Prostate specific membrane antigen (PSMA) avid nonprostatic benign and malignant disease: a pictorial review.

Prostate specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is revolutionising the management of prostate cancer (PC) in primary staging and assessment of biochemical recurrence (BCR) through its higher diagnostic accuracy compared to both conventional imaging and previously available PET radiopharmaceuticals. PSMA is a transmembrane glycoprotein, highly expressed in prostate cancer, with its extracellular domain the target for PSMA PET radiopharmaceuticals. However, PSMA expression is not prostate specific and resultant PSMA uptake on PET-CT is not restricted to pathologies arising from the prostate gland. The increasing use of PSMA PET-CT has revealed PSMA uptake in a variety of non-prostatic benign and malignant diseases, which adds complexity to PET-CT interpretation and subsequent clinical management. This pictorial review will provide a thorough knowledge and understanding of the comprehensive range of PSMA avid non-prostatic benign and malignant diseases demonstrable on PSMA PET-CT, whilst highlighting the complimentary nature of other imaging modalities.

Multiple staging investigations may not change management in patients with high-grade dysplasia or early esophageal adenocarcinoma.

The clinical value of multiple staging investigations for high-grade dysplasia or early adenocarcinoma of the esophagus is unclear. A single-center prospective cohort of patients treated for early esophageal cancer between 2000 and 2019 was analyzed. This coincided with a transition period from esophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice. Patients were staged with computed tomography (CT), endoscopic ultrasound (EUS) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography(PET)/CT. The aim of this study was to assess their accuracy and impact on clinical management. 297 patients with high-grade dysplasia or early adenocarcinoma were included (endoscopic therapy/EMR n = 184; esophagectomy n = 113 [of which a 'combined' group had surgery preceded by endoscopic therapy n = 23]). Staging accuracy was low (accurate staging EMR: CT 40.1%, EUS 29.6%, FDG-PET/CT 11.0%; Esophagectomy: CT 43.3%, EUS 59.7%, FDG-PET/CT 29.6%; Combined: CT 28.6%, EUS46.2%, FDG-PET/CT 30.0%). Staging inaccuracies across all groups that could have changed management by missing T2 disease were CT 12%, EUS 12% and FDG-PET/CT 1.6%. The sensitivity of all techniques for detecting nodal disease was low (CT 12.5%, EUS 12.5%, FDG-PET/CT0.0%). Overall, FDG-PET/CT and EUS changed decision-making in only 3.2% of patients with an early cancer on CT and low-risk histology. The accuracy of staging with EUS, CT and FDG-PET/CT in patients with high-grade dysplasia or early adenocarcinoma of the esophagus is low. EUS and FDG-PET/CT added relevant staging information over standard CT in very few cases, and therefore, these investigations should be used selectively. Factors predicting the need for esophagectomy are predominantly obtained from EMR histology rather than staging investigations.

The frequency of change in five-point scale score with a Bayesian penalised likelihood PET reconstruction algorithm on interim FDG PET-CT and its potential implications for therapy decisions in Hodgkin's lymphoma.

AIM: To assess the effect of a Bayesian penalised likelihood (BPL) reconstruction algorithm on the five-point scale (5-PS) score, response categorisation, and potential implications for therapy decisions after interim 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) (iPET-CT) to guide treatment in classical Hodgkin's lymphoma (HL). MATERIALS AND METHODS: The present study included new patients with HL undergoing iPET-CT from 2014-2019 after two cycles of doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine (ABVD). Two reporters categorised response using the 5-PS and measured maximum standardised uptake values (SUVmax) of the most avid tumour residuum, mediastinal blood pool, and normal liver with ordered subset expected maximisation (OSEM) and BPL reconstructions. RESULTS: Eighty-one iPET-CT examinations were reviewed. Compared with OSEM, BPL increased the 5-PS score by a single score in 18/81 (22.2%) patients. The frequency of potential treatment intensification by changing a score of 3-4 was 13.6% (11/81) and represented 25% (11/44) of patients with a score of 3 on OSEM. All 11 patients remained in remission without a change in therapy (mean 63 months) except one who required second-line treatment for refractory disease. Median SUVmax of tumour residuum was significantly higher with BPL compared with OSEM (2.7 versus 2.4, p<<0.0001), whilst liver SUVmax was significantly lower for both reporters (up to 6.6%, p<0.0001). CONCLUSION: BPL PET reconstruction increased the 5-PS score on iPET-CT in 22% of HL patients and can potentially result in unnecessary treatment escalation in over half of these patients.

Multi-observer concordance and accuracy of the British Thoracic Society scale and other visual assessment qualitative criteria for solid pulmonary nodule assessment using FDG PET-CT.

AIM: To compare the interobserver reliability and diagnostic accuracy of the British Thoracic Society (BTS) scale and other visual assessment criteria in the context of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) evaluation of solid pulmonary nodules (SPNs). MATERIALS AND METHODS: Fifty patients who underwent FDG PET-CT for assessment of a SPN were identified. Seven reporters with varied experience at four centres graded FDG uptake visually using the British Thoracic Society (BTS) four-point scale. Five reporters also scored SPNs according to three- and five-point visual assessment scales and using semi-quantitative assessment (maximum standardised uptake value [SUVmax]). Interobserver reliability was assessed with the intra-class correlation coefficient (ICC) and weighted Cohen's kappa (κ). Diagnostic performance was evaluated by receiver operator characteristic (ROC) analysis. RESULTS: Good interobserver reliability was demonstrated with the BTS scale (ICC=0.78, 95% confidence interval [CI]: 0.69-0.85) and five-point scale (ICC=0.78, 95 CI 0.68-0.86), whilst the three-point scale demonstrated moderate reliability (ICC=0.70, 95% CI: 0.59-0.80). Almost perfect agreement was achieved between two consultants (κ=0.85), and substantial agreement between two other consultants (κ=0.78) using the BTS scale. ROC curves for the BTS and five-point scales demonstrated equivalent accuracy (BTS area under the ROC curve [AUC]=0.768; five-point AUC=0.768). SUVmax was no more accurate compared to the BTS scale (SUVmax AUC=0.794; BTS AUC=0.768, p=0.43). CONCLUSIONS: The BTS scale can be applied reliably by reporters with varied levels of PET-CT reporting experience, across different centres and has a diagnostic performance that is not surpassed by alternative scales.

Correction: Long-term clinical outcomes in a cohort of patients with solitary plasmacytoma treated in the modern era.

[This corrects the article DOI: 10.1371/journal.pone.0219857.].

The effect of a novel Bayesian penalised likelihood PET reconstruction algorithm on the assessment of malignancy risk in solitary pulmonary nodules according to the British Thoracic Society guidelines.

PURPOSE: British Thoracic Society (BTS) guidelines advocate using FDG PET-CT with the Herder model to estimate malignancy risk in solitary pulmonary nodules (SPNs). Qualitative and semi-quantitative assessment of SPN uptake is based upon analysis of Ordered Subset Expected Maximisation (OSEM) PET images. Our aim was to assess the effect of a Bayesian Penalised Likelihood (BPL) PET reconstruction on the assessment of SPN FDG uptake and estimation of malignancy risk (Herder score). METHODS: Subjects with SPNs who underwent FDG PET-CT between 2014-2017, with histological confirmation of malignancy or histological/imaging follow-up confirmation of benignity were included. Two blinded readers independently classified SPN uptake on both OSEM and BPL (BTS score; 1 = none; 2 = ≤ mediastinal blood pool (MBP); 3 = >MBP but ≤ 2x liver; 4 = >2x liver), with resultant calculation of the Herder score (%) for both reconstructions. RESULTS: 97 subjects with 75 (77%) malignant SPNs were included. BPL increased the BTS score in 25 (26%) SPNs; 9 SPNs (7 malignant) increased from BTS score 2 to 3, 16 (13 malignant) from BTS score 3 to 4, with a mean Herder score increase of 18 ±â€¯22%. The mean Herder score for all SPNs with BPL was higher than OSEM (73 ±â€¯29 vs 68 ±â€¯32%, p = 0.001). There was no difference in Herder model diagnostic performance between BPL and OSEM, with similar areas under the curve (0.84 vs 0.83, p = 0.39). CONCLUSION: BPL increases the Herder score in 26% of SPNs compared to OSEM but does not alter the diagnostic performance of the Herder model.

Long-term clinical outcomes in a cohort of patients with solitary plasmacytoma treated in the modern era.

BACKGROUND: The risk of recurrence of solitary plasmacytoma (SP)/progression to MM is well established, but patient, imaging and treatment factors influencing risk of progression require further evaluation. METHODS: This is a retrospective analysis of 66 SP patients (23 UK, 43 Brazil) diagnosed 1989-2016. Patient baseline characteristics were recorded. The incidence of progression to MM was calculated, including biochemical and imaging findings and the treatment modality received. Survival estimates were determined by Kaplan-Meier analyses. RESULTS: With a median follow-up of 53.6 months the 5 year overall survival (OS) was 90.7% (95%CI 79-96%). The median progression free survival (PFS) from diagnosis was 61 months. Cumulative incidence of progression to MM was 49.9% at 5 years (95% CI 35.6-62.6%) and was significantly higher with bone plasmacytoma (47.2%, 95%CI 31.9-61.1%), than an extramedullary location (8.3%, 95%CI 0.4-32.3%, Gray test p = 0.0095)). The majority of patients with solitary bony plasmacytoma (SBP) received radiotherapy (RT) (51/53, 96.2%) whereas most extramedullary cases were treated with surgical resection (7/13, 53.8%). A small proportion of SBP patients received additional upfront chemotherapy, with 5/6 in remission after a median follow-up (FU) of 10 years. The diagnostic yield of surveillance functional FU imaging without other indications of relapse/progression was low. The positive predictive value of functional FU imaging was high but with a low negative predictive value, especially in cases of suspected relapse/progression. CONCLUSION: Our data suggests functional imaging should be used if clinical suspicion of relapse/progression, rather than a routine surveillance tool, and upfront adjuvant chemotherapy is worthy of prospective evaluation.

No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer.

Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.

Assessment of outcomes with delayed (18)F-FDG PET-CT response assessment in head and neck squamous cell carcinoma.

OBJECTIVE: To assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC). METHODS: 105 patients who underwent a baseline and response assessment (18)F-FDG PET-CT scan between 2008 and April 2013 were identified. (18)F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes. RESULTS: 79 of 105 (75%) (18)F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (n = 10) or positive (n = 9). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%). CONCLUSION: (18)F-FDG PET-CT 4 months post treatment has a very high NPV. A positive (18)F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV. ADVANCES IN KNOWLEDGE: Response assessment (18)F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.

Delayed response assessment with FDG-PET-CT following (chemo) radiotherapy for locally advanced head and neck squamous cell carcinoma.

AIMS: To analyse the diagnostic accuracy of delayed response assessment 2-[¹8F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography-computed tomography (PET-CT) following (chemo)radiation for locally advanced head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: Forty-four consecutive patients who underwent a baseline and response assessment using FDG PET-CT for HNSCC following (chemo)radiation between August 2008 and April 2011 were identified retrospectively. Clinicopathological findings and serial clinical follow-up provided the reference standard. RESULTS: Median follow-up was 14 months (range 5-43 months). Response assessment FDG PET-CT was performed at 16.8 weeks (inter-quartile range 15.8-18.6 weeks). Thirty-one out of 44 (70%) response assessment examinations showed a complete metabolic response. Seven out of 40 (18%) assessable primary tumours were positive. Eight out of 41 (20%) patients with pre-treatment nodal disease had equivocal or positive FDG uptake at response assessment. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for primary disease and nodal disease were 100, 89, 43, 100, and 100%, and 92, 63, and 100%, respectively. Seven patients had residual FDG-negative soft tissue detectable on the unenhanced CT component of the response assessment images; all remained disease free after clinical observation. Distant metastases were detected on response assessment FDG PET-CT in four out of the 44 patients (10%). CONCLUSION: The diagnostic accuracy of response assessment with FDG PET-CT performed at approximately 16 weeks post-(chemo)radiotherapy is good. The very high NPV of a complete metabolic response can be used to guide management decisions. Although the PPV is limited for local residual disease, FDG PET-CT is a powerful screening tool for the detection of interim metastatic disease.