Node Uptake Research Articles

V10-06 INTRAOPERATIVE USE OF PET/CT SPECIMEN IMAGER TO GUIDE ROBOTIC RADICAL PROSTATECTOMY AND PELVIC LYMPH NODE DISSECTION

You have accessJournal of UrologyCME1 Apr 2023V10-06 INTRAOPERATIVE USE OF PET/CT SPECIMEN IMAGER TO GUIDE ROBOTIC RADICAL PROSTATECTOMY AND PELVIC LYMPH NODE DISSECTION Marco Oderda, Serena Grimaldi, Giorgio Calleris, Daniele D'Agate, Federico Lavagno, Alessandro Marquis, Giancarlo Marra, Desireé Deandreis, and Paolo Gontero Marco OderdaMarco Oderda More articles by this author , Serena GrimaldiSerena Grimaldi More articles by this author , Giorgio CallerisGiorgio Calleris More articles by this author , Daniele D'AgateDaniele D'Agate More articles by this author , Federico LavagnoFederico Lavagno More articles by this author , Alessandro MarquisAlessandro Marquis More articles by this author , Giancarlo MarraGiancarlo Marra More articles by this author , Desireé DeandreisDesireé Deandreis More articles by this author , and Paolo GonteroPaolo Gontero More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003328.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Today, PSMA is the most accurate radiopharmaceutical in PCa and it can be used as a tracer to identify PCa foci in resected specimens. To do so, a small, high-resolution PET/CT-imaging device (XEOS AURA®) was developed, with near five-fold optimization in spatial resolution as opposed to the standard clinical PET/CT devices. Aim of this feasibility study was to test the intraoperative use of this brand-new PET/CT specimen imager to guide robot-assisted radical prostatectomy (RARP) and pelvic lymph node dissection (PLND). METHODS: To date, we performed three cases of RARP and PLND with intraoperative use of XEOS AURA® specimen imager. All patients underwent preoperative staging with MRI and PSMA PET/CT. Surgeries were performed with Da Vinci Xi robot. During trocar placement, an intravenous injection of 68-Ga PSMA, 2 mBq/kg, was performed. Lymph nodes were immediately removed through the 12-mm assistant trocar and inserted into the specimen imager for analysis. After complete excision, the prostate was removed through a short Pfannestiel incision while maintaining CO2 insufflation, and analysed with the specimen imager to check for positive margins (PSM) before doing the urethra-vesical anastomosis. RESULTS: On average, the time required by XEOS AURA® to analyse each specimen was 12 minutes (SD 3). Total and positive nodal yield were 17.3 (5.8) and 0.3 (0.5 SD), respectively. PET/CT specimen imager showed a marked uptake for the only positive node retrieved, and a diffuse, weak uptake in several negative nodes. There was a good correspondence between marked uptake and node positivity, reflecting also preoperative PET/CT findings (Table 1). XEOS AURA® was useful to predict negative surgical margins, although in one locally advanced case this evaluation was uncertain. CONCLUSIONS: The use of PET/CT specimen imager is safe and feasible. The intraoperative knowledge of prostate cancer (PCa) location within lymph nodes or inside the prostate is essential to improve the oncological radicality of the procedure while safely pushing the boundaries of a hyper-conservative surgery. Source of Funding: University of Turin © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e927 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco Oderda More articles by this author Serena Grimaldi More articles by this author Giorgio Calleris More articles by this author Daniele D'Agate More articles by this author Federico Lavagno More articles by this author Alessandro Marquis More articles by this author Giancarlo Marra More articles by this author Desireé Deandreis More articles by this author Paolo Gontero More articles by this author Expand All Advertisement PDF downloadLoading ...

PD09-12 THE USE OF 68 Ga-FAP-2286 PET IMAGING IN PATIENTS WITH LOCALIZED BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD09-12 THE USE OF 68Ga-FAP-2286 PET IMAGING IN PATIENTS WITH LOCALIZED BLADDER CANCER Domenique Escobar, Vadim Koshkin, Brad Kline, Jonathan Chou, Maxwell Meng, Terence Friedlander, Vipul Kumar, Thomas Hope, and Sima Porten Domenique EscobarDomenique Escobar More articles by this author , Vadim KoshkinVadim Koshkin More articles by this author , Brad KlineBrad Kline More articles by this author , Jonathan ChouJonathan Chou More articles by this author , Maxwell MengMaxwell Meng More articles by this author , Terence FriedlanderTerence Friedlander More articles by this author , Vipul KumarVipul Kumar More articles by this author , Thomas HopeThomas Hope More articles by this author , and Sima PortenSima Porten More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003240.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer is a common and often aggressive malignancy. Computed tomography (CT), magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) are used for staging but have limitations in identifying nodal or metastatic disease. Fibroblast activation protein (FAP) is a cell surface protein that is highly expressed on cancer-associated fibroblasts present in many cancers, including bladder cancer. We present the results of a pilot study assessing the diagnostic performance of 68Ga-FAP-2286 (FAP)-PET imaging in a cohort of patients with bladder cancer. METHODS: Patients with solid tumors underwent FAP-PET as part of a clinical trial (NCT04621435), including 16 patients with bladder cancer. We report on ten patients with clinically localized disease treated with curative intent at the time of imaging. Standard imaging with CT, MRI, FDG-PET, or bone scan was performed within 8 weeks of FAP-PET. The maximum standardized uptake value (SUV) and size of FAP-PET-positive lesions (defined as any focus of activity with at least 1.5 times higher SUV compared with mediastinal blood pool) were documented. RESULTS: Patient demographics and clinical stage are summarized in Table 1. Concordance of 12 FAP-PET scans was 33% with standard imaging and 43% with FDG-PET. Of 8 patients with pathologic or radiographic follow up, FAP-PET was concordant with true disease status in 100%. Two patients had FAP-PET before and after neoadjuvant chemotherapy; one had resolution of lymph node uptake and one had decreased but persistent uptake on (pathology from pelvic lymph node dissection positive for urothelial carcinoma). We highlight two cases where FAP-PET altered treatment decisions (Figure 1). CONCLUSIONS: FAP-PET has the potential to change treatment pathways and improve patient care by better identifying metastatic sites or falsely positive lymph nodes in cancers considered clinically localized and by improving response assessment to systemic therapy. Source of Funding: IIT from Clovis © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e245 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Domenique Escobar More articles by this author Vadim Koshkin More articles by this author Brad Kline More articles by this author Jonathan Chou More articles by this author Maxwell Meng More articles by this author Terence Friedlander More articles by this author Vipul Kumar More articles by this author Thomas Hope More articles by this author Sima Porten More articles by this author Expand All Advertisement PDF downloadLoading ...

MP61-12 WHICH MEN WITH CN1 PROSTATE CANCER AT PSMA PET/CT REPRESENT THE IDEAL CANDIDATE TO RADICAL PROSTATECTOMY? DEVELOPMENT OF A NOVEL RISK STRATIFICATION TOOL FOR INDIVIDUALIZED APPROACHES BASED ON A LARGE, MULTI-INSTITUTIONAL SERIES

MP61-12 WHICH MEN WITH CN1 PROSTATE CANCER AT PSMA PET/CT REPRESENT THE IDEAL CANDIDATE TO RADICAL PROSTATECTOMY? DEVELOPMENT OF A NOVEL RISK STRATIFICATION TOOL FOR INDIVIDUALIZED APPROACHES BASED ON A LARGE, MULTI-INSTITUTIONAL SERIES

A machine learning tool to improve prediction of mediastinal lymph node metastases in non-small cell lung cancer using routinely obtainable [18F]FDG-PET/CT parameters

BackgroundIn patients with non-small cell lung cancer (NSCLC), accuracy of [18F]FDG-PET/CT for pretherapeutic lymph node (LN) staging is limited by false positive findings. Our aim was to evaluate machine learning with routinely obtainable variables to improve accuracy over standard visual image assessment.MethodsMonocentric retrospective analysis of pretherapeutic [18F]FDG-PET/CT in 491 consecutive patients with NSCLC using an analog PET/CT scanner (training + test cohort, n = 385) or digital scanner (validation, n = 106). Forty clinical variables, tumor characteristics, and image variables (e.g., primary tumor and LN SUVmax and size) were collected. Different combinations of machine learning methods for feature selection and classification of N0/1 vs. N2/3 disease were compared. Ten-fold nested cross-validation was used to derive the mean area under the ROC curve of the ten test folds (“test AUC”) and AUC in the validation cohort. Reference standard was the final N stage from interdisciplinary consensus (histological results for N2/3 LNs in 96%).ResultsN2/3 disease was present in 190 patients (39%; training + test, 37%; validation, 46%; p = 0.09). A gradient boosting classifier (GBM) with 10 features was selected as the final model based on test AUC of 0.91 (95% confidence interval, 0.87–0.94). Validation AUC was 0.94 (0.89–0.98). At a target sensitivity of approx. 90%, test/validation accuracy of the GBM was 0.78/0.87. This was significantly higher than the accuracy based on “mediastinal LN uptake > mediastinum” (0.7/0.75; each p < 0.05) or combined PET/CT criteria (PET positive and/or LN short axis diameter > 10 mm; 0.68/0.75; each p < 0.001). Harmonization of PET images between the two scanners affected SUVmax and visual assessment of the LNs but did not diminish the AUC of the GBM.ConclusionsA machine learning model based on routinely available variables from [18F]FDG-PET/CT improved accuracy in mediastinal LN staging compared to established visual assessment criteria. A web application implementing this model was made available.

Impact of 18 F-Fluciclovine PET/CT Findings on Failure-Free Survival in Biochemical Recurrence of Prostate Cancer Following Salvage Radiation Therapy.

We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.

Added Value of Abnormal Lymph Nodes Detected with FDG-PET/CT in Suspected Vascular Graft Infection

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal (18F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on 18F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. 18F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). 18F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ2: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of 18F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ2: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on 18F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used 18F-FDG PET/CT interpretation criteria.

Role of [18F] FDG PET-CT in detection of COVID-19 vaccine-associated hypermetabolic lymphadenopathy (VAHL) in lymphoma patients: with serologic testing correlation

BackgroundCOVID-19 vaccination of the population has a great importance, especially in oncological patients. The high incidence of vaccine-associated hypermetabolic lymphadenopathy (VAHL) makes a difficulty in the diagnosis of PET-CT of oncological patients. They should be vaccinated in the side opposite to the expected malignant LNs to avoid unnecessary biopsy and change in therapy. The aim of this study was to assess the role of PET-CT in detection of VAHL after the 2nd dose of Pfizer-BioNTech vaccine in lymphoma patients and compare the incidence of VAHL among lymphoma patients treated with B cell depletion therapy during the 6 months prior to vaccination and those treated > 6 months before vaccination.ResultsThis study comprised 120 lymphoma patients, referred for FDG PET/CT 1–3 weeks after the 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Hypermetabolic LNs were identified in 55%. The incidence of VAHL in lymphoma patients treated with anti-CD20 antibody rituximab during the 6 months prior to vaccination (9%) was significantly lower compared with other lymphoma patients treated with anti-CD20 antibody rituximab > 6 months before vaccination (91%). The incidence and grades of VAHL are significantly high within the 1st week after the 2nd dose of Pfizer-BioNTech vaccine in patients younger than 60 years of age. Only 7 of 37 patients with negative serology had VAHL on PET-CT, whereas 10 of 26 patients with decreased anti-spike titers and 49 of 57 patients with increased anti-spike titers had VAHL on PET-CT.ConclusionsVAHL makes challenges in the interpretation of FDG PET/CT in oncology patients. Accurate data collection, regarding the time and site of COVID vaccination, is important to help radiologists in identifying the cause of abnormal nodal FDG uptake. We suggest to schedule FDG PET-CT for lymphoma patients at least 3 weeks after the 2nd dose of Pfizer-BioNTech vaccine.

Dual-tracer 99mTc-sestamibi/ 123I imaging in primary hyperparathyroidism.

Surgery is the only curative treatment for primary hyperparathyroidism (PHPT). Preoperative imaging is always recommended. 99mTc-sestamibi scintigraphy is often used in combination with neck ultrasonography as first-line imaging. 99mTc-sestamibi scintigraphy plays a major role in depicting ectopic parathyroid lesions, as well as in guiding a targeted, minimally invasive parathyroidectomy (MIP). Detecting multiple gland disease (MGD) is important to reduce the risks of surgical failure or unplanned conversion to bilateral surgery. However, the ability to recognize MGD varies greatly depending on the 99mTc-sestamibi imaging protocol that is used. Dual-tracer 99mTc-sestamibi/123I highly improves MGD detection compared to single-tracer "dual-phase" 99mTc-sestamibi imaging. It can thus improve patient selection for MIP. The main requirements for successful dual-tracer imaging are: 1) to acquire 99mTc-sestamibi and 123-iodine images simultaneously, thus avoiding motion artifacts on subtraction images; to use neck pinhole imaging, in addition to planar imaging, to improve resolution and MGD detection; to follow with dual-tracer SPECT/CT imaging to better define anatomic position of detected parathyroid lesions. If dual-tracer 99mTc-sestamibi/123I and neck ultrasonography are negative or inconclusive, the second-line imaging in our practice is 18F-fluorocholine PET/CT. The CT component of 18F-fluorocholine PET/CT is performed as non-enhanced acquisition plus a contrast-enhanced arterial phase acquisition, to minimize the risk from false-positives due to choline uptake in inflammatory lymph nodes. We use the same strategy of first-line dual-tracer 99mTc-sestamibi/123I plus neck ultrasonography, followed if necessary by second-line contrast-enhanced 18F-fluorocholine PET/CT, in patients requiring reoperation for persistent or recurrent PHPT. Additional localization techniques are now rarely necessary.

Axillary Lymph Node Uptake on 18F-FDG PET/CT after COVID-19 Vaccination: A Direct Comparison Study with Influenza Vaccination.

To compare vaccinated-side axillary lymph node uptake on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) after coronavirus disease-2019 (COVID-19) and influenza vaccination. We retrospectively analyzed 177 patients who underwent 18F-FDG PET/CT after COVID-19 or influenza vaccination. We compared the uptake of the vaccinated-side axillary lymph nodes of 109 COVID-19 vaccinated patients with those of a lot of influenza-vaccinated patients. We also compared the uptake between 66 patients who received the first COVID-19 vaccination with 43 who received the second COVID-19 vaccination. 18F-FDG-avid axillary lymph nodes on the vaccinated side were significantly more frequently observed in the COVID-19 group (45%) than in the influenza group (19%) (p<0.001). When the interval between vaccination to PET/CT was within 7 days, there was no significant difference in the frequency of 18F-FDG-avid vaccinated-side axillary lymph nodes between the groups (COVID-19 group: 41% vs. influenza group: 45%, p=0.724). When the interval was over 7 days, 18F-FDG-avid lymph nodes were much more frequent in the COVID-19 group (47%) than in the influenza group (7%) (p<0.001). Comparing the first and second COVID-19 groups, 18F-FDG-avid lymph nodes were more frequent in the second vaccination group than in the first vaccination group, but the difference was not significant. 18F-FDG-avid vaccinated-side axillary lymph nodes were more frequently observed in the COVID-19 group than in the influenza group. In the case of the COVID-19 vaccine, a delay of 18F-FDG PET/CT examination is recommended by a longer interval from vaccination than in the influenza vaccine.

Primary Isolated Breast Lymphoma Presenting as Primary Breast Cancer with 18F-FDG PET/CT.

A 40-year-old woman with a palpable mass lesion in her right breast suggested as breast cancer was admitted to 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) unit for the metabolic characterization of the lesion and for the staging of the disease. The patient had no fever and no evidence of weight loss or night sweats. 18F-FDG PET/CT revealed an isolated solid mass lesion with increased 18F-FDG uptake in the upper outer quadrant of the right breast and increased 18F-FDG uptake in the lymph nodes of the right axilla suspected as primary breast cancer and its local lymph node metastasis. There was no other pathological 18F-FDG uptake in the whole body. Excisional biopsy histopathology revealed diffuse large B-cell non-Hodgkin lymphoma.

Clinical Utility of Second-Look FDG PET-CT to Stratify Incomplete Metabolic Response Post (Chemo) Radiotherapy in Oropharyngeal Squamous Cell Carcinoma.

Incomplete response on FDG PET-CT following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC) hinders optimal management. The study assessed the utility of an interval (second look) PET-CT. Patients with oropharyngeal squamous cell carcinoma cancer (OPSCC) treated with CRT at a single centre between 2013 and 2020 who underwent baseline, response, and second-look PET-CT were included. Endpoints were conversion rate to complete metabolic response (CMR) and test characteristics of second-look PET-CT. In total, 714 patients with OPSCC underwent PET-CT post-radiotherapy. In total, 88 patients with incomplete response underwent second-look PET-CT a median of 13 weeks (interquartile range 10-15 weeks) after the initial response assessment. In total, 27/88 (31%) second-look PET-CTs showed conversion to CMR, primary tumour CMR in 20/60 (30%), and nodal CMR in 13/37 (35%). In total, 1/34 (3%) with stable tumour/nodal uptake at the second-look PET-CT relapsed. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of second-look PET-CT were 95%, 49%, 50%, and 95% for tumour and 92%, 50%, 50%, and 92% for nodes, respectively. Primary tumour progression following CMR occurred in one patient, two patients with residual nodal uptake at second-look PET-CT progressed locoregionally, and one patient developed metastatic disease following CMR in residual nodes. Most patients undergoing second-look PET-CT converted to CMR or demonstrated stable PET signal. NPV was high, suggesting the potential to avoid unnecessary surgical intervention.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging.

We observed several patients presenting 2-[18F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [18F]Choline PET/CT. The aim of our study was to describe this source of false positive cases. All patients examined by PET/CT were included in the study. Data concerning patient anamnesis, laterality, and time interval from recent COVID-19 vaccination were recorded. SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination. Among 712 PET/CT scans with 2-[18F]FDG, 104 were submitted to vaccination; 89/104 patients (85%) presented axillary and/or deltoid tracer uptake, related to recent COVID-19 vaccine administration (median from injection: 11 days). The mean SUVmax of these findings was 2.1 (range 1.6-3.3). Among 89 patients with false positive axillary uptake, 36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas, prior to the scan: 6/36 patients with lymph node metastases showed no response to therapy or progression disease. The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8. Only 1/31 prostate cancer patients examined by [18F]Choline PET/CT showed post-vaccine axillary lymph node uptake. These findings were not recorded at PET/CT scans with [18F]-6-FDOPA, [68Ga]Ga-DOTATOC, and [18F]-fluoride. Following COVID-19 mass vaccination, a significant percentage of patients examined by 2-[18F]FDG PET/CT presents axillary, reactive lymph node uptake. Anamnesis, low-dose CT, and ultrasonography facilitated correct diagnosis. Semi-quantitative assessment supported the visual analysis of PET/CT data; SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes. [18F]Choline uptake in reactive lymph node after vaccination was confirmed. After the COVID-19 pandemic, nuclear physicians need to take these potential false positive cases into account in daily clinical practice.

Lymphoscintigraphy in patients with breast cancer-related lymphedema after sentinel lymph node dissection and axillary radiation therapy

The purpose of this study was to investigate lymphoscintigraphy pattern according to the presence or absence of axillary site radiation therapy (aRTx) in breast cancer-related lymphedema (BCRL) patients who underwent sentinel lymph node dissection (SLND). The participants were patients who visited our facility from July 2014 to June 2021 due to upper extremity edema. Among them, patients who underwent SLND after the diagnosis of breast cancer were included. The participants were divided into a group without aRTx (group A) and a group with aRTx (group B). In each patient's lymphoscintigraphy, axillary lymph node uptake (ALNU), lymphatic flow delay, dermal back flow, and the presence of any collateral pathway were checked. Thirty-three patients were enrolled. In all, 27 patients were classified in Group A, and 6 patients were classified in Group B. Between the 2 groups, we found a significant difference (P value < .05) between groups at ALNU and lymphatic flow delay. However, there was no significant difference between groups at the dermal backflow and the presence of a collateral pathway (P value > .05). And 24.2% of patients who developed lymphedema after SLND showed normal lymphoscintigraphy. In this study we suggest that SLND and aRTx affects the activity of the axillary lymph node and ultimately adversely affects lymphatic flow, becoming a risk factor for lymphedema. In addition, regardless of SLND or aRTx, lymphedema may eventually occur in the patient with normal lymphoscintigraphy.

Novel 68Ga-FAPI PET/CT Offers Oncologic Staging Without COVID-19 Vaccine-Related Pitfalls.

In the setting of ongoing coronavirus disease 2019 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by 18F-FDG PET/CT. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT is a new oncologic imaging tool that may overcome this limitation. Methods: We assessed postvaccine head-to-head and same-day 18F-FDG and 68Ga-FAPI-46 PET/CT findings in a series of 11 patients from a large, prospective imaging registry. All patients with documented tracer uptake in locoregional lymph nodes on PET/CT or PET/MRI, after vaccination within 6 wk, were eligible for investigation. Result: Significant visual lymph node uptake adjacent to the injection site was noted in 11 of 11 (100%) patients with 18F-FDG PET/CT, versus 0 of 11 (0%) with 68Ga-FAPI PET/CT. 18F-FDG detected 73% and 68Ga-FAPI PET/CT 94% of all tumor lesions. Conclusion: In this case-series study, 68Ga-FAPI showed its potential to avoid 18F-FDG PET/CT postvaccination pitfalls and presented superior tumor localization.

O-31 - [89Zr]Zr(oxinate)4 radiolabelling of human neutrophil extracellular microvesicles (EVs): in vivo PET imaging reveals extensive uptake in lymph nodes and brain in a mouse model of rheumatoid arthritis

O-31 - [89Zr]Zr(oxinate)4 radiolabelling of human neutrophil extracellular microvesicles (EVs): in vivo PET imaging reveals extensive uptake in lymph nodes and brain in a mouse model of rheumatoid arthritis

PSAT041 A Rare Case of Severe Cyclical Cushing Syndrome Due to Ectopic ACTH Secretion by Appendiceal Carcinoid

Abstract Cushing syndrome (CS) secondary to ectopic ACTH secretion (EAS) is rare and accounts for 10% of CS with majority being bronchial or gut neuroendocrine tumors (NETs) and squamous cell lung cancer. There are only a few case reports of EAS due to appendiceal carcinoid. A 24-year-old woman was referred to endocrinology for 60-pound weight gain, acne, hirsutism, generalized weakness, heat intolerance, and hot flashes. She had secondary amenorrhea for 6 months prior to presentation. Family history was significant for bronchial carcinoid in mother. On examination, she had moon facies, wide purple striae on abdomen, hirsutism, dorsocervical and supraclavicular fat pads. She had normal blood pressure. Her laboratory workup showed potassium 3.2 mmol/L (N, 3.5-5.3), urine free cortisol (UFC) 539 mcg/24 hours (N&amp;lt;50), ACTH 54 pg/ml (N, 6-50) and post 1-mg dexamethasone suppression test cortisol 8.8 mcg/dL. CT abdomen revealed a 3-cm enhancing appendiceal mass, enlarged periappendiceal mesenteric lymph nodes and a 4-cm enhancing right hepatic lobe lesion. Ga-68 Dotatate PET/CT confirmed increased radiotracer uptake in appendiceal mass, lymph nodes and hepatic mass. On liver biopsy, pathology showed well differentiated NET Grade 1 and positive ACTH stain. Repeat UFC was 65 mcg/24 hrs and serum cortisol went down to &amp;lt;1 mcg/dL indicating severe cyclical CS. She was referred to surgical oncology for opinion on debulking surgery. Her genetic testing was negative. She was started on Lanreotide. Given severe cyclical CS with extensive tumor burden, she underwent robotic bilateral adrenalectomy with a plan for cytoreductive surgery once she is on physiologic doses of steroids. Appendiceal NET causing Ectopic CS is exceedingly rare. In 20 years’ experience at NIH, there was only one case of appendiceal NET reported. First reported case was in 1971, when CS was cured by resection of an appendiceal carcinoid incidentally detected on laparotomy for adrenalectomy. There are 3 additional case reports in literature of appendiceal carcinoid with ectopic CS. Management can be challenging particularly in patients with metastatic disease. Medical therapy should be individualized, and adrenalectomy should be considered early in patients with uncontrolled CS due to EAS. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Association of Pretreatment Circulating Tumor Tissue–Modified Viral HPV DNA With Clinicopathologic Factors in HPV-Positive Oropharyngeal Cancer

Circulating tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA is a dynamic, clinically relevant biomarker for HPV-positive oropharyngeal squamous cell carcinoma. Reasons for its wide pretreatment interpatient variability are not well understood. To characterize clinicopathologic factors associated with TTMV HPV DNA. This cross-sectional study included patients evaluated for HPV-positive oropharyngeal squamous cell carcinoma at Dana-Farber Cancer Institute in Boston, Massachusetts, between December 2019 and January 2022 and who were undergoing curative-intent treatment. Clinicopathologic characteristics including demographic variables, tumor and nodal staging, HPV genotype, and imaging findings. Pretreatment circulating TTMV HPV DNA from 5 genotypes (16, 18, 31, 33, and 35) assessed using a commercially available digital droplet polymerase chain reaction-based assay, considered as either detectable/undetectable or a continuous score (fragments/mL). Among 110 included patients, 96 were men (87%) and 104 were White (95%), with a mean (SD) age of 62.2 (9.4) years. Circulating TTMV HPV DNA was detected in 98 patients (89%), with a median (IQR) score of 315 (47-2686) fragments/mL (range, 0-60 061 fragments/mL). Most detectable TTMV HPV DNA was genotype 16 (n = 86 [88%]), while 12 patients (12%) harbored other genotypes. Circulating TTMV HPV DNA detection was most strongly associated with clinical N stage. Although few patients had clinical stage N0 disease, only 4 of these 11 patients (36%) had detectable DNA compared with 94 of 99 patients (95%) with clinical stage N1 to N3 disease (proportion difference, 59%; 95% CI, 30%-87%). Among patients with undetectable TTMV HPV DNA, more than half (7 of 12 [58%]) had clinical stage N0 disease. The TTMV HPV DNA prevalence and score increased with progressively higher clinical nodal stage, diameter of largest lymph node, and higher nodal maximum standardized uptake value on positron emission tomography/computed tomography. In multivariable analysis, clinical nodal stage and nodal maximum standardized uptake value were each strongly associated with TTMV HPV DNA score. Among 27 surgically treated patients, more patients with than without lymphovascular invasion had detectable TTMV HPV DNA (12 of 12 [100%] vs 9 of 15 [60%]). In this cross-sectional study, circulating TTMV HPV DNA was statistically significantly associated with nodal disease at HPV-positive OPSCC diagnosis. The few patients with undetectable levels had predominantly clinical stage N0 disease, suggesting assay sensitivity for diagnostic purposes may be lower among patients without cervical lymphadenopathy. Mechanisms underlying this association, and the use of this biomarker for surveillance of patients with undetectable baseline values, warrant further investigation.

Development and Validation of Diagnostic Interpretation Criteria for Evaluation of F-18 Fluoromisonidazole Hypoxia PET/CT – Inter-Reader Reliability and Accuracy

<h3>Purpose/Objective(s)</h3> F-18 Fluoromisonidazole (FMISO) is a robust imaging biomarker for tumor hypoxia. Hypoxia limits effective cancer treatment, specifically radiotherapy in head and neck cancers. We have completed and have ongoing trials using hypoxia imaging to guide radiation dose de-escalation. To ensure wide applicability, we sought to develop and validate standardized qualitative and quantitative criteria to accurately and reliably interpret clinical FMISO PET/CT images. <h3>Materials/Methods</h3> All HPV+ oropharyngeal cancer patients who had FMISO PET/CT imaging before and about 2 weeks into chemoradiation therapy and pre-treatment F-18 FDG PET/CT were included. 4 independent nuclear medicine (NM) physicians with varying clinical experience of 1, 3, 5, and 15 years with no FMISO experience interpreted images. Training and reference interpretations were performed by a 5^th NM physician with 30 years of clinical and 15 years of FMISO experience. Suspicious cervical lymph nodes (LN) > 1 cm in short axis with abnormal FDG avidity on FDG PET/CT were categorized as positive or negative for FMISO uptake. A LN was considered positive if it demonstrated SUVmax visually greater than floor of mouth (FOM). FMISO SUVmax of the LN and FOM were obtained using a 3D VOI. The training and validation process consisted of: (1) initial instruction; (2) practice interpretation; (3) one on one re-training on contentious group reads; (4) final group training; (5) validation interpretation of new scans. Qualitative, visual comparison of FMISO uptake in LN to FOM, and quantitative, ratio of FMISO SUVmax of LN to FOM, were analyzed. The Fleiss κ coefficient (κ) was calculated to measure inter-reader agreement. <h3>Results</h3> 192 FMISO scans were included. Qualitative criteria mean sensitivity and specificity (SE/SP) after initial instruction were 0.773 and 0.809. κ was 0.338. Mean SE/SP after additional training were 0.976 and 0.869. κ was 0.864 [95%CI: 0.782 to 0.944]. For the quantitative criteria, ROC curve analysis was used to estimate the best threshold by maximizing the Youden index, which was determined to be SUVmax LN/SUVmax FOM > 1.2. Quantitative criteria mean SE/SP after additional training were 0.896 and 0.953. κ was 0.859 (95%CI: 0.761 to 0.944). The quantitative criteria alone demonstrated a lower sensitivity than the qualitative, 0.896 vs. 0.976. Therefore, we suggest using a hybrid method with quantitative criteria as a guide with the ultimate decision based on qualitative assessment to minimize the number of patients with false negatives and subsequent undertreatment. <h3>Conclusion</h3> The hybrid qualitative/quantitative diagnostic interpretation criteria developed for evaluating FMISO PET/CT in combination with dedicated training has substantial inter-reader agreement and excellent diagnostic performance. This suggests that multi-institutional studies that employ FMISO PET for patient stratification in prospective trials are feasible and can be implemented.

Immuno-PET Monitoring of CD8+ T Cell Infiltration Post ICOS Agonist Antibody Treatment Alone and in Combination with PD-1 Blocking Antibody Using a 89Zr Anti-CD8+ Mouse Minibody in EMT6 Syngeneic Tumor Mouse

PurposeThe presence and functional competence of intratumoral CD8+ T cells is often a barometer for successful immunotherapeutic responses in cancer. Despite this understanding and the extensive number of clinical-stage immunotherapies focused on potentiation (co-stimulation) or rescue (checkpoint blockade) of CD8+ T cell antitumor activity, dynamic biomarker strategies are often lacking. To help fill this gap, immuno-PET nuclear imaging has emerged as a powerful tool for in vivo molecular imaging of antibody targeting. Here, we took advantage of immuno-PET imaging using 89Zr-IAB42M1-14, anti-mouse CD8 minibody, to characterize CD8+ T-cell tumor infiltration dynamics following ICOS (inducible T-cell co-stimulator) agonist antibody treatment alone and in combination with PD-1 blocking antibody in a model of mammary carcinoma.Procedures.Female BALB/c mice with established EMT6 tumors received 10 µg, IP of either IgG control antibodies, ICOS agonist monotherapy, or ICOS/PD-1 combination therapy on days 0, 3, 5, 7, 9, 10, or 14. Imaging was performed at 24 and 48 h post IV dose of 89Zr IAB42M1-14. In addition to 89Zr-IAB42M1-14 uptake in tumor and tumor-draining lymph node (TDLN), 3D radiomic features were extracted from PET/CT images to identify treatment effects. Imaging mass cytometry (IMC) and immunohistochemistry (IHC) was performed at end of study.Results89Zr-IAB42M1-14 uptake in the tumor was observed by day 11 and was preceded by an increase in the TDLN as early as day 4. The spatial distribution of 89Zr-IAB42M1-14 was more uniform in the drug treated vs. control tumors, which had spatially distinct tracer uptake in the periphery relative to the core of the tumor. IMC analysis showed an increased percentage of cytotoxic T cells in the ICOS monotherapy and ICOS/PD-1 combination group compared to IgG controls. Additionally, temporal radiomics analysis demonstrated early predictiveness of imaging features.ConclusionTo our knowledge, this is the first detailed description of the use of a novel immune-PET imaging technique to assess the kinetics of CD8+ T-cell infiltration into tumor and lymphoid tissues following ICOS agonist and PD-1 blocking antibody therapy. By demonstrating the capacity for increased spatial and temporal resolution of CD8+ T-cell infiltration across tumors and lymphoid tissues, these observations underscore the widespread potential clinical utility of non-invasive PET imaging for T-cell-based immunotherapy in cancer.

Omicron Variant of COVID-19: Imaging Pattern on F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

We report a case of omicron infection in a biopsy-proven case of carcinoma breast sent for staging F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) during the omicron COVID wave. FDG PET/computed tomography (CT) revealed increased FDG uptake in nasopharyngeal, oropharynx, and tonsillar regions and bilateral cervical lymph nodes along with uptake in primary carcinoma and locoregional lymph nodes. Based on the clinical history and specific pattern of FDG PET/CT findings (as suggested by SNMMI Taskforce), COVID history and reverse transcription polymerase chain reaction positivity was elicited.