Change In Standardized Uptake Value Research Articles

Fluorine-18 fluorodeoxyglucose uptake change in liver, mediastinal blood pool, and lymphoid cell-rich organs during programmed cell death-1 immunotherapy in lymphoma.

The aim of this study was to evaluate metabolism change in reference organs (liver and mediastinum) and lymphoid cell-rich organs (spleen and bone marrow) during programmed cell death-1 immunotherapy in relapsed or refractory lymphoma patients. A total of 66 patients with baseline and serial monitoring fluorodeoxyglucose (FDG) PET/computed tomography scans were retrospectively enrolled. Mean standardized uptake value (SUV) and maximum SUV of evaluated organs were obtained by two reviewers, and their association with tumor burden and clinical response were evaluated. Immune-related adverse events detected by FDG PET/computed tomography were also recorded. The SUV values of reference organs and lymphoid cell-rich organs did not change significantly during the immunotherapy process. The intersubject variability of these values ranged from 13.0 to 28.5%. Meanwhile, metabolism of reference organs was affected by neither the tumor burden nor clinical response. SUV change of lymphoid cell-rich organs was associated with clinical response to immunotherapy. Responders showed decreased metabolism, while nonresponders showed a reverse trend (spleen SUVmaximum: -0.30 ± 0.47 vs. 0.18 ± 0.39, P = 0.001, spleen SUVmean: -0.24 ± 0.39 vs. 0.14 ± 0.31, P = 0.001; and bone marrow SUVmaximum: -0.14 ± 0.37 vs. 0.07 ± 0.46, P = 0.042, respectively). The influence of immune-related adverse events on the SUV change in evaluated organs was NS. During programmed cell death-1 immunotherapy, metabolism change of reference organs is influenced neither by tumor burden nor by clinical response, while FDG uptake change of lymphoid cell-rich organs is significantly associated with clinical response.

Abstract PO2-07-07: The role of PET imaging with [18F]16α-fluoro-17β-fluoroestradiol in predicting response to endocrine therapies in patients with breast cancer

Abstract Background Fluoroestradiol F18 is a radioactive diagnostic agent (18F-FES) used with positron emission tomography (PET) imaging to detect estrogen-receptor (ER)-positive lesions in patients with breast cancer. Convened by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an expert working group published appropriate use criteria (AUC) for 18F-FES PET including, but not limited to, use of 18F-FES for selection of endocrine therapies. Quantitative determination of ER status, and thus treatment response, has the potential to prevent ineffective courses of endocrine therapies and associated therapeutic/financial burden. This meta-analysis reviewed the AUC-cited studies to assess the utility of 18F-FES in predicting treatment response to endocrine therapies. Methods Eight studies cited in the AUC were selected based on having comparable 18F-FES PET standardized uptake values (SUV) and progression-free survival (PFS) measures, and one additional study was included upon further systematic search of the same selected parameters defined in the AUC. With the nine studies (n = 327), we conducted three investigations to explore the association between: (1) the patient baseline 18F-FES PET SUVmean, across all lesions or across up to seven of the most intense lesions, and patient response to endocrine therapy (response/no response); (2) in the same population as investigation 1, the change (%) in 18F-FES PET SUV from baseline to at 7 to 10 days post-treatment; (3) the 18F-FES interlesional heterogeneity and PFS (months). Interlesional heterogeneity was qualitatively defined as patients displaying both 18F-FES positive and negative lesions versus those with all FES-positive lesions. Results A fixed effects model was used to analyze three studies (n = 102). Findings reveal that patients who responded to endocrine therapy had a significantly higher baseline SUVmean versus non-responders (mean difference 0.91; CI 95% 0.49 to 1.34; P < 0.001); a sensitivity analysis was conducted via random effects modelling and revealed similar results (mean difference 0.92; CI 95% 0.48 to 1.36; P < 0.001). This was consistent with findings from an additional analysis performed on two papers (n = 62), whereby odds ratio estimates indicated that a response to therapy is 89% less likely to occur when baseline 18F-FES SUVmax is < 1.5 (OR 0.11; CI 95% 0.02 to 0.72 P = 0.02). Findings from the analysis of mean percentage change in 18F-FES SUV from baseline to 7-10 days post-treatment initiation showed no significant difference in the percentage change of SUV observed between responders and non-responders (mean difference -0.22; 95% CI -0.69 to 0.26; P = 0.37). The final heterogeneity analysis revealed higher median PFS in all FES-positive cohort, suggesting that this group may respond better to endocrine therapy (Table 1). Conclusion The AUC states that the presence of ER by immunohistochemistry may not be the optimal predictive biomarker for the success of endocrine therapies. Our findings support this statement, as a significantly higher baseline SUVmean of 18F-FES may serve as a predictive biomarker for endocrine therapy response. Patients with a 18F-FES lesion SUVmax < 1.5 are 89% less likely to respond to endocrine therapies; patients demonstrating heterogeneity (FES+/FES- lesions) have a lower median PFS, reinforcing the predictive value of 18F-FES. Table 1. Median PFS scores from FES heterogeneity analysis *Patients with all FES positive lesions were categorised by the median ratio of FES/FDG SUVmax into low FES/FDG ( <0.96), and high FES/FDG (>0.96); only patients with FES/FDG of >0.96 were included in the positive lesions arm. Citation Format: Nicholas DiGregorio, Christine Brand, Dustin Dunham, Eleanor McManus. The role of PET imaging with [18F]16α-fluoro-17β-fluoroestradiol in predicting response to endocrine therapies in patients with breast cancer [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 PO2-07-07.

Monitoring tafamidis treatment with quantitative SPECT/CT in transthyretin amyloid cardiomyopathy.

Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy. Forty wild-type ATTR-CM patients who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging at baseline and after treatment with tafamidis 61 mg once daily [median, 9.0 months (interquartile range 7.0-10.0)] were divided into two cohorts based on the median (-32.3%) of the longitudinal percent change in standardized uptake value (SUV) retention index. ATTR-CM patients with a reduction greater than or equal to the median (n = 20) had a significant decrease in SUV retention index (P < 0.001) at follow-up, which translated into significant benefits in serum N-terminal prohormone of brain natriuretic peptide levels (P = 0.006), left atrial volume index (P = 0.038), as well as LV [LV global longitudinal strain: P = 0.028, LV ejection fraction (EF): P = 0.027, LV cardiac index (CI): P = 0.034] and right ventricular (RV) [RVEF: P = 0.025, RVCI: P = 0.048] functions compared with patients with a decrease less than the median (n = 20). Treatment with tafamidis in ATTR-CM patients results in a significant reduction in SUV retention index, associated with significant benefits for LV and RV function and cardiac biomarkers. Serial quantitative 99mTc-DPD SPECT/CT imaging with SUV may be a valid tool to quantify and monitor response to tafamidis treatment in affected patients. 99mTc-DPD SPECT/CT imaging with determination of SUV retention index as part of a routine annual examination can provide evidence of treatment response in ATTR-CM patients receiving disease-modifying therapy. Further long-term studies with 99mTc-DPD SPECT/CT imaging may help to evaluate the relationship between tafamidis-induced reduction in SUV retention index and outcome in patients with ATTR-CM and will demonstrate whether highly disease-specific 99mTc-DPD SPECT/CT imaging is more sensitive than routine diagnostic monitoring.

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

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.

The Role of 18F-FLT PET/CT in Assessing Early Response to Transarterial Radioembolization and Chemoembolization in Patients with Primary and Metastatic Liver Tumors.

Objectives:Metastases and primary malignancies are common in the liver. Local ablative applications such as transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) provide minimally invasive and safe treatment in unresectable liver tumors. Early detection of response to treatment prevents unnecessary toxicity and cost in non-responder patients and provides an earlier use of other options that may be effective. This study aimed to identify the role of 18F-fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) in the assessment of early response to TACE and TARE treatments in patients with unresectable primary and metastatic liver tumorsMethods:This single-center study included 63 patients who underwent 18F-FLT PET/CT for response evaluation after TACE and TARE. After excluding 20 patients whose data were missing 43 TARE-receiving patients were analyzed. The compatibility of change in semi-quantitative values obtained from the 18F-FLT PET/CT images with the treatment responses detected in 18F-fluorodeoxyglucose PET/CT, CT, and MR images and survival was evaluated.Results:There was no correlation between early metabolic, morphological response, and 18F-FLT uptake pattern, and change in standardized uptake values (SUV) which were ΔSUVmax, ΔSUVmean, ΔSUVpeak., ΔSUVmean, Δ SUVpeak values. There was no significant correlation between 18F-FLT uptake pattern, ΔSUVmax, ΔSUVmean, ΔSUVpeak, and overall survival, progression-free survival (PFS) for the target lobe PFS for the whole-body. The survival distributions for the patients with >30% change in Δ SUVmax and ΔSUVpeak values were statistically significantly longer than the patients with <30% change (p<0.009 and p<0.024, respectively).Conclusion:There was significant longer PFS for target liver lobe in patients with more than 30% decrease in 18F-FLT SUVmax and SUVpeak of the liver lesion in primary and metastatic unresectable liver tumors undergoing TARE.

191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026)

Predictive biomarkers of response to HER2-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early changes in tumor standardized uptake values corrected for lean body mass (SULmax) on FDG-PET/CT predicted pathologic complete response (pCR) to neoadjuvant trastuzumab and pertuzumab (HP) in HER2-positive breast cancer (PMID:33999652). We hypothesized that early changes on FDG-PET/CT will predict RFS/OS.

18F]Fluorothymidine(FLT)-PET imaging of thymidine kinase 1 pharmacodynamics in non-small cell lung cancer treated with pemetrexed.

3070 Background: Imaging of tumor proliferation has been studied with FLT-PET in various tumor types including NSCLC. Pemetrexed inhibits thymidylate synthase(TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). TS inhibition upregulates the thymidine salvage pathway including relocalisation of ENT1 to membrane and TK1 activation as a transient “flare” response. We hypothesise that this can be detected as an increase in FLT tumoral uptake that subsequently decreases with reduced proliferation. This study was conducted to assess FLT uptake as an early pharmacodynamics(PD) marker of pemetrexed response. Methods: This was an open-label imaging study in 21 patients with Stage 3/4 NSCLC treated with pemetrexed and platinum-based chemotherapy. Patients underwent FLT PET/CT scan at baseline and 4h after administration of pemetrexed. Platinum component of treatment was administered on the day after second FLT scan for cycle 1. Plasma for TK1 activity expression were collected before each scan time point and analysed by ELISA. Percentage change in standardized uptake value (%ΔSUV) was calculated as [SUV(PET2) – SUV(PET1)]/ SUV(PET1)*100. Treatment response calculated by RECIST 1. 1 and survival data were collected. Results: 17 patients had evaluable PET/CT scans for pemetrexed response. Median percentage difference for SUVmean and SUVmax in tumour lesions increased by 3% and 10.3% respectively. 5 patients showed homogeneous FLT flare at 4h after pemetrexed, 2 patients had decrease, 10 patients had heterogeneous FLT response (regardless of platinum doublet). There was no significant correlation between plasma TK1 activity and FLT flare. At 9 weeks, 4 patients had partial response, 9 stable disease and 4 progressive disease. Baseline and weighted average ΔSUVmax were not associated with survival. The 5 patients with FLT flare in all lesions showed a median OS of 31 months, unlike the group with heterogenous or decrease uptake(15 months). FLT uptake in bone marrow and small bowel significantly increased at 4h (t test p = 0.004, p = 0.004, respectively) indicating increased thymidine salvage activity. Early FLT uptake was not predictive for tumour RECIST response or OS. In multivariable cox regression analysis, pre-treatment TK1 activity, adjusted for performance status, smoking history and age, independently affected survival in this group (p = 0.011). Conclusions: Early FLT flare at 4h was seen in NSCLC post pemetrexed administration indicating activation of thymidine salvage pathway. Median overall survival of patients with an FLT flare response was more than twice longer than patients with mixed or no response. However, the small sample size lacked power to show statistical significance in the OS comparison. Further studies should evaluate this and the relationship to other prognostic variables in a larger cohort of patients. Clinical trial information: NCRI UK badge 9249.

Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer.

The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer. Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years. Patients underwent a PET/MRI scan pretreatment and at fraction 10. Change in value of imaging means were analyzed by analysis of variance. K-means clustering with Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters. Linear regression was performed on all radiographic metrics using patient and disease characteristics. Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Pretreatment imaging characteristics between LR and IR patients were similar. Patients with LR disease exhibited a larger reduction in maximum standardized uptake value (SUV) compared with IR patients (P<0.05). Cluster analysis defined 2 cohorts that exhibited a similar intratreatment response. Cluster 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cluster 2 contained 3 of 11 IR patients. Cluster 2 exhibited significant differences compared with cluster 1 in the change in primary tumor peak SUV and largest lymph node median SUV. We identified that IR p16-positive oropharynx cancers exhibit heterogeneity in their PET/MRI response to chemoradiotherapy. These data support further study of intratreatment imaging response as a potential mechanism to identify patients with IR oropharynx cancer suitable for treatment deintensification.

Cardiac metabolic changes on 18 F-positron emission tomography after thoracic radiotherapy predict for overall survival in esophageal cancer patients.

Heart doses have been shown to be predictive of cardiac toxicity and overall survival (OS) for esophageal cancer patients. There is potential for functional imaging to provide valuable cardiac information. The purpose of this study was to evaluate the cardiac metabolic dose-response using 18 F-deoxyglucose (FDG)-PET and to assess whether standard uptake value (SUV) changes in the heart were predictive of OS. Fifty-one patients with esophageal cancer treated with radiation who underwent pre- and post-treatment FDG-PET scans were retrospectively evaluated. Pre- and post-treatment PET-scans were rigidly registered to the planning CT for each patient. Pre-treatment to post-treatment absolute mean SUV (SUVmean) changes in the heart were calculated to assess dose-response. A dose-response curve was generated by binning each voxel in the heart into 10Gy dose-bins and analyzing the SUVmean changes in each dose-bin. Multivariate cox proportional hazard models were used to assess whether pre-to-post treatment cardiac SUVmean changes predicted for OS. The cardiac dose-response curve demonstrated a trend of increasing cardiac SUV changes as a function of dose with an average increase of 0.044 SUV for every 10Gy dose bin. In multivariate analysis, disease stage and SUVmean change in the heart were predictive (p<0.05) for OS. Changes in pre- to post-treatment cardiac SUV were predictive of OS with patients having a higher pre- to post-treatment cardiac SUV change surviving longer.

Prediction of cardiac events following concurrent chemoradiation therapy for non-small-cell lung cancer using FDG PET.

No imaging biomarkers are available for the prediction of cardiac events following concurrent chemoradiation therapy (CCRT) for non-small-cell lung cancer (NSCLC). We evaluated whether F-18 fluorodeoxyglucose positron emission tomography (FDG PET) early after CCRT, in addition to cardiac dosimetry, could predict late cardiac events in NSCLC. We retrospectively enrolled 133 consecutive patients with locally advanced, unresectable stage III NSCLC, who underwent FDG PET early after CCRT and survived at least 6months. The primary endpoint was cardiac event ≥ grade 2 according to the Common Terminology Criteria for Adverse Events (version 5.0). Myocardial FDG uptake was measured and its association with the risk of cardiac events was evaluated. FDG PET was performed after a median interval of 11days of completing CCRT. Overall, 42 (32%) patients experienced cardiac events during a median follow-up of 45months. The mean heart dose, maximum left ventricular (LV) standardized uptake value (SUV), changes in maximum and mean LV SUV, right ventricular uptake, tumor stage, white blood cell count, and diabetes were associated with cardiac events in univariable analysis. In multivariable analysis, maximum LV SUV (cutoff > 12.84; hazard ratio [95% confidence interval] = 2.140 [1.140-4.016]; p = 0.018) was an independent predictor of cardiac events along with the mean heart dose (> 11.1Gy; 3.646 [1.792-7.417]; p < 0.001) and tumor stage (IIIB; 1.986 [1.056-3.734]; p = 0.033). It remained predictive of cardiac events in those with higher mean heart dose but not in those with lower mean heart dose. Early FDG PET after CCRT for NSCLC could aid in predicting late cardiac events, especially in patients with higher mean heart dose.

Abstract P3-02-03: Quantitative molecular breast imaging for early prediction of neoadjuvant systemic therapy response in locally advanced breast cancer patients

Abstract BACKGROUND: Increasing use of neoadjuvant systemic therapy (NAT) for early and locally advanced breast cancer led to critical need for development of tools capable of early treatment response assessment after NAT. Tc-99m sestamibi Molecular breast Imaging (MBI) as a functional imaging modality has a promise to detect changes in the tumor prior to anatomical changes detected by mammogram or ultrasound. PURPOSE: To evaluate the ability of quantitative MBI parameters to predict pathologic complete response (pCR) after completion of NAT in breast cancer patients. MATERIALS AND METHODS: Patients with invasive breast cancer (T1-T4, N0-N3, M0) planned for NAT followed by surgery were enrolled in a prospective IRB approved trial. MBI was performed at baseline and after two cycles of NAT. Patient demographic and tumor biology information (Ki-67, HER2, ER/PR) was collected. MBI images were quantified using a novel approach with corrections for scatter and attenuation and regions of interest (ROI) were drawn over tumors to compute three quantitative MBI uptake metrics for correlation with pathologic response: MBI-specific standardized uptake value (SUV), tumor to background ratio (TBR), and tumor volume. Pathologic complete response was determined based on final histopathology report at the time of surgery as absence of the invasive disease in the breast and axillary lymph nodes. MBI metrics at baseline, after 2 cycles of NAT and interval change were correlated with pCR and tumor biology using the Wilcoxon Rank Sum test, Kruskal-Wallis test or Fisher’s exact test. Statistical analysis was carried out using R (version 3.6.3, R Development Core Team). RESULTS: A total of 70 patients with median age 47.5 years (range 30-77) were included in the analysis. Breast cancer subtypes were: HER2 negative (ER/PR+) 35.7% (25/70), HER2 positive (ER/PR +/-) 35.7% (25/70), and triple negative (HER2-, ER/PR-) 28.6% (20/70). Change in SUV after 2 cycles of NAT was higher in patients with pCR compared to those who did not achieve pCR (mean decrease in SUV of 15.57 and 4.83 respectively, p&amp;lt;0.001). Additionally, change in TBR in patients with pCR was also higher compared to patients who did not achieve pCR (mean decreases of 1.14 and 0.56, respectively, p&amp;lt;0.001). No correlation was found between baseline SUV, baseline TBR, change in volume, and pCR. CONCLUSION: MBI-specific SUV and TBR changes after two cycles of NAT correlate and may predict pCR in patients with locally advanced breast cancer. Quantitative MBI parameters are novel promising imaging tools that may help to detect early clinical benefit and optimize management in patients receiving NAT. Citation Format: Miral M Patel, Beatriz E Adrada, Benjamin Lopez, Rosalind P Candelaria, Jia Sun, Medine Boge, Rania M Mohamed, Nabil Elshafeey, Gary Whitman, MD, Huong T Le-Petross, Lumarie Santiago, Marion E Scoggins, Deanna Lane, Tanya Moseley, Galit Zylberman, Jerica Saddler, Jessica WT Leung, Wei T Yang, Vincente Valero, S Cheenu Kappadath, Gaiane M Rauch. Quantitative molecular breast imaging for early prediction of neoadjuvant systemic therapy response in locally advanced breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-03.

Maximum standardized uptake value change rate before and after neoadjuvant chemotherapy can predict early recurrence in patients with locally advanced esophageal cancer: a multi-institutional cohort study of 220 patients in Japan.

Neoadjuvant chemotherapy (NAC) followed by esophagectomy can improve the prognosis of locally advanced esophageal cancer (LAEC). However, LAEC reportedly recurred in 17-21% of patients within 6 months post surgery. Thus, current treatment strategies may be inadequate for LAECs with poor prognosis. Preoperative identification of patients with poor prognosis might aid in modification of treatment strategies. This study aimed to evaluate the usefulness of the maximum standardized uptake value change rate (ΔSUVmax) in predicting treatment effects on the primary lesion, prognosis, and LAEC recurrence. This study involved 220 esophageal cancer patients who underwent esophagectomy after NAC at three facilities in Japan. The optimal cut-off point for ΔSUVmax in predicting tumor regression grade (TRG) was calculated and used to assess the correlation between ΔSUVmax and postoperative survival. The optimal cut-off point for ΔSUVmax was 0.5. The 5-year overall survival rate in patients with ΔSUVmax ≥ 0.5 was significantly higher than that in patients with ΔSUVmax < 0.5 (71.5% vs. 50.5%, P = 0.001). Multivariate analysis identified ΔSUVmax (hazards ratio, 0.496; P = 0.004) as an independent prognostic factor. Among 199 patients evaluated for recurrence, 24 (12.1%) showed recurrence within 6 months post surgery. Univariate analysis revealed ΔSUVmax as the only predictor for early recurrence (odds ratio, 0.222; P = 0.004). ΔSUVmax before and after NAC is clinically useful as it could help predict TRG, survival outcome, and early recurrence within 6 months post esophagectomy and is easily obtainable in general clinical practice. We believe that it may also help determine suitable treatment strategies for LAEC.

Data-driven gated PET/CT: implications for lesion segmentation and quantitation

BackgroundData-driven gating (DDG) can improve PET quantitation and alleviate many issues with patient motion. However, misregistration between DDG-PET and CT may occur due to the distinct temporal resolutions of PET and CT and can be mitigated by DDG-CT. Here, the effects of misregistration and respiratory motion on PET quantitation and lesion segmentation were assessed with a new DDG-PET/CT method.MethodsA low-dose cine-CT was acquired in misregistered regions to enable both average CT (ACT) and DDG-CT. The following were compared: (1) baseline PET/CT, (2) PET/ACT (attenuation correction, AC = ACT), (3) DDG-PET (AC = helical CT), and (4) DDG-PET/CT (AC = DDG-CT). For DDG-PET, end-expiration (EE) data were derived from 50% of the total PET data at 30% from end-inspiration. For DDG-CT, EE phase CT data were extracted from cine-CT data by lung Hounsfield unit (HU) value and body contour. A total of 91 lesions from 16 consecutive patients were assessed for changes in standard uptake value (SUV), lesion glycolysis (LG), lesion volume, centroid-to-centroid distance (CCD), and DICE coefficients.ResultsRelative to baseline PET/CT, median changes in SUVmax ± σ for all 91 lesions were 20 ± 43%, 26 ± 23%, and 66 ± 66%, respectively, for PET/ACT, DDG-PET, and DDG-PET/CT. Median changes in lesion volume were 0 ± 58%, − 36 ± 26%, and − 26 ± 40%. LG for individual lesions increased for PET/ACT and decreased for DDG-PET, but was not different for DDG-PET/CT. Changes in mean HU from baseline PET/CT were dramatic for most lesions in both PET/ACT and DDG-PET/CT, especially for lesions with mean HU < 0 at baseline. CCD and DICE were both affected more by motion correction with DDG-PET than improved registration with ACT or DDG-CT.ConclusionAs misregistration becomes more prominent, the impact of motion correction with DDG-PET is diminished. The potential benefits of DDG-PET toward accurate lesion segmentation and quantitation could only be fully realized when combined with DDG-CT. These results impress upon the necessity of ensuring both misregistration and motion correction are accounted for together to optimize the clinical utility of PET/CT.

Generation of parametric Ki images for FDG PET using two 5‐min scans

AbstractPurposeThe net uptake rate constant (Ki) derived from dynamic imaging is considered the gold standard quantification index for FDG PET. In this study, we investigated the feasibility and assessed the clinical usefulness of generating Ki images for FDG PET using only two 5‐min scans with population‐based input function (PBIF).MethodsUsing a Siemens Biograph mCT, 10 subjects with solid lung nodules underwent a single‐bed dynamic FDG PET scan and 13 subjects (five healthy and eight cancer patients) underwent a whole‐body dynamic FDG PET scan in continuous‐bed‐motion mode. For each subject, a standard Ki image was generated using the complete 0–90 min dynamic data with Patlak analysis (t* = 20 min) and individual patient's input function, while a dual‐time‐point Ki image was generated from two 5‐min scans based on the Patlak equations at early and late scans with the PBIF. Different start times for the early (ranging from 20 to 55 min with an increment of 5 min) and late (ranging from 50 to 85 min with an increment of 5 min) scans were investigated with the interval between scans being at least 30 min (36 protocols in total). The optimal dual‐time‐point protocols were then identified. Regions of interest (ROI) were drawn on nodules for the lung nodule subjects, and on tumors, cerebellum, and bone marrow for the whole‐body‐imaging subjects. Quantification accuracy was compared using the mean value of each ROI between standard Ki (gold standard) and dual‐time‐point Ki, as well as between standard Ki and relative standardized uptake value (SUV) change that is currently used in clinical practice. Correlation coefficients and least squares fits were calculated for each dual‐time‐point protocol and for each ROI. Then, the predefined criteria for identifying a reliable dual‐time‐point Ki estimation for each ROI were empirically determined as: (1) the squared correlation coefficient (R2) between standard Ki and dual‐time‐point Ki is larger than 0.9; (2) the absolute difference between the slope of the equality line (1.0) and that of the fitted line when plotting standard Ki versus dual‐time‐point Ki is smaller than 0.1; (3) the absolute value of the intercept of the fitted line when plotting standard Ki versus dual‐time‐point Ki normalized by the mean of the standard Ki across all subjects for each ROI is smaller than 10%. Using Williams’ one‐tailed t test, the correlation coefficient (R) between standard Ki and dual‐time‐point Ki was further compared with that between standard Ki and relative SUV change, for each dual‐time‐point protocol and for each ROI.ResultsReliable dual‐time‐point Ki images were obtained for all the subjects using our proposed method. The percentage error introduced by the PBIF on the dual‐time‐point Ki estimation was smaller than 1% for all 36 protocols. Using the predefined criteria, reliable dual‐time‐point Ki estimation could be obtained in 25 of 36 protocols for nodules and in 34 of 36 protocols for tumors. A longer time interval between scans provided a more accurate Ki estimation in general. Using the protocol of 20–25 min plus 80–85 or 85–90 min, very high correlations were obtained between standard Ki and dual‐time‐point Ki (R2 = 0.994, 0.980, 0.971 and 0.925 for nodule, tumor, cerebellum, and bone marrow), with all the slope values with differences ≤0.033 from 1 and all the intercept values with differences ≤0.0006 mL/min/cm3 from 0. The corresponding correlations were much lower between standard Ki and relative SUV change (R2 = 0.673, 0.684, 0.065, 0.246). Dual‐time‐point Ki showed a significantly higher quantification accuracy with respect to standard Ki than relative SUV change for all the 36 protocols (p &lt; 0.05 using Williams’ one‐tailed t test).ConclusionsOur proposed approach can obtain reliable Ki images and accurate Ki quantification from dual‐time‐point scans (5‐min per scan), and provide significantly higher quantification accuracy than relative SUV change that is currently used in clinical practice.

End-of-treatment 18F-FDG PET/CT in diffuse large B cell lymphoma patients: ΔSUV outperforms Deauville score

In DLBCL, the Deauville scoring system (DS) is the standard for PET/CT response assessment. An alternative system, based on the semi-quantitative change in standardized uptake values, namely ΔSUVmax, has been reported to be more objective than the DS. We aimed to compare ΔSUVmax and DS for risk stratification of DLBCL patients on end-of-treatment (EoT) PET. 108 consecutive patients were included. 2-year EFS Kaplan–Meier survival analyses and Cox regression models were performed. 2-year EFS was significantly different between favorable ΔSUVmax (favΔ < −86.5%) and unfavorable ΔSUVmax (unfavΔ ≥ −86.5%) patients: 100.0% ± 0.0 versus 58.3% ± 14.2 (p = 0.001). On Cox multivariable regression, ΔSUVmax status was the only independent predictor of 2-year EFS, outperforming DS. Therefore, ΔSUVmax should be computed for non-responder patients, especially DS4, as the 2-year EFS is not different between responders and non-responders in the case of favΔ. Further studies are needed in order to confirm this hypothesis.

Improvement of image quality using amplitude-based respiratory gating in PET-computed tomography scanning.

This study sought to provide data supporting the expanded clinical use of respiratory gating by assessing the diagnostic accuracy of breathing motion correction using amplitude-based respiratory gating. A respiratory movement tracking device was attached to a PET-computed tomography scanner, and images were obtained in respiratory gating mode using a motion phantom that was capable of sensing vertical motion. Specifically, after setting amplitude changes and intervals according to the movement cycle using a total of nine combinations of three waveforms and three amplitude ranges, respiratory motion-corrected images were reconstructed using the filtered back projection method. After defining areas of interest in the acquired images in the same image planes, statistical analyses were performed to compare differences in standardized uptake value (SUV), lesion volume, full width at half maximum (FWHM), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). SUVmax increased by 89.9%, and lesion volume decreased by 27.9%. Full width at half maximum decreased by 53.9%, signal-to-noise ratio increased by 11% and contrast-to-noise ratio increased by 16.3%. Optimal results were obtained when using a rest waveform and 35% duty cycle, in which the change in amplitude in the respiratory phase signal was low, and a constant level of long breaths was maintained. These results demonstrate that respiratory-gated PET-CT imaging can be used to accurately correct for SUV changes and image distortion caused by respiratory motion, thereby providing excellent imaging information and quality.

Prognostic and predictive values of interim 18F-FDG PET during neoadjuvant chemoradiotherapy for esophageal cancer: a systematic review and meta-analysis.

To determine the prognostic and predictive value of early metabolic response assessed by a change in standardized uptake value (SUV) on interim 18F-FDG PET in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. PubMed and Embase were searched up until 10 September, 2020, for studies evaluating a change in SUV on interim 18F-FDG PET for predicting a pathologic response, progression-free survival (PFS), or overall survival (OS) in patients with esophageal cancer. The sensitivity and specificity for predicting a pathologic response were pooled using bivariate and hierarchical summary receiver operating characteristic (HSROC) models. Meta-analytic pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were derived using a random-effects model. A total of 11 studies (695 patients) were included in the meta-analysis. For nine studies assessing predictive accuracy, the pooled sensitivity and specificity of an early metabolic response for predicting a pathologic response were 0.80 (95% CI 0.61-0.91) and 0.54 (95% CI 0.45-0.63), respectively. The area under the HSROC curve was 0.64 (95% CI 0.60-0.68). Across the nine studies assessing prognostic value, an early metabolic response determined by interim PET showed pooled HRs for predicting PFS and OS of 0.44 (95% CI, 0.30-0.63) and 0.42 (95% CI, 0.31-0.56), respectively. Change in SUV on interim 18F-FDG PET had significant prognostic value and moderate predictive value for a pathologic response in esophageal cancer treated with neoadjuvant chemoradiotherapy. Interim 18F-FDG PET may help prognostic stratification and guide treatment planning in oncologic practice.

11C]PIB amyloid quantification: effect of reference region selection

BackgroundThe standard reference region (RR) for amyloid-beta (Aβ) PET studies is the cerebellar grey matter (GMCB), while alternative RRs have mostly been utilized without prior validation against the gold standard. This study compared five commonly used RRs to gold standard plasma input-based quantification using the GMCB.MethodsThirteen subjects from a test–retest (TRT) study and 30 from a longitudinal study were retrospectively included (total: 17 Alzheimer’s disease, 13 mild cognitive impairment, 13 controls). Dynamic [11C]PiB PET (90 min) and T1-weighted MR scans were co-registered and time–activity curves were extracted for cortical target regions and the following RRs: GMCB, whole cerebellum (WCB), white matter brainstem/pons (WMBS), whole brainstem (WBS) and eroded subcortical white matter (WMES). A two-tissue reversible plasma input model (2T4k_Vb) with GMCB as RR, reference Logan and the simplified reference tissue model were used to derive distribution volume ratios (DVRs), and standardized uptake value (SUV) ratios were calculated for 40–60 min and 60–90 min intervals. Parameter variability was evaluated using TRT scans, and correlations and agreements with the gold standard (DVR from 2T4k_Vb with GMCB RR) were also assessed. Next, longitudinal changes in SUVs (both intervals) were assessed for each RR. Finally, the ability to discriminate between visually Aβ positive and Aβ negative scans was assessed.ResultsAll RRs yielded stable TRT performance (max 5.1% variability), with WCB consistently showing lower variability. All approaches were able to discriminate between Aβ positive and Aβ negative scans, with highest effect sizes obtained for GMCB (range − 0.9 to − 0.7), followed by WCB (range − 0.8 to − 0.6). Furthermore, all approaches provided good correlations with the gold standard (r ≥ 0.78), while the highest bias (as assessed by the regression slope) was observed using WMES (range slope 0.52–0.67), followed by WBS (range slope 0.58–0.92) and WMBS (range slope 0.62–0.91). Finally, RR SUVs were stable across a period of 2.6 years for all except WBS and WMBS RRs (60–90 min interval).ConclusionsGMCB and WCB are considered the best RRs for quantifying amyloid burden using [11C]PiB PET.

Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial

AbstractAs part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.