68 Ga-DOTATATE PET/CT in the Initial Diagnosis of Patients With Clinical, Imaging, and/or Biochemical Suspicion of a Neuroendocrine Tumor.

PURPOSE: The aim of this study was to assess the yield of somatostatin receptor PET in patients with clinical, imaging, and/or biochemical suspicion of a neuroendocrine tumor (NET). PATIENTS AND METHODS: This analysis includes patients referred for the initial diagnosis of an unconfirmed NET, as part of a prospective, single-arm registry study (NCT03873870) assessing the utility of 68 Ga-DOTATATE PET/CT in the management of NETs. Inclusion criteria to this cohort consisted of elevated biomarkers and/or clinical presentation suspicious for a NET, with negative conventional cross-sectional imaging, or presence of a lesion suspicious for a NET on conventional imaging, not amenable for biopsy. Patients with histological confirmation of a NET were excluded. RESULTS: There were 220 patients included between April 2019 and March 2022 with a mean age ± SD of 59.5 ± 16.1 years with biochemical, morphological, and/or clinical suspicion of a NET. Overall, 132/220 patients (60%) had a positive 68 Ga-DOTATATE PET/CT. 68 Ga-DOTATATE PET/CT confirmed a type 2 somatostatin receptor overexpressing tumor in 123/171 (71.9%) of patients with a radiographically suspicious abnormality. The positivity rate for pancreatic, small bowel/mesenteric, adrenal, and other sites was 78/96 (81.2%), 38/57 (66.7%), 7/7 (100%), and 1/11 (9.1%), respectively. 68 Ga-DOTATATE PET/CT was positive in 9/49 (18.4%) of those with a biochemical and/or clinical suspicion of a NET. CONCLUSIONS: 68 Ga-DOTATATE PET/CT is positive in nearly 3 of 4 patients with morphological suspicion of a NET, with the highest yield in those with pancreatic and small bowel or mesenteric masses, and in approximately 1 of 6 patients with biochemical and/or clinical suspicion of a NET.

[18F]FDG PET/CT in the Initial Staging and Restaging of Soft-Tissue or Bone Sarcoma in Patients with Negative or Equivocal Findings for Metastases or Limited Recurrence on Conventional Work-up: Results of a Prospective Multicenter Registry.

The purpose of this study was to determine the impact of [18F]FDG PET/CT on the initial staging, restaging, clinical management, and outcomes of patients with soft-tissue and bone sarcomas. Methods: This single-arm, prospective multicenter registry enrolled 304 patients with 320 [18F]FDG PET/CT scans (November 2018 to October 2021). Eligibility included the initial staging of a grade 2 or higher or ungradable soft-tissue or bone sarcoma, with negative or equivocal findings for nodal or distant metastases on conventional imaging before curative-intent therapy, or restaging of patients with a history of treated sarcoma with a suspicion or confirmation of local recurrence or limited metastatic disease who were being considered for curative-intent or salvage therapy. The presence of local recurrence or metastases on [18F]FDG PET/CT was recorded. Clinical management after [18F]FDG PET/CT compared with pre-[18F]FDG PET/CT planned management and quantitative metabolic tumor parameters (SUVmax, metabolic tumor volume, total lesion glycolysis) were correlated with the outcome data for 171 patients. Results: At the initial staging, [18F]FDG PET/CT detected metastases in 17 of 105 patients (16.2%) with no metastases on conventional work-up and confirmed metastases in 44 of 92 patients (47.8%) with equivocal findings for metastases. At the time of restaging, [18F]FDG PET/CT detected local recurrence in 37 of 123 patients (30.1%) and distant metastases in 71 of 123 patients (57.7%). Overall, the change in treatment intent and treatment type was recorded in 64 of 171 cases (37.4%) and 56 of 171 cases (32.8%), respectively. The presence of metastases on [18F]FDG PET/CT was associated with shorter progression-free survival at the initial staging (P = 0.04) and shorter overall survival at the time of recurrence (P = 0.002). All quantitative metabolic tumor parameters correlated with progression-free survival and overall survival. Conclusion: [18F]FDG PET/CT frequently detects additional sites of disease compared with conventional imaging in patients with sarcomas that were being considered for curative-intent or salvage therapy. This increased detection impacts the clinical management in a third of patients referred for initial staging or presumed limited recurrence after primary therapy. The presence of metastases on [18F]FDG PET/CT is associated with poorer outcomes.

18F-FET-PET imaging in high-grade gliomas and brain metastases: a systematic review and meta-analysis.

PURPOSE: To provide a summary of the diagnostic performance of 18F-FET-PET in the management of patients with high-grade brain gliomas or metastases from extracranial primary malignancies. METHODS: MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases were searched for studies that reported on diagnostic test parameters in radiotherapy planning, response assessment, and tumour recurrence/treatment-related changes differentiation. Radiomic studies were excluded. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool and the GRADE approach. A bivariate, random-effects model was used to produce summary estimates of sensitivity and specificity. RESULTS: Twenty-six studies with a total of 1206 patients/lesions were included in the analysis. For radiotherapy planning of glioma, the pooled proportion of patients from 3 studies with 18F-FET uptake extending beyond the 20 mm margin from the gadolinium enhancement on standard MRI was 39% (95% CI, 10-73%). In 3 studies, 18F-FET-PET was also shown to be predictive of early responders to treatment, whereas MRI failed to show any prognostic value. For the differentiation of glioma recurrence from treatment-related changes, the pooled sensitivity and specificity of TBRmax 1.9-2.3 from 6 studies were 91% (95% CI, 74-97%) and 84% (95% CI, 69-93%), respectively. The respective values for brain metastases from 4 studies were 82% (95% CI, 74-88%) and 82% (95% CI, 74-88%) using TBRmax 2.15-3.11. CONCLUSION: While 18F-FET shows promise as a complementary modality to standard-of-care MRI for the management of primary and metastatic brain malignancies, further validation with standardized image interpretation methods in well-designed prospective studies are warranted.

MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases.

The blood-brain barrier (BBB) is an important factor limiting the effectiveness of central nervous system (CNS) therapeutics. MR-guided focused ultrasound (MRgFUS) is a noninvasive, spatially precise technology that enhances drug delivery across a temporarily permeable BBB. However, despite promising preclinical data, successful drug delivery has yet to be proven in human patients. In this study, we provide primary evidence of enhanced brain penetration of trastuzumab with MRgFUS in patients with Her2-positive breast cancer and brain metastases (NCT03714243). Four patients with progressive intracranial disease and stable systemic disease were enrolled in a single-arm open-labeled study. Twenty treatments combining transcranial MRgFUS with concomitant standard-of-care intravenous trastuzumab-based therapies were administered as outpatient procedures. The primary outcome was safety, and there were no treatment-related serious adverse events. The efficacy of trastuzumab delivery was demonstrated using 111In-BzDTPA-NLS-trastuzumab SPECT imaging. The standardized uptake value ratio (SUVR) of MRgFUS-treated lesions increased, on average, by 101 ± 71%, compared to −18 ± 26% in control lesions. MRgFUS enhanced drug uptake in 87 ± 17% of sonicated voxels (>20% increase in SUVR), with up to a 450% voxel-wise increase detected. Control lesions had 8 ± 8% voxels with >20% increase in SUVR. With treatment, unidimensional tumor measurements decreased by 19 ± 12%. This study provides first-in-human evidence of noninvasive, spatially targeted monoclonal antibody delivery across the BBB using MRgFUS, demonstrating the promise of this technology for a broad range of CNS diseases.

The impact of synchronous malignancies on survival in patients with early stage curable non-small-cell lung cancer.

BACKGROUND: To determine if synchronous extrapulmonary malignancies in early stage lung cancer impact survival and cost of care in the current era of improved therapies and diagnostics. METHODS: Patients with stage I and II lung cancer were identified from the Ontario Cancer Registry and prognostic factors were obtained from provincial health administrative databases. Synchronous extrapulmonary malignancies were defined as those detected within 6 months from diagnosis of the lung primary. Survival was calculated using the Kaplan-Meier method and examined based on a 6-month landmark time point. The log-rank test and Cox proportional hazards regression was used to examine the effect of synchronous primaries on survival, univariately and after adjusting for prognostic factors. Cost of care was calculated by summing fees for all provincially funded services over 3 years. RESULTS: In a cohort of 6890 patients, those with synchronous malignancy had a HR of 1.32 (p = 0.026) for death in stage I patients, adjusted for other factors, while no association was found for stage II patients (HR=1.00, p = 0.99). 18F-FDG-PET/CT up to 6 months prior to lung cancer diagnosis had a HR of 0.84 (p = 0.003) for death adjusted for other factors. 3-year costs of care for these patients were $79,540 versus $54,520 in those without a synchronous malignancy (p<0.001). CONCLUSION: Extrapulmonary malignancies in stage I lung cancer patients may negatively impact survival with no such association for stage II patients. 18F-FDG-PET/CT performed before lung cancer diagnosis is associated with better survival. Cost of care is higher in patients with synchronous malignancies.

Effect of PET/CT on the Management and Outcomes of Participants with Hodgkin and Aggressive Non-Hodgkin Lymphoma: A Multicenter Registry.

Purpose To determine the relationship of PET/CT staging to the management and outcomes of participants with apparent limited-stage (LS) Hodgkin lymphoma (HL) or aggressive non-HL (ANHL) treated with curative intent. Materials and Methods This prospective multicenter registry included 850 participants (467 men and 383 women; median age, 54.1 years) from nine centers who had LS HL or ANHL on the basis of clinical data and CT, or with equivocal CT for advanced stage, who were considered for curative-intent first-line therapy. Participants were recruited between May 1, 2013, and December 31, 2015. Pre-PET/CT treatment plan was compared with treatment provided. Survival and second-line therapy initiation were compared with an historical control pool staged by using CT alone. Administrative data sources were used to control for baseline characteristics. Outcomes were assessed by using adjusted Cox proportional hazards regression and propensity score matching. Results PET/CT helped to upstage 150 of 850 participants (17.6%). There was a change in planned therapy in 224 of 580 (38.6%) of participants after PET/CT. There was a lower 1-year mortality for participants with ANHL in the PET/CT versus CT cohort (hazard ratio, 0.63; 95% confidence interval: 0.40, 1.0; P < .05) and for those with LS at PET/CT compared with those with LS at CT (hazard ratio, 0.40; 95% confidence interval: 0.21, 0.74; P = .004). For participants with HL, no 1-year outcome difference was found (P = .16). Conclusion PET/CT helped to upstage approximately 18% of participants and planned management was frequently altered. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had significantly better survival compared with participants whose treatment was guided by CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Scott in this issue.

Comparison of 18F-FDG-PET/CT and 18F-FDG-PET/MR imaging in oncology: a systematic review.

OBJECTIVE: The aim of this study was to systematically review the literature to evaluate the clinical performance of integrated 18F-FDG PET/MR as compared with 18F-FDG PET/CT in oncologic imaging. METHODS: The literature was searched using MEDLINE and EMBASE via OVID. Studies comparing the diagnostic accuracy of integrated 18F-FDG PET/MR and 18F-FDG PET/CT in the diagnosis, staging/restaging, assessment of treatment response, or evaluation of metastasis in patients with suspected or diagnosed cancers were deemed eligible for inclusion. Risk of bias and applicability concerns were assessed using the QUADAS-2 tool. RESULTS: Twenty studies met the inclusion criteria. The overall quality of the studies was rated favorably with bias or applicability concerns in a few studies. Our review suggests that 18F-FDG PET/MR performs comparably to 18F-FDG PET/CT in the detection of local lymph node and distant metastases and superiorly in determining the local extent of tumor. SUV obtained from 18F-FDG PET/MR correlated highly with those obtained from 18F-FDG PET/CT. CONCLUSIONS: Based on early evidence, 18F-FDG PET/MR is comparable to 18F-FDG PET/CT in the clinical scenarios examined in this review. The potential for interchangeability of 18F-FDG PET/MR with 18F-FDG PET/CT will vary by indication and the body site that is being imaged, with PET scanners integrated with MRI predicted to provide greater detail in the evaluation of local tumor extent, where 18F-FDG PET/CT can be limited.

Imaging Biomarkers in Immunotherapy.

Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer.

18F-FDG-PET/CT in the Staging and Management of Melanoma: A Prospective Multicenter Ontario PET Registry Study.

PURPOSE: The Ontario PET Registry was established to provide evidence on the clinical impact of 18-FDG-PET/CT (PET) imaging to inform Ontario Health Insurance Plan funding decisions. The melanoma registry assessed the use of melanoma staging by PET in advanced or high-risk melanoma as a useful adjunct to clinical and standard radiologic investigation. MATERIALS AND METHODS: Between January 2011 and July 2013, approximately 319 consecutive patients with potentially resectable localized high-risk melanoma or recurrent disease under consideration for metastasectomy underwent PET imaging for staging across 9 institutions in Ontario. Pre-PET stage information was provided by the referring clinician and compared with post-PET stage. The ability of PET to reclassify disease from M0 to M1 status was assessed. The registry data were then linked to provincial administrative databases using deidentified health insurance numbers to determine PET stage-based rates of systemic therapy, radiotherapy, and surgery. RESULTS: There was a significant increase in stage to M1 status after PET in 56 of 319 patients (17.6%) (P < 0.0001). There was no significant relationship between upstaging with PET and the proportion of patients receiving radiation therapy (P = 0.066) or systemic therapy (P = 0.072). There was a significant relationship between upstaging with PET and the proportion of patients undergoing surgical resection of metastases distant to the primary melanoma site (P = 0.034). CONCLUSIONS: This prospective, multicenter registry of high-risk or advanced melanoma found that PET significantly upstages patients and impacts surgical management.

Diagnostic accuracy of dynamic gadoxetic-acid-enhanced MRI and PET/CT compared in patients with liver metastases from neuroendocrine neoplasms.

PURPOSE: To evaluate the diagnostic accuracy of dynamic-contrast-enhanced (DCE) MRI in comparison to both (18)F-FDG- and (68)Ga-DOTATATE-PET/CT in patients with liver metastases of neuroendocrine neoplasms (NEN). MATERIALS AND METHODS: Thirty-two patients with hepatic metastases from NEN were examined both in DCE-MRI and positron emission tomography/computed tomography (PET/CT), using either (18)F-fluorodeoxyglucose ((18)F-FDG) or (68)Ga-DOTATATE as tracer. DCE-MRI was performed at 3 Tesla with Gd-EOB-DTPA acquiring 48 slices every 2.2 s for 5 min. Three regions of interest (ROIs) representing liver background and liver metastases were defined in fat-saturated T1w three-dimensional GRE MRI sequences in the hepatobiliary phase. Corresponding ROIs were then defined in the DCE-MRI- and in the PET/CT-dataset. Area under the curve (AUC) was calculated for the differentiation between metastases and liver background for DCE-MRI and PET-CT parameters. RESULTS: AUC was very high for SUVmean (mean standardized uptake value) derived from (68)Ga-DOTATATE- (AUC = 0.966), and (18)F-FDG-PET/CT (AUC = 0.989). For DCE-MRI parameters, arterial flow fraction and intracellular uptake fraction showed the highest AUCs (AUC = 0.826, AUC = 0.819, respectively). The combination of those two had an AUC of 0.949. The combination of DCE-MRI and PET-CT parameters resulted in the highest AUC. CONCLUSION: Both PET/CT parameters and DCE-MRI perfusion parameters show a high diagnostic accuracy in the distinction between liver metastases and liver tissue. Our data suggest that both modalities provide complementary information.

18F-FDG PET/CT for the prediction and detection of local recurrence after radiofrequency ablation of malignant lung lesions.

UNLABELLED: The utility of (18)F-FDG PET/CT for response assessment in malignant lung tumors treated with radiofrequency ablation (RFA) and for the detection and prediction of local recurrence was investigated. METHODS: Between December 17, 2003, and April 9, 2008, 68 consecutive patients (mean age, 68 y) with 94 pulmonary lesions, including metastases (n = 38) and primary lung cancers (n = 44), underwent RFA. Because of inadequate imaging follow-up in 12 patients, only 82 lesions were analyzed (CT scans, n = 82; (18)F-FDG PET/CT scans, n = 62). The median follow-up was 25 mo (range, 12-66 mo). A baseline study was defined as (18)F-FDG PET/CT performed no more than 3 mo before RFA. The first postablation scan was defined as PET/CT performed between 1 and 4 mo after RFA; additional follow-up studies were obtained in some cases between 6 and 12 mo after RFA. The unidimensional maximum diameter of the lesion was recorded on a pretherapy diagnostic CT scan or on the CT component of a pretherapy (18)F-FDG PET/CT scan, whichever was obtained most recently, using lung windows. Maximum standardized uptake values (SUVs) were recorded for all lesions imaged by (18)F-FDG PET/CT. (18)F-FDG uptake patterns on post-RFA scans were classified as favorable or unfavorable. Survival and recurrence probabilities were estimated using the Kaplan-Meier method. Uni- and multivariate analyses were also performed. RESULTS: Before RFA, factors predicting greater local recurrence-free survival included initial lesion size less than 3 cm (P = 0.01) and SUV less than 8 (P = 0.02), although the latter was not an independent predictor in multivariate analysis. Treated metastases recurred less often than treated primary lung cancers (P = 0.03). Important post-RFA factors that related to reduced recurrence-free survival included an unfavorable uptake pattern (P < 0.01), post-RFA SUV (P < 0.01), and an increase in SUV over time after ablation (P = 0.05). CONCLUSION: (18)F-FDG PET/CT parameters on both preablation and postablation scans may predict local recurrence in patients treated with RFA for lung metastases and primary lung cancers.

Intensity of FDG uptake is not everything: synchronous liposarcoma and fibrous dysplasia in the same patient on FDG PET-CT imaging.

A growing number of studies have demonstrated the usefulness of FDG PET-CT in the preoperative assessment of soft tissue sarcomas. We report a case of a patient with a known low-grade liposarcoma demonstrating only mild hypermetabolism on a FDG PET-CT study. An incidental osseous lesion was found in the distal tibia of the same extremity during the initial workup. This tibial lesion was significantly more intense on the FDG PET-CT study than the primary sarcoma. Further investigation showed this to be an unexpected benign fibrous dysplasia. We present this case as an example of the discrepancy of FDG activity, which may exist between truly malignant and benign lesions that may arise from soft tissue and osseous structures. A benign process should remain in the differential diagnosis for hypermetabolic lesions when evaluating a case of known malignancy, especially when the degree of uptake of that lesion differs significantly from that of the primary lesion.

The appearance of Mazabraud's syndrome on 18F-FDG PET/CT.

Mazabraud's syndrome is a rare disorder, the main characteristics of which are fibrous dysplasia of bone associated with intramuscular myxomas. The metabolic characteristics of intramuscular myxomas, associated with fibrous dysplasia, have not previously been described with 18F-FDG-PET. Our case demonstrates that there is low, but not insignificant uptake associated with these intramuscular myxomas, with a standardized uptake value (SUV) range between 1.3 and 2.6. As such, this entity merits consideration when evaluating hypoattenuating intramuscular masses, particularly in the context of fibrous dysplasia.

The "pirate sign" in fibrous dysplasia.

Fibrous dysplasia commonly involves the skull in both its monostotic and polyostotic variants. We present two cases of fibrous dysplasia involving the sphenoid wing, which were strikingly similar in their bone scan appearance. Both patients demonstrated intense increased uptake of Tc-99m MDP in a pattern reminding us of a "pirate wearing an eyepatch." We propose that this characteristic appearance of fibrous dysplasia of the sphenoid wing be called the "pirate sign." A review of the literature revealed several other pathologic conditions that have been reported to involve the sphenoid bone and should be considered in the differential diagnosis of abnormal bone tracer uptake in this region.