FDG PET in Evaluation of Patients With Fever of Unknown Origin: AJR Expert Panel Narrative Review.

Fever of unknown origin (FUO) is a diagnostic challenge, with its cause remaining undiagnosed in approximately half of patients. Nuclear medicine tests typically are performed after a negative or inconclusive initial workup. Gallium-67 citrate and labeled leukocytes were previous mainstays of radionuclide imaging for FUO, although they had limited diagnostic performance. FDG PET/CT has subsequently emerged as the nuclear medicine imaging test of choice, supported by a growing volume of evidence. A positive FDG PET/CT result contributes useful information by identifying potential causes of fever, localizing sites for further evaluation, and guiding further management; a negative result contributes useful information by excluding focal disease as the cause of fever and predicts a favorable prognosis. In 2021, CMS rescinded a prior national noncoverage determination for FDG PET for infection and inflammation, leading to increasing national utilization of FDG PET/CT for FUO workup. This article reviews the current status of the role of FDG PET/CT in the evaluation of patients with FUO. The literature reporting the diagnostic performance and yield of FDG PET/CT in FUO workup is summarized, with comparison with historically used nuclear medicine tests included. Attention is also given to the test's clinical impact; protocol, cost, and radiation considerations; and application in children.

Death attitudes among older Asian and Pacific Islander Americans: The role of religiosity, spirituality, and psychosocial health factors.

With the growth of older minorities in the United States, more attention is needed on what the experience of dying means in this population. Previous research has overlooked older Asians and Pacific Islanders. This study examined death attitudes among 69 diverse nursing home residents in Hawai'i. Results from correlational and regression analyses showed religiosity and spirituality had significantly distinct impacts on death attitudes and psychosocial health. Ethnicity and religious/spiritual affiliation had significant effects on study outcomes, even between minority subgroups. These findings highlight the importance of exploring the differential impact of religious/spiritual and cultural factors on death attitudes among older minorities.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

Increased Risk of Radioiodine Treatment Failure Associated with Graves Disease Refractory to Methimazole.

OBJECTIVE: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment. METHODS: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure. RESULTS: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002). CONCLUSION: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.

Postbiopsy Pigmentation is Prognostic in Head and Neck Melanoma.

PURPOSE: To assess postbiopsy pigmentation (PBP) as a prognostic feature in patients with cutaneous head and neck (H&N) melanoma. METHODS: Retrospective review of patients undergoing sentinel lymph node biopsy (SLNB) for H&N melanoma (1998-2018). PBP was defined as visible remaining pigment at the scar or biopsy site that was documented on physical exam by both a medical oncologist and a surgeon at initial consultation. Variables associated with disease-free survival (DFS) and overall survival (OS) were analyzed using multivariable Cox proportional hazards models. RESULTS: Among 300 patients, 34.3% (n = 103) had PBP and 44.7% (n = 134) had microscopic residual disease on final pathology after wide local excision. Prognostic factors associated with DFS included advanced age, tumor depth, ulceration, PBP, and positive SLNB (p < 0.05). Patients with PBP fared worse than their counterparts without PBP in 5-year DFS [44.1% (31.1-56.3%) vs. 73.0% (64.1-80.0%); p < 0.001] and 5-year OS [65.0% (50.0-76.6%) vs. 83.6% (75.7-89.2%); p = 0.005]. After multivariable adjustment, PBP remained associated with shorter DFS [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.01-2.93; p = 0.047], but was not prognostic of OS. CONCLUSIONS: In patients with H&N melanoma, PBP is associated with significantly shorter DFS. Patients with PBP may warrant greater consideration for SLNB and closer postoperative surveillance.

Frequency and implications of occipital and posterior auricular sentinel lymph nodes in scalp melanoma.

BACKGROUND: Patients with scalp melanoma have poor oncologic outcomes compared with those with other cutaneous sites. Sentinel lymph node (SLN) biopsy provides prognostic information but is challenging in the head and neck. We explore the anatomic distribution of scalp melanoma and describe the most common sites of SLN drainage and of SLN metastatic disease. METHODS: Retrospective review of scalp melanoma patients who underwent SLN biopsy. Melanoma location was classified as frontal, coronal apex, coronal temporal, or posterior scalp. SLN location was classified by lymph node level and region. RESULTS: We identified 128 patients with scalp melanoma. The most common primary tumor location was the posterior scalp (43%) and the most frequent SLN drainage site was the level 2 lymph node basin (48%). Total 31 patients (24%) had metastatic disease in an SLN. Scalp SLNs, classified as being in the posterior auricular or occipital region, were localized in 26% of patients. For patients in which a scalp SLN was identified, 30% had a positive scalp SLN (n = 10). CONCLUSIONS: Scalp SLNs are frequent drainage sites for scalp melanoma and, when found, have a 30% chance of harboring metastatic disease. Surgeons, radiologists, and pathologists should be vigilant in identifying, removing, and analyzing scalp SLNs.

SPECT/CT Adds Distinct Lymph Node Basins and Influences Radiologic Findings and Surgical Approach for Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

BACKGROUND: Planar lymphoscintigraphy (PL) has a lower detection rate of sentinel lymph nodes (SLNs) in head and neck melanoma compared with other sites. We assessed situations when single-photon emission computed tomography/computed tomography (SPECT/CT) identified nodes not seen by PL. We also evaluated the impact of SPECT/CT on surgical approach and oncologic outcomes. METHODS: Patients who underwent SLN biopsy (SLNB) for head and neck melanoma with PL and SPECT/CT between November 2011 and December 2016 were included. Surgeons and radiologists completed a real-time survey inquiring about the utility of SPECT/CT. Patients were divided into two groups: patients with nodal basins identified by both PL and SPECT/CT ('PL + SPECT/CT'), and patients in whom SPECT/CT identified additional nodal basins not seen on PL ('SPECT/CT only'). Patient demographics and long-term outcomes including follow-up duration, recurrence, and survival are described. RESULTS: In the PL + SPECT/CT group, 73 (61.9%) patients were included and 45 (38.1%) patients were included in the SPECT/CT-only group. SPECT/CT added 51 basins to those seen on PL, primarily in the supraclavicular region (43.1%). Eighteen patients had positive node(s) in the PL + SPECT/CT group compared with two patients in the SPECT/CT-only group. Surgeons reported that 81% of the time, SPECT/CT influenced the location of incision for SLNB. CONCLUSIONS: SPECT/CT influences the location of incision and contributes most to identification of nodes in the supraclavicular region. It also detects additional SLN basins when compared with PL. Further studies are necessary to determine when these additional basins require sampling.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. METHODS: This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. RESULTS: Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p = 0.050) but the groups did not differ in gender (p = 0.447), Breslow thickness (p = 0.744), or total number of SLNs identified (p = 0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95 % confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95 % CI 1.24-10.4) were associated with a positive SLN. CONCLUSION: The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy.

AIMS: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). METHODS: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. RESULTS: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. CONCLUSION: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients.

The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis.

PURPOSE: This study was performed to evaluate the efficacy of (177)Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). METHODS: Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of "neuroendocrine", "(177)Lu" and "prognosis". All published studies of neuroendocrine tumours treated with (177)Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. RESULTS: Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8% with a pooled effect of 29% [95% confidence interval (CI) 24-34%]. Disease control rates ranged from 71.8 to 100%. The random-effects model showed an average disease control rate of 81% (95% CI 71-91%). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5% with a pooled effect of 23% (95% CI 11-38%). Disease control rates ranged from 73.9 to 89.1%. The random-effects model showed an average disease control rate of 82% (95% CI 71-91%). CONCLUSION: (177)Lu-labelled PRRT is an effective treatment option for patients with inoperable or metastatic NETs.

Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events.

Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression.

Novel Imaging of Prostate Cancer with MRI, MRI/US, and PET.

Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PET on the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer.

Molecular and Anatomic Imaging of Neuroendocrine Tumors.

Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we review the role of SSTR PET scan in the management of NETs, including the indications for the scan, pitfalls in interpretation, and imaging selection criteria for peptide receptor radionuclide therapy. We also discuss the complementary role of fluorodeoxyglucose PET particularly for patients with high-grade disease.

18F-fluorodeoxyglucose positron emission tomography/ computed tomography in the diagnosis of a rare mycotic aneurysm of the thoracic aorta in a patient with fever of unknown origin.

Fever of unknown origin (FUO) is a condition with high mortality that often presents a diagnostic challenge to clinicians. We present the case of a patient with FUO who was discovered to have a rare mycotic aneurysm of the thoracic aorta by 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Mycotic aneurysm, also known as an infected aneurysm, is a highly lethal condition due to the risk of sepsis and aneurysmal rupture. While unusual to present in this manner, it is of utmost importance to promptly recognize a mycotic aneurysm as a potential diagnosis because initiation of treatment is critical in reversing the natural history of the disease.

Multiple Sclerosis, Cannabis Use, and Clinical Disability: A Preliminary [18F]-Fluorodeoxyglucose Positron Emission Tomography Study.

Introduction: Long-term consequences of medicinal cannabis use in people with multiple sclerosis (PwMS) are unknown. This study investigated whether PwMS using cannabis had lower resting brain glucose uptake (GU) and worse clinical test results compared with nonusers. Methods: Sixteen PwMS, eight users, underwent clinical testing followed by [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography imaging. Results: Users had lower cognitive function test scores, but performed similarly on the other clinical evaluations. Accounting for disease duration, resting brain GU was similar between the groups. Conclusions: Lower cognitive function was not associated with resting brain GU. Cognitive dysfunction may be a contraindication or consequence of cannabis use in PwMS.

Interim Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Pathologic Response to Preoperative Chemoradiotherapy and Prognosis in Patients With Locally Advanced Rectal Cancer.

INTRODUCTION: The goal of the present study was to investigate the predictive and prognostic values of interim fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters for the prediction of a complete pathologic response (pCR) in patients with locally advanced rectal cancer (LARC) who had received preoperative chemoradiotherapy (PCRT). PATIENTS AND METHODS: A total 103 patients with LARC were included in the present study. All the patients were evaluated by 18F FDG PET/CT before and after 45 Gy of radiotherapy with concurrent oral capecitabine chemotherapy. The quantitative, volumetric parameters and their percentage of change (Δ%) were used to predict the pCR and calculate the overall survival (OS). The predictive value for a pCR of 18F FDG PET/CT cutoff values were determined by receiver operating characteristic analysis. The prognostic significance was assessed using Kaplan-Meier analysis. RESULTS: A pCR occurred in 22 patients (21.4%). Univariate and multivariate analyses demonstrated that the post-PCRT maximum standardized uptake value (SUVmax2) and change in the SUVmax (ΔSUVmax) as significant factors for the prediction of pCR, with a sensitivity of 68.2% and specificity of 87.7% and sensitivity of 90.9% and specificity of 80.3%, respectively. Kaplan-Meier analysis showed that a low SUVmax2 (< 2.5) and high ΔSUVmax (≥ 62.2%) were potent predictors for OS. CONCLUSION: The present study has shown the capability of interim 18F FDG PET/CT parameters to predict the achievement of pCR after PCRT in patients with LARC. Of the parameters, SUVmax2 and ΔSUVmax were potent predictors for pCR and well associated with OS.

Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma.

PURPOSE: Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on (18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy. MATERIALS AND METHODS: Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax. RESULTS: The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23-189.42, P=0.002). CONCLUSION: Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.

Frequency based gating: An alternative, conformal, approach to 4D PET data utilization.

PURPOSE: Respiratory gating is a strategy for overcoming image degradation caused by patient motion in Positron Emission Tomography (PET) imaging. Traditional methods for sorting data, namely, phase-based gating or amplitude-based gating, come with an inherent trade-off between resolution improvements and added noise present in the subjugated data. If the goal of motion correction in PET is realigned from creating 4D images that attempt to mimic nongated images, towards ideal utilization of the information available, then new paths for data management emerge. In this work, the authors examine the application of a method in a new class of frequency based data subjugation algorithms, termed gating +. This strategy utilizes data driven information to locally adapt signal to its optimal segregation, thereby creating a new approach to 4D data utilization PET. METHODS: 189 (18)F-fluorodeoxyglucose (FDG) PET scans were acquired at a single bed position centered on the thorax region. 4D gated image sets were reconstructed using data driven gating. The gating+ signal optimization algorithm, previously presented in small animal PET images and simulations, was used to segregate data in frequency space to generate optimized 4D images in the population-the first application and analysis of gating+ in human PET scans. The nongated, phase gated, and gating+ representations of the data were compared using FDG uptake analysis in the identified lesions and noise measurements from background regions. RESULTS: Optimized processing required less than 1 min per scan on a standard PC (plus standard reconstruction time), and yielded entire 4D optimized volumes plus motion maps. Optimized scans had noise characteristics similar to nongated images, yet also contained much of the resolution and motion information found in the gated images. The average SUVmax increase in the lesion sample between gated/nongated and gating+/nongated (±SD in population) was 35.8% ± 34.6% and 28.6% ± 27.9%, respectively. The average percent standard deviation (%SD ± SD in population) in liver volumes of interest (VOIs) across the sample for the nongated, gated, and gating+ scans was 6.7% ± 2.4%, 13.6% ± 3.3%, and 7.1% ± 2.5%, respectively. In all cases, the noise in the gating+ liver VOIs was closer to the nongated measurements than to the gated. CONCLUSIONS: The gating+ algorithm introduces the notion of conforming 4D data segregation to the local information and statistics that support it. By segregating data in frequency space, the authors are able to generate low noise motion information rich image sets, derived solely from selective use of raw data. Their work shows that the gating+ algorithm can be robustly applied in populations, and across varying qualities of motion and scans statistics, and be integrated as part of a fully automated motion correction workflow. Furthermore, the idea of smart signal utilization underpins a new concept of low risk or even risk-free motion correction application in PET.