PET-MRI for evaluation of response to radiochemotherapy in patients with locally advanced cervical cancer.

OBJECTIVE: We aimed to analyze the diagnostic test accuracy of positron emission tomography and a magnetic resonance imaging scan (PET-MRI) fusion in evaluating tumor response after radiochemotherapy in patients with locally advanced cervical cancer. METHODS: Patients treated at two institutes between January 2008 and December 2016 were studied retrospectively. Re-evaluation by positron emission tomography (PET) and magnetic resonance imaging (MRI) was performed in a non-concurrent way 4-8 weeks after treatment. A nuclear medicine doctor and a radiologist (subsequently referred as "radiologists"), both experts in gynecological oncology, re-examined the post-treatment MRI and positron emission tomography-computed tomography (PET-CT) separately, and then performed a fusion of these examinations. In this study we describe this "a posteriori fusion methodology", with two levels, enabling limitation of anatomical shifts. The gold standard was anatomical pathology analysis of the surgical specimen, since all patients underwent surgery following this radiological re-evaluation. The radiologists' degree of certainty in their diagnoses, and the impact of fusion on their diagnostic confidence were assessed by the radiologists, using two Likert judgment scales. They also adjudicated on possible changes of interpretation after the fusion. RESULTS: Thirty-one patients were included. The PET-MRI fusion has a sensitivity of 79% and a specificity of 90%. The positive predictive value (PPV) was 94%, and the negative predictive value (NPV) was 69%. In 45% of cases (n=13), radiologists reported an improvement in their degree of certainty in their diagnosis using a Likert judgment scale, due to inspecting the PET and MRI fused. A change in interpretation of tumor response was observed using a Likert judgment scale in 31% of cases. CONCLUSION: PET-MRI fusion improves the radiologist's own diagnostic confidence in assessing response to concurrent radiochemotherapy in locally advanced cervical cancer. More studies using a latest generation hybrid system will be necessary to further compare to MRI and PET-CT.

Age is a prognostic factor even among patients with multiple myeloma younger than 66 years treated with high-dose melphalan: the IFM experience on 2316 patients.

Age is a strong prognostic factor in multiple myeloma. The overall survival is shorter in patients older than 66 years, and even shorter in those older than 75 years. Whether age is also a prognostic parameter in patients younger than 66 years treated homogeneously with intensive approaches is unknown. To address this issue, we retrospectively analyzed a series of 2316 patients treated homogeneously with 3-4 cycles of induction chemotherapy followed by a high-dose melphalan course, without any consolidation or maintenance. We show that patients older than 60 years have a statistically significant shorter overall survival. The analysis of prognostic parameters did not show a higher incidence of high-risk cytogenetics, but a higher incidence of International Staging System (ISS) stages 2 and 3, mainly due to higher ß2-microglobulin levels. This study is the first to demonstrate the impact of age in the outcome of 'young' patients with multiple myeloma, and suggests that this parameter should be included in the stratification factors for future prospective clinical trials.

PICALM-MLLT10 acute myeloid leukemia: a French cohort of 18 patients.

The PICALM-MLLT10 fusion gene, generated by the t(10;11)(p12-13;q14-21) translocation, is a rare but recurrent event in acute leukemias. In this study, we assessed the characteristics and outcome of 18 PICALM-MLLT10 AML patients. As compared with non PICALM-MLLT10 patients (n=72), PICALM-MLLT10 AML were characterized by more frequent extramedullary diseases, CD7 expression and higher platelet counts. Three out of four therapy-related PICALM-MLLT10 AMLs had been previously treated for diffuse large B-cell lymphoma. The complete response rate was 71% after intensive chemotherapy. PICALM-MLLT10 patients had a shorter median overall survival than patients with favorable cytogenetics (12 months vs. not reached, p=0.07) but not significantly different from those of intermediate (26 months, p=0.32) or unfavorable cytogenetic groups (8 months, p=0.13). Long term responses were achieved in a subset of patients after allogeneic stem-cell transplantation but also after high-dose cytarabine.

Branching patterns for arterioles and venules of the human cerebral cortex.

Branching patterns of microvascular networks influence vascular resistance and allow control of peripheral flow distribution. The aim of this paper was to analyze these branching patterns in human cerebral cortex. Digital three-dimensional images of the microvascular network were obtained from thick sections of India ink-injected human brain by confocal laser microscopy covering a large zone of secondary cortex. A novel segmentation method was used to extract the skeletons of 228 vascular trees (152 arterioles and 76 venules) and measure the diameter at every vertex. The branching patterns (area ratios and angles of bifurcations) of nearly 10,000 bifurcations of cortical vascular trees were analyzed, establishing their statistical properties and structural variations as a function of the vessel nature (arterioles versus venules), the parent vessel topological order or the bifurcation type. We also describe their connectivity and discuss the relevance of the assumed optimal design of vascular branching to account for the complex nature of microvascular architecture. The functional implications of some of these structural variations are considered. The branching patterns established from a large database of a human organ contributes to a better understanding of the bifurcation design and provides an essential reference both for diagnosis and for a future large reconstruction of cerebral microvascular network.

Evaluation of O-(2-[18F]-Fluoroethyl)-L-Tyrosine in the Diagnosis of Glioblastoma.

OBJECTIVE: To assess the feasibility of synthesis of O-(2-[(18)F]-fluoroethyl)-l-tyrosine (FET), a new positron emission tomographic (PET) tracer described in several studies but not yet considered standard in management of glioma, in routine practice and to determine FET uptake in a homogeneous group of patients with suspected high-grade glioma. DESIGN: Prospective nonrandomized trial. PATIENTS: Twelve patients with suspicion of high-grade glioma. RESULTS: The mean (SD) FET uptake ratio was 3.15 (0.72) for the 12 patients and 3.16 (0.75) for the 11 patients with glioblastoma. CONCLUSION: The initial results are promising and indicate that FET PET is a valuable and applicable tool for the imaging of high-grade glioma.

Indium-111-pentetreotide scintigraphy and somatostatin receptor subtype 2 expression: new prognostic factors for malignant well-differentiated endocrine tumors.

PURPOSE: Well-differentiated metastatic endocrine carcinomas are difficult to manage because of variable disease outcome. New prognostic factors are required. These tumors overexpress somatostatin receptors (sst), implying the use of somatostatin analogs for tumor localization by somatostatin receptor scintigraphy using indium-111-pentetreotide ((111)In-pentetreotide) and for medical treatment. The aim of the present study was to evaluate the correlation between (111)In-pentetreotide scintigraphy, sst receptor expression, and prognosis. PATIENTS AND METHODS: Between 1994 and 2002, 48 consecutive patients with well-differentiated endocrine carcinomas and a negative (111)In-pentetreotide scintigraphy were retrospectively paired according to sex, age, and tumor localization with 50 patients with well-differentiated endocrine carcinomas and a positive tracer uptake at (111)In-pentetreotide scintigraphy. Overall survival and expression of sst1 to sst5 receptors by immunohistochemistry were assessed. RESULTS: The lack of tracer uptake at the (111)In-pentetreotide scintigraphy seemed to be a poor prognostic factor (P = .007) for overall survival by Kaplan-Meier test and in multivariate analysis; age and absence of clinical secretory syndrome also seemed to be poor prognostic factors. The tracer uptake (positive (111)In-pentetreotide scintigraphy) correlated with the tumor expression of somatostatin receptor sst2 (P < .001) but not with that of sst1, sst3, sst4, or sst5. In a bivariate analysis, lack of sst2 expression also significantly correlated with poor prognosis. CONCLUSION: We demonstrate the prognostic value of (111)In-pentetreotide scintigraphy in well-differentiated malignant endocrine tumors. In these tumors, sst2 somatostatin receptor expression correlates with both tracer uptake and a better prognosis.