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Purpose: To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. Methods: One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018–June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs' histopathological prognostic factors were evaluated using Spearman's coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters' predictive performance. Results: Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). Conclusion: This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness. [ABSTRACT FROM AUTHOR]

Purpose: To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. Methods: Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. Results: Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7–0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. Conclusions: Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients. [ABSTRACT FROM AUTHOR]

Background and purpose Atypical Parkinsonian disorders ( APD) frequently overlap in clinical presentations, making the differential diagnosis challenging in the early stages. The present study aimed to evaluate the accuracy of the [18F]fluoro-deoxy-glucose positron emission tomography Statistical Parametric Mapping ( SPM) optimized procedure in supporting the early and differential diagnosis of APD. Methods Seventy patients with possible APD were retrospectively included from a large clinical cohort. The included patients underwent [18F]fluoro-deoxy-glucose positron emission tomography within 3 months of the first clinical assessment and a diagnostic follow-up. An optimized SPM voxel-wise procedure was used to produce t-maps of brain hypometabolism in single subjects, which were classified by experts blinded to any clinical information. We compared the accuracy of both the first clinical diagnosis and the SPM t-map classifications with the diagnosis at follow-up as the reference standard. Results At first diagnosis , 60% of patients were classified as possible APD (progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy) and about 40% as APD with uncertain diagnosis, providing 52% sensitivity, 97% specificity and 86% accuracy with respect to the reference standard. SPM t-map classification showed 98% sensitivity, 99% specificity and 99% accuracy, and a significant agreement with the diagnosis at follow-up ( P < 0.001). Conclusions The SPM t-map classification at entry predicted the second diagnosis at follow-up. This indicates its significantly superior role for an early identification of APD subtypes, particularly in cases of uncertain diagnosis. The use of a metabolic biomarker at entry in the instrumental work-up of APD may shorten the diagnostic time, producing benefits for treatment options and support to the patients. [ABSTRACT FROM AUTHOR]

Background and aim Despite adequate preoperative staging, 25% of patients with oesophageal cancer treated with primary surgery have microscopically positive resection margins (R1), and the 5-year survival rate rarely exceeds 40%. The CROSS trial demonstrated that neoadjuvant chemoradiotherapy (nCRT) double the median overall survival, with 29% of patients achieving a pathological complete response. Many authors suggest that this subgroup of patients do not benefit from additional surgery also having regard to the fact that oesophageal resections are associated with substantial morbidity and postoperative mortality rates of 3–5%. On the other hand 18% of patients who underwent nCRT were found to be non-responders, only suffering from nCRT side effects. Thus, rationale exists for identifying novel biomarkers allowing early, non-invasive prediction of pathological tumour response. Methods Starting from January 2020, all consecutive patients with biopsy proven potentially resectable oesophageal cancer scheduled to receive nCRT (CROSS regimen) were prospectively enrolled. In addition to standard of care imaging, a fully integrated hybrid PET/MR was performed at three time points (prior to, during and six weeks after treatment completion). For each patient, an early regression index (ERI) was computed according to the formula: ERI = ln [1—(tumour volume mid/tumour volume pre) tumour volume pre]. Tumour volumes were contoured on axial high resolution T2 weighted images by an experienced radiologist. Finally, after surgery, these data were systematically correlated with the pathological outcome in terms of Tumour Regression Grade(TRG). TRG = 1 refers to pathological complete response status. Results At present, of ten patients enrolled, seven underwent surgery after completion of nCRT; of these, three patients had TRG = 1. Interestingly, patients with a pathological complete response demonstrated significantly lower ERI values when compared with those patients with TRG ≥ 2 (4.09 vs. 27.94, P  < 0.001). Of note, no PET parameter was significantly associated with subsequent pathological complete response status. Conclusion Preliminary results point out the existence of a novel imaging, MR based biomarker (ERI), able to early predict pathological tumour response during nCRT, thus providing an actual aid for patients' management. The research leading to these results has received funding from AIRC (Italian Association for Cancer Research) under Investigator Grant—IG 2019—ID. 23015 project; NCT04359732. [ABSTRACT FROM AUTHOR]

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate, in prostate cancer (PCa) patients the potential of C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. Methods: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA) who showed pathological findings on C-choline PET/CT only at the LN site. C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA) and compared with PSA to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. Results: PET/CT revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA, PSA (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. Conclusion: C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the predictive role of pre-therapy fluorodeoxyglucose (FDG) uptake parameters of primary tumour in head and neck cancer (HNC) patients undergoing intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) on FDG-positive volume—positron emission tomography (PET) gross tumour volume (PET-GTV). Methods: This retrospective study included 19 patients (15 men and 4 women, mean age 59.2 years, range 23–81 years) diagnosed with HNC between 2005 and 2011. Of 19 patients, 15 (79 %) had stage III–IV. All patients underwent FDG PET/CT before treatment. Metabolic indexes of primary tumour, including metabolic tumour volume (MTV), maximum and mean standardized uptake value (SUV max, SUV mean) and total lesion glycolysis (TLG) were considered. Partial volume effect correction (PVC) was performed for SUV mean and TLG estimation. Correlations between PET/CT parameters and 2-year disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were assessed. Median patient follow-up was 19.2 months (range 4–24 months). Results: MTV, TLG and PVC-TLG predicting patients’ outcome with respect to all the considered local and distant disease control endpoints (LRFS, DMFS and DFS) were 32.4 cc, 469.8 g and 547.3 g, respectively. SUV mean and PVC-SUV mean cut-off values predictive of LRFS and DFS were 10.8 and 13.3, respectively. PVC was able to compensate errors up to 25 % in the primary HNC tumour uptake. Moreover, PVC enhanced the statistical significance of the results. Conclusion: FDG PET/CT uptake parameters are predictors of patients’ outcome and can potentially identify patients with higher risk of treatment failure that could benefit from more aggressive approaches. Application of PVC is recommended for accurate measurement of PET parameters. [ABSTRACT FROM AUTHOR]

Abstract: Background: The recurrence rate for stage I non-small cell lung cancer is high, with 20–40% of patients that relapse after surgery. The aim of this study was to evaluate new F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) derived parameters, such as standardized uptake value index (SUVindex), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as predictive factors for recurrence in resected stage I non-small cell lung cancer. Methods: We retrospectively reviewed 99 resected stage I non-small cell lung cancer patients that were grouped by SUVindex, TLG and MTV above or below their median value. Disease free survival was evaluated as primary end point. Results: The 5-year overall survival and the 5-year disease free survival rates were 62% and 73%, respectively. The median SUVindex, MTL and TLG were 2.73, 2.95 and 9.61, respectively. Patients with low SUVindex, MTV and TLG were more likely to have smaller tumors (p ≤ 0.001). Univariate analysis demonstrated that SUVindex (p = 0.027), MTV (p = 0.014) and TLG (p = 0.006) were significantly related to recurrence showing a better predictive performance than SUVmax (p = 0.031). The 5-year disease free survival rates in patients with low and high SUVindex, MTV and TLG were 84% and 59%, 86% and 62% and 88% and 60%, respectively. The multivariate analysis showed that only TLG was an independent prognostic factor (p = 0.014) with a hazard ratio of 4.782. Conclusion: Of the three PET-derived parameters evaluated, TLG seems to be the most accurate in stratifying surgically treated stage I non-small cell lung cancer patients according to their risk of recurrence. [Copyright &y& Elsevier]

Purpose: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. Methods: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (βHCG) and in 4 with βHCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. Results: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after βHCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with βHCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative βHCG. Conclusion: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of βHCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment. [ABSTRACT FROM AUTHOR]

We have developed, optimized, and validated a method for partial volume effect (PVE) correction of oncological lesions in positron emission tomography (PET) clinical studies, based on recovery coefficients (RC) and on PET measurements of lesion-tobackground ratio (L/Bm) and of lesion metabolic volume. An operator-independent technique, based on an optimised threshold of the maximum lesion uptake, allows to define an isocontour around the lesion on PET images in order to measure both lesion radioactivity uptake and lesion metabolic volume. RC are experimentally derived from PET measurements of hot spheres in hot background, miming oncological lesions. RC were obtained as a function of PET measured sphere-to-background ratio and PET measured sphere metabolic volume, both resulting from the threshold-isocontour technique. PVE correction of lesions of a diameter ranging from 10 mm to 40 mm and for measured L/Bm from 2 to 30 was performed using measured RC curves tailored at answering the need to quantify a large variety of real oncological lesions by means of PET. Validation of the PVE correction method resulted to be accurate (>89%) in clinical realistic conditions for lesion diameter > 1 cm, recovering >76% of radioactivity for lesion diameter < 1 cm. Results from patient studies showed that the proposed PVE correction method is suitable and feasible and has an impact on a clinical environment. [ABSTRACT FROM AUTHOR]

Objective To evaluate the stress-redistribution myocardial perfusion pattern in patients with angina, positive exercise test and angiographically smooth coronary arteries (syndrome X). Design Prospective study. Patients and methods Twenty-five consecutive patients (seven males, mean age 54 ± 8 years) with typical angina, positive exercise test, normal coronary arteries and no inducible spasm, underwent stress-redistribution thallium- 201 myocardial perfusion scintigraphy. Thirty-two consecutive patients (14 males, mean age 49 ± 7 years) with atypical chest pain and negative exercise test, undergoing stress redistribution thallium scan, served as controls. Resuits Exercise was discontinued for angina and/or ST segment depression after 12 ± 3 min. Thallium stress images revealed 40 hypoperfused segments in 27 patients (77%); after 4 h, 16 of these segments had completely normalized, 10 remained unchanged, six exhibited partial reperfusion and eight worsened. Twenty-four patients (69%) exhibited thallium reverse redistribution in 33 segments. Thirty-four patients (97%) had at least one hypoperfused segment in one of the two scintigraphic phases. Of the 24 patients with reverse redistribution, eight also underwent stress-rest 99mTc-MIBI SPECT: six exhibited reduced tracer uptake that was present at rest, but not on stress images, in the same segments showing thallium reverse redistribution. Thallium stress images revealed four hypoperfused segments in three controls (9%) at redistribution, one segment normalized, two remained unchanged and one exhibited partial reperfusion. Additionally, there were four new underperfused segments appearing on redistribution in four patients (13%). Overall, there were seven controls (22%) with at least one hypoperfused myocardial segment in one of the two scintigraphic phases. Conclusions Our study confirms that perfusion abnormalities are present in most syndrome X patients. Additionally, the data show that reverse redistribution (a perfusion defect that develops or becomes more evident on delayed imaging) is a common finding in these patients. The mechanisms of the phenomenon remain obscure: we suggest that it is due to inhomogeneous perfusion, and the hyperaemic response induced by exercise masks resting underperfusion of certain areas. [ABSTRACT FROM PUBLISHER]

We have developed, optimized, and validated a method for partial volume effect (PVE) correction of oncological lesions in positron emission tomography (PET) clinical studies, based on recovery coefficients (RC) and on PET measurements of lesion-to-background ratio (L/B m) and of lesion metabolic volume. An operator-independent technique, based on an optimised threshold of the maximum lesion uptake, allows to define an isocontour around the lesion on PET images in order to measure both lesion radioactivity uptake and lesion metabolic volume. RC are experimentally derived from PET measurements of hot spheres in hot background, miming oncological lesions. RC were obtained as a function of PET measured sphere-to-background ratio and PET measured sphere metabolic volume, both resulting from the threshold-isocontour technique. PVE correction of lesions of a diameter ranging from 10 mm to 40 mm and for measured L/B m from 2 to 30 was performed using measured RC curves tailored at answering the need to quantify a large variety of real oncological lesions by means of PET. Validation of the PVE correction method resulted to be accurate (>89%) in clinical realistic conditions for lesion diameter > 1 cm, recovering >76% of radioactivity for lesion diameter < 1 cm. Results from patient studies showed that the proposed PVE correction method is suitable and feasible and has an impact on a clinical environment. [ABSTRACT FROM AUTHOR]