SUVmax Reduction Research Articles

NIMG-34. CXCR4-TARGETED PET IMAGING OF CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOMA USING [68GA]GA-PENTIXAFOR

Abstract BACKGROUND Initial results suggest that PET imaging of the chemokine receptor CXCR4 is of considerable interest for differential diagnosis and theranostic approaches. Here, we summarized findings of CXCR4 PET imaging in an institutional series of lymphoma of the central nervous system (CNSL) and glioma. METHODS Twenty-three patients with CNSL and 16 patients with glioma (IDH-wildtype, n=9) underwent PET imaging using the CXCR4-directed tracer [68Ga]Ga-Pentixafor. In 18 patients, serial PET imaging was performed (range, 2-14 scans), resulting in a total of 104 PET scans. For evaluation, PET scans were classified as [68Ga]Ga-Pentixafor-positive and -negative visually, and the maximum standardized uptake value (SUVmax) was obtained from [68Ga]Ga-Pentixafor-PET. RESULTS Twenty-four of all 39 patients (62%) had at least one [68Ga]Ga-Pentixafor-positive PET (CNSL, 57%; glioma, 69%). [68Ga]Ga-Pentixafor-positive PET scans were more common in patients with IDH-wildtype gliomas (89%) than in IDH-mutant gliomas (43%). In patients with [68Ga]Ga-Pentixafor-positive PET, the average SUVmax was 6.4±4.0 in CNSL, and 3.4±1.0 in gliomas (P=0.155). Besides visualization of tumors, [68Ga]Ga-Pentixafor uptake was observed in two patients with radionecrosis. In four CNSL patients who had undergone methotrexate/cytarabine-based first-line therapy, serial PET revealed a significant reduction of SUVmax after chemotherapy completion (average decrease of SUVmax from 4.5±3.8 to 0.6±0.7; P=0.044). In three of those four patients, tumor progression has not been reached (range of time after the follow-up PET, 4-55 months); one patient deceased 44 months after the follow-up PET. In contrast, another patient with an increase in SUVmax from 6.9 to 11.0 after first-line treatment died one month after the follow-up PET. DISCUSSION [68Ga]Ga-Pentixafor PET seems to be of value for non-invasively visualizing and quantifying CXCR4 receptor binding. In CNSL, changes in [68Ga]Ga-Pentixafor uptake following therapy may indicate potential for response assessment. CXCR4-targeting radioligand therapies might be more promising in CNSL than in glioma.

Chemoradiotherapy treatment increases cardiac and aortic [18F]FDG uptake ratios in lung cancer patients

[18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is an indispensable non-invasive imaging tool to aid diagnosis, prognostication, and therapeutic monitoring in oncology, but it can also evaluate cardiovascular inflammation1,2. Previously, cardiac metabolic changes using [18F]FDG with chemoradiotherapy have been explored3 but changes in the rest of the cardiovascular system remain undetermined. To investigate the cardiovascular metabolic changes pre- and post-chemoradiotherapy in stage 3b non-small cell lung cancer (NSCLC) patients. A retrospective analysis of 26 patients (43-82 years) with stage 3b NSCLC from the American College of Radiology Imaging Network (ACRIN 6668) trial was performed3. All available pre- and post-treatment imaging were retrieved from the Cancer Imaging Archive (TCIA)4 and regions of interest for the left ventricle and calcified large arteries were contoured on all PET-CT scans using PMOD version 4.0 software. The mean, maximum standard uptake value (SUVmean and SUVmax) and target-to-background ratio (TBR) were quantified on PMOD. At approximately 14 weeks post-chemoradiotherapy, there was a higher SUVmean (mean difference 0.81, p=0.01) and SUVmax (mean difference 2.20, p=0.006) in the left ventricle compared with pretreatment scans. TBR for aorta was higher post-treatment (mean difference 0.06, p=0.005). However, SUVmean for carotid arteries and right brachiocephalic artery was reduced post-chemoradiotherapy (mean difference 0.15, p=0.008 and mean difference 0.28, p=0.03). A reduction in SUVmax was also seen for aortic arch (mean difference 0.58, p=0.03) and right brachiocephalic artery (mean difference 0.42, p=0.03 and mean difference 0.42, p=0.03). Cardiovascular glucose metabolism is selectively increased in the left ventricle and aorta post-chemoradiotherapy. Changes in glucose metabolism of atherosclerotic plaques vary across different vessels throughout the body. Please click on the 'PDF' for the full abstract!

Prognostic significance of fludeoxyglucose positron emission tomography delta radiomics following bridging therapy in patients with large B-cell lymphoma undergoing CAR T-cell therapy.

Bridging radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of cytoreduction during bRT impacts outcomes. We retrospectively reviewed patients with LBCL treated with bRT followed by CAR T-cell therapy. Metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were extracted from F18-fluorodeoxyglucose positron emission tomography (PET) scans acquired prior to bRT and between completion of bRT and CAR T-cell infusion. Delta radiomics based on changes of these values were then calculated. The association between delta radiomics and oncologic outcomes [progression-free survival (PFS), freedom from distant progression (FFDP), and local control (LC)] were then examined. Thirty-three sites across 23 patients with LBCL were irradiated. All metabolically active disease was treated in 10 patients. Following bRT, median overall decreases (including unirradiated sites) in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. Median follow-up was 15.2 months. A decrease in SUVmax of at least 54% was associated with improved PFS (24-month PFS: 83.3% vs. 28.1%; p = 0.037) and FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). A decrease in MTV of at least 90% was associated with improved FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). LC was improved in sites with decreases in SUVmax of at least 71% (24-month LC: 100% vs. 72.7%; p < 0.001). Decreases of MTV by at least 90% (100% vs. 53.3%; p = 0.038) and TLG by at least 95% (100% vs. 56.3%; p = 0.067) were associated with an improved complete response rate. bRT led to substantial reductions in MTV, SUVmax, SUVmean, and TLG. The relative extent of these decreases correlated with improved outcomes after CAR T-cell infusion. Prospective cohorts should validate the value of interim PET following bRT for quantifying changes in disease burden and associated prognosis.

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.

The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy. Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response. Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5. MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response. The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic. gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

Meta-analysis of [18F]FDG-PET/CT in pulmonary sarcoidosis.

18F-Fluorodeoxyglucose (FDG) PET/CT is emerging as a tool in the diagnosis and evaluation of pulmonary sarcoidosis, however, there is limited consensus regarding its diagnostic performance and prognostic value. A meta-analysis was conducted with PubMed, Science Direct, MEDLINE, Scopus, and CENTRAL databases searched up to and including September 2023. 1355 studies were screened, with seventeen (n = 708 patients) suitable based on their assessment of the diagnostic performance or prognostic value of FDG-PET/CT. Study quality was assessed using the QUADAS-2 tool. Forest plots of pooled sensitivity and specificity were generated to assess diagnostic performance. Pooled changes in SUVmax were correlated with changes in pulmonary function tests (PFT). FDG-PET/CT in diagnosing suspected pulmonary sarcoidosis (six studies, n = 400) had a pooled sensitivity of 0.971 (95%CI 0.909-1.000, p = < 0.001) and specificity of 0.873 (95%CI 0.845-0.920)(one study, n = 169). Eleven studies for prognostic analysis (n = 308) indicated a pooled reduction in pulmonary SUVmax of 4.538 (95%CI 5.653-3.453, p = < 0.001) post-treatment. PFTs displayed improvement post-treatment with a percentage increase in predicted forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) of 7.346% (95%CI 2.257-12.436, p = 0.005) and 3.464% (95%CI -0.205-7.132, p = 0.064), respectively. Reduction in SUVmax correlated significantly with FVC (r = 0.644, p < 0.001) and DLCO (r = 0.582, p < 0.001) improvement. In cases of suspected pulmonary sarcoidosis, FDG-PET/CT demonstrated good diagnostic performance and correlated with functional health scores. FDG-PET/CT may help to guide immunosuppression in cases of complex sarcoidosis or where treatment rationalisation is needed. FDG-PET/CT has demonstrated a high diagnostic performance in the evaluation of suspected pulmonary sarcoidosis with radiologically assessed disease activity correlating strongly with clinically derived pulmonary function tests. In diagnosing pulmonary sarcoidosis, FDG-PET/CT had a sensitivity and specificity of 0.971 and 0.873, respectively. Disease activity, as determined by SUVmax, reduced following treatment in all the included studies. Reduction in SUVmax correlated with an improvement in functional vital capacity, Diffusion Capacity of the Lungs for Carbon Monoxide, and subjective health scoring systems.

18F-FDG PET/CT for early prediction of pathological complete response in breast cancer neoadjuvant therapy: a retrospective analysis.

Neoadjuvant treatment has been developed as a systematic approach for patients with early breast cancer and has resulted in improved breast-conserving rate and survival. However, identifying treatment-sensitive patients at the early phase of therapy remains a problem, hampering disease management and raising the possibility of disease progression during treatment. In this retrospective analysis, we collected 2-deoxy-2-[F-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) images of primary tumor sites and axillary areas and reciprocal clinical pathological data from 121 patients who underwent neoadjuvant treatment and surgery in our center. The univariate and multivariate logistic regression analyses were performed to investigate features associated with pathological complete response (pCR). An 18F-FDG PET/CT-based prediction model was trained, and the performance was evaluated by receiver operating characteristic curves (ROC). The maximum standard uptake values (SUVmax) of 18F-FDG PET/CT were a powerful indicator of tumor status. The SUVmax values of axillary areas were closely related to metastatic lymph node counts (R = 0.62). Moreover, the early SUVmax reduction rates (between baseline and second cycle of neoadjuvant treatment) were statistically different between pCR and non-pCR patients. The early SUVmax reduction rates-based model showed great ability to predict pCR (AUC = 0.89), with all molecular subtypes (HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-) considered. Our research proved that the SUVmax reduction rate of 18F-FDG PET/CT contributed to the early prediction of pCR, providing rationales for utilizing PET/CT in NAT in the future.

Clinical significance of the maximum standardized uptake value on positron emission tomography to predict treatment response and outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

The association between the reduction rate of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) during neoadjuvant chemoradiotherapy (NACRT) and the prognosis in patients with locally advanced rectal cancer is unknown. We retrospectively analyzed 62 patients with locally advanced rectal cancer who underwent curative surgery after NACRT at Kobe University between 2008 and 2021. The SUVmax reduction rate was calculated from preoperative and postoperative PET scans, and its association with the prognosis was investigated. The cutoff value for SUVmax reduction rate was 61.5%. Twenty patients had an SUVmax reduction rate > 61.5% (SUV responder group) and 38 patients had an SUVmax reduction rate ≤ 61.5% (SUV nonresponder group). Regarding pathological outcomes, the rate of a good histological response was significantly higher in the SUV responder group than in the SUV nonresponder group (80.0% vs. 21.1%, p < 0.001). Both the overall (OS) and relapse-free survival (RFS) rates were significantly better in the SUV responder group than in the SUV nonresponder group (OS, p = 0.035; RFS, p = 0.019). In the SUV responder group, only 1 case of recurrence was observed, with a median follow-up period of 56months. The rate of SUVmax reduction during NACRT might predict the long-term prognosis of patients with locally advanced rectal cancer.

Abstract PO5-01-05: An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging

Abstract Background: Pathological complete response (pCR) has been demonstrated as a surrogate endpoint for disease-free and overall survival in HER2-positive early-stage breast cancer (EBC). Trastuzumab (H) plus pertuzumab (P) improved pCR rates in patients with HER2-positive early-stage breast cancer. Nevertheless, biomarkers to assess the effectiveness of this treatment in the neoadjuvant setting are still unclear. This study aims to evaluate the effectiveness of fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and 68 Ga-Affibody HER2 Imaging PET (HER2-PET) in HER2 EBC neoadjuvant therapy, and to identify novel biomarkers for this regimen. Methods: HER2-positive EBC patients were prospectively recruited at Fudan University Shanghai Cancer Center between April 2020 and March 2022. All patients received the 1 dose of HP, followed by 6 cycles of docetaxel (T), carboplatin (Cb), and HP. We use FoundationOne to evaluate the genomic alterations before treatment. In addition, 18F-FDG-PET and HER2 PET were performed at baseline, after 1 cycle of HP, and after 6 cycles of TCbHP, to assess the effectiveness of these examinations in the prediction of pCR and correlation to disease burden. All patients were received surgery and completed 1 year of HP-based regimen in the adjuvant setting. Results: A total of 61 patients with a median age of 49 years were included. Among them, 93.5% of patients are node positive. 75.8% of the patients reported adverse events (AEs), primarily grade 1 and 2. The incidence of serious AEs was 6.6%. Patients exhibiting a greater than 40% reduction in SUVmax of 18-FDG-PET or HER2-PET scans from baseline to the fifth day after the initial HP treatment were classified as the treatment-sensitive group. The pCR rate for the 18-FDG-PET-sensitive group was 79.3%, while for the insensitive group was 48.1%. For HER2-PET scans, the pCR rate was 70.0% in the sensitive group and 59.3% in the non-sensitive group. To evaluate the potential biomarkers, 25 patients (13 pCR and 12 non-pCR) were evaluated with FoundationOne, with the identification of 1,321 somatic alterations. The most frequently altered genes were ERBB2 (100%), TP53 (96%), CDK12 (76%), MYC (56%), CCND1 (44%), PIK3CA (40%), and SRSF2 (36%). In the pCR group, we found PPM1D (38.5%) and RAD21 (38.5%) were altered more frequently than the non-pCR group. PIK3CA alterations were significantly reduced in pCR group, only 23% of cases are affected compared to 58.3% in non-pCR group. Patients were non-pCR had more MDM4 (41.7%) and ZNF217 (41.7%) alterations than pCR patients. Conclusion: The SUVmax value of 18-FDG-PET and HER2-PET scans are correlated well with the tumor burden and the residual disease in the HER2 EBCs. The reduction of SUVmax could predict pCR but need further exploration. Patients with alterations in PPM1D and RAD21 have a favorable response to the TCbHP regimen. Conversely, alterations in PIK3CA, MDM4, and ZNF217 are associated with treatment resistance. These results indicate the significance of 18-FDG-PET and HER2-PET in monitoring treatment effectiveness. The biomarker analysis in this study will help us understand the mechanism of HER2 positive breast cancer treatment resistance and assisting in tailoring personalized therapy. Clinical trial information: NCT04281641. Citation Format: Ming Chen, Benlong Yang, Sun Yuyun, Linxiaoxi Ma, Song Shaoli, Min He, Zhi-Ming Shao, Bingqiu Xiu, Jiong Wu. An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-05.

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer

PurposeEmerging data suggest metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease and has been proposed as a biomarker for treatment response. Herein we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and materialsWe performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation therapy who underwent PSMA-PET/CT prior to and after (median 6.2 months, range 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT SUVmax was measured for all lesions and PSMA response was defined as percent change in SUVmax of the least responsive lesion. PSMA response was evaluated as both a continuous variable and dichotomized as PSMA responders with a complete/partial response (at least 30% reduction in SUVmax) and PSMA non-responders with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated conventional imaging defined metastasis-free survival (MFS) with Kaplan-Meier and cox regression. ResultsA total of 131 patients with 261 treated metastases were included in the analysis, with median follow-up of 29 months (IQR 18.5-41.3). Following SABR, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated PSMA response as a continuous variable was associated with significantly worse MFS (HR=1.003, 95%CI 1.001-1.006; p=0.016). Patients classified as PSMA responders were found to have significantly improved median MFS of 39.9 vs 12 months (p=0.001) compared to PSMA non-responders. Our study is limited as it is a retrospective review of a heterogenous population. ConclusionsFollowing SABR, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

Optimal [18F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial.

The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [18F]FDG PET/CT. [18F]FDG PET/CT responders were defined as patients with an SUVmax reduction (ΔSUVmax) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy). Pathologic complete response (pCR), defined as ypT0/isN0, was achieved in 37.9% of the patients. Here, we describe the secondary preplanned analysis of the best cutoff of ΔSUVmax for pCR prediction. Methods: Receiver-operating-characteristic analysis was applied to look for the most appropriate ΔSUVmax cutoff in HER2-positive early breast cancer patients treated exclusively with neoadjuvant HP (with or without endocrine therapy). Results: The ΔSUVmax capability of predicting pCR in terms of the area under the receiver-operating-characteristic curve was 72.1% (95% CI, 65.1-79.2%). The optimal ΔSUVmax cutoff was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity. With this cutoff, 74 of 285 patients (26%) would be classified as metabolic responders, increasing the pCR rate from 37.9% (cutoff ≥ 40%) to 59.5% (44/74 patients) (P < 0.01). With this optimized cutoff, 44 of 285 patients (15.4%) would avoid chemotherapy in either the neoadjuvant or the adjuvant setting compared with 86 of 285 patients (30.2%) using the original cutoff (P < 0.001). Conclusion: In the PHERGain trial, an increased SUVmax cutoff (≥77%) after 2 cycles of exclusive HP (with or without endocrine therapy) achieves a pCR in the range of the control arm with chemotherapy plus HP (59.5% vs. 57.7%, respectively), further identifying a subgroup of patients with HER2-addicted tumors. However, the original cutoff (≥40%) maximizes the number of patients who could avoid chemotherapy.

Role of serial 18F-fludeoxyglucose positron emission tomography in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis

BackgroundMyocardial inflammation and perfusion defects detected by 18F-fludeoxyglucose (FDG) and Rubidium-82 positron emission tomography (PET) may be associated with ventricular arrhythmias (VAs) in cardiac sarcoidosis (CS). The role of serial quantitative PET in determining the effect of treatment on myocardial inflammation and clinical outcomes is yet to be defined. MethodsNewly diagnosed CS patients with active myocardial inflammation (maximum standardised uptake value (SUVmax) ≥ 2.5) were treated with immunosuppression, then underwent repeat FDG-PET, Rubidium-82, and echocardiographic imaging 6–12 months later. Serial changes in SUVmax, SUVmean, inflammatory extent, perfusion defect (PD) extent, metabolism/perfusion mismatch extent, global cardiac metabolic activity, and left ventricular ejection fraction (LVEF) were assessed. The primary endpoint was a composite of all-cause mortality, serious VA and heart-failure (HF) hospitalisation. Event data were recorded from the date of the second FDG-PET. ResultsThe study population consisted of 113 patients (66% male, age: 55 ± 11 years, LVEF: 54 ± 13%). SUVmax reduced from 4.5 (interquartile range: 3.3–7.1) to 2.7 (2.2–3.6). Overall, 94 (83%) patients saw serial reduction in SUVmax, with 42 (37%) demonstrating complete response (SUVmax <2.5).Following a median of 46 (25–57) months, 28 (25%) patients reached the endpoint (8 deaths, 17 VAs, and 3 HF hospitalisations). PD extent (Hazard ratio 1.03, 95% confidence interval: 1.01–1.05; p = 0.035) was a significant predictor of outcome following treatment, even after accounting for LVEF and change in SUVmean. The risk of adverse events was the greatest in those with a pre-treatment or post-treatment PD extent of >10%. ConclusionIn our cohort with active CS, following a treatment-induced reduction in myocardial inflammation, PD extent was the main predictor of adverse events.

Early response monitoring during [177Lu]Lu-PSMA I&T therapy with quantitated SPECT/CT predicts overall survival of mCRPC patients: subgroup analysis of a Swiss-wide prospective registry study

PurposeTo assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy.MethodsSingle-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021–01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan–Meier methodology (log-rank test).ResultsBetween 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4–26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09–0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07–0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16–0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01–0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02–0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively).ConclusionSix weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.

Analysis of redox status and HDL subclasses in patients with lymphoma and the associations with FDG-PET/CT findings.

Newer research points to alterations in the plasma redox status and the HDL subclass distributions in cancer. We aimed to assess the redox status and the HDL subclass distributions, lipids, and inflammatory markers in lymphoma patients in order to determine whether they were correlated with changes in FDG-PET/CT scans. At the beginning of this study, redox status, HDL subclasses, lipids, and inflammation biomarkers were determined in 58 patients with lymphoma (Hodgkin lymphoma, n=11 and non-Hodgkin lymphoma, n=47), and these same measurements were reassessed during their ensuing treatment (in 25 patients). Initially, the total oxidation status (TOS), the prooxidant-antioxidant balance (PAB), the OS index (OSI), the total protein sulfhydryl groups (SH-groups), and the advanced oxidation protein products (AOPP) were significantly higher in lymphoma patients as compared to healthy subjects, but the total antioxidant status (TAS) was significantly reduced. The PAB had a strong correlation with the CRP and interleukin-6 (rho=0.726, p<0.001; rho=0.386, p=0.003). The correlations between these parameters and the maximum standardized uptake values (SUVmax) were: PAB, rho=0.335 and p=0.010; SH-groups, rho=0.265 and p=0.044; CRP, rho=0.391 and p=0.002; HDL3b, rho=0.283 and p=0.031; HDL2b, rho= -0.294 and p=0.025; and HDL size, rho= -0.295 and p=0.024. The reductions in SUVmax between two follow-up points were associated with increases in the OSI, TOS, and SH-groups, as well as a reduction in the PAB and TAS. In conclusion, the redox parameters in patients with lymphoma were consistent with FDG-PET/CT findings. Targeting the redox status parameters and the HDL subclasses could be potential strategies in the molecular fight against lymphoma.

18F]NaF PET/CT imaging of response to single fraction SABR to bone metastases from breast cancer.

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0-20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%-34% for non-tumour bone in each dose level.

Post-treatment PET/CT for p16-positive oropharynx cancer treated with definitive proton therapy.

Given emerging data suggesting that uncertainty in the relative biologic effectiveness at the distal end of the Bragg peak results in increased mucosal injury in patients with oropharynx cancer receiving adjuvant proton therapy, we evaluated the results of post-treatment positron emission tomography-computed tomography (PET/CT) in patients with p16-positive oropharynx cancer (p16+OPC) treated with definitive intensity-modulated proton therapy (IMPT). A retrospective cohort study of patients with p16+OPC treated with definitive IMPT between 2016 and 2022 was performed at a single institution. Patients with PET/CT scans within 6 months following completion of IMPT were included in the study. Positive post-treatment scans were defined by a maximum standard uptake values (SUVmax) >4.0 or a <65% reduction in SUVmax in either the primary tumor or lymph node. The Fisher's exact test was used to evaluate factors associated with positive post-treatment PET/ CT values. Sixty-two patients were included for analysis. Median follow-up was 21 months (range: 3-71 months) with a median time to post-treatment PET/CT of 3 months (range: 2-6 months). Median post-treatment SUVmax of the primary disease and nodal disease was 0 (mean: 0.8, range: 0-7.7) and 0 (mean: 0.7, range: 0-9.5), respectively. Median post-treatment percent reduction in SUVmax for the primary site and lymph node was 100% (mean: 94%, range: 31.3-100%) and 100% (mean: 89%, range: 23-100%), respectively. Eleven patients had a positive post-treatment PET/CT with one biopsy-proven recurrence. Negative and positive predictive values (NPV and PPV) were 98% and 9.1%, respectively. There were no factors associated with positive post-treatment PET/CT. Similar to patients treated with photon-based radiation therapy, post-treatment PET/CT has a high NPV for patients with p16+OPC treated with definitive proton therapy and should be used to guide patient management. Additional patients and more events are needed to confirm the PPV of a post-treatment PET/CT in this favorable patient cohort.

Prognostic Significance of Positron Emission Tomography Delta Radiomics Following Bridging Therapy in Patients with Large B-Cell Lymphoma Undergoing CAR T-Cell Therapy

CAR T-cell therapy is routinely used as a treatment option for relapsed/refractory large B-cell lymphoma (LBCL). Bridging therapy radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of debulking as a result of bRT impacts outcomes following CAR T-cell infusion. We hypothesized that the extent of debulking is prognostic of overall response to therapy. We reviewed patients with LBCL treated with bRT followed by commercially available CAR T-cell therapy between 2017 and 2022. Patients required a F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan prior to bRT and between completion of bRT and CAR T-cell infusion. On each scan, metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were determined. Delta-radiomics based on changes of these values between scans in patients overall and irradiated sites were then calculated. Optimal cut points were determined using maximally selected log-rank. The primary endpoints were progression-free survival (PFS) and local control (LC), measured from CAR T-cell infusion by Kaplan-Meier and Fine-Gray competing risk survival analyses, respectively. Twenty-three patients with LBCL with 33 irradiated sites were reviewed. All metabolically active disease was treated in 10 patients. Median equivalent dose in 2 Gy fractions (EQD2) was 26 Gy (14-44). Median interval from bRT to PET was 9 days (2-30). Following bRT, 2 patients achieved complete responses, 16 had partial responses, and 5 had progressive disease. Five irradiated sites progressed through bRT. No local failures were observed when EQD2>32.5 Gy was given. LC was improved with EQD2>20 Gy (24 mo LC: 94.5% vs 68.6%; p = 0.075). Following BRT, median overall decreases in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. PFS was significantly improved in patients with reductions of MTV of at least 36 cc (24 mo PFS: 69.2% vs 0%; p = 0.047) or SUVmax of at least 15 (24-mo PFS: 80.0% vs 28.1%; p < 0.001). LC was significantly improved in lesions with reductions of SUVmax of at least 14 (24-mo LC: 100% vs 67.3%; p < 0.001) or SUVmean of at least 7 (24-mo LC: 100% vs 74.4%; p < 0.001). bRT led to significant reductions in MTV, SUVmax, SUVmean, and TLG. The extent of these decreases correlated with improved PFS and LC. There appears to be a dose-response relationship. Larger cohorts should validate the value of interim PET following bRT, and associated changes in disease burden as a means of prognosticating patients. Future work might evaluate whether escalation of BT in patients with suboptimal response, using either systemic therapy or higher radiation doses, has an impact on outcomes.

327. ANALYSING THE ROLE OF PET-CT IN ESOPHAGEAL CANCER: A SINGLE CENTRE COHORT STUDY

Abstract Background While PET-CT is considered the gold standard imaging investigation in diagnosing esophageal cancer, its role in determining management is controversial. It demonstrates increased sensitivity for detection of occult M1 disease in comparison with endosonography or CT alone, however its accuracy in assessment of histopathologic response to neoadjuvant therapy is unclear. The aim of this study was to evaluate the clinical utility of PET-CT in staging, response evaluation and prognostication in esophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC). Methods Patients with esophageal cancer undergoing treatment with curative intent were studied prospectively. Baseline imaging (PET1) was carried out at diagnosis. Repeat scanning (PET2) was performed at 4 weeks post-completion of neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT). Pathological complete response (pCR) was defined as TRG1, ypN0. Major pathologic response was defined as TRG1–2, ypN0. Metabolic complete response (mCR) was defined as absence of abnormal FDG uptake at the primary site, nodal sites or suspected metastatic sites. The association between 18F-FDG-uptake (SUVmax) and PET-predicted nodal status, histopathologic parameters and survival were determined using univariable and multivariable regression models. Results 730 patients were studied. PET identified CT-occult M1 disease in 2.9% and synchronous neoplasms in 1.4%. The relative reduction in SUVmax was greater among patients treated with nCRT compared with nCT (P = 0.021). SUVmax correlated with pT stage among patients treated with primary surgery (P &amp;lt; 0.001), however 32.3% with AC and 15.8% with SCC who were predicted node negative were pN+. Post neoadjuvant therapy, PET parameters showed modest associations with mCR, but no parameter accurately predicted pCR. Among patients with mCR, 90.9% with AC post-nCT, 84.1% with AC post-nCRT and 54.8% with SCC post-nCRT had residual disease. Lower preoperative SUVmax was independently associated with improved survival in AC, but not SCC. Conclusion PET-CT identifies CT-occult M1 disease or synchronous neoplasms in 4.3% at initial staging. PET-CT poorly predicts ypN status, particularly in AC. After neoadjuvant therapy, PET-CT is poorly predictive of histopathologic response—the majority of patients with an mCR have residual disease. Nonetheless, improvements in SUVmax may reflect a greater chance of achieving major pathologic response and more favourable long-term outcomes in AC.

1254 Examining the Role of PET-CT in the Management of Oesophageal Cancer: A Single Institution Experience

Abstract Aim The role of PET-CT in oesophageal cancer is controversial. The aim of this study was to evaluate the utility of PET-CT in staging and response evaluation in oesophageal squamous cell carcinoma (SCC) and adenocarcinoma (AC). Method Patients undergoing curative-intent treatment were studied prospectively. PET1 was carried out at diagnosis and repeat scanning (PET2) was performed 2-4 weeks post-completion of neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT). The association between PET parameters, histopathologic response and survival was determined using univariable and multivariable regression models. Results 730 consecutive patients were studied. PET identified CT-occult M1 disease in 2.9% and synchronous neoplasm in 1.4%. Similar PET1 SUVmax values were observed in AC and SCC. The reduction in SUVmax was greater post-nCRT versus nCT (P = 0.021). SUVmax correlated with pT stage among patients treated with primary surgery (P&amp;lt;0.001), however 32.3% with AC and 15.8% with SCC who were predicted node negative were pN+. Post neoadjuvant therapy, PET parameters showed modest associations with major pathologic response, but no parameter accurately predicted complete pathologic response. Among patients with a metabolic complete response (mCR), 90.9% with AC post-nCT, 84.1% with AC post-nCRT and 54.8% with SCC post-nCRT had residual disease. Lower preoperative SUVmax was independently associated with improved survival outcomes in AC, but not SCC. Conclusions PET-CT identified CT-occult M1 disease or synchronous neoplasms in 4.3% at initial staging. After neoadjuvant therapy, PET is poorly predictive of histopathologic response – most patients with an mCR have residual disease. Nonetheless, improvements in SUVmax may reflect a more favourable long-term outcome in AC.

Improved arterial inflammation with high dose omega-3 fatty acids in patients with elevated lipoprotein(a): Selective effect of eicosapentaenoic acid?

Elevated lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease. However, there are no approved and effective treatments for lowering Lp(a) and the associated cardiovascular risks. Omega-3 fatty acids (ω-3FAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have both triglyceride-lowering and anti-inflammatory properties. This pilot study investigated the effect of high dose ω-3FAs (3.6 g/day) on arterial inflammation in 12 patients with elevated Lp(a) (> 0.5 g/L) and stable coronary artery disease (CAD) receiving cholesterol-lowering treatment. Arterial inflammation was determined using 18F-fluorodexoyglucose positron emission tomography/computed tomography before and after 12-weeks intervention. ω-3FAs significantly lowered plasma concentrations of triglycerides (–17%, p < 0.01), Lp(a) (-5%, p < 0.01) as well as aortic maximum standardized uptake value (SUVmax) (–4%, p < 0.05). The reduction in SUVmax was significantly inversely associated with average on-treatment EPA (r = -0.750, p < 0.01), but not DHA and triglyceride, concentrations. In conclusion, high dose ω-3FAs decrease arterial inflammation in patients with elevated Lp(a) and stable CAD, which may involve a direct arterial effect of EPA.

Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients with oesophageal adenocarcinoma

Objectives2-deoxy-2[18F]Fluoro-d-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival.MethodsCohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy’s and St Thomas’ NHS Foundation Trust, London (2017–2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression.ResultsOptimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03–0.34; mTR HR 0.17 95% CI 0.06–0.48; pNR HR 0.17 95% CI 0.06–0.54; mNR HR 0.13 95% CI 0.02–0.66).ConclusionsMetabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival.Key Points• FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer.• Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection.• Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.