Laetitia Vercellino

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.

18F-FDG PET/CT Imaging for an Early Assessment of Response to Sunitinib in Metastatic Renal Carcinoma: Preliminary Study

PURPOSE Sunitinib is a new standard for the treatment of metastatic renal-cell carcinoma (RCC). We evaluated the accuracy of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in assessing early response to this antiangiogenic drug, which cannot be obtained with conventional CT. PROCEDURES Patients had an FDG-PET/CT at baseline and another one for follow-up at the end of the first cycle (at day 42). For each examination, all lesions were registered and the maximum standardized uptake value (SUV(max)) was measured. The metabolic response on PET at day 42 was assessed, using European Organization for Research and Treatment of Cancer criteria. Morphologic response on CT at day 84 (after two cycles), using Response Evaluation Criteria in Solid Tumors criteria, was used as the reference standard. The long-term outcome was assessed by the progression-free survival. RESULTS Twelve (12) patients who completed at least two cycles of sunitinib were assessed. The SUV(max) for the lesions with the highest uptake ranged between 2.9 and 11.8 for the 12 patients (mean = 6.3). Early PET/CT findings, after one cycle of sunitinib, were consistent with later CT results in 9 patients of 11 assessable patients: 1 patient progressed on PET and CT, 7 patients had stable disease, and 1 had a partial response. The other 2 patients had a metabolic partial response on PET and stable disease on CT. However, 1 patient achieved a partial response later in follow-up, suggesting that metabolic early changes are an indication of sunitinib activity. CONCLUSION FDG-PET/CT seems to be an interesting tool for the early evaluation of response to sunitinib in metastatic RCC. Larger studies are needed to confirm these preliminary results and establish a prognostic value for PET/CT.

HER2-overexpressing breast cancer: FDG uptake after two cycles of chemotherapy predicts the outcome of neoadjuvant treatment.

Background:Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes.Methods:During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) was performed at baseline (PET1) and after two cycles of chemotherapy (PET2). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUVmax at PET1, PET2 and ΔSUVmax) was examined with the t-test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis.Results:Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them 18F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUVmax value at PET2 (AUC=0.91) vs 0.67 for SUVmax at PET1 and 0.86 for ΔSUVmax. The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET2, no matter whether in breast or axilla, vs 11.8% in patients with uptake ⩽3 (P=0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%.Conclusion:The level of residual 18F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.

Lymphoscintigraphy Can Select Breast Cancer Patients for Internal Mammary Chain Radiotherapy

PURPOSE Given the risk of undesired toxicity, prophylactic internal mammary (IM) chain irradiation should be offered only to patients at high risk of occult involvement. Lymphoscintigraphy for axillary sentinel node biopsy might help in selecting these patients. METHODS AND MATERIALS We reviewed published studies with the following selection criteria: ≥ 300 breast cancer patients referred for axilla sentinel node biopsy; scintigraphy performed after peritumoral or intratumoral tracer injection; IM biopsy in the case of IM drainage; and axilla staged routinely independent of IM status. RESULTS Six prospective studies, for a total of 3,876 patients, fulfilled the inclusion criteria. Parasternal drainage was present in 792 patients (20.4%). IM biopsy was performed in 644 patients and was positive in 111 (17.2%). Of the positive IM biopsies, 40% were associated with tumors in the lateral breast quadrants. A major difference in the IM positivity rate was found according to the axilla sentinel node status. In patients with negative axilla, the IM biopsy was positive in 7.8% of cases. In patients with positive axilla, however, the IM biopsy was positive in 41% (p < .00001). Because biopsy of multiple IM hot nodes is difficult, the true risk could be even greater, probably close to 50%. CONCLUSIONS Patients with IM drainage on lymphoscintigraphy and a positive axilla sentinel node have a high risk of occult IM involvement. These women should be considered for IM radiotherapy.

Role of SPECT/CT in sentinel lymph node detection in patients with breast cancer.

Aim The purpose of this study was to conduct a systematic review of the published literature to assess the role (indications, advantages, and limitations) of SPECT/CT for the detection of sentinel lymph node (SLN) in breast cancer. Methods The authors searched PubMed for published literature in English addressing this topic. Results Eleven studies, published since 2006, focused on the role and value of SPECT/CT for SLN detection (SLND). They showed that SPECT/CT improved sentinel node detection and anatomical localization. One study suggested that SPECT/CT may provide a more accurate staging. Limitations for SLND with SPECT/CT include extra time and inconvenience for the patient and additional radiation dose. Conclusions SPECT/CT is a valuable tool for SLND, especially in difficult cases, when planar lymphoscintigraphy shows no SLN or unexpected lymphatic drainage.

Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor‐2 (FGF‐2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF‐2 limited hypoxia‐induced downregulation of HGF release. Using three‐dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF‐2 treatment increased the fraction of Stro‐1+/CD146+ progenitor cells. We then applied in vitro FGF‐2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF‐2 priming is more efficient than hypoxia at increasing SHED‐induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF‐2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF.

Hypoxia Imaging of Uterine Cervix Carcinoma With 18F-FETNIM PET/CT

Purpose Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with 18F-fluoroerythronitroimidazole (18F-FETNIM) and to compare 18F-FETNIM uptake with metabolic uptake of 18F-FDG. Patients and Methods We included 16 patients with cervical carcinoma. After imaging with FDG, 18F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. 18F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients’ outcomes. Results All tumors were detected by 18F-FDG PET. 18F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between 18F-FETNIM and 18F-FDG uptake. High 18F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 &mgr;g/L (median, 102.5 &mgr;g/L). Patients with OPN greater than 144 &mgr;g/L had reduced progression-free survival compared with those with OPN less than 144 &mgr;g/L (log-rank = 0.03). We found no significant correlation between 18F-FETNIM uptake and OPN blood levels. Conclusions Our preliminary results showed that a high uptake of 18F-FETNIM was associated with a worse progression-free and overall survival.

Fatal Heart Failure After a 26-Month Combination of Tyrosine Kinase Inhibitors in a Papillary Thyroid Cancer

BACKGROUND Patients with progressive refractory thyroid cancer are potential candidates for clinical trials using tyrosine kinase inhibitors (TKIs), and a promising proportion of patients in these trials have achieved stable disease. Here we report an unusual adverse experience in a patient receiving a combination of TKIs. SUMMARY The patient was a 62-year-old man with chronic myloid leukemia (CML) and thyroid carcinoma that did not concentrate iodide and had metastases. He was started on imatinib for his CML. About 5 months later he was started on sorafenib for his thyroid cancer. At this time he had no risk factors for cardiac disease except moderate obesity. He had a complete cytogenetic response in his CML, and a partial response in his thyroid cancer. Twenty-one months after starting the combination of TKIs, he manifested signs of coronary artery disease. He received a combination of medications and his TKIs were continued. He died of a sudden myocardial infarction with cardiogenic shock 28 months after starting the combination of TKIs. A retrospective analysis of sequential 18-fludeoxyglucose positron emission tomography scans (18-FDG PET scans) were indicative of cardiac toxicity developing during the period of concomitant administration of TKIs. CONCLUSION We report the first case of apparent lethal cardiotoxicity with imatinib-sorafenib combined therapy. Combination TKI treatment may enhance the risk of adverse effects. Our experience with this patient suggests that cardiac PET scan should be monitored closely in these type of patients.