Review on radiomic analysis in 18F-fluorodeoxyglucose positron emission tomography for prediction of melanoma outcomes.

Over the past decade, several strategies have revolutionized the clinical management of patients with cutaneous melanoma (CM), including immunotherapy and targeted tyrosine kinase inhibitor (TKI)-based therapies. Indeed, immune checkpoint inhibitors (ICIs), alone or in combination, represent the standard of care for patients with advanced disease without an actionable mutation. Notably BRAF combined with MEK inhibitors represent the therapeutic standard for disease disclosing BRAF mutation. At the same time, FDG PET/CT has become part of the routine staging and evaluation of patients with cutaneous melanoma. There is growing interest in using FDG PET/CT measurements to predict response to ICI therapy and/or target therapy. While semiquantitative values such as standardized uptake value (SUV) are limited for predicting outcome, new measures including tumor metabolic volume, total lesion glycolysis and radiomics seem promising as potential imaging biomarkers for nuclear medicine. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on radiomics approaches that could improve outcomes in CM.

Prediction of Acute Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy Using Dose-Volume Parameters From Functional Mapping on Gallium 68 Perfusion Positron Emission Tomography/Computed Tomography.

PURPOSE: The aim of this work was to compare anatomic and functional dose-volume parameters as predictors of acute radiation-induced lung toxicity (RILT) in patients with lung tumors treated with stereotactic body radiation therapy. METHODS AND MATERIALS: Fifty-nine patients treated with stereotactic body radiation therapy were prospectively included. All patients underwent gallium 68 lung perfusion positron emission tomography (PET)/computed tomography (CT) imaging before treatment. Mean lung dose (MLD) and volumes receiving x Gy (VxGy, 5-30 Gy) were calculated in 5 lung volumes: the conventional anatomic volume (AV) delineated on CT images, 3 lung functional volumes (FVs) defined on lung perfusion PET imaging (FV50%, FV70%, and FV90%; ie, the minimal volume containing 50%, 70%, and 90% of the total activity within the AV), and a low FV (LFV; LFV = AV - FV90%). The primary endpoint of this analysis was grade ≥2 acute RILT at 3 months as assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Dose-volume parameters in patients with and without acute RILT were compared. Receiver operating characteristic curves assessing the ability of dose-volume parameters to discriminate between patients with and without acute RILT were generated, and area under the curve (AUC) values were calculated. RESULTS: Of the 59 patients, 10 (17%) had grade ≥2 acute RILT. The MLD and the VxGy in the AV and LFV were not statistically different between patients with and without acute RILT (P > .05). All functional parameters were significantly higher in acute RILT patients (P < .05). AUC values (95% CI) for MLD AV, LFV, FV50%, FV70%, and FV90% were 0.66 (0.46-0.85), 0.60 (0.39-0.80), 0.77 (0.63-0.91), 0.77 (0.64-0.91), and 0.75 (0.58-0.91), respectively. AUC values for V20Gy AV, LFV, FV50%, FV70%, and FV90% were 0.65 (0.44-0.87), 0.64 (0.46-0.83), 0.82 (0.69-0.95), 0.81 (0.67-0.96), and 0.75 (0.57-0.94), respectively. CONCLUSIONS: The predictive value of PET perfusion-based functional parameters outperforms the standard CT-based dose-volume parameters for the risk of grade ≥2 acute RILT. Functional parameters could be useful for guiding radiation therapy planning and reducing the risk of acute RILT.

Clinical application of a population-based input function (PBIF) for a shortened dynamic whole-body FDG-PET/CT protocol in patients with metastatic melanoma treated by immunotherapy.

BACKGROUND: The aim was to investigate the feasibility of a shortened dynamic whole-body (dWB) FDG-PET/CT protocol and Patlak imaging using a population-based input function (PBIF), instead of an image-derived input function (IDIF) across the 60-min post-injection period, and study its effect on the FDG influx rate (Ki) quantification in patients with metastatic melanoma (MM) undergoing immunotherapy. METHODS: Thirty-seven patients were enrolled, including a PBIF modeling group (n = 17) and an independent validation cohort (n = 20) of MM from the ongoing prospective IMMUNOPET2 trial. All dWB-PET data were acquired on Vision 600 PET/CT systems. The PBIF was fitted using a Feng's 4-compartments model and scaled to the individual IDIF tail's section within the shortened acquisition time. The area under the curve (AUC) of PBIFs was compared to respective IDIFs AUC within 9 shortened time windows (TW) in terms of linear correlation (R2) and Bland-Altman tests. Ki metrics calculated with PBIF vs IDIF on 8 organs with physiological tracer uptake, 44 tumoral lesions of MM and 11 immune-induced inflammatory sites of pseudo-progression disease were also compared (Mann-Whitney test). RESULTS: The mean ± SD relative AUC bias was calculated at 0.5 ± 3.8% (R2 = 0.961, AUCPBIF = 1.007 × AUCIDIF). In terms of optimal use in routine practice and statistical results, the 5th-7th pass (R2 = 0.999 for both Ki mean and Ki max) and 5th-8th pass (mean ± SD bias = - 4.9 ± 6.5% for Ki mean and - 4.8% ± 5.6% for Ki max) windows were selected. There was no significant difference in Ki values from PBIF5_7 vs IDIF5_7 for physiological uptakes (p > 0.05) as well as for tumor lesions (mean ± SD Ki IDIF5_7 3.07 ± 3.27 vs Ki PBIF5_7 2.86 ± 2.96 100ml/ml/min, p = 0.586) and for inflammatory sites (mean ± SD Ki IDIF5_7 1.13 ± 0.59 vs Ki PBIF5_7 1.13 ± 0.55 100ml/ml/min, p = 0.98). CONCLUSION: Our study showed the feasibility of a shortened dWB-PET imaging protocol with a PBIF approach, allowing to reduce acquisition duration from 70 to 20 min with reasonable bias. These findings open perspectives for its clinical use in routine practice such as treatment response assessment in oncology.

New Automated Method for Lung Functional Volumes Delineation with Lung Perfusion PET/CT Imaging.

BACKGROUND: Gallium-68 lung perfusion PET/CT is an emerging imaging modality for the assessment of regional lung function, especially to optimise radiotherapy (RT) planning. A key step of lung functional avoidance RT is the delineation of lung functional volumes (LFVs) to be integrated into radiation plans. However, there is currently no consistent and reproducible delineation method for LFVs. The aim of this study was to develop and evaluate an automated delineation threshold method based on total lung function for LFVs delineation with Gallium-68 MAA lung PET/CT imaging. MATERIAL AND METHOD: Patients prospectively enrolled in the PEGASUS trial-a pilot study assessing the feasibility of lung functional avoidance using perfusion PET/CT imaging for lung stereotactic body radiotherapy (SBRT) of primary or secondary lesion-were analysed. Patients underwent lung perfusion MAA-68Ga PET/CT imaging and pulmonary function tests (PFTs) as part of pre-treatment evaluation. LFVs were delineated using two methods: the commonly used relative to the maximal pixel value threshold method (pmax threshold method, X%pmax volumes) and a new approach based on a relative to whole lung function threshold method (WLF threshold method, FVX% volumes) using a dedicated iterative algorithm. For both methods, LFVs were expressed in terms of % of the anatomical lung volume (AV) and of % of the total lung activity. Functional volumes were compared for patients with normal PFTs and pre-existing airway disease. RESULTS: 60 patients were analysed. Among the 48 patients who had PFTs, 31 (65%) had pre-existing lung disease. The pmax and WLF threshold methods clearly provided different functional volumes with a wide range of relative lung function for a given pmax volume, and conversely, a wide range of corresponding pmax values for a given WLF volume. The WLF threshold method provided more reliable and consistent volumes with much lower dispersion of LFVs as compared to the pmax method, especially in patients with normal PFTs. CONCLUSIONS: We developed a relative to whole lung function threshold segmentation method to delineate lung functional volumes on perfusion PET/CT imaging. The automated algorithm allows for reproducible contouring. This new approach, relatively unaffected by the presence of hot spots, provides reliable and consistent functional volumes, and is clinically meaningful for clinicians.

Prognostic value of pre-therapeutic FDG-PET radiomic analysis in gastro-esophageal junction cancer.

The main aim of this study was to evaluate the prognostic value of radiomic approach in pre-therapeutic 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) in a large cohort of patients with gastro-esophageal junction cancer (GEJC). This was a retrospective monocenter study including 97 consecutive patients with GEJC who underwent a pre-therapeutic FDG-PET and were followed up for 3 years. Standard first-order radiomic PET indices including SUVmax, SUVmean, SUVpeak, MTV and TLG and 32 textural features (TFs) were calculated using LIFEx software on PET imaging. Prognostic significance of these parameters was assessed in univariate and multivariate analysis. Relapse-free survival (RFS) and overall survival (OS) were respectively chosen as primary and secondary endpoints. An internal validation cohort was used by randomly drawing one-third of included patients. The main characteristics of this cohort were: median age of 65 years [41-88], sex ratio H/F = 83/14, 81.5% of patients with a histopathology of adenocarcinoma and 43.3% with a stage IV disease. The median follow-up was 28.5 months [4.2-108.5]. Seventy-seven (79.4%) patients had locoregional or distant progression or recurrence and 71 (73.2%) died. In univariate analysis, SUVmean, Histogram-Entropy and 2 TFs (GLCM-Homogeneity and GLCM-Energy) were significantly correlated with RFS and OS, as well as 2 others TFs (GLRLM-LRE and GLRLM-GLNU) with OS only. In multivariate analysis, Histogram-Entropy remained an independent prognostic factor of both RFS and OS whereas SUVmean was an independent prognostic factor of OS only. These results were partially confirmed in our internal validation cohort of 33 patients. Our results suggest that radiomic approach reveals independent prognostic factors for survival in patients with GEJC.

A Feasibility Study of Functional Lung Volume Preservation during Stereotactic Body Radiotherapy Guided by Gallium-68 Perfusion PET/CT.

The aim of this study was to assess the feasibility of sparing functional lung areas by integration of pulmonary functional mapping guided by 68Ga-perfusion PET/CT imaging in lung SBRT planification. Sixty patients that planned to receive SBRT for primary or secondary lung tumors were prospectively enrolled. Lung functional volumes were defined as the minimal volume containing 50% (FV50%), 70% (FV70%) and 90% (FV90%) of the total activity within the anatomical volume. All patients had a treatment planning carried out in 2 stages: an anatomical planning blinded to the PET results and then a functional planning respecting the standard constraints but also incorporating "lung functional volume" constraints. The mean lung dose (MLD) in functional volumes and the percentage of lung volumes receiving xGy (VxGy) within the lung functional volumes using both plans were calculated and compared. SBRT planning optimized to spare lung functional regions led to a significant reduction (p < 0.0001) of the MLD and V5 to V20 Gy in all functional volumes. Median relative difference of the MLD in the FV50%, FV70% and FV90% was -8.0% (-43.0 to 1.2%), -7.1% (-34.3 to 1.2%) and -5.7% (-22.3 to 4.4%), respectively. Median relative differences for VxGy ranged from -12.5% to -9.2% in the FV50%, -11.3% to -7.2% in the FV70% and -8.0% to -5.3% in the FV90%. This study shows the feasibility of significantly decreasing the doses delivered to the lung functional volumes using 68Ga-perfusion PET/CT while still respecting target volume coverage and doses to other organs at risk.

Lung Stereotactic Body Radiation Therapy in a Patient with Severe Lung Function Impairment Allowed by Gallium-68 Perfusion PET/CT Imaging: A Case Report.

Lung stereotactic body radiotherapy (SBRT) is increasingly proposed, especially for patients with poor lung function who are not eligible for surgery. However, radiation-induced lung injury remains a significant treatment-related adverse event in these patients. Moreover, for patients with very severe COPD, we have very few data about the safety of SBRT for lung cancer. We present the case of a female with very severe chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in one second (FEV1) of 0.23 L (11%), for whom a localized lung tumor was found. Lung SBRT was the only possible treatment. It was allowed and safely performed, based on a pre-therapeutic evaluation of regional lung function with Gallium-68 perfusion lung positron emission tomography combined with computed tomography (PET/CT). This is the first case report to highlight the potential use of a Gallium-68 perfusion PET/CT in order to safely select patients with very severe COPD who can benefit from SBRT.

Comparison of Volumetric Quantitative PET Parameters Before and After a CT-Based Elastic Deformation on Dual-Time 18FDG-PET/CT Images: A Feasibility Study in a Perspective of Radiotherapy Planning in Head and Neck Cancer.

BACKGROUND: The use of 18FDG-PET/CT for delineating a gross tumor volume (GTV, also called MTV metabolic tumor volume) in radiotherapy (RT) planning of head neck squamous cell carcinomas (HNSCC) is not included in current recommendations, although its interest for the radiotherapist is of evidence. Because pre-RT PET scans are rarely done simultaneously with dosimetry CT, the validation of a robust image registration tool and of a reproducible MTV delineation method is still required. OBJECTIVE: Our objective was to study a CT-based elastic registration method on dual-time pre-RT 18FDG-PET/CT images to assess the feasibility of PET-based RT planning in patients with HNSCC. METHODS: Dual-time 18FDG-PET/CT [whole-body examination (wbPET) + 1 dedicated step (headPET)] were selected to simulate a 2-times scenario of pre-RT PET images deformation on dosimetry CT. ER-headPET and RR-headPET images were, respectively, reconstructed after CT-to-CT rigid (RR) and elastic (ER) registrations of the headPET on the wbPET. The MTVs delineation was performed using two methods (40%SUVmax, PET-Edge). The percentage variations of several PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were calculated between wbPET, ER-headPET, and RR-headPET. Correlation between MTV values was calculated (Deming linear regression). MTVs intersections were assessed by two indices (OF, DICE) and compared together (Wilcoxon test). Additional per-volume analysis was evaluated (Mann-Whitney test). Inter- and intra-observer reproducibilities were evaluated (ICC = intra-class coefficient). RESULTS: 36 patients (30M/6F; median age = 65 y) were retrospectively included. The changes in SUVmax, SUVmean and SUVpeak values between ER-headPET and RR-headPET images were <5%. The variations in MTV values between ER-headPET and wbPET images were -6 and -3% with 40%SUVmax and PET Edge, respectively. Their correlations were excellent whatever the delineation method (R2 > 0.99). The ER-headPET MTVs had significant higher mean OF and DICE with the wbPET MTVs, for both delineation methods (p ≤ 0.002); and also when lesions had a volume > 5cc (excellent OF = 0.80 with 40%SUVmax). The inter- and intra-observer reproducibilities for MTV delineation were excellent (ICC ≥ 0.8, close to 1 with PET-Edge). CONCLUSION: Our study demonstrated no significant changes in MTV after an elastic deformation of pre-RT 18FDG-PET/CT images acquired in dual-time mode. This opens possibilities for HNSCC radiotherapy planning improvement by transferring GTV-PET on dosimetry CT.

Hotspot on 18F-FET PET/CT to Predict Aggressive Tumor Areas for Radiotherapy Dose Escalation Guiding in High-Grade Glioma.

The standard therapy strategy for high-grade glioma (HGG) is based on the maximal surgery followed by radio-chemotherapy (RT-CT) with insufficient control of the disease. Recurrences are mainly localized in the radiation field, suggesting an interest in radiotherapy dose escalation to better control the disease locally. We aimed to identify a similarity between the areas of high uptake on O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography/computed tomography (PET) before RT-CT, the residual tumor on post-therapy NADIR magnetic resonance imaging (MRI) and the area of recurrence on MRI. This is an ancillary study from the IMAGG prospective trial assessing the interest of FET PET imaging in RT target volume definition of HGG. We included patients with diagnoses of HGG obtained by biopsy or tumor resection. These patients underwent FET PET and brain MRIs, both after diagnosis and before RT-CT. The follow-up consisted of sequential brain MRIs performed every 3 months until recurrence. Tumor delineation on the initial MRI 1 (GTV 1), post-RT-CT NADIR MRI 2 (GTV 2), and progression MRI 3 (GTV 3) were performed semi-automatically and manually adjusted by a neuroradiologist specialist in neuro-oncology. GTV 2 and GTV 3 were then co-registered on FET PET data. Tumor volumes on FET PET (MTV) were delineated using a tumor to background ratio (TBR) ≥ 1.6 and different % SUVmax PET thresholds. Spatial similarity between different volumes was performed using the dice (DICE), Jaccard (JSC), and overlap fraction (OV) indices and compared together in the biopsy or partial surgery group (G1) and the total or subtotal surgery group (G2). Another overlap index (OV') was calculated to determine the threshold with the highest probability of being included in the residual volume after RT-CT on MRI 2 and in MRI 3 (called "hotspot"). A total of 23 patients were included, of whom 22% (n = 5) did not have a NADIR MRI 2 due to a disease progression diagnosed on the first post-RT-CT MRI evaluation. Among the 18 patients who underwent a NADIR MRI 2, the average residual tumor was approximately 71.6% of the GTV 1. A total of 22% of patients (5/23) showed an increase in GTV 2 without diagnosis of true progression by the multidisciplinary team (MDT). Spatial similarity between MTV and GTV 2 and between MTV and GTV 3 were higher using a TBR ≥ 1.6 threshold. These indices were significantly better in the G1 group than the G2 group. In the FET hotspot analysis, the best similarity (good agreement) with GTV 2 was found in the G1 group using a 90% SUVmax delineation method and showed a trend of statistical difference with those (poor agreement) in the G2 group (OV' = 0.67 vs. 0.38, respectively, p = 0.068); whereas the best similarity (good agreement) with GTV 3 was found in the G1 group using a 80% SUVmax delineation method and was significantly higher than those (poor agreement) in the G2 group (OV'= 0.72 vs. 0.35, respectively, p = 0.014). These results showed modest spatial similarity indices between MTV, GTV 2, and GTV 3 of HGG. Nevertheless, the results were significantly improved in patients who underwent only biopsy or partial surgery. TBR ≥ 1.6 and 80-90% SUVmax FET delineation methods showing a good agreement in the hotspot concept for targeting standard dose and radiation boost. These findings need to be tested in a larger randomized prospective study.

18F-FET PET/CT in Early Subventricular Zone Recurrence of Adult Glioblastoma.

ABSTRACT: Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.

Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors.

To present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1-5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs.

Diagnostic value of positron-emission tomography textural indices for malignancy of 18F-fluorodeoxyglucose-avid adrenal lesions.

BACKGROUND: PET Textural indices could have an add-on diagnostic value for diagnosis of malignancy in patients with FDG-avid adrenal lesions. METHODS: Consecutive patients referred for a FDG-PET/CT to our nuclear medicine department from June 2012 to June 2017 were retrospectively screened. Inclusion criteria were: patients with a FDG-avid adrenal lesion (uptake≥liver background); malignant/benign lesion confirmed histologically or with follow-up imaging examination. Pheochromocytomas were not included in the analysis. For each adrenal lesion, 5 quantitative PET parameters (SUVmax, MTV, TLG, TLRmax and TLRmean) were calculated. Thirty-seven textural indices were extracted using LIFEx software®. Diagnostic performance to determine malignancy was assessed with a ROC analysis. Parameters with a significantly AUC>0.5 were selected and groups of highly correlated (r>0.8) parameters were created. A scoring system combining PET and textural indices was examined. RESULTS: PET textural indices were calculated for 53 lesions (37 malignant, 16 benign). Three PET metabolic parameters (SUVmax, TLRmax, TLRmean) and 13 textural indices had an AUC>0.5. Seven groups of highly correlated parameters (r>0.8) were extracted. For PET parameters, SUVmax had the best AUC (0.89 95% CI [0.79-0.98]; cut-off=7.0). For textural indices, ZLNU had the best AUC (0.87 95% CI [0.78-0.96]; cut-off=34.7) and specificity of 100%. Three scores combining the best four textural indices alone (ContrastGLCM, LRHGE, SZE and ZLNU) or with one PET parameters (SUVmax, TLRmax) were developed but did not increase the diagnostic performance (AUC≤0.89). ZLNU was the best parameter to distinguish primary adrenal cancer from adrenal metastases in malignant lesions (P<0.001). CONCLUSIONS: Our study highlighted excellent diagnostic performance of several PET textural indices comparable to that of PET metabolic parameters. However, our results did not find any additional diagnostic value of textural indices when combined with metabolic parameters.

Clinical Assessment of 177Lu-DOTATATE Quantification by Comparison of SUV-Based Parameters Measured on Both Post-PRRT SPECT/CT and 68Ga-DOTATOC PET/CT in Patients With Neuroendocrine Tumors: A Feasibility Study.

PATIENTS AND METHODS: Patients with WD-GEP-NET who benefited from a pretherapeutic 68Ga-DOTATOC PET/CT and a 177Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1-10/patient; SUVmax, SUVmean, SUVpeak, MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUVmax and SUVmean (TLRmax, TLRmean, TSRmax, and TSRmean, respectively). RESULTS: Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV (P < 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR (P < 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779-0.845), weak for TLR parameters (0.365-0.394), and moderate-to-strong for TSR parameters (0.676-0.750). CONCLUSIONS: Our results suggest the feasibility of 177Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68Ga-DOTATOC PET/CT.

Diagnostic performance of a whole-body dynamic 68GA-DOTATOC PET/CT acquisition to differentiate physiological uptake of pancreatic uncinate process from pancreatic neuroendocrine tumor.

To evaluate the diagnostic performance of net influx rate (Ki) values from a whole-body dynamic (WBD) Ga-DOTATOC-PET/CT acquisition to differentiate pancreatic neuroendocrine tumors (pNETs) from physiological uptake of pancreatic uncinate process (UP).Patients who were benefited from a WBD acquisition for the assessment of a known well-differentiated neuroendocrine tumor (NET)/suspicion of disease in the prospective GAPET-NET cohort were screened. Only patients with a confirmed pNET/UP as our gold standard were included. The positron emission tomography (PET) procedure consisted in a single-bed dynamic acquisition centered on the heart, followed by a whole-body dynamic acquisition and then a static acquisition. Dynamic (Ki calculated according to Patlak method), static (SUVmax, SUVmean, SUVpeak) parameters, and tumor-to-liver and tumor-to-spleen ratio (TLRKi and TSRKi (according to hepatic/splenic Ki)), tumor SUVmax to liver SUVmax (TM/LM), tumor SUVmax to liver SUVmean (TM/Lm), tumor SUVmax to spleen SUVmax (TM/SM), and tumor SUVmax to spleen SUVmean (TM/Sm) (according to hepatic/splenic SUVmax and SUVmean respectively) were calculated. A Receiver Operating Characteristic (ROC) analysis was performed to evaluate their diagnostic performance to distinguish UP from pNET.One hundred five patients benefited from a WBD between July 2018 and July 2019. Eighteen (17.1%) had an UP and 26 (24.8%) a pNET. For parameters alone, the Ki and SUVpeak had the best sensitivity (88.5%) while the Ki, SUVmax, and SUVmean had the best specificity (94.4%). The best diagnostic accuracy was obtained with Ki (90.9%). For ratios, the TLRKi and the TSRKi had the best sensitivity (95.7%) while the TM/SM and TM/Sm the best specificity (100%). TLRKi had the best diagnostic accuracy (95.1%) and the best area under the curve (AUC) (0.990).Our study is the first one to evaluate the interest of a WBD acquisition to differentiate UP from pNETs and shows excellent diagnostic performances of the Ki approach.

Correlation Between FDG Hotspots on Pre-radiotherapy PET/CT and Areas of HNSCC Local Relapse: Impact of Treatment Position and Images Registration Method.

Aim: Several series have already demonstrated that intratumoral subvolumes with high tracer avidity (hotspots) in 18F-flurodesoxyglucose positron-emission tomography (FDG-PET/CT) are preferential sites of local recurrence (LR) in various solid cancers after radiotherapy (RT), becoming potential targets for dose escalation. However, studies conducted on head and neck squamous cell carcinoma (HNSCC) found only a moderate overlap between pre- and post-treatment subvolumes. A limitation of these studies was that scans were not performed in RT treatment position (TP) and were coregistred using a rigid registration (RR) method. We sought to study (i) the influence of FDG-PET/CT acquisition in TP and (ii) the impact of using an elastic registration (ER) method to improve the localization of hotpots in HNSCC. Methods: Consecutive patients with HNSCC treated by RT between March 2015 and September 2017 who underwent FDG-PET/CT in TP at initial staging (PETA) and during follow-up (PETR) were prospectively included. We utilized a control group scanned in non treatment position (NTP) from our previous retrospective study. Scans were registered with both RR and ER methods. Various sub-volumes (AX; x = 30, 40, 50, 60, 70, 80, and 90%SUVmax) within the initial tumor and in the subsequent LR (RX; x = 40 and 70%SUVmax) were overlaid on the initial PET/CT for comparison [Dice, Jaccard, overlap fraction = OF, common volume/baseline volume = AXnRX/AX, common volume/recurrent volume = AXnRX/RX]. Results: Of 199 patients included, 43 (21.6%) had LR (TP = 15; NTP = 28). The overlap between A30, A40, and A50 sub-volumes on PETA and the whole metabolic volume of recurrence R40 and R70 on PETR showed moderate to good agreements (0.41-0.64) with OF and AXnRX/RX index, regardless of registration method or patient position. Comparison of registration method demonstrated OF and AXnRX/RX indices (x = 30% to 50%SUVmax) were significantly higher with ER vs. RR in NTP (p < 0.03), but not in TP. For patient position, the OF and AXnRX/RX indices were higher in TP than in NTP when RR was used with a trend toward significance, particularly for x=40%SUVmax (0.50±0.22 vs. 0.31 ± 0.13, p = 0.094). Conclusion: Our study suggested that PET/CT acquired in TP improves results in the localization of FDG hotspots in HNSCC. If TP is not possible, using an ER method is significantly more accurate than RR for overlap estimation.

Radiotherapy target volume definition in newly diagnosed high grade glioma using 18F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

PURPOSE: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG). MATERIALS AND METHODS: Thirty patients with histologically confirmed HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated. RESULTS: The 18F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between 18F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89)). CONCLUSION: We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas 18F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. 18F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning.

Prognostic value of 18F-FET PET/CT in newly diagnosed WHO 2016 high-grade glioma.

O-(2-[F]fluoroethyl)-L-tyrosine positron-emission tomography/computed tomography (F-FET PET/CT) is well known in brain tumor management. Our study aimed to identify the prognostic value of F-FET PET/CT in high-grade gliomas (HGG) according the current 2016 World Health Organization (WHO) classification.Patients with histologically proven WHO 2016 HGG were prospectively included. A dynamic F-FET PET/CT was performed allowing to obtain 2 static PET frames (static frame 1: 20-40 minutes and static frame 2: 2-22 minutes). We analyzed static parameters (standard uptake value [SUV]max, SUVmean, SUVpeak, TBRmax, TBRmean, tumoral lesion glycolysis, and metabolic tumoral volume) for various isocontours (from 10% to 90%). PET parameters, clinical features, and molecular biomarkers were compared with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analysis.Twenty-nine patients were included (grade III n = 3, grade IV n = 26). Mean PFS and OS were, respectively, 8.8 and 13.9 months. According to univariate analysis, SUVmean, SUVpeak, TBRmax, and TBRmean were significantly correlated with OS. In static 1 analysis, TBRmax seemed to be the best OS prognostic parameter (P = .004). In static 2 analysis, TBRmean was the best parameter (P = .01). In static 1 analysis, only SUVpeak was significant (P = .05) for PFS. Good performance status (PS < 2; P < .0001) and extent of resection (P = .019) identified the subgroup of patients with the best OS. Only TBRmax (P = .026) and extent of resection (P = .025) remained significant parameters in multivariate analysis.Our data suggested that high TBRmax seemed to be the most significant OS independent prognostic factor in patients with newly diagnosed HGG.

Inter-observer and segmentation method variability of textural analysis in pre-therapeutic FDG PET/CT in head and neck cancer.

AIM: Characterizing tumor heterogeneity with textural indices extracted from 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) is of growing interest in oncology. Several series showed promising results to predict survival in patients with head and neck squamous cell carcinoma (HNSCC), analyzing various tumor segmentation methods and textural indices. This preliminary study aimed at assessing the inter-observer and inter-segmentation method variability of textural indices in HNSCC pre-therapeutic FDG PET/CT. MATERIALS AND METHODS: Consecutive patients with HNSCC referred in our department for a pre-therapeutic FDG PET/CT from January to March 2016 were retrospectively included. Two nuclear medicine physicians separately segmented all tumors using 3 different segmentation methods: a relative standardized uptake value (SUV) threshold (40%SUVmax), a signal-to-noise adaptive SUV threshold (DAISNE) and an image gradient-based method (PET-EDGE). SUV and metabolic tumor volume were recorded. Thirty-one textural indices were calculated using LIFEx software (www.lifexsoft.org). After correlation analysis, selected indices' inter-segmentation method and inter-observer variability were calculated. RESULTS: Forty-three patients (mean age 63.8±9.3y) were analyzed. Due to a too small segmented tumor volume of interest, textural analysis could not be performed in 6, 11 and 15 cases with respectively DAISNE, 40%SUVmax and PET-EDGE segmentation methods. Five independent textural indices were selected (Homogeneity, Correlation, Entropy, Busyness and LZLGE). There was a high inter-contouring method variability for Homogeneity, Correlation, Entropy and LZLGE (p<0.0001 for each index). The inter-observer reproducibility analysis revealed an excellent agreement for 3 indices (Homogeneity, Correlation and Entropy) with an intraclass correlation coefficient higher than 0.90 for the 3 methods. CONCLUSIONS: This preliminary study showed a high variability of 4 out of 5 textural indices (Homogeneity, Correlation, Entropy and LZLGE) extracted from pre-therapeutic FDG PET/CT in HNSCC using 3 different contouring methods. However, for each method, there was an excellent agreement between observers for 3 of these textural indices (Homogeneity, Correlation and Entropy).