David Groheux

18F-FDG PET Uptake Characterization Through Texture Analysis: Investigating the Complementary Nature of Heterogeneity and Functional Tumor Volume in a Multi–Cancer Site Patient Cohort

Intratumoral uptake heterogeneity in 18F-FDG PET has been associated with patient treatment outcomes in several cancer types. Textural feature analysis is a promising method for its quantification. An open issue associated with textural features for the quantification of intratumoral heterogeneity concerns its added contribution and dependence on the metabolically active tumor volume (MATV), which has already been shown to be a significant predictive and prognostic parameter. Our objective was to address this question using a larger cohort of patients covering different cancer types. Methods: A single database of 555 pretreatment 18F-FDG PET images (breast, cervix, esophageal, head and neck, and lung cancer tumors) was assembled. Four robust and reproducible textural feature–derived parameters were considered. The issues associated with the calculation of textural features using co-occurrence matrices (such as the quantization and spatial directionality relationships) were also investigated. The relationship between these features and MATV, as well as among the features themselves, was investigated using Spearman rank coefficients for different volume ranges. The complementary prognostic value of MATV and textural features was assessed through multivariate Cox analysis in the esophageal and non–small cell lung cancer (NSCLC) cohorts. Results: A large range of MATVs was included in the population considered (3–415 cm3; mean, 35; median, 19; SD, 50). The correlation between MATV and textural features varied greatly depending on the MATVs, with reduced correlation for increasing volumes. These findings were reproducible across the different cancer types. The quantization and calculation methods both had an impact on the correlation. Volume and heterogeneity were independent prognostic factors (P = 0.0053 and 0.0093, respectively) along with stage (P = 0.002) in non–small cell lung cancer, but in the esophageal tumors, volume and heterogeneity had less complementary value because of smaller overall volumes. Conclusion: Our results suggest that heterogeneity quantification and volume may provide valuable complementary information for volumes above 10 cm3, although the complementary information increases substantially with larger volumes.

Performance of FDG PET/CT in the Clinical Management of Breast Cancer

In this analysis, the role of metabolic imaging with fluorine 18 fluorodeoxyglucose (FDG) in breast cancer is reviewed. The analysis was limited to recent works by using state-of-the-art positron emission tomography (PET)/computed tomography (CT) technology. The strengths and limitations of FDG PET/CT are examined in various clinical settings, and the following questions are answered: Is FDG PET/CT useful to differentiate malignant from benign breast lesions? Can FDG PET/CT replace sentinel node biopsy for axillary staging? What is the role of FDG PET/CT in initial staging of inflammatory or locally advanced breast cancer? What is the role of FDG PET/CT in initial staging of clinical stage IIA and IIB and primary operable stage IIIA breast cancer? How does FDG PET/CT compare with conventional techniques in the restaging of cancer in patients who are suspected of having disease recurrence? What is the role of FDG PET/CT in the assessment of early response to neoadjuvant therapy and of response to therapy for metastatic disease? Some recommendations for clinical practice are given.

Effect of 18F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

PURPOSE To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

Prognostic Impact of 18FDG-PET-CT Findings in Clinical Stage III and IIB Breast Cancer

Background This study prospectively evaluated the yield of fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET-CT) in patients with clinical stages II and III breast cancer and the impact of PET-CT results on prognosis. Methods In the course of 71 months, 254 consecutive patients with clinical stages II and III breast cancer (based on clinical examination, mammography, breast magnetic resonance imaging, and locoregional ultrasonography) underwent 18FDG-PET-CT. The yield was assessed in the whole population and for each American Joint Committee on Cancer subgroup. The prognostic impact of PET-CT findings was analyzed. Tests of statistical significance were two-sided. Results 18FDG-PET-CT changed the clinical stage in 77 of 254 patients (30.3%; 95% confidence interval [CI] = 25.0% to 36.2%). It showed unsuspected N3 disease (infraclavicular, supraclavicular, or internal mammary nodes) in 40 patients and distant metastases in 53. PET-CT revealed distant metastases in 2.3% (1 of 44) of clinical stage IIA, 10.7% (6 of 56) of stage IIB, 17.5% (11 of 63) of stage IIIA, 36.5% (27 of 74) of stage IIIB, and 47.1% (8 of 17) of stage IIIC patients. Among 189 patients with clinical stage IIB or higher disease and adequate follow-up, disease-specific survival was statistically significantly shorter in the 47 patients scored M1 on 18FDG-PET-CT in comparison with those scored M0, with a three-year disease-specific survival of 57% vs 88% (P < .001). In multivariable analysis, only distant disease on PET-CT and triple-negative phenotype were statistically significant prognostic factors. The relative risk of death was 26.60 (95% CI = 6.60 to 102.62) for M1 vs M0 patients. Conclusions The yield of 18FDG-PET-CT appeared substantial in patients with clinical stage IIB or higher breast cancer. In these patients, 18FDG-PET-CT provided powerful prognostic stratification.

The Yield of 18F-FDG PET/CT in Patients with Clinical Stage IIA, IIB, or IIIA Breast Cancer: A Prospective Study

The purpose of this study was to prospectively evaluate the role of 18F-FDG PET/CT in patients with stage IIA, IIB, or IIIA breast cancer. Methods: During 56 mo, 131 consecutive patients with large (>2 cm) breast cancer and clinical stage IIA, IIB, or IIIA (based on clinical examination, mammography, breast MRI, and ultrasonography) underwent 18F-FDG PET/CT. The nuclear physician was unaware of the results of any other procedure (bone scan, chest radiography, liver ultrasound, or thoracoabdominal CT scan). Results: Of the 131 examined patients, 36 had clinical stage IIA (34 T2N0 and 2 T1N1), 48 stage IIB (20 T3N0 and 28 T2N1), and 47 stage IIIA (29 T3N1, 9 T2N2, and 9 T3N2). 18F-FDG PET/CT modified staging for 5.6% of stage IIA patients, for 14.6% of stage IIB patients, and for 27.6% of stage IIIA patients. However, within stage IIIA, the yield was specifically high among the 18 patients with N2 disease (56% stage modification). When considering stage IIB and primary operable IIIA (T3N1) together, the yield of 18F-FDG PET/CT was 13% (10/77); extraaxillary regional lymph nodes were detected in 5 and distant metastases in 7 patients. In this series, 18F-FDG PET/CT outperformed bone scanning, with only 1 misclassification versus 8 for bone scanning (P = 0.036). Conclusion: 18F-FDG PET/CT provided useful information in 13% of patients with clinical T3N0, T2N1, or T3N1 disease. The yield was more modest in patients with stage IIA. The high yield in the case of N2 disease demonstrates that stage IIIA comprises 2 quite distinct groups of patients.

18F-FDG PET/CT in Staging Patients with Locally Advanced or Inflammatory Breast Cancer: Comparison to Conventional Staging

The prognosis of patients with locally advanced breast cancer (LABC) remains poor. We prospectively investigated the impact of 18F-FDG PET/CT at initial staging in this clinical setting and compared PET/CT performance with that of conventional distant work-up. Methods: During 60 mo, consecutive patients with LABC (clinical T4 or N2–N3 disease) underwent 18F-FDG PET/CT. The yield was assessed in the whole group and separately for noninflammatory and inflammatory cancer. The performance of PET/CT was compared with that of a conventional staging approach including bone scanning, chest radiography, or dedicated CT and abdominopelvic sonography or contrast-enhanced CT. Results: 117 patients with inflammatory (n = 35) or noninflammatory (n = 82) LABC were included. 18F-FDG PET/CT confirmed N3 nodal involvement in stage IIIC patients and revealed unsuspected N3 nodes (infraclavicular, supraclavicular, or internal mammary) in 32 additional patients. Distant metastases were visualized on PET/CT in 43 patients (46% of patients with inflammatory carcinoma and 33% of those with noninflammatory LABC). Overall, 18F-FDG PET/CT changed the clinical stage in 61 patients (52%). Unguided conventional imaging detected metastases in only 28 of the 43 patients classified M1 with PET/CT (65%). 18F-FDG PET/CT outperformed conventional imaging for bone metastases, distant lymph nodes, and liver metastases, whereas CT was more sensitive for lung metastases. The accuracy in diagnosing bone lesions was 89.7% for planar bone scanning versus 98.3% for 18F-FDG PET/CT. The accuracy in diagnosing lung metastases was 98.3% for dedicated CT versus 97.4% for 18F-FDG PET/CT. Conclusion: 18F-FDG PET/CT had the advantage of allowing chest, abdomen and bone to be examined in a single session. Almost all distant lesions detected by conventional imaging were depicted with PET/CT, which also showed additional lesions.

Comparison Between 18F-FDG PET Image–Derived Indices for Early Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer

The goal of this study was to determine the best predictive factor among image-derived parameters extracted from sequential 18F-FDG PET scans for early tumor response prediction after 2 cycles of neoadjuvant chemotherapy in breast cancer. Methods: 51 breast cancer patients were included. Responder and nonresponder status was determined by histopathologic examination according to the tumor and node Sataloff scale. PET indices (maximum and mean standardized uptake value [SUV], metabolically active tumor volume, and total lesion glycolysis [TLG]), at baseline and their variation (Δ) after 2 cycles of neoadjuvant chemotherapy were extracted from the PET images. Their predictive value was investigated using Mann–Whitney U tests and receiver-operating-characteristic analysis. Subgroup analysis was also performed by considering estrogen receptor (ER)–positive/human epidermal growth factor receptor 2 (HER2)–negative, triple-negative, and HER2-positive tumors separately. The impact of partial-volume correction was also investigated using an iterative deconvolution algorithm. Results: There were 24 pathologic nonresponders and 27 responders. None of the baseline PET parameters was correlated with response. After 2 neoadjuvant chemotherapy cycles, the reduction of each parameter was significantly associated with response, the best prediction of response being obtained with ΔTLG (96% sensitivity, 92% specificity, and 94% accuracy), which had a significantly higher area under the curve (0.91 vs. 0.82, P = 0.01) than did ΔSUVmax (63% sensitivity, 92% specificity, and 77% accuracy). Subgroup analysis confirmed a significantly higher accuracy for ΔTLG than ΔSUV for ER-positive/HER-negative but not for triple-negative and HER2-positive tumors. Partial-volume correction had no impact on the predictive value of any of the PET image–derived parameters despite significant changes in their absolute values. Conclusion: Our results suggest that the reduction after 2 neoadjuvant chemotherapy cycles of the metabolically active volume of primary tumor measurements such as ΔTLG predicts histopathologic tumor response with higher accuracy than does ΔSUV measurements, especially for ER-positive/HER2-negative breast cancer. These results should be confirmed in a larger group of patients as they may potentially increase the clinical value and efficiency of 18F-FDG PET for early prediction of response to neoadjuvant chemotherapy.

Early monitoring of response to neoadjuvant chemotherapy in breast cancer with 18F-FDG PET/CT: defining a clinical aim

In Europe, in 2008, it was estimated that 421,000 new cases of breast cancer were diagnosed; 129,000 women died from breast cancer in the same year [1]. Neoadjuvant chemotherapy (NAC), initially used only for locally advanced breast cancer, is now commonly used in patients with operable but large breast cancer. This strategy allows patients to undergo breast-conserving surgery (BCS) and gives information on the efficacy of chemotherapy [2]. Long-term outcomes are significantly correlated with pathological tumour response rates [3]. In the present paper we here focus on what could be the role of an early evaluation with F-FDG PET/CT of the response to NAC in patients with operable breast cancer.

Estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast tumors: Early prediction of chemosensitivity with (18) F-fluorodeoxyglucose positron emission tomography/computed tomography during neoadjuvant chemotherapy.

The objective of this prospective study was to evaluate the ability of 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) to predict chemosensitivity in patients with estrogen receptor (ER)‐positive/human epidermal growth factor receptor 2 (HER2)‐negative breast cancer.

Early assessment with 18F-fluorodeoxyglucose positron emission tomography/computed tomography can help predict the outcome of neoadjuvant chemotherapy in triple negative breast cancer

BACKGROUND In patients with triple-negative breast cancer (TNBC), pathology complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This prospective study was designed and powered to investigate the ability of interim (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) to predict pathology outcomes to NAC early during treatment. PATIENTS AND METHODS Consecutive TNBC women underwent (18)FDG-PET/CT at baseline and after two courses of NAC. Maximum standardised uptake value (SUV(max)) in the primary tumour and lymph nodes at each examination and the evolution (ΔSUV(max)) between the two scans were measured. NAC was continued irrespective of PET results. Correlations between PET parameters and pathology response, and between PET parameters and event-free survival (EFS), were examined. RESULTS Fifty patients without distant metastases were enroled. At completion of NAC, surgery showed pCR in 19 patients, while 31 had residual tumour. Mean follow-up was 30.3 months. Thirteen patients, all with residual tumour, experienced relapse. Of all assessed clinical, biological and PET parameters, ΔSUV(max) in the primary tumour was the most predictive of pathology results (p<0.0001; Mann-Whitney-U test) and EFS (p=0.02; log rank test). A threshold of 42% decrease in SUV was identified because it offered the best accuracy in predicting EFS. There were 32 metabolic responders (⩾ 42% decrease in SUV(max)) and 18 non-responders. Within responders, the pCR rate was 59% and the 3-year EFS 77.5%. In non-responders, the pCR rate was 0% and the 3-year EFS 47.1%. CONCLUSION Interim (18)FDG can early predict the inefficacy of NAC in TNBC patients. It shows promise as a potential contributory biomarker in these patients.