Metabolically active volumes automatic delineation methodologies in PET imaging: review and perspectives

International audiencePET imaging is now considered a gold standard tool in clinical oncology, especially for diagnosis purposes. More recent applications such as therapy follow up or tumor targeting in radiotherapy require a fast, accurate and robust metabolically active tumor volumes on emission images, which cannot be obtained through manual contouring. This clinical need has sprung a large number of methodological developments regarding automatic methods to defined tumor volumes on PET images. This paper reviews most of the methodologies that have been recently proposed and discusses their framework and methodological and/or clinical validation. Perspectives regarding the future work to be done are also suggested

Impact of tumor size and tracer uptake heterogeneity in (18)F-FDG PET and CT non-small cell lung cancer tumor delineation.: 18F-FDG PET and CT tumor delineation in NSCLC

International audienceUNLABELLED: The objectives of this study were to investigate the relationship between CT- and (18)F-FDG PET-based tumor volumes in non-small cell lung cancer (NSCLC) and the impact of tumor size and uptake heterogeneity on various approaches to delineating uptake on PET images. METHODS: Twenty-five NSCLC cancer patients with (18)F-FDG PET/CT were considered. Seventeen underwent surgical resection of their tumor, and the maximum diameter was measured. Two observers manually delineated the tumors on the CT images and the tumor uptake on the corresponding PET images, using a fixed threshold at 50% of the maximum (T(50)), an adaptive threshold methodology, and the fuzzy locally adaptive Bayesian (FLAB) algorithm. Maximum diameters of the delineated volumes were compared with the histopathology reference when available. The volumes of the tumors were compared, and correlations between the anatomic volume and PET uptake heterogeneity and the differences between delineations were investigated. RESULTS: All maximum diameters measured on PET and CT images significantly correlated with the histopathology reference (r > 0.89, P < 0.0001). Significant differences were observed among the approaches: CT delineation resulted in large overestimation (+32% ± 37%), whereas all delineations on PET images resulted in underestimation (from -15% ± 17% for T(50) to -4% ± 8% for FLAB) except manual delineation (+8% ± 17%). Overall, CT volumes were significantly larger than PET volumes (55 ± 74 cm(3) for CT vs. from 18 ± 25 to 47 ± 76 cm(3) for PET). A significant correlation was found between anatomic tumor size and heterogeneity (larger lesions were more heterogeneous). Finally, the more heterogeneous the tumor uptake, the larger was the underestimation of PET volumes by threshold-based techniques. CONCLUSION: Volumes based on CT images were larger than those based on PET images. Tumor size and tracer uptake heterogeneity have an impact on threshold-based methods, which should not be used for the delineation of cases of large heterogeneous NSCLC, as these methods tend to largely underestimate the spatial extent of the functional tumor in such cases. For an accurate delineation of PET volumes in NSCLC, advanced image segmentation algorithms able to deal with tracer uptake heterogeneity should be preferred

Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study

This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33–72 years) were to receive 4 infusions of 360 mg/m(2 )epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a ≥20% improvement in at least two of the aforementioned parameters, with ≥20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at ≥20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%–50% responded at the ≥30% level, while 10%–45% responded at the ≥50% level for 10–32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted

FDG PET uptake characterization through texture analysis: investigating the complementary nature of heterogeneity and functional tumor volume in a multi-cancer site patient cohort.: FDG-PET heterogeneity and volume

International audienceIntra-tumor uptake heterogeneity in 18F-FDG PET has been associated with patient treatment outcomes in several cancer types. Textural features (TF) analysis is a promising method for its quantification. An open issue associated with the use of TF for the quantification of intratumoral heterogeneity concerns its added contribution and dependence on the metabolically active tumor volume (MATV), which has already been shown as 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 pre-treatment 18F-FDG PET images (breast, cervix, esophageal, head & neck and lung cancer tumors) was assembled. Four robust and reproducible TF-derived parameters were considered. The issues associated with the calculation of TF 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 TF was assessed through multivariate Cox analysis in the esophageal and 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 TF varied greatly depending on the MATVs, with reduced correlation for increasing volumes. These findings were reproducible across the different cancer types. The quantization and the calculation method 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 NSCLC, but in the esophageal tumors, volume and heterogeneity had less complementary value due to smaller overall volumes.CONCLUSION:Our results suggest that heterogeneity quantification and volume may provide valuable complementary information for volumes above 10cm3, although the complementary information increases substantially with larger volumes

HLA-DR expression in melanoma: from misleading therapeutic target to potential immunotherapy biomarker

Since the advent of anti-PD1 immune checkpoint inhibitor (ICI) immunotherapy, cutaneous melanoma has undergone a true revolution with prolonged survival, as available 5-year updates for progression-free survival and overall survival demonstrate a durable clinical benefit for melanoma patients receiving ICI. However, almost half of patients fail to respond to treatment, or relapse sooner or later after the initial response to therapy. Little is known about the reasons for these failures. The identification of biomarkers seems necessary to better understand this resistance. Among these biomarkers, HLA-DR, a component of MHC II and abnormally expressed in certain tumor types including melanoma for unknown reasons, seems to be an interesting marker. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on the potential interest of HLA-DR expression in melanoma as a predictive biomarker of ICI outcome

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe