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Breast cancer preoperative 18FDG-PET, overall survival prognostic separation compared with the lymph node ratio

Abstract

Purpose

To evaluate the overall survival prognostic value of preoperative 18F-fluorodeoxyglucose positron emission tomography (PET) in breast cancer, as compared with the lymph node ratio (LNR).

Methods

Data were abstracted at a median follow-up 14.7 years from a retrospective cohort of 104 patients who underwent PET imaging before curative surgery. PET-Axillary|Sternal was classified as PET-positive if hypermetabolism was visualized in ipsilateral nodal axillary and/or sternal region, else as PET-negative. The differences of 15 years restricted mean survival time RMST according to PET and LNR were computed from Kaplan–Meier overall survival. The effect of PET and other patients' characteristics was analyzed through rankit normalization, which provides with Cox regression the Royston–Sauerbrei D measure of separation to compare the characteristics (0 indicating no prognostic value). Multivariate analysis of the normalized characteristics used stepwise selection with the Akaike information criterion.

Results

In Kaplan–Meier analysis, LNR > 0.20 versus ≤ 0.20 showed RMST = 3.4 years, P = 0.003. PET-Axillary|Sternal positivity versus PET-negative showed a RMST = 2.6 years, P = 0.008. In Cox univariate analyses, LNR appeared as topmost prognostic separator, D = 1.50, P < 0.001. PET ranked below but was also highly significant, D = 1.02, P = 0.009. In multivariate analyses, LNR and PET-Axillary|Sternal were colinear and mutually exclusive. PET-Axillary|Sternal improved as prognosticator in a model excluding lymph nodes, yielding a normalized hazard ratio of 2.44, P = 0.062.

Conclusion

Pathological lymph node assessment remains the gold standard of prognosis. However, PET appears as a valuable surrogate in univariate analysis at 15-year follow-up. There was a trend towards significance in multivariate analysis that warrants further investigation.

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Data availability

Data is available on Mendeley. Temporary link for review: https://data.mendeley.com/datasets/sfvtmrd8z9/draft?a=f1f1fe69-2387-4d9a-92ca-e564faa046de. Reserved https://doi.org/10.17632/sfvtmrd8z9.1.

Protocol availability

The protocol is available at: https://www.protocols.io/view/pet2015uz-prognostic-value-of-pre-treatment-18fdg-bf7jjrkn/abstract. http://www.isrctn.com/ISRCTN17962845.

Code availability

The study used software applications available at: https://cran.r-project.org/. Function rnktt is available in Appendix A and shared with the data at: reserved https://doi.org/10.17632/sfvtmrd8z9.1.

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Funding

The study received no funding.

Author information

Affiliations

Authors

Contributions

VVH and HE designed and conceptualized the study; VVH, HE and MDR drafted the study protocol; VVH and HE analyzed the PET-scan images; VVH, HVP, GV, MV, GS, CF, JL, and MDR contributed patients data; VVH, OG, NPN and CV analyzed the data and wrote the first draft; VVH, OG, HVP, GV, MV, GS, CF, JL, JP, KF, NPN, CV, and MDR revised the manuscript; all authors critically reviewed the manuscript and gave final approval.

Corresponding author

Correspondence to Vincent Vinh-Hung.

Ethics declarations

Conflict of interest

Vincent Vinh-Hung received non-financial support from AddMedica, AstraZeneca, Bayer HealthCare SAS, Bristol-Myers Squibb, Ipsen Pharma, Janssen-Cilag, GlaxoSmithKline, Pfizer SAS, Roche SAS, Sanofi Aventis France, Sepropharm International. Vincent Vinh-Hung and Nam P. Nguyen hold a patent on the Mean absolute dose deviation, unrelated to the present study. Olena Gorobets received non-financial support from AstraZeneca. The other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. The study was approved by the Medical Ethics Committee of the Universitair Ziekenhuis Brussel. Informed consent was obtained from all individual participants included in the study. The study was registered at: http://www.isrctn.com/ISRCTN17962845.

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Cite this article

Vinh-Hung, V., Everaert, H., Gorobets, O. et al. Breast cancer preoperative 18FDG-PET, overall survival prognostic separation compared with the lymph node ratio. Breast Cancer 28, 956–968 (2021). https://doi.org/10.1007/s12282-021-01234-z

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Keywords

  • Positron emission tomography
  • 18F-fluorodeoxyglucose
  • Predictive factor
  • D measure of prognostic separation
  • Normalized hazard ratio
  • Prognostic ranking method
  • Lymph node ratio