Radiotherapy Target Volume Definition in Newly Diagnosed High-Grade Glioma Using 18F-FET PET Imaging and Multiparametric MRI: An Inter Observer Agreement Study.

Background: The aim of this prospective monocentric study was to assess the inter-observer agreement for tumor volume delineations by multiparametric MRI and 18-F-FET-PET/CT in newly diagnosed, untreated high-grade glioma (HGG) patients. Methods: Thirty patients HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine(18F-FET) positron emission tomography (PET), and multiparametric MRI with computation of rCBV map and K2 map. Three nuclear physicians and three radiologists with different levels of experience delineated the 18-F-FET-PET/CT and 6 MRI sequences, respectively. Spatial similarity (Dice and Jaccard: DSC and JSC) and overlap (Overlap: OV) coefficients were calculated between the readers for each sequence. Results: DSC, JSC, and OV were high for 18F-FET PET/CT, T1-GD, and T2-FLAIR (>0.67). The Spearman correlation coefficient between readers was ≥0.6 for these sequences. Cross-comparison of similarity and overlap parameters showed significant differences for DSC and JSC between 18F-FET PET/CT and T2-FLAIR and for JSC between 18F-FET PET/CT and T1-GD with higher values for 18F-FET PET/CT. No significant difference was found between T1-GD and T2-FLAIR. rCBV, K2, b1000, and ADC showed correlation coefficients between readers <0.6. Conclusion: The interobserver agreements for tumor volume delineations were high for 18-F-FET-PET/CT, T1-GD, and T2-FLAIR. The DWI (b1000, ADC), rCBV, and K2-based sequences, as performed, did not seem sufficiently reproducible to be used in daily practice.

Assessment of Image Quality and Lesion Detectability With Digital PET/CT System.

Purpose: The aim of this study was to assess image quality and lesion detectability acquired with a digital Positron Emission Tomography/Computed Tomography (PET/CT) Siemens Biograph Vision 600 system. Material and Methods: Consecutive patients who underwent a FDG PET/CT during the first week of use of a digital PET/CT (Siemens Biograph Vision 600) at the nuclear medicine department of the university hospital of Brest were analyzed. PET were realized using list mode acquisition. For all patients, 4 datasets were reconstructed. We determined, according to phantom measurements, an equivalent time acquisition/reconstruction parameters pair of the digital PET/CT corresponding to an analog PET/CT image quality ("analog-like") as reference dataset. We compared the reference dataset with 3 others digital PET/CT reconstruction parameters, allowing a decrease of emission duration: 60, 90, and 120 s per bed position. Three nuclear medicine physicians evaluated independently, for each dataset, overall image quality [Maximal Intensity Projection (MIP), noise, sharpness] using a 4-point scale. Physicians assessed also lesion detection capability by reporting new visible lesions on each digital datasets with their confidence level in comparison with analog-like dataset. Results: Ninety-eight patients were analyzed. Image quality of MIP (IQMIP), sharpness (IQSHARPNESS), and noise (IQNOISE) of all digital datasets (60, 90, and 120 s) were better than those evaluated with analog-like reconstruction. Moreover, digital PET/CT system improved IQMIP, IQNOISE, and IQSHARPNESS whatever the BMI. Lesion detection capability and confidence level were higher for 60, 90, 120 s per bed position, respectively, than for analog-like images. Conclusion: Our study demonstrated an improvement of image quality and lesion detectability with a digital PET/CT system.

Prediction of response to immune checkpoint inhibitor therapy using 18F-FDG PET/CT in patients with melanoma.

We aimed to assess serial F-FDG PET/CT imaging according to morphological (RECIST1.1, iRECIST) and functional (PERCIST, PECRIT) criteria to predict clinical response to therapy in patients with advanced melanoma receiving immune checkpoint blocking agents.Retrospective data collection and analysis was done for 37 patients with unresectable metastatic cutaneous melanoma eligible for immunotherapy (cycles: 4 for ipilimumab and pembrolizumab/ 6 for nivolumab).F-FDG PET/CT imaging was performed prior to (F-FDG PET/CT 0) and 14 weeks after ICI onset (F-FDG PET/CT 1). Some cases during the follow-up required imaging (F-FDG PET/CT 2). Assessment of patient response to treatment was done according to RECIST1.1, iRECIST, PERCIST and PECRIT criteria.Among 37 assessed patients, 27 had 1 line of ICI, 8 had 2 lines of ICI and 2 patients had 3 lines of ICI: total of 49 PET/CTs. Mean time between initiation of ICI and F-FDG PET/CT (1 or 2) were respectively 13.82 ±â€Š4.32 and 24.73 ±â€Š9.53 weeks. Time between F-FDG PET/CT 1 and F-FDG PET/CT 2 was at mean +/- SD: 11.19w ±â€Š5.59. Median PFS was 29.62 months (range 22.52-36.71) (P = .001: RECIST 1.1), (P < .0001: iRECIST), (P = .000: PERCIST), (P = .072: PECRIT). Median OS was 36.62 months (30.46-42.78) (P = .005: RECIST 1.1), (P < .0001: iRECIST), (P = .001: PERCIST), (P = .082 PECRIT).F-FDG PET/CT could detect eventual ICI-response in patients with metastatic melanoma undergoing ICI using iRECIST and PERCIST criteria.

Diagnostic performance of 18 fluorodesoxyglucose positron emission/computed tomography and magnetic resonance imaging in detecting T1-T2 head and neck squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: The aim of this study was to assess and compare the diagnostic accuracy of 18 fluorodesoxyglucose positron emission/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) to detect T1-T2 head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Prospective case series. METHODS: Thirty-five consecutive patients with histologically proven T1-T2 HNSCC were prospectively included. All patients underwent pretherapeutic FDG-PET/CT and MRI. Two nuclear medicine physicians and 2 radiologists blindly reviewed all FDG-PET/CT and MRI, respectively. A five-point qualitative scale was used to estimate tumor detection ability. Sensitivity of each modality was compared together using a McNemar test. Interobserver variability was assessed by kappa index (κ) of Cohen statistics. Maximal standardized uptake value (SUVMAX ), metabolic tumor volume (MTV) in FDG-PET/CT, and gadolinium enhancement (%GE) in MRI of each tumor were recorded and compared with T stage using a Mann-Whitney test. Tumor-to-normal tissue ratios in FDG-PET/CT and MRI (TNRPET and TNRMRI ) were calculated and compared together using a Student t test. RESULTS: Among the 35 primary tumors, 29 were detected by FDG-PET/CT and 22 by MRI. MRI detected none of the six lesions incorrectly identified by FDG-PET/CT. FDG-PET/CT correctly identified seven of the 13 MRI false-negative results. Sensitivity of FDG-PET/CT to detect T1-T2 HNSCC was significantly higher than MRI (83% vs. 63%, P = .015). T stage was significantly correlated with MTV (P = .002) unlike with SUVMAX (P = .06) and %GE (P = .70). TNRPET was significantly higher than TNRMRI (3.5 ± 3.2 vs. 1.2 ± 0.3, P < .0001). CONCLUSIONS: Our study showed a higher diagnostic accuracy of FDG-PET/CT than MRI to detect T1-T2 HNSCC with a good interobserver agreement. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:378-385, 2018.

Clinical Validation of a Pixon-Based Reconstruction Method Allowing a Twofold Reduction in Planar Images Time of 111In-Pentetreotide Somatostatin Receptor Scintigraphy.

OBJECTIVE: The objective of this study was to evaluate the diagnostic efficacy of Pixon-based reconstruction method on planar somatostatin receptor scintigraphy (SRS). METHODS: All patients with neuroendocrine tumors (NETs) disease who were referred for SRS to our department during 1-year period from January to December 2015 were consecutively included. Three nuclear physicians independently reviewed all the data sets of images which included conventional images (CI; 15 min/view) and processed images (PI) obtained by reconstructing the first 450 s extracted data using Oncoflash® software package. Image analysis using a 3-point rating scale for abnormal uptake of 111 Indium-DTPA-Phe-octreotide in any lesion or organ was interpreted as positive, uncertain, or negative for the evidence of NET disease. A maximum grade uptake of the radiotracer in the lesion was assessed by the Krenning scale method. The results of image interpretation by the two methods were considered significantly discordant when the difference in organ involvement assessment was negative vs. positive or in lesion uptake was ≥2 grades. Agreement between the results of two methods and by different scan observers was evaluated using Cohen κ coefficients. RESULTS: There was no significant (p = 0.403) correlation between data acquisition protocol and quality image. The rates of significant discrepancies for exam interpretation and organs involvement assessment were 2.8 and 2.6%, respectively. Mean κ values revealed a good agreement for concordance between CI and PI interpretation without difference of agreement for inter/intra-observer analysis. CONCLUSION: Our results suggest the feasibility to use a Pixon-based reconstruction method for SRS planar images allowing a twofold reduction of acquisition time and without significant alteration of image quality or on image interpretation.

Incremental diagnostic utility of systematic double-bed SPECT/CT for bone scintigraphy in initial staging of cancer patients.

BACKGROUND: SPECT/CT has been shown to increase the diagnostic performance of bone scintigraphy for staging of malignancies. A systematic double-bed SPECT/CT of the trunk may allow further improvement. However, this would be balanced by higher dosimetry and longer acquisition time. The objective was to assess the incremental diagnostic utility of a systematic double-bed SPECT/CT acquisition for bone scintigraphy in initial staging of cancer patients, especially compared with the usual approach consisting in a whole body planar scan (WBS) plus one single-bed targeted SPECT/CT. METHODS: One hundred two consecutive patients referred for bone scintigraphy for initial staging of malignancy were analyzed. All patients underwent a double-bed SPECT/CT acquisition of the trunk. Images were interpreted by two nuclear medicine physicians in a 3-step procedure. Firstly, only WBS planar images were used; secondly, one additional single-bed SPECT/CT chosen based on planar images was used; finally, WBS planar and double-bed SPECT/CT images were interpreted. Lesions were classified as benign, equivocal or suspicious for metastasis. A per-lesion, per-anatomical region and per-patient analysis was performed. RESULTS: In a per-lesion analysis, the number of equivocal and suspicious lesions was 91 and 241 using WBS planar images, 17 and 259 using a single-bed SPECT/CT acquisition and 11 and 269 using double-bed SPECT/CT images, respectively. In a per-patient analysis, the diagnostic conclusion was negative, equivocal or suspicious for malignancy in 35, 53 and 14 patients using WB planar images, 77, 6 and 19 patients using an additional single-bed SPECT/CT and 76, 7 and 19 using double-bed SPECT/CT images, respectively. Seventeen lesions unseen on WBS images were interpreted as suspicious (n = 12) or equivocal (n = 5) on double-bed SPECT/CT images. Six lesions unseen on "WBS + targeted single-bed SPECT/CT" were interpreted as suspicious on double-bed SPECT/CT, with no shift in the metastatic status of patients. CONCLUSION: A systematic double-bed SPECT/CT acquisition has a limited incremental diagnostic value over an oriented single-bed SPECT/CT in terms of specificity and conclusiveness of bone scintigraphy in the initial staging of cancer patients. However, it slightly improved the sensitivity of the test by detecting unseen lesions on WBS, which may be of value for initial staging of cancer.

Prognostic evaluation of percentage variation of metabolic tumor burden calculated by dual-phase (18) FDG PET-CT imaging in patients with head and neck cancer.

BACKGROUND: The purpose of this study was to investigate the prognostic value of percentage variation of metabolic tumor burden in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients referred to undergo (18) fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT for staging of HNSCC were included in this study. Using a dual-phase method, standardized uptake value maximum (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded and respectively used to calculate retention index (RI), %ΔMTV, and %ΔTLG. Recurrence-free survival (RFS) was determined by Kaplan-Meier method and compared with studied PET parameters in univariate and multivariate. RESULTS: Seventy patients (61 men/9 women; 62.9 ± 9.1 years old) were included. In univariate, SUVmax, RI, MTV, and TLG (p ≤ .0001) were significantly correlated with RFS, unlike %ΔMTV (p = 137) and %ΔTLG (p = .517). In multivariate, RI (p = .005) and MTV (p = .022) persisted as independent prognostic factors. CONCLUSION: Our results did not prove a prognostic interest of percentage variation of metabolic tumor burden in patients with HNSCC but confirmed that RI and MTV are independently correlated with RFS. © 2015 Wiley Periodicals, Inc. Head Neck 38: E600-E606, 2016.

Diagnostic performance of FDG PET/CT to detect subclinical HNSCC recurrence 6 months after the end of treatment.

PURPOSE: Posttreatment follow-up for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination or conventional imaging. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is widely validated for the diagnosis of suspected recurrence. Moreover, we have shown in a previous prospective study the high effectiveness of FDG PET/CT in the assessment of subclinical recurrence 12 months after treatment. The aim of this prospective study was to evaluate the effectiveness of an earlier FDG PET/CT, at 6 months after the end of treatment. METHODS: All patients treated for histologically proven HNSCC from April 2009 to May 2012 at the University Hospital of Brest who did not show any findings suggestive of recurrence at 6 months of their usual follow-up underwent an FDG PET/CT examination. FDG PET/CT findings were correlated with histopathology or imaging follow-up. RESULTS: The study included 116 patients. FDG PET/CT examinations were performed within a mean period ± SD of 5.6 ± 1.8 months after treatment. FDG PET/CT examinations exhibited abnormal FDG uptake in 34 patients and found no suspected recurrence in 82 cases. Of these 82 FDG PET/CT considered as negative, only 1 had a recurrence. Among the 34 positive FDG PET/CT, 22 relapsed whereas 12 did not show evidence of recurrence. The sensitivity and specificity of FDG PET/CT in this study for the diagnosis of occult HNSCC recurrence were 96 (22/23) and 87 % (81/93), respectively. The positive predictive value was 65 % (22/34). The negative predictive value was 99 % (81/82). The overall accuracy was 89 % (103/116). Of the 116 patients, FDG PET/CT highlighted 22 (19 %) subclinical recurrences. CONCLUSION: Our study showed the high effectiveness of FDG PET/CT in the assessment of subclinical HNSCC recurrence 6 months after completion of treatment. These results confirmed that FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC, as we previously demonstrated in patients clinically asymptomatic at 12 months.

Prognostic value of volumetric parameters measured by 18F-FDG PET/CT in patients with head and neck squamous cell carcinoma.

PURPOSE: The objective of this study was to investigate the value of metabolic tumour volume (MTV) assessed with (18)F-FDG PET/CT in predicting event-free survival (EFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC), and particularly to compare it with more conventional parameters such as maximum standardized uptake value (SUVmax). METHODS: Patients referred to our department for (18)F-FDG PET/CT for staging of HNSCC were prospectively included between February 2009 and March 2011. Each patient was scanned using a Philips Gemini PET/CT system at 1 h after injection. The MTV was calculated semiautomatically for the primary site using methods based on SUV with various thresholds: 3-D contour around voxels equal to or greater than 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 and 7.0 times SUV, or more than 30%, 40% and 50% of SUVmax. ROC analysis was used to test the statistical significance of the differences among the calculated MTVs. EFS and OS were determined using the Kaplan-Meier method and compared with MTV in univariate and multivariate analyses, including the usual prognostic factors: age, sex, primary site, treatment, SCC histologic grade, AJCC stage, TNM classification, tumour SUVmax and SUVpeak. RESULTS: The study included 80 consecutive patients (70 men, 10 women; mean age 62.4 ± 9.0 years). ROC analysis revealed that pretreatment MTV using a threshold of 5.0 times SUV (MTV5.0) was the best parameter to predict recurrence and death after treatment. In univariate analysis, MTV5.0 >4.9 ml was predictive of poor EFS (p < 0.0001) and poor OS (p < 0.0001). In multivariate, MTV5.0 persisted as an independent predictive factor for EFS (p = 0.011) and OS (p = 0.010), while SUVmax became nonsignificant (p = 0.277 for EFS, p = 0.975 for OS). CONCLUSION: Our results suggest that MTV measured by (18)F-FDG PET/CT has independent prognostic value of in patients with HNSCC, stronger than SUVmax.

Early prediction of survival following induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) using FDG PET/CT imaging in patients with locally advanced head and neck squamous cell carcinoma.

PURPOSE: Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population. METHODS: Patients with stage III/IV HNSCC, in whom DCF induction chemotherapy followed by concurrent chemoradiotherapy had been validated by a multidisciplinary team, were prospectively included in the study. FDG PET/CT scans were performed in all patients before and after two of the three cycles of DCF. EORTC99 criteria were used to evaluate PET responses as follows: group 1 (metabolic responders) showing a complete response (CR) or partial response (PR), and subgroup 0 (metabolic nonresponders) showing stable disease (SD) or progressive disease (PD). The primary endpoint for monitoring patients was event-free survival (EFS). EFS probabilities between the two groups were estimated by the Kaplan-Meier method and statistically compared using the log-rank test. RESULTS: Fifteen consecutive patients (14 men, 1 woman; age 57.5 ± 6.2 years, mean ± SD) were analysed. Therapeutic assessment by PET/CT demonstrated CR in four patients, PR in six, SD in four and PD in one. Among the ten patients with a metabolic response (group 1), none had relapsed at the time of this report, while four of five patients with no metabolic response (group 0) showed recurrence within an average of 9.0 ± 1.6 months. Median EFS was, respectively, 18.9 months (3.8-25.3 months) and 10.2 months (7.5-12.7 months) in group 1 and group 0. The corresponding 1-year EFS rates were 100 % and 20 %, respectively. The difference in EFS between the two groups was statistically significant (p = 0.0014). CONCLUSION: Early therapeutic response demonstrated on FDG PET/CT after two cycles of induction chemotherapy with DCF in patients with inoperable stage III/IV HNSCC seems to be a predictive factor for EFS.

Clinical and therapeutic impact of 18F-FDG PET/CT whole-body acquisition including lower limbs in patients with malignant melanoma.

OBJECTIVES: To assess the added benefit of scanning lower limbs in addition to the usual whole-body positron emission tomography/computed tomography (PET/CT) scan in patients with no known or suspected primary or metastatic melanoma involving the lower limbs. MATERIALS AND METHODS: This is a retrospective study of 122 consecutive patients [174 2-[¹8F]-fluoro-2-deoxy-D-glucose (FDG) PET/CT] who underwent FDG PET/CT for staging of melanoma at different time points in the course of the disease from October 2005 to February 2009 at the Brest University Hospital. Reports of whole-body PET/CT scans including lower limbs were reviewed. PET/CT abnormalities on the lower extremities were tabulated by location and correlated with pathology, other imaging studies and at least a 6-month clinical follow-up. The usefulness of lower limbs acquisition in clinical management was evaluated according to imagery findings. RESULTS: Among the 174 consecutive PET/CT scans performed in 122 patients, 33 scans in 28 patients highlighted abnormal FDG uptakes considered as equivocal or suggestive of malignancy in the lower limbs. In 28 cases, uptakes were located at once in the lower limbs and in the rest of the body (lung, liver, mediastinal and sub-diaphragmatic lymph nodes, adrenal glands, bone) corresponding to disseminated disease. In five cases, PET/CT uptakes were located only in lower limbs; each pathological uptake corresponded to benign lesions. Lower limbs findings never impacted clinical and therapeutic decision. CONCLUSION: Lower limbs additional PET/CT acquisition seems to offer poor additional benefit with none unexpected lesion detected and routine skull base to upper thigh images might be sufficient for this subset of patients.