Alexandre Cochet

[18F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy

PurposeTo evaluate, in breast cancer patients treated by neoadjuvant chemotherapy, the predictive value of reduction in FDG uptake with regard to complete pathological response (pCR).MethodsForty-seven women with non-metastatic, non-inflammatory, large or locally advanced breast cancer were included. Tumour uptake of FDG was evaluated before and after the first course of neoadjuvant chemotherapy. Four indices were used: maximal and average SUV without or with correction by body surface area and glycaemia (SUVmax, SUVavg, SUVmax-BSA-G and SUVavg-BSA-G, respectively). The predictive value of reduction in FDG uptake with respect to pCR was studied by logistic regression analysis. Relationships between baseline [18F]FDG uptake and prognostic parameters were assessed.ResultsThe relative decrease in FDG uptake (ΔSUV) after the first course of neoadjuvant chemotherapy was significantly greater in the pCR group than in the non-pCR group (p < 0.000066). The four FDG uptake indices were all strongly correlated with each other. A decrease in SUVmax-BSA-G of 85.4% ± 21.9% was found in pCR patients, versus 22.6% ± 36.6% in non-pCR patients. ΔSUVmax-BSA-G <−60% predicted the pCR with an accuracy of 87% and ΔSUVs were found to be only factors predictive of the pCR at multivariate analysis. An elevated baseline SUV was associated with high mitotic activity (p < 0.0016), tumour grading (p < 0.004), high nuclear pleomorphism score (p < 0.03) and negative hormonal receptor status (p < 0.005).ConclusionIn breast cancer patients, after only one course of neoadjuvant chemotherapy the reduction in FDG uptake is an early and powerful predictor of pCR.

Prognostic Value of Microvascular Obstruction and Infarct Size, as Measured by CMR in STEMI Patients

The aim of this study was to evaluate the value of microvascular obstruction (MO) and infarct size as a percentage of left ventricular mass (IS%LV), as measured by contrast-enhanced cardiac magnetic resonance, in predicting major cardiovascular adverse events (MACE) at 2 years in patients with ST-segment elevation myocardial infarction reperfused by primary percutaneous coronary intervention. Individual data from 1,025 patients were entered into the pooled analysis. MO was associated with the occurrence of MACE, defined as a composite of cardiac death, congestive heart failure, and myocardial re-infarction (adjusted hazard ratio: 3.74; 95% confidence interval: 2.21 to 6.34). IS%LV ≥25% was not associated with MACE (adjusted hazard ratio: 0.90; 95% confidence interval: 0.59 to 1.37). The authors conclude that MO is an independent predictor of MACE and cardiac death, whereas IS%LV is not independently associated with MACE.

In Newly Diagnosed Diffuse Large B-Cell Lymphoma, Determination of Bone Marrow Involvement with 18F-FDG PET/CT Provides Better Diagnostic Performance and Prognostic Stratification Than Does Biopsy

In newly diagnosed diffuse large B-cell lymphoma (DLBCL), the sensitivity of bone marrow biopsy (BMB) for the detection of bone marrow involvement (BMI) can be low because of sampling error if the BMI is focal and not diffuse. Although 18F-FDG PET/CT is now recommended for initial staging of DLBCL, its role regarding BMI is not well defined. This study evaluated whether 18F-FDG PET/CT, in comparison with BMB, is useful for the detection of BMI and predictive of outcome. Methods: From the 142 patients who were referred to our institution for newly diagnosed DLBCL from June 2006 to October 2011, 133 were retrospectively enrolled in our study. All patients underwent whole-body 18F-FDG PET/CT and a BMB from the iliac crest before any treatment. 18F-FDG PET/CT was considered positive for BMI in cases of uni- or multifocal bone marrow 18F-FDG uptake that could not be explained by benign findings on the underlying CT image or history. A final diagnosis of BMI was considered if the BMB was positive or if the positive 18F-FDG PET/CT was confirmed by guided biopsy or targeted MR imaging or in cases of disappearance of focal bone marrow uptake concomitant with the disappearance of uptake in other lymphoma lesions on 18F-FDG PET/CT monitoring. Progression-free survival and overall survival were analyzed using the Cox proportional hazards regression model. Results: Thirty-three patients were considered to have BMI. Of these, 8 were positive according to the BMB and 32 were positive according to 18F-FDG PET/CT. 18F-FDG PET/CT was more sensitive (94% vs. 24%; P < 0.001), showed a higher negative predictive value (98% vs. 80%), and was more accurate (98% vs. 81%) than BMB. Median follow-up was 24 mo (range, 1–67 mo). Twenty-nine patients (22%) experienced recurrence or disease progression during follow-up, and 20 patients died (15%). In multivariate analysis, only the International Prognostic Index and the 18F-FDG PET/CT bone marrow status were independent predictors of progression-free survival (P = 0.005 and 0.02, respectively), whereas only the International Prognostic Index remained an independent predictor of overall survival (P = 0.004). Conclusion: Assessment of BMI with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification in newly diagnosed DLBCL than does BMB.

Major prognostic impact of persistent microvascular obstruction as assessed by contrast-enhanced cardiac magnetic resonance in reperfused acute myocardial infarction

The aim of this study was to compare the prognostic significance of microvascular obstruction (MO) and persistent microvascular obstruction (PMO) as assessed by cardiac magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). CMR was performed in 184 patients within the week following successfully reperfused first AMI. First-pass images were performed to evaluate extent of MO and late gadolinium-enhanced images to assess PMO and infarct size (IS). Major adverse cardiac events (MACE) were collected at 1-year follow-up. MO and PMO were found in 127 (69%) and 87 (47%) patients, respectively. By using univariate logistic regression analysis, high Global Registry of Acute Coronary Events (GRACE) risk score (odds ratio [OR] 95% confidence interval [CI]: 3.6 [1.8–7.4], p < 0.001), IS greater than 10% (OR [95% CI]: 2.7 [1.1–6.9], p = 0.036), left ventricular ejection fraction less than 40% (OR [95% CI]: 2.4 [1.1–5.2], p = 0.027), presence of MO (OR [95% CI]: 3.1 [1.3–7.3], p = 0.004) and presence of PMO (OR [95% CI]:10 [4.1–23.9], p < 0.001) were shown to be significantly associated with the outcome. By using multivariate analysis, presence of MO (OR [95% CI]: 2.5 [1.0–6.2], p = 0.045) or of PMO (OR [95% CI]: 8.7 [3.6–21.1], p < 0.001), associated with GRACE score, were predictors of MACE. Presence of microvascular obstruction and persistent microvascular obstruction is very common in AMI patients even after successful reperfusion and is associated with a dramatically higher risk of subsequent cardiovascular events, beyond established prognostic markers. Moreover, our data suggest that the prognostic impact of PMO might be superior to MO.

Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how?

Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.

Visual estimation of the global myocardial extent of hyperenhancement on delayed contrast-enhanced MRI

MRI with paramagnetic contrast agent allows the assessment of the extent of myocardial tissue injury after infarction. Visual segmental scoring has been widely used to define the transmural extent of myocardial infarction, but no attempt has been made to use visual scores in order to assess the percentage of the whole myocardium infarcted. By summing all the segmental scores using a 17-segment model, a global index of the size of the infarcted myocardium is easily obtained. The entire left ventricle of 60 patients with a recent myocardial infarction was scanned using an ECG-gated gradient echo sequence after injection of gadolinium contrast agent. The global score was defined as the sum of the scores on each segment, and expressed as a percentage of the maximum possible score. This index was compared with a planimetric evaluation of hyperenhancement, expressed as a percentage of the left ventricle myocardial volume. There is a good correlation between the two methods (r=0.91; y=1.06x+0.20), and the Bland-Altman plot shows a high concordance between the two approaches (mean of the differences =1.45%). A visual approach based on a 17-segment model can be used to evaluate the global myocardial extent of the hyperenhancement with similar results to planimetry.

The extent of myocardial damage assessed by contrast‐enhanced MRI is a major determinant of N‐BNP concentration after myocardial infarction

To evaluate the relationship between N‐terminal Pro‐Brain Natriuretic Peptide (N‐BNP) level and contrast‐enhanced MRI in patients after acute myocardial infarction (MI).

Role of Positron Emission Tomography for the Monitoring of Response to Therapy in Breast Cancer

This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with (18)F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype. The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor.

Evaluation of Breast Tumor Blood Flow with Dynamic First-Pass 18F-FDG PET/CT: Comparison with Angiogenesis Markers and Prognostic Factors

The purpose of this study was to prospectively evaluate the relationship between tumor blood flow and glucose metabolism as evaluated by dynamic first-pass 18F-FDG PET and by proliferation and endothelial pathologic markers in the setting of newly diagnosed breast cancer. Methods: Forty patients were prospectively included. Biopsy samples of each tumor were used to assess the Ki67 index of proliferation and immunostaining for CD34 (a panendothelial cell marker) and CD105 (a proliferation-related endothelial cell marker). All patients underwent 18F-FDG PET/CT at least 1 wk after sample biopsy and before any treatment. A dynamic 2-min acquisition was performed immediately after intravenous injection of a 5 MBq/kg dose of 18F-FDG; tumor blood flow was then calculated using a single-compartment kinetic model. A static acquisition was performed 90 min after injection for quantification of delayed 18F-FDG tumor uptake (standardized uptake value maximal index [SUVmax]), reflecting tumor metabolism. Results: Pathologic and PET/CT data were available for all patients. The SUVmax measured on delayed PET images correlated strongly and positively with the expression of Ki67 (r = +0.69; P < 0.0001). In contrast, there was no significant correlation between SUVmax and endothelial markers (CD34 and CD105). Tumor blood flow correlated positively with the expression of CD34 and CD105 (P = 0.016 and P = 0.007, respectively) and with the expression of Ki67 (P = 0.028). By logistic regression analysis, only expression of Ki67 remained an independent predictor of high (supramedian) SUVmax; CD105 score and histopathologic grade 3 were independently associated with a high (supramedian) tumor blood flow level. Conclusion: Tumor blood flow quantified by dynamic first-pass 18F-FDG PET/CT is significantly associated with tumor angiogenesis as evaluated by immunohistochemistry in the setting of breast cancer, whereas tumor metabolism appears to be more associated with markers of proliferation. Thus, determination of tumor blood flow and metabolism with a single injection of 18F-FDG could be an exciting alternative to more complex and less available techniques.

Pattern of occult nodal relapse diagnosed with 18F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy

INTRODUCTION The purpose of this study was to describe the pattern of nodal relapse with (18)F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. MATERIALS AND METHODS Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. RESULTS Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ⩾2 positive nodes on FCH PET/CT (OR=8.75, [95% CI: 1.38-54.80], p=0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. CONCLUSION 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.