Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

De Novo Metastatic Prostate Cancer Presenting With Atypical Lower-Limb Skeletal Metastases Detected on 68 Ga-PSMA PET/CT.

ABSTRACT: Metastatic prostate cancer to the appendicular skeleton is rare. We present an 86-year-old man with undiagnosed prostate cancer presenting with unilateral foot pain. CT and MRI demonstrated a sclerotic midfoot suggestive of an infiltrative process. In view of an elevated PSA, metastatic disease was suspected, and bone scan confirmed osteoblastically active pelvic and lower-limb skeletal lesions. Subsequent prostate biopsy confirmed prostate adenocarcinoma. Staging 68 Ga-PSMA PET/CT demonstrated PSMA-avid intraprostatic malignancy with pelvic and right lower-limb skeletal metastases. This is an unusual case of de novo 68 Ga-PSMA-avid metastatic prostate cancer with atypical lower-limb skeletal metastases presenting with foot pain.

Novel 5-point 18-FDG-PET/CT visual scoring system for assessing treatment response in patients with oesophageal or gastro-oesophageal junction carcinoma.

INTRODUCTION: The purpose of this study was to investigate the prognostic utility and reproducibility of a qualitative 5-point 18-fluorodeoxyglucose (FDG)-PET primary visual score (PVS) in patients with oesophageal and gastro-oesophageal junction (GOJ) cancer. METHODS: This was a retrospective review of patients with histologically proven oesophageal or GOJ cancer who received curative intent therapy. Clinical, pathological and imaging data were extracted from electronic medical records. Patients were required to have pre-treatment and post-treatment FDG-PET scans, that were evaluated with a 5-point primary visual score (prePVS, postPVS). The changes in PVS (ΔPVS) were correlated with progression-free survival and overall survival. Interobserver variability was assessed using Cohen's Kappa intraclass correlation and agreement. RESULTS: Sixty-seven patients were retrospectively identified. Two (3%), 36 (54%) and 29 (43%) of the patients had stage I, II and III disease respectively. Twenty-five (37%) patients had squamous cell carcinoma. Thirty-seven (55%) patients proceeded onto surgical resection. postPVS was associated with both PFS (P = 0.013) and OS (P = 0.0002). ΔPVS predicted for PFS (P = 0.002) and OS (P = 0.0003). When thresholds of response were considered, agreement was 80.6% (K = 0.78) and 74.6% (K = 0.69) for postPVS and ΔPVS respectively. CONCLUSION: Qualitative assessment of oesophageal and GOJ cancers utilising FDG-PET is reproducible and may be able to prognosticate outcomes in patients undergoing treatment. Prospective validation is required.

High negative predictive value of 68Ga PSMA PET-CT for local lymph node metastases in high risk primary prostate cancer with histopathological correlation.

BACKGROUND: Current guidelines highlight the importance of accurate staging in the management and prognostication of high risk primary prostate cancer. Conventional radiologic imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Despite promising results, there is limited published data on the diagnostic accuracy of PSMA PET-CT to assess local nodal metastases prior to radical prostatectomy. This study aims to assess the diagnostic efficacy of 68Ga PSMA PET-CT in local lymph node staging of high risk primary prostate cancer when compared to histopathological findings following radical prostatectomy with pelvic lymph node dissection. METHODS: We retrospectively analysed consecutive patients with high risk primary prostate cancer referred by urologists for primary staging PSMA PET-CT using a 68Ga-labeled PSMA ligand, Glu-NH-CO-NHLys-(Ahx)-[HBEDD-CC], from October 2015 to October 2017. The scans of patients who underwent radical prostatectomy with pelvic lymph node dissection were interpreted by the consensus reading of two experienced nuclear medicine physicians blinded to clinical and histopathological data. The contemporaneous records of the referring urologists were retrospectively reviewed for noteworthy unexpected PET findings that altered their personal preference for surgical management. RESULTS: Seventy-one patients were recruited and analysed. PSMA PET-CT showed findings compatible with local disease in 47 patients (66.2%), lymph node metastases in 10 patients (14.1%) and distant metastases in 14 patients (19.7%). Twenty-eight patients (twenty-seven of whom had local disease only) underwent surgery yielding 214 lymph nodes, all of which were negative on histopathological analysis. On a node-based analysis, 213 of 214 lymph nodes were accurately identified as negative for disease with a negative predictive value of 100%. 11 patients had unexpected PET findings contemporaneously documented by urologists to alter their preference for surgical management. CONCLUSIONS: PSMA PET-CT appears to have a high negative predictive value for local lymph node metastases in high risk primary prostate cancer when compared to histopathological findings following radical prostatectomy with pelvic lymph node dissection.

Serial imaging using [18F]Fluorodeoxyglucose positron emission tomography and histopathologic assessment in predicting survival in a population of surgically resectable distal oesophageal and gastric adenocarcinoma following neoadjuvant therapy.

BACKGROUND AND OBJECTIVES: We retrospectively evaluated the value of PET/CT in predicting survival and histopathological tumour-response in patients with distal oesophageal and gastric adenocarcinoma following neoadjuvant treatment. METHODS: Twenty-one patients with resectable distal oesophageal adenocarcinoma and 14 with gastric adenocarcinoma between January 2002 and December 2011, who had undergone serial PET before and after neoadjuvant therapy followed by surgery, were enrolled. Maximum standard uptake value (SUVmax) and metabolic tumour volume were measured and correlated with tumour regression grade and survival. RESULTS: Histopathological tumour response (PR) is a stronger predictor of overall and disease-free survival compared to metabolic response. ∆%SUVmax ≥70% was the only PET metric that predicted PR (82.4% sensitivity, 61.5% specificity, p = 0.047). Histopathological non-responders had a higher risk of death (HR 8.461, p = 0.001) and recurrence (HR 6.385, p = 0.002) and similarly in metabolic non-responders for death (HR 2.956, p = 0.063) and recurrence (HR 3.614, p = 0.028). Ordinalised ∆%SUVmax showed a predictive trend for OS and DFS, but failed to achieve statistical significance. CONCLUSIONS: PR was a stronger predictor of survival than metabolic response. ∆%SUVmax ≥70% was the best biomarker on PET that predicted PR and survival in oesophageal and gastric adenocarcinoma. Ordinalisation of ∆%SUVmax was not helpful in predicting primary outcomes.

Detection of synchronous gastric schwannoma on FDG PET/CT aided by discordant metabolic response.

This is a case of an unsuspected synchronous gastric schwannoma demonstrating increased F-FDG accumulation on PET/CT in a 65-year-old female patient diagnosed with non-Hodgkin lymphoma on the basis of different metabolic activity to other sites of disease at staging and discordant metabolic response to therapy. The gastric schwannoma was confirmed by histopathology and immunohistochemistry after surgical resection. This case adds to the limited literature on FDG-avid gastric schwannoma and highlights the importance of investigating differential metabolic activity and response on serial PET/CT imaging.

Metabolic information on staging FDG-PET-CT as a prognostic tool in the evaluation of 97 patients with gastric cancer.

BACKGROUND AND OBJECTIVE: Gastric cancer remains a leading cause of malignancy-related mortality. Many patients with locally advanced disease succumb despite peri-operative chemotherapy and the survival benefit of chemotherapy for advanced disease is modest, suggesting that current staging is imperfect. The role of fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging of gastric cancer remains to be determined. This study aimed to determine, and compare with computerized tomography (CT), the association between FDG-PET uptake in the primary tumour and regional lymph nodes, and overall survival in patients with all stage gastric cancer. METHODS: Patients with histologically confirmed gastric cancer (any stage) who, at diagnosis, had received a staging FDG-PET-CT at our institution between 2006 and 2011 were included. Records were retrospectively analysed. Patients with >50 % of tumour above the gastro-oesophageal junction or an active second malignancy were excluded. RESULTS: 97 patients were included in the analysis. Surgery with curative intent was performed in 68 patients. In univariate analysis, an association with overall survival was seen in patients who had FDG-PET-positive primary tumours (hazard ratio (HR) for death 3.33, 95 % confidence interval (95 % CI) 1.63-6.80, p = 0.001). FDG-PET lymph node positive (vs node negativity) was associated with inferior overall survival (HR 8.66, 95 % CI 4.59-16.37, p < 0.0001), and remained an independent predictor in the multivariate analysis. In contrast, positive lymphadenopathy identified on CT was not associated with overall survival (HR 1.34, 95 % CI 0.79-2.29, p = 0.82). CONCLUSION: FDG-PET-positive tumours are associated with an inferior overall survival. In contrast to CT, FDG-PET-positive lymphadenopathy is associated with a decreased overall survival.

FDG PET in the evaluation of phaeochromocytoma: a correlative study with MIBG scintigraphy and Ki-67 proliferative index.

To compare 123I-metaiodobenzylguanidine (MIBG) and [Fluorine-18]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in 22 patients with phaeochromocytomas and paragangliomas (PGL) retrospectively and to evaluate the correlation between FDG uptake and Ki-67 proliferative index. Fourteen of 17 (82%) patients at initial diagnosis had positive FDG uptake, more intensely in PGL. Eleven of 12 (92%) patients had positive MIBG uptake. PET and MIBG scintigraphy were concordant in 10 patients, discordant in 6. Combined results yielded no false negative findings and are complementary. Neither maximum standardised uptake value nor visual scores on MIBG correlated with Ki-67.

Diagnostic and staging impact of radiotherapy planning FDG-PET-CT in non-small-cell lung cancer.

BACKGROUND AND PURPOSE: To evaluate whether FDG-PET performed for radiotherapy (RT) planning can detect disease progression, compared with staging PET. MATERIALS AND METHODS: Twenty-six patients with newly-diagnosed non-small-cell lung cancer underwent planning PET-CT for curative RT within 8 weeks (mean: 33±14days) of staging PET-CT. Progressive disease (PD) was defined as >25% increase in tumour size (transaxial) or volume, as delineated by SUV threshold of 2.5, or new sites (SUV>2.5). RESULTS: The planning PET detected PD in 16 patients (61%), compared to four patients (15%) by CT component of PET-CT. The mean scan interval was longer in patients with progression: 40±12days, compared to 22±11days without progression. Planning PET detected PD in 13/17 (76%), 12/14 (86%) and 7/7 patients if the interval was ≥4, 5 and 6 weeks, respectively, compared with 3/9 patients if interval <4 weeks. Planning PET detected PD in primary metabolic volume in seven patients, 20 new nodal sites in 12 new nodal stations and nine patients, five extra-nodal sites in five patients. This resulted in upstaging in nine patients (35%): stage IIIA in three, IIIB in three and IV in three. CONCLUSIONS: RT-planning FDG-PET can provide incremental diagnostic information and may impact on staging in a significant number of patients.