Use of Dynamic Contrast-enhanced MR Imaging to Predict Survival in Patients with Primary Breast Cancer Undergoing Neoadjuvant Chemotherapy

Li, Sonia P.; Makris, Andreas; Beresford, Mark; Taylor, N. Jane; Ah-See, Mei-Lin W.; Stirling, James; d’Arcy, James A.; Collins, David J.; Kozarski, Robert; Padhani, Anwar R.

doi:10.1148/radiol.11102493

Cited by 97 publications

(71 citation statements)

References 27 publications

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“…In the neoadjuvant setting of breast cancer, these modalities demonstrated that maintained tumor BF at therapy midpoint was associated with poorer survival (12,13). Dynamic contrastenhanced MRI is widely available and frequently used in studies evaluating tumor BF response to treatment (28,29). Dynamic contrastenhanced-MRI derived biomarkers, particularly those involving tumor kinetic textures, are able to predict tumor histologic response early (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…Dynamic contrastenhanced MRI is widely available and frequently used in studies evaluating tumor BF response to treatment (28,29). Dynamic contrastenhanced-MRI derived biomarkers, particularly those involving tumor kinetic textures, are able to predict tumor histologic response early (28,29). The clinical value of monitoring tumor BF using 15 O-water PET has also been evaluated: BF in breast cancer is highly variable and women with persistent or elevated tumor BF on interim PET experienced poorer tumor response and outcomes (11)(12)(13), thus paralleling our results in the specific TNBC population.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…However, it was not designed to assess the ability of DCE as an overall technique to assess pathological response, which has been explored by other studies. 1,2 As discussed previously, there are a number of methods to measure the AIF and this study addressed only the use of differing population AIFs. Although this is the most commonly used technique, there are others in use, and the comparison with these also needs to be made.…”

Section: Limitationsmentioning

confidence: 99%

“…2 There are, however, other parameters which we did not evaluate including k ep (rate constant) and IAUGC (initial area under the gadolinium concentration-time curve) whose test performance may be affected.…”

Section: Limitationsmentioning

confidence: 99%

“…Clinical studies using dynamic contrast-enhanced MRI (DCE-MRI) have established that changes in kinetic parameters after 1-2 cycles of NAC can predict for clinical and pathological response 1 as well as disease-free and overall survival. 2 Quantitative kinetic parameters, and in particular changes in forward transfer constant (K trans ), provide the majority of the evidence for clinical utility in the setting of NAC for breast cancer. 3 To calculate quantitative DCE-MRI kinetic parameters, the concentration of the contrast medium in the vasculature supplying the tumour, known as the arterial input function (AIF), needs to be defined.…”

Section: Introductionmentioning

confidence: 99%

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Arterial input functions in dynamic contrast-enhanced magnetic resonance imaging: which model performs best when assessing breast cancer response?

Woolf

Taylor

Makris

et al. 2016

BJR

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Objective: To evaluate the performance of six models of population arterial input function (AIF) in the setting of primary breast cancer and neoadjuvant chemotherapy (NAC). The ability to fit patient dynamic contrastenhanced MRI (DCE-MRI) data, provide physiological plausible data and detect pathological response was assessed. Methods: Quantitative DCE-MRI parameters were calculated for 27 patients at baseline and after 2 cycles of NAC for 6 AIFs. Pathological complete response detection was compared with change in these parameters from a reproduction cohort of 12 patients using the Bland-Altman approach and receiver-operating characteristic analysis. Results: There were fewer fit failures pre-NAC for all models, with the modified Fritz-Hansen having the fewest pre-NAC (3.6%) and post-NAC (18.8%), contrasting with the femoral artery AIF (19.4% and 43.3%, respectively).Median transfer constant values were greatest for the Weinmann function and also showed greatest reductions with treatment (268%). Reproducibility (r) was the lowest for the Weinmann function (r 5 249.7%), with other AIFs ranging from r 5 227.8 to 239.2%. Conclusion: Using the best performing AIF is essential to maximize the utility of quantitative DCE-MRI parameters in predicting response to NAC treatment. Applying our criteria, the modified Fritz-Hansen and cosine bolus approximated Parker AIF models performed best. The Fritz-Hansen and biexponential approximated Parker AIFs performed less well, and the Weinmann and femoral artery AIFs are not recommended. Advances in knowledge: We demonstrate that using the most appropriate AIF can aid successful prediction of response to NAC in breast cancer.

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Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling

Simrick

Szumska

Gardiner

et al. 2012

Developmental Dynamics

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Background 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans, characterised by cardiovascular defects such as interrupted aortic arch, outflow tract defects, thymus and parathyroid hypo- or aplasia and cleft palate. Heterozygosity of Tbx1, the mouse homologue of the candidate TBX1 gene, results in mild defects dependent on genetic background, whereas complete inactivation results in severe malformations in multiple tissues. Results The loss of function mutations in two Sprouty genes, which encode feedback antagonists of receptor tyrosine kinase (RTK) signaling, phenocopy many defects associated with the syndrome in the mouse. The stepwise reduction of Sprouty gene dosage resulted in different phenotypes emerging at specific steps, suggesting that the threshold up to which a given developmental process can tolerate increased RTK signaling is different. Tbx1 heterozygosity significantly exacerbated the severity of all these defects, which correlated with a substantial increase in RTK signaling. Conclusions Our findings suggest that TBX1 functions as an essential component of a mechanism that protects the embryo against perturbations in RTK signaling that may lead to developmental defects characteristic of 22q11.2 deletion syndrome. We propose that genetic factors that enhance RTK signalling ought to be considered as potential genetic modifiers of this syndrome.

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Use of Dynamic Contrast-enhanced MR Imaging to Predict Survival in Patients with Primary Breast Cancer Undergoing Neoadjuvant Chemotherapy

Cited by 97 publications

References 27 publications

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

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

Arterial input functions in dynamic contrast-enhanced magnetic resonance imaging: which model performs best when assessing breast cancer response?

Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling

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Use of Dynamic Contrast-enhanced MR Imaging to Predict Survival in Patients with Primary Breast Cancer Undergoing Neoadjuvant Chemotherapy

Cited by 97 publications

References 27 publications

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

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

Arterial input functions in dynamic contrast-enhanced magnetic resonance imaging: which model performs best when assessing breast cancer response?

Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling

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

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