Per-lesion Analysis Research Articles

Comparison of radiomics approaches to predict resistance to 1st line chemotherapy in liver metastatic colorectal cancer.

Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases (mts) at the time of diagnosis, and more than 50% of patients with CRC develop metastases during their disease. Unfortunately, only 45% of patients after a chemotherapy will respond to treatment. The aim of this study is to develop and validate a machine learning algorithm to predict response of individual liver mts, using CT scans. Understanding which mts will respond or not will help clinicians in providing a more efficient per-lesion treatment based on patient specific response and not only following a standard treatment. A group of 92 patients was enrolled from two Italian institutions. CT scans were collected, and the portal venous phase was manually segmented by an expert radiologist. Then, 75 radiomics features were extracted both from 7x7 ROIs that moved across the image and from the whole 3D mts. Feature selection was performed using a genetic algorithm. Results are presented as a comparison of the two different approaches of features extraction and different classification algorithms. Accuracy (ACC), sensitivity (SE), specificity (SP), negative and positive predictive values (NPV and PPV) were evaluated for all lesions (per-lesion analysis) and patients (per-patient analysis) in the construction and validation sets. Best results were obtained in the per-lesion analysis from the 3D approach using a Support Vector Machine as classifier. We reached on the training set an ACC of 81%, while on test set, we obtained SE of 76%, SP of 67%, PPV of 69% and NPV of 75%. On the validation set a SE of 61%, SP of 60%, PPV of 57% and NPV of 64% were reached. The promising results obtained in the validation dataset should be extended to a larger cohort of patient to further validate our method.Clinical Relevance- to develop a radiomics signatures predicting single liver mts response to therapy. A personalized mts approach is important to avoid unnecessary toxicity offering more suitable treatments and a better quality of life to oncological patients.

EP.TU.701Colon Capsule Endoscopy versus Computed Tomographic Colonography for identifying Colorectal Cancer and Polyps: a systemic review and meta-analysis

AimEarly diagnosis and treatment of Colorectal Cancer can improve outcomes. Polypectomy with colonoscopy has failure and incompletion rates with risk of aerosol-generation. Computed Tomographic Colonography, second investigation, is limited by radiation exposure and aerosol generation. Colon Capsule endoscopy is a novel technique without gas insufflation, therefore avoiding the discomfort and aerosol-generation.Our aim is to compare the yield of the CCE with CTC in CRC and polyps in patients with positive stool tests or diagnosed colorectal lesions.MethodsReview followed PRISMA standards. Electronic database (EMBASE, MEDLINE, PubMed, CINAHL) searched for RCTs and Observational studies. MedCalc Statistical Software used for the synthesis of results. Primary (Per-Lesion and Per-Patient sensitivity analysis) and secondary (Other lesion and completion rate sensitivity analysis) outcomes measured using a random-effect model.ResultsWe found one RCT and three observational studies. Per-Lesion Sensitivity Analysis of CCE versus CTC showed overall effect of 1.903 (0.990- 1.937), p-value-0.057. Per-Patient Sensitivity Analysis of showed overall effect of 1.928 (0.995-1.892), p-value-0.054. Other lesions Sensitivity Analysis showed overall effect of 0.810 (0.121-161.995), p-value-0.418. Completion Rate Sensitivity Analysis showed overall effect of -0.419 (0.526-1.516), p-value-0.676.ConclusionCCE had a better detection rate for colorectal cancer and polyp than the CTC, but this was not statistically significant. Therefore, this study failed to prove CCE's superiority over CTC. A careful decision can be made in current COVID-19 pandemic since its advantage of zero aerosolisation. Researchers should focus on innovation in techniques and simultaneous high-quality studies to evaluate them.

MP15-19 68Ga-PSMA PET/CT For RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY: WHAT IS NEXT?

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy I (MP15)1 Sep 2021MP15-19 68Ga-PSMA PET/CT For RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY: WHAT IS NEXT? Giorgio Gandaglia, Daniele Robesti, Nicola Fossati, Armando Stabile, Enrico Camisassa, Vito Cucchiara, Marco Moschini, Andrea Necchi, Giuseppe Rosiello, Riccardo Leni, Renzo Colombo, Pierre I. Karakiewicz, Francesco Montorsi, and Alberto Briganti Giorgio GandagliaGiorgio Gandaglia More articles by this author , Daniele RobestiDaniele Robesti More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Armando StabileArmando Stabile More articles by this author , Enrico CamisassaEnrico Camisassa More articles by this author , Vito CucchiaraVito Cucchiara More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Riccardo LeniRiccardo Leni More articles by this author , Renzo ColomboRenzo Colombo More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001996.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The use of 68Ga-PSMA PET/CT is recommended for prostate cancer (PCa) re-staging in patients with either PSA persistence or biochemical recurrence (BCR) after radical prostatectomy (RP). Although PSMA PET/CT is characterized by a high sensitivity even at low PSA values, its prognostic implications as well as the patterns of subsequent progression has been poorly addressed METHODS: We retrospectively identified 182 patients who were evaluated with 68Ga-PSMA PET/CT for BCR after RP between 2016 and 2020. Patients were stratified according to PSMA PET/CT into two groups: positive (n=116) vs. negative (n=66) scan. Pathological features and salvage treatments were compared. Kaplan-Meier analyses assessed the time the first PSMA PET/CT to disease progression. Cox regression analyses assessed the impact of a positive PSMA PET/CT on progression after adjusting for confounders. Per-lesion analysis using Pearson Chi-square assessed the impact of a positive PSMA PET/CT on the location of clinical recurrence after PSMA PET/CT RESULTS: Median PSA at PSMA PET/CT scan and time from surgery to BCR were 0.7 ng/ml and 49 months. At a median follow-up of 16 months after the first PSMA PET/CT, 46 patients experienced progression. Overall, 13 vs. 33 patients experienced progression in negative vs. positive groups. No differences were observed for pathologic stage, ISUP group grade, pN status and the rate of salvage RT and HT (all p≥0.07). The 3-year progression-free survival rates were 75 vs. 40% for negative vs. positive PSMA PET/CT scan at the time of BCR. At MVA, a positive PSMA PET/CT scan was associated with a 2-fold higher risk of progression compared to a negative PSMA PET/CT (p=0.01). Median time to secondary progression in PSMA negative and positive PET was 44 and 25 months (p=0.006). In men with negative PSMA (n=66) patterns of recurrence was not influenced by receipt of salvage RT (no SRT: 37% pelvic, 62% lung vs. SRT 30% pelvic, 70% lung). In men with positive PSMA PET/CT no differences in terms of site of recurrences were seen between those receiving metastasis directed therapy (MDT) vs androgen deprivation therapy (ADT: pelvic 28%, bone 35% visceral 35% vs MDT pelvic 50% bone 10% visceral 40%). CONCLUSIONS: A negative PSMA PET/CT scan is a protective factor for metastases during follow-up. Patents with negative PSMA did not show any bony progression during follow-up. The pattern of recurrence was not influenced by the use of any salvage treatment both in negative and positive PSMA PET patients. Salvage therapies might impact on disease progression but do not alter patterns of PCa dissemination Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e271-e271 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giorgio Gandaglia More articles by this author Daniele Robesti More articles by this author Nicola Fossati More articles by this author Armando Stabile More articles by this author Enrico Camisassa More articles by this author Vito Cucchiara More articles by this author Marco Moschini More articles by this author Andrea Necchi More articles by this author Giuseppe Rosiello More articles by this author Riccardo Leni More articles by this author Renzo Colombo More articles by this author Pierre I. Karakiewicz More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Loading ...

Repeatability of 68Ga-PSMA-HBED-CC PET/CT-Derived Total Molecular Tumor Volume.

Molecular tumor volume (MTV) is a parameter of interest in prostate cancer for assessing total disease burden on prostate-specific membrane antigen (PSMA) PET. Although software segmentation tools can delineate whole-body MTV, a necessary step toward meaningful monitoring of total tumor burden and treatment response through PET is establishing the repeatability of these metrics. The present study assessed the repeatability of total MTV and related metrics for 68Ga-PSMA-HBED-CC in prostate cancer. Methods: Eighteen patients from a prior repeatability study who underwent 2 test-retest PSMA PET/CT scans within a mean interval of 5 d were reanalyzed. Within-subject coefficient of variation and repeatability coefficients (RCs) were analyzed on a per-lesion and per-patient basis. For the per-lesion analysis, individual lesions were segmented for analysis by a single reader. For the per-patient analysis, subgroups of up to 10 lesions (single reader) and the total tumor volume per patient were segmented (independently by 2 readers). Image parameters were MTV, SUVmax, SUVpeak, SUVmean, total lesion PSMA, and the related metric PSMA quotient (which integrates lesion volume and PSMA avidity). Results: In total, 192 segmentations were analyzed for the per-lesion analysis and 1,662 segmentations for the per-patient analysis (combining the 2 readers and 2 scans). The RC of the MTV of single lesions was 77% (95% CI, 63%-96%). The RC improved to 33% after aggregation of up to 10 manually selected lesions into subgroups assessed per patient (95% CI, 25%-46%). The RC of the semiautomatic MTVtotal (the sum of all voxels in the whole-body total tumor segmentation per patient) was 35% (95% CI, 25%-50%), the Bland-Altman bias was -6.70 (95% CI, -14.32-0.93). Alternating readers between scans led to a comparable RC of 37% (95% CI, 28%-49%) for MTVtotal, meaning that the metric is robust between scanning sessions and between readers. Conclusion:68Ga-PSMA-HBED-CC PET-derived semiautomatic MTVtotal is repeatable and reader-independent, with a change of ±35% representing a true change in tumor volume. Volumetry of single manually selected lesions has considerably lower repeatability, and volumetry based on subgroups of these lesions, although showing acceptable repeatability, is less systematic. The semiautomatic analysis of MTVtotal used in this study offers an efficient and robust means of assessing response to therapy.

Feasibility of automatic detection of small hepatocellular carcinoma (≤2 cm) in cirrhotic liver based on pattern matching and deep learning

Background and objective. Early detection of hepatocellular carcinoma (HCC) is crucial for clinical management. Current studies have reported large HCC detections using automatic algorithms, but there is a lack of research on automatic detection of small HCCs (sHCCs). This study is to investigate the feasibility of automatic detection of sHCC (≤2 cm) based on pattern matching and deep learning (PM-DL) model. Materials and methods. A retrospective study included 5376 image sets from 56 cirrhosis patients (28 sHCC patients with 32 pathologically confirmed lesions and 28 non-HCC cirrhosis patients) in the training-validation cohort to build and validate the model through five-fold cross-validation. In addition, an external test cohort including 6144 image sets from 64 cirrhosis patients (32 sHCC patients with 38 lesions and 32 non-HCC cirrhosis patients) was applied to further verify the generalization ability of the model. The proposed PM-DL model consisted of three main steps: 3D co-registration and liver segmentation, screening of suspicious lesions on diffusion-weighted imaging images based on pattern matching algorithm, and identification/segmentation of sHCC lesions on dynamic contrast-enhanced images with convolutional neural network. Results. The PM-DL model achieved a sensitivity of 89.74% and a positive predictive value of 85.00% in the external test cohort for per-lesion analysis. No significant difference was observed in volumes (P = 0.13) and the largest sizes (P = 0.89) between manually delineated and segmented lesions. The DICE coefficient reached 0.77 ± 0.16. Similar performances were identified in the validation cohort. Moreover, the PM-DL model outperformed Liver Imaging Reporting and Data System (LI-RADS) in sensitivity (probable HCCs: LR-5 or LR-4, P = 0.18; definite HCCs: LR-5, P < 0.001), with a similar high specificity for per-patient analysis. Conclusion. The PM-DL model may be feasible for accurate automatic detection of sHCC in cirrhotic liver.

Sex differences in coronary plaque changes assessed by serial computed tomography angiography

Long-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to evaluate the role of sex on long-term plaque progression and evolution of plaque composition. Furthermore, the influence of menopause on plaque progression and composition was also evaluated. Patients that underwent a coronary computed tomography angiography (CTA) were prospectively included to undergo a follow-up coronary CTA. Total and compositional plaque volumes were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). To investigate the influence of menopause on plaque progression, patients were divided into two groups, under and over 55 years of age. In total, 211 patients were included in this analysis, 146 (69%) men. The mean interscan period between baseline and follow-up coronary CTA was 6.2 ± 1.4 years. Women were older, had higher HDL levels and presented more often with atypical chest pain. Men had 434 plaque sites and women 156. On a per-lesion analysis, women had less fibro-fatty PAV compared to men (β -1.3 ± 0.4%; p < 0.001), with no other significant differences. When stratifying patients by 55 years age threshold, fibro-fatty PAV remained higher in men in both age groups (p < 0.05) whilst women younger than 55 years demonstrated more regression of fibrous (β -0.8 ± 0.3% per year; p = 0.002) and non-calcified PAV (β -0.7 ± 0.3% per year; p = 0.027). In a low-to-intermediate risk population of stable CAD patients, no significant sex differences in total PAV increase over time were observed. Fibro-fatty PAV was lower in women at any age and women under 55 years demonstrated significantly greater reduction in fibrous and non-calcified PAV over time compared to age-matched men. (ClinicalTrials.gov number, NCT04448691.)

Colorectal liver metastases: ADC as an imaging biomarker of tumor behavior and therapeutic response

PurposeTo correlate the ADC values of colorectal liver metastases, evaluated before (preADC) and after (postADC) neoadjuvant chemotherapy (ChT), as well as their difference (ΔADC), with the histological tumor regression grade (TRG) and to determine whether the preADC value can be predictive of the lesion ChT response. MethodTwenty-four patients with colorectal liver metastases, who had undergone 3 T-MRI before and after ChT and were subsequently treated by parenchymal-spearing surgery, were retrospectively included. Diffusion-weighted MRI (DW-MRI) was performed using a spin-echo echo-planar sequence with multiple b values, obtaining an ADC map. Fitted ADC values were calculated for each lesion before and after ChT. The maximum diameter of each lesion in both examinations was recorded. Diameter variations and RECIST1.1 criteria were assessed. All MRI findings were histopathologically correlated to TRG of resected liver metastases. Statistical analysis was performed on a per-lesion basis. ResultsA total of 58 colorectal liver metastases were analysed; after ChT, 8 out of 58 lesions disappeared. TRG1, TRG2, TRG3, TRG4 and TRG5 were observed in 6, 12, 12, 13 and 7 lesions, respectively. The preADC values showed a different distribution according to the TRG scores (p = 0.0027), even though the distribution was not linear. The postADC and ΔADC values were significant different based on the TRG system (both p < 0.0001). A significant correlation between the lesion TRG and the evaluation according to RECIST1.1 criteria was observed by a per-lesion analysis (p = 0.0009). ConclusionsPostADC and ΔADC could be proposed as reliable biomarkers to assess tumor treatment response after preoperative ChT in patients with colorectal liver metastases.

The significance of equivocal bone findings in staging PSMA imaging in the preoperative setting: validation of the PSMA-RADS version 1.0

BackgroundAssessing the extent of disease in newly diagnosed prostate cancer (PC) patients is crucial for tailoring an appropriate treatment approach. Prostate-specific membrane antigen (PSMA)–targeted positron emission tomography/computed tomography (PET/CT) reportedly has greater accuracy than conventional imaging for staging PC. As with any imaging modality, pitfalls and nonspecific findings do occur. The PSMA reporting and data system (PSMA-RADS) version 1.0 offers structured interpretation of PSMA-targeted studies and classifies lesions by likelihood of clinical significance. The aim of this retrospective study was to evaluate the clinical significance of equivocal bone findings on staging PSMA-targeted imaging, as defined by PSMA-RADS version 1.0, in the preoperative setting. Fifteen of 406 consecutive patients staged by PET/CT prior to radical prostatectomy had equivocal bone lesions. The scans were retrospectively scored with the PSMA-RADS version 1.0 system, blinded to disease course and follow-up data. Postoperative persistence of prostate-specific antigen levels supported by imaging and histological findings was used as the reference standard for the true significance of equivocal imaging findings.ResultsThirteen of the 15 patients had an overall PSMA-RADS score of 3B, of whom only two had true metastatic disease. The remaining patients had scores of 4 (n = 1) or 5 (n = 1), all confirmed as true positive prostate-related malignant lesions. A per-lesion analysis identified 29 bone lesions, of which 27 were scored PSMA-RADS 3B, and only three of them were true metastases. Thus, debatable lesions proved to have no clinical significance in 84.6% of cases, and only 11% of equivocal PSMA-RADS 3B bone lesions were true positive.ConclusionsIn intermediate and high-risk patients staged prior to radical prostatectomy, the majority of PSMA-RADS 3B lesions are of no clinical relevance. Bone lesions judged as being highly suspicious for metastases (PSMA-RADS 4/5) were all validated as true positives.

Sex differences in the natural history of plaque progression by serial coronary computed tomography angiography

Abstract Background Sex related differences exist for coronary artery disease (CAD). Women tend to be older when presenting with CAD and have lower rates of obstructive disease. Invasive intravascular ultrasound studies have shown differences in plaque composition between males and females. However, these studies were performed in a high risk population needing invasive imaging. Coronary computed tomography angiography (CTA) allows for a fast and non-invasive quantification of CAD in low risk patients. Sex differences and quantitative analysis of plaque progression and changes in plaque composition have not been studied intensively. Purpose To evaluate the role of sex on long term plaque progression and on the change of plaque composition in a population with low-intermediate risk. Methods Patients that received a coronary CTA were prospectively included in the SMARTool study to receive a follow-up coronary CTA. In total, 275 patients from 5 European countries were recruited in 7 centers. Baseline and follow-up coronary CTA were quantitative analyzed on a per-lesion basis using dedicated software package. Patients without coronary plaques at follow-up or with uninterpretable coronary CTA results were excluded. Total plaque volume and compositional volumes, calcified or non-calcified (defined as fibrous, fibro-fatty or necrotic core), were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). Lesions between males and females were compared using linear mixed models. We further classified patients into age groups &amp;lt;55 and ≥55 years to evaluate the influence of menopause on plaque progression. Results In total, 211 patients were included in this analysis, 146 (69%) were male and 65 (31%) were female. Mean interscan period was 6.2±1.4 years. Females were older (64±7 vs 61±8 years; p&amp;lt;0.001), had higher HDL levels (56±15 vs 49±15 mg/dL; p=0.003) and presented more often with atypical chest pain (62 vs 38%; p=0.017). Males had 434 plaque sites and females 156. On a per-lesion analysis females had less fibro-fatty PAV compared to males (β −1.3±0.4%; p&amp;lt;0.001), no other differences were seen (p&amp;gt;0.05). When stratifying the patients in above and below 55 years old, females still had less fibro-fatty PAV compared to males in both age groups (p&amp;lt;0.05). However, females in the age group &amp;lt;55 years showed more regression of fibrous PAV compared to males (β −0.8±0.3% per year; p=0.002) and non-calcified plaque PAV (β −0.7±0.3% per year; p=0.027) (Figure). Conclusions Males have larger fibro-fatty PAV compared to females, however the rate of change did not differ. Younger women showed more regression of fibrous PAV and non-calcified PAV compared to males. No differences in the rate of plaque progression or plaque composition changes were seen between males and females in the older age group. Figure plaque progression and sex diff Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EU H2020 research and innovation program

Standardization of CT radiomics features for multi-center analysis: impact of software settings and parameters

The aim of this multicentric study is an inter-center benchmarking, to assess how different set tools applied to the same radiomics workflow affected the radiomics features (RFs) values. This topic is of key importance to start collaboration between different centers and to bring radiomic studies from benchmark to bedside. A per-lesion analysis was performed on 56 metastases (mts) selected from 14 patients. A single radiologist performed the segmentation of all mts, and RFs were extracted from the same segmentation of each mts, using two different software and file formats. Potential sources of discrepancies were evaluated. The intraclass correlation coefficient was used to describe how strongly the same radiomic measurements calculated in the two different centers resemble each other. Moreover, means of the relative changes of each RF were calculated, compared and gradually reduced. We showed that, after matching all formulas, discrepancies in RFs calculation between two centers ranged from 1% to 277%. Therefore, we evaluated other sources of variability using a stepwise approach, which led us to reduce the inter-center discrepancies to 0% for 22/25 RFs and below 2% for 3 RFs out of 25. In this study we demonstrated that different radiomic applications and masks formats might strongly impact the computation of some RFs. Therefore, when dealing with multi-center studies it is mandatory to adopt all strategies that can help in limiting the differences, thus keeping in mind the feasibility of these strategies in large cohort studies.

Intraindividual comparison of 18 F-FDOPA and 68 Ga-DOTATOC PET/CT detection rate for metastatic assessment in patients with ileal neuroendocrine tumours.

In patients with ileal neuroendocrine tumours (ileal NETs), head-to-head evaluation of diagnostic performances of 68 Ga-DOTA-peptides and 18 F-fluorodihydroxyphenylalanine (18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare 68 Ga-DOTATOC and 18 F-FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well-differentiated ileal NETs. All patients with ileal NETs who underwent both 18 F-FDOPA and 68 Ga-DOTATOC PET/CT within a 3-month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per-patient, per-region and per-lesion analyses. Forty one patients with ileal NETs were evaluated. 18 F-FDOPA and 68 Ga-DOTATOC showed similar detection rates according to per-patient (97% for both) and per-region analyses (94% for 18 F-FDOPA vs 88% for 68 Ga-DOTATOC, P=.35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by 18 F-FDOPA PET/CT, and 25 (4%) by 68 Ga-DOTATOC PET/CT only. In a per-lesion analysis, 18 F-FDOPA PET/CT performed better than 68 Ga-DOTATOC PET/CT (overall detection rates of 96% vs 80%; P<.001). 18 F-FDOPA PET/CT detected significantly more metastases than 68 Ga-DOTATOC PET/CT in the liver, peritoneum, abdominal and supra-diaphragmatic lymph nodes. 18 F-FDOPA PET/CT seems not inferior than 68 Ga-DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, 18 F-FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, 68 Ga-DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection.

Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study

This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120nmol of TF2 followed 30h later by 150MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98-13.94, SD 3.37], 8.63cm3 [1.98-46.64; SD 14.83] and 37.90cm3 [8.07-127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. ClinicalTrials.gov NCT02587247 Registered 27 October 2015.

Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.

Exendin-4-based imaging in endogenous hyperinsulinemic hypoglycaemia cohort: A tertiary Endocrine centre experience.

Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results. To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities. Retrospective cross-sectional study. We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n=11), Munchausen syndrome (MS) (n=2) and inconclusive (n=1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma. True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization. In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS. 68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.

Role of [99mTc]Tc-Galacto-RGD2 SPECT/CT in identifying metastatic differentiated thyroid carcinoma after thyroidectomy and radioactive iodine therapy

PurposeIntegrin αvβ3, a member of the arginine-glycine-aspartate (RGD)-binding subfamily, is associated with tumor angiogenesis and metastasis. The aim of study is to investigate the clinical role of [99mTc]Tc-Galacto-RGD2 SPECT/CT in high-risk differentiated thyroid carcinoma (DTC) after thyroidectomy and radioactive iodine (RAI) therapy. MethodsThirty-six patients with high-risk DTC (20 males, 16 females; mean age: 59.9 ± 16.6 y) who underwent thyroidectomy and RAI therapy were consecutively enrolled in this study. All patients underwent [99mTc]Tc-Galacto-RGD2 SPECT/CT and diagnostic 131I whole-body scan 6 months after the last RAI treatment. A region of interest (ROI) was drawn and the ratio of tumor/non-target (T/NT) was calculated. Per-patient and per-lesion analysis was performed to evaluate the diagnostic efficacy. The final diagnosis was confirmed by histopathology and follow-up. Integrin αvβ3, CD31, and Ki-67 expression in the tumor were also analyzed for evaluation of angiogenesis and proliferation. ResultsOut of 36 patients, twenty-two had metastatic disease. By per-patient analysis, the area under the curve of [99mTc]Tc-Galacto-RGD2 SPECT/CT was marginally significantly higher than that of 131I whole-body scan and morphological imaging (P = 0.0034 and 0.0006). For per-lesion analysis, [99mTc]Tc-Galacto-RGD2 SPECT/CT identified 67 metastatic lymph nodes in 14 patients, 12 lung metastases in four patients, and 12 bone metastases in six patients; its sensitivity was significantly higher than that of 131I whole-body scan in detection of lymphatic (90.54% vs. 55.41%, P = 0.0124) and bone metastasis (92.31% vs. 30.77%, P = 0.046). The ratio of T/NT in metastatic lesions increased with the DTC upstaging. Conclusions[99mTc]Tc-Galacto-RGD2 SPECT/CT has high sensitivity in the detection of metastasis in high-risk DTC and further contributes to evaluation of tumor angiogenesis and radio‑iodine refractory status.

Imaging of colorectal cancer liver metastases using contrast-enhanced US, multidetector CT, MRI, and FDG PET/CT: a meta-analysis

Imaging of colorectal cancer liver metastases (CRCLMs) has improved in recent years. Therefore, the role of current imaging techniques needs to be defined. To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS), multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the detection of CRCLMs. PubMed database was searched for articles published during 2000-2019. Inclusion criteria were as follows: diagnosis/suspicion of CRCLMs; CEUS, MDCT, MRI, or FDG PET/CT performed for the detection of CRCLMs; prospective study design; histopathologic examination, intraoperative findings and/or follow-up used as reference standard; and data for calculating sensitivity and specificity reported. Twelve prospective studies were assessed, including 536 patients with CRCLMs (n = 1335). On a per-lesion basis, the sensitivity of CEUS, MDCT, MRI, and FDG PET/CT was 86%, 84%, 89%, and 62%, respectively. MRI had the highest sensitivity on a per-lesion analysis. CEUS and MDCT had comparable sensitivities. On a per-patient basis, the sensitivity and specificity of CEUS, MDCT, MRI, and FDG PET/CT was 80% and 97%, 87% and 95%, 87% and 94%, and 96% and 97%, respectively. The per-patient sensitivities for MRI and MDCT were similar. The sensitivity for MRI was higher than that for CEUS, MDCT, and FDG PET/CT for lesions <10 mm and lesions at least 10 mm in size. Hepatospecific contrast agent did not improve diagnostic performances. MRI is the preferred imaging modality for evaluating CRCLMs. Both MDCT and CEUS can be used as alternatives.

A prospective intra-individual comparison of [68Ga]Ga-PSMA-11 PET/CT, [68Ga]Ga-NODAGAZOL PET/CT, and [99mTc]Tc-MDP bone scintigraphy for radionuclide imaging of prostate cancer skeletal metastases

Prostate cancer (PCa) commonly metastasizes to the bones. There are several radionuclide techniques for imaging PCa skeletal metastases. We aimed to compare the lesion detection rate of [68Ga]Ga-PSMA-11 PET/CT, [68Ga]Ga-NODAGA-zoledronate ([68Ga]Ga-NODAGAZOL) PET/CT, and [99mTc]Tc-MDP bone scan in the assessment of bone metastases in patients with advanced PCa. We prospectively recruited two cohorts of patients (staging and re-staging cohorts) with advanced prostate cancer. The staging cohort was treatment-naïve PCa patients who showed skeletal metastases on bone scan. These patients were subsequently imaged with [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-NODAGAZOL PET/CT. Re-staging cohort was patients who were previously treated with PSMA-based radioligand therapy and were experiencing PSA progression. The re-staging cohort was imaged with [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-NODAGAZOL PET/CT. We performed a per-patient and per-lesion analysis of skeletal metastases in both cohorts and made a comparison between scan findings. Eighteen patients were included with a median age of 68years (range = 48-80) and a median Gleason score of 8. There were ten patients in the staging cohort with a median PSA of 119.26ng/mL (range = 4.63-18,948.00) and eight patients in the re-staging cohort with a median PSA of 48.56ng/mL (range = 6.51-3175.00). In the staging cohort, skeletal metastases detected by [68Ga]Ga-PSMA-11 PET/CT, [68Ga]Ga-NODAGAZOL PET/CT, and bone scan were 322, 288, and 261, respectively, p= 0.578. In the re-staging cohort, [68Ga]Ga-PSMA-11 PET/CT and [68Ga]Ga-NODAGAZOL PET/CT detected 152 and 191 skeletal metastases, respectively, p= 0.529. In two patients with negative [68Ga]Ga-PSMA-11 PET/CT findings, [68Ga]Ga-NODAGAZOL detected one skeletal metastasis in one patient and 12 skeletal metastases in the other. In patients with advanced prostate cancer, [68Ga]Ga-PSMA-11 PET/CT may detect more lesions than [68Ga]Ga-NODAGAZOL PET/CT and [99mTc]Tc-MDP bone scan for the staging of skeletal metastases. In patients who experience PSA progression on PSMA-based radioligand therapy, [68Ga]Ga-NODAGA PET/CT is a more suitable imaging modality for the detection of skeletal lesions not expressing PSMA. In the setting of re-staging, [68Ga]Ga-NODAGAZOL PET/CT may detect more lesions than [68Ga]Ga-PSMA-11 PET/CT.

Role of aspirin and statin therapy in patients with cerebral cavernous malformations

Stagnant blood flow and organizing thrombus are intralesional components of patients with cerebral cavernous malformations (CCM). Stasis and inflammation are mechanisms of growth, lesional instability and acute hemorrhages with or w/o symptoms. We evaluate the association of pre-diagnostic aspirin and/or statin use with acute hemorrhages at diagnosis. Patients with a CCM diagnosis were identified and categorized according to their medications on admission into four groups (no therapy, statin, aspirin, combined). The primary outcome was an acute hemorrhage (with or w/o symptoms) at diagnosis reported in a standardized manner from the T2 weighted magnetic resonance image. A multivariate generalized linear mixed models (GLMM) was utilized to conduct per-lesion analysis. We identified 446 patients with 635 lesions. An acute hemorrhage at diagnosis was observed in 31% of the patients. There were 328 patients without statin or aspirin therapy, 34% of whom presented with acute hemorrhage. Of patients on aspirin therapy at diagnosis, 25% presented with hemorrhage. Of patients on statin therapy, 26% had a hemorrhage at diagnosis. Combined therapy in 44 patients demonstrated a lower proportion of patients with acute hemorrhages (7 patients, 16% incidence). A GLMM showed that patients in the combined therapy group to have significantly lower odds of having an acute hemorrhage at diagnosis compared to the reference group of no therapy (OR 0.24; 95% CI 0.09–0.59; P = 0.002). Patients with a CCM receiving therapy with both aspirin and statins were less likely to present at diagnosis with acute hemorrhage.

MP13-12 IMPROVING THE IDENTIFICATION OF CLINICALLY SIGNIFICANT PROSTATE CANCER USING MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING (MPMRI)

INTRODUCTION AND OBJECTIVE: The aim of this study is to validate PIRADSv2 on biopsy-naive – mpMRI in detecting all prostate cancer lesions and clinically significant prostate cancer by correlation with whole-mount pathology after radical prostatectomy, using a per-lesion analysis. And using the correlation study, we will attempt to establish a new model with additional clinical variables to improve the identification of clinically significant prostate cancer using mpMRI. METHODS: Retrospective review of our institutional database of men who have radical prostatectomies operated between 1st Jan 2015 to 31st Dec 2017. The inclusion criteria were pre-operative mp-MRI performed in our institution, either pre-biopsy or >1 year from biopsy, and available whole-mount histology. PIRADSv2 was used to assess the imaging. Each lesion was outlined on wholemount histology, with the low grade (LG) (Gleason 3) and high-grade (HG) (Gleason 4 and 5) colour coded differently. Lesions on imaging were matched to wholemount histology and measured at the same axial plane taking the mean of 2 readings. For the model derivation, data from PIRADSv2 and other clinical parameters were used. Receiving operator characteristic curves was generated and the area under curves (AUC) were compared. RESULTS: A total of 70 patients met criteria. mpMRI had a sensitivity of 76% (95% CI: 0.69 – 0.83) and a positive predictive value of 72% (95% CI: 0.64 – 0.78) for prostate cancer detection. Patients with at least 1 HG lesion has median PSA density of 0.24 ng/ml2 which is significantly higher than patients with no HG lesion which have a median PSA density of 0.17 ng/ml2 (p = 0.008). Most missed lesions by mpMRI were LG. Missed HG lesions tended to be at least 50% smaller compared to HG lesions detected by mpMRI with a median area of 21.7mm2 versus 45.8 mm2 (p < 0.001). Our model using a combination of PIRADSv2, PSA density and MRI Volume of lesion showed improved predictive performance of AUC=0.799, superior to that of mpMRI using PIRADSv2 alone (AUC=0.769, p=0.001). A cut-off point of predicted probability of HG, P(HG) ≥ 20% corresponded to a negative predictive value of 87.5% and a positive predictive value (PPV) of 59.7%. Which means that for P(HG)< 20%, the lesion is most likely to be a LG. Whereas a cut-off point of P(HG) ≥ 50% corresponded to a NPV of 70.8% and a PPV of 74.0%. CONCLUSIONS: Our study derived a risk model using PIRADSv2 score and PSA density and mpMRI volume of lesion to better differentiate a LG or HG lesion compared to PIRADSv2 alone. This could help clinicians better select for gland sparing strategies and/or, avoid unnecessary biopsies. Source of Funding: N.A.

Prospective comparison of 68Ga-RM2 PET/CT and 68Ga-PSMA-617 PET/CT for initial staging of prostate cancer.

21 Background: PSMA ( Prostate Specific Membrane Antigen) and GRP-R ( Gastrin Releasing Peptide Receptor) are overexpressed on prostatic cancer cells and can be targeted with a PSMA inhibitor such as 68Ga-PSMA-617 (Liu 2018) or a GRP-R antagonist such as 68Ga-RM2 (Touijer 2019). We aimed to compare 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT at initial staging of prostate cancer. Methods: We prospectively enrolled 10 treatment-naïve patients with biopsy-confirmed prostate cancer. Fifteen lesions were found (two with Gleason score (GS) 6; seven GS 7(3+4), two GS 7(4+3) and four GS ≥ 8). 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT were randomly performed before prostatectomy with imaging at 1 and 2 hours after injection (2MBq/kg). Manual (MS) and automatic (AS) segmentation were performed on each PET imaging and then compared to histology (standard-of- truth). Prostatectomy samples were analyzed by an experimented pathologist who identified and staged each lesion according to GS. Each prostatectomy slice available was scanned for comparison between PET and histologic segmentation. Uptake intensity (SUVmax) and signal-to-noise ratio (SNR) relative to non-lesional prostate gland parenchyma were analyzed. Per-lesion analysis was performed on final GS (prostatectomy). Results: Using AS, 68Ga-RM2 PET/CT showed better sensitivity (Se) than 68Ga-PSMA-617 PET/CT: (0.85 vs 0.75) and better specificity (Sp) (0.89 vs 0.60). MS found similar Se (0.94 vs 0.93) but better Sp (0.89 vs 0.80) with 68Ga-RM2 PET/CT. SNR of 68Ga-RM2 PET/CT was high whatever the GS was; while 68Ga-PSMA-617 PET/CT exhibited higher SNR in high GS (p = 0.044). Finally, in low GS, SNR of 68Ga-RM2 PET/CT was significantly higher than 68Ga-PSMA-617 PET/CT (p = 0.004). Conclusions: GRP-R-targeting and PSMA-targeting have been previously compared in patients with biochemically recurrence (Minamimoto 2016) but not at primary staging. Our initial results, in this indication, showed great diagnostic performance of 68Ga-RM2 PET/CT compared to 68Ga-PSMA-617 PET/CT to characterize low Gleason score tumors. 68Ga-PSMA-617 PET/CT is promising for initial staging of high Gleason score tumors. These results need to be confirmed in a larger study.