Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography in Monitoring the Response of Breast Cancer to Neoadjuvant Chemotherapy: A Meta–Analysis

Abstract

Introduction

To evaluate the diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in monitoring the response of breast cancers to neoadjuvant chemotherapy.

Methods

Articles published in medical and oncologic journals between January 2000 and June 2012 were identified by systematic MEDLINE, Cochrane Database for Systematic Reviews, and EMBASE, and by manual searches of the references listed in original and review articles. Quality of the included studies was assessed by using the quality assessment of diagnosis accuracy studies score tool. Meta-DiSc statistical software was used to calculate the summary sensitivity and specificity, positive predictive and negative predictive values, and the summary receiver operating characteristics curve (SROC).

Results

Fifteen studies with 745 patients were included in the study after meeting the inclusion criteria. The pooled sensitivity and specificity of FDG-PET or PET/CT were 80.5% (95% CI, 75.9%-84.5%) and 78.8% (95% CI, 74.1%-83.0%), respectively, and the positive predictive and negative predictive values were 79.8% and 79.5%, respectively. After 1 and 2 courses of chemotherapy, the pooled sensitivity and false-positive rate were 78.2% (95% CI, 73.8%-82.5%) and 11.2%, respectively; and 82.4% (95% CI, 77.4%-86.1%) and 19.3%, respectively.

Conclusions

Analysis of the findings suggests that FDG-PET has moderately high sensitivity and specificity in early detection of responders from nonresponders, and can be applied in the evaluation of breast cancer response to neoadjuvant chemotherapy in patients with breast cancer.

Introduction

Neoadjuvant chemotherapy (NACT) is administered to cancer patients before surgery or radical radiotherapy to reduce tumor size by allowing for more women to become candidates for breast conserving therapy. NACT is often used in the management of large, locally advanced breast cancers (stages IIb, IIIa, and IIIb of the TNM classification), and in large operable tumors that would otherwise require mastectomy.¹ The therapy aims at shrinking the size of the primary breast cancer by reducing the tumor volume and to provide disease-free survival, overall survival, and local control. If followed by surgery, the NACT also helps in the evaluation of histologic response of the tumor.1, 2, 3 Because the rationale for NACT is to assess for chemosensitivity to allow for changes in the therapy regimen if needed, knowledge about affects of treatment is important to determine if the current treatment should be continued, stopped, or switched to a more-aggressive second-line regimen.

Monitoring of tumor response to NACT is usually by histopathologic assessment, clinical and physical assessment, or anatomic and physiologic imaging.1, 4, 5 However, clinical examination has been reported to be an unreliable diagnostic tool, and conventional imaging modalities lack accuracy,4, 5 and, because of the difficulty in differentiating fibrosis from residual tumor, conventional imaging modalities are of limited use for monitoring the treatment response.⁴ On the contrary, fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a valuable metabolic tool for monitoring the effects of chemotherapy.1, 6, 7, 8, 9, 10 Being a metabolic and functional imaging modality, positron emission tomography (PET) can demonstrate changes in tumor metabolism before morphologic changes occur, so unresponsive tumors can be identified quickly. The uptake of FDG in a tumor after chemotherapy is predictive of the response to therapy; a treatment-induced reduction in metabolic activity correlates with a positive clinical response.11, 12 Hybrid PET–computed tomography (PET/CT) helps improve the accuracy of evaluation of treatment response beyond that achievable with PET alone by directly depicting metabolic and anatomic changes.¹²

Tumor response after initiation of chemotherapy has been previously reported to occur, usually after the first and second cycles. A more notable decrease in FDG uptake has been reported after the first and second courses of NACT in responders than in nonresponders.9, 12, 13 The definition of a treatment response as a reference for a metabolic response as well as the histopathologic response criteria used, however, was found to vary from one study to another, with response rates that ranged from 16.3% to 55.6%.12, 13 Because there is no consensus on the precise timing of PET, that is, whether PET imaging should be performed after the first, second, or third cycle of chemotherapy, translating these findings into clinical practice poses certain difficulties.

Previous studies used different thresholds for the relative changes in tumor metabolic activity, eg, standardized uptake value (SUV), to predict tumor response to NACT, which results in variations in sensitivities and specificities.6, 7, 8, 9, 10, 11, 12 One multicenter trial reported a positive correlation between histopathologic response and the level of FDG uptake after the first and second courses of NACT; however, it failed to show which SUV cutoff value was more appropriate to distinguish responders from nonresponders.¹⁴ This meta-analysis was aimed at reviewing the current literature and at evaluating the diagnostic role of FDG-PET or PET/CT in the monitoring of tumor response to NACT in patients with breast cancer.