Brain metabolic differences between pure bulbar and pure spinal ALS: a 2-[18F]FDG-PET study.

BACKGROUND: MRI studies reported that ALS patients with bulbar and spinal onset showed focal cortical changes in corresponding regions of the motor homunculus. We evaluated the capability of brain 2-[18F]FDG-PET to disclose the metabolic features characterizing patients with pure bulbar or spinal motor impairment. METHODS: We classified as pure bulbar (PB) patients with bulbar onset and a normal score in the spinal items of the ALSFRS-R, and as pure spinal (PS) patients with spinal onset and a normal score in the bulbar items at the time of PET. Forty healthy controls (HC) were enrolled. We compared PB and PS, and each patient group with HC. Metabolic clusters showing a statistically significant difference between PB and PS were tested to evaluate their accuracy in discriminating the two groups. We performed a leave-one-out cross-validation (LOOCV) over the entire dataset. Four classifiers were considered: support vector machines (SVM), K-nearest neighbours, linear classifier, and decision tree. Then, we used a separate test set, including 10% of patients, with the remaining 90% composing the training set. RESULTS: We included 63 PB, 271 PS, and 40 HC. PB showed a relative hypometabolism compared to PS in bilateral precentral gyrus in the regions of the motor cortex involved in the control of bulbar function. SVM showed the best performance, resulting in the lowest error rate in both LOOCV (4.19%) and test set (9.09 ± 2.02%). CONCLUSIONS: Our data support the concept of the focality of ALS onset and the use of 2-[18F]FDG-PET as a biomarker for precision medicine-oriented clinical trials.

18F-FDG PET/CT Imaging Biomarkers for Early and Late Evaluation of Response to First-Line Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma.

The purpose of this study was to evaluate 18F-FDG PET/CT as an early and late interim imaging biomarker in patients with pancreatic ductal adenocarcinoma who undergo first-line systemic therapy. Methods: This was a prospective, single-center, single-arm, open-label study (IRB12-000770). Patient receiving first-line chemotherapy were planned to undergo baseline 18F-FDG PET/CT, early interim 18F-FDG PET/CT, and late interim 18F-FDG PET/CT. Cutoffs for metabolic and radiographic tumor response assessment as selected and established by receiver-operating-characteristic analysis were applied (modified PERCIST/RECIST1.1). Patients were followed to collect data on further treatments and overall survival. Results: The study population consisted of 28 patients who underwent baseline 18F-FDG PET/CT. Twenty-three of these (82%) underwent early interim 18F-FDG PET/CT, and 21 (75%) underwent late interim 18F-FDG PET/CT. Twenty-three deaths occurred during a median follow-up period of 14 mo (maximum follow-up, 58.3 mo). The median overall survival was 36.2 mo (95% CI, 28 mo to not yet reached [NYR]) in early metabolic responders (6/23 [26%], P = 0.016) and 25.4 mo (95% CI, 19.6 mo-NYR) in early radiographic responders (7/23 [30%], P = 0.16). The median overall survival was 27.4 mo (95% CI, 21.4 mo-NYR) in late metabolic responders (10/21 [48%], P = 0.058) and 58.2 mo (95% CI, 21.4 mo-NYR) in late radiographic responders (7/21 [33%], P = 0.008). Conclusion: 18F-FDG PET may serve as an early interim imaging biomarker (at ∼4 wk) for evaluation of response to first-line chemotherapy in patients with pancreatic ductal adenocarcinoma. Radiographic changes might be sufficient for response evaluation after the completion of first-line chemotherapy.

Predictive Value of Baseline [18F]FDG PET/CT for Response to Systemic Therapy in Patients with Advanced Melanoma.

BACKGROUND/AIM: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. MATERIALS AND METHODS: Forty four melanoma patients, who underwent [18F]FDG-PET/CT before first-line target therapy (28/44) or immunotherapy (16/44), were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared using the Mann-Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan-Meier analysis. RESULTS: Median (IQR) MTVwb and TLGwb were 13.1 mL and 72.4, respectively. Non-responder patients were 38/44, 26/28 and 12/16 at early evaluation, and 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target, and immunotherapy subgroup, respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p < 0.037) in the whole-cohort and target subgroup and MTVwb and TLGwb (all p < 0.022) in target subgroup. No significant differences were found for the immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversially, MTVlfn, TLGlfn, MTVsoft + lfn, TLGsoft + lfn, MTVwb and TLGwb were significantly associated (all p < 0.05) with OS in both the whole-cohort and target therapy subgroup. CONCLUSIONS: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.

Artificial intelligence for reduced dose 18F-FDG PET examinations: a real-world deployment through a standardized framework and business case assessment.

BACKGROUND: To determine whether artificial intelligence (AI) processed PET/CT images of reduced by one-third of 18-F-FDG activity compared to the standard injected dose, were non-inferior to native scans and if so to assess the potential impact of commercialization. MATERIALS AND METHODS: SubtlePET™ AI was introduced in a PET/CT center in Italy. Eligible patients referred for 18F-FDG PET/CT were prospectively enrolled. Administered 18F-FDG was reduced to two-thirds of standard dose. Patients underwent one low-dose CT and two sequential PET scans; "PET-processed" with reduced dose and standard acquisition time, and "PET-native" with an elapsed time to simulate standard acquisition time and dose. PET-processed images were reconstructed using SubtlePET™. PET-native images were defined as the standard of reference. The datasets were anonymized and independently evaluated in random order by four blinded readers. The evaluation included subjective image quality (IQ) assessment, lesion detectability, and assessment of business benefits. RESULTS: From February to April 2020, 61 patients were prospectively enrolled. Subjective IQ was not significantly different between datasets (4.62±0.23, p=0.237) for all scanner models, with "almost perfect" inter-reader agreement. There was no significant difference between datasets in lesions' detectability, target lesion mean SUVmax value, and liver mean SUVmean value (182.75/181.75 [SD:0.71], 9.8/11.4 [SD:1.13], 2.1/1.9 [SD:0.14] respectively). No false-positive lesions were reported in PET-processed examinations. Agreed SubtlePET™ price per examination was 15-20% of FDG savings. CONCLUSION: This is the first real-world study to demonstrate the non-inferiority of AI processed 18F-FDG PET/CT examinations obtained with 66% standard dose and a methodology to define the AI solution price.

Impact of segmentation and discretization on radiomic features in 68Ga-DOTA-TOC PET/CT images of neuroendocrine tumor.

OBJECTIVE: To identify the impact of segmentation methods and intensity discretization on radiomic features (RFs) extraction from 68Ga-DOTA-TOC PET images in patients with neuroendocrine tumors. METHODS: Forty-nine patients were retrospectively analyzed. Tumor contouring was performed manually by four different operators and with a semi-automatic edge-based segmentation (SAEB) algorithm. Three SUVmax fixed thresholds (20, 30, 40%) were applied. Fifty-one RFs were extracted applying two different intensity rescale factors for gray-level discretization: one absolute (AR60 = SUV from 0 to 60) and one relative (RR = min-max of the VOI SUV). Dice similarity coefficient (DSC) was calculated to quantify segmentation agreement between different segmentation methods. The impact of segmentation and discretization on RFs was assessed by intra-class correlation coefficients (ICC) and the coefficient of variance (COVL). The RFs' correlation with volume and SUVmax was analyzed by calculating Pearson's correlation coefficients. RESULTS: DSC mean value was 0.75 ± 0.11 (0.45-0.92) between SAEB and operators and 0.78 ± 0.09 (0.36-0.97), among the four manual segmentations. The study showed high robustness (ICC > 0.9): (a) in 64.7% of RFs for segmentation methods using AR60, improved by applying SUVmax threshold of 40% (86.5%); (b) in 50.9% of RFs for different SUVmax thresholds using AR60; and (c) in 37% of RFs for discretization settings using different segmentation methods. Several RFs were not correlated with volume and SUVmax. CONCLUSIONS: RFs robustness to manual segmentation resulted higher in NET 68Ga-DOTA-TOC images compared to 18F-FDG PET/CT images. Forty percent SUVmax thresholds yield superior RFs stability among operators, however leading to a possible loss of biological information. SAEB segmentation appears to be an optimal alternative to manual segmentation, but further validations are needed. Finally, discretization settings highly impacted on RFs robustness and should always be stated.

[18F]FDG PET/CT for evaluating early response to neoadjuvant chemotherapy in pediatric patients with sarcoma: a prospective single-center trial.

INTRODUCTION: This is a prospective, single-center trial in pediatric patients with sarcoma aiming to evaluate [18F]FDG PET/CT as a tool for early response assessment to neoadjuvant chemotherapy (neo-CTX). METHODS: Bone or soft tissue sarcoma patients with (1) baseline [18F]FDG PET/CT within 4 weeks prior to the start of neo-CTX (PET1), (2) early interim [18F]FDG PET/CT (6 weeks after the start of neo-CTX (PET2), (3) evaluation of neo-CTX response by histology or MRI, and (4) definitive therapy after neo-CTX (surgery or radiation) were included. Semiquantitative PET parameters (SUVmax, SUVmean, SUVpeak, MTV and TLG) and their changes from PET1 to PET2 (ΔPET) were obtained. The primary endpoint was to evaluate the predictive value of PET1, PET2 and ΔPET parameters for overall survival (OS) and time to progression (TTP). The secondary outcome was to evaluate if [18F]FDG PET/CT can predict the response to neo-CTX assessed by histopathology or MRI. Primary and secondary outcomes were also evaluated in a subpopulation of patients with bone involvement only. RESULTS: Thirty-four consecutive patients were enrolled (10 females; 24 males; median age 15.1 years). 17/34 patients (50%) had osteosarcoma, 13/34 (38%) Ewing's sarcoma, 2/34 (6%) synovial sarcoma and 2/34 (6%) embryonal liver sarcoma. Median follow-up was 39 months (range 16-84). Eight of 34 patients (24%) died, 9/34 (27%) were alive with disease, and 17/34 (50%) had no evidence of residual/recurrent disease. Fifteen of 34 (44%) and 19/34 (56%) were responders and non-responders, respectively. PET2-parameters were associated with longer TTP (p < 0.02). ΔMTV was associated with tissue response to neo-CTX (p = 0.047). None of the PET1, PET2 or ΔPET parameters were associated with OS. CONCLUSION: [18F]FDG PET/CT performed 6 weeks after the start of neo-CTX can serve as an early interim biomarker for TTP and pathologic response but not for OS in pediatric patients with sarcoma.

Clinical application of Fluciclovine PET, choline PET and gastrin-releasing polypeptide receptor (bombesin) targeting PET in prostate cancer.

PURPOSE OF REVIEW: The aim of this review is to explore the clinical application of different PET radiopharmaceuticals in prostate cancer (PCa), beyond inhibitors of the prostate-specific membrane antigen (PSMA). RECENT FINDINGS: Choline PET represented in the last decades the standard of reference for PET imaging in PCa and has been recently included in clinical trials evaluating the efficacy of metastasis-directed therapy in oligo-metastatic disease. Fluciclovine, as synthetic amino acid, has been proposed for investigating PCa. The results obtained by the first prospective studies led to FDA approval in 2016 in patients with biochemical recurrence. Recently, phase II/III trials explored its accuracy compared with PSMA PET and its impact on patient management. Imaging the gastrin-releasing polypeptide receptor (GRPR) recently drawn attention. Radio-labelled GRPR antagonists have the potential to be used as theranostic agents. Further evaluation is needed to understand the relation between GRPR expression and hormonal-resistant PCa, and for tumors characterized by heterogeneity of receptors expressed (e.g. PSMA-negative) on their cell surface. SUMMARY: Other new generation PET tracers may play an important role in PCa, namely in case of PSMA-negative phenotypes.

18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival.

OBJECTIVES: (1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the application of radiomics analysis of the primary lesion to identify features predictive of response to immunotherapy; (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT (N and M factors) is associated with PFS and OS. MATERIALS AND METHODS: we retrospectively analyzed clinical records of advanced NCSLC patients (stage IIIb/c or stage IV) candidate to immunotherapy who performed 18F-FDG PET/CT before treatment to stage the disease. Fifty-seven (57) patients were included in the analysis (F:M 17:40; median age = 69 years old). Notably, 38/57 of patients had adenocarcinoma (AC), 10/57 squamous cell carcinoma (SCC) and 9/57 were not otherwise specified (NOS). Overall, 47.4% patients were stage IVA, 42.1% IVB and 8.8% IIIB. Immunotherapy was performed as front-line therapy in 42/57 patients and as second line therapy after chemotherapy platinum-based in 15/57. The median follow up after starting immunotherapy was 10 months (range: 1.5-68.6). Therapy response was assessed by RECIST 1.1 criteria (CT evaluation every 4 cycles of therapy) in 48/57 patients or when not feasible by clinical and laboratory data (fast disease progression or worsening of patient clinical condition in nine patients). Radiomics analysis was performed by applying regions of interest (ROIs) of the primary tumor delineated manually by two operators and semi-automatically applying a threshold at 40% of SUVmax. RESULTS: (1.1) metabolic tumor volume (MTV) (p = 0.028) and total lesion glycolysis (TLG) (p = 0.035) were significantly associated with progressive vs. non-progressive disease status. Patients with higher values of MTV and TLG had higher probability of disease progression, compared to those patients presenting with lower values. SUVmax did not show correlation with PD status, PFS and OS. MTV (p = 0.027) and TLG (p = 0.022) also resulted in being significantly different among PR, SD and PD groups, while SUVmax was confirmed to not be associated with response to therapy (p = 0.427). (1.2) We observed the association of several radiomics features with PD status. Namely, patients with high tumor volume, TLG and heterogeneity expressed by "skewness" and "kurtosis" had a higher probability of failing immunotherapy. (1.3) M status at 18F-FDG PET/CT was significantly associated with PFS (p = 0.002) and OS (p = 0.049). No significant associations were observed for N status. CONCLUSIONS: 18F-FDG PET/CT performed before the start of immunotherapy might be an important prognostic tool able to predict the disease progression and response to immunotherapy in patients with advanced NSCLC, since MTV, TLG and radiomics features (volume and heterogeneity) are associated with disease progression.

Predictive accuracy and clinical benefit of a nomogram aimed to predict 68Ga-PSMA PET/CT positivity in patients with prostate cancer recurrence and PSA < 1 ng/ml external validation on a single institution database.

PURPOSE: To perform an external validation of a recently published nomogram aimed to predict positive 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) by Rauscher et al. (Eur Urol 73(5):656-661, 2018). METHODS: Overall, 413 PCa patients with BCR after RP (two consecutive PSA ≥ 0.2 ng/ml) and PSA value between 0.2 and 1 ng/ml were included. A multivariable logistic regression model was produced to assess the predictors of positive 68Ga-PSMA-11 PET/CT results. The performance characteristics of the model were assessed by quantifying the predictive accuracy, according to model calibration. Yuden's index was used to find the best nomogram's cut-off. Finally, decision curve analysis (DCA) was implemented to quantify the nomogram's clinical value. RESULTS: In the external cohort, the overall detection rate of 68Ga-PSMA-11 PET/CT was 44% vs. 64.7% in the original population. At multivariate analysis, PSA at 68Ga-PSMA-11 PET/CT (OR: 7.06, p < 0.001) and ongoing ADT at time of 68Ga-PSMA-11 PET/CT (OR: 2.07, p = 0.03) were the only independent predictors of PET/CT positivity. The predictive accuracy of nomogram was suboptimal and comparable to that reported in the original model (64% vs. 67%, respectively). The calibration plot indicated suboptimal concordance. The best nomogram's cut-off to predict positive 68Ga-PSMA-11 PET/CT was 35% (AUC = 0.61). In DCA, the nomogram revealed clinical net benefit when the threshold probabilities of positive 68Ga-PSMA-11 PET/CT is > 35%. CONCLUSION: We assessed similar suboptimal predictive accuracies in the external cohort compared to the original one. PSA and ongoing ADT were confirmed as positive predictors, and the most informative nomogram cut-off resulted 35%.

Prediction nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for prostate cancer.

OBJECTIVE: The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. MATERIALS AND METHODS: Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced-stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram's derived cutoff. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. RESULTS: 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cutoff value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. CONCLUSIONS: This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cutoff in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.

The role of 18F-FDG PET/CT in the detection of osteosarcoma recurrence.

AIM: The aim of this study was to investigate the diagnostic accuracy of 18F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy. METHODS: Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) 18F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of 18F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). 18F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated. RESULTS: 18F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis 18F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after 18F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively. CONCLUSION: 18F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.

(11)C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series.

PURPOSE: To evaluate (11)C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing (11)C-choline PET/CT during BCR. METHODS: We retrospectively analysed 9,632 (11)C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. RESULTS: Overall, 52.8 % of the (11)C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 - 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive (11)C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 (11)C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans. CONCLUSION: In a large cohort of patients, the feasibility of (11)C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.

Prognostic Value of 68Ga-DOTANOC PET/CT SUVmax in Patients with Neuroendocrine Tumors of the Pancreas.

UNLABELLED: This study was performed to investigate the role of (68)Ga-DOTANOC SUVmax as a potential prognostic factor in patients with pancreatic neuroendocrine tumor (pNET). METHODS: Among the patients who underwent (68)Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. RESULTS: Overall, 43 patients were included. No significant differences in SUVmax were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20-48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14-26 mo) had progressive disease. SUVmax at 24 mo of follow-up was significantly higher (P = 0.022) in patients with stable disease than in patients with progressive disease. The best SUVmax cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUVmax of no more than 37.8 (hazard ratio, 3.09; P = 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P = 0.009), and medical therapy alone (hazard ratio, 2.36; P = 0.018). Advanced stage (IV) (P = 0.026), an SUVmax of less than 37.8 (P = 0.043), and medical therapy alone (P = 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 ≤ 5% and 20 mo for Ki-67 > 5%; P = 0.005), SUVmax (<37.8 vs. >38.0: 16.0 vs. 27.0 mo; P = 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P = 0.014). CONCLUSION: (68)Ga-DOTANOC SUVmax is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior.