18F-FDG PET-Derived Tumor Blood Flow Changes After 1 Cycle of Neoadjuvant Chemotherapy Predicts Outcome in Triple-Negative Breast Cancer.
Previous studies have suggested that early changes in blood flow (BF) in response to neoadjuvant chemotherapy and evaluated with15O-water are a surrogate biomarker of outcome in women with breast cancer. This study investigates, in the triple-negative breast cancer subtype, the prognostic relevance of tumor BF changes (ΔBF) in response to chemotherapy, assessed using a short dynamic18F-FDG PET acquisition.


METHODS
Forty-six consecutive women with triple-negative breast cancer and an indication for neoadjuvant chemotherapy were prospectively included. Women benefited from a baseline18F-FDG PET examination with a 2-min chest-centered dynamic acquisition, started at the time of18F-FDG injection. Breast tumor perfusion was calculated from this short dynamic image using a first-pass model. This dynamic PET acquisition was repeated after the first cycle of chemotherapy to measure early ΔBF. Delayed static PET acquisitions were also performed (90 min after18F-FDG injection) to measure changes in tumor glucose metabolism (ΔSUVmax). The association between tumor BF, clinicopathologic characteristics, and patients' overall survival (OS) was evaluated.


RESULTS
Median baseline tumor BF was 21 mL/min/100 g (range, 6-46 mL/min/100 g) and did not significantly differ according to tumor size, Scarf-Bloom-Richardson grade, or Ki-67 expression. Median tumor ∆BF was -30%, with highly scattered values (range, -93% to +118%). A weak correlation was observed between ΔBF and ∆SUVmax(r = +0.40, P = 0.01). The median follow-up was 30 mo (range, 6-73 mo). Eight women developed recurrent disease, 7 of whom died. Low OS was associated with menopausal history (P = 0.03), persistent or increased tumor vascularization on the interim PET (ΔBF cutoff = -30%; P = 0.03), non-breast-conserving surgery (P = 0.04), and the absence of a pathologic complete response (pCR) (P = 0.01). ΔBF and pCR provided incremental prognostic stratification: 3-y OS was 100% in pCR women, 87% in no-pCR women but achieving an early tumor BF response, and only 48% in no-pCR/no-BF-response women (ΔBF cutoff = -30%, P < 0.001).


CONCLUSIONS
This study suggests the clinical usefulness of an early user- and patient-friendly 2-min dynamic acquisition to monitor breast tumor ΔBF to neoadjuvant chemotherapy using18F-FDG PET/CT. Monitoring tumor perfusion and angiogenesis response to treatment seems to be a promising target for PET tracers.
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France ohumbert@cgfl.fr.|LE2I UMR 6306, CNRS, Arts et Métiers, Université de Bourgogne Franche-Comté, Besançon, France.
Olivier
O
Humbert
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.|Departments of Biology and Pathology, Centre GF Leclerc, Dijon, France.
Jean-Marc
JM
Riedinger
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.|LE2I UMR 6306, CNRS, Arts et Métiers, Université de Bourgogne Franche-Comté, Besançon, France.
Jean-Marc
JM
Vrigneaud
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.|LE2I UMR 6306, CNRS, Arts et Métiers, Université de Bourgogne Franche-Comté, Besançon, France.|Imaging Department, CHU Le Bocage, Dijon, France; and.
Salim
S
Kanoun
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.
Inna
I
Dygai-Cochet
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.
Alina
A
Berriolo-Riedinger
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.
Michel
M
Toubeau
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.
Edouard
E
Depardon
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.
Maud
M
Lassere
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.
Simon
S
Tisserand
Department of Medical Oncology, Centre GF Leclerc, Dijon, France.
Pierre
P
Fumoleau
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.|LE2I UMR 6306, CNRS, Arts et Métiers, Université de Bourgogne Franche-Comté, Besançon, France.|Imaging Department, CHU Le Bocage, Dijon, France; and.
François
F
Brunotte
Department of Nuclear Medicine, Centre GF Leclerc, Dijon, France.|LE2I UMR 6306, CNRS, Arts et Métiers, Université de Bourgogne Franche-Comté, Besançon, France.|Imaging Department, CHU Le Bocage, Dijon, France; and.
Alexandre
A
Cochet
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography / Q000379:methods; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001783:Blood Flow Velocity; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000517:prevention & control*; D017063:Outcome Assessment, Health Care / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*
D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
PET; blood flow; breast cancer; perfusion; triple-negative