluoroestradiol uptake and the 18F-fluoroestradiol/ 18F-FDG ratio varied greatly between patients but were usually consistent across lesions in the same scan. The average 18F-fluoroestradiol SUV and 18F-fluoroestradiol/ 18F-FDG ratio for a limited sample of lesions appear to provide a reasonable summary of synchronous ER expression for most patients. However, imaging the entire disease burden remains important to identify the subset of patients with mixed uptake, who may be at a critical point in their disease evolution.

KW - F-FES PET

KW - Breast cancer

KW - Estrogen receptor imaging

KW - Heterogeneity

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