90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial.

Background Transarterial chemoembolization (TACE) is the recommended treatment for intermediate hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer guidelines. Prospective uncontrolled studies suggest that yttrium 90 (90Y) transarterial radioembolization (TARE) is a safe and effective alternative. Purpose To compare the efficacy and safety of TARE with TACE for unresectable HCC. Materials and Methods In this single-center prospective randomized controlled trial (TRACE), 90Y glass TARE was compared with doxorubicin drug-eluting bead (DEB) TACE in participants with intermediate-stage HCC, extended to Eastern Cooperative Oncology Group performance status 1 and those with early-stage HCC not eligible for surgery or thermoablation. Participants were recruited between September 2011 and March 2018. The primary end point was time to overall tumor progression (TTP) (Kaplan-Meier analysis) in the intention-to-treat (ITT) and per-protocol (PP) groups. Results At interim analysis, 38 participants (median age, 67 years; IQR, 63-72 years; 33 men) were randomized to the TARE arm and 34 (median age, 68 years; IQR, 61-71 years; 30 men) to the DEB-TACE arm (ITT group). Median TTP was 17.1 months in the TARE arm versus 9.5 months in the DEB-TACE arm (ITT group hazard ratio [HR], 0.36; 95% CI: 0.18, 0.70; P = .002) (PP group, 32 and 34 participants, respectively, in each arm; HR, 0.29; 95% CI: 0.14, 0.60; P < .001). Median overall survival was 30.2 months after TARE and 15.6 months after DEB-TACE (ITT group HR, 0.48; 95% CI: 0.28, 0.82; P = .006). Serious adverse events grade 3 or higher (13 of 33 participants [39%] vs 19 of 36 [53%] after TARE and DEB-TACE, respectively; P = .47) and 30-day mortality (0 of 33 participants [0%] vs three of 36 [8.3%]; P = .24) were similar in the safety groups. At the interim, the HR for the primary end point, TTP, was less than 0.39, meeting the criteria to halt the study. Conclusion With similar safety profile, yttrium 90 radioembolization conferred superior tumor control and survival compared with chemoembolization using drug-eluting beads in selected participants with early or intermediate hepatocellular carcinoma. Clinical trial registration no. NCT01381211 © RSNA, 2022 Online supplemental material is available for this article.

Hemodynamic changes in ALPPS influence liver regeneration and function: results from a prospective study.

BACKGROUND: Excessive increase of portal flow and pressure following extended hepatectomy have been associated to insufficient growth or function of the future liver remnant (FLR), with the risk of post-hepatectomy liver failure (PHLF). We prospectively assess the influence of liver hemodynamics on FLR regeneration and function in Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). METHODS: Twenty-three patients underwent ALPPS; liver hemodynamics were assessed throughout the procedures. Volume and function of the FLR were evaluated by angio-CT and 99mTc-Mebrofenin-scintigraphy. RESULTS: The portal vein flow at the end of stage-1 correlated with the increase of the FLR volume (p = 0.002). Patients with portal vein pressure (PVP) < 20 mmHg and hepatic to portal vein gradients (HVPG) < 15 mmHg at the end of ALPPS-1 showed higher FLR regeneration (76.7% vs. 30.6%, p = 0.04) and function (26.7% vs. -0.13%, p = 0.02). FLR regeneration was inversely correlated with baseline FLR/Total Liver Volume (p = 0.002) and FLR/Body Weight (p = 0.02). No correlation was found between volumes and function (p = 0.13). CONCLUSION: Liver hemodynamic stress at the end of ALPPS-1 influences the increase of the FLR volume and function, which is higher with PVP < 20 and HVPG < 15 mmHg. Liver volume overestimates liver function and could be imprecise to set stage-2 timing.

Guidelines on nuclear medicine imaging in neuroblastoma.

Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials.

BACKGROUND: Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations. RESULTS: The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0-6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response. CONCLUSIONS: Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.

Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy.

OBJECTIVES: To describe the anatomical patterns of prostate cancer (PCa) recurrence after primary therapy and to investigate if patients with low-volume disease have a better prognosis as compared with their counterparts. MATERIALS AND METHODS: Patients eligible for an 18-F choline positron-emission tomography (PET)-computed tomography (CT) were enrolled in a prospective cohort study. Eligible patients had asymptomatic biochemical recurrence after primary PCa treatment and testosterone levels >50 ng/mL. The number of lesions was counted per scan. Patients with isolated local recurrence (LR) or with ≤3 metastases (with or without LR) were considered to have low-volume disease and patients with >3 metastases to have high-volume disease. Descriptive statistics were used to report recurrences. Cox regression analysis was used to investigate the influence of prognostic variables on the time to developing castration-resistant PCa (CRPC). RESULTS: In 208 patients, 625 sites of recurrence were detected in the lymph nodes (N1/M1a: 30%), the bone (18%), the prostate (bed; 11%), viscera (4%), or a combination of any of the previous (37%). In total, 153 patients (74%) had low-volume recurrence and 55 patients (26%) had high-volume recurrence. The 3-year CRPC-free survival rate for the whole cohort was 79% (95% confidence interval 43-55), 88% for low-volume recurrences and 50% for high-volume recurrences (P < 0.001). Longer PSA doubling time at time of recurrence and low-volume disease were associated with a longer time to CRPC. CONCLUSIONS: Three out of four patients with PCa with a 18-F choline PET-CT-detected recurrence have low-volume disease, potentially amenable to local therapy. Patients with low-volume disease have a better prognosis as compared with their counterparts. Lymph node recurrence was the most dominant failure pattern.

MIBG scans in patients with stage 4 neuroblastoma reveal two metastatic patterns, one is associated with MYCN amplification and in MYCN-amplified tumours correlates with a better prognosis.

PURPOSE: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. METHODS: Diagnostic (123)I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: "focal" (clear margins distinguishable from adjacent background) or "diffuse" (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse. RESULTS: Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: "limited-focal" and "extensive-diffuse". The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60% and 70%, respectively) than patients with the other types of metastases (23% and 28%, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01). CONCLUSION: Two metastatic patterns were found: a "limited and focal" pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an "extensive and diffuse" pattern found mainly in patients with MYCNsc neuroblastoma.

Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer.

BACKGROUND: In non-castrate prostate cancer (PCa), the prognostic value of the number of metastases on prostate cancer-specific survival (PCSS) is not well studied. METHODS: We retrospectively analyzed the medical records of 1,206 patients, referred for radiotherapy of the prostate (bed) following diagnosis of PCa. Distant metastases (nodal, skeletal, and/or visceral) developed in 121 patients following curative treatment, of which 80 with complete records were not castrated at time of metastasis. The treatment at time of metastases was androgen deprivation therapy (ADT; n = 22), active surveillance (n = 10) or metastasis-directed therapy (MDT; n = 48). Cox-regression analyses were used to examine the influence of different variables on PCSS. RESULTS: The median follow-up from primary PCa treatment was 6.9 years with a median interval from diagnosis to first metastatic event of 4.1 year (range: 0.2-15 years). The primary site of metastases was limited to lymph nodes (48%), bone (39%), and viscera (1%) or a combination (12%). Median PCSS from diagnosis of noncastrate metastases was 6.6 years (95% confidence interval [CI], 5.6-7.7 years). A longer premetastatic PSA doubling time (DT) (hazard ratio [HR] 0.73; 95% CI: 0.57-0.92), a lower number of metastases at first presentation (HR 1.07; 95% CI: 1.02-1.12) and pattern of metastatic spread (HR 3.6; 95% CI: 1.13-11.8 for extensive vs. minimal) were associated with improved PCSS. CONCLUSION: A longer PSA DT, involvement of nodes or axial skeleton and a lower number of metastases are associated with an improved PCSS in non-castrated patients developing metastases.

Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence (STOMP): study protocol for a randomized phase II trial.

BACKGROUND: Metastases-directed therapy (MDT) with surgery or stereotactic body radiotherapy (SBRT) is emerging as a new treatment option for prostate cancer (PCa) patients with a limited number of metastases (≤3) at recurrence - so called "oligometastases". One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life. However, the lack of a control group, selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies.The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance. METHODS/DESIGN: Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time (≤3 vs. > 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival. DISCUSSION: This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01558427.

Value of magnetic resonance and ¹8FDG PET-CT in predicting tumor response and resectability of primary locally advanced cervical cancer after treatment with intensity-modulated arc therapy: a prospective pathology-matched study.

OBJECTIVE: To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose positron emission tomography computed tomography (¹8FDG PET-CT) in predicting resectability and pathological response of primary locally advanced cervical cancer after neoadjuvant intensity-modulated arc therapy (IMAT) with or without cisplatin (C). METHODS AND MATERIALS: Twenty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVA cervical cancer were treated with IMAT-C followed by extrafascial hysterectomy (EH). All patients received MRI and ¹8FDG PET-CT after IMAT-C. The end points of this study were to: 1. Assess the ability of MRI to predict negative surgical margins (R0). 2. Assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI in predicting the following situation at the EH specimen: "no residual disease or minimal microscopically visible residual tumor." 3. Assess the sensitivity, specificity, PPV, and NPV value of ¹8FDG PET-CT in predicting "no residual viable tumor cells" at the EH specimen. RESULTS: An R0 resection was obtained in all patients. None of the EH specimens contained macroscopically visible tumor. In 13 patients, no viable tumor cells were found and only 14 had residual microscopic disease. Twenty-four of 27 MRIs were able to correctly predict R0 resection. A negative MRI was 100% predictive for the end point "R0 resection." The specificity and NPV of MRI (end point 2) were 74% and 100%, respectively. No sensitivity or PPV could be calculated. The sensitivity, specificity, PPV, and NPV of ¹8FDG PET-CT were 29%, 62%, 44%, and 44%, respectively (end point 3). CONCLUSIONS: A negative MRI after IMAT-C predicts 100% correctly for R0 resection. The role of FDG PET-CT in predicting viable tumor cells at EH specimen is at least debatable.

18F-PSMA-11 Versus 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial.

BACKGROUND: Fluorine-18 (18F)-labelled prostate-specific membrane antigen (PSMA) offers several advantages over gallium-68 (68Ga) in terms of costs, yield, transport/distribution, and image resolution. OBJECTIVE: This trial investigates the new radiotracer 18F-PSMA-11 via a prospective, intraindividual crossover design. The trial was powered for noninferiority of 18F-PSMA-11 over 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) in terms of the number of positive PET scans. Secondary endpoints were as follows: (1) superiority of 18F-PSMA-11 over 68Ga-PSMA-11 with respect to the number of positive PET scans, the total number of suspicious prostate cancer lesions, and the miPSMA expression score of corresponding lesions; (2) correlation of the PET/CT images with available follow-up data for 18F-PSMA-11 and 68Ga-PSMA-11; and (3) assessment of the interobserver variability. DESIGN, SETTING, AND PARTICIPANTS: Prostate cancer patients (primary or biochemical recurrence) were randomised in a double-blind crossover design whereby each patient received both 18F-PSMA-11 and 68Ga-PSMA-11 PET/CT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All scans were reviewed and scored by three independent experienced nuclear physicians following the proposed guideline for the interpretation of PSMA-ligand PET/CT, as described by Eiber et al. RESULTS AND LIMITATIONS: In total, 82 patients were included for scan analyses. The primary endpoint was met: per patient, the proportions of positive scans rated by the three readers were 67%/67%, 65%/65%, and 73%/70% for 18F-PSMA-11/68Ga-PSMA-11 PET/CT. The miPSMA expression score was higher for 18F-PSMA-11 than for 68Ga-PSMA-11 for the reference reader. Follow-up data showed identical estimated sensitivity for both the 18F-PSMA-11 and the 68Ga-PSMA-11 scan (0.92, 0.83, and 0.92 for the three readers). A fair to good agreement among readers (at patient level) was obtained, which was demonstrated by a Light's kappa value of 0.59 for both tracers. CONCLUSIONS: The tracer 18F-PSMA-11 is noninferior to68Ga-PSMA-11. Superiority of 18F-PSMA-11 was limited to the miPSMA expression score, given by the reference reader. Inter-rater agreement was fair to good, and equal for both radiotracers. PATIENT SUMMARY: In this study, we compared two radiotracers: 18F-PSMA-11 and 68Ga-PSMA-11. We proved that 18F-PSMA-11 is not inferior to 68Ga-PSMA-11 for detecting prostate cancer and thus can be used as an alternative. Possible superiority of this tracer should be further investigated in specific subpopulations.

Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Intra-arterial treatment with 9°Y microspheres for hepatocellular carcinoma: 4 years experience at the Ghent University Hospital.

PURPOSE: We report on our experience in terms of eligibility, safety, response and survival for treatment of hepatocellular carcinoma (HCC) with (90)Y microspheres. Secondly, we investigated the urinary excretion of (90)Y following treatment. METHODS: We retrospectively reviewed all HCC patients referred to our department for (90)Y microsphere treatment. We recorded reasons for not proceeding to actual treatment. In case treatment was performed, we assessed the tolerance (Common Terminology Criteria for Adverse Events v3.0, CTCAE v3.0), the response [modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria] and long-term survival (Kaplan-Meier). The urinary excretion was estimated by 12-h urine collections post-injection for analysis in a gamma counter. RESULTS: Forty-three HCC patients were referred for radioembolization. Fourteen patients were excluded, mainly due to unfavourable (99m)Tc-macroaggregated albumin (MAA) distribution. Twenty-nine patients were treated with (90)Y microspheres (TheraSphere, mean activity 2.17 GBq). In four patients severe clinical adverse events were encountered, however only in one case clearly related to the therapy. Twenty patients were assessable by mRECIST: complete response in 15%, partial response in 35%, stable disease in 30% and progression in 20% were observed. A median survival of 12.3 months (95% confidence interval 9.4-15.2) was estimated. Concerning the substudy on urinary excretion, only 0.0025% of the administered activity was excreted in the urine within the first 12 h following TheraSphere. CONCLUSION: Following a strict workup before admitting patients to radioembolization with TheraSphere, we found good clinical tolerance in the vast majority of patients. Radiological response assessment yielded an overall response rate of 50%, when evaluated early following treatment. Urine analysis showed consistently only low activities of (90)Y excreted in the urine.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10-20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918-928, 1985); Schafer and Sorrell (Lancet 353:1253-1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for (131)I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901-906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical (131)I-Lipiodol (Lipiocis®, IBA, Brussels, Belgium) and include the newer medical devices with (90)Y-microspheres. (90)Y is either bound to resin (SIR-Spheres®, Sirtex Medical, Lane Cove, Australia) or embedded in a glass matrix (TheraSphere®, MDS Nordion, Kanata, ON, Canada). Since (90)Y-microspheres are not metabolized, they are not registered as unsealed sources. However, the microspheres are delivered in aqueous solution: radioactive contamination is a concern and microspheres should be handled, like other radiopharmaceuticals, as open sources. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

Bone SPECT/CT in the Evaluation of Painful Total Ankle Replacement: Validation of Localization Scheme and Preliminary Evaluation of Diagnostic Patterns.

PURPOSE: Third-generation total ankle replacement (TAR) is an increasingly popular and effective treatment for end-stage osteoarthritis, yet identifying causes of failure remains challenging. We evaluated integrated bone SPECT/CT in recurrent pain after TAR by validating a standardized reporting scheme, identifying uptake patterns, and assessing diagnostic performance and impact on clinical management. PATIENTS AND METHODS: A total of 24 TARs in 16 patients with persistent or recurrent pain received integrated bone SPECT/CT using diagnostic CT settings. Images were retrospectively reviewed, and a novel localization scheme was validated by assessing interrater agreement. Distinct uptake patterns were identified, and diagnostic test characteristics were estimated. Reference standard consisted of clinical follow-up, laboratory findings, and subsequent procedures, including revision surgery. RESULTS: Standardized scoring of bone SPECT/CT uptake was highly reproducible (intraclass correlation coefficient, 0.79; 95% confidence interval [CI], 0.75-0.82). The final diagnoses were gutter impingement (n = 12), periprosthetic (stress) fracture (n = 5), loosening (n = 5), tarsal arthritis (n = 1), and erysipelas (n = 1). Overall, the diagnostic test characteristics of bone SPECT/CT were as follows: sensitivity of 100% (95% CI, 82%-100%), specificity of 80% (95% CI, 28%-99%), and accuracy of 96% (95% CI, 79%-100%). Gutter impingement, periprosthetic fracture, and loosening were correctly identified in all cases revealing distinct uptake patterns. Importantly, persistent diffuse uptake was frequently observed, warranting cautious interpretation. Bone SPECT/CT impacted clinical management in 86%, with symptomatic improvement in 83% of patients. CONCLUSIONS: Integrated bone SPECT/CT of painful TARs may benefit from standardized localization to reveal distinct uptake patterns representing common complications after TAR. Initial results show highly promising diagnostic value with potentially important impact on clinical management.

99mTc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment with 90Y microspheres.

PURPOSE: 90Y microspheres are used for intra-arterial treatment of liver tumours. In the patient preparation, a hepatic angiogram is performed and all arteries that could transport microspheres from the targeted liver vasculature to extrahepatic organs are blocked. 99mTc-labelled macroaggregated albumin (MAA) is injected intra-arterially to simulate the treatment and whole-body scintigraphy and single photon emission computed tomography (SPECT) of the abdomen are performed. METHODS: Various aspects of lung shunt fraction (LSF) estimation were studied: interobserver and intrapatient variability, influence of scan quality and underlying disease. Secondly, the interobserver variability in reading the MAA SPECT of the abdomen was investigated. We reviewed 90 whole-body scans and 20 SPECT scans performed at our institution. Readers were blinded to each other's findings. Scoring the scan quality was based on the visualization of tracer degradation. RESULTS: The mean difference in LSF between the readers was 1%. In 1 of 23 patients who underwent repeated MAA injections a marked change in LSF was observed. No significant differences in LSF were recorded for primary versus secondary liver tumours. There was a correlation between scan quality and LSF, suggesting that low scan quality leads to overestimation of the LSF. Concordant results in ruling out the presence of extrahepatic tracer deposition were reached in 17 of 20 scans (85%). CONCLUSION: Interobserver and intrapatient variability in LSF calculation was limited. LSF was clearly dependent on scan quality. The underlying disease had no significant impact on the LSF. Interobserver variability for reading the MAA SPECT scans was acceptable.

PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature.

PURPOSE: To give an up-to-date overview of the potential clinical utility of (18)F-labelled choline derivatives for tumour imaging with positron emission tomography. METHODS: A PubMed search for (18)F-labelled choline analogues was performed. Review articles and reference lists were used to supplement the search findings. RESULTS: (18)F-labelled choline analogues have been investigated as oncological PET probes for many types of cancer on the basis of enhanced cell proliferation. To date, studies have focused on the evaluation of prostate cancer. Available studies have provided preliminary results for detecting local and metastatic disease. Experience with (18)F-fluorocholine PET in other tumour types, including brain and liver tumours, is still limited. In the brain, excellent discrimination between tumour and normal tissue can be achieved due to the low physiological uptake of (18)F-fluorocholine. In the liver, in which there is a moderate to high degree of physiological uptake in normal tissue, malignancy discrimination may be more challenging. CONCLUSION: PET/CT with (18)F-fluorocholine can be used to detect (recurrent) local prostate cancer, but seems to have limited value for T (tumour) and N (nodal) staging. In patients presenting with recurrent biochemical prostate cancer, it is a suitable single-step examination with the ability to exclude distant metastases when local salvage treatment is intended. In the brain, high-grade gliomas, metastases and benign lesions can be distinguished on the basis of (18)F-fluorocholine uptake. Moreover, PET imaging is able to differentiate between radiation-induced injury and tumour recurrence. In the liver, (18)F-fluorocholine PET/CT seems promising for the detection of hepatocellular carcinoma.

Nodal Oligorecurrent Prostate Cancer: Anatomic Pattern of Possible Treatment Failure in Relation to Elective Surgical and Radiotherapy Treatment Templates.

BACKGROUND: Patients with biochemical recurrence following primary prostate cancer (PCa) treatment often experience relapse in the lymph nodes (LNs). Both salvage LN dissection (sLND) and elective nodal radiotherapy (ENRT) are potential treatment options. OBJECTIVE: To describe anatomic patterns of nodal oligorecurrent PCa in relation to different surgical and radiotherapy templates. DESIGN, SETTING, AND PARTICIPANTS: Patients with biochemical recurrence following primary PCa treatment were eligible for 18F-choline positron emission tomography/computed tomography (CT). Patients with five or fewer LN recurrences (N1/M1a) were eligible for the current retrospective analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All LN recurrences were mapped on a reference patient CT, as well as different surgical templates (limited to superextended) and an adapted version of the PIVOTAL ENRT template, blinded for the recurrences. Descriptive statistics were used to report recurrences in relation to the different templates and to compare LN coverage between templates. RESULTS AND LIMITATIONS: In total, 158 LN recurrences (N1: 88; M1a: 70) in 82 patients (median age: 67yr; prostate-specific antigen [PSA]: 3.1ng/ml; PSA doubling time of 7.8mo at the time of clinical recurrence) were mapped. In 49% of patients, recurrences were exclusively located in the true pelvis, followed by the common iliac LN (10%), retroperitoneal/inguinal LN (10%), or a combination (31%). There was up to 40% volume overlap between ENRT and the surgical templates. Theoretically, with ENRT more patients are fully covered (p<0.02) and the total number of covered lesions is higher (p<0.001) when compared to all types of sLND, except for superextended sLND, which is comparable to ENRT (patient-level: p=0.6; lesion-level: p=0.09). With 22% of all 158 lesions located outside all templates (N1: 7%; M1a: 15%), at least 31% of all 82 patients would not be salvaged using any of the templates. CONCLUSIONS: More than half of nodal recurrences are located outside the true pelvis. Limited or standard extended sLND is considered insufficient as a salvage treatment approach and is thus not recommended for use. To maximize treatment outcomes for nodal recurrences, ENRT or superextended sLND should be preferred. PATIENT SUMMARY: We compared two possible treatment options, elective nodal radiotherapy and salvage lymph node dissection, for patients with prostate cancer recurrence limited to five or fewer lymph nodes and reported the nodal distrubution. Radiotherapy and surgery cover different areas with possible different outcomes.

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial.

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.