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The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

to investigate the preoperative role of ML-based classification using conventionalretrospective study, including 123 EC patients who underwenton the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) forML-based classification using conventional

Objectives To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab. Methods Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed. Results Forty-one patients were included. Starting infliximab dose was 5 mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26–61) months in the standard-dose group and 68 (38–87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31–71) months, due to loss of response (n = 7) or patient’s request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6–2.3] vs 1.3 [1–1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation. Conclusion In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages.

BACKGROUND Qualitative assessment using the Deauville five-point scale (DS) is the gold standard for interim and end-of treatment PET interpretation in lymphoma. In the present study we assessed the reliability and the prognostic value of different semi- quantitative (SQ) parameters in comparison with DS for interim PET (iPET) interpretation in Hodgkin lymphoma (HL). METHODS A cohort of 82 out of 260 patients with advanced stage HL enrolled in the International Validation Study (IVS), scored as 3 to 5 by the expert panel was included in the present report. Two nuclear medicine physicians blinded to patient history, clinical data and treatment outcome reviewed independently the iPET using the following parameters: DS, SUVMax, SUVPeak of the most active lesion, QMax (ratio of SUVMax of the lesion to liver SUVMax) and QRes (ratio of SUVPeak of the lesion to liver SUVMean). The optimal sensitivity, specificity, positive and negative predictive value to predict treatment outcome was calculated for all the above parameters with the Receiver Operator Characteristics analysis. RESULTS The prognostic value of all parameters were similar, the best cut-off value being 4 for DS (Area Under the Curve, AUC, 0.81 CI95%: 0.72-0.90), 3.81 for SUVMax (AUC 0.82 CI95%: 0.73-0.91), 3.20 for SUVPeak (AUC 0.86 CI95%: 0.77-0.94), 1.07 for QMax (AUC 0.84 CI95%: 0.75-0.93) and 1.38 for QRes (AUC 0.84 CI95%: 0.75-0.93). The reproducibility of different parameters was similar as the inter-observer variability measured with Cohen's kappa were 0.93 (95% CI 0.84-1.01) for the DS, 0.88 (0.77-0.98) for SUVMax, 0.82 (0.70-0.95) for SUVPeak, 0.85 (0.74-0.97) for QRes and 0.78 (0.65-0.92) for QMax. Due to the high specificity of SUVPeak (0.87) and to the good sensitivity of DS (0.86), upon the use of both parameters the positive predictive value increased from 0.65 of the DS alone to 0.79. When both parameters were positive in iPET, 3-years Failure-Free Survival (FFS) was significantly lower compared to patients whose iPET was interpreted with qualitative parameters only (DS 4 or 5): 21% vs 35%. On the other hand, the FFS of patients with negative results was not significantly different (88% vs 86%). CONCLUSIONS In this study we demonstrated that, combining semi-quantitative parameters with SUVPeak to a pure qualitative interpretation key with DS, it is possible to increase the positive predictive value of iPET and to identify with higher precision the patients subset with a very dismal prognosis. However, these retrospective findings should be confirmed prospectively in a larger patient cohort.

Purpose: To present the progresses of hybrid 18F-FDG PET/MR imagingin the staging/restaging setting of endometrial cancer (EC), with particular focus on performance evaluations and biomarker analyses. Methods: Original articles were searched on PubMed, EMBASE and Web of Science, until March 2021. Reports were screened to select studies using simultaneous PET/MR acquisition, discarding those using sequential protocols. Studies including heterogeneous and/or homogeneous cohorts of pelvic tumor patients were considered, while works for which the exact number of EC patients was not reported have been discarded. Evaluations of selected articles were focused on (i) performance evaluation, (ii) biomarker analysis. The quality of papers was assessed by QUADAS-2. Results: Eleven articles involving 18F-FDGPET/MRI EC-related objectives were selected. The quality of papers was generally high. Compared to other imaging techniques, PET/MRI seems to show a higher diagnostic accuracy in detecting soft tissue invasion and abdominopelvic metastases from primary EC. Among different PET- and MRI-derived biomarkers, SUV-to-ADC ratio seems to be the most informative index in differentiating EC aggressiveness. Moreover, PET/MRI provided the chance to differentiate post-therapeutic changes from local relapse, and to detect small, morphologically unsuspicious lymph node metastases in patients with recurrent EC, with better performances compared to other imaging modalities. Conclusions: Preliminary results demonstrated how 18F-FDG PET/MRI could be a valid imaging technique in patients with EC, both in staging and restaging, also considering the limited radiation exposure. From the limited availability of the existing literature, it is clear that further prospective trials on larger and homogeneous cohorts are needed.

Purpose: The aim of this study was to investigate the role of 18F-FDG PET/CT in predicting pathological prognostic factors, including tumor type and International Federation of Gynecology and Obstetrics (FIGO) score, in gestational trophoblastic disease (GTD). Methods: Retrospective monocentric study including 24 consecutive patients who underwent to 18F-FDG PET/CT from May 2005 to March 2021 for GTD staging purpose. The following semiquantitative PET parameters were measured from the primary tumor and used for the analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolisis (TLG). Statistical analysis included Spearman correlation coefficient to evaluate the correlations between imaging parameters and tumor type (nonmolar trophoblastic vs postmolar trophoblastic tumors) and risk groups (high vs low, defined according to the FIGO score), whereas area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive value of the PET parameters. Mann-Whitney U test was used to further describe the parameter's potential in differentiating the populations. Results: SUVmax and SUVmean resulted fair (AUC, 0.783; 95% confidence interval [CI], 0.56-0.95) and good (AUC, 0.811; 95% CI, 0.59-0.97) predictors of tumor type, respectively, showing a low (ρ = 0.489, adjusted P = 0.030) and moderate (ρ = 0.538, adjusted P = 0.027) correlation. According to FIGO score, TLG was instead a fair predictor (AUC, 0.770; 95% CI, 0.50-0.99) for patient risk stratification. Conclusions: 18F-FDG PET parameters have a role in predicting GTD pathological prognostic factors, with SUVmax and SUVmean being predictive for tumor type and TLG for risk stratification.

Aim The assessment of deep myometrial invasion (MI) and lymph node involvement is of utmost importance in the preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. The main aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and lymphnodal involvement detection. Patients and Methods Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI (December 2018-March 2021) for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean with a threshold of 40% of SUVmax-SUVmean40, metabolic tumor volume, total lesion glycolysis) and MRI (volume index [VI], total tumor volume, tumor volume ratio [TVR], mean apparent diffusion coefficient, minimum apparent diffusion coefficient) parameters were calculated on the primary tumor, and their role in predicting EC risk group, the presence of lymphovascular space invasion (LVSI), and MI was assessed. Receiver operating characteristics analysis was used to assess the predictive value of PET and MRI parameters on EC characteristics. Results Patients' median age was 66.57 years (SD, 10.21 years). 18F-FDG PET/MRI identified the primary tumor in all patients. Twenty-two of 35 patients had high-risk EC and 13/35 low-risk disease; 13/35 presented LVSI, 22/35 had deep MI at histological examination, and 13/35 had p53 hyperexpression. PET/MRI was able to detect lymphnodal involvement with high accuracy and high specificity (sensitivity of 0.8571, specificity of 0.9286, accuracy of 0.9143), also showing a high negative predictive value (NPV) for lymphnodal involvement (NPV of 0.9630, positive predictive value [PPV] of 0.7500). The assessment of deep MI using PET/MRI correctly staged 27 patients (77.1%; sensitivity of 0.7273, specificity of 0.8462, accuracy of 0.7714), with also a good PPV (PPV of 0.8889, NPV of 0.647). MRI-derived total tumor volume, VI, and TVR were significant in predicting EC groups (high-risk vs low-risk patients) (P = 0.0059, 0.0235, 0.0181, respectively). MRI-derived volume, VI, TVR, and PET-derived metabolic tumor volume and total lesion glycolysis were able to predict LVSI (P = 0.0023, 0.0068, 0.0068, 0.0027, 0.01394, respectively). Imaging was not able to predict grading, presence of deep MI, nor hyperexpression of p53. Conclusions 18F-FDG PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk group.

Purpose: to investigate the preoperative role of ML-based classification using conventional 18F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. Methods: retrospective study, including 123 EC patients who underwent 18F-FDG PET (2009–2021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80–20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. Results: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. Conclusions: ML-based classification using conventional 18F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients.

Purpose: PET with radiolabeled somatostatin receptors (SSTR) analogues, such as 68Ga-DOTATOC, is commonly used in all stages of gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Magnetic resonance Imaging (MRI) has excellent soft-tissue contrast and it is mainly applied in this oncological setting for assessing liver disease. Simultaneous PET/MRI scanners allow the combined acquisition of PET and MRI data with improved patient comfort and reduced radiation dose. The aim of the present pictorial essay is to highlight the assets and limits of fully hybrid PET/MRI in the field of GEP-NETs, presenting significant clinical cases performed in our Centre. Technique and findings: PET/MRI protocol: simultaneous PET/MRI acquisition started approximately 60min after 68Ga-DOTATOC tracer injection; MR localizer was performed to define the number of table positions (PET-FOV) for PET/MRI whole-body acquisition. A dedicated MRI protocol was performed on the abdomen, following the whole-body PET/MRI scan. Conclusion: 68Ga-DOTATOC PET/MRI combines the high sensitivity and specificity of 68Ga-DOTATOC PET tracer and MR high-quality imaging, especially for the liver. The clinical setting of GEP-NETs represents an interesting setting of application of this imaging technique, although the pros and cons should be taken into account until further methodological improvements will occur, especially for the characterization of lung findings.

Introduction The diagnostic accuracy of fluorine-18–fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging mantle-cell lymphoma has not yet investigated. The aim of this 2-center retrospective study was to investigate the utility of 18F-FDG PET/CT in assessing nodal, splenic, bone marrow (BM), and gastrointestinal (GI) disease compared to CT, BM, and GI endoscopy; and to assess its clinical impact. Patients and Methods One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ. Results All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2. Conclusion 18F-FDG PET/CT showed excellent detection rate in nodal and splenic disease—a rate better than CT. For BM and GI evaluation, in order to reach good accuracy, the selection of patients and the use of specific criteria for evaluation of these organs seems to be crucial. Moreover, PET/CT altered the management and therapeutic approach in about 20% of patients.

Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 μg/m2) afterward. This trial included 2 phases: an “explorative phase” addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid–single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an “expansion phase” with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.

Purpose: The role for [18F]FDG-PET in supporting amyotrophic lateral sclerosis (ALS) diagnosis is not fully established. In this study, we aim at evaluating [18F]FDG-PET hypo- and hyper-metabolism patterns in spinal- and bulbar-onset ALS cases, at the single-subject level, testing the diagnostic value in discriminating the two conditions, and the correlations with core clinical symptoms severity. Methods: We included 95 probable-ALS patients with [18F]FDG-PET scan and clinical follow-up. [18F]FDG-PET images were analyzed with an optimized voxel-based-SPM method. The resulting single-subject SPM-t maps were used to: (a) assess brain regional hypo- and hyper-metabolism; (b) evaluate the accuracy of regional hypo- and hyper metabolism in discriminating spinal vs. bulbar-onset ALS; (c) perform correlation analysis with motor symptoms severity, as measured by ALS-FRS-R. Results: Primary motor cortex showed the most frequent hypo-metabolism in both spinal-onset (∼57%) and bulbar-onset (∼64%) ALS; hyper-metabolism was prevalent in the cerebellum in both spinal-onset (∼56.5%) and bulbar-onset (∼55.7%) ALS, and in the occipital cortex in bulbar-onset (∼62.5%) ALS. Regional hypo- and hyper-metabolism yielded a very low accuracy (AUC

espanolObjetivo Investigar el papel pronostico preoperatorio de la PET/TC con 18F-FDG en pacientes con carcinoma de endometrio (CE). Material y metodos Se realizo PET/TC con 18F-FDG en 57 pacientes para el estudio preoperatorio del CE. Se evaluaron los valores de captacion estandarizados maximos y medios (SUVmax, media), volumen tumoral metabolico (MTV) y glicolisis de lesion total (TLG) de tumores primarios, a diferentes umbrales de 40%, 50%, 60% (40-50-60), comparandose con las caracteristicas anatomopatologicas. Se evaluo el rendimiento diagnostico de los parametros PET (categorizados por analisis ROC) en la discriminacion de la enfermedad de bajo y mediano riesgo y el papel pronostico en la supervivencia (supervivencia global-OS, supervivencia libre de enfermedad-SSE). Resultados Los TLG40-50-60 categorizados fueron los unicos parametros relacionados con FIGO estadio I versus II-III-IV (p = 0,0035 para todos). Los puntos de corte para la estratificacion del riesgo fueron 83,69, 61,81 y 41,32, respectivamente (sensibilidad: 60%; especificidad, 71,43% para todos los parametros. El estadio patologico 1 (pT1) del tumor primario se predijo con MTV60 y TLG40-50 (p = 0,0328, 0,0240 y 0,0147, respectivamente). Los umbrales optimos fueron 7,795, 99,55 y 77,58, respectivamente (sensibilidad: 38,46%, 53,85% y 53,85%, respectivamente; especificidad: 88,64%, 79,55% y 81,82%, respectivamente). SUVmax y SUVmean40-50-60 fueron los unicos parametros que discriminaron el subtipo endometrioide del no endometrioide. La sensibilidad fue del 64,86% y 62,16% para SUVmax y SUVmean50-60, y 62,16% para SUVmean40; la especificidad fue del 70% para todos los parametros. La SG media (DE) fue del 79,77% (3,34%) y la SSE media fue del 77,89% (3,73%). El tipo de tumor fue la unica variable significativamente asociada a la SG (p = 0,0486). TLG50 > 77,58 cm3 fue la unica variable asociada a un mayor riesgo de recaida (p = 0,0472). Conclusion TLG40-50-60 y MTV60 de EC primaria tienen valor pronostico para discriminar FIGO y estadificacion patologica. Estos resultados sugieren un posible papel de estos parametros en la prediccion de la agresividad de la CE, mejorando asi la caracterizacion preoperatoria del cancer de endometrio. EnglishPurpose To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40–50–60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival –OS; disease free survival – DFS) was evaluated. Results The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). Conclusion TLG40–50–60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

Purpose. Assessment of deep myometrial invasion (MI) and lymphovascular space invasion (LVSI) is of utmost importance in preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. Aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and LVSI detection.Methods. Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean40, MTV40, TLG40) and MRI (volume index-VI, total tumor volume-TTV, tumor volume ratio-TVR, ADCmean, ADCmin) parameters were calculated on the primary tumor, and their role in predicting histological findings (grade, high- vs. low-risk groups, LVSI, MI, p53 hyper-expression) was assessed through a ROC analysis.Results. 18F-FDG-PET/MRI identified the primary tumor in all patients. In the LVSI detection, PET/MRI demonstrated high accuracy, specificity and negative predictive value (sensitivity=0.8571, specificity=0.9286, accuracy=0.9143, NPV=0.9630, PPV=0.7500). Assessment of MI using PET/MRI correctly staged 27 patients, showing a good positive predictive value (77.1%; sensitivity= 0.7273, specificity=0.8462, accuracy=0.7714, PPV=0.8889, NPV=0.647). VI, TTV, and TVR significantly predicted risk groups (p=0.0059, 0.0235, 0.0181, respectively). VI, TTV, TVR, MTV40 and TLG40 significantly predicted LVSI (p=0.0023, 0.0068, 0.0068, 0.0027, 0.0139, respectively). Imaging was not able to predict grading, MI nor p53 hyper-expression.Conclusion. 18F-FDG-PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk groups.

BACKGROUND To investigate the correlation between 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG). PATIENTS AND METHODS Prospective study including 20 patients with brain MRI suggestive for HGG and undergoing 18F-FAZA PET/CT before treatment for hypoxia assessment. For each 18F-FAZA PET scan SUVmax, SUVmean and 18F-FAZA tumour volume (FTV) at 40, 50 and 60% threshold of SUVmax were calculated; hypoxic volume was estimated by applying different thresholds (1.2, 1.3 and 1.4) to tumour/blood ratio. Seventeen patients were analysed. The immunohistochemical analysis assessed the following parameters: hypoxia-inducible factor 1α, carbonic anhydrase IX (CA-IX), glucose transporter-1, tumour vascularity and Ki-67. RESULTS 18F-FAZA PET showed a single lesion in 15/17 patients and multiple lesions in 2/17 patients. Twelve/17 patients had grade IV glioma and 5/17 with grade III glioma. Bioptic and surgical samples have been analysed separately. In the surgical subgroup (n = 7) a positive correlation was observed between CA-IX and SUVmax (P = 0.0002), SUVmean40 (P = 0.0058), SUVmean50 (P = 0.009), SUVmean60 (P = 0.0153), FTV-40-50-60 (P = 0.0424) and hypoxic volume1.2-1.3-1.4 (P = 0.0058). In the bioptic group (n = 10) tumour vascularisation was inversely correlated with SUVmax (P = 0.0094), SUVmean40 (P = 0.0107), SUVmean50 (P = 0.0094) and SUVmean60 (P = 0.0154). CONCLUSIONS The correlation of 18F-FAZA PET parameters with CD31 and CA-IX represents a reliable method for assessing tumour hypoxia in HGG. The inverse correlation between tumour vascularisation, SUVmax and SUVmean suggest that highly vascularized tumours might present more oxygen supply than hypoxia.

Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps, and consequently PET images, more accurate than segmentation or atlas-registration strategies. As first objective, we aim to investigate the best MR image to be used and the best point of the AC pipeline to insert the synthetic map in. Sixteen patients underwent a 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) and a PET/MR brain study in the same day. PET/CT images were reconstructed with attenuation maps obtained: (1) from CT (reference), (2) from MR with an atlas-based and a segmentation-based method and (3) with a 2D UNet trained on MR image/attenuation map pairs. As for MR, T1-weighted and Zero Time Echo (ZTE) images were considered; as for attenuation maps, CTs and 511 keV low-resolution attenuation maps were assessed. As second objective, we assessed the ability of DL strategies to provide proper AC maps in presence of cranial anatomy alterations due to surgery. Three 11C-methionine (METH) PET/MR studies were considered. PET images were reconstructed with attenuation maps obtained: (1) from diagnostic coregistered CT (reference), (2) from MR with an atlas-based and a segmentation-based method and (3) with 2D UNets trained on the sixteen FDG anatomically normal patients. Only UNets taking ZTE images in input were considered. FDG and METH PET images were quantitatively evaluated. As for anatomically normal FDG patients, UNet AC models generally provide an uptake estimate with lower bias than atlas-based or segmentation-based methods. The intersubject average bias on images corrected with UNet AC maps is always smaller than 1.5%, except for AC maps generated on too coarse grids. The intersubject bias variability is the lowest (always lower than 2%) for UNet AC maps coming from ZTE images, larger for other methods. UNet models working on MR ZTE images and generating synthetic CT or 511 keV low-resolution attenuation maps therefore provide the best results in terms of both accuracy and variability. As for METH anatomically altered patients, DL properly reconstructs anatomical alterations. Quantitative results on PET images confirm those found on anatomically normal FDG patients.

Background The aim of the present study is to explore the correlation between PET and MRI parameters of primary tumour and clinicopathological features and to determine their synergic predictive role in patients with endometrial cancer candidate to surgery. Methods Retrospective study including 27 patients with endometrial cancer and preoperative 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI scan. The following parameters, calculated on the primary tumour, were used for analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for PET scans; mean apparent diffusion coefficient (ADCmean) and volume index for MRI scans. FIGO stage, grade, histotype, lymphovascular space invasion (LVSI) and myometrial invasion were the considered clinicopathological features. Results MRI volume index was a good predictor for deep myometrial invasion [area under the curve (AUC) = 0.85; P = 0.003] and for LVSI (AUC = 0.74; P = 0.039). A cutoff value of 9.555 for MRI volume index was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%); a cutoff of 12.165 was predictive for LVSI (sensitivity = 69.2%; specificity = 83.3%). A TLG cutoff value of 26.03 was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%). A high-direct correlation was found with MRI volume index (rho = 0.722; P < 0.001); low-direct correlation with SUVmax (rho = 0.484; P = 0.012), SUVmean (rho = 0.47; P = 0.015) and TLG (rho = 0.482; P = 0.013) were identified. The SUVmax/ADCmean ratio showed a low-direct correlation with percentage of myometrial invasion (rho = 0.467; P = 0.016). Conclusion Volume index, TLG and SUVmax/ADCmean ratio are associated with deep myometrial invasion. As myometrial invasion is the index used to predict lymph node involvement in endometrial cancer, the synergic use of these imaging parameters may be suggested to predict lymphnodal metastases.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR–human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF/R-CHOP would be declared active if ≥12 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11.

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613 ), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

In the present case, we report the first experience of a patient with high-grade glioma who underwent dual F-FAZA PET/CT imaging for intratumoral hypoxia assessment, before treatment, and for therapy monitoring in the suspicious of recurrence, as part of a clinical research protocol. In addition, despite the diagnosis of glioblastoma, the patient at 3 years from diagnosis was alive and underwent C-methionine simultaneous PET/MRI for disease monitoring after treatment, showing stability of disease. The multitracer capability of PET in assessing different and complementary metabolic features along with the use of a last-generation scanner as PET/MRI in brain oncology are here enlighten.

Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis. The wall of inflamed arteries contains an abundant infiltrate of lymphocytes and macrophages and undergoes substantial remodeling, with hyperplasia of the intimal layer, luminal occlusion and potentially aneurysm formation and

Objective: Positron Emission Tomography (PET) with F-18-Fluoro-deoxy-glucose (FDG) emerged as a prognostic tool to predict treatment outcome in Hodgkin Lymphoma (HL). Moreover, a FDG-PET adapted strategy is currently assessed in clinical trial to minimize the toxic effect while maintaining the efficacy of treatment in HL. Purpose was to analyze the quantitative parameters to support the prognostic role of FDG-PET today based on the semi-quantitative Deauville 5-point Scale (D5-PS). Methods: This retrospective study included 53 patients diagnosed with advanced-stage HL between 2009 and 2014, enrolled in the PET response-adapted clinical trial HD 0607. FDG-PET was performed at baseline (PET0) and after two cycles of chemotherapy (PET2). Analysis was based on two main approaches: on the single lesion presenting the higher FDG uptake and on the five hottest lesions. Different metabolic parameters were analyzed. Patients were classified into responders and nonresponders. Optimal cut-offs were derived from Receiver Operating Characteristic (ROC) curves. Results were correlated with Progression Free Survival (PFS) using Kaplan-Meier. Results: A 71% threshold in SUVmax reduction (?SUVmax) was found to be the best cutoff quantitative parameter able to identify responders vs. non-responders, also with a multivariate analysis, joining clinical data with SUVmax. After a mean follow-up of 34.2 months (95% CI, 26.2 to 39.1), the median PFS for non-responders was 8 months vs. not reached for responders. These results were superimposable to that obtained by an independent group of reviewers using the D5-PS. Conclusion: Semi-quantitative analysis by ?SUVmax outperforms qualitative assessment by D5-PS in predicting treatment outcome in ABVD-treated advanced-stage HL.

Purpose: The aim of the present systematic review was to provide an overview on the different positron emission tomography (PET) hypoxia radiotracers in the clinical setting of lung cancer. Methods: We performed a comprehensive literature review on the role of PET hypoxia imaging in lung cancer using the electronic databases PubMed and Scopus to select English written language articles on humans from January 2007 to February 2017. The following keywords have been used: “hypoxia” or “hypoxic” and “PET” and “lung cancer”. Reviews, clinical reports, and editorial articles were excluded. Results: Originally, we considered 76 manuscripts, coming to a selection of 37 original articles. In particular, the selected original articles included the following PET radiotracer categories: nitroimidazole compounds, glucose analogue and bis(thiosemicarbazone) complexes. PET radiotracers, particularly nitroimidazole compounds, are the most suitable method to directly identify the presence of hypoxia in lung cancer. Conclusions: Based on the literature review, the definition of the role of clinical application of PET hypoxia radiotracers has been provided reporting that in vivo hypoxia imaging is needed for effective treatment selection, individual treatment planning, and treatment monitoring in oncology.

Purpose: The object of this study was to assess whether18F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu’s arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions

The diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ.All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2.

Purpose To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40–50–60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival –OS; disease free survival – DFS) was evaluated. Results The categorized TLG40–50–60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40–50–60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50–60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). Conclusion TLG40–50–60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

Background:Most published evidence on infliximab (IFX) in Takayasu arteritis (TAK) refers to its use at the standard dose of 5 mg/kg every 6-8 weeks1. However, in other diseases such as rheumatoid arthritis or Crohn’s disease2,3, it has been already demonstrated that IFX often requires a dose escalation to maintain its response.Objectives:To evaluate effectiveness and safety of IFX dose escalation in TAK patients. To identify predictors of refractoriness to standard-dose IFX.Methods:Medical records of IFX-treated TAK patients from a large single-centre observational cohort were reviewed. Decisions on IFX start, interruption, and dose modification were always made by the same experienced physician (EB). IFX therapy duration and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained IFX standard-dose and those who needed dose-escalation was performed. Factors predicting standard-dose refractoriness were analyzed.Results:Forty-one patients were included (38 women; median age at IFX start, 36 [IQR, 28-45] years; median disease duration, 22 [13-60] months). Starting IFX dose was 5 mg/kg 6-weekly; 39 patients (95%) were on concomitant csDMARD and 38 patients (93%) on systemic glucocorticoids (GC). IFX dose escalation was performed in the majority of patients (n=28, 68%) (Figure 1). Persistence/recurrence of clinical symptoms was the most frequent reason for dose escalation (62%). Median IFX therapy duration was 39 (26-61) months in the standard-dose and 68 (38-87) months in the intensified-dose group. Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient), expression of a more aggressive disease phenotype. Nevertheless, in only 8 patients (29%) from this group IFX was suspended, after a median of 38 (31-71) months. Causes of suspension were loss of response (n=7) or patient’s request (n=1). GC were successfully suspended in 4 patients from the standard-dose (36%) and 3 patients from intensified-dose (11%) group. Median daily prednisone dose was reduced from 10 (6-10) to 3 (0-5) mg in the standard-dose group, and from 13 (9-18) to 5 (4-5) mg in the intensified-dose group. Three patients from the intensified-dose group had a serious infection; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, younger age at diagnosis and at IFX start were associated with IFX escalation (Table 1).Table 1.Factors influencing IFX dose escalation in patients with TAK (Cox proportional hazards model)Standard-dose IFXIntensified-dose IFXP-valueAge at diagnosis, years40 (34-46)30 (23-40)0.031Diagnostic delay, months12 (7-77)27 (15-50)0.73Age at IFX start, years42 (38-61)34 (27-44)0.040Delay before IFX start, months33 (14-90)24 (11-53)0.48Daily PDN at IFX start, mg8.75 (5-10)11.25 (8.5-16.25)0.051CRP at IFX start, mg/L6.5 (2.1-9.3)10.7 (5.2-20.9)0.07Class V Numano, n (%)3 (30)16 (57)0.133PETVAS score8 (6-12)12 (9-16)0.056Figure 1.Infliximab dose escalation regimens (the cross (x) indicates treatment suspension)Conclusion:In TAK, dose escalation can be a safe strategy to optimize IFX durability in refractory patients. Younger patients seem to be more refractory to standard dosages.References:[1]Mekinian A, Néel A, Sibilia J, et al. Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study. Rheumatology. 2012; 51:882–6[2]Ollendorf DA, Massarotti E, Birbara C, et al. Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis. J Manag Care Pharm. 2005;11(5):383-93[3]Taxonera C, Olivares D, Mendoza JL, et al. Need for infliximab dose intensification in Crohn’s disease and ulcerative colitis. World J Gastroenterol. 2014;20(27):9170-7Disclosure of Interests:Alessandro Tomelleri: None declared, Corrado Campochiaro: None declared, Silvia Sartorelli: None declared, Francesco Baldassi: None declared, Federico Fallanca: None declared, Maria Picchio: None declared, Elena Baldissera Speakers bureau: Pfizer, Roche, Sanofi-Genzyme, Consultant of: Novartis, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline,Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI

Purpose: To evaluate the accuracy and prognostic value of FDG PET/CT for response assessment after treatment in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) when using the Deauville Criteria (DC) and the International Harmonization Project Criteria (IHPC). Methods: This retrospective study included 101 patients (35 HL, 66 NHL) who underwent early restaging FDG PET/CT after treatment. Scans were evaluated using the IHPC and DC. Two thresholds of positivity for the DC were used: a score of at least 3 (DC3, i.e. scores 3 – 5) and a score of at least 4 (DC4, i.e. a score of 4 or 5). Accuracy was assessed using conventional diagnostic procedures, multidisciplinary team case notes, further PET/CT scans and/or follow-up. Progression-free survival and overall survival were computed using the Kaplan-Meier method. The Cox proportional hazards model was used to identify predictors of outcome. Results: Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FDG PET/CT for early restaging were, respectively, 92 %, 87 %, 74 %, 92 % and 86 % using DC4, 97 %, 76 %, 64 %, 98 % and 84 % using DC3, and 97 %, 67 %, 57 %, 98 % and 76 % using the IHPC. FDG PET/CT positivity was associated with a worse cumulative survival rate over a 2-year period when using DC4 in comparison with the IHPC (20 % vs. 49 %; p < 0.05) and DC3 (47 %; p < 0.05). Cox regression analysis showed different risks of progression in patients positive on FDG PET/CT using the IHPC, DC3 and DC4 (hazard ratios 1.57, 0.7 and 3.2, respectively). Conclusion: FDG PET/CT using DC4 showed higher diagnostic accuracy for HL and NHL than FDG PET/CT using either the IHPC or DC3, indicating its value in predicting clinical outcome after treatment.

The diagnostic approach to gynecological tumors includes anatomical and molecular imaging methods, representing a strong support for clinicians to define tumor extension, to plan the best treatment strategy and patient management. The possibility of combining morphological and functional information in a single examination, using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) technique, represents a very promising tool in the different settings of gynaecologic tumors. In the present review, the current literature and potential clinical applications of PET/MRI in the most common types of gynecological tumors are discussed. The role of PET/MRI is in staging, restaging and after treatment of gynecological tumors is presented, focusing on cervical, endometrial and ovarian cancer. Moreover, the diagnostic accuracy of PET/MRI and the correlation between quantitative parameters (standardized uptake value and apparent diffusion coefficient) of PET/MRI hybrid systems are briefly reviewed.

A 76-year-old man underwent F-FDG PET/CT to complete staging and characterize a suspicious lung mass. Images showed intense uptake in the lung lesion and faint uptake in correspondence of a gastric mass, which was subsequently biopsied revealing a gastrointestinal stromal tumor. A F-FAZA PET/CT was also performed because of patient’s enrollment in a prospective clinical trial (trial registration no. EudraCT 2011-002647-98), showing heterogeneous uptake of F-FAZA in the pulmonary lesion and faint uptake in correspondence of the gastrointestinal stromal tumor.

To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations.Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated withA large disagreement between manual and SUV_max method was found for thresholds ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%.About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses.

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD–negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

PURPOSE To assess the capability of 18F-FAZA PET/CT in identifying intratumoral hypoxic areas in early and locally advanced non-small cell lung cancer (NSCLC) patients and to compare 18FFAZA PET/CT with 18F-FDG PET/CT and histopathological biomarkers and to investigate whether the assessment of tumour to blood (T/B) and tumour to muscle (T/M) ratios provide comparable information regarding the hypoxic fractions of the tumour. MATERIALS AND METHODS Seven patients with NSCLC were prospectively enrolled (3 men, 4 women; median age: 71 years; range 63-80). All patients underwent to 18F-FDG PET/CT and 18F-FAZA PET/CT before surgery. Maximum standardized uptake value (SUVmax) was used to evaluate 18FFDG PET/CT images, while 18F-FAZA PET/CT images have been interpreted by using tumour-toblood (T/B) and tumour-to-muscle (T/M) ratio. Surgery was performed in all patients; immunohistochemical analysis for hypoxia biomarkers was performed on histologic tumor samples. RESULTS All lung lesions showed intense 18F-FDG uptake (mean SUVmax: 7.35; range: 2.35-25.20). A faint 18F-FAZA uptake was observed in 6/7 patients (T/B < 1.2) while significant uptake was present in the remaining 1/7 (T/B and T/M=2.24). On both 2 and 4 h imaging after injection, no differences were observed between T/M and T/B (p=0.5), suggesting that both blood and muscle are equivalent in estimating the background activity for image analysis. Immunohisotchemical analysis showed low or absent staining for hypoxia biomarkers in 3 patients (CA-IX and GLUT-1: 0%; HIF-1α: mean 3.3%; range 0-10). Two patients showed staining for HIF-1α of 5%, with CA-IX being 60% and 30%, respectively and GLUT-1 being 30% and 80%, respectively; in 1/7 HIF-1α was 10%, CA-IX was 50% and GLUT-1 was 90%. In one patient a higher percentage of HIF-1α and CA-IX (20% and 70%, respectively) positive cells was present, with GLUT-1 being 30%. CONCLUSIONS To the best of our knowledge, this is the first paper assessing hypoxia and glucose metabolism in comparison with immunohistochemistry in patients candidate to surgery for NSCLC. Although including a small number of patients, useful insight regarding correlation between imaging and immunohistochemistry are reported along with methodological suggestions for clinical practice.

Background/aims In this multicentre study in clinical settings, we assessed the accuracy of optimized procedures for FDG-PET brain metabolism and CSF classifications in predicting or excluding the conversion to Alzheimer's disease (AD) dementia and non-AD dementias. Methods We included 80 MCI subjects with neurological and neuropsychological assessments, FDG-PET scan and CSF measures at entry, all with clinical follow-up. FDG-PET data were analysed with a validated voxel-based SPM method. Resulting single-subject SPM maps were classified by five imaging experts according to the disease-specific patterns, as “typical-AD”, “atypical-AD” (i.e. posterior cortical atrophy, asymmetric logopenic AD variant, frontal-AD variant), “non-AD” (i.e. behavioural variant FTD, corticobasal degeneration, semantic variant FTD; dementia with Lewy bodies) or “negative” patterns. To perform the statistical analyses, the individual patterns were grouped either as “AD dementia vs. non-AD dementia (all diseases)” or as “FTD vs. non-FTD (all diseases)”. Aβ42, total and phosphorylated Tau CSF-levels were classified dichotomously, and using the Erlangen Score algorithm. Multivariate logistic models tested the prognostic accuracy of FDG-PET-SPM and CSF dichotomous classifications. Accuracy of Erlangen score and Erlangen Score aided by FDG-PET SPM classification was evaluated. Results The multivariate logistic model identified FDG-PET “AD” SPM classification (Expβ = 19.35, 95% C.I. 4.8–77.8, p, Highlights • Appropriate biomarkers measures improve early dementia diagnosis in MCI. • FDG-PET-SPM maps and CSF Aβ42 are the best predictors of AD dementia conversion. • FDG-PET-SPM maps accurately predict conversion to different dementia conditions. • A negative FDG-PET-SPM pattern characterizes stable or reverter MCI cases.

Purpose: To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations. Methods: Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated with18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based planning optimization were considered. Seven FDG-based contours were delineated for tumour (T) and positive lymph nodes (N, for HN patients only) following manual (2 observers), semi-automatic (based on SUV maximum gradient: PET_Edge) and automatic (40%, 50%, 60%, 70% SUV_max thresholds) methods. Seventy-three RF (14 of first order and 59 of higher order) were extracted using the CGITA software (v.1.4). The impact of delineation on volume agreement and RF was assessed by DICE and Intra-class Correlation Coefficients (ICC). Results: A large disagreement between manual and SUV_max method was found for thresholds ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC < 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC < 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%. Conclusions: About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses.

Purpose: To determine the performance accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) after primary tumor treatment for both bladder cancer (BC) and upper tract urothelial cancer (UTUC). To compare the accuracy of FDG PET/CT with that of contrast-enhanced-ceCT and magnetic resonance imaging (MRI). Methods: Data of patients with recurrent urothelial carcinomas (UC) after primary treatment were collected in a retrospective, international multicenter study. Inclusion criteria were (1) patients with a known history of UC in the BC and/or in the UTUC; (2) PET/CT images after curative intent treatment of the primary tumor; (3) conventional imaging modalities (abdominal ceCT or MRI, or total body ceCT, and chest X-ray: called C.I.) performed no more than 3 months from PET/CT; (4) available standard of reference (e.g., histological data or follow-up imaging modalities) for the validation of PET/CT findings. Exclusion criteria were other abdominal tumors, chemotherapy administration prior to and/or concomitant to imaging, and non-urothelial histologic variants. Sensitivities, specificities, positive, and negative predictive values were evaluated for all patients and separately for bladder and UTUC. Results: Overall, 287 patients were enrolled. Two-hundred thirteen patients underwent cystectomy (74.2%), 35 nephroureterectomy (12.2%), 31 both cystectomy + nephroureterectomy (10.8%), 5 both cystectomy + conservative treatment for UTUC (1.4%), and 3 (1%) other types of nephron-sparing treatments for UTUC. Neoadjuvant and adjuvant treatments were performed in 36 (12.5%) and 111 (38.7%) patients, respectively. Sensitivity and specificity (95% confidence intervals) of PET/CT for the detection of recurrent UC were 94% (91% to 96%) and 79% (68% to 88%), respectively. However, sensitivity was higher for BC than UTUC (95% vs. 85%) while specificity was lower in BC (78% vs. 85% for BC and UTUC, respectively). PET/CT and C.I. findings were available in 198 patients. The results were positively concordant in 137 patients, negatively concordant in 23 patients, and discordant in 38 patients (20 negative at C.I. vs. positive at PET/CT and 18 positives at ceCT/MRI vs. negative at PET/CT) (K Cohen = 0.426; p < 0.001). Sensitivities, specificities, and accuracies (95% confidence intervals) of PET/CT vs. C.I. for the detection of recurrent BC and UTUC were 94% (90% to 97%) vs. 86% (81% to 92%), 79% (67% to 92%) vs. 59% (44% to 74%), and 91% (87% to 95%) vs. 81% (75% to 86%), respectively. Conclusions: FDG PET/CT has a high diagnostic accuracy for the identification of recurrent UC, particularly in patients with BC. Moreover, its accuracy outperforms C.I. for both BC and UTUC.

Objective: To evaluate the predictive value of FDG-PET/CT parameters on outcome of oropharyngeal squamocellular cancer (OSCC) patients undergoing helical tomotherapy (HTT), with dose escalation to FDG-PET/CT positive tumour volumes using the simultaneous integrated boost (SIB) technique. Materials and Methods: We analysed 41 patients studied by FDG-PET/CT and treated with radical intent between 2005 and 2014 for OSCC. HTT-SIB was delivered in 30 fractions concomitantly: 69 Gy, as SIB, to the PET-positive volume (biological target volume - BTV-PET), both to the primary tumour (T) and lymph nodes (N), 66 Gy to the T and positive N, 54 Gy to the laterocervical nodes at risk. Selected PET parameters were recovered: maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) obtained with different thresholds (40-50-60% of the SUVmax) for T and N. The correlation between these parameters and the 3-year overall (OS), cancer specific (CSS), disease free (DFS), local relapse free for T and N (LRFS-T and LRFS-N) and distant metastasis free (DMFS) survivals was investigated. Results: The median follow-up was 37 months (range: 3-125). The 3-year OS, CSS, DFS, LRFST, LRFS-N and DMFS were 86%, 88%, 76%, 83%, 88% and 91%, respectively. BTVT+ N>30.9cc and BTV-T>22.4cc were correlated with CSS (p=0.02) and OS (p=0.006) respectively; TLG-T-60>34.6cc was correlated with CSS (p=0.04) and OS (p=0.01). MTV-T-60>4.4cc could predict a higher risk of relapse/death (CSS: p=0.033; hazard ratio (HR) =10.92; OS: p=0.01; HR=16.4; LRFS-T: p=0.02; HR=13.90; LRFS-T+N: p=0.03; HR=6.50). Conclusion: PET parameters predicted survival outcomes and may be considered in the future in the implementation of more personalized treatment schedules in patients affected by OSCC undergoing radiotherapy. FDG-PET/CT dose escalated HTT-SIB allowed very promising 3-year disease control rates in OSCC patients.

BACKGROUND To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. METHODS This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). RESULTS All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. CONCLUSION CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity.

Purpose: Hypoxia can influence response to chemo and radiotherapy in different tumours, including non-small cell lung cancer (NSCLC) and high-grade gliomas (HGG). PET/CT can non-invasively investigate hypoxia and18F-FAZA seems to be the most promising radiotracer. However, there are still controversial issues related to image analysis and data interpretation hampering the effective possibility to translate the use of this imaging modality in clinical applications. The aim of the present pictorial review is to provide insights and answers on the open issues related to the potential clinical applicability of18F-FAZA PET/CT for hypoxia delineation. Methods: From Pubmed and Scopus databases, a literature research has been performed with the following research filters for both NSCLC and HGG: (1) time frame: last 10 years; (2) language: English; (3) species: human. Applied searching keywords were “hypoxia” or “hypoxic” and “PET” and “lung cancer” for NSCLS and “hypoxia”, “PET” and “glioma” for HGG. Papers not strictly matching the imposed search filters have not been considered. Results: The literature search led to 76 papers for NSCLC, but for the purpose of the review only 10 have been considered, after double-checking and exclusion if not matching the imposed search filters. For HGG, the selected filters lead to 19 papers but only 8 have been considered for data analysis. Results on the use of18F-FAZA PET/CT in two different settings are reported in the present pictorial essay and methodological suggestions for clinical practice are presented through the description of addressed representative case reports. Conclusions: Based on literature evidence and presentation of relevant clinical case reports, issues related to18F-FAZA PET/CT in clinical settings have been addressed, providing possible solutions that may help the reliable use of this imaging method in clinical practice.

OBJECTIVES: This study investigated the incidence and clinical significance of arterial graft-associated uptake of fluorodeoxyglucose in large-vessel vasculitis (LVV). BACKGROUND: The role of (18)F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) in the management of LVV remains to be defined. Although [(18)F]FDG uptake at arterial graft sites raises concerns regarding active arteritis or infection, its clinical significance in LVV has never been formally studied. METHODS: An observational prospective study sought to identify patients with Takayasu arteritis (TA) undergoing [(18)F]FDG-PET/CT more than 6 months after graft surgery from a large cohort of patients from 2 tertiary referral centers. [(18)F]FDG uptake by the graft and native arteries was scored on a scale of 0 to 3 relative to hepatic uptake, and periprosthetic maximum standardized uptake value (SUVmax) was calculated. Periprosthetic [(18)F]FDG uptake in active disease was compared with that in inactive disease, and arterial progression was assessed by prospective magnetic resonance angiography (MRA). RESULTS: Twenty-six subjects with TA were enrolled. All were afebrile with negative blood culture. Periprosthetic uptake was significant in 23 of 26 patients, and the mean SUVmax was 4.21 ± 1.46. Median periprosthetic [(18)F]FDG uptake score (3; interquartile range [IQR]: 3 to 3) was higher than in native aorta (1; IQR: 0 to 1; p < 0.001). Graft-specific [(18)F]FDG uptake was unrelated to disease activity. Despite the high frequency of graft-associated [(18)F]FDG uptake, sequential MRAs did not reveal arterial progression in 25 of 26 patients; the 1 remaining case showed minor progression limited to native arteries. Nine patients underwent repeated PET/CT scanning without showing changes in graft-specific uptake, despite increased treatment. CONCLUSIONS: Significant [(18)F]FDG uptake that is confined to arterial graft sites in patients with LVV does not reflect clinically relevant disease activity or progression. To minimize exposure to immunosuppression and in the face of negative blood culture, clinically quiescent arteritis, normal or stably raised C-reactive protein levels, we elected not to escalate treatment and monitor progression with MRA.

Purpose: The role of 18F-FDG-PET/CT in evaluating gastric MALT lymphoma is still controversial. In the literature the detection rate of 18F-FDG-PET/CT in patients with gastric MALT lymphoma is variable, and the reason for this heterogeneity is not still clear. Our aim was to investigate the particular metabolic behavior of these lymphoma. Materials and methods: Sixty-nine patients (26 female, 43 male) with histologically confirmed gastric MALT lymphoma who underwent a 18F-FDG-PET/CT for initial staging from two centers were included. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax), lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio and compared with Ann Arbor stage, epidemiological (age, sex), histological (presence of gastritis, ulcer, H. pylori infection, plasmacytic differentiation, Ki-67 index), and morphological (tumor size, superficial lesions or mass-forming) characteristics. Results: Thirty-six patients (52 %) had positive PET/CT (average SUVmax was 9±6.7; lesion-to-liver SUVmax ratio 3.7±2.6, lesion-to-blood pool SUVmax ratio 4.8±3.3) at the corresponding gastric lesion; the remaining 33 were not 18F-FDG-avid. In the univariate analysis, 18F-FDG avidity was significantly associated with morphological features (mass forming p