Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Prognostic Value of Baseline Tumor Burden and Tumor Dissemination Extracted From 18 F-FDG PET/CT in a Cohort of Adult Patients With Early or Advanced Hodgkin Lymphoma.

PURPOSE: We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). PATIENTS AND METHODS: Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%). CONCLUSIONS: Combining baseline TLG with IPS could improve PFS prediction.

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. Objective: To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. Design, Setting, and Participants: This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. Interventions: The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). Main Outcomes and Measures: The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. Results: A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. Conclusions and Relevance: This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. Trial Registration: ClinicalTrials.gov Identifier: NCT01874587.

Dissemination patterns of Hodgkin lymphoma using a probability network model based on [18F]-FDG PET/CT.

PURPOSE: The preferred hypothesis for the dissemination patterns of Hodgkin lymphoma (HL) is the contiguity hypothesis. However, this hypothesis is based on studies performed before the advent of [18F]-FDG PET/CT which is now the established reference for HL staging. This study aims to extract the dissemination patterns of HL using [18F]-FDG PET/CT and a probability network model. METHODS: We retrospectively analyzed [18F]-FDG PET/CT performed for initial staging of patients with classical HL. The HL involvement status (presence of absence) was reported for 19 supra- and infra-diaphragmatic lymph node regions and 4 extranodal regions (lung, spleen, liver, and osteo- medullary). The analysis of HL dissemination was carried out using HL involvement status for all regions through 3 distinct methods: comparison of nearby lymph node regions, correlation assessment between all regions and relationship strength between all regions using Ising network model. RESULTS: A total of 196 patients were included. Our results showed strong relationships between nearby involved lymph node regions (for example between the left pelvic and the abdominal lymph node regions (relationship strength = 0.980)) and between more distant regions (for example between right and left axillary lymph node regions (strength = 0.714)). Furthermore, involvement of the infra-diaphragmatic lymph node regions was significantly correlated with Ann Arbor stage IV (phi = 0.56, p < 0.001). CONCLUSION: This study confirms the hypothesis of lymphatic dissemination of HL in a contiguous mode, with additional links between more distant regions. These predictable dissemination patterns could be useful for the initial staging assessment of patients with HL using [18F]-FDG PET/CT.

Delayed [ 18 F]-FDG PET Imaging Increases Diagnostic Performance and Reproducibility to Differentiate Recurrence of Brain Metastases From Radionecrosis.

PURPOSE: Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging. METHODS: Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared. RESULTS: Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61). CONCLUSIONS: [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy.

Impact of point-spread function reconstruction on dynamic and static 18F-DOPA PET/CT quantitative parameters in glioma.

BACKGROUND: Quantification of dynamic and static parameters extracted from 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA, FDOPA) positron emission tomography (PET)/computed tomography (CT) plays a critical role for glioma assessment. The objective of the present study was to investigate the impact of point-spread function (PSF) reconstruction on these quantitative parameters. METHODS: Fourteen patients with untreated gliomas and investigated with FDOPA PET/CT were analyzed. The distribution of the 14 cases was as follows: 6 astrocytomas-isocitrate dehydrogenase-mutant; 2 oligodendrogliomas/1p19q-codeleted-isocitrate dehydrogenase-mutant; and 6 isocitrate dehydrogenase-wild-type glioblastomas. A 0-20-min dynamic images (8×15, 2×30, 2×60, and 3×300 s post-injection) and a 0-20-min static image were reconstructed with and without PSF. Tumoral volumes-of-interest were generated on all of the PET series and the background volumes-of-interest were generated on the 0-20-min static image with and without PSF. Static parameters (SUVmax and SUVmean) of the tumoral and the background volumes-of-interest and kinetic parameters (K1 and k2) of the tumoral volumes-of-interest extracted from using full kinetic analysis were provided. PSF and non-PSF quantitative parameters values were compared. RESULTS: Thirty-three tumor volumes-of-interest and 14 background volumes-of-interest were analyzed. PSF images provided higher tumor SUVmax than non-PSF images for 23/33 VOIs [median SUVmax =3.0 (range, 1.4-10.2) with PSF vs. 2.7 (range, 1.4-9.1) without PSF; P<0.001] and higher tumor SUVmean for 13/33 volumes-of-interest [median SUVmean =2.0 (range, 0.8-7.6) with PSF vs. 2.0 (range, 0.8-7.4) without PSF; P=0.002]. K1 and k2 were significantly lower with PSF than without PSF [respectively median K1 =0.077 mL/ccm/min (range, 0.043-0.445 mL/ccm/min) with PSF vs. 0.101 mL/ccm/min (range, 0.055-0.578 mL/ccm/min) without PSF; P<0.001 and median k2 =0.070 min-1 (range, 0.025-0.146 min-1) with PSF vs. 0.081 min-1 (range, 0.027-0.180 min-1) without PSF; P<0.001]. Background SUVmax and SUVmean were statistically unaffected [respectively median SUVmax =1.7 (range, 1.3-2.0) with PSF vs. 1.7 (range, 1.3-1.9) without PSF; P=0.346 and median SUVmean =1.5 (range, 1.0-1.8) with PSF vs. 1.5 (range, 1.0-1.7) without PSF; P=0.371]. CONCLUSIONS: The present study confirms that PSF significantly increases tumor activity concentrations measured on PET images. PSF algorithms for quantitative PET/CT analysis should be used with caution, especially for quantification of kinetic parameters.

18F-FDG PET/CT-Based Prognostic Survival Model After Surgery for Head and Neck Cancer.

The aims of this multicenter study were to identify clinical and preoperative PET/CT parameters predicting overall survival (OS) and distant metastasis-free survival (DMFS) in a cohort of head and neck squamous cell carcinoma patients treated with surgery, to generate a prognostic model of OS and DMFS, and to validate this prognostic model with an independent cohort. Methods: A total of 382 consecutive patients with head and neck squamous cell carcinoma, divided into training (n = 318) and validation (n = 64) cohorts, were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and distance parameters for the primary tumor and lymph nodes defined by 2 segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The concordance index (c-index) was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and nodal MTV, with a c-index of 0.64 (P < 0.001). For DMFS, the significant parameters were T stage, nodal MTV, and maximal tumor-node distance, with a c-index of 0.76 (P < 0.001). These combinations of parameters were externally validated, with c-indices of 0.63 (P < 0.001) and 0.71 (P < 0.001) for OS and DMFS, respectively. Conclusion: The nodal MTV associated with the maximal tumor-node distance was significantly correlated with the risk of DMFS. Moreover, this parameter, in addition to clinical parameters, was associated with a higher risk of death. These prognostic factors may be used to tailor individualized treatment.

Combining 18F-DOPA PET and MRI with perfusion-weighted imaging improves delineation of high-grade subregions in enhancing and non-enhancing gliomas prior treatment: a biopsy-controlled study.

PURPOSE: We aimed to compare spatial extent of high-grade subregions detected with combined [18F]-dihydroxyphenylalanine (18F-DOPA) PET and MRI to the one provided by advanced multimodal MRI alone including Contrast-enhanced (CE) and Perfusion weighted imaging (PWI). Then, we compared the accuracy between imaging modalities, in a per biopsy analysis. METHODS: Participants with suspected diffuse glioma were prospectively included between June 2018 and September 2019. Volumes of high-grade subregions were delineated respectively on 18F-DOPA PET and MRI (CE and PWI). Up to three per-surgical neuronavigation-guided biopsies were performed per patient. RESULTS: Thirty-eight biopsy samples from sixteen participants were analyzed. Six participants (38%) had grade IV IDH wild-type glioblastoma, six (38%) had grade III IDH-mutated astrocytoma and four (24%) had grade II IDH-mutated gliomas. Three patients had intratumoral heterogeneity with coexisting high- and low-grade tumor subregions. High-grade volumes determined with combined 18F-DOPA PET/MRI (median of 1.7 [interquartile range (IQR) 0.0, 19.1] mL) were larger than with multimodal MRI alone (median 1.3 [IQR 0.0, 12.8] mL) with low overlap (median Dice's coefficient 0.24 [IQR 0.08, 0.59]). Delineation volumes were substantially increased in five (31%) patients. In a per biopsy analysis, combined 18F-DOPA PET/MRI detected high-grade subregions with an accuracy of 58% compared to 42% (p = 0.03) with CE MRI alone and 50% (p = 0.25) using multimodal MRI (CE + PWI). CONCLUSIONS: The addition of 18F-DOPA PET to multimodal MRI (CE and PWI) enlarged the delineation volumes and enhanced overall accuracy for detection of high-grade subregions. Thus, combining 18F-DOPA with advanced MRI may improve treatment planning in newly diagnosed gliomas.

Additive Value of Dynamic FDOPA PET/CT for Glioma Grading.

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas. Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC). Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min-1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP). Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.

Whole-body MR imaging in suspected physical child abuse: comparison with skeletal survey and bone scintigraphy findings from the PEDIMA prospective multicentre study.

OBJECTIVES: To assess the contribution of whole-body magnetic resonance imaging (WBMRI) and bone scintigraphy (BS) in addition to skeletal survey (SS) in detecting traumatic bone lesions and soft-tissue injuries in suspected child abuse. METHODS: In this prospective, multicentre, diagnostic accuracy study, children less than 3 years of age with suspected physical abuse were recruited. Each child underwent SS, BS and WBMRI. A blinded first review was performed in consensus by five paediatric radiologists and three nuclear medicine physicians. A second review investigated discrepancies reported between the modalities using a consensus result of all modalities as the reference standard. We calculated the sensitivity, specificity and corresponding 95% confidence interval for each imaging modality (SS, WBMRI and BS) and for the combinations [SS + WBMRI] and [SS + BS]. RESULTS: One hundred seventy children were included of which sixty-four had at least one lesion. In total, 146 lesions were included. The sensitivity and specificity of each examination were, respectively, as follows: 88.4% [95% CI, 82.0-93.1] and 99.7% [95% CI, 99.5-99.8] for the SS, 69.9% [95% CI, 61.7-77.2] and 99.5% [95% CI, 99.2-99.7] for WBMRI and 54.8% [95% CI, 46.4-63.0] and 99.7% [95% CI, 99.5-99.9] for BS. Sensitivity and specificity were, respectively, 95.9% [95% CI, 91.3-98.5] and 99.2% [95% CI, 98.9-99.4] for the combination SS + WBMRI and 95.2% [95% CI, 90.4-98.1] and 99.4% [95% CI, 99.2-99.6] for the combination SS + BS, with no statistically significant difference between them. CONCLUSION: SS was the most sensitive independent imaging modality; however, the additional combination of either WBMRI or BS examinations offered an increased accuracy. KEY POINTS: • SS in suspected infant abuse was the most sensitive independent imaging modality in this study, especially for detecting metaphyseal and rib lesions, and remains essential for evaluation. • The combination of either SS + BS or SS + WBMRI provides greater accuracy in diagnosing occult and equivocal bone injuries in the difficult setting of child abuse. • WBMRI is a free-radiation technique that allows additional diagnosis of soft-tissue and visceral injuries.

The Added Value of Bloodpool SPECT/CT in Painful Non-Operated Foot and Ankle Undiagnosed With Standard Three-Phase Bone Scintigraphy.

Purpose: To evaluate the interest of adding a bloodpool SPECT/CT to standard three-phase bone scintigraphy (BS) for etiological diagnosis of subacute and chronic lower extremity pains. Methods: We prospectively included patients addressed for pain of lower extremities lasting for at least 6 weeks, without previous surgery. They underwent a standard three-phase BS including late phase SPECT/CT, modified with an additional bloodpool SPECT/CT acquisition. Two independent physicians interpreted the images provided by both protocols. Diagnostic conclusion, diagnostic confidence, and interrater agreements were compared. Results: One hundred and eighteen lower extremities from 113 patients were analyzed (71 men, median age of 53 years). Adding bloodpool SPECT/CT to standard three-phase BS changed diagnostic conclusions in 24.6% (29/118) of lower extremities. The modified protocol revealed at least one diagnostic conclusion explaining the pain in 89% of extremities, rather than 83.1% with the standard protocol (p = 0.02). Tendinopathies were diagnosed in 12.7% of lower extremities, rather than 4.2% with standard BS (p = 0.002). Adding bloodpool SPECT/CT substantially increased overall confidence of each reader (p < 0.001). Inter-reader agreement was not significantly impacted. Conclusion: Adding bloodpool SPECT/CT to standard three-phase BS impacted diagnostic conclusion in a quarter of the patients with painful lower extremities, notably by revealing significantly more tendonitis.

Impact of Systematic Whole-body 18F-Fluorodeoxyglucose PET/CT on the Management of Patients Suspected of Infective Endocarditis: The Prospective Multicenter TEPvENDO Study.

BACKGROUND: Diagnostic and patients' management modifications induced by whole-body 18F-FDG-PET/CT had not been evaluated so far in prosthetic valve (PV) or native valve (NV) infective endocarditis (IE)-suspected patients. METHODS: In sum, 140 consecutive patients in 8 tertiary care hospitals underwent 18F-FDG-PET/CT. ESC-2015-modified Duke criteria and patients' management plan were established jointly by 2 experts before 18F-FDG-PET/CT. The same experts reestablished Duke classification and patients' management plan immediately after qualitative interpretation of 18F-FDG-PET/CT. A 6-month final Duke classification was established. RESULTS: Among the 70 PV and 70 NV patients, 34 and 46 were classified as definite IE before 18F-FDG-PET/CT. Abnormal perivalvular 18F-FDG uptake was recorded in 67.2% PV and 24.3% NV patients respectively (P < .001) and extracardiac uptake in 44.3% PV and 51.4% NV patients. IE classification was modified in 24.3% and 5.7% patients (P = .005) (net reclassification index 20% and 4.3%). Patients' managements were modified in 21.4% PV and 31.4% NV patients (P = .25). It was mainly due to perivalvular uptake in PV patients and to extra-cardiac uptake in NV patients and consisted in surgery plan modifications in 7 patients, antibiotic plan modifications in 22 patients and both in 5 patients. Altogether, 18F-FDG-PET/CT modified classification and/or care in 40% of the patients (95% confidence interval: 32-48), which was most likely to occur in those with a noncontributing echocardiography (P < .001) or IE classified as possible at baseline (P = .04), while there was no difference between NV and PV. CONCLUSIONS: Systematic 18F-FDG-PET/CT did significantly and appropriately impact diagnostic classification and/or IE management in PV and NV-IE suspected patients. CLINICAL TRIALS REGISTRATION: NCT02287792.

Add-on bone scintigraphy after negative radiological skeletal survey for the diagnosis of skeletal injury in children suspected of physical abuse: a systematic review and meta-analysis.

OBJECTIVES: To systematically assess the extent to which bone scintigraphy (BS) could improve the detection rate of skeletal injury in children suspected of physical abuse with an initial negative radiological skeletal survey (RSS). STUDY DESIGN: We searched MEDLINE and Web of Science for series of ≥20 children suspected of physical abuse who underwent RSS and add-on BS. We assessed the risk of bias and the heterogeneity and performed random-effects meta-analyses. RESULTS: After screening 1140 unique search results, we reviewed 51 full-text articles, and included 7 studies (783 children, mostly ≤3 years old). All studies were of either high or unclear risk of bias. Substantial heterogeneity was observed in meta-analyses. The summary detection rate of skeletal injury with RSS alone was 52% (95% CI 37 to 68). The summary absolute increase in detection rate with add-on BS was 10 percentage points (95% CI 6 to 15); the summary relative detection rate was 1.19 (95% CI 1.13 to 1.25); the summary number of children with a negative RSS who needed to undergo a BS to detect one additional child with skeletal injury (number needed to test) was 3 (95% CI 2 to 7). CONCLUSIONS: From the available evidence, add-on BS in young children suspected of physical abuse with a negative RSS might allow for a clinically significant improvement of the detection rate of children with skeletal injury, for a limited number of BS procedures required. The quality of the reviewed evidence was low, pointing to the need for high-quality studies in this field.

Increased thyroid uptake on 18F-FDG PET/CT is associated with the development of permanent hypothyroidism in stage IV melanoma patients treated with anti-PD-1 antibodies.

PURPOSE: To determine performances of 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) to detect the development of permanent thyroid dysfunction (PTD), and to evaluate the prognostic value of early increased thyroid uptake in stage IV melanoma patients treated with anti-programmed death 1 (anti-PD-1) antibodies. METHODS: Twenty-nine patients were retrospectively enrolled. PTD was defined as symptomatic thyroid disorder requiring long-term specific treatment. On the first PET performed during follow-up, maximal standardized uptake value of the thyroid (SUVmax-Th) and SUVmax-Th/SUVmax-blood-pool ratio (Th/B) were measured. Areas under ROC curves (AUC) of these parameters for the diagnostic of PTD were compared. Cutoff values were defined to maximize the Youden's index. Survival analyses were performed according to the Kaplan-Meier method and compared using the log-rank method between patients with and without enhanced thyroid uptake according to cutoff values defined with the Hothorn and Lausen method. RESULTS: Four patients presented PTD. Median SUVmax-Th and Th/B were, respectively, 2.11 and 1.00. The median follow-up period was 21.7 months. AUC were 1.0 (CI95% 0.88-1.0) for both parameters. Optimal cutoff values were, respectively, SUVmax-Th > 4.1 and Th/B > 2.0, both conferring sensitivities of 100% (CI95% 40-100%) and specificities of 100% (CI95% 86-100%). The median progression-free survival and overall survival were 11.3 months and 33.5 months, respectively. Using optimized cutoffs, there was no statistically significant difference of survival. CONCLUSION: SUVmax-Th > 4.1 and Th/B > 2.0 provided perfect diagnostic performances to detect patients that developed PTD. No significant survival difference was found between patients with and without increased thyroid uptake.

Optimization of time frame binning for FDOPA uptake quantification in glioma.

INTRODUCTION: 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA) uptake quantification in glioma assessment can be distorted using a non-optimal time frame binning of time-activity curves (TAC). Under-sampling or over-sampling dynamic PET images induces significant variations on kinetic parameters quantification. We aimed to optimize temporal time frame binning for dynamic FDOPA PET imaging. METHODS: Fourteen patients with 33 tumoral TAC with biopsy-proven gliomas were analysed. The mean SUVmax tumor-to-brain ratio (TBRmax) were compared at 20 min and 35 min post-injection (p.i). Five different time frame samplings within 20 min were compared: 11x10sec-6x15sec-5x20sec-3x300sec; 8x15sec- 2x30sec- 2x60sec- 3x300sec; 6x20sec- 8x60sec- 2x300sec; 10x30sec- 3x300sec and 4x45sec- 3x90sec- 5x150sec. The reversible single-tissue compartment model with blood volume parameter (VB) was selected using the Akaike information criterion. K1 values extracted from 1024 noisy simulated TAC using Monte Carlo method from the 5 different time samplings were compared to a target K1 value as the objective, which is the average of the K1 values extracted from the 33 lesions using an imaging-derived input function for each patient. RESULTS: The mean TBRmax was significantly higher at 20 min p.i. than at 35 min p.i (respectively 1.4 +/- 0.8 and 1.2 +/- 0.6; p <0.001). The target K1 value was 0.161 mL/ccm/min. The 8x15sec- 2x30sec- 2x60sec- 3x300sec time sampling was the optimal time frame binning. K1 values extracted using this optimal time frame binning were significantly different with K1 values extracted from the other time frame samplings, except with K1 values obtained using the 11x10sec- 6x15sec -5x20sec-3x300sec time frame binning. CONCLUSIONS: This optimal sampling schedule design (8x15sec- 2x30sec- 2x60sec- 3x300sec) could be used to minimize bias in quantification of FDOPA uptake in glioma using kinetic analysis.

Evaluation of the Prognostic Value of FDG PET/CT Parameters for Patients With Surgically Treated Head and Neck Cancer: A Systematic Review.

Importance: Head and neck squamous cell cancer (HNSCC) represents the seventh most frequent cancer worldwide. More than half of the patients diagnosed with HNSCC are treated with primary surgery. Objective: To report the available evidence on the value of quantitative parameters of fluorodeoxyglucose F 18-labeled positron emission tomography and computed tomography (FDG-PET/CT) performed before surgical treatment of HNSCC to estimate overall survival (OS), disease-free survival (DFS), and distant metastasis (DM) and to discuss their limitations. Evidence Review: A systematic review of the English-language literature in PubMed/MEDLINE and ScienceDirect published between January 2003 and February 15, 2019, was performed between March 1 and July 27, 2019, to identify articles addressing the association between preoperative FDG-PET/CT parameters and oncological outcomes among patients with HNSCC. Articles included those that addressed the following: (1) cancer of the oral cavity, oropharynx, hypopharynx, or larynx; (2) surgically treated (primary or for salvage); (3) pretreatment FDG-PET/CT; (4) quantitative or semiquantitative evaluation of the FDG-PET/CT parameters; and (5) the association between the value of FDG-PET/CT parameters and clinical outcomes. Quality assessment was performed using the Oxford Centre for Evidence-Based Medicine level of evidence. Findings: A total of 128 studies were retrieved from the databases, and 36 studies met the inclusion criteria; these studies comprised 3585 unique patients with a median follow-up of 30.6 months (range, 16-53 months). Of these 36 studies, 32 showed an association between at least 1 FDG-PET/CT parameter and oncological outcomes (OS, DFS, and DM). The FDG-PET/CT volumetric parameters (metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) were independent prognostic factors in most of the data, with a higher prognostic value than the maximum standard uptake value (SUVmax). For example, in univariate analysis of OS, the SUVmax was correlated with OS in 5 of 11 studies, MTV in 11 of 12 studies, and TLG in 6 of 9 studies. The spatial distribution of metabolism via textural indices seemed promising, although that factor is currently poorly evaluated: only 3 studies analyzed data from radiomics indices. Conclusions and Relevance: The findings of this study suggest that the prognostic effectiveness of FDG-PET/CT parameters as biomarkers of OS, DFS, and DM among patients with HNSCC treated with surgery may be valuable. The volumetric parameters (MTV and TLG) seemed relevant for identifying patients with a higher risk of postsurgical disease progression who could receive early therapeutic intervention to improve their prognosis. However, further large-scale studies including exclusively surgery-treated patients stratified according to localization and further analysis of the textural indices are required to define a reliable FDG-PET/CT-based prognostic model of mortality and recurrence risk for these patients.

Prognostic Value of Baseline Total Metabolic Tumor Volume Measured on FDG PET in Patients With Richter Syndrome.

PURPOSE: We evaluated the prognostic value of baseline total metabolic tumor volume (TMTV) measured using pretreatment FDG PET for patients with transformation of chronic lymphocytic leukemia (CLL) into diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 28 patients with transformation of CLL into DLBCL who had undergone FDG PET before treatment were retrospectively reviewed. Univariate and multivariate analysis of conventional clinicopathologic variables (sex, age, World Health Organization performance status score, International Prognostic Index score, Binet stage, lactate dehydrogenase serum level [LDH], platelet count, presence or not of prior therapies for CLL, the time from CLL to Richter syndrome, Ann Arbor stage, Bulky or not) and metabolic parameters (SUVmax, SUVmean, TMTV, and total lesion glycolysis) at the time of the transformation of CLL into DLBCL were tested for overall survival (OS). RESULTS: Of the 28 patients, 14 patients (50%) died during the follow-up period. Low platelet count, World Health Organization performance status score >1, high LDH, and high TMTV were found to be significant prognostic factors for OS on univariate analysis. The 5-year estimates of OS were 63% in the low metabolic burden group (TMTV ≤1200 cm) and 0% in the high metabolic burden group (TMTV >1200 cm). Multivariate analysis revealed that only high LDH was a significant predictor after adjustment for other variables of OS. CONCLUSIONS: TMTV extracted from FDG PET at the time of the transformation of CLL into DLBCL is a predictor of OS.

Pretreatment 18F-FDG PET/CT Radiomics Predict Local Recurrence in Patients Treated with Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: A Multicentric Study.

The aim of this retrospective multicentric study was to develop and evaluate a prognostic 18F-FDG PET/CT radiomic signature in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy (SBRT). Methods: Patients from 3 different centers (n = 27, 29, and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control. The primary tumor was semiautomatically delineated in the PET images using the fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. In total, 184 Image Biomarkers Standardization Initiative-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the 4 institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model, and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 mo (range, 1.7-63.4 mo) and 25.5 mo (range, 7.7-57.8 mo) in training and testing sets, respectively. In univariate analysis, none of the clinical variables, 2 PET features, and 2 CT features were significantly predictive of local control. The best predictive models in the training set were obtained by combining one feature from PET (Information Correlation 2) and one feature from CT (flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (Information Correlation 2 and strength) reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (P < 0.001). The latter model obtained an accuracy of 0.91 (sensitivity, 100%; specificity, 81%), with a hazard ratio undefined (P = 0.023) in the testing set; however, other models relying on CT radiomic features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that 2 radiomic features derived from 18F-FDG PET were independently associated with local control in patients with non-small cell lung cancer undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision making.

Comparison of 18F-Choline PET/CT and MRI functional parameters in prostate cancer.

AIM: 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. MATERIALS AND METHODS: Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. RESULTS: The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). CONCLUSIONS: No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.