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Introduction: The aim of this study was to evaluate the impact of the contouring methods on dose metrics and their predictive value on tumor control and survival, in both situations of pre-treatment and post-treatment dosimetry, for patients with advanced HCC treated with SIRT., Methods: Forty-eight patients who underwent SIRT between 2012 and 2020 were retrospectively included in this study. Target volumes were delineated using two methods: MRI-based contours manually drawn by a radiologist and then registered on SPECT/CT and PET/CT via deformable registration (Pre-C MRI and Post-C MRI ), 99m Tc-MAA-SPECT and 90 Y-microspheres-PET 10% threshold contouring (Pre-C SPECT and Post-C PET ). The mean absorbed dose (Dm) and the minimal absorbed dose delivered to 70% of the tumor volume (D70) were evaluated with both contouring methods; the tumor-to-normal liver uptake ratio (TNR) was evaluated with MRI-based contours only. Tumor response was assessed using the mRECIST criteria on the follow-up MRIs., Results: No significant differences were found for Dm and TNR between pre- and post-treatment. TNR evaluated with radiologic contours (Pre-C MRI and Post-C MRI ) were predictive of tumor control at 6 months on pre- and post-treatment dosimetry (OR 5.9 and 7.1, respectively; p = 0.02 and 0.01). All dose metrics determined with both methods were predictive of overall survival (OS) on pre-treatment dosimetry, but only Dm with MRI-based contours was predictive of OS on post-treatment images with a median of 23 months for patients with a supramedian Dm versus 14 months for the others (p = 0.04)., Conclusion: In advanced HCC treated with SIRT, Dm and TNR determined with radiologic contours were predictive of tumor control and OS. This study shows that a rigorous clinical workflow (radiologic contours + registration on scintigraphic images) is feasible and should be prospectively considered for improving therapeutic strategy.

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres ® or TheraSphere ® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26-0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

Context: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC)., Objectives: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC., Design: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3)., Results: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors., Conclusions: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years., (Copyright © 2019 Endocrine Society.)

Aim: Evaluate response and predict prognosis of patients with newly diagnosed metastatic breast cancer treated with first line systemic therapy using European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in solid Tumours (PERCIST)., Methods: From December 2006 to August 2013, 57 women with newly diagnosed metastatic breast cancer were retrospectively evaluated. FDG-PET/CT was performed within one month before treatment and repeated after at least 3 cycles of treatment. Metabolic response evaluation was evaluated by two readers according to both EORTC criteria and PERCIST, classifying the patients into 4 response groups: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD)., Results: With EORTC criteria, 22 patients had CMR, 17 PMR, 6 SMD and 12 PMD. With PERCIST, 20 patients had CMR, 15 PMR, 10 SMD and 12 PMD. There was agreement between EORTC and PERCIST in 84% of the patients. By log-rank analysis, metabolic response evaluated with both EORTC criteria and PERCIST was able to predict overall survival (p = 0.028 and 0.002 respectively). CMR patient group had longer median OS than patients in the combined PMR+SMD+PMD group (60 vs 26 months both with EORTC and PERCIST; p = 0.009 and 0.006 respectively). By multivariate analysis, CMR either with EORTC or PERCIST remained an independent predictor of survival., Conclusion: Metabolic response evaluation with EORTC criteria and PERCIST gave similar prognostic stratification for metastatic breast cancer treated with a first line of systemic therapy., Competing Interests: The authors have declared that no competing interests exist.

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 (ΔBF) 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 ΔBF. Delayed static PET acquisitions were also performed (90 min after 18 F-FDG injection) to measure changes in tumor glucose metabolism (ΔSUV 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-Bloom-Richardson grade, or Ki-67 expression. Median tumor ∆BF was -30%, with highly scattered values (range, -93% to +118%). A weak correlation was observed between ΔBF and ∆SUV max (r = +0.40, P = 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 = 0.03), persistent or increased tumor vascularization on the interim PET (ΔBF cutoff = -30%; P = 0.03), non-breast-conserving surgery (P = 0.04), and the absence of a pathologic complete response (pCR) (P = 0.01). ΔBF 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 (ΔBF cutoff = -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 ΔBF 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., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective working memory deficits, with borderline intellectual functioning. Further investigations identified a defect in executive function, and auditory-verbal processes. These data were consistent with brain MRI and FDG-PET functional brain imaging, which, when compared with controls, revealed abnormal brain volume and hypometabolism of gray matter structures implicated in working memory. We performed electron microscopy immunogold labeling demonstrating the localization of LRFN2 at synapses of cerebellar and hippocampal rat neurons, often associated with the NR1 subunit of N-methyl-D-aspartate receptors (NMDARs). Altogether, the combined approaches imply a role for LRFN2 in LD, specifically for working memory processes and executive function. In conclusion, the identification of familial cases of clinically homogeneous endophenotypes of LD might help in both the management of patients and genetic counseling for families.

Introduction: The management of metastatic cutaneous melanoma is changing, marked by innovative therapies. However, their respective use and place in the therapeutic strategy continue to be debated by healthcare professionals., Objective: The French national cancer institute has led a national clinical practice guideline project since 2008. It has carried out a review of these modalities of treatment and established recommendations., Methods: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery., Results: This article presents the results of bibliographic search, the conclusions of the literature and the recommendations concerning locoregional treatments of brain metastases for patients with metastatic cutaneous melanoma., (Copyright © 2014. Published by Elsevier Masson SAS.)

Purpose: The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study., Methods: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease., Results: Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p = 0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p = 0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = <71 % or TMTV0 >225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = <71 % and TMTV0 >225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively., Conclusion: TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.

Purpose: To investigate the value of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer., Material and Methods: Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET₁.SUVmax) and after the first course of NAC (PET₂.SUVmax). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUVmax and ΔTLG) was calculated., Results: In univariate analysis, negative hormonal receptor status (p = 0.04), high tumor grade (p = 0.03), and low tumor PET₂.SUVmax (p = 0.001) were predictive of pCR. Tumor ΔSUVmax correlated with pCR (p = 0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET₂.SUVmax < 2.1 was the best independent predictive factor (Odds ratio =14.3; p = 0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p = 0.01 and p = 0.03, respectively)., Conclusion: In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUVmax < 2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.

Unlabelled: PET performed after 2 cycles of chemotherapy (PET2) allows prediction of outcome in most patients with Hodgkin lymphoma (HL). Visual analysis using a 5-point scale was proposed to assess PET response, but a semiquantitative approach using maximum standardized uptake value (SUVmax) reduction between baseline and interim PET was shown to be superior to the 5-point scale in patients with diffuse large B-cell lymphoma and may also improve the accuracy of interim PET interpretation in HL. To compare the clinical usefulness of both methods in HL patients, we analyzed PET2 according to visual and ΔSUVmax criteria in a retrospective single-center study., Methods: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated with 4-8 cycles of anthracycline-based chemotherapy. Radiotherapy was performed in 19 responding patients with localized disease. PET was done at baseline (PET0) and after 2 cycles of chemotherapy, and treatment was not modified according to the PET2 result. PET2 was interpreted using the 5-point scale (positivity for score 4 or 5). The SUVmax reduction between PET0 and PET2 (ΔSUVmax) was computed for all patients, and patients with a ΔSUVmax greater than 71% were considered good responders., Results: When the 5-point scale was used, 46 patients (78%) achieved a negative PET2 result, 7 of whom failed treatment (negative predictive value, 85%). Forty-nine patients (83%) had a ΔSUVmax greater than 71%, 6 of whom failed treatment (negative predictive value, 88%). The PET2 positive predictive value was significantly better for ΔSUVmax (70%) than for the 5-point scale (46%). When ΔSUVmax was used, 6 (46%) of the 13 PET2-positive patients could be reclassified as good responders. Although visual PET2 positivity was related to a lower 4-y progression-free survival (45%) compared with PET2 negativity (81%, P < 0.002), ΔSUVmax (>71 vs ≤71%) was more accurate for identifying patients with different 4-y progression-free survivals (82% vs. 30%; P < 0.0001). In multivariate analysis using the international prognosis score and ΔSUVmax as covariates, ΔSUVmax remained the unique independent predictor for progression-free survival (P = 0.0001; relative risk, 8.1)., Conclusion: Semiquantitative analysis was more accurate than visual analysis based on the 5-point scale to interpret PET2 and predict the outcome of HL patients. These encouraging results warrant further confirmation in larger and prospective series.

Purpose: The objective of this study was to assess the impact on management and the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for initial staging of newly diagnosed large breast cancer (BC) when compared with conventional staging., Methods: We prospectively included 142 patients with newly diagnosed BC and at least grade T2 tumour. All patients were evaluated with complete conventional imaging (CI) procedures (mammogram and/or breast ultrasound, bone scan, abdominal ultrasound and/or CT, X-rays and/or CT of the chest), followed by FDG PET/CT exploration, prior to treatment. The treatment plan based on CI staging was compared with that based on PET/CT findings. CI and PET/CT findings were confirmed by imaging and clinical follow-up and/or pathology when assessable. Progression-free survival (PFS) was analysed using the Cox proportional hazards regression model., Results: According to CI staging, 79 patients (56%) were stage II, 46 (32%) stage III and 17 (12%) stage IV (distant metastases). Of the patients, 30 (21%) were upstaged by PET/CT, including 12 (8%) from stage II or III to stage IV. On the other hand, 23 patients (16%) were downstaged by PET/CT, including 4 (3%) from stage IV to stage II or III. PET/CT had a high or medium impact on management planning for 18 patients (13%). Median follow-up was 30 months (range 9-59 months); 37 patients (26%) experienced recurrence or progression of disease during follow-up and 17 patients (12%) died. The Cox model indicated that CI staging was significantly associated with PFS (p = 0.01), but PET/CT staging provided stronger prognostic stratification (p < 0.0001). Moreover, Cox regression multivariate analysis showed that only PET/CT staging remained associated with PFS (p < 0.0001)., Conclusion: FDG PET/CT provides staging information that more accurately stratifies prognostic risk in newly diagnosed large BC when compared with conventional explorations alone.

Purpose: The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC)., Methods: This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∆SUV) was calculated., Results: Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16%, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2%. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15%, respectively., Conclusion: In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response.

Background: Recent years have seen the emergence of new molecules for the treatment of patients with metastatic cutaneous melanoma, with significant benefits in terms of survival and the opening of new therapeutic perspectives. In addition, many techniques are currently being developed for locoregional treatment of metastatic sites. Management of metastatic melanoma is thus fast-changing and is marked by innovative therapeutic approaches. However, the availability of these new treatments has prompted debate among healthcare professionals concerning their use and their place in therapeutic strategy., Aims: Since 2008, the French National Cancer Institute (INCa) has been leading a project to define and diffuse national clinical practice guidelines. It has performed a review of these treatment methods, which it aims to circulate, and it is seeking to develop recommendations in order to allow nationwide implementation of innovative approaches while promoting good use thereof., Methods: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts within a multidisciplinary working group, with feedback from specialists in cancer care delivery. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery., Results: This article presents the national recommendations for first- and second-line systemic treatment and for locoregional treatment of metastatic sites in patients presenting metastatic cutaneous melanoma., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: The last years are marked by the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival. Besides, some techniques are in development for the loco-regional treatment of the metastatic sites, bringing new therapeutic perspectives. However, their respective use and place in the therapeutic strategy are debated by healthcare professionals., Objective: The French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and developed recommendations., Methods: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary expert workgroup. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery., Results: This article presents recommendations for loco-regional treatments of the pulmonary, bone, cutaneous, hepatic and digestive metastatic sites for patients with pauci-metastatic cutaneous melanoma.

Unlabelled: 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 (18)F-FDG PET/CT is now recommended for initial staging of DLBCL, its role regarding BMI is not well defined. This study evaluated whether (18)F-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 (18)F-FDG PET/CT and a BMB from the iliac crest before any treatment. (18)F-FDG PET/CT was considered positive for BMI in cases of uni- or multifocal bone marrow (18)F-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 (18)F-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 (18)F-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 (18)F-FDG PET/CT. (18)F-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 (18)F-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 (18)F-FDG PET/CT provides better diagnostic performance and prognostic stratification in newly diagnosed DLBCL than does BMB.

Objective: To identify the predictive factors of myocardial stunning as assessed by the drop in post-stress Left Ventricular Ejection Fraction (LVEF) in patients with a recent history of myocardial infarction (MI)., Methods: We prospectively included 215 consecutive patients admitted for acute MI who underwent percutaneous coronary intervention with a greater than or equal to grade-3 TIMI flow in the culprit vessel. Six months after discharge, a post-stress/rest 99mTc-sestamibi gated SPECT was performed. The perfusion score was evaluated visually using a 17-segment model. The LVEF drop was considered significant if the post-stress LVEF was ≥ 5% below the rest LVEF (QGS® software)., Results: A post-stress LVEF drop was observed in 51 (24%) patients. Patients with an LVEF drop were more likely than patients with a stable post-stress LVEF to have diabetes (22% vs. 10%, p = 0.048), significant ischemia (SDS > 2) (51% vs. 28% p = 0.003) and higher rest LVEF [62% (56-69) vs. 56% (49-63) p < 0.001]. In contrast, summed rest score, related to infarct size, did not differ between the groups. Multivariate logistic regression analysis identified SDS > 2 (OR 3.78, 95% CI 1.8-7.92, p < 0.001), diabetes (OR 3.35, 95% CI 1.33-8.49; p = 0.011) and rest LVEF (OR 1.08, 95% CI 1.04-1.12, p < 0.001) as independent explanatory variables of an LVEF drop., Conclusion: In patients with recent MI and post-procedural grade-3 TIMI flow, ischemia and diabetes were independent predictive factors of myocardial stunning. The higher incidence of reversible perfusion abnormalities validates the model of myocardial stunning in the post-MI period, and excludes the potential involvement of myocardial necrosis.

Unlabelled: The purpose of this study was to prospectively evaluate the relationship between tumor blood flow and glucose metabolism as evaluated by dynamic first-pass (18)F-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 (18)F-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 (18)F-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 (18)F-FDG tumor uptake (standardized uptake value maximal index [SUV(max)]), reflecting tumor metabolism., Results: Pathologic and PET/CT data were available for all patients. The SUV(max) 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 SUV(max) 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) SUV(max); 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 (18)F-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 (18)F-FDG could be an exciting alternative to more complex and less available techniques.

To evaluate the interest in assessing left ventricular diastolic function at baseline for prediction of trastuzumab-mediated cardiotoxicity (TMC) in the setting of adjuvant treatment for breast cancer. The study included 118 women presenting with HER2-positive early-stage invasive breast cancer. Patients received trastuzumab therapy over 1 year, concurrent with six cycles of docetaxel (n = 53), or following anthracycline-based chemotherapy with a cumulative dose of 300 mg/m(2) (n = 45) or 600 mg/m(2) (n = 20) of epirubicine. RNA was performed before anthracycline-based chemotherapy, before trastuzumab treatment (baseline), and every 3 months during treatment. Left ventricular ejection fraction (LVEF) and peak ejection rate (PER) were calculated to evaluate LV systolic function; peak filling rate (PFR), and time to peak filling rate (TPFR) were also calculated to evaluate LV diastolic function. Eighteen patients (15%) developed grade 1 or 2 TMC during follow-up. No significant difference was observed for age, cardiovascular risk factors, fasting blood glucose level, heart rate, systolic blood pressure, baseline LVEF, PER, and PFR between patients with and without TMC. In contrast, patients with TMC showed a longer TPFR at baseline (median [Q1-Q3]: 165 ms [149-190] vs. 142 ms [130-162]; P < 0.001). Furthermore, by logistic regression analysis, baseline TPFR >180 ms and the cumulative dose of epirubicin remained independent predictors of TMC. Patients receiving 600 mg/m(2) of epirubicin before trastuzumab showed a higher incidence of TMC (35%) than did both patients who previously received 300 mg/m(2) of epirubicin (13%) and those who received only docetaxel associated with trastuzumab (9%). Impaired left ventricular diastolic function before treatment is an independent predictor of trastuzumab-mediated cardiotoxicity. The evaluation of diastolic function could allow optimal risk stratification before the introduction of trastuzumab.