FDG Avidity Research Articles

NCMP-16. A CASE OF WIDESPREAD EXTRACRANIAL METASTASES FROM A GLIOSARCOMA

Abstract BACKGROUND: Glioblastoma (GBM) with sarcomatous features (gliosarcoma) accounts for 2-8% of all glioblastomas1,2, characterized by a biphasic histopathology pattern consisting of glial and sarcomatous components. While GBMs generally do not metastasize outside the central nervous system (CNS), GS has been associated with extracranial metastases in up to 11% of cases3. Case presentation: A 58-year-old right-handed woman with a GBM presented to our institution for a second opinion. She was initially diagnosed 18 months prior and had received radiotherapy with concurrent temozolomide. Her adjuvant temozolomide was discontinued due to rash, and she started on bevacizumab. Her tumor progressed and she sought additional treatment options. On her initial presentation, she was tachycardic with leukocytosis, prompting admission. A chest CT showed thoracic adenopathy, multiple bilateral pulmonary nodules, and a large left malignant pleural effusion. Bronchoscopy revealed spindle cell sarcomatoid neoplasm raising the possibility of metastasis from a CNS primary tumor. Additionally, the patient endorsed development of subacute radicular pain in her bilateral lower extremities as well as weakness. MRI of total spine revealed multilevel osseous and epidural lesions, infiltrating the paraspinal muscles and thickening of cauda roots with concern for leptomeningeal disease. A subsequent PET-CT showed increased FDG avidity in these lesions. Reevaluation of the initial CNS pathology confirmed the presence of mesenchymal/sarcomatous differentiation, consistent with a diagnosis of GS. As confirmed by autopsy, the patient eventually passed away due to widespread and metastatic disease. Discussion: While GBM rarely metastasizes outside the CNS, GBM with sarcomatous features are more likely to exhibit extracranial metastasis. Our patient had widespread involvement, including the lungs, heart, liver, omentum, and bone. Metastasis was thought most likely once EBUS of the lung returned with sarcomatous features. Clinicians should therefore maintain a high suspicion for metastases when dealing with patients diagnosed with GS.

Clinical value of [18F]F-FDG PET/CT in patients with suspected paraneoplastic dermatoses: Diagnostic performance and impact on clinical management

PurposeWe retrospectively evaluate the diagnostic performance of 2-deoxy-2[18F]fuoro-D-glucose([18F]F-FDG) PET/CT and its impact on clinical management in patients with suspected paraneoplastic dermatoses (PD). Materials and MethodsFrom an institutional PET/CT database (2014–2022), we retrospectively analyzed patients who were clinically suspected with PD and underwent [18F]F-FDG PET/CT for screening an underlying malignancy. For all scans, positive mucocutaneous lesions and PET-indicated malignancies were assessed, and the degree of FDG avidity among different dermatoses were quantified. The final diagnoses of dermatoses and neoplasms were based on pathologic results, international diagnostic standard and follow-up. We assessed the recommended and applied therapies before and after [18F]F-FDG PET/CT and noted whether the patient management changed on the basis of the [18F]F-FDG PET/CT results. ResultsWe analyzed 60 patients with 10 types of dermatoses in this study. Finally, 19 of the 60 patients who had both of specific dermatosis and contemporaneous neoplasm were diagnosed with PD. [18F]F-FDG PET could identify the underlying neoplasms in 18/19 (94.7%) PD patients, and led to a change of the management in 9/19 (47.4%) PD patients. In addition, the mucocutaneous manifestations of [18F]F-FDG PET/CT associated with several specific dermatoses were characteristic. ConclusionsThis study highlighted the value of [18F]F-FDG PET/CT as a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients.

Correlation of Post-Treatment Biopsy and Fluorodeoxyglucose PET/CT Findings Following Definitive Chemotherapy and Radiation for Cervical Cancer

Concurrent chemotherapy and external beam radiation with brachytherapy boost is considered standard of care for treatment of locally advanced cervical cancer. Post treatment surveillance fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging is recommended 3-6 months after completion of therapy. Persistent FDG avidity is commonly observed at the cervix on surveillance scans, indeterminate for residual malignancy versus post treatment inflammatory change. To better understand the clinical significance of residual hypermetabolic activity, we performed an analysis of surveillance FDG-PET/CT images, correlating findings with post treatment cervical biopsy results after completion of therapy. The medical records of all patients treated with definitive chemotherapy and radiation for locally advanced (FIGO IB3 to IVA) cervical cancer at a single academic medical center between 2017 and 2022 were reviewed. Patients were treated with curative intent using a combination of pelvic external beam radiation with concurrent cisplatin chemotherapy followed by intracavitary or combined intracavitary/interstitial brachytherapy boost. Patients underwent FDG-PET/CT imaging at 3-6 months upon completion of therapy, followed by biopsy either for suspected residual disease or equivocal findings on physical exam or FDG-PET/CT scans. Biopsies were obtained within 100 days of FDG-PET/CT imaging (median, 14 days). Twenty-three patients met inclusion criteria. One patient was excluded from analysis due to lack of FDG avidity on her pre-treatment FDG-PET/CT. Among the 22 evaluable scans, median pre-treatment FDG- PET/CT SUVmax of the cervix was 16.3 (range, 4.9-55). Median post-treatment SUVmax was 4.4 (range, 2.1-7.4). Median change in SUVmax from pre-treatment to post-treatment was 11.8 (range, 1.1 to 50.6). Twenty patients had a post-treatment SUVmax of greater than 3. Among post treatment scans, eight showed no residual uptake; two showed uptakes equal to the liver; eleven showed uptakes moderately higher than liver; and one showed uptake markedly increased relative to liver. None of the biopsy specimens showed evidence of residual malignancy, instead showing fibroinflammatory necrosis and reactive changes. None of the patients developed clinical evidence of disease progression at the cervix within one year of treatment completion. Residual hypermetabolic activity at the cervix is common following definitive chemotherapy and radiation for cervical cancer. This is unlikely to represent residual viable malignancy. Post treatment FDG-PET/CT imaging remains valuable for detecting locoregional or distant disease progression/persistence following therapy.

Positive Predictive Value of PET CT in HPV Associated Oropharyngeal Cancers Treated with Definitive Proton Therapy

Proton therapy (PT) offers attractive dosimetric advantages but there is emerging literature suggesting relative biological effectiveness (RBE) differences at the distal end of the Bragg peak may result in increased posttreatment FDG avidity. While the utility of PET CT is well established, lingering posttreatment inflammation from PT may affect the interpretation of posttreatment scans (PTS). We seek to characterize the positive predictive value (PPV) and negative predictive value (NPV) for residual disease/locoregional recurrence in patients undergoing definitive PT with HPV associated oropharyngeal cancer. We performed a single institution retrospective analysis of patients with HPV associated oropharyngeal cancer treated with PT between 2016-2022. Patients were included if they had both pretreatment and initial posttreatment restaging PET/CT available for analysis. SUVmax was recorded in both the primary tumor and involved lymph nodes. Patients were considered to have a positive PET CT if there was an SUV decrease of less than 65% from the baseline exam or if there was SUV > 4.0 based on thresholds defined by previous studies. Chi-square analysis was used to compare patients who had a positive PTS to those who did not. Sixty-two patients were included for analysis with a median age of 62. The entire cohort had a median follow up of 21 months (Range 2-71 months) of whom 86% received chemotherapy. Eleven patients (17%) had PTS defined as positive, of whom only one (PPV 9%) was found to have residual/locoregionally recurrent disease within an area of FDG avidity on PTS. Another patient developed a new primary tumor 9 months later in an area outside of FDG avidity on PTS. The remainder were followed with serial clinical exam with or without the compliment of repeat imaging. They remained without evidence of residual/locoregionally recurrent disease at the time of last follow up. Fifty-one patients had negative posttreatment scans, with only one patient having residual/locoregionally recurrent disease (NPV 98%). On Chi-square analysis T1-2 vs T3-4 tumor, use of CTV margin vs no margin, chemotherapy vs no chemotherapy, smoking history, and tonsil vs base of tongue subsite were not statistically significant in association with positive PTS. PET/CT for post-treatment evaluation of patients treated with PT had an expectedly high NPV of 98% for residual/locoregionally recurrent disease; however, the PPV was 9% (1/11) which is much lower than would be expected with photon-based treatment. These findings may be the result of lingering acute inflammation caused by RBE differences at the distal end of the Bragg peak. Our findings are hypothesis generating and require validation with larger well-matched patient cohorts.

Sarcoidosis associated with Trastuzumab in a young female with carcinoma of breast

Trastuzumab is a humanized monoclonal antibody against human epidermal growth factor, useful in breast cancer. It is well tolerated but sometimes may associate with significant adverse effects. Sarcoidosis is a granulomatous disease involving multiple organs with poorly understood aetiology. Mediastinal lymphadenopathy is the most common presenting feature of Sarcoidosis. Reported cases of Sarcoidosis associated with Trastuzumab are quite less in number. High degree of suspicion of the above is thought of in a scenario of malignancy patients receiving chemotherapy. Newly appearing FDG avid lymph node in PET scan may give first impression of metastasis and treatment failure or infection. However correct diagnosis is a must (differentiating metastasis, treatment failure or infection) to provide correct treatment and avoid side effects of inappropriate therapies. Correct diagnosis also helps in appropriate prognostication and unnecessary stoppage of Trastuzumab. Here we are describing Sarcoidosis associated with Trastuzumab in a patient with breast cancer.

Safety and early efficacy results of phase 1 study of affinity tuned and trackable AIC100 CAR T cells in ICAM-1 positive relapsed and/or refractory advanced poorly differentiated and anaplastic thyroid cancers.

6095 Background: ICAM-1, a cell surface glycoprotein, is overexpressed in most ATC and PDTC. AIC100 is a 3rd-generation CAR T cell with micromolar affinity to ICAM-1, tuned lower than most CARs used to date in pre-/clinical studies. Affinity tuned AIC100 are expected to selectively bind and kill tumor cells while safely sparing healthy cells. AIC100 also co-expresses somatostatin receptor 2 (SSTR2), which enables in vivo monitoring of AIC100 distribution and expansion by DOTATATE PET/CT scan. Methods: The objectives of this phase 1 dose escalation study are to assess the safety, preliminary efficacy and to determine RP2D of AIC100 in patients with ICAM-1+ relapsed/refractory PDTC or ATC. 3 dose levels (DL) are being explored-DL1 at 1x 107, DL2 at 1 x 108 and DL3 at 5 x 108 AIC100. AIC100 is received as a single infusion two days after completing lymphodepletion with Fludarabine/Cyclophosphamide. FDG and DOTATATE PET/CT scans are used to assess response and to track AIC100 in vivo, respectively. Response is assessed by RECIST1.1, starting at end of treatment (day 42 post AIC100). AIC100 is manufactured using AffyImmune’s Tune and Track CAR T cell platform. Results: As of Feb 14, 2023, 6 pts (4 ATC; 2 PDTC) with a median age of 59.5 yrs (48-70) were infused with AIC100, 3 each in DL 1 and 2. AIC100 was successfully manufactured for all patients and all infusion products met target transduction efficiency. No serious adverse events or DLTs were reported. Two patients had grade 1 CRS. No ICANs was reported. In 3 evaluable patients in DL1, 1 patient had stable disease with decreased FDG activity in PET that correlated with increased activity in the DOATATE scan. From the 3 pts infused in the DL2, one is evaluable for efficacy at day 42. This is a patient with relapsed ATC who achieved PR with 42% reduction in target tumor lesion and remains in PR at 3 mths. The target lesion in this patient showed increased DOTATE avidity at d14 post AIC100 infusion. This was followed by decreased FDG and DOTATE avidity at d42 post AIC100 infusion, concomitant with decreased size, suggesting biological activity 42 days after CAR T infusion. Evaluation of CAR transgene demonstrated transient peripheral blood CAR T cell expansion. The second patient couldn’t be assessed due to early withdrawal for disease-related toxicity. The 3rd patient in DL2 remains in the DLT period, pending efficacy evaluation. Conclusions: AIC100 demonstrated an excellent safety profile in DL1/DL2 treated patients with ATC and PDTC with no DLTs observed. The objective and relatively durable partial response in the first evaluable patient in the DL2, a patient with metastatic ATC who failed multiple lines of therapy, is unprecedented and very encouraging. Further investigations of AIC100 are ongoing at DL2 and DL3 to determine the RP2D. Clinical trial information: NCT04420754 .

Post-neoadjuvant treatment pancreatic cancer resectability and outcome prediction using CT, 18F-FDG PET/MRI and CA 19–9

BackgroundCT prediction of resectability and prognosis following neoadjuvant treatment (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC) remains challenging. This study aims to determine whether addition of 18F-fluorodeoxyglucose (FDG) postiron emission tomography (PET)/MRI and carbohydrate antigen (CA) 19–9 to contrast-enhanced CT (CECT) can improve accuracy of predicting resectability compared to CECT alone and predict prognosis in PDAC patients after NAT.MethodsIn this retrospective study, 120 PDAC patients (65 women; mean age, 66.7 years [standard deviation, 8.4]) underwent CECT, PET/MRI, and CA 19–9 examinations after NAT between January 2013 and June 2021. Three board-certified radiologists independently rated the overall resectability on a 5-point scale (score 5, definitely resectable) in three sessions (session 1, CECT; 2, CECT plus PET/MRI─no FDG avidity and no diffusion restriction at tumor-vessel contact indicated modification of CECT scores to ≥ 3; 3, CECT plus PET plus CA 19–9─no FDG avidity at tumor-vessel contact and normalized CA 19–9 indicated modification of CECT scores to ≥ 3). Jackknife free-response receiver operating characteristic method and generalized estimating equations were used to compare pooled area under the curve (AUC), sensitivity, and specificity of three sessions. Predictors for recurrence-free survival (RFS) were assessed using Cox regression analyses.ResultsEach session showed different pooled AUC (session 1 vs. 2 vs. 3, 0.853 vs. 0.873 vs. 0.874, p = 0.026), sensitivity (66.2% [137/207] vs. 86.0% [178/207] vs. 84.5% [175/207], p < 0.001) and specificity (67.3% [103/153] vs. 58.8% [90/153] vs. 60.1% [92/153], p = 0.048). According to pairwise comparison, specificity of CECT plus PET/MRI was lower than that of CECT alone (adjusted p = 0.042), while there was no significant difference in specificity between CECT alone and CECT plus PET plus CA 19–9 (adjusted p = 0.081). Twenty-eight of 69 patients (40.6%) with R0 resection experienced tumor recurrence (mean follow-up, 18.0 months). FDG avidity at tumor-vessel contact on post-NAT PET (HR = 4.37, p = 0.033) and pathologically confirmed vascular invasion (HR = 5.36, p = 0.004) predicted RFS.ConclusionCombination of CECT, PET and CA 19–9 increased area under the curve and sensitivity for determining resectability, compared to CECT alone, without compromising the specificity. Furthermore, 18F-FDG avidity at tumor-vessel contact on post-NAT PET predicted RFS.

C14 CASE REPORT: MULTIMODALITY IMAGE–CHALLENGE IN PRIMARY CARDIAC DIFFUSE LARGE B–CELL LYMPHOMA

Abstract A 76–year–old Caucasian woman presented to our hospital with progressive exertional fatigue and weight–loss over 2 months.Her past medical history revealed a recent local–hospital admission because of atrioventricular third–degree block, requiring permanent pacemaker implan­tation. At presentation her cardiovascular exam was normal.Laboratory studies revealed elevated LDH and PCR; electrolytes, cardiac biomarkers and complete blood count were normal. ECG demonstrated AF and ventricular stimulation.Transtoracich echocardiography showed LV hypertrophy in the basal segments, with normal ejection fraction and a reduced LV–GLS with a relative apical sparing pattern.There was a large, well–circumscribed mass arising from the right atrium, with a contextual moderate pericardial effusion (Fig1).Vasculitic, thrombophilic and infectious work–up were negative.The patient was immunocompetent. CMR was proposed but could not be performed due to patient claustrophobia. ECG gated cardiac CT was carried out for a better differential diagnosis of the mass, as well as to look for possible embolization or primary tumours, in the hypothesis of cardiac metastases. A CT total body showed a large ill–defined mass invading the interatrial and interventricular septum with projections into the left ventricle. Not enlarged lymph nodes were detected with neither hepatosplenomegaly nor abdominal lymphadenopathy. A total body 18FDG PET revealed significant tracer uptake in the heart and pericardium without extracardiac uptake, consistent with a malignant cardiac mass (Fig2).LV endomyocardial biopsy was attempted: pathology revealed large B–cell lymphoma expressing CD20, Bcl–2, Bcl–6, Mum–1, C–myc and with a high Ki67 proliferation rate. The patient underwent six cycles of chemotherapy(R–POCH).Echocardiography imaging after the second cycle showed significant reduction in myocardial wall thickness and concomitant improvement in LV–GLS. Repeated PET–CT scans 6 months post–chemotherapy showed complete remission with no evidence of FDG–avid lymphoma (Fig3). Primary cardiac lymphoma (PCL) is an extranodal non–Hodgkin’s B–cell lymphoma exclusively located in the heart or pericardium, accounting for 1–2% of primary cardiac tumours. PCL often presents with non–specific clinical symptoms making the diagnosis challenging. Multimodality approach and myocardial biopsy are essential in the diagnostic work–up. Early diagnosis and treatment are crucial since a good response to chemotherapy is expected.

FDG and Non-FDG Radiopharmaceuticals for PET Imaging in Invasive Lobular Breast Carcinoma.

Invasive lobular cancer (ILC) is the second most frequent histological type of breast cancer (BC) and includes a heterogeneous spectrum of diseases with unique characteristics, especially the infiltrative growth pattern and metastatic spread. [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is extensively used in oncology and BC patient evaluation. Its role in ILCs is considered suboptimal due to its low FDG avidity. Therefore, ILCs could benefit from molecular imaging with non-FDG tracers that target other specific pathways, contributing to precision medicine. This narrative review aims to summarize the current literature on the use of FDG-PET/CT in ILC and to discuss future opportunities given by the development of innovative non-FDG radiotracers.

Overview and Recent Advances in 18F-FDG PET/CT for Evaluation of Pediatric Lymphoma

Pediatric lymphoma is the third most common childhood cancer, representing 15% of all pediatric malignancies. Evaluation of the extent of disease with imaging is essential for appropriate risk stratification and treatment planning, and has evolved extensively over the past several decades. At present, PET/CT plays a key role in the diagnostic evaluation of these patients, particularly for staging, treatment planning, and therapy response assessment. The vast majority of pediatric lymphomas are FDG avid and as a result, FDG PET/CT has a higher sensitivity for detecting sites of disease compared to conventional imaging modalities, as well as a higher sensitivity for detecting focal bone marrow lesions compared to standard bone marrow biopsy of the iliac crest. PET/CT can be used to identify early responders, helping to minimize overtreatment with intensive chemotherapy and radiotherapy, thereby reducing the risk of secondary malignancies and cardiovascular complications. Conversely, PET/CT can identify patients with an inadequate metabolic response during treatment, who can then benefit from earlier treatment intensification. A negative interim or end of treatment FDG PET/CT is highly predictive for a complete remission, although positive PET/CT scans, particularly at end of treatment, have a lower PPV and must be interpreted cautiously. Nevertheless, PET/CT is more accurate than conventional imaging alone, as well as in the case of conflicting results, such as residual lymph node enlargement and soft tissue lesions that can that can persist despite resolution of the underlying malignancy. For these reasons, FDG PET/CT has been incorporated into the standard diagnostic procedures for lymphoma staging and treatment response evaluation, using the visual Deauville 5-point scale and Lugano classification. In the future, innovations in low-dose ultrafast total-body PET/CT, increased use of PET/MR and incorporation of quantitative parameters from PET such as total metabolic tumor volume may allow even more precise prediction of response and personalized therapy while minimizing radiation exposure and adverse effects and complications of treatment.

MP50-08 POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR SEMINOMA: IS SURGERY EFFECTIVE?

You have accessJournal of UrologyCME1 Apr 2023MP50-08 POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) FOR SEMINOMA: IS SURGERY EFFECTIVE? Isamu Tachibana, Andre Alabd, Rumeal Whaley, Jacob Mcfadden, Alex Piroozi, Sean Kern, Nabil Adra, Richard Foster, Lawrence Einhorn, Clint Cary, and Timothy Masterson Isamu TachibanaIsamu Tachibana More articles by this author , Andre AlabdAndre Alabd More articles by this author , Rumeal WhaleyRumeal Whaley More articles by this author , Jacob McfaddenJacob Mcfadden More articles by this author , Alex PirooziAlex Piroozi More articles by this author , Sean KernSean Kern More articles by this author , Nabil AdraNabil Adra More articles by this author , Richard FosterRichard Foster More articles by this author , Lawrence EinhornLawrence Einhorn More articles by this author , Clint CaryClint Cary More articles by this author , and Timothy MastersonTimothy Masterson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with relapsed seminoma after first-line chemotherapy can be treated with salvage chemotherapy or post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND). Based on prior reported experience, surgical management can have worse efficacy and increased morbidity compared to non-seminomatous germ cell tumor. Our aim was to characterize the surgical efficacy and difficulty in a specific cohort of patients with definite progression but minimal disease burden. METHODS: The Indiana University testis cancer database was queried to identify men who underwent PC-RPLND for seminoma between January 2011 to December 2021. Included patients only underwent first-line chemotherapy and could not have any evidence of non-seminomatous elements on orchiectomy or have elevated serum alpha-fetoprotein (AFP). All patient demonstrated high suspicion of retroperitoneal disease prior to PC-RPLND was based on increasing size of tumor on standard CT imaging, progression of FDG avidity on PET imaging, or elevated tumor markers. RESULTS: We identified 889 patients that underwent PC-RPLND, of which only 14 patients were operated on for seminoma. One patient was excluded for lack of meaningful follow-up. Out of 13 patients, only 3 patients were disease free with surgery and did not have to undergo salvage chemotherapy. Median follow up time was 29.9 months (IQR: 22.6-53.7). Two patients died due to testicular cancer. The remaining 8 patients were treated successfully with salvage chemotherapy. For additional procedures, 4 patients required a nephrectomy, 1 patient required an aortic graft, 2 patients required a partial ureterectomy, and 3 patients required partial or complete caval resection CONCLUSIONS: The decision between salvage chemotherapy and PC-RPLND as second-line therapy can be challenging. Salvage chemotherapy is effective but is associated with short and long-term morbidity. Surgical efficacy in this setting seems to be limited, but careful selection of patients may lead to surgical success without life threatening morbidity or adjunctive procedures that may compromise the ability to receive salvage chemotherapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e687 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Isamu Tachibana More articles by this author Andre Alabd More articles by this author Rumeal Whaley More articles by this author Jacob Mcfadden More articles by this author Alex Piroozi More articles by this author Sean Kern More articles by this author Nabil Adra More articles by this author Richard Foster More articles by this author Lawrence Einhorn More articles by this author Clint Cary More articles by this author Timothy Masterson More articles by this author Expand All Advertisement PDF downloadLoading ...

PET imaging characteristics of neuromuscular choristoma and associated desmoid-type fibromatosis.

Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion characterized by abnormal presence of muscle within nerve. Associated desmoid-type fibromatosis (NMC-DTF) often develops. We report 18F-fluorodeoxyglucose positron emission tomography (FDG PET) characteristics of NMC and NMC-DTF and propose that increased FDG activity within NMCs may be associated with subclinical NMC-DTF or NMC-DTF "precursor" tissue. Our institutional database was searched for all NMC cases. Inclusion criteria were 1) confirmed diagnosis of NMC with or without biopsy, and 2) available PET and MRI studies. PET data included SUVmax and SUVmean of NMCs, contralateral limb normal skeletal muscle and unaffected nerves, and SUVmax of NMC-DTF if present. SUV values were compared using paired t-test. A p value of < 0.05 was considered statistically significant. Our cohort consisted of 9 patients with NMC, 8 cases involving sciatic nerve and 1 of brachial plexus. On PET imaging, all NMC-affected nerve segments showed significantly higher FDG uptake (SUVmax/mean) compared to both contralateral normal nerve and normal skeletal muscle (all P < 0.05). Similar to sporadic DTF, NMC-DTF was highly FDG-avid (average SUVmax of 4.2). SUVmax in NMC with or without concurrent NMC-DTF did not differ (p = 0.76). Within NMC-affected nerve segment, FDG activity was relatively higher in areas with low T1/T2 MR signal. All NMCs were more FDG avid compared to both normal skeletal muscle and contralateral unaffected nerve, arguing against the presence of heterotopic muscle in NMC asthe source of FDG avidity. FDG avidity within NMC may reflect subclinical NMC-DTF or a precursor lesion, as NMC-DTF are highly FDG-avid, and the highest regions of FDG avidity in NMC occurred in regions with MR characteristics associated with NMC-DTF (i.e., lower T1/T2 signal). We believe that the integration of FDG PET with serial MR imaging in patient follow up will clarify its utility in both detection and surveillance of NMC-DTF.

Imaging Recommendations for Diagnosis, Staging, and Management of Carcinoma of Unknown Origin (Lymph Node, Pulmonary, Liver, Skeletal, and Brain) with Emphasis on the Current Position of PET-CT in Carcinoma of Unknown Origin (CUP)

AbstractMost of the established guidelines mention and recommend the use of FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) in carcinoma of unknown primary (CUP) especially in head–neck squamous cell carcinoma; as described in this article, this forms a powerful one-stop shop in diagnosing and staging modality and has multiple applications in difficult situations of CUPs. Although not used as a screening modality, FDG-PET/CT is recommended as the primary imaging modality in the evaluation of primary, staging, and response evaluation for CUP with histology known to demonstrate FDG avidity, especially patients presenting with lymph nodal disease. It should be remembered that many histological types do not concentrate on FDG and FDG also shows false-positive results in many other conditions like infection-inflammation; however, at the same time, it delivers high negative predictive values, an important consideration when employing FDG-PET/CT in the CUP scenario. SSTR-based PET/CT plays a pivotal role in primary diagnosis, staging, therapy planning, and response assessment in CUPs with neuroendocrine tumor or neuroendocrine neoplasm histology. The last two decades has witnessed great advancement in PET instrumentation and radiopharmaceuticals: particularly techniques like PET/magnetic resonance imaging and radiopharmaceuticals like FAPI (fibroblast-activation protein inhibitor)-based PET tracers. Hence, the role of PET/CT is expected to expand its reach in the coming years in line with accruing literature evidence, thereby upgrading its role and reliability in oncological practice strategies.

Patient with Rosai-Dorfman-Destombes disease: 18F-FDG-PET/CT scan as a diagnostic tool

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis, with sinus involvement and massive lymphadenopathy. RDD is usually self-limited; it can appear alone or related to other diseases. We present a 9-year-old male with biopsy of that lesion was taken, giving as result a benign histiocytosis, compatible with RDD. The patient was scanned with full body 18F-FDG PET/CT, the results of the study showed hypermetabolic focal lesions in the sphenoid sinus, ethmoid sinus, and bilateral nasal involvement with hypermetabolic focal injury in the middle third of the left tibia, findings in relation to high-grade expansive injury. The study of 18F-FDG PET/CT demonstrated avid FDG lesions at nodal and extranodal sites, and it also can be used in monitoring and/or evaluating response to treatment.

Real-Time Split-Dose PET/CT-Guided Ablation Improves Colorectal Liver Metastasis Detection and Ablation Zone Margin Assessments without the Need for Repeated Contrast Injection.

Real-time split-dose PET can identify the targeted colorectal liver metastasis (CLM) and eliminate the need for repeated contrast administration before and during thermal ablation (TA). This study aimed to assess the added value of pre-ablation real-time split-dose PET when combined with non-contract CT in the detection of CLM for ablation and the evaluation of the ablation zone and margins. A total of 190 CLMs/125 participants from two IRB-approved prospective clinical trials using PET/CT-guided TA were analyzed. Based on detection on pre-TA imaging, CLMs were categorized as detectable, non-detectable, and of poor conspicuity on CT alone, and detectable, non-detectable, and low FDG-avidity on PET/CT after the initial dose. Ablation margins around the targeted CLM were evaluated using a 3D volumetric approach. We found that 129/190 (67.9%) CLMs were detectable on CT alone, and 61/190 CLMs (32.1%) were undetectable or of poor conspicuity, not allowing accurate depiction and targeting by CT alone. Thus, the theoretical 5- and 10-mm margins could not be defined in these tumors (32.1%) using CT alone. When TA intraprocedural PET/CT images are obtained and inspected (fused PET/CT), only 4 CLM (2.1%) remained undetectable or had a low FDG avidity. The addition of PET to non-contrast CT improved CLM detection for ablation targeting, margin assessments, and continuous depiction of the FDG avid CLMs during the ablation without the need for multiple intravenous contrast injections pre- and intra-procedurally.

OGC P20 Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients undergoing surgical resection for locally advanced oesophageal adenocarcinoma

Abstract Background 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is routinely used for staging of oesophageal cancer and has an emerging role in assessing response to neoadjuvant therapy. Several studies have demonstrated that a reduction in FDG avidity of the primary tumour and loco-regional lymph nodes following neoadjuvant chemotherapy predicts pathological response and survival in this patient group. However, no studies have evaluated the prognostic significance of metabolic parameters with respect to pathological response in lymph nodes. Change in primary tumour maximum standardised uptake value (SUVmax) is the most widely used FDG PET-CT parameter to define metabolic response, with various thresholds described. The most commonly utilised are a 35% reduction in SUVmax (MUNICON), and a 30% reduction in SUVmax (PERCIST). However, there is no consensus regarding the optimal classification; the MUNICON threshold was derived from only 40 patients and PERCIST is not tumour specific. The primary aim of this study was to evaluate the ability of FDG PET-CT to predict pathological response in the primary tumour (pTR) and lymph nodes (pNR) in patients with oesophageal adenocarcinoma undergoing neoadjuvant chemotherapy before surgery. Secondary aims were to assess the prognostic effect of metabolic and pathological response and evaluate the predictive ability of response classifications. Methods Cohort study of 75 patients with locally advanced oesophageal or oesophago-gastric junctional adenocarcinoma who underwent FDG-PET-CT before and after neoadjuvant chemotherapy, prior to surgical resection at Guy's and St Thomas’ NHS Foundation Trust, London, UK, between 2017–2020. SUV metrics related to the primary tumour and loco-regional lymph nodes were derived on pre- and post- treatment FDG PET-CT. pTR and pNR were evaluated using the Mandard classification. Patients with Mandard scores of 1–3 were classified as pathological responders and those with Mandard scores of 4–5 as non-responders. Clinicopathological characteristics were compared using the Chi-squared test. Receiver operator characteristic (ROC) analysis was performed and area under the curve (AUC) calculated to determine optimum SUVmax thresholds for metabolic response in the primary tumour (mTR) and lymph nodes (mNR). Survival curves were created using the Kaplan-Meier method, with subgroups compared using the log-rank test. Survival analysis was performed using Cox proportional hazards regression providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age (continuous), sex (male or female), chemotherapy regimen (ECX or FLOT), cT stage (cT1–2 or cT3–4), cN stage (cN0 or cN+), tumour grade (well / moderately differentiated or poorly differentiated) and presence of signet ring cells (yes or no). Results Mean age was 63 years with the majority male (86.7%). Almost two thirds received FLOT (48/75, 64.0%) with the remainder receiving ECX chemotherapy. There was discordance between pathological response in the primary tumour and lymph nodes in several patients, including 23.1% (6/26) who demonstrated a lymph node response in the absence of a response in the primary tumour. ROC analysis demonstrated an optimum tumour SUVmax decrease of 51.2% for predicting pTR. Using a pragmatic cut-off of 50% this provided better prediction of pTR (AUC 0.714, sensitivity 73.5%, specificity 69.2%, p&amp;lt;0.001) than PERCIST (AUC 0.631, sensitivity 87.8%, specificity 38.5%, p=0.008) and MUNICON (AUC 0.659, sensitivity 85.7%, specificity 46.2%, p=0.003) criteria. ROC analysis demonstrated an optimum nodal SUVmax decrease of 32.6% for predicting pNR or pathological node negativity. Using a pragmatic 30% SUVmax cut-off and excluding metabolically negative nodes, mNR demonstrated high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p=0.010) for predicting pNR. pTR, mTR, pNR and mNR were independent predictive factors for overall survival on adjusted analysis (pTR responder HR 0.10 95% CI 0.03–0.34; mTR responder HR 0.17 95% CI 0.06–0.48; pNR responder HR 0.17 95% CI 0.06–0.54; mNR responder HR 0.13 95% CI 0.02–0.66). Conclusions In this study metabolic response on FDG PET-CT after neoadjuvant chemotherapy was predictive of pathological response in both the primary tumour and lymph node metastases of patients with oesophageal adenocarcinoma. Patients who had a favourable metabolic or pathological response in the primary tumour or lymph nodes had improved survival compared to non-responders. It has been suggested that commonly utilised thresholds of SUVmax are not optimal for response assessment in this patient group. This is supported by the results of the present study which suggest a reduction in SUVmax of 50% in the primary tumour was not only a better predictor of pathologic response, but also tumour recurrence and survival compared with PERCIST and MUNICON criteria. No previous studies have evaluated the ability of FDG PET-CT to predict pathologic nodal response despite recent findings suggesting it is an independent predictor of survival and evidence of a discrepancy, in some patients, who demostrate a nodal response in the absence of a response in the primary tumour. The use of FDG PET-CT in assessing response to neoadjuvant chemotherapy remains an under researched area and further evaluation is needed to establish whether it could be used to tailor individualised treatment strategies.

Glial Fibrillary Acidic Protein (GFAP) Antibody-Associated Astrocytopathy in Systemic Sarcoidosis

Objective To report two cases of glial fibrillary acidic protein (GFAP) antibody-associated meningoencephalitis in patients with biopsy-proven systemic sarcoidosis. Background GFAP astrocytopathy is an autoimmune neurologic disease first defined in 2016. To our knowledge, no association with systemic sarcoidosis has been previously reported. Design/Methods Case Series Results Patient 1 is a 47-year-old woman with pre-existing pulmonary sarcoidosis treated with steroids and methotrexate with remission 6 years prior. She subsequently developed new-onset epilepsy, progressive ataxia and vertical diplopia. GFAP antibodies were positive in the cerebrospinal fluid (CSF) by cell-based assay (CBA). Body PET scan showed diffuse FDG avidity in her lungs, spleen, and lymph nodes, suggesting simultaneous reactivation of her systemic sarcoidosis. She was treated with steroids followed by infliximab with resolution of her symptoms. Patient 2 is a 58-year-old man with known pulmonary sarcoidosis, who was off immunosuppression at the time of his presentation but had received steroids 17 years prior. He presented with progressive apathy, memory disturbance, dysarthria, and gait instability. MRI revealed widespread T2 hyperintensities. GFAP antibodies were positive in CSF on CBA and confirmed by tissue-based immunofluorescence assay. He received steroids with initial response but relapsed after steroid discontinuation. He improved after restarting steroids and was subsequently transitioned to infliximab with sustained neurologic recovery. Conclusions Sarcoidosis is a poorly understood multi-system disorder that is presumably an immune-mediated response to yet unidentified antigen(s). It is known to co-exist with other autoimmune diseases, with autoimmune thyroiditis being most common. GFAP astrocytopathy is also poorly understood. GFAP is found intracellularly and similar to other antibody-mediated diseases against intracellular epitopes, the antibodies are believed to be a biomarker of underlying autoimmunity but not directly pathogenic. We report these cases to highlight a potential association between production of intrathecal GFAP antibodies and systemic sarcoidosis, which may provide insights into the pathogenesis of these two diseases.

Automated lesion detection of breast cancer in [18F] FDG PET/CT using a novel AI-Based workflow.

One hundred thirty baseline PET/CT studies from two multi-institutional preoperative clinical trials in early-stage breast cancer were semi-automatically segmented using techniques based on PERCIST v1.0 thresholds and the individual segmentations classified as to tissue type by an experienced nuclear medicine physician. These classifications were then used to train a convolutional neural network (CNN) to automatically accomplish the same tasks. Our CNN-based workflow demonstrated Sensitivity at detecting disease (either primary lesion or lymphadenopathy) of 0.96 (95% CI [0.9, 1.0], 99% CI [0.87,1.00]), Specificity of 1.00 (95% CI [1.0,1.0], 99% CI [1.0,1.0]), DICE score of 0.94 (95% CI [0.89, 0.99], 99% CI [0.86, 1.00]), and Jaccard score of 0.89 (95% CI [0.80, 0.98], 99% CI [0.74, 1.00]). This pilot work has demonstrated the ability of AI-based workflow using DL-CNNs to specifically identify breast cancer tissue as determined by [18F]FDG avidity in a PET/CT study. The high sensitivity and specificity of the network supports the idea that AI can be trained to recognize specific tissue signatures, both normal and disease, in molecular imaging studies using radiopharmaceuticals. Future work will explore the applicability of these techniques to other disease types and alternative radiotracers, as well as explore the accuracy of fully automated and quantitative detection and response assessment.

End of Treatment Positron Emission Tomography Response and Outcomes in Post-Transplant Lymphoproliferative Disorder

Introduction: Although end of treatment (EOT) response assessment using Fluorine-18-fluorodeoxyglucose positron emission tomography (PET) has proven highly predictive of disease remission in Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma, there is little data on the prognostic significance of PET response in patients with post-transplant lymphoproliferative disorder (PTLD). Optimal treatment of patients with PTLD is complex and better understanding of the significance of EOT imaging could help guide subsequent therapeutic decisions. Methods: As part of a multi-institutional study of viral genomes in PTLD, we collected clinical data (demographics, transplant and PTLD characteristics, treatment, imaging, and patient survival) from three large organ transplant centers in the United States from 1991 onwards. Patients who were PET negative at EOT considered to have a complete remission (CR), patients with decrease in FDG avidity who were still PET positive considered to have a partial remission (PR), and patients with stable or increasing FDG avidity considered to have no remission or progressive disease (NR/PD). Time-to-event outcomes (time to death and time to death or relapse) were analyzed using the Kaplan Meier method. Results: Among 147 pediatric and adult patients with PTLD, imaging at diagnosis and EOT included PET n=94 (64%), computed tomography (CT) n=77 (53%), and/or magnetic resonance imaging (MRI) n=14 (10%). Median recipient age at first transplant was 29.6 years (IQR 14.8 to 25.9), and 57.5% were male. Transplants included kidney (29%), heart (27%), liver (18%), lung (18%), hematopoietic (7%), intestine (6%), or pancreas (3%). Sites of PTLD were lymph node (57%), gastrointestinal tract (34%), lung (19%), disseminated (10%), liver (8%), central nervous system (4%), kidney (3%), bone marrow (3%), or other (41%). PTLD subtypes included monomorphic diffuse large B-cell lymphoma (DLBCL) (69%), polymorphic (17%), classical HL (8%), or non-destructive (5%). All non-destructive and polymorphic PLTD was Epstein-Barr virus (EBV) positive while 60.6% of DLBCL and 75% of classical HL were EBV positive. Treatments varied but included reduction of immunosuppression in 65.6% and rituximab or chemotherapy in 62.4% of patients. For 84 patients with PET scans and outcome data, patients who achieved CR (59/84; 70.2%) experienced a subsequent progression-free median survival of 13.5 years compared with 8.8 years for patients with PR (11/84; 13.1%) and 1.4 years for patients with NR/PD (14/84; 16.7%) (p<0.0001, Figure A). Median overall survival was 14.7 years for patients with CR (60/85; 70.6%), not reached for patients with PR (11/85; 12.9%), and 1.4 years for patients with NR/PD (14/85; 16.5%) (p=0.0026, Figure B). 20.8% of patients who achieved CR subsequently relapsed compared to 42.9% of patients with PR. 81.8% of patients with NR/PD experienced relapse or death. Conclusion: End of therapy PET identifies a subgroup of patients with CR who are at low risk for relapse. While patients with NR/PD had poor prognosis, patients with PR represent an intermediate group who are PET positive at the EOT but can achieve long-term remission without additional therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Predictive Value of Staging PET/CT to Detect Bone Marrow Involvement in Marginal Zone Lymphoma (MZL): An Analysis from LEO MZL Working Group

Introduction: Bone marrow (BM) involvement impacts stage and prognosis in lymphoma, remaining an important factor in risk-stratification scores, including the MALT-IPI. PET/CT is routinely implemented in the staging and response assessment of patients with lymphoma. However, FDG avidity to detect marginal zone lymphoma (MZL) remains debatable. In this study we aimed to assess the predictive value of PET/CT to detect BM involvement and survival implications in MZL using prospectively collected data from the Lymphoma Epidemiology of Outcomes (LEO) cohort. Methods: The LEO cohort is a prospective cohort from 8 academic cancer centers in which patients are enrolled within 6 months of lymphoma diagnosis and followed. We extracted baseline data of MZL patients enrolled in the LEO cohort between 5/2015 and 2/2020. BM biopsy was used as a gold standard for BM involvement. In addition, radiology reports were reviewed for PET/CT-suggested BM involvement. Event-free survival (EFS) defined as time from diagnosis to relapse/progression, retreatment, or death due to any cause and overall survival (OS) defined as time from diagnosis to death due to any cause were estimated by Kaplan-Meier. Results: Of 706 MZL patients enrolled in LEO, 311 (44%) with data on BM status by both biopsy and PET/CT were included in the analysis. Patients’ characteristics were median age 64 (range 24-89) years with most <70 years (n=217, 69.8%), non-Hispanic (n=264, 84.9%) white (n=276, 88.7%), without B symptoms (n=246, 79.1%), and normal LDH (n=185, 59.5%). The most common MZL subtype was extranodal (EMZL, n=208, 66.9%) followed by nodal (NMZL, n=61, 19.6%) and splenic (SMZL, n=42, 13.5%). Stage distribution was as follows: early-stage (I-II; n=134, 43.1%), advanced-stage (III-IV; n=159, 51.1%), and unknown (n=18, 5.8%). BM biopsy was positive in 99 (31.8%) and negative in 212 (68.2%) patients. Across all MZL subtypes, biopsy-proven and PET/CT-suggested BM involvement was present in 11.6% (n=36/311), and positive BM biopsy with negative PET/CT was observed in 20.3% (n=63/311) (EMZL=9.6%, n=20/208; NMZL=31.1%, n=19/61; and SMZL=57.1%, n=24/42). For EMZL, 15.9% (n=33) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 39.4% (n=13) and negative in 60.6% (n=20). For NMZL, 50.8% (n=31) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 38.7% (n=12) and negative in 61.3% (n=19). Most patients (83.3%, n=35) with SMZL demonstrated pathologically confirmed BM involvement, with positive PET/CT in 31.4% (n=11) and negative in 68.6% (n=24). Considering BM result from biopsy as the standard, PET/CT-based sensitivity and specificity in EMZL, NMZL, and SMZL were 39.4% & 98.9%, 38.7% & 100%, and 31.4% & 100%, respectively. PET/CT-based positive and negative predictive values in EMZL, NMZL, and SMZL were 86.7% & 89.6%; 100% & 61.2%; and 100% & 22.6%, respectively. With a median follow up of 35.4 months there were 70 EFS events and 18 OS events across all MZL subtypes. The 2-year EFS and OS were 81.7% (95%CI 76.8-85.7%) and 96.8% (95%CI 93.9-98.3%), respectively. The 2-year EFS and OS by histology were EMZL= 84.7% (95%CI 78.7-89.1%) & 97.2% (95%CI 93.5-98.8%); NMZL= 69.6% (95%CI 56.1-79.6%) & 96.5% (95%CI 86.9-99.1%); and SMZL= 85.6% (95%CI 70.7-93.3%) & 95.2% (95%CI 82.3-98.8%), respectively. Acknowledging the low number of events and unspecific criteria for treatment selection, those patients exhibiting pathological BM involvement (n= 99) did not show significantly different EFS (p=0.097) (EMZL p=0.48; NMZL p=0.68; and SMZL p=0.75, respectively) or OS (p=0.978) (EMZL p=0.46; NMZL=0.53; and SMZL=0.21, respectively) compared to those without BM disease. Conclusions: While PET/CT may be positive in nodal and some extranodal locations, assessment of BM involvement by PET/CT is characterized by a low sensitivity across all MZL subtypes and low negative predictive value in SMZL, underscoring the limitations of current Lugano criteria in staging MZL. With currently relatively limited follow-up, we did not observe significantly different survival based on BM status.