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Background: Fluorine-18-fluorodeoxyglucose ([18F]-FDG) Positron Emission Tomography/ Computed Tomography (PET/CT) is a useful tool that assesses glucose metabolism in tumor cells to help guide the management of cancer patients. However, the clinical relevance of glucose metabolism in healthy tissues, including hematopoietic tissues such as the spleen, has been potentially overlooked. Recent studies suggested that spleen glucose metabolism could improve the management of different cancers., Study Eligibility Criteria: Overall, the current literature includes 1,157 patients, with a wide range of tumor types. The prognostic and/or predictive value of spleen metabolism has been demonstrated in a broad spectrum of therapies, including surgery and systemic cancer therapies. Most of these studies showed that high spleen glucose metabolism at baseline is associated with a poor outcome while treatment-induce change in spleen glucose metabolism is a multi-faceted surrogate of cancer- related inflammation, which correlates with immunosuppressive tumor microenvironment as well as with immune activation., Conclusion: In this systematic review, we seek to unravel the prognostic/predictive significance of spleen glucose metabolism on [18F]-FDG PET/CT and discuss how it could potentially guide cancer patient management in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Malignant struma ovarii (MSO) is a rare malignant ovarian tumor, histologically identical to differentiated thyroid cancers. Given the rarity of this disease, there are no treatment guidelines, and the place of imaging for response assessment remains controversial. We report a metabolic response assessed by F-FDG PET/CT in a 71-year-old woman with radioiodine-refractory metastatic MSO treated by targeted therapies (first line with lenvatinib and second line with pazopanib). This case of exceptional response also highlights the usefulness of F-FDG PET/CT for therapeutic assessment of targeted drugs in such a rare clinical entity of malignant MSO.

Objective: To determine FDG-PET biomarkers associated with long-term benefit (LTB) and survival in advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy., Methods: In this multicenter study, we retrospectively analyzed advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥ 50%, who underwent FDG-PET/CT before first-line pembrolizumab, received from August 2017 to September 2019. Parameters extracted were SUVmax, SUVmean, TMTV (total metabolic tumor volume) and TLG (total lesion glycolysis). LTB was defined as objective (complete or partial) response or stable disease as best overall response, maintained for ≥ 12 months. A multivariate prediction model was developed using logistic regression for LTB and Cox models for progression-free survival (PFS) and overall survival (OS)., Results: On the 63 eligible patients, with a median follow-up of 13.4 (range, 1.5-29.1) months, 17 (27%) had LTB. Median PFS and OS were 7.7 months (95%CI 5.0-10.5) and 12.1 months (95%CI 8.6-15.6). In multivariate analyses, high TMTV (> 84cm 3 ) and high tumor SUVmean (> 10.1) remained independent factors for predicting LTB (OR 0.2; p = 0.03 and OR 3.7; p = 0.04) and PFS (HR 2.2; p = 0.02 and HR 0.5; p = 0.045). High TMTV was significantly associated with poor OS (HR 3.1; p = 0.03). No association was observed between tumor SUVmax or TLG and clinical outcomes., Conclusions: In patients with advanced NSCLC and PD-L1 TPS ≥ 50%, baseline low TMTV and high tumor SUVmean correlate with survival and LTB from upfront pembrolizumab. Beyond the initial staging, FDG-PET/CT scan could provide relevant biomarkers associated with clinical outcomes that should be taken into account when considering first-line treatment options.

Background CT and fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET/CT performances following immune therapy are not well known in patients with relapsed or refractory Hodgkin lymphoma (RRHL). Purpose To compare CT and PET/CT for prognostic value of early response evaluation following nivolumab therapy. Materials and Methods This retrospective study included patients from 34 institutions who underwent early imaging response evaluation from July 2013 to April 2017. Three experienced readers classified imaging response by using Cheson et al and 2016 Lymphoma Response to Immunomodulatory Therapy Criteria as follows: complete (metabolic) response, partial (metabolic) response, stable disease or no metabolic response, or progressive (metabolic) disease. Primary CT and PET assessments were performed at a median of 2.0 months (interquartile range, 1.7-3.7 months) after nivolumab initiation. Kaplan-Meier analysis was used to determine the relationship of primary CT and PET assessment response categories to overall survival (OS). Agreements between primary and secondary imaging assessments were assessed by using κ analysis. Results A total of 45 patients (median age, 37 years; range, 18-77 years; 25 men) underwent a primary assessment using CT and PET/CT; 36 patients also underwent a subsequent assessment. Eleven patients (24%) died after a median follow-up of 21.2 months. CT and PET response categories were associated with OS ( P = .03 for primary CT assessment; P = .02 for primary PET assessment). There was no pseudoprogression at primary CT and PET assessments. At the primary assessment, response categories by using CT were reclassified by using PET in 44% (20 of 45) of patients. Among these, 55% (11 of 20) were reclassified to complete metabolic response (complete metabolic response rate: 29% [13 of 45 patients] vs complete response rate: 4% [two of 45 patients]), with a 2-year OS probability of 100%. At the secondary assessment, complete response rate using CT increased to 17% (six of 36 patients), hence a better agreement with PET (κ = 0.78; P < .001). Conclusion Early CT and PET/CT at a median of 2 months after initiation of nivolumab predicted overall survival in relapsed or refractory Hodgkin lymphoma. Early PET detected additional patients with complete metabolic response. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Scott and Wang in this issue.

The majority of glomus tumors are localized to cutaneous sites and are benign. However, extracutaneous malignant glomus tumors have been reported and are aggressive. Here, we report a case of a 45-year-old man who presented severe dysphagia, diagnosed with malignant glomus tumor of the esophagus. F-FDG PET/CT played a decisive role in several phases of the patient management offering previously unknown accuracy. It was first performed in the initial staging of local tumor extent before surgery. A year and a half after, F-FDG PET/CT helped to detect recurrence and, finally, was performed for response evaluation of several systemic therapies.

Monoclonal antibodies (mAbs) against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, are associated with high response rates in patients with relapsed or refractory classic Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using 18 F-FDG PET/CT may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a masked, centralized review, 3 independent radiologists classified PET/CT scans obtained at a median of 2.0 mo (interquartile range, 1.7-3.7 mo) after nivolumab initiation using existing criteria (i.e., 2014 Lugano classification and 2016 LYRIC). Patients were classified according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). Because the OS of patients with NMR and PMR was similar, they were grouped together. OS was estimated using the Kaplan-Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 mo. The classification was identical between Lugano and LYRIC because all 16 progression events classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC classified patients as CMR in 13 cases (29%), PMD in 16 (36%), NMR in 4 (9%), and PMR in 12 (27%). The 2-y OS probability was significantly different in patients with PMD (0.53; 95% confidence interval [95%CI], 0.32-0.87), NMR or PMR (0.80; 95%CI, 0.63-1.00), and CMR (1.00; 95%CI, 1.00-1.00) in the overall population ( P = 0.02, 45 patients), as well as according to a landmark analysis at 3 mo ( P = 0.05, 32 patients). Conclusion: In relapsed or refractory HL patients treated with anti-PD-1 mAbs, the first early PET/CT assessment using either Lugano or LYRIC predicted OS and allowed early risk stratification, suggesting that PET/CT might be used to develop risk-adapted strategies., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo 18 F-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti-programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. 18 F-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective response at any time during the anti-PD1 treatment were classified as responders. Results: Sixteen relapsed or refractory classic HL patients were included. The median age was 39 y (age range, 19-69 y). The median previous lines of therapy was 6 (range, 3-13). The mean follow-up was 22.6 mo. Nine of 16 patients (56%) achieved an objective response. Two deaths occurred due to progressive disease at 7 mo. 18 F-FDG PET/CT detected all responders at 3 mo and reclassified best overall response in 5 patients compared with CT alone. A decrease in tumor metabolism and volume (SUV mean , metabolic tumor volume) and increase in healthy splenic metabolism at 3 mo were observed in responders (area under the curve > 0.85, P < 0.04). Five of 16 patients (31%) displayed new imaging patterns related to anti-PD1; we observed 2 transient progressions consistent with indeterminate response according to the LYRIC (2016) (IR2b at 14 mo and IR3 at 18 mo) and 3 patients with new lesions associated with immune-related adverse events. Conclusion: Three-month 18 F-FDG PET/CT scans detected HL patients responding to anti-PD1. New patterns were encountered in 31% of patients, emphasizing the need for further evaluation in larger series and close collaboration between imaging and oncology specialists on a per-patient basis., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Fusariosis is an opportunistic infection, caused by a filamentous fungus, found on plants and in soil. The treatment of disseminated pattern, seen in immunocompromised patients with severe neutropenia, is difficult because of antifungal therapy resistance. A 12-year-old girl, who was diagnosed with B-cell acute lymphoblastic leukemia, developed multiple widespread skin papules and subcutaneous nodules, at day 20 of consolidation therapy. Histological examination with cultures of skin tissue revealed Fusarium species. Treatment was started with intravenous liposomal amphotericin B and voriconazole. To assess treatment response, FDG PET/CT performed at baseline, at 2 and 4 months, showed a partial response.

Simple Summary: Radiation therapy has long been reported to affect tumors distal to the site of irradiation, in what is known as the abscopal effect; the synergy of radiation with immune-oncological agents has also been studied and exploited for greater anti-cancer effect. We believe that PET/CT imaging can offer insight into the mechanism of this synergy and thereby optimize the dosing and timing as well as monitoring the response to and adverse effects of radiation therapy in tandem with immunotherapy. Herein, we offer a commentary to better integrate PET/CT into recently released joint guidelines, to exploit radiation and immunotherapy synergy. [18F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer. Furthermore, it holds the potential to offer insight into the synergic effect of combining radiation therapy (RT) with immuno-oncological (IO) agents. This is achieved by evaluating treatment responses both at the RT and distant tumor sites, thereby encompassing the phenomenon known as the abscopal effect. In this context, PET/CT can play an important role in establishing timelines for RT/IO administration and monitoring responses, including novel patterns such as hyperprogression, oligoprogression, and pseudoprogression, as well as immune-related adverse events. In this commentary, we explore the incremental value of PET/CT to enhance the combination of RT with IO in precision therapy for solid tumors, by offering supplementary insights to recently released joint guidelines. [ABSTRACT FROM AUTHOR]

18356138 3 Uematsu T., Kasami M., Yuen S. Comparison of FDG PET and MRI for Evaluating the Tumor Extent of Breast Cancer and the Impact of FDG PET on the Systemic Staging and Prognosis of Patients Who Are Candidates for Breast-Conserving Therapy. Breast cancer is the most common cancer in women around the world and the fifth leading cause of cancer-related death [[1]]. [18F]FDG PET/CT is a promising theranostic tool for first-line immunotherapy [[10]] in patients with metastatic triple-negative breast cancer because increased tumor metabolism is associated with poorer prognosis and response to treatment. Among these, [18F]Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography ([18F]FDG PET/CT) imaging currently plays a crucial role in determining the extent of the disease [[2]] and in ensuring that the treatment is effective [[4]]. [Extracted from the article]

Purpose: We evaluated whether biomarkers on baseline [18F]-FDG PET/CT are associated with recurrence after surgery in patients with invasive breast cancer of no special type (NST). Methods: In this retrospective single-center study, we included consecutive patients with non-metastatic breast cancer of NST who underwent [18F]-FDG PET/CT before treatment, including surgery, between 2011 and 2016. Clinicopathological data were collected. Tumor SUVmax, total metabolic tumor volume (TMTV), and spleen- and bone marrow-to-liver SUVmax ratios (SLR, BLR) were measured from the PET images. Cut-off values were determined using predictiveness curves to predict 5-year recurrence-free survival (5y-RFS). A multivariable prediction model was developed using Cox regression. The association with stromal tumor-infiltrating lymphocytes (TILs) levels (low if <50%) was studied by logistic regression. Results: Three hundred and three women were eligible, including 93 (31%) with triple-negative breast carcinoma. After a median follow-up of 6.2 years, 56 and 35 patients experienced recurrence and death, respectively. The 5y-RFS rate was 86%. In multivariable analyses, high TMTV (>20 cm3) and high SLR (>0.76) were associated with shorter 5y-RFS (HR 2.4, 95%CI 1.3–4.5, and HR 1.9, 95%CI 1.0–3.6). In logistic regression, high SLR was the only independent factor associated with low stromal TILs (OR 2.8, 95%CI 1.4–5.7). Conclusion: High total metabolic tumor volume and high spleen glucose metabolism on baseline [18F]-FDG PET/CT were associated with poor 5y-RFS after surgical resection in patients with breast cancer of NST. Spleen metabolism was inversely correlated with stromal TILs and might be a surrogate for an immunosuppressive tumor microenvironment. [ABSTRACT FROM AUTHOR]

Dostarlimab is an immune checkpoint inhibitor (ICI) targeting the Programmed-Death-1 (PD-1) co-receptor, recently approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) as a novel therapy for recurrent or advanced endometrial cancer. We report the case of a 64-year-old woman, experiencing vaginal recurrence with microsatellite instability high/hypermutated of a FIGO stage IA grade 2 endometrial endometrioid adenocarcinoma. She received preoperative chemotherapy with four cycles of carboplatin plus paclitaxel, with stable disease on pelvic magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). Dostarlimab (500 mg intravenously every 3 weeks) was then introduced. The subsequent evaluation after three perfusions demonstrated a complete metabolic response on 18F-FDG PET/CT according to immunotherapy-modified PET response criteria in solid tumors (imPERCIST) criteria, then confirmed by MRI according to immune response evaluation criteria in solid tumors (iRECIST). This clinical description suggests that 18F-FDG PET/CT might take place among available tools for guiding the preoperative management for recurrent endometrial cancer patients receiving dostarlimab immunotherapy that should be further explored through clinical trials. [ABSTRACT FROM AUTHOR]

Early detection of immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) is crucial, particularly when these are likely to mimic tumor progression, as well as sarcoid-like reactions. Here, we report the case of a 68-year woman, with a history of four primary cutaneous melanomas (thickest lesion with BRAF mutation removed from the left axilla 2 years before), who was diagnosed with BRAF V600E-mutant metastatic melanoma and treated by ICI targeting the PD-1 receptor. Follow-up whole-body positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose ([18F]-FDG) was performed at 15 months, and FDG-avid subcutaneous nodules on her legs were detected. A biopsy from a lesion on her right leg was obtained, and histology strongly suggested erythema nodosum. Given the isolated nature of these lesions, the normal serum Angiotensin-Converting Enzyme and the context of ICI, an immune-related sarcoid-like reaction was retained as the most likely diagnosis. Recent literature in immune-oncology suggests that erythema nodosum could be directly related to ICI(s). Although erythema nodosum is a rare occurrence with imaging features overlapping with malignancy, it should be considered in the differential diagnosis of suspicious in-transit metastasis, especially when the patient is treated with ICIs and when lesions follow a bilateral distribution. In conclusion, nuclear medicine physicians should keep in mind this irAE when interpreting PET/CT scans in clinical practice in order to avoid false-positive findings. [ABSTRACT FROM AUTHOR]

Worldwide deployment of COVID-19 vaccines is in progress. Recent immune activation following vaccination can sometimes be seen in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT). As previously evidenced, FDG-avid axillary lymph node(s) are common in patients receiving vaccines against SARS-CoV-2, influenza virus, or human papillomavirus, and reflect a regional immune response. In addition, these findings may also be accompanied by an increased spleen glucose metabolism after the COVID-19 vaccine, which captures a systemic immune response. Hence, we provide here a clinical example demonstrating that immune response could be associated with increased glucose metabolism in lymphoid organs such as lymph nodes and the spleen, which are critical modulators of T cell immunity. We believe that it is of paramount importance that nuclear physicians should be able to recognize clinical and imaging features of such immune responses upon vaccination for COVID-19 and beyond. [ABSTRACT FROM AUTHOR]