¹⁸F-FDG PET–Derived Tumor Blood Flow Changes After 1 Cycle of Neoadjuvant Chemotherapy Predicts Outcome in Triple-Negative Breast Cancer

Abstract

Previous studies have suggested that early changes in blood flow (BF) in response to neoadjuvant chemotherapy and evaluated with 15 O-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 (DBF) in response to chemotherapy, assessed using a short dynamic 18 F-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 baseline 18 F-FDG PET examination with a 2-min chest-centered dynamic acquisition, started at the time of 18 F-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 DBF. Delayed static PET acquisitions were also performed (90 min after 18 F-FDG injection) to measure changes in tumor glucose metabolism (DSUV max ). 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-BloomRichardson grade, or Ki-67 expression. Median tumor ΔBF was −30%, with highly scattered values (range, −93% to 1118%). A weak correlation was observed between DBF and ΔSUV max (r 5 10.40, P 5 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 5 0.03), persistent or increased tumor vascularization on the interim PET (DBF cutoff 5 −30%; P 5 0.03), non-breast-conserving surgery (P 5 0.04), and the absence of a pathologic complete response (pCR) (P 5 0.01). DBF 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 (DBF cutoff 5 −30%, P , 0.001). Conclusion: This study suggests the clinical usefulness of an early user-and patient-friendly 2-min dynamic acquisition to monitor breast tumor DBF to neoadjuvant chemotherapy using 18 F-FDG PET/CT. Monitoring tumor perfusion and angiogenesis response to treatment seems to be a promising target for PET tracers.

Getting the Most out of 18F-FDG PET Scans: The Predictive Value of 18F-FDG PET–Derived Blood Flow Estimates for Breast Cancer

“…In this issue of The Journal of Nuclear Medicine, Humbert et al report that low overall survival is associated with triple-negative breast cancer patients whose tumors experienced a less than 30% drop in tumor first-pass BF after neoadjuvant therapy (8). Humbert et al also found their firstpass BF estimates capable of stratifying between patients with 87% versus 48% overall survival (P , 0.001) in women without a pathologic complete response (8). The results of Humbert et al support using first-pass 18 F-FDG PET scans as an alternative to 15 O-water PET scans for estimating BF to tumors.…”

“…In Humbert et al, results are reported from analyses of a 2-part imaging protocol in which patients were positioned prone followed by a 1-bed-position 18 F-FDG 2-min dynamic PET scan, which was followed by an additional PET scan starting 90 min after injection that was completed over prone patients in a region that included the first scan's imaging area (8) (7) whereas the Humbert et al protocol was completed in patients undergoing neoadjuvant therapy before and after the first course of chemotherapy (8). Analyses of the Humbert et al 2-part set of PET images (2-min dynamic and 90-min static) yielded estimates of BF (first-pass BF from 18 F-FDG scans) and tumor metabolism (SUV) in a manner analogous to the kinetic analysis of a single 60-min dynamic 18 F-FDG scan yielding estimates of tracer transport ( 18 F-FDG transport) and tumor metabolism (flux, metabolic rate of 18 F-FDG, or SUV).…”

“…An alternative method for estimating BF from 18 F-FDG PET uses the first-pass extraction model of Mullani et al (5), which assumes highly extracted tracers can be used to estimate BF with a 1-compartment model during the first pass of the tracer through the tissue that in practice requires only a 2-min dynamic PET scan starting simultaneously with injection of 18 F-FDG (6)(7)(8). The average first-pass 18 F-FDG BF (first-pass BF) estimates using this method were found to correlate with 15 O-water (R 2 5 0.74), with first-pass BF estimates being on average 14% below BF estimates from 15 O-water PET scans (6).…”

2-18F-Fluoroethanol Is a PET Reporter of Solid Tumor Perfusion

“…Tumor perfusion itself is also a primary variable of interest, because tumor perfusion influences nutrient delivery to the tumor with potential effects on tumor metabolism and progression, and tumor perfusion also affects delivery of chemotherapeutics. Measuring tumor perfusion either at baseline or before and after a therapy cycle has predicted disease-free survival in patients with breast cancer (8,9), response to chemotherapy in head and neck cancer (10), response of cervical cancer to radiation therapy (11), and response of glioblastoma to antiangiogenic therapy (12). In addition to complementing hypoxia reporters and independently providing prognostic data, noninvasive imaging of tumor perfusion could be used preclinically to study strategies for modifying tumor perfusion for either radiosensitization or manipulating chemotherapy delivery.…”

Compact ultrasound-guided diffuse optical tomography system for breast cancer imaging

“…Ultrasound (US) and mammography show moderate sensitivity in the assessment of tumor response. 5 Dynamic contrast-enhanced MRI and 18Ffluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) have been utilized to predict breast cancer response to neoadjuvant therapy, [6][7][8] and have shown their ability in early identification of response. However, MRI and PET/CT are expensive and require injection of contrast agents and their repeated use in monitoring patients during treatment is not feasible.…”