Somatostatin receptor activity assessed by 68Ga-DOTATOC PET can preoperatively predict DAXX/ATRX loss of expression in well-differentiated pancreatic neuroendocrine tumors.

PURPOSE: To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery. METHODS: This retrospective study included 72 consecutive patients with PanNET (January 2018-March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE. RESULTS: Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01%; cut-off = 46.96; sensitivity = 77.78%; specificity = 88.89%). In the sub-analysis performed on 55 patients with biopsy availability, SRD demonstrated its role in providing useful and additional information (multivariate logistic regression: SRD p = 0.007; grade p = 0.040). CONCLUSION: SRD has a predictive role on DAXX LoE in PanNETs, with higher probability of LoE at increasing SRD values. SRD provides complementary/additional information to grade assessed on biopsy material, and the combined use of these approaches might support patients' management by preoperatively identifying subjects with more aggressive diseases.

Role of [68Ga]Ga-PSMA-11 PET radiomics to predict post-surgical ISUP grade in primary prostate cancer.

PURPOSE: The aim of this study is to investigate the role of [68Ga]Ga-PSMA-11 PET radiomics for the prediction of post-surgical International Society of Urological Pathology (PSISUP) grade in primary prostate cancer (PCa). METHODS: This retrospective study included 47 PCa patients who underwent [68Ga]Ga-PSMA-11 PET at IRCCS San Raffaele Scientific Institute before radical prostatectomy. The whole prostate was manually contoured on PET images and 103 image biomarker standardization initiative (IBSI)-compliant radiomic features (RFs) were extracted. Features were then selected using the minimum redundancy maximum relevance algorithm and a combination of the 4 most relevant RFs was used to train 12 radiomics machine learning models for the prediction of PSISUP grade: ISUP ≥ 4 vs ISUP < 4. Machine learning models were validated by means of fivefold repeated cross-validation, and two control models were generated to assess that our findings were not surrogates of spurious associations. Balanced accuracy (bACC) was collected for all generated models and compared with Kruskal-Wallis and Mann-Whitney tests. Sensitivity, specificity, and positive and negative predictive values were also reported to provide a complete overview of models' performance. The predictions of the best performing model were compared against ISUP grade at biopsy. RESULTS: ISUP grade at biopsy was upgraded in 9/47 patients after prostatectomy, resulting in a bACC = 85.9%, SN = 71.9%, SP = 100%, PPV = 100%, and NPV = 62.5%, while the best-performing radiomic model yielded a bACC = 87.6%, SN = 88.6%, SP = 86.7%, PPV = 94%, and NPV = 82.5%. All radiomic models trained with at least 2 RFs (GLSZM-Zone Entropy and Shape-Least Axis Length) outperformed the control models. Conversely, no significant differences were found for radiomic models trained with 2 or more RFs (Mann-Whitney p > 0.05). CONCLUSION: These findings support the role of [68Ga]Ga-PSMA-11 PET radiomics for the accurate and non-invasive prediction of PSISUP grade.

Evaluation of a 2D UNet-Based Attenuation Correction Methodology for PET/MR Brain Studies.

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.

The role of 18F-FAZA PET/CT in detecting lymph node metastases in renal cell carcinoma patients: a prospective pilot trial.

BACKGROUND: The accurate detection of nodal invasion is an unmet need in the clinical staging of renal cancer. Positron emission tomography (PET) with 18F-fluoroazomycin arabinoside (18F-FAZA), a hypoxia specific tracer, is a non-invasive imaging method that detects tumour hypoxia. The aim of this work was to evaluate the role of 18F-FAZA PET/CT in the identification of lymph node metastases in renal cancer. METHODS: A proof-of-concept phase 2 study including 20 kidney cancer patients ( ClinicalTrials.gov Identifier: NCT03955393) was conducted. Inclusion criteria were one or more of the following three criteria: (1) clinical tumour size > 10 cm, (2) evidence of clinical lymphadenopathies at preoperative CT scan and (3) clinical T4 cancer. Before surgery, 18F-FAZA PET/CT was performed, 2 h after the intravenous injection of the radiotracer. An experienced nuclear medicine physician, aware of patient's history and of all available diagnostic imaging, performed a qualitative and semi-quantitative analysis on 18F-FAZA images. Histopathological analysis was obtained in all patients on surgical specimen. RESULTS: Fourteen/19 (74%) patients had a non-organ confined renal cell carcinoma (RCC) at final pathology (either pT3 or pT4). Median number of nodes removed was 12 (IQR 7-15). The rate of lymph node invasion was 16%. No patient with pN1 disease showed positive 18F-FAZA PET, thus suggesting the non-hypoxic behaviour of the lesions. In addition, neither primary tumour nor distant metastases presented a pathological 18F-FAZA uptake. No adverse events were recorded during the study. CONCLUSIONS: 18F-FAZA PET/CT scan did not detect RCC lymph neither nodal nor distant metastases and did not show any uptake in the primary renal tumour.

Renal Function Assessment Gap in Clinical Practice: An Awkward Truth.

INTRODUCTION: An accurate assessment of renal function is needed in the majority of clinical settings. Unfortunately, the most used estimated glomerular filtration rate (eGFR) formulas are affected by significant errors in comparison to gold standards methods of measured GFR (mGFR). OBJECTIVE: The objective of the study is to determine the extent of the error of eGFR formulas compared to the mGFR in different specific clinical settings. METHODS: A total retrospectively consecutive cohort of 1,320 patients (pts) enrolled in 2 different European Hospitals (Center 1: 470 pts; Center 2: 850 pts) was collected in order to compare the most common eGFR formulas used by physicians with the most widespread mGFR methods in daily clinical practice (Iohexol Plasma Clearance -Center 1 [mGFR-iox] and Renal Scintigraphy -Center 2 [mGFR-scnt]). The study cohort was composed by urological, oncological, and nephrological pts. The agreement between eGFR and mGFR was evaluated using bias (as median of difference), precision (as interquartile range of difference) accuracy (as P30), and total deviation index. RESULTS: The most accurate eGFR formula in the comparison with gold standard method (Iohexol plasma clearance) in Center 1 was represented by s-creatinine and cystatin C combined Chronic Kidney Disease-Epidemiology Collaboration-cr-cy, even though the P30 is reduced (84%) under the threshold of 60 mL/min/1.73 m2. Similar results were found in Center 2, with a wider discrepancy between mGFR-scnt and eGFR formulas due to the minor accuracy of the nuclear tool in respect to the mGFR-iox. CONCLUSIONS: The loss of accuracy observed for the formulas at lower values of GFR suggests the mandatory use of gold standards methods as Iohexol Plasma Clearance to assess the correct status of renal function for critical cases. The center 2 showed lower levels of agreement between mGFR and eGFR suggesting that the errors are partially accounted for the Renal Scintigraphy technique too. In particular, we suggest the use of mGFR-iox in oncological urological and nephrological pts with an eGFR lower than 60 mL/min/1.73 m2.

11C-choline PET/CT predicts survival in prostate cancer patients with PSA < 1 NG/ml.

PURPOSE: The main drawback of 11C-choline PET/CT for restaging prostate cancer (PCa) patients with biochemical failure is the relatively low positive detection rate for prostate specific antigen (PSA) < 1 ng/ml. This study assessed whether 11C-choline PET/CT predicts survival in PCa patients with PSA < 1 ng/ml. METHODS: This retrospective study included 210 PCa patients treated with radical prostatectomy who underwent 11C-choline PET/CT from December 1, 2004 to July 31, 2007 due to biochemical failure. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathologic variables and PCa-specific survival. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. RESULTS: Median follow-up after radical prostatectomy was 6.9 years (95% confidence interval, CI, 2.0-14.5 years). 11C-choline PET/CT was positive in 20.5% of patients. Median PCa-specific survival was 13.4 years (95% CI, 9.9-16.8 years) in patients with positive 11C-choline PET/CT, and it was not achieved in patients with negative 11C-choline PET/CT (log-rank, chi-square = 15.0, P < 0.001). Ten-year survival probabilities for patients with negative 11C-choline PET/CT and for patients with positive 11C-choline PET/CT were 86.0% (95% CI: 80.7%-91.3%) and 63.6% (95% CI: 54.5-72.7%). At multivariate analysis, only 11C-choline PET/CT significantly predicted PCa-specific survival (hazard ratio = 2.54, 95% CI, 1.05-6.13, P = 0.038). Patients with pathological 11C-choline uptake in the prostatic bed or in pelvic lymph nodes had longer PCa-specific survival in comparison to patients with pathological tracer uptake in the skeleton (log-rank: chi-square = 27.4, P < 0.001). CONCLUSION: Despite the relatively low positive detection rate for PSA < 1 ng/ml, positive 11C-choline PET/CT predicts PCa-specific survival in this low PSA range. As long as more sensitive radiotracers, such as 68Ga-PSMA-11, do not become more widely available, these results might support a broader use of radiolabeled choline in restaging PCa for PSA < 1 ng/ml.

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma.

AIM: The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of 18F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). MATERIALS AND METHODS: From the databases of two centers including 31,500 18F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent 18F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted 18F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. RESULTS: Recurrent GCT was confirmed in 47 of 52 patients with pathological 18F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of 18FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively.18F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from "wait and watch" to new chemotherapy in six patients and the "wait-and-watch" approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological 18F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological 18F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological 18F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. 18F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). CONCLUSION: 18F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, 18F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process.

The relationship between local recurrences and distant metastases in prostate cancer: can 11C-choline PET/CT contribute to understand the link?

PURPOSE: Previous studies in prostate cancer (PCa) patients tried to correlate the onset of local recurrence (LR) with the development of distant metastases and formulated, based on theoretical and experimental data, hypotheses linking the two events. We aimed to address this issue with 11C-choline positron emission tomography/computed tomography (PET/CT). METHODS: This retrospective study included 491 PCa patients previously treated with radical prostatectomy who had undergone 11C-choline PET/CT owing to biochemical failure. Further inclusion criteria were availability of clinical and pathological variables for survival analysis. Statistical significance was taken at P < 0.05. RESULTS: Seventy-two patients (14.7%) had evidence of LR at 11C-choline PET/CT. The frequency of LR increased from 13.8% in the interval 0-4 years after prostatectomy, to 23.9% in the 12-16-year interval (P = 0.080). On the contrary, the frequency of lymph node metastases (overall rate in the 0-16 years interval after prostatectomy: 26.3%) and of bone metastases (overall rate: 13.8%) decreased significantly over time. Kaplan-Meier curves showed no significant group difference in the rates of lymph node or bone metastases between patients with LR and patients without LR. LR significantly predicted PCa-specific survival at univariate analysis, but the statistical significance was lost at multivariate analysis. CONCLUSION: We found no differences in the rates of lymph node and bone metastases between patients with and without LR. An inverse time-dependent trend was observed in the frequency of LR on one side and of lymph node and bone metastases on the other side. These findings were discussed in relation to previous theories linking LR to distant metastases and our study design.

Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease.

Objective: [18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Methods: Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation. Results: Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal < 3). Serum IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVC-SUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P < 0.05 for all comparisons). Conclusions: 18F-FDG uptake of IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4 levels, do not appear to correlate with the radiometabolic activity of IgG4-RD lesions. In light of our results PET/CT represents a reliable instrument for assessing IgG4-RD activity, although lymph-node uptake deserves careful interpretation.

18F-FDG PET/CT in gastric MALT lymphoma: a bicentric experience.

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<0.001 and high maximum diameter p<0.001), Ann Arbor stage (p=0.010), and Ki67 index (p<0.001) and not correlated with age, sex, presence of gastritis, ulcer, Helicobacter pylori infection, and plasmacytic differentiation. In the multivariate analysis, the correlations with gross morphological appearance, Ann Arbor stage, and Ki-67 score were confirmed. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio correlated significantly only with Ki67 index (p=0.047; p=0.012; p=0.042). CONCLUSIONS: 18F-FDG avidity was noted in 52 % of gastric MALT lymphoma and this avidity is correlated with gross morphological characteristics, tumor stage, and Ki-67 index. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio are correlated only with Ki-67 index, and only lesion-to-liver SUVmax ratio was independently associated with Ki-67 score.

18F-FDG PET reveals unique features of large vessel inflammation in patients with Takayasu's arteritis.

PURPOSE: The object of this study was to assess whether 18F-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 <4 mm thick. METHODS: We studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUVmax), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated. RESULTS: Increased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUVmax values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUVmax in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria. CONCLUSIONS: PET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potential confounder. Prospective studies are required to correlate PET findings with relevant clinical outcomes.

Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

OBJECTIVE: To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. PATIENTS AND METHODS: From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). RESULTS: With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. CONCLUSIONS: 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients.

PET imaging for lymph node dissection in prostate cancer.

The detection of neoplastic lymph nodal involvement in prostate cancer (PCa) patients has relevant therapeutic and prognostic significance, both in the clinical settings of primary staging and restaging. Lymph nodal dissection (LND) currently represents the gold standard for evaluating the presence of lymph nodal involvement. However, this procedure is invasive, associated with morbidity, and may fail in detecting all potential lymph nodal metastatic regions. Currently the criteria for lymph nodal detection using conventional imaging techniques mainly rely on morphological assessment with unsatisfactory diagnostic accuracy. Positron emission tomography (PET) represents a helpful imaging technique for a proper staging of lymph nodal status. The most investigated PET radiotracer is choline, although many others have been explored as guide for both primary and salvage LND, such as fluorodeoxyglucose, acetate, fluorocyclobutanecarboxylic acid and prostate-specific membrane antigen. In the present review, a comprehensive literature review addressing the role of PET for LND in PCa patients is reported, with the use of the above-mentioned radiotracers.

Biomarkers from in vivo molecular imaging of breast cancer: pretreatment 18F-FDG PET predicts patient prognosis, and pretreatment DWI-MR predicts response to neoadjuvant chemotherapy.

OBJECTIVE: Human cancers display intra-tumor phenotypic heterogeneity and recent research has focused on developing image processing methods extracting imaging descriptors to characterize this heterogeneity. This work assesses the role of pretreatment 18F-FDG PET and DWI-MR with respect to the prognosis and prediction of neoadjuvant chemotherapy (NAC) outcomes when image features are used to characterize primitive lesions from breast cancer (BC). MATERIALS AND METHODS: A retrospective protocol included 38 adult women with biopsy-proven BC. Patients underwent a pre-therapy 18F-FDG PET/CT whole-body study and a pre-therapy breast multi-parametric MR study. Patients were then referred for NAC treatment and then for surgical resection, with an evaluation of the therapy response. Segmentation methods were developed in order to identify functional volumes both on 18F-FDG PET images and ADC maps. Macroscopic and histogram features were extracted from the defined functional volumes. RESULTS: Our work demonstrates that macroscopic and histogram features from 18F-FDG PET are able to biologically characterize primitive BC, and define the prognosis. In addition, histogram features from ADC maps are able to predict the response to NAC. CONCLUSION: Our work suggests that pre-treatment 18F-FDG PET and pre-treatment DWI-MR provide useful complementary information for biological characterization and NAC response prediction in BC.

Diagnostic accuracy of FDG PET/CT for clinical evaluation at the end of treatment of HL and NHL: a comparison of the Deauville Criteria (DC) and the International Harmonization Project Criteria (IHPC).

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.

Recurrent renal cell carcinoma: clinical and prognostic value of FDG PET/CT.

PURPOSE: The purpose of our study was 1) to evaluate the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 2) to assess the impact of FDG PET/CT on treatment decision-making, and 3) to estimate the prognostic value of FDG PET/CT in the restaging process among patients with renal cell carcinoma (RCC). METHODS: From the FDG PET/CT databases of San Raffaele Hospital in Milan, Italy, and the Veneto Institute of Oncology in Padua, Italy, we selected 104 patients with a certain diagnosis of RCC after surgery, and for whom at least 24 months of post-surgical FDG PET/CT, clinical, and instrumental follow-up data was available. The sensitivity and specificity of FDG PET/CT were assessed by histology and/or other imaging as standard of reference. Progression-free survival (PFS) and overall survival (OS) were computed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to identify predictors of outcome. RESULTS: FDG PET/CT resulted in a positive diagnosis in 58 patients and a negative diagnosis in 46 patients. Sensitivity and specificity were 74% and 80%, respectively. FDG PET/CT findings influenced therapeutic management in 45/104 cases (43%). After a median follow-up period of 37 months (± standard deviation 12.9), 51 (49%) patients had recurrence of disease, and 26 (25%) had died. In analysis of OS, positive versus negative FDG PET/CT was associated with worse cumulative survival rates over a 5-year period (19% vs. 69%, respectively; p <0.05). Similarly, a positive FDG PET/CT correlated with a lower 3-year PFS rate. In addition, univariate and multivariate analysis revealed that a positive scan, alone or in combination with disease stage III-IV or nuclear grading 3-4, was associated with high risk of progression (multivariate analysis = hazard ratios [HRs] of 4.01, 3.7, and 2.8, respectively; all p < 0.05). CONCLUSIONS: FDG PET/CT is a valuable tool both in treatment decision-making and for predicting survival and progression in patients affected by RCC.

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting.

PURPOSE: The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). METHODS: We evaluated the supportive role of CSF Aß42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. RESULTS: Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aß42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. CONCLUSION: In this clinical setting, FDG PET SPM t-maps and the p-tau/Aß42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.

Imaging biomarkers in ovarian cancer: the role of ¹8F-FDG PET/CT.

Ovarian cancer represents one of the major form of cancer in women in the western world and its silent nature leads to a late clinical manifestation at advanced stage in many patients. Therefore the role of imaging techniques is very important for the correct management of these patients. In the present review, the role of 18F-FDG-PET/CT in the different clinical settings is presented and a comparison with other imaging modalities and serum biomarker CA-125 are discussed.

An update on technical and methodological aspects for cardiac PET applications.

Positron emission tomography (PET) is indicated for a large number of cardiac diseases: perfusion and viability studies are commonly used to evaluate coronary artery disease; PET can also be used to assess sarcoidosis and endocarditis, as well as to investigate amyloidosis. Furthermore, a hot topic for research is plaque characterization. Most of these studies are technically very challenging. High count rates and short acquisition times characterize perfusion scans while very small targets have to be imaged in inflammation/infection and plaques examinations. Furthermore, cardiac PET suffers from respiratory and cardiac motion blur. Each type of studies has specific requirements from the technical and methodological point of view, thus PET systems with overall high performances are required. Furthermore, in the era of hybrid PET/computed tomography (CT) and PET/Magnetic Resonance Imaging (MRI) systems, the combination of complementary functional and anatomical information can be used to improve diagnosis and prognosis. Moreover, PET images can be qualitatively and quantitatively improved exploiting information from the other modality, using advanced algorithms. In this review we will report the latest technological and methodological innovations for PET cardiac applications, with particular reference to the state of the art of the hybrid PET/CT and PET/MRI. We will also report the most recent advancements in software, from reconstruction algorithms to image processing and analysis programs.

[¹¹C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy.

PURPOSE: Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [(11)C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [(11)C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. METHODS: This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [(11)C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. RESULTS: Median follow-up was 7.2 years (1.4 - 18.9 years). [(11)C]Choline PET/CT was positive in 101 of 302 patients (33%). Median PCa-specific survival after prostatectomy was 14.9 years (95% CI 9.7 - 20.1 years) in patients with positive [(11)C]choline PET/CT. Median survival was not achieved in patients with negative [(11)C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4% (95% CI 31.7 - 53.1%) in patients with positive [(11)C]choline PET/CT and 95.5% (95% CI 93.5 - 97.5 %) in patients with negative [(11)C]choline PET/CT. In multivariate analysis, [(11)C]choline PET/CT (hazard ratio 6.36, 95% CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95% CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80%. CONCLUSION: Positive [(11)C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone-naive PCa patients. Prospective studies are warranted to confirm our results before more extensive use of [(11)C]choline PET/CT for prognostic stratification of PCa patients.