High Standardized Uptake Value Research Articles

The utility of PET-CT in baseline and sequential characterisation of Pulmonary Pleomorphic Carcinoma

Pulmonary Pleomorphic Carcinomas (PPCs) represent a rare and aggressive subtype of Non-Small Cell Lung Cancer (NSCLC) that can only be definitively diagnosed on a surgical specimen. This study utilised PET-CT to evaluate radiological characteristics of PPCs. This study retrospectively evaluated the radiological characteristics of PCCs diagnosed in St James’s Hospital Dublin between 2012-2023. Computed Tomography (CT) and Positron Emission Tomography (FDG-PET) imaging features (size, location, density, shape, invasion, and growth kinetics) and standard uptake value for each lesion were evaluated. 39 PCCs were identified with a mean age of 66.5 years (range: 49-82 years). FDG-PET was performed in all 39 cases. Tumours demonstrated a high FDG uptake at baseline with a mean (SUV) of 12.6 (range: 1.4 - 36.9). A second interval PET-CT on average 3.3 months after the first in 3 cases demonstrated over 120% increase in SUV. The mean tumour size was 4.3 cm (range: 1.0 - 14.5 cm). Tumours developed rapid interval growth, reaching a mean maximum diameter of 6.6 cm (53.4%) within a mean of 2.1 months. Tumours were predominantly located in the upper lobe (71.8 %) and displayed necrotic features in 53.8 % of cases. 82.1% of tumours invaded the mediastinum. This study describes the largest cohort of Pulmonary Pleomorphic Carcinoma in the literature. Tumours demonstrate a high SUV on baseline imaging and demonstrate rapid growth on interval imaging and central necrosis. Please click on the 'PDF' for the full abstract!

Feasibility of Biology-guided Radiotherapy (BgRT) Targeting Fluorodeoxyglucose (FDG) avid liver metastases

IntroductionBiology-guided radiotherapy (BgRT) is a novel radiation delivery approach utilizing fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) imaging performed in real-time to track and direct RT. Our institution recently acquired the RefleXion X1 BgRT system and sought to assess the feasibility of targeting metastatic sites in various organs, including the liver. However, in order for BgRT to function appropriate, adequate contrast in FDG activity between the tumor and the background tissue, referred to as the normalized SUV (NSUV), is necessary for optimal functioning of BgRT.MethodsWe reviewed the charts of 50 lung adenocarcinoma patients with liver metastases. The following variables were collected: SUVmax and SUVmean for each liver metastasis, SUVmean and SUVmax at 5 and 10 mm radially from the lesion, and NSUV at 5 mm and 10 mm (SUVmax of the liver metastasis divided by SUV mean at 5 mm at 10 mm respectively).Results82 measurable liver metastases were included in the final analysis. The average SUVbackground of liver was 2.26 (95% confidence interval [CI] 2.17–2.35); average SUVmean for liver metastases was 5.31 (95% CI 4.87–5.75), and average SUVmax of liver metastases was 9.19 (95% CI 7.59–10.78). The average SUVmean at 5 mm and 10 mm radially from each lesion were 3.08 (95% CI 3.00-2.16) and 2.60 (95% CI 2.52–2.68), respectively. The mean NSUV at 5 mm and 10 mm were 3.13 (95% CI 2.53–3.73) and 3.69 (95% CI 3.00-4.41) respectively. Furthermore, 90% of lesions had NSUV greater than 1.45 at 5 mm and greater than 1.77 at 10 mm.ConclusionsThis is the first study to comprehensively characterize FDG contrast between the liver tumor and background, referred to as NSUV. Due to the high background SUV normally found in the liver, this work will be valuable for guiding optimization of BgRT for treating liver metastases in the future using the RefleXion® X1 and potentially other similar BgRT platforms.

Relationships between postoperative recurrences and standardized uptake value on 18F-fluorodeoxyglucose-positron emission tomography in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma who underwent curative pancreatic resection after neoadjuvant chemoradiotherapy

BackgroundThis study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). MethodThe postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed. ResultsAfter a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01–2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32–3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis. ConclusionR- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.

Interim 18F-FDG-PET based response-adaptive dose escalation of proton therapy for head and neck cancer: a treatment planning feasibility study

BackgroundImage-driven dose escalation to tumor subvolumes has been proposed to improve treatment outcome in head and neck cancer (HNC). We used 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) acquired at baseline and into treatment (interim) to identify biologic target volumes (BTVs). We assessed the feasibility of interim dose escalation to the BTV with proton therapy by simulating the effects to organs at risk (OARs). MethodsWe used the semiautomated just-enough-interaction (JEI) method to identify BTVs in 18F-FDG-PET images from nine HNC patients. Between baseline and interim FDG-PET, patients received photon radiotherapy. BTV was identified assuming that high standardized uptake value (SUV) at interim reflected tumor radioresistance. Using Eclipse (Varian Medical Systems), we simulated a 10% (6.8 Gy(RBE1.1)) and 20% (13.6 Gy(RBE1.1)) dose escalation to the BTV with protons and compared results with proton plans without dose escalation. ResultsAt interim 18F-FDG-PET, radiotherapy resulted in reduced SUV compared to baseline. However, spatial overlap between high-SUV regions at baseline and interim allowed for BTV identification. Proton therapy planning demonstrated that dose escalation to the BTV was feasible, and except for some 20% dose escalation plans, OAR doses did not significantly increase. ConclusionOur in silico analysis demonstrated the potential for interim 18F-FDG-PET response-adaptive dose escalation to the BTV with proton therapy. This approach may give more efficient treatment to HNC with radioresistant tumor subvolumes without increasing normal tissue toxicity. Studies in larger cohorts are required to determine the full potential for interim 18F-FDG-PET-guided dose escalation of proton therapy in HNC.

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

In order to elucidate the relationship between pretreatment radiomic parameters and the proportions of various tumor-infiltrating (TI) cells, we retrospectively analyzed the association of total metabolic tumor volume (TMTV) and TI cells on biopsied tumor lesions in 171 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The surface markers of TI cells were analyzed by multicolor flow cytometry using a dissected single-cell suspension. In examining the correlation between TI cells and positron-emission tomography-derived parameters (maximum standardized uptake value [SUVmax], total metabolic tumor volume [TMTV], and total lesion glycolysis), intratumoral 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<0.001) demonstrated a similarly weak inverse correlation. High TMTV and low TI CD4+ cells were independently associated with poor prognosis and their combination identified the most adverse population (3-year progression-free survival: 32.3%, 95% confidence interval [CI]: 19.4-53.7; 3-year overall survival: 48.4%, 95% CI: 33.6-69.6). Moreover, radiomic parameters incorporating the international prognostic index significantly improved the 3-year survival prediction (area under the curve: 0.76, P<0.05) compared to their standalone use. This study underscores the prognostic impact of TI CD4+ cells on DLBCL and suggests that integration of TMTV and TI cell analysis enhances the accuracy of prognostic prediction.

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.

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

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.

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.