Node Uptake Research Articles

Abstract P2-12-07: Fdg PET/CT early response prediction for triple negative breast cancer neoadjuvant chemotherapy with addition of carboplatin

Abstract Introduction. The addition of carboplatin to standard neoadjuvant chemotherapy (NAC) including dose-dense (dd) anthracycline-cyclophosphamide (AC) combination followed by taxanes in triple negative breast cancer (TNBC) is the most intense routinely used approach, not widely accepted and potentially of increased toxicity. Fluorodeoxyglucose PET/CT ealy response assessment may aid to decide about treatment intensification. The aim of our study was to define the optimal cut-off of SUVmax decrease for pathological complete response (pCR) prediction after one cycle of AC regimen, in patients who received further AC and taxane plus carboplatin. Material and Methods. 122 patients with TNBC were enrolled into neoadjuvant chemotherapy (NAC) within STRATEGMED 2/267398/4/NCBR/2015 research project in our center between Jan 2018 and Dec 2020, upon approval of Ethics Commitee. Among them 15 patients still continued neoadjuvant treatment at the time of data cut-off, 3 patients did not receive anthracyclines because of lifetime cumulative dose with previous treatments, in 2 patients treatment was interrupted during first cycles of anthracycline-based treatment and in one patient there was no evident (18)F-fluorodeoxyglucose uptake. Remaining 101 patients were enrolled into this study. Baseline PET/CT study before NAC was performed in all patients, 73 patients had baseline PET/CT as well as additional study performed after 1st cycle of chemotherapy. Majority of patients received ddAC followed by docetaxel plus every-three-week carboplatin or weekly paclitaxel plus weekly carboplatin. Patients with residual disease received 8 cycles of capecitabine treatment adjuvantly. Radiation therapy was performed according to guidelines, concurrently or before capecitabine treatment. Mann-Whitney U test was used to assess differences in variables, predictive value was evaluated by receiver-operating characteristic (ROC) curve analysis. Results. 54 patients (53,5%) achieved pCR after neoadjuvant chemotherapy. At baseline, median of SUVmax in breast was 10.2 (IQR 7.2-14.4), whereas median of SUVmax in lymph nodes was 3.7 (IQR 0-10.0). In 16 patients (16%) baseline SUVmax in lymph nodes was higher than in breast (ratio>1). Higher baseline value of SUVmax was associated with pCR achievement (p=0.037). Median SUVmax decrease in breast after one cycle of chemotherapy was 33% (IQR 11%-52%) and was predictive for pCR (p=0.000021). Median decrease of 18-FDG uptake in lymph nodes was more pronounced than in breast (53%; IQR 29%-84%) and was also associated with pCR achievement (p=0.012). For pCR prediction SUVmax decrease cut-off of 40% provided optimal trade-off between sensitivity and specificity, with positive likelihood ratio 2.35, negative likelihood ratio 0.33, positive predictive value 80% and negative predictive value 64%. By ROC analysis, AUC for the prediction of pCR was 0.7604 (p=0.036). Conclusions. While high decrease of SUVmax relatively strongly indicates high pCR chance in TNBC neoadjuvant chemotherapy, lower decrease does not preclude pCR occurrence when intensive four-drug sequential regimen with carboplatin is used. Studies assessing response in reverse sequence chemotherapy with carboplatin are warranted. The study was supported by the Polish National Center of Research and Development MILESTONE project - Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015. Citation Format: Marcin Kubeczko, Anna Michalik, Agnieszka Badora-Rybicka, Anna Polakiewicz-Gilowska, Andrea d'Amico, Michał Kalemba, Aleksandra Leśniak, Katarzyna Świderska, Marta Mianowska-Malec, Agnieszka Pasierbek, Barbara Łanoszka, Konstanty Chomik, Barbara Bobek-Billewicz, Michał Jarząb. Fdg PET/CT early response prediction for triple negative breast cancer neoadjuvant chemotherapy with addition of carboplatin [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-07.

18F-Alfatide II for the evaluation of axillary lymph nodes in breast cancer patients: comparison with 18F-FDG.

18F-Alfatide II has been translated into clinical use and been proven to have good performance in identifying breast cancer. In this study, we investigated 18F-Alfatide II for evaluation of axillary lymph nodes (ALN) in breast cancer patients and compared the performance with 18F-FDG. A total of 44 female patients with clinically suspected breast cancer were enrolled and underwent 18F-Alfatide II and 18F-FDG PET/CT within a week. Tracer uptakes in ALN were evaluated by visual analysis, semi-quantitative analysis with maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and SUVmax ratio of target/non-target (T/NT). Among 44 patients, 37 patients were pathologically diagnosed with breast cancer with metastatic (17 cases) or non-metastatic (20 cases) ALN. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of visual analysis were 70.6%, 90%, 81.1%, 85.7%, and 78.3% for 18F-Alfatide II, 64.7%, 90%, 78.4%, 84.6%, and 75% for 18F-FDG, respectively. By combining 18F-Alfatide II and 18F-FDG, the sensitivity significantly increased to 82.4%, the specificity was 85%, the accuracy increased to 83.8%, the PPV was 82.4%, and the NPV significantly increased to 85.0%. Three cases of luminal B subtype were false negative for both 18F-Alfatide II and 18F-FDG. The other 2 false negative cases of 18F-Alfatide II were triple-negative subtype and 3 false negative cases of 18F-FDG were luminal B subtype too. The AUCs of three semi-quantitative parameters (SUVmax, SUVmean, T/NT) for 18F-Alfatide II were between 0.8 and 0.9, whereas those for 18F-FDG were more than 0.9. 18F-Alfatide II T/NT had the highest Youden index (76.5%), specificity (100%), accuracy (89.2%), and PPV (100%) among these semi-quantitative parameters. 18F-Alfatide II uptake as well as 18F-FDG uptake in metastatic axillary lymph nodes (MALN) was significantly higher than that in benign axillary lymph nodes (BALN). Both 18F-Alfatide II and 18F-FDG did not show difference in primary tumor uptake irrespective of ALN status. 18F-Alfatide II can be used in breast cancer patients to detect metastatic ALN, however, like 18F-FDG, with high specificity but relatively low sensitivity. The combination of 18F-Alfatide II and 18F-FDG can significantly improve sensitivity and NPV. 18F-Alfatide II T/NT may serve as the most important semi-quantitative parameter to evaluate ALN.

18F]FDG uptake in axillary lymph nodes and deltoid muscle after COVID-19 mRNA vaccination: a cohort study to determine incidence and contributing factors using a multivariate analysis.

PurposeReactive FDG uptake in the axillary lymph nodes (ALN) and deltoid muscle (DM) after COVID-19 mRNA vaccination has been recognized, although the actual situation in the Japanese population remains unknown. To determine the incidence of reactive FDG uptake and its contributing factors, we retrospectively studied a cohort of subjects who were vaccinated at our hospital.MethodsWhole-body FDG-PET/CT examinations performed in 237 subjects out of 240 subjects with a definite history of COVID-19 vaccination (BNT162b2; BioNTech-Pfizer) were analyzed. Positivity and SUVmax of FDG uptake in the ALN and DM ipsilateral to vaccination, various subject characteristics, and the grade of the pathological FDG-PET/CT findings were evaluated using a multivariate analysis.ResultsFDG uptake in the ALN and DM ipsilateral to vaccination was seen in about 60% of the subjects even soon (0–4 days) after the first vaccination, with percentages reaching 87.5% and 75.0%, respectively, after the second vaccination. DM uptake had almost disappeared at around 2 weeks, while ALN uptake persisted for 3 weeks or longer. A multivariate analysis showed that a short duration since vaccination, a younger age, a female sex, and a low FDG-PET/CT grade (minimal pathological FDG uptake) contributed significantly to positive ALN uptake, while a short duration since vaccination and a female sex were the only significant contributors to positive DM uptake. This study is the first to identify factors contributing to positive FDG uptake in ALN and DM after COVID-19 vaccination.ConclusionA high incidence of FDG uptake in ALN and DM was observed after vaccination. ALN uptake seemed to be associated with a younger age, a female sex, and minimal pathological FDG uptake. After vaccination, an acute inflammatory reaction in DM followed by immune reaction in ALN linked to humoral immunity may be speculated.

Use of Fluoro-[18F]-Deoxy-2-D-Glucose Positron Emission Tomography/Computed Tomography to Predict Immunotherapy Treatment Response in Patients With Squamous Cell Oral Cavity Cancers

Neoadjuvant immunotherapy is a novel approach with the potential to improve outcomes for patients with oral cavity squamous cell cancer (OCSCC). Adverse events of varying severity are reported with immunotherapy, and a biomarker to predict response would be clinically useful to avoid toxic effects in those unlikely to benefit. To correlate changes on fluoro-[18F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans with primary tumor pathologic response and immunologic biomarkers in patients with OCSCC receiving neoadjuvant immunotherapy. This was a retrospective analysis of serial FDG-PET/CT scans obtained prospectively as part of a phase 2 open-label randomized clinical trial investigating neoadjuvant immunotherapy in patients with untreated OCSCC between 2016 and 2019. Included were a total of 29 patients from a single academic medical center with untreated OCSCC (≥T2, or clinically node positive) randomized 1:1 to receive neoadjuvant therapy with single agent nivolumab or combination nivolumab and ipilimumab followed by surgery and standard of care adjuvant therapy. The interventions in this study were FDG-PET/CT scans before (T0) and after (T1) preoperative immunotherapy. Data collected from FDG-PET/CT scans included maximum standardized uptake value (SUVmax) of primary OCSCC and cervical lymph nodes (LNs) at T0 and T1 and new LN uptake and uptake consistent with radiologic immune-related adverse events (irAEs) at T1. Primary OCSCC pathologic response reported as percentages of viable vs nonviable tumor. The number of CD8+ cells/mm2 was determined in the primary tumor biopsy specimen and at surgery. There was no correlation between pathologic response and change in SUVmax in the primary OCSCC between T0 and T1. Out of 27 total participants, 13 had newly FDG-avid ipsilateral LNs at T1, most negative on pathology. A total of 9 had radiologic irAEs, most commonly sarcoid-like LN (7 of 27). No correlations were found between primary OCSCC SUVmax at T0 and CD8+ T-cell number in the primary tumor biopsy, and no correlations were found between primary OCSCC SUVmax at T1 and CD8+ T-cell number in the primary tumor at surgery. There were no correlations between changes in FDG uptake after neoadjuvant immunotherapy and pathologic primary tumor response. Importantly, newly FDG-avid ipsilateral LNs following neoadjuvant immunotherapy were commonly observed but did not represent progressive disease or indicate pathologically disease positive nodes in most cases. These findings argue against altering surgical plans in this setting and suggest that the role of FDG-PET/CT may be limited as an early imaging biomarker for predicting pathologic response to preoperative immunotherapy for OCSCC. ClinicalTrials.gov Identifier: NCT02919683.

Differentiation of Reactive Lymph Nodes and Tumor Metastatic Lymph Nodes With 68Ga-FAPI PET/CT in a Patient With Squamous Cell Lung Cancer.

False-positive findings of mediastinal lymph node often confound the image interpretation of the preoperative PET/CT in non-small cell lung cancer. In this case, we reported 18F-FDG and 68Ga-FAPI PET/CT findings in a patient with squamous cell lung cancer. 18F-FDG-based TNM stage was stage IIIA (T1bN2M0) due to increased uptake in the enlarged right lower paratracheal lymph node. However, no abnormal 68Ga-FAPI uptake was observed in this lymph node. Subsequent histopathological examination revealed no evidence of malignancy in the mediastinal lymph nodes. Therefore, the tumor stage was downstaged to stage IA (T1bN0M0), which was in accordance with 68Ga-FAPI-based TNM stage.

LYMPH NODE UPSTAGING AFTER SURGERY IN PATIENTS WITH NEGATIVE MEDIASTINAL STAGING BY EBUS.

Mediastinal staging is a hot topic in thoracic oncology. According to the guidelines, and besides other criteria, in the presence of a primary lung cancer with increased mediastinal lymph node uptake on PET-CT, a negative result after lymph node sampling by Endobronchial Ultrasound (EBUS) is not enough to rule out mediastinal lymph node involve- ment, demanding a cervical mediastinoscopy to vouch for the results. In order to study the percentage of lymph node surgical upstaging in patients with neg- ative mediastinal node staging by EBUS and evaluate the role of mediastinoscopy in these patients, we conducted a search in our department's database using the key-word EBUS in the period concerned between January 2014 and August 2020. A total of 302 patients were found. After applying defined criteria, we obtained 42 cases. Lymph node surgical upstaging occurred in 11 (26%) patients, of which 8 were upstaged to N2 and 3 to N1. Most of the cases were single station. Only in 5 (12% of the total) of the 11 patients, the upstaging was related to lymph node stations previously sampled by EBUS. Upstaging was more frequent among males and lower lobe tumours. Regarding the 8 upstage cases for N2, 5 were single station. Of these 8 cases, only 5 would be approachable by cervical mediastinoscopy. Furthermore, 2 of them were single station, eligible for upfront surgery. Then, only in 3 (7%) of the 42 cases cervical mediastinoscopy would be of foremost importance.

Node Positivity in T1b Gallbladder Cancer: A High Volume Centre Experience

Introduction: Identification of early stage gallbladder cancer is difficult which is why about half of the patients are diagnosed post simple cholecystectomy . Simple cholecystectomy is considered adequate for T1a gall bladder cancer, however T1b requires radical cholecystectomy due to chances of lymph node metastasis. Methods: A retrospective review of a prospectively maintained database of gall bladder cancer patients operated at our institute from March 2010 to March 2021 was conducted. Only patients with proven gallbladder adenocarcinoma on final histopathology report were included. Results: There were a total of 1,245 patients of upfront and revision surgery for gall bladder cancer in this period. There were 76 patients of T1b stage of which 11 patients underwent upfront surgery and 65 patients were diagnosed as incidental gall bladder carcinoma. Neoadjuvant treatment was given to 9 patients due to uptake in periportal nodes and they were excluded from final analysis. The median age was 50 years (28-72 years). The median nodal harvest was 8 nodes (2-24 nodes). Positive nodes were found in 7 (10.44%) out of 67 patients with pT1b in final histopathology report. After a median follow up of 47.5 months (range 2-120 months), 7 (10.4%) patients had succumbed due to disease, 2 were alive with disease and 3 were lost to follow up with an OS of 89% and DFS of 86%. Conclusion: Nodal positivity for T1b gall bladder cancer ranges around 10% and radical surgery with complete peri –portal lymphadenectomy should be considered as standard of care.

Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA

PurposeThe fibroblast activation protein (FAP) is an emerging target for molecular imaging and therapy in cancer. OncoFAP is a novel small organic ligand for FAP with very high affinity. In this translational study, we establish [68Ga]Ga-OncoFAP-DOTAGA (68Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging, and evaluate its application in clinical PET scanning.Methods68Ga-OncoFAP was synthesized in a cassette-based fully automated labeling module. Lipophilicity, affinity, and serum stability of 68Ga-OncoFAP were assessed by determining logD7.4, IC50 values, and radiochemical purity. 68Ga-OncoFAP tumor uptake and imaging properties were assessed in preclinical dynamic PET/MRI in murine subcutaneous tumor models. Finally, biodistribution and uptake in a variety of tumor types were analyzed in 12 patients based on individual clinical indications that received 163 ± 50 MBq 68Ga-OncoFAP combined with PET/CT and PET/MRI.Results68Ga-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity, and stability of 68Ga-OncoFAP measured are ideally suited for PET imaging. PET and gamma counting–based biodistribution demonstrated beneficial tracer kinetics and high uptake in murine FAP-expressing tumor models with high tumor-to-blood ratios of 8.6 ± 5.1 at 1 h and 38.1 ± 33.1 at 3 h p.i. Clinical 68Ga-OncoFAP-PET/CT and PET/MRI demonstrated favorable biodistribution and kinetics with high and reliable uptake in primary cancers (SUVmax 12.3 ± 2.3), lymph nodes (SUVmax 9.7 ± 8.3), and distant metastases (SUVmax up to 20.0).ConclusionFavorable radiochemical properties, rapid clearance from organs and soft tissues, and intense tumor uptake validate 68Ga-OncoFAP as a powerful alternative to currently available FAP tracers.

Factors associated with lymph node metastasis upstage after resection for patients with micropapillary lung adenocarcinoma.

BackgroundMicropapillary adenocarcinoma has a poor prognostic histological pattern. Additionally, preoperative detection of lymph node metastases by preoperative examination is difficult in some patients with micropapillary adenocarcinoma, and postoperative upstage may occur. However, clinicopathological features of patients with micropapillary adenocarcinoma with nodal upstage have not been established, therefore this study aimed to identify the factors associated with potential lymph node metastases during preoperative examination to ensure effective surgical procedures.MethodsBetween January 2011 and December 2020, 1029 patients received complete resection for primary non‐small‐cell lung cancer by lobectomy or more extensive resection with systematic lymph node dissection at this institution. One hundred and thirty‐one patients diagnosed with adenocarcinoma with micropapillary component were included in this study. The clinicopathological features of patients with nodal upstage whose postoperative N stage was more advanced than the preoperative N stage were examined.ResultsForty patients had nodal upstage after resection. 18F‐fluorodeoxyglucose (FDG) positron emission tomography‐computed tomography (PET‐CT) revealed that a maximum standardized uptake value (SUVmax) ≥5 for the primary lesion was significantly associated with postoperative nodal upstage. There were no significant differences in terms of sex, age, smoking history, surgical procedure, and diabetes. Among 38 patients with nodal upstage, 23 patients had no significant preoperative lymphadenopathy and showed no abnormal FDG uptake in the lymph nodes on 18F‐FDG‐PET‐CT, respectively.ConclusionsLymph node metastases were suspected in patients preoperatively diagnosed with micropapillary adenocarcinoma with FDG SUVmax ≥5 for the primary tumor. Therefore, standard surgical resection and careful lymph node dissection should be performed for such patients.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema: a preliminary study

BackgroundWe investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema.Materials and methodsA total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and four types of dermal backflow patterns (absent; distal only; proximal only; whole lower limb) were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole lower limb at 3 months (early response) and 1 year (late response) was measured. Volume difference ratios (continuous variable and binary variable with a cut-off value of zero) were compared according to the lymphoscintigraphic variables.ResultsThe group with whole lower limb dermal backflow had a greater volume change than the other groups (p = 0.047). The group with dermal backflow in the whole lower limb OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p = 0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p = 0.016, p = 0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p = 0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p = 0.040).ConclusionsPreoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

ASSESSMENT OF LYMPHEDEMA WITH LYMPHOSCINTIGRAPHY: CAN NODAL QUANTIFICATION HELP?

Lymphoscintigraphy with combined qualitative and quantitative analysis is reported to be a more sensitive approach to diagnose lymphedema in comparison with the conventional clinical analysis. Our study seeks to evaluate the diagnostic performance of lower limb lymphoscintigraphy with amalgamation of qualitative and quantitative analysis by measuring the ilio-inguinal nodal uptake. This prospective observational study was comprised of 86 patients (172 limbs) diagnosed with lower limb lymphedema. After a thorough clinical grading of edema, radionuclide lymphoscintigraphy was performed as per a dedicated institutional protocol. Ilio-inguinal nodal quantification of tracer uptake was computed along with the visual study of the scans. Additionally, the corresponding mean nodal uptake percentage for each grade of lymphedema was assessed and a cut off nodal uptake percentage to differentiate between normal and abnormal limbs was defined. Although quantitative analysis with nodal uptake percentage provides objective criteria to diagnose lymphedema, it can only act as an adjunct to qualitative method without replacing it. Finally, standardization of procedure for quantitative lymphoscintigraphy is needed including the potential for combining both rate of clearance of tracer from injection site and nodal uptake for quantification.

Initial Institutional Experience with 18F-Fluciclovine PET-CT in Biochemical Recurrence of Prostate Cancer.

18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

Intraindividual comparison of [68\xa0Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

BackgroundThe analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice.MethodsA retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [68Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed.ResultsDifferences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%).ConclusionIn terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

P07 Rheumatoid arthritis, joint pain with raised CRP: more than a flare

Case report - IntroductionRheumatoid arthritis is a chronic inflammatory autoimmune systemic disorder of unknown aetiology that predominantly affects the joints. Moreover, it is a systemic illness associated with a variety of extraarticular manifestations, including haematological complications such as lymphoma. We are presenting a case highlighting the importance of surveillance in these patients, particularly elderly patients with longstanding disease. Case report - Case descriptionA 72-year-old female patient of African-Caribbean origin was referred to the rheumatology department from the community clinic for RA deterioration. She was diagnosed with RA RF anti-CCP positive in 2007 and was treated with sc MTX 25 mg weekly, HQ 200 mg bd, pred 5 mg and naproxen 250 mg. Her past medical history included HTN, OA, R TKR and degenerative lower back pain.Patient reported: ‘Doctor, I ‘ve had RA for many years, but never before I had such a pain’.She was complaining of multiple joint pains, morning stiffness of up to 2hrs, widespread pain and fatigue. She reported weight loss of 5 pounds in the last 2 months. For the last 2 weeks, she was suffering from lower back pain, L leg sciatica, with pins and needles, L leg weakness and incontinence. She was otherwise well.On examination she had 8 mildly swollen, 0 tender joints, VAS score was 90/100. DAS-28 was 4.92.Blood tests showed normocytic anaemia Hb 107, raised ESR 58 and CRP 124, previously 22 and 5.8. Anaemia screening, immunoglobulins and free light chains were normal. Biologic screening was normal. Repeating the blood tests following IM steroid injection, ESR was 81 and CRP 187. Alternative diagnosis such as infection and malignancy were suspected. A plan was made to review in the clinic and arrange further investigations with a CT scan. MRI spine was arranged which identified multiple osseous deposits L3-L5, T8-T12, T1, C2, retroperitoneal psoas mass, paravertebral mass and multiple retroperitoneal lymph nodes.CT revealed lung nodules and splenic lesions possible metastatic and right ileac destructive lesion. PET CT showed multiple active uptake in lymph nodes above and below diaphragm, the spleen and lung nodules, axial and appendicular skeleton.Patient had a bone marrow biopsy which revealed diffuse large B-cell lymphoma.Case report - DiscussionThis is a case of a patient with a 13-year history of rheumatoid arthritis, who was stable until last year and presented with worsening joint pain. Joint examination did not correlate with the severity of her pain. However. fluctuations in disease activity and variation throughout the day are common in rheumatoid arthritis and patient reported morning stiffness. Differential diagnosis initially included RA flare up with the possibility that osteoarthritis, fibromyalgia and degenerative spinal disease could also exacerbate her pain. However, ESR and CRP were significantly raised disproportionally for the joint count. Moreover, she had systemic symptoms with weight loss and fatigue raising the question of an alternative diagnosis such as malignancy or infection. Patient did not have obvious symptoms or signs of infection, and baseline investigations, such as CXR and urine dipstick were normal and TB spot was negative. However, there was concern for an occult infection. Malignancy could be a potential diagnosis as the risk increases with age, and haematological malignancies, particularly lymphoma, have been associated with RA. Myeloma could be an alternative diagnosis, based on anaemia and back pain; however, myeloma screening came back normal.Patient was diagnosed with stage IVB diffuse large B-cell lymphoma with metastatic bone disease, paravertebral mass, retroperitoneal lymph nodes, psoas mass, pulmonary nodules, and splenic lesions. Her joint and back pain were related to metastatic bone disease. She was treated with 2 cycles R-CHOP, 4 cycles R mini-CHOP. She repeated the PET CT which showed improvement. CRP dropped to 1.3.Case report - Key learning pointsRheumatoid arthritis is a systemic disease and the raised inflammatory markers do not necessarily indicate RA flare. We should consider other causes in our differential diagnosis, such as infection and malignancy.Studies have shown 2-fold increased risk for lymphoma in RA patients, HL, NHL and particularly the diffuse large B-cell Lymphoma. The risk of having lymphoma correlates with disease activity. DMARD treatment including anti-TNF does not seem to increase the risk which is probably driven by the systemic inflammation causing persistent immunologic stimulation, B cell clonal expansion and transformation along with decreased T suppressor cells and NK activity.Therefore, EULAR recommends systemic screening for infections and malignancy, along with other co-morbidities as part of the routine care in patients with rheumatoid arthritis. At the end, we should always listen to the patient’s story.

Clinical Significance of Peritumoral Adipose Tissue PET/CT Imaging Features for Predicting Axillary Lymph Node Metastasis in Patients with Breast Cancer.

We investigated whether textural parameters of peritumoral breast adipose tissue (AT) based on F-18 fluorodeoxyglucose (FDG) PET/CT could predict axillary lymph node metastasis in patients with breast cancer. A total of 326 breast cancer patients with preoperative FDG PET/CT were retrospectively enrolled. PET/CT images were visually assessed and the maximum FDG uptake of axillary lymph nodes (LN SUVmax) was measured. From peritumoral breast AT, 38 textural features of PET imaging were extracted. The diagnostic ability of PET based on visual analysis, LN SUVmax, and textural features of peritumoral breast AT for predicting axillary lymph node metastasis were assessed using the area under the receiver operating characteristic curve (AUC) values. Among the 38 peritumoral breast AT textural features, grey-level co-occurrence matrix (GLCM) entropy showed the highest AUC value (0.830) for predicting axillary lymph node metastasis. The value of GLCM entropy was higher than that of visual analysis (0.739; p < 0.05) and the AUC value was comparable to that of LN SUVmax (0.793; p > 0.05). In the subgroup analysis of patients with negative findings on visual analysis, GLCM entropy still showed a high diagnostic ability (AUC: 0.759) in predicting lymph node metastasis. The findings suggest a potential diagnostic role of PET/CT imaging features of peritumoral breast AT in predicting axillary lymph node metastasis in patients with breast cancer.

Clinical Significance of [18F] Fluoro-2-Deoxy-d-Glucose/Computed Tomographic Avid Hilar Lymph Nodes in Esophageal Carcinoma Patients

BackgroundThe assumption that increased [18F] fluoro-2-deoxy-d-glucose (FDG) uptake in hilar nodes on positron emission tomography/computed tomography (PET/CT) imaging is indicative of distant metastasis can result in palliative rather than curative care in patients with esophageal cancer. This study aimed to determine the significance of increased FDG uptake in hilar nodes in patients with potentially curable, locally advanced disease at initial staging. MethodsWe included patients with biopsy specimen-proven esophageal carcinoma who had pretreatment FDG-PET/CT at initial staging and follow-up imaging >1 year. We excluded patients with distant hematogeneous metastases. Hilar nodes were considered concerning for metastatic disease when the maximum standardized uptake value was >2.5 or FDG uptake was visually greater than the mediastinal background. ResultsWe reviewed FDG-PET CT scans from 806 patients treated for esophageal cancer from 2010 to 2018 and identified 42 patients with FDG-avid hilar adenopathy. Thirteen patients underwent histologic assessment, and 29 were monitored with imaging. None of the 42 patients had distant metastatic disease on the initial workup, and all were treated curatively. In follow-up, 2 of 42 patients eventually manifested hilar nodal metastases after treatment; 1 who had a biopsy specimen-negative hilar node at initial staging and another who did not have a biopsy of the hilar node. ConclusionsIncreased FDG uptake in hilar nodes in patients with localized esophageal cancer was not indicative of nonregional nodal metastasis. Patients in these situations should be approached with curative intent. The need for biopsy of FDG-avid hilar nodes in this cohort should be carefully considered due to the low diagnostic utility.

Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model.

Simple SummaryIn this study, the following injection characteristics were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model: (a) iron dose, (b) effect of dilution, (c) effect of injecting at different time courses and (d) effect of massaging the injection site. In conclusion, injection dose and time were primary factors for the SLN iron uptake. The result from this study will provide a background for magnetic procedures.The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 μg, showing a plateau uptake of 80 μg in the SLN around 1000 μg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose.

Imaging of ανβ3 integrin expression in rheumatoid arthritis with [68Ga]Ga-NODAGA-RGDyk PET/CT in comparison to [18F]FDG PET/CT

[68Ga]Ga-NODAGA-RGDyk PET/CT and [18F]FDG PET/CT were performed in a 65-year-old woman during the work-up of a squamous cell carcinoma of the tongue within a clinical study protocol. Images revealed both tracers’ uptake in the primary tumor and cervical lymph nodes, but also bilaterally in the shoulders, elbows, wrists, metacarpophalangeal, interphalangeal, and hip joints. The patient had been diagnosed with rheumatoid arthritis 8 years prior to the examination. Images showed a significantly higher [18F]FDG than [68Ga]Ga-NODAGA-RGDyk uptake in primary tumor and cervical lymph nodes. However, the patient with moderately active rheumatoid arthritis had similar levels of [68Ga]Ga-NODAGA-RGDyk and [18F]FDG uptake in the involved joints, but with no [68Ga]Ga-NODAGA-RGDyk uptake in the surrounding muscles, unlike with [18F]FDG. Our case suggests that [68Ga]Ga-NODAGA-RGDyk PET/CT allows imaging of integrins expression in rheumatoid arthritis, including integrins expressed in synovial angiogenesis, with potentially a better signal-to-noise ratio than on [18F]FDG PET/CT.

S3686 A Rare Case of Duodenal Neuroendocrine Tumor

Introduction: Neuroendocrine tumors of the duodenum (D-NET) are rarely seen constituting less than 2-3% of gastrointestinal tumors. With NET on rising, it is important to recognize this rare tumor and treat it with early surgical or endoscopic resection. Case Description/Methods: A 52-year-old white male was seen in the office for new onset of dysphagia worse with solid food for few months. He had a history of squamous cell carcinoma of the tongue and had undergone surgical resection with concurrent chemotherapy with cisplatin. His examination and laboratory findings were unremarkable. On endoscopic examination, the patient was found to have a 5 mm size nodule in the second part of the duodenum which was removed with a cold biopsy (Figure A&B). The histopathologic findings were consistent with a well-differentiated neuroendocrine tumor (NET) (figure C&D). The tumor cells were strongly positive for synaptophysin (figure-D), CD56, chromogranin and showed < 1% of Ki-67 labeling index supporting the diagnosis of NET. A PET/CT- GA-68 Dotatate scan confirmed no residual tumor but an increased uptake in the lymph nodes above and below the diaphragm was noted (figure E). These lymphadenopathies are likely falsely positive given the symmetric uptake with awaiting biopsy on follow up. Three months later a repeat endoscopy with biopsy of previous polypectomy site did not show any evidence of remnant NET. Oncology was consulted with suspected disseminated NET and is awaiting further investigation. Discussion: NET is a type of epithelial tumor with predominant neuroendocrine differentiation arising from various organs of the body. The majority of these cases arise from the gastrointestinal tracts followed by lungs, pancreas, ovaries, and head & neck region. Although the GI tract is the most common site of occurrence the NET-D are very rarely seen, constituting less than 3% of GI NET. The overall rate of the NET is on rising with an annual rate of 6.3%. This rise to some extent can be attributed to increased diagnostic imaging utilization. D-NETs produce symptoms based on their location resulting in abdominal pain, intestinal obstruction, jaundice, or rarely pancreatitis. By the virtue of their hormonal production, they can lead to flushing, diarrhea, skin rashes, nausea, or peptic ulcer disease. It is important to recognize these rare tumors and treat them either with surgical or endoscopic resection.Figure 1:: Figure A& B: Esophagogastroduodenoscopy (EGD) – A 5 mm size nodule seen in the second part of the duodenum with normal covering mucosa removed with cold biopsy. Figure C: Duodenal nodule on biopsy (H & E stain @ 4X) - The nested appearance of monomorphic population of tumor cells without nucleoli, necrosis or brisk mitotic activity consistent with neuroendocrine tumor. Figure D: Duodenal nodule on biopsy (4X)- Synaptophysin Immunohistochemical Stain positive consistent with neuroendocrine tumor. Figure E: PET/CT- GA-68 Dotatate: No duodenal uptake noted. Multiple radiotracer acid lymph nodes above and below the diaphragm with prominent on the axilla and bilateral iliac chain & inguinal region.

ABCL-087: Lymphocytic Pleural Effusion: An Unusual Initial and Isolated Presentation of Non-Hodgkin Lymphoma

Pleural involvement from diffuse large B-cell lymphoma (DLBCL) has been reported in the literature, and it is associated with poor outcome. However, non-Hodgkin lymphoma presenting as an isolated pleural effusion is unusual. Here we report the case of 84-year-old female patient, without past medical history, who presented for worsening shortness of breath. Investigations were pertinent for a left pleural effusion without other clinically significant findings in the laboratory and radiological work-up. A left pleural thoracentesis showed a lymphocytic exudative effusion. The complete screening for fungal or bacterial etiologies, including mycobacterium tuberculosis, was negative. The cytology didn't reveal any abnormal or malignant cells. Unfortunately, the effusion worsened 48 hours after the prior pleural tap. We repeated the thoracentesis, and we were able to obtain a cell block. Microscopic evaluation and immunohistochemistry were relevant for numerous intermediate to large-sized tumor cells with round nuclei; they stained positive for CD20, multiple myeloma-1 (MUM1), B-cell chronic lymphocytic leukemia/lymphoma (Bcl6), Bcl2, and negative for CD3, CD138, CD10. The Ki67 was 95%. Thus, she was diagnosed with DLBCL involving the left pleura. 18-fluorodeoxyglucose (FDG) PET-CT scan showed an isolated hypermetabolic left pleural effusion without any other nodal or skeletal uptake. Bone marrow biopsy was negative for any lymphomatous infiltration. Taking into consideration her age, she was started on R-mini-CHOP chemotherapy protocol with drastic improvement of the pleural effusion after the first session. She completed 6 cycles of R-mini-CHOP with primary G-CSF prophylaxis and is currently in complete remission. Although it is a rare entity, isolated pleural DLBCL should be considered whenever we have a non-resolving lymphocytic pleural effusion. Clinicians and pathologists must be aware of this diagnosis which is made by cytopathology, immunohistochemistry, and flow cytometry on pleural fluid.