High Standardized Uptake Value Research Articles

Imaging findings of Epstein-Barr Virus-positive inflammatory follicular dendritic cell sarcoma of spleen: A case report.

Spleen Epstein-Barr Virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (FDCS) is rare, and the imaging signs are unclear. The COVID-19 has been confirmed to be the cause of pneumonia and can cause a variety of diseases including myocarditis. However, it has not been reported to be the cause of the exacerbation or activation of EBV-positive inflammatory FDCS. The objective is to extract the imaging features of EBV-positive inflammatory FDCS in the spleen and analyze the reasons for the special features of this case. By analyzing the patient's treatment process and imaging examinations (A 77-year-old female was admitted to the hospital due to generalized discomfort and pain symptoms. When she was admitted to the hospital a year earlier with COVID-19 pneumonia, a chest CT scan showed that she had a splenic tumor. During this admission, CT scans showed two irregularly shaped and unevenly dense soft tissue density masses within the spleen, with uneven enhancement on contrast-enhanced im-aging within the solid components and along the edges. PET/CT scans revealed elevated glucose metabolism in the masses. Postoperative pathological diagnosis confirmed splenic EBV-positive inflammatory FDCS.), reading the literature, sorting out the disease cognitive process, epidemiology, and pathological data of EBV-positive inflammatory FDCS, we discussed the imaging manifestations and possible differential diagnosis of the disease. The patient was finally diagnosed with splenic EBV-positive inflammatory FDCS. Imaging features of EBV-positive inflammatory FDCS in the spleen include a high incidence of hemorrhage and necrosis, persistent moderate enhancement of the solid portion, a "capsular-like enhancement" structure at the tumor edge, and possibly active glucose metabolism with high Standardized Uptake Values (SUVs). COVID-19 infection and long-term COVID-19 sequelae may exacerbate and activate EBV-positive inflammatory FDCS in the spleen, and the mechanism remains to be further studied.

Prognostic relevance of tumor-infiltrating CD4+ cells and total metabolic tumor volume-based risk stratification in diffuse large B-cell lymphoma.

To elucidate the relationship between pre-treatment radiomic parameters and the proportions of various tumour-infiltrating (TI) cells, we retrospectively analysed the association of total metabolic tumour volume (TMTV) and TI cells on biopsied tumour lesions in 171 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The surface markers of TI cells were analysed by multicolour flow cytometry using a dissected single-cell suspension. In examining the correlation between TI cells and PET-derived parameters (SUVmax, TMTV, and total lesion glycolysis), intratumoural cell types minimally influenced the results, except for a weak negative correlation between CD4+ cells and SUVmax (R=-0.16, P=0.045). Even for the lesion fluorodeoxyglucose uptake at the biopsied site, CD19+ cells (indicative of malignant burden) showed only a weak correlation with the highest SUV (R=0.21, P=0.009), whereas CD3+ (R=-0.25, P=0.002) and CD4+ cells (R=-0.29, P.

Differentiation of benign and metastatic lymph nodes in soft tissue sarcoma

Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients. In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined LN were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and imaging parameters. Patients with LNM exhibited significantly larger short axis diameter (SAD) and long axis diameter (LAD) vs. patients with benign LN (median 22.5 vs. 14 mm, p < 0.001 and median 29.5 vs. 21 mm, p = 0.003, respectively). Furthermore, the presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scans were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression over time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/L, p = 0.005 and 1.5 vs. 0.55 mg/dL, p = 0.039, respectively). This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.

Imaging to predict early relapses after treatment discontinuation in patients with large vessel giant cell arteritis – A cohort study

ObjectivesTo investigate the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in predicting relapse after treatment discontinuation in patients with large-vessel giant cell arteritis (LV-GCA). MethodsThis study included patients with LV-GCA whose treatment was discontinued between 2018 and 2023. All patients underwent PET/CT and/or MRI at the time of treatment discontinuation in clinical remission. Qualitative and quantitative PET/CT scores, by measuring standardized uptake values (SUV), and semiquantitative MRI scores of the aorta and supraaortic vessels were compared between patients who relapsed within 4 months after treatment discontinuation and those who did not. ResultsForty patients were included (median age 67.4 years, interquartile range (IQR) 60.8–74.0; 77.5 % females). Eleven patients (27.5 %) relapsed after treatment discontinuation (time to relapse 1.9 months, IQR 1.4–3.3). Patients who relapsed were comparable to those who remained in remission with respect to the presence of active vasculitis on MRI and/or PET/CT (54.5% vs. 58.6 %, p = 1.0), the number of segments with vasculitic findings on MRI (0, IQR 0.0–1.5, vs. 2, IQR 0.0–3.0, p = 0.221) or the highest SUV artery/liver ratio on PET/CT (1.5, IQR 1.4–1.6, vs. 1.3, IQR 1.2–1.6, p = 0.505). The median number of vasculitic segments on PET/CT was 2.5 (IQR 0.5–4.5) in those with vs. 0 (IQR 0.0–1.5, p = 0.085) in those without relapse, and the PET/CT scores 4.5 (IQR 0.75–8.25) vs. 0 (IQR 0.0–3.0, p = 0.172). ConclusionPET/CT or MRI at treatment stop did not predict relapse and may not be suited to guide treatment decisions in patients with LV-GCA in remission.

Outcomes of Patients with Richter Transformation without Prior Chemoimmunotherapy for CLL/SLL: An International Multicenter Retrospective Study

Background: Richter Transformation (RT) refers to the development of an aggressive lymphoma in the setting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Small molecule inhibitors (SMI), such as the Bruton tyrosine kinase inhibitors (BTKi) and BCL2 inhibitors (BCL2i), have revolutionized the treatment of CLL/SLL. Prior studies evaluated outcomes of patients (pts) with RT in an era where chemoimmunotherapy (CIT) was typically used to treat CLL/SLL. Now that SMI are standard of care, fewer pts with CLL/SLL receive CIT, therefore we sought to determine which variables predict survival in pts who developed RT without prior CIT exposure for CLL/SLL. Methods: We conducted an international multicenter retrospective study of pts from 11 academic centers. Pts with RT occurring as large B-cell lymphoma who did not previously receive CIT (e.g., fludarabine, cyclophosphamide, bendamustine, chlorambucil) for their CLL/SLL were included. We collected pt, disease, and treatment (tx) characteristics. RT was categorized into 3 groups: “Concurrent RT,” defined as RT and CLL/SLL diagnosed simultaneously (within 3 months [mos]); “RT w/o prior CLL/SLL tx,” defined as RT and CLL/SLL diagnosed &amp;gt;3 mos apart with the CLL/SLL never treated; and “RT with prior non-CIT tx for CLL/SLL” defined as having received prior CLL/SLL tx. Overall survival (OS) was measured from RT diagnosis (Dx) and estimated using the Kaplan-Meier method. Cox regression model was used to identify prognostic factors associated with OS. Results: 242 pts were identified. At CLL/SLL Dx, 66% of pts had unmutated IGHV, 37% had del17p/ TP53 disruption, and 20% had trisomy 12. At RT Dx, 56% of the RT with prior non-CIT tx for CLL/SLL group had a del17p/ TP53 disruption versus 27% for the concurrent RT group and 18% for the RT w/o prior CLL/SLL tx groups. Median time from CLL/SLL Dx to RT Dx was 47 mos (range 3-394) for RT w/o prior CLL/SLL tx and 46 mos (range 4-218) for RT with prior non-CIT tx for CLL/SLL. Pts with prior non-CIT tx for CLL/SLL received a median of 1 (range 1-5) prior tx. 86% of pts previously received a BTKi or a BCL2i for tx of CLL/SLL (54% BTKi only, 5% BCL2i only, 27% both). The remaining 14% had been treated with an anti-CD20 monoclonal antibody (MoAb), steroids, lenalidomide, radiation, or alemtuzumab. 85% of pts developed RT while on active tx with SMI. Median age at RT Dx was 69 years (range 37-92). At RT Dx, 38% and 21% of pts had del17p/ TP53 disruption, and trisomy 12 in CLL/SLL tissue, respectively. At RT Dx, there was no difference in highest SUV on PET (median 16, range 2.9-65.6), LDH (median 325, range 103-8162, ULN range 180-271), largest lymph node in diameter (median 4.9 cm, range 0-17.1), Ki-67 (median 80%, range 5%-100%), rate of GCB subtype (27%), presence of MYC translocation (20%), or CLL/SLL and RT clonal relationship (81%) for those pts tested amongst the 3 groups ( Table). The most common 1 st line tx for RT was CIT with or w/o radiation and/or steroids (76%), followed by CIT plus SMI (13%), SMI single agent or combination (7%), and other (4%, which includes anti-CD20 MoAb). Median follow-up from RT Dx was 42.3 mos; the median OS for the entire cohort was 25.8 mos (95% CI: 16.8-49.1). Pts with RT after non-CIT tx for CLL/SLL had a significantly worse OS (median 8.2 mos [95% CI: 5.6-14.3]) than pts with concurrent RT (median 46.3 mos [95% CI: 23.8-96.9]) and RT w/o prior CLL/SLL tx (median 63.5 mos [95% CI: 28.3-70.3]) ( Figure). From an exploratory univariable analysis, we found RT after non-CIT tx for CLL/SLL compared to concurrent RT (HR 2.32 [95% CI: 1.55-3.46]), RT Dx age (HR for 5-year increase 1.14 [95% CI: 1.05-1.23]), del17p/ TP53 disruption (HR 2.27 [95% CI: 1.45-3.56]), and LDH (HR for 2-fold increase 1.37 [95% CI: 1.20-1.58]) were prognostic for worse OS. Conclusions: This is the largest cohort of pts who developed RT having received only SMI with no CIT for their CLL reported, thus reflecting the current treatment landscape. Despite being CIT-naïve, pts in our series who received tx for their CLL/SLL and then developed RT had a short OS, underscoring the need to develop better therapies for these pts. In contrast, as in other published analyses (Wang Haematologica 2020), pts w/o prior tx for CLL/SLL had more favorable outcomes, with a median OS of approximately 5 years. Further analysis to determine PFS and OS by tx for RT for pts who have been treated with SMI for their CLL/SLL is ongoing.

The Nature of High-Risk Defining Events in Follicular Lymphoma Determines Overall Survival

Background: A subset of follicular lymphoma (FL) patients will experience a ‘high-risk defining event’ (HRDE) that portends poor survival due to early progression of disease or transformation to diffuse large B cell lymphoma (TFL). Progression of disease within 24 months (POD24) from front-line immunochemotherapy (ICT) identifies patients with a subsequent five-year OS of 50% compared to a reference group of 90% (Casulo et al. JCO 2015). Although a robust surrogate endpoint for OS in clinical trials (Casulo et al. Blood 2022), it remains to be established if the OS of patents is influenced by the nature of the HRDE. In this study, we examined whether characteristics and clinical trajectory of those with relapsed/progressive FL is the same as that of patients experiencing TFL. Methods: We conducted an international retrospective analysis of newly diagnosed FL patients requiring treatment across 14 academic centres between 2002 and 2021 in the era of rituximab and PET-CT staging. Patients were included with grade 1-3A FL requiring first-line (1L) treatment (ICT, rituximab monotherapy or radiotherapy). We excluded patients with untreated FL, de novo TFL and those with &amp;lt;24 months follow up provided they did not experience a HRDE. Baseline clinical, imaging and laboratory values, treatment details and outcomes were collected. We defined HRDE groups as persistent (relapse or progression) FL within 24 months of 1L treatment (FL24), early TFL (&amp;lt;24 months of 1L treatment) or late TFL (&amp;gt;24 months of 1L treatment). Patients not experiencing a HRDE formed the FL reference group. Landmark overall survival (OS) analysis was performed by Cox regression using risk status as a time-varying covariate for time of HRDE. For the FL reference group, landmark was defined at 24 months after 1L treatment. Results: 501 patients met the inclusion criteria and were categorised as: reference FL (n=378), FL24 (n=50), early TFL (n=28), late TFL (n=15). 24 patients who died within 24 months of 1L treatment without documentation of preceding HRDE and were omitted. Median follow up for patients alive beyond 24 months was 5.1 years. Median age at diagnosis was 60 years, 91% had ECOG performance status 0-1 and 38% were high-risk (&amp;gt;3) FLIPI. 1L chemotherapy regimens included: bendamustine (59%), CHOP (24%), CVP (8%), other (9%); a majority received rituximab (80%) vs obinutuzumab (20%). Maintenance therapy was used in 54% of pts. Expectedly, those experiencing HRDE had an inferior OS compared to the reference group (HR 5.23, p&amp;lt;0.001)(Figure 1). However, among HRDE group, median OS significantly differed: early TFL patients (3.0 yrs) and FL24 (12.6yrs)(HR 2.27, p=0.02) (Table 1). There was no difference in OS after HRDE between early TFL and late TFL ( p=0.81). Biopsy was performed in 84% of TFL cases with no difference in OS between biopsy-proven vs clinically suspected cases ( p=0.23). Multivariate OS analysis assessing HRDE and treatment demonstrated no significant interaction between HRDE group and 1L chemotherapy ( p=0.52), monoclonal antibody ( p=0.29) or maintenance therapy ( p=0.27). Several established prognostic features at baseline were enriched in patients who went on to experience HRDE including: ECOG &amp;gt;1 ( p&amp;lt;0.001), raised LDH ( p&amp;lt;0.001), advanced-stage disease (( p&amp;lt;0.011) and high risk FLIPI ( p=0.005). Baseline FDG-PET was available in 259 patients. Adverse PET metrics were enriched in only early TFL, and not FL24 or late TFL patients, including high SUV max( p=0.009), total metabolic tumor volume ( p=0.015) and total lesional glycolysis ( p=0.01). Conclusions: HRDEs after 1L treatment are associated with inferior OS in FL compared with standard-risk patients. Unlike POD24, this study demonstrates disparate clinical outcomes between patients experiencing early progression with persistent FL and those experiencing TFL. Adverse metabolic characteristics on baseline FDG-PET also suggest biological distinction between HRDE subsets. These findings have important implications for epidemiological studies, biomarker development and clinical trials aiming to improve outcomes in this underserved high-risk FL cohort.

Association between the Preoperative Standard Uptake Value (SUV) and Survival Outcomes after Robotic-Assisted Segmentectomy for Resectable Non-Small Cell Lung Cancer (NSCLC).

Lung-sparing procedures, specifically segmentectomies and wedge resections, have increased over the years to treat early-stage non-small cell lung cancer (NSCLC). We investigate here the perioperative and long-term outcomes of patients who underwent robotic-assisted segmentectomy (RAS) at an NCI-designated cancer center and aim to show associations between the preoperative standard update value (SUV) to tumor stage, recurrence patterns, and overall survival. A retrospective analysis was performed on 166 consecutive patients who underwent RAS at a single institution from 2010 to 2021. Of this number, 121 robotic-assisted segmentectomies were performed for primary NSCLC, and a total of 101 patients were evaluated with a PET-CT scan. The SUV from the primary tumor was determined from the PET-CT. The clinical, surgical, and pathologic profiles and perioperative outcomes were summarized via descriptive statistics. Numerical variables were described as the median and interquartile range because all numerical variables were not normally distributed as assessed by the Shapiro-Wilk test of normality. Categorical variables were described as the count and proportion. Chi-square or Fisher's exact test was used for association. The main outcomes were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier (KM) curves were constructed to visualize the OS and RFS, which were also stratified according to tumor histology, the pathologic stage, and standard uptake value. A log-rank test for the equality of survival curves was performed to determine significant differences between groups. The most common postoperative complications were atrial fibrillation (8.8%, 9/102), persistent air leak (7.84%, 8/102), and pneumonia (4.9%, 5/102). The median operative duration was 168.5 min (IQR 59), while the median estimated blood loss was 50 mL (IQR 125). The conversion rate to thoracotomy in this cohort was 3.9% (4/102). Intraoperative complications occurred in 2.9% (3/102). The median hospital length of stay was 3 days (IQR 3). The median chest tube duration was 3 days (IQR 2), but 4.9% (5/102) of patients were sent home with a chest tube. The recurrence for this cohort was 28.4% (29/102). The time to recurrence was 353 days (IQR 504), while the time to mortality was 505 days (IQR 761). The NSCLC patients were divided into the following two groups: low SUV (<5, n = 55) and high SUV (≥5, n = 47). Statistically significant associations were noted between SUV and the tumor histology (p = 0.019), tumor grade (p = 0.002), lymph-vascular invasion (p = 0.029), viscera-pleural invasion (p = 0.008), recurrence (p < 0.001) and the site of recurrence (p = 0.047). KM survival analysis showed significant differences in the curves for OS (log-rank p-value 0.0204) and RFS (log-rank p-value 0.0034) between the SUV groups. Robotic-assisted segmentectomy for NSCLC has reasonable perioperative and oncologic outcomes. Furthermore, we demonstrate here the prognostic implication of preoperative SUV to pathologic outcomes, recurrence-free survival, and overall survival.

Novel SPECT/CT biomarker in transthyretin cardiac amyloidosis: correlation with myocardial amyloid load and cardiac structure and function

Abstract Background Single photon emission computed tomography/computed tomography (SPECT/CT) with determination of standardized uptake value (SUV) allows quantification of cardiac amyloid deposition. Purpose We aimed to investigate the relationship between quantitative cardiac tracer uptake determined by SPECT/CT and myocardial amyloid load, as well as cardiac structure and function in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), and to identify nuclear imaging biomarkers for monitoring disease progression. Methods ATTR-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) scintigraphy and SPECT/CT imaging (n=40) with determination of SUV, as well as cardiac magnetic resonance imaging (CMR, n=25) and transthoracic echocardiography (TTE, n=40). Results We observed significant correlations (r, Pearson's correlation coefficient) between SUV retention index and myocardial amyloid load [CMR extracellular volume (ECV): r=0.565, p=0.004, Figure 1A], cardiac structure [CMR interventricular septum: r=0.409, p=0.042, Figure 1B; CMR left ventricular mass index: r=0.508, p=0.010, Figure 1C], longitudinal cardiac function [TTE left ventricular global longitudinal strain (LV GLS): r=0.531, p=0.003, Figure 1D; TTE right ventricular free wall longitudinal strain: r=0.470, p=0.024, Figure 1E; TTE left atrial reservoir strain (LASr): r=-0.434, p=0.038, Figure 1F] and cardiac biomarkers [N-terminal prohormone of brain natriuretic peptide (NT-proBNP): r=0.475, p=0.004; high-sensitive troponin T (hs-TnT): r=0.358, p=0.027]. ATTR-CM patients were divided into two cohorts based on the median (4.32 mg/dL) of SUV retention index (low SUV uptake cohort: ≤4.32 mg/dL, n=20; high SUV uptake cohort: &amp;gt;4.32 mg/dL, n=20). We observed significant between-cohort differences with respect to LV ejection fraction (low SUV uptake: 51.8% vs. high SUV uptake: 46.2%, p=0.045), LV GLS (-14.5% vs. -11.1%, p=0.001), LASr (11.6% vs. 7.1%, p=0.023), NT-proBNP (1300 pg/mL vs. 2786 pg/mL, p&amp;lt;0.001), hs-TnT (42.9 ng/L vs. 62.2 ng/L, p=0.016) and 6-min walk distance (440.1 m vs. 330.1 m, p=0.022). Conclusions Using quantitative SPECT/CT imaging, we demonstrated that SUV retention index correlates with myocardial amyloid load, cardiac structure and function, and cardiac biomarkers. Our data suggest that quantitative SPECT/CT imaging with determination of SUV retention index may be a valid tool to monitor disease progression in ATTR-CM patients.Figure 1

Metabolic parameters predict survival and toxicity in chimeric antigen receptor T-cell therapy-treated relapsed/refractory large B-cell lymphoma.

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7months [interquartile range (IQR): 2.6-25.5months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (n=45) and 53% (n=31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR=4.7, p=0.01, OR=9.5, p=0.03, respectively) and CR post-CAR T (OR=12.4, p=0.0004, OR=10.9, p=0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR=3.25, p=0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR=4.3, p=0.01), and high SUV pre-CAR T was associated with grade 3-4 neurological events (OR=12, p=0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR=2.4, p=0.03), age ≥60 (HR=2.7, p=0.03), and bulky disease (≥5cm) at the time of apheresis (HR=2.5, p=0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.

Enhancing PSMA PET/CT imaging of prostate cancer: investigating the impact of multiple time point evaluation, diuretic administration, cribriform pattern, and intraductal carcinoma.

Our objective was to correlate staging PSMA PET imaging parameters to final histopathology. Second objective was to assess the performance of standard versus delayed PSMA PET to detect primary prostate tumor. Thirty-one patients (mean age, 61.4 ± 8.2) who underwent radical prostatectomy and preoperative staging PSMA PET scans were included in the study. After defining dominant lesion in pathology, correlations with PET images were performed. Additionally, two physicians blind to clinical and pathological information retrospectively reviewed staging Ga-68 PSMA PET scans with standard and delayed imaging. Dominant lesion SUV's increased with time 8.2(± 4.5), 10(± 7.1), and 10.2(± 7.8) at 1, 2, and 3h (P = .03 T1-T3). WHO Grade group 3 had highest SUV (group 3 11.9 ± 5.6 vs. group 2 7.9 ± 1.5, p = .02). Addition of cribriform pattern on intraductal component was associated with higher SUV's (11 ± 2.9 vs. 6.5 ± 2.1, p = .01) and higher Gleason four ratios (64 ± 9% vs. 37 ± 17%, p = .01). Intraductal carcinoma was associated with larger tumors (6.3 ± 2.3cm3 vs. 2.6 ± 1.7cm3, p < .001). Physician sensitivities ranged from 61 to 81%. Excluding Gleason 3 + 3 lesions and small lesions (< 1cm3), sensitivities increased to 80-100%. Differences of sensitivity between different time points were not significant. Combined evaluation of all time points did not increase sensitivity. Cribriform pattern correlates with higher Gleason 4 ratios and SUVs in PSMA PET. Intraductal carcinoma is associated with larger tumors but not higher Gleason 4 ratios and SUVs. Multiple late imaging times did not enhance tumor detection and may pose tolerability issues for some patients.

Predictive Factors for Response to Adaptive Therapy in Thoracic Stereotactic Ablative Radiotherapy

Online adaptive radiotherapy (ART) has been increasingly adopted for clinical use. However, ART for thoracic malignancies has lagged beyond its implementation for other primary cancers. Efforts are needed to identify optimal patients for ART by finding trends for changes in tumor position, shape, or proximity to OARs are needed. We hypothesized tumor size, histology, pre-RT SUV value, and intrathoracic location could influence how tumors change during cone beam computed tomography (CBCT)-based ART Stereotactic Ablative Radiotherapy (SAbR) for thoracic disease. Data was collected from a prospective registry of patients who received CBCT-ART and SAbR for primary and secondary lung tumors. Dosimetry data was obtained from the simulation planning and the daily adaptive workflow. Central lung tumors were defined as those located within 2 cm of the bronchial tree. Plans were either delivered as per simulation or through the online adaptive workflow delivery (AD). Change in planning tumor volumes (PTV) were calculated between initial and final fractions (ΔPTV). A total of 42 patients with a median age of 67 (range 17-90) and median 8.3 months follow up, treated between June 2021 and December 2022 were included. Most patients had NSCLC or presumed NSCLC (73.85%, 31/42), and most lesions were peripheral (61.9%, 26/42) versus central (31%, 13/42) or apical (7.1%, 3/42). Mean dose and median fractions were 52.5 Gy (SD 8.07) and 5 (range 3-5) while median initial (i) PTV was 31.75 cm3 (IQR 42.3 cm3). On average, ΔPTV decreased by 4.9% (SD 21) and volume shrunk by 5 cm3 (SD 14.5). AD improved per fraction PTV coverage and conformality while esophageal, cardiac, and spinal cord dose were significantly decreased (all p < 0.05), and most fractions were delivered with AD (73.4%, 138/188). AD was aborted most often for small iPTVs. ΔPTV grew >10% for two lesions though their iPTV were < 10 cm3. 12/42 ΔPTV were >10% smaller by the end of RT and corresponded to larger iPTVs. Age, lung primary, metastatic disease, smoking status, and tumor location were not predictive for >10% decrease in ΔPTV. Among 24 biopsy-proven NSCLC ΔPTV was >10% smaller in 6/12 patients (50%) with adenocarcinoma and only in 2/12 (16.7%) with SCC, although this was not significant on χ2 testing (p = 0.08). There were no differences in local, regional, distant failure or death comparing those with a ΔPTV of >10% vs <10% (all p > 0.1). Comparing pre-treatment PET SUV and tumor response, lower SUVs appear to be associated with more PTV shrinkage, with no significant PTV change plateauing at SUV 20. However, this analysis was limited by the number of patients with high SUV values. CBCT-ART SAbR is associated with improved PTV coverage, target conformality, and reduced OAR dose. Large iPTV and adenocarcinomas were more likely to decrease >10%. High metabolic activity appeared predictive for a lack of significant ΔPTV. Further clinical and radiographic features should be explored to predict response to ART.

Combined Metabolic and Functional Tumor Volumes on [18F]FDG-PET/MRI in Neuroblastoma Using Voxel-Wise Analysis.

The purpose of our study was to evaluate the association between the [18F]FDG standard uptake value (SUV) and the apparent diffusion coefficient (ADC) in neuroblastoma (NB) by voxel-wise analysis. From our prospective observational PET/MRI study, a subcohort of patients diagnosed with NB with both baseline imaging and post-chemotherapy imaging was further investigated. After registration and tumor segmentation, metabolic and functional tumor volumes were calculated from the ADC and SUV values using dedicated software allowing for voxel-wise analysis. Under the mean of thresholds, each voxel was assigned to one of three virtual tissue groups: highly vital (v) (low ADC and high SUV), possibly low vital (lv) (high ADC and low SUV), and equivocal (e) with high ADC and high SUV or low ADC and low SUV. Moreover, three clusters were generated from the total tumor volumes using the method of multiple Gaussian distributions. The Pearson's correlation coefficient between the ADC and the SUV was calculated for each group. Out of 43 PET/MRIs in 21 patients with NB, 16 MRIs in 8 patients met the inclusion criteria (PET/MRIs before and after chemotherapy). The proportion of tumor volumes were 26%, 36%, and 38% (v, lv, e) at baseline, 0.03%, 66%, and 34% after treatment in patients with response, and 42%, 25%, and 33% with progressive disease, respectively. In all clusters, the ADC and the SUV correlated negatively. In the cluster that corresponded to highly vital tissue, the ADC and the SUV showed a moderate negative correlation before treatment (R = -0.18; p < 0.0001) and the strongest negative correlation after treatment (R = -0.45; p < 0.0001). Interestingly, only patients with progression (n = 2) under therapy had a relevant part in this cluster post-treatment. Our results indicate that voxel-wise analysis of the ADC and the SUV is feasible and can quantify the different quality of tissue in neuroblastic tumors. Monitoring ADCs as well as SUV levels can quantify tumor dynamics during therapy.

Methodology dependent sex differences in Aβ‐PET measured with SUVR

AbstractBackgroundDetermining Aβ‐PET status is crucial for Alzheimer’s disease trials. Standard uptake value ratio (SUVR) using a reference region is a common semi‐quantitative technique. Sex differences in regional blood flow and white matter (WM) could impact SUVR differentially depending on the reference region. It is important to understand how methodological factors can influence SUVR derived Aβ status.MethodIndividuals from Insight 46 (1946 British birth cohort) underwent PET/MR scanning with [18F]florbetapir (N = 425; mean age (SD) 70.6 (0.7); 49% female). Regions derived from T1‐weighted MRI with geodesic information flows (GIF) were resampled to PET space. SUVR was calculated (50‐60 mins post‐injection) using a cortical composite target normalised to whole cerebellum (WC) or eroded WM, with/without partial volume correction (PVC). Additionally, SUV was calculated normalising to injected dose and weight. Distribution volume ratio (DVR) from Logan graphical analysis (cerebellar grey matter reference) was calculated for N = 391 (51% female). Linear regression was used to investigate differences in Aβ‐PET measures by sex adjusting for region volumes. Aβ status was defined with Gaussian‐mixture modelling. Sex differences in SUVR and DVR were investigated in individuals rated concordantly Aβ‐ with all four SUVR methods. SUVR Aβ status discordance was examined in relation to sex and APOE e4 genotype.ResultFemales had significantly higher SUVR with a WC reference; and there were no sex differences with a WM reference or with dynamic DVR (Figure 1). Males had higher SUV in all regions and the difference was greater in the WC compared to WM (Figure 2). PVC decreased the influence of volume on SUV in the WC but not WM. 87% of individuals were classified concordantly Aβ+/‐ on SUVR measures with equal proportion of males/females. More females were Aβ+ only with WC reference with PVC, whereas more males were Aβ‐ only on WC without PVC (Figure 3).

The effect of high standard uptake value in lung cancer metastatic lesions on survival

The effect of high standard uptake value in lung cancer metastatic lesions on survival

Abstract #1384628: An Incidental Thyroid Lesion on FDG-PET Scan in a Patient with Long History of Hypothyroidism and Radiation Exposure

An 81-year-old woman with history of lung cancer and hypothyroidism with an incidental thyroid lesion on (FDG)-positron emission tomography (PET) scan is subsequently diagnosed with primary thyroid lymphoma (PTL) using flow cytometry. An 81-year-old woman with a history of lung cancer and hypothyroidism presented to the endocrinology office for evaluation of a thyroid lesion. Primary hypothyroidism was diagnosed 30 years prior to presentation and was controlled with levothyroxine 88 mcg daily. Lung cancer was diagnosed 8 years prior, and treated with radiation therapy. Patient had an FDG-PET scan obtained for the evaluation of lung nodules, and a hypermetabolic focus was noted in the left thyroid region with a max SUV of 18. On thyroid ultrasound, the left thyroid lobe appeared heterogenous with solid nodular areas. The physical exam revealed a smooth but firm thyroid gland, without cervical lymphadenopathy. Laboratory workup showed thyroid stimulating hormone and free thyroxine in the normal range. Microsomal antibody was 4.2 IU/mL (< 5.6 IU/mL), and thyroglobulin antibody was 356.4 IU/mL (< 14.4 IU/mL). Fine needle aspiration (FNA) biopsy showed a polymorphous lymphoid sample. Given the high SUV on PET-scan and longstanding history of Hashimoto’s thyroiditis, repeat FNA biopsy with flow cytometry was subsequently performed and showed a lymphoid population consistent with a non-Hodgkin lymphoma (NHL). The patient was referred to oncology and diagnosed with indolent NHL. Further staging revealed interval growth in lung nodules, with biopsy showing recurrence of adenocarcinoma, but no other metastatic disease. The patient underwent radiation therapy for both her lung adenocarcinoma and primary thyroid lymphoma (PTL). Primary thyroid lymphoma accounts for less than 5% of thyroid cancers. It presents with a female predominance in the 7th decade of life, with Hashimoto’s thyroiditis as the main risk factor. Patients may present with an enlarging neck mass, with or without compressive symptoms, and cervical lymphadenopathy. Diagnosis of PTL can be made through FNA biopsy, core biopsy, or open surgical biopsy. It is important to note that because these lesions have few pathognomonic features, diagnosis with FNA biopsy alone can be difficult, and sensitivity is increased to 97% with the use of flow cytometry, as was demonstrated in our case. Treatment is with radiation therapy or combined chemoradiotherapy. Surgery has a role limited to the management of airway compromise, as surgical resection has not proven to improve overall survival. This case highlights the utility of including flow cytometry with FNA sample when diagnosing PTL.

Mycoplasma infection mimicking a malignancy in a waldenstrom macroglobulinemia patient

BackgroundMycoplasma hominis infection is common in urinary tract. 18F-FDG-PET/CT is a valuable tool for tumor and infection diagnosis. Few studies have shown the 18F-FDG-PET/CT images after mycoplasma infection.Case presentationHere we described a case of Waldenstrom macroglobulinemia with thickened bladder wall. The 18F-FDG-PET/CT showed the SUVmax up to 36.1 mimicking bladder cancer. The results of histopathological examination and metagenomic sequencing of the blood and urinary revealed the Mycoplasma hominis infection.ConclusionThe full consideration should be given to the possibility of infection besides tumor in lesions with high SUV value in 18F-FDG-PET/CT, especially in immunodeficiency patients.

Prediction of Treatment Failure in Hodgkin Lymphoma: A Machine Learning Radiomic Approach in Baseline 18F-FDG PET/CT

Purpose: Hodgkin Lymphoma staging and prognostic evaluation through radiomic and machine learning (ML) methods has been little explored. This study explores radiomic features and proposes a new ML radiomic model to predict treatment failure in Hodgkin lymphoma patients from PET images. Methods: 13 radiomic features were extracted from PET images of 51 subjects with Hodgkin’s Lymphoma with response to therapy and 6 subjects with treatment failure as classified by the Lugano criteria for lymphoma response. Univariate analysis was performed for feature selection by means of the areas under ROC curves (AUC), and Pearson correlation was assessed to reduce redundancy in the feature space. A ML algorithm was developed and trained-validated with a six-fold stratified cross validation. The ML performance was assessed through the results of 15 combinations of two-fold validation samples, deriving two ML methods (M1 and M2) for tumor classification at the tumor and patient levels. Results: The features zone percentage (ZP), high intensity large area emphasis (HILAE), entropy and standardized uptake value of maximum pixel (SUVmax) were independent predictors of treatment failure. The ML algorithm performed with AUC=0.86 (M1) and AUC=0.96 (M2) to classify “individual tumors” and at “patient level” performed with sensitivity = 80.0% /specificity = 88.3% (M1) and sensitivity = 100% /specificity = 100% (M2). The ML outperformed the Ann Arbor staging that achieved, respectively, 83.3% and 31.7% for sensitivity and specificity. Conclusions: Evaluation of baseline 18F-FDG PET scans of individuals with Hodgkin’s lymphoma using a ML radiomic model enabled accurate classification of patients at higher risk of treatment failure.

Neutrophil-to-lymphocyte ratio as an independent factor for worse prognosis in radioiodine refractory thyroid cancer patients.

This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS). We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status. NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population.

Do fine needle aspirate cytomorphological features correlate with positron emission tomography findings of metastatic non-small cell lung carcinoma in lymph nodes?

Our objective was to correlate cytomorphological features of metastatic non-small cell lung carcinoma (mNSCLC) with maximal standardized uptake value (mSUV) of positron emission tomography (PET) in Lymph nodes (LNs). Positive cytology slides of 114 LNs were reviewed from 100 patients with mNSCLC who had undergone PET study. Student's t-test was used for statistical comparisons. Mean patients' age: 68.5, 54% male. LNs locations were: mediastinum: 99, lung hilum: 13, peribronchial: 1, axilla: 1. Final diagnoses were: Adenocarcinoma: 86, squamous cell carcinoma: 28 LNs. Within the adenocarcinoma subgroup, histological patterns correlate with mSUV. Acinar and papillary patterns were associated with significantly lower mSUVs (mean± standard error (SE): 7.9± 0.9 and 9.2± 0.8, respectively) than solid pattern (13.0± 1.2; p values: 0.001 and 0.009, respectively). Similar difference exists between patterns associated with low- and high-grade adenocarcinoma (Mean±SE: 9.2± 0.8 and 12.0± 1.0, respectively. p value: 0.02). Interestingly, micropapillary pattern was associated with the lowest mSUV amongst all patterns (Mean±SE: 5.4± 1.1). Other features that correlated with higher mSUV were necrosis, moderate/severe nuclear atypia, lower lymphoid tissue yield, and contralateral LN involvement. In LNs with mNSCLC, certain cytomorphological features are associated with higher mSUV. Micropapillary, a pattern considered as high-grade, is associated with lower SUV values; hence, a lower SUV threshold may raise concern for metastasis. Although high SUV is associated with LN metastasis, lower SUV levels in certain adenocarcinomas suggest correlation with clinical and morphological characteristics could be valuable in tailoring therapeutic management.

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.