Changes In Metabolic Tumor Volume Research Articles

10213-GMC-16 A DECADE REVIEW: BEVACIZUMAB'S IMPACT ON GLIOBLASTOMA TREATMENT

Abstract OBJECTIVE This study aims to assess the efficacy of Bevacizumab (Bev) therapy, ten years after its initiation in treating glioblastoma patients at our department. METHODS Eighty-four patients treated with Bev from July 2013 to December 2022 were classified into three groups: the initial treatment group given the Stupp regimen with Bev (first-dose group), the group given the Stupp regimen plus Bev followed by tumor resection (neoadjuvant group), and those receiving the Stupp regimen post tumor resection (recurrence group). PET scans were conducted pre- and post- Bev therapy, and variations in Tumor-to-Normal ratio (TNR), Tumor-to-Blood ratio (TBR), and Metabolic Tumor Volume (MTV) were investigated. RESULTS The median Progression-Free Survival (PFS) and Overall Survival (OS) rates in the first, neoadjuvant, and recurrence groups were respectively (7.86, 14.27, 4.33) and (12.53, 21.57, 13.23) months. Notably, changes in MET and FMISO MTV in the first-treatment group, MET MTV and FMISO TBR changes in the recurrence group, and MET MTV change in the neoadjuvant group significantly influenced prognosis. In the recurrence group, patients who underwent total resection during initial treatment experienced a prolonged period of 25.9 months from initial treatment to the administration of Bev due to recurrence. Furthermore, cases where the FMISO TBR at recurrence was higher than at the initial treatment observed an extended median OS of 18.63 months upon administering Bev treatment at recurrence. CONCLUSION Bev neoadjuvant therapy demonstrated a significant correlation with enhanced PFS and OS outcomes, notably in patients subjected to total resection. In the context of recurrent disease, while the initiation of Bev administration was delayed, a distinct elevation in treatment effectiveness was observed in patients exhibiting an augmented FMISO TBR at the point of recurrence. The observed decreases in MET MTV and FMISO TBR emerge as robust predictors of the efficacy of Bev treatment.

NIMG-58. PET IMAGING AS A RELIABLE INDICATOR FOR EVALUATING BEVACIZUMAB TREATMENT RESPONSE IN GBM

Abstract OBJECTIVE PET scans are crucial for glioma diagnosis and treatment planning, but assessing the efficacy of Bevacizumab (Bev) treatment using MRI alone is challenging. Our study aimed to evaluate the effectiveness of Bev-based glioblastoma treatment using PET scans. METHODS We included ninety glioblastoma patients treated with Bev between July 2013 and May 2023. Patients were divided into three groups: the first group received Bev in addition to the Stupp regimen after biopsy or subtotal resection (first-dose group), the second group received Bev after biopsy followed by tumor resection (neoadjuvant group), and the third group received the Stupp regimen followed by TMZ + Bev at recurrence (recurrent group). PET scans (FDG, MET, FLT, and FMISO) were performed before and 4 weeks after starting Bev treatment. Tumor-to-normal ratio (TNR) was calculated for FDG, MET, and FLT, and tumor-to-blood ratio (TBR) was determined for FMISO. We used the Cox proportional hazards model to assess the percent change in TNR, TBR, and metabolic tumor volume (MTV) as prognostic factors. RESULTS The median PFS and OS (month) from Bev treatment were as follows: first-dose group (PFS: 8.87, OS: 12.53), neoadjuvant group (PFS: 16.53, OS: 22.13), and recurrent group (PFS: 4.0, OS: 8.0). In the first-line group, significant differences were found in the percent change in MTV for MET, FLT, and FMISO. In the recurrent group, significant differences were observed in the percent change in MTV for FDG and MET, as well as in FDG TNR and FMISO TBR. In the neoadjuvant group, significant differences were found in the percent change in MTV for MET and FLT. CONCLUSION Neoadjuvant Bev treatment led to prolonged PFS and OS in glioblastoma patients. Decreases in MET MTV change rate and FMISO TBR change rate were identified as potential indicators for assessing Bev treatment efficacy after recurrence.

18F-AlF-NOTA-FAPI-04 PET/CT can Predict Treatment Response and Survival in Patients with Inoperable Pancreatic Adenocarcinoma

We investigated whether uptake of 18F-AlF-NOTA-FAPI-04 on positron emission tomography/computed tomography (PET/CT) could predict treatment response and survival in patients with pancreatic adenocarcinoma (PAAD). We prospectively evaluated 47 patients with histopathologically confirmed primary PAAD and pretreatment 18F-FAPI PET/CT scans to determine uptake of fibroblast activation protein (FAP) and compare the findings with those from blood tests and immunohistochemically stained tumor specimens. Cox regression and Kaplan-Meier methods were used to assess relationships between disease progression and potential predictors. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cutoff points for distinguishing patients according to good response vs poor response per RECIST v. 1.1. The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean); metabolic tumor volume (MTV); and total lesion FAP expression (TLF) were positively correlated with cancer-associated fibroblast (CAF) markers (FAP, α-smooth muscle actin, vimentin, S100A4, and platelet-derived growth factor receptor α/β, all P<0.05). MTV and Log2TLF were associated with survival in patients with inoperable PAAD (all P<0.05). Analyses controlling for sex, age, cTNM, and performance status showed that MTV and Log2TLF were associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016 and Log2TLF HR = 4.093, P = 0.003). ROC cutoff analysis indicated that elevated MTV and TLF were associated with poorer survival. Greater changes from before to after chemotherapy in SUVmax, MTV, and TLF were associated with good treatment response (all P<0.05). ΔMTV, ΔTLF and ΔSUVmax had larger areas under the curve than ΔCA19-9 for predicting treatment response. Kaplan-Meier analysis showed that the extent of change in MTV and TLF from before to after treatment predicted progression-free survival, with cutoff values (based on medians) of -4.95 for ΔMTV (HR = 8.09, P = 0.013) and -77.83 for ΔTLF (HR = 4.62, P = 0.012). Higher baseline MTV on 18F-FAPI-04 PET/CT scans was associated with poorer survival in patients with inoperable PAAD. ΔMTV was more sensitive for predicting response than ΔCA19-9. These results are clinically meaningful for identifying patients with PAAD who are at high risk of disease progression.

Automated Brain Tumor Detection and Segmentation for Treatment Response Assessment Using Amino Acid PET.

Evaluation of metabolic tumor volume (MTV) changes using amino acid PET has become an important tool for response assessment in brain tumor patients. MTV is usually determined by manual or semiautomatic delineation, which is laborious and may be prone to intra- and interobserver variability. The goal of our study was to develop a method for automated MTV segmentation and to evaluate its performance for response assessment in patients with gliomas. Methods: In total, 699 amino acid PET scans using the tracer O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) from 555 brain tumor patients at initial diagnosis or during follow-up were retrospectively evaluated (mainly glioma patients, 76%). 18F-FET PET MTVs were segmented semiautomatically by experienced readers. An artificial neural network (no new U-Net) was configured on 476 scans from 399 patients, and the network performance was evaluated on a test dataset including 223 scans from 156 patients. Surface and volumetric Dice similarity coefficients (DSCs) were used to evaluate segmentation quality. Finally, the network was applied to a recently published 18F-FET PET study on response assessment in glioblastoma patients treated with adjuvant temozolomide chemotherapy for a fully automated response assessment in comparison to an experienced physician. Results: In the test dataset, 92% of lesions with increased uptake (n = 189) and 85% of lesions with iso- or hypometabolic uptake (n = 33) were correctly identified (F1 score, 92%). Single lesions with a contiguous uptake had the highest DSC, followed by lesions with heterogeneous, noncontiguous uptake and multifocal lesions (surface DSC: 0.96, 0.93, and 0.81 respectively; volume DSC: 0.83, 0.77, and 0.67, respectively). Change in MTV, as detected by the automated segmentation, was a significant determinant of disease-free and overall survival, in agreement with the physician's assessment. Conclusion: Our deep learning-based 18F-FET PET segmentation allows reliable, robust, and fully automated evaluation of MTV in brain tumor patients and demonstrates clinical value for automated response assessment.

18F] AlF-NOTA-FAPI-04 PET/CT can predict treatment response and survival in patients receiving chemotherapy for inoperable pancreatic ductal adenocarcinoma.

We investigated whether uptake of [18F] AlF-NOTA-FAPI-04 on positron emission tomography/computed tomography (PET/CT) could predict treatment response and survival in patients with pancreatic ductal adenocarcinoma (PDAC). We prospectively evaluated 47 patients with histopathologically confirmed primary PDAC who provided pretreatment [18F] AlF-NOTA-FAPI-04 scans to detect fibroblast activation protein (FAP) on the tumor surface by uptake of [18F] AlF-NOTA-FAPI-04. PDAC specimens were immunohistochemically stained with cancer-associated fibroblast (CAF) markers. We obtained a second PET scan after one cycle of chemotherapy to study changes in FAPI uptake variables from before to during treatment. Correlations between baseline PET variables and CAF-related immunohistochemical markers were assessed with Spearman's rank test. Cox regression and Kaplan-Meier methods were used to assess relationships between disease progression and potential predictors. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cut-off points for distinguishing patients according to good response vs. poor response per RECIST v.1.1. The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion FAP expression (TLF) were positively correlated with CAF markers (FAP, α-smooth muscle actin, vimentin, S100A4, and platelet-derived growth factor receptor α/β, all P < 0.05). MTV was associated with survival in patients with inoperable PDAC (all P < 0.05). Cox multivariate regression showed that MTV was associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016). Greater changes from before to during chemotherapy in SUVmax, MTV, and TLF were associated with good treatment response (all P < 0.05). ΔMTV, ΔTLF, and ΔSUVmax had larger areas under the curve than ΔCA19-9 for predicting treatment response. Kaplan-Meier analysis showed that the extent of change in MTV and TLF from before to after treatment predicted progression-free survival, with cut-off values (based on medians) of - 4.95 for ΔMTV (HR = 8.09, P = 0.013) and - 77.83 for ΔTLF (HR = 4.62, P = 0.012). A higher baseline MTV on [18F] AlF-NOTA-FAPI-04 scans was associated with poorer survival in patients with inoperable PDAC. ΔMTV was more sensitive for predicting response than ΔCA19-9. These results are clinically meaningful for identifying patients with PDAC who are at high risk of disease progression.

Prognostic value of PERCIST and PET/CT metabolic parameters after neoadjuvant treatment in patients with esophageal cancer

AimTo assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival (CSS) in patients with esophageal cancer treated by chemoradiotherapy. Material and methodsFifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan–Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. ResultsThe average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in CSS curves for PERCIST criteria and variation of MTV and TLG. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither SUVmax nor tumor size were predictors for any of the assessment criteria. ConclusionApplication of PERCIST criteria as well as change in MTV and TLG from PET/CT studies proved to be prognostic factors for CSS in patients in our setting treated for esophageal cancer. The results could help to personalize treatment.

Valor pronóstico de los criterios PERCIST y los parámetros metabólicos de la PET/TC en pacientes con cáncer de esófago tras tratamiento neoadyuvante

AimTo assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival in patients with esophageal cancer treated by chemoradiotherapy. Material and methodsFifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV, metabolic tumor volume and total lesion glycolysis between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. ResultsThe average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in cancer-specific survival curves for PERCIST criteria and variation of metabolic tumor volume and total lesion glycolysis. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither maximum SUV nor tumor size were predictors for any of the assessment criteria. ConclusionApplication of PERCIST criteria as well as change in metabolic tumor volume and total lesion glycolysis from PET/CT studies proved to be prognostic factors for cancer-specific survival in patients in our setting treated for esophageal cancer. The results could help to personalize treatment.

Quantitative Change in Metabolic Tumor Volume May Assist in Distinguishing between Pseudoprogressors and Responders in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma Treated with PD-1 Blockade

Quantitative Change in Metabolic Tumor Volume May Assist in Distinguishing between Pseudoprogressors and Responders in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma Treated with PD-1 Blockade

Correlation of 18-fluorodeoxyglucose PET/computed tomography parameters and clinical features to predict outcome for diffuse large B-cell lymphoma.

To determine if the correlation between different metabolic parameters along with clinical features can create an improved model of prognostication for diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively evaluated 89 patients with DLBCL. All patients had a baseline and an interim 18F-FDG PET/CT. Seventy-nine also had an end-of-treatment PET/CT (EOT-PET). For each scan, we collected standardized uptake value (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmaxsum, SUVmeansum, MTVsum, and TLGsum. These metabolic parameters were combined with clinical features in order to identify a new prognostic model. The predictive value of interim PET and EOT-PET using Deauville score was also determined. Baseline SUVmaxsum and SUVmeansum were significantly correlated to overall survival (OS) (P value = 0.012 and 0.011, respectively). The percentage change of MTV and TLG sum from baseline to EOT was predictive of progression-free survival (PFS) (P value = 0.003 and 0.022, respectively). The combination of either Deauville score at the EOT and SUVmaxsum at baseline significantly predicted OS (P value <0.001); Eastern Cooperative Oncology Group performance status, presence of extranodal disease and percentage change of MTVsum from baseline to EOT were significant predictors of PFS (P value = 0.001). SUVmaxsum and SUVmeansum at baseline and percentage change in MTV and TLG sum from baseline to EOT are predictors of outcome in DLBCL patients. These metabolic parameters combined to Deauville score and some clinical features could be used together to stratify patients.

Parametric Response Mapping of Coregistered Positron Emission Tomography and Dynamic Contrast Enhanced Computed Tomography to Identify Radioresistant Subvolumes in Locally Advanced Cervical Cancer

To identify subvolumes that may predict treatment response to definitive concurrent chemoradiation therapy using parametric response mapping (PRM) of coregistered positron emission tomography (PET) and dynamic contrast-enhanced (DCE) computed tomography (CT) in locally advanced cervical carcinoma. Pre- and midtreatment (after 23 ± 4 days of concurrent chemoradiation therapy) DCE CT and PET imaging were performed on 21 patients with cervical cancer who were enrolled in a pilot study to evaluate the prognostic value of CT perfusion for primary cervical cancer (NCT01805141). Three-dimensional coregistered maps of PET/CT standardized uptake value (SUV) and DCE CT blood flow (BF) were generated. PRM was performed using voxel-wise joint histogram analysis to classify voxels within the tumor as highly metabolic and perfused (SUVhiBFhi), highly metabolic and hypoxic (SUVhiBFlo), low metabolic activity and hypoxic (SUVloBFlo), or low metabolic activity and perfused (SUVloBFhi) tissue based on thresholds determined from population means of pretreatment PET SUV and DCE CT BF. Relationships between baseline pretreatment imaging metrics and relative changes in metabolic tumor volume (ΔMTV), calculated from before treatment and during treatment imaging, were determined using univariable and multivariable linear regression models. The relative volume of three PRM subvolumes significantly changed during treatment (SUVhiBFhi: P = .04; SUVhiBFlo: P = .0008; SUVloBFhi: P = .02), whereas SUVloBFlo did not (P = .9). Pretreatment PET SUVmax (r = -.58, P = .006), PET SUVmean (ρ = -.59, P = .005), DCE CT BFmean (r = -.50, P = .02), tumor volume (ρ = -.65, P = .001) and PRM SUVhiBFhi (ρ = -.59, P = .004) were negatively correlated with ΔMTV, whereas PRM SUVloBFlo was positively related to ΔMTV (r = .77, P < .0001). In a multivariable model that predicted ΔMTV, PRM SUVloBFlo, which combines both PET/CT and DCE CT, was the only significant variable (β = 1.825, P = .03), dominating both imaging modalities independently. PRM was applied in locally advanced cervical carcinoma treated definitively with chemoradiation, and radioresistant subvolumes were identified that correlated with changes in MTV and predicted treatment response. Identification of these subvolumes may assist in clinical decision making to tailor therapies, such as brachytherapy, in an effort to improve patient outcomes.

Metabolic Tumor Volume Change Predicts Long-term Survival and Histological Response to Preoperative Chemotherapy in Locally Advanced Esophageal Cancer.

Here, we assess the ability of metabolic tumor volume (MTV) as measured by F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG PET/CT) to evaluate neoadjuvant chemotherapy response for patients with locally advanced esophageal cancer (EC). Optimal methods to evaluate treatment response for EC patients have not yet been established. Although previous studies have reported the value of standardized uptake value (SUV), the accuracy of predicting histological response or long-term survival in EC is limited. In all, 102 EC patients without distant metastasis who underwent F-FDG PET/CT both before and after the preoperative chemotherapy series were analyzed. The median primary tumor MTV values before and after preoperative chemotherapy were 22.55 (range 0.4-183.1) and 2.75 (0-52.9), respectively, and the median MVT reduction rate was 86.5%. We found the most significant difference in survival between PET responders and nonresponders with a cut-off value of 60% MTV reduction, using a 10% stepwise cut-off analysis [2-year progression-free survival (PFS): 79.2 vs 44.4%; hazard ratio (HR) 3.397; P < 0.0001). With this cut-off value, histological response (P = 0.0091), tumor location (P = 0.0102), pT (P = 0.0011), and pN (P = 0.0110) were significantly associated with PET response. Univariate analysis of PFS indicated a correlation between PFS and tumor size, cT, decrease of primary lesion by CT, SUVmax reduction rate, MTV reduction rate, pT, pN, and pM. Multivariate analysis further identified pM (HR 3.063; P = 0.0279) and MTV reduction rate (HR 2.471; P = 0.0263) to be independent prognostic predictors, but not decrease of primary lesion by CT or SUVmax reduction rate. MTV change is clinically useful in predicting both long-term survival and histological response to preoperative chemotherapy in EC patients, after determining the optimal cut-off value based on survival analysis.

Metabolic Tumor Volume for Early Response Assessment in Early-Stage Unfavorable Hodgkin Lymphoma Treated with Nivolumab in the GHSG Nivahl Phase II Trial

Background: Metabolic tumor volume (MTV) measured by FDG-PET/CT is becoming established as an independent risk factor for treatment failure in Hodgkin lymphoma (HL). Moreover, response to treatment with novel agents including checkpoint inhibitors may be better reflected by a decrease in MTV than by currently used response criteria. Our aim was to evaluate the early response to first-line HL treatment with the PD-1 inhibitor nivolumab using MTV. Methods: The analysis set included 59 patients with newly diagnosed, early-stage unfavorable HL treated within the prospective, multicenter, open label, randomized, phase II NIVAHL trial of the German Hodgkin Study Group (GHSG). Patients in NIVAHL were randomized to receive either four double cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine (4x Nivo-AVD, group A, n=31) or a sequential therapy starting with 4x nivolumab monotherapy followed by 2xNivo-AVD and 2x AVD (group B, n=28). Early response to treatment was assessed at a 1st interim restaging after either 2x Nivo-AVD or 4x nivolumab. All NIVAHL patients who underwent PET at both initial staging and early response assessment, with images available to the central review panel for quantitative analysis before April 30th 2019, were included. MTV was calculated using a fixed SUV threshold of 4 for both staging and restaging. Results: Patient characteristics of the MTV analysis subset presented here did not differ in any relevant way from the overall NIVAHL trial population. Median age of the 59 patients was 27 years (range 18-57) with a female predominance (61%). All patients presented with stage II disease (IIB 27%) and ≥3 involved areas was the most common risk factor (75%) followed by elevated erythrocyte sedimentation rate (51%), extranodal disease (17%) and large mediastinal mass (14%). Mean MTV at initial staging was 124 ml (range 4 - 578 ml) and 177 ml (11 - 581 ml) in groups A and B, respectively. In both groups a marked decrease in MTV was observed at the 1st interim restaging (Figure 1): After 2x Nivo-AVD all patients in group A showed a reduction of MTV &gt;80% (mean percentage change in MTV -99.8%). In group B a reduction of MTV &gt;80% was observed in 26/28 patients (93%), while in 2/28 patients an increase &lt;10% was observed (mean percentage change in MTV -91%; Figure 1). The mean residual MTV at interim restaging after 2x Nivo-AVD was 0.4 ml (range 0 - 8) in group A and 11 ml after 4x nivolumab in group B (range 0 - 176). The reduction of MTV was observed irrespective of initial MTV with a similar mean percentage change in patients above and below the median MTV in both groups. When applying the Deauville score, however, the number of patients presenting with a Deauville score ≥4 was higher in the group with an initial MTV above the median MTV than in the group where initial MTV lay below the median value. Using the Lugano criteria and a Deauville score of 4 or higher as cut-off for PET-positivity, early interim complete remission was observed in 81% of patients after 2xNivo-AVD, as compared to 51% after 4x nivolumab monotherapy. Further analyses regarding MTV and response at the 2nd and end-of-treatment restaging as well as survival data are not yet available due to limited follow-up. These data will be available at the time of presentation and shown at the meeting. Conclusions: Marked reductions of MTV demonstrate an excellent early efficacy for both 2x Nivo-AVD and 4x nivolumab as 1st-line therapy for early-stage unfavorable HL. The unexpectedly and previously unreported high MTV reduction with nivolumab monotherapy indicates a relevant potential of anti-PD1 mono- or debulking-therapy in the 1st-line treatment of early-stage unfavorable HL. Early interim response assessment based on MTV may help to identify HL patients treated with anti-PD1 antibodies in whom a significant reduction or even omission of chemotherapy could be considered. MTV appears to have the potential to accurately measure response to immune checkpoint inhibition. However, correlation of early MTV reduction with response at the end of treatment or with survival data is pending. Disclosures Borchmann: Novartis: Honoraria, Research Funding. Bröckelmann:Bristol-Myers Squibb: Honoraria, Other: Travel Support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding; MSD Sharpe &amp; Dohme: Research Funding.

Prognostic Value of the Volumetric Parameters of Dual-Time-Point 18F-FDG PET/CT in Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy.

OBJECTIVE. The purpose of this study is to assess the effectiveness of the volumetric parameters of dual-time-point imaging (DTPI) with 18F-FDG PET (DTPI FDG PET) in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). MATERIALS AND METHODS. The records of consecutive patients who received definitive RT for NSCLC from April 2010 to April 2017 were retrospectively reviewed. Pretreatment DTPI FDG PET images were routinely obtained as part of the PET/CT examination. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor (SUVmax-T, MTV-T, and TLG-T, respectively) and those of the primary tumor and lymph nodes (N) combined (SUVmax-TN, MTV-TN, and TLG-TN, respectively) were used as variables, and the percentage change in these parameters (change in SUVmax [ΔSUVmax], change in MTV [ΔMTV], and change in TLG [ΔTLG]) on DTPI FDG PET were analyzed. RESULTS. Of the 118 patients identified and reviewed, 59 met the study eligibility criteria. After a median follow-up of 23.3 months, the 3-year local control rate (LCR) and disease-specific survival rates were 53.5% and 45.0%, respectively. On multivariate analysis, significant predictors of LCR were TLG-T and change in TLG-TN (ΔTLG-TN), and significant predictors of disease-specific survival were adjuvant chemotherapy, treatment response, TLG-T, and change in TLG-T (ΔTLG-T). Low percentage changes in ΔTLG (< 41.0% for ΔTLG-T and < 32.0% for ΔTLG-TN) correlated with poor LCR and disease-specific survival. SUVmax and MTV were not significant predictors of both LCR and disease-specific survival. CONCLUSION. TLG and ΔTLG were significant prognostic factors in patients with NSCLC treated with definitive RT. In particular, a relatively low ΔTLG resulted in poor outcomes in terms of LCR and disease-specific survival.

Prognostic values of mid-radiotherapy 18F-FDG PET/CT in patients with esophageal cancer

BackgroundTo identify whether early metabolic responses as determined using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) during radiotherapy (RT) predict outcomes in patients with esophageal cancer.MethodsTwenty-one patients with esophageal cancer who received pre-treatment 18F-FDG PET/CT (PET1) and inter-fractional 18F-FDG PET/CT (PET2) after 11 fractions of RT (median 23.1 Gy, 2.1 Gy per fraction) were retrospectively reviewed. The region of interest for each calculation was delineated using “PET Edge”. We calculated PET parameters including maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The relative changes (%) were calculated using the logarithmically transformed parameter values for the PET1 and PET2 scans. Multivariate analysis of locoregional recurrence and distant failures were performed using Cox regression analysis. After identifying statistically significant PET parameters for discriminating responders from non-responders, receiver operating characteristics curve analyses were used to assess the potentials of the studied PET parameters.ResultsAfter a median follow-up of 13 months, the 1-year overall and progression-free survival rates were 79.0% and 34.4%, respectively. Four patients developed locoregional recurrences (LRRs) and 8 had distant metastases (DMs). The 1-year overall LRR-free rate was 76.9% while the DM-free rate was 60.6%. The relative changes in MTV (ΔMTV) were significantly associated with LRR (p = 0.03). Conversely, the relative changes in SUVmean (ΔSUVmean) were associated with the risk of DM (p = 0.02). An ΔMTV threshold of 1.14 yielded a sensitivity of 60%, specificity of 94%, and an accuracy of 86% for predicting an LRR. Additionally, a ΔSUVmean threshold of a 35% decrease yielded a sensitivity of 67%, specificity of 83%, and accuracy of 76% for the prediction DM.Trial registrationRetrospectively registered.ConclusionsChanges in tumor metabolism during RT could be used to predict treatment responses, recurrences, and prognoses in patients with esophageal cancer.

Increases in Serial Pretreatment 18F-FDG PET-CT Metrics Predict Survival in Early Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy

PurposeQuantitative changes in positron emission tomography with computed tomography imaging metrics over serial scans may be predictive biomarkers. We evaluated the relationship of pretreatment metabolic tumor growth rate (MTGR) and standardized uptake value velocity (SUVV) with disease recurrence or death in patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy (SABR). Methods and MaterialsUnder institutional review board approval, we retrospectively identified patients who underwent positron emission tomography with computed tomography at diagnosis and staging and simulation for SABR. Two cohorts underwent SABR between November 2005 to October 2012 (discovery) and January 2012 to April 2016 (validation). MTGR and SUVV were calculated as the daily change in metabolic tumor volume and maximum standardized uptake value, respectively. Cox proportional hazard models identified predictors of local, regional, and distant recurrence and death for the combined cohort. MTGR and SUVV thresholds dichotomizing risk of death in the discovery cohort were applied to the validation cohort. ResultsA total of 152 lesions were identified in 143 patients (92 lesions in 83 discovery cohort patients). In multivariable models, increasing MTGR trended toward increased hazard of distant recurrence (hazard ratio, 6.98; 95% confidence interval, 0.67-72.61; P = .10). In univariable models, SUVV trended toward risk of death (hazard ratio, 11.8, 95% confidence interval, 0.85-165.1, P = .07). MTGR greater than 0.04 mL/d was prognostic of decreased survival in discovery (P = .048) and validation cohorts (P < .01). ConclusionsMTGR greater than 0.04 mL/d is prognostic of death in patients with non-small cell lung cancer treated with SABR. Increasing SUVV trends, nonsignificantly, toward increased risk of recurrence and death. MTGR and SUVV may be candidate imaging biomarkers to study in trials evaluating systemic therapy with SABR for patients at high risk of out-of-field recurrence.

Predicting Per-Lesion Local Recurrence in Locally Advanced Lung Cancer using Metabolic Tumor Volume on Pre- and Mid-Radiation FDG-PET

PET metrics, including metabolic tumor volume (MTV), have been proposed as prognostic imaging biomarkers in patients treated with definitive radiation therapy (RT) for locally advanced non-small cell lung cancer (NSCLC). We evaluated whether the per-lesion change in MTV (ΔMTV) between pre- and mid-treatment PET can be used to predict individual sites of disease progression in this setting. We retrospectively reviewed the records of patients with stage III NSCLC treated with definitive RT (dose≥60 Gy) from 2006 to 2017. We included patients with pre- and mid-RT PET/CT and follow up >3 months. PET Edge, a gradient-based method included in a commercially available deformable registration algorithm, was used to delineate treated lesions (lung tumors and regional lymph nodes) and measure MTVs. The distributions of pre-RT (MTVpre) and mid-RT (MTVmid) MTVs were right-skewed and thus log transformed for analysis. ΔMTV was defined as (MTVmid-MTVpre)/MTVpre. Local recurrence (LR) was defined per lesion (lung tumor or lymph node) as recurrence within the planning target volume based on review of follow-up imaging. Cumulative incidence rates and uni- and multivariate (MVA) Cox regression were used to evaluate the association between ΔMTV and LR for each lesion. Models were adjusted for the competing risk of death. Receiver operating characteristic (ROC) curves were developed to assess the utility of MTV parameters as predictors of LR (R, version 3.3). We identified 80 patients with 272 treated lesions (84 lung tumors and 188 lymph nodes; median 3 lesions per patient). Patients had median age 68 years (IQR 64-76 years). 65% (n=52) of patients were male, 48.8% (n=39) had adenocarcinoma, and 36.3% (n=29) had squamous cell carcinoma. 73 (91.3%) patients received concurrent chemotherapy. Median follow-up was 14 months. Overall survival was 75.0% at 1 year and 50.6% at 2 years. Cumulative incidence of LR was 20.3% at 1 year and 21.3% at 2 years per lesion. When adjusting for lesion location (lung primary versus lymph node) and age in MVA, MTVpre (HR=1.47, 95% CI=1.09-1.99, p=0.02) and ΔMTV (HR=1.06, 95% CI=1.04-1.10, p<0.001) were significantly associated with LR. We did not observe a higher rate of LR for nodal vs primary lesions. We developed a point-based model (0-2) where target lesions accumulate 1 point each for MTVpre>25cc and decrease in ΔMTV<65%. At 1 year, lesions with 0, 1, and 2 points had predicted LR rates of 14%, 21%, and 36%, respectively (p=0.02). We found that high MTVpre and low ΔMTV were independently associated with per-lesion LR in locally advanced lung cancer, suggesting that both pre- and mid-RT PET provide complementary predictive information. If validated in larger cohorts, this may be the basis for designing adaptive dose painting strategies to maximize therapeutic index.

Metabolic tumor volume changes assessed by interval 18fluorodeoxyglucose positron emission tomography-computed tomography for the prediction of complete response and survival in patients with diffuse large B-cell lymphoma.

An early discrimination of survival probability is required for patients with diffuse large B cell lymphoma (DLBCL), which may identify patients that require other treatment options, for example clinical trials. To the best of our knowledge, the impact of interim evaluation with 18fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has not yet been determined in this type of neoplasia. The aim of the present study was to determine the role of changes in metabolic tumor volume (MTV) between baseline and interim 18F-FDG PET/CT scans, following three courses of chemotherapy in order to predict complete response (CR) and overall survival (OS) in patients with DLBCL. Patients with previously untreated DLBCL who had received the standard 6–8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were included in the present study. A predictive model was constructed using changes in MTV and other clinical factors including age, gender, East Cooperative Oncology Group (ECOG) status, clinical stage, B symptoms, the presence of bulky disease and elevated lactate dehydrogenase levels, and data were analyzed using logistic regression analysis. In total, 50 patients with DLBCL were included in the present study. The majority of patients presented with stage III/IV disease (64%), B symptoms (72%) and bulky disease (58%). According to the International Prognostic Index score, 44% of patients were in the intermediate-high or high-risk categories for risk of relapse, and therefore considered to have poor prognosis. In total, ≥94% of patients achieving a decrease in total MTV had a 2-year OS rate of 95%, compared with the 58% OS rate of those with a suboptimal response. A multivariate model, including a change in MTV (a decrease of ≥94%), the ECOG performance status ≥2, a change in leukocyte counts and age, was used to predict CR. This model was used to define two groups according to the predicted probability of recurrence (cutoff, 0.69). The 2-year survival rates of the two groups were 95 and 59%, respectively. Analysis of changes in MTV in the interim 18F-FDG PET/CT revealed significant prognostic value for the prediction of CR and OS in patients with DLBCL.

18F-FDG-PET/CT based total metabolic tumor volume change during neoadjuvant chemotherapy predicts outcome in advanced epithelial ovarian cancer.

To evaluate the predictive potential of total metabolic tumor volume (MTV) reduction during neoadjuvant chemotherapy (NACT) with 18F-FDG-PET/CT in an advanced FIGO stage III/IV epithelial ovarian cancer (EOC) patient cohort. Twenty-nine primarily inoperable EOC patients underwent 18F-FDG-PET/CT before and after NACT. The pre- and post-NACT total MTV, in addition to the percentage MTV reduction during NACT, were compared with primary therapy outcome and progression-free survival (PFS). ROC-analysis determined an optimal threshold for MTV reduction identifying patients with progressive or stable disease (PD/SD) at the end of primary therapy. A multivariate analysis with residual tumor (0/>0), FIGO stage (III/IV) and MTV reduction compared to PFS was performed. The association between MTV reduction and overall survival (OS) was evaluated. The median pre- and post-NACT total MTV were 352cm3 (range 150 to 1322cm3) and 51cm3 (range 0 to 417cm3), respectively. The median MTV reduction during NACT was 89% (range 24% to 100%). Post-NACT MTV and MTV reduction associated with primary therapy outcome (MTV post-NACT p = 0.007, MTV reduction p = 0.001) and PFS (MTV post-NACT p = 0.005, MTV reduction p = 0.005). MTV reduction <85% identified the PD/SD patients (sensitivity 70%, specificity 78%, AUC 0.79). In a multivariate analysis, MTV reduction (p = 0.002) and FIGO stage (p = 0.003) were statistically significant variables associated with PFS. MTV reduction during NACT corresponded to OS (p = 0.05). 18F-FDG-PET/CT is helpful in NACT response evaluation. Patients with total MTV reduction <85% during NACT might be candidates for second-line chemotherapy and clinical trials, instead of interval debulking surgery.

Quantitative PET-MRI for early treatment response assessment in pancreatic ductal adenocarcinoma.

520 Background: There is an unmet need for improved non-invasive markers to assess early treatment response in pancreatic ductal adenocarcinoma (PDAC). Assessing early treatment response using tumor size on anatomic imaging or serum carbohydrate antigen 19-9 (CA19-9) level is unreliable. In contrast, metabolic and functional imaging is a promising new tool that may differentiate responders from non-responders early on during therapy. Therefore, the objective of this pilot study was to explore the potential of integrated positron emission tomography-magnetic resonance imaging (PET-MRI) to provide imaging biomarkers of early (4 weeks post treatment initiation) response in patients with advanced PDAC. Methods: 13 patients with biopsy-proven locally advanced or metastatic PDAC underwent integrated 18F-fluorodeoxyglucose PET-MRI through the abdomen prior to, and again at 4 weeks post, treatment initiation. Patients also had computed tomography (CT) imaging of the chest, abdomen, and pelvis and serum CA19-9 levels measured, as per standard of care. Patients were classified as responders or non-responders according to RECIST (Response Evaluation Criteria In Solid Tumors) on delayed CT, at 8-12 weeks interval post treatment initiation. Changes in metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from PET, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI at 4 weeks were compared between responders and non-responders. Results: Of the 13 patients, there were 7 responders (partial response by RECIST) and 6 non-responders (progressive or stable disease by RECIST). After 4 weeks of therapy, responders had a significantly greater decrease in MTV (p = 0.003) and TLG (p = 0.006) compared to non-responders. Responders also had a significantly greater increase in mean and minimum ADC (p = 0.004 and p = 0.024, respectively) compared to non-responders. Change in tumor size at 4 weeks was not significantly different between responders and non-responders (p = 0.11). Conclusions: Integrated PET-MRI can provide early assessment of treatment response in patients with advanced PDAC.

18F-FDOPA PET/MRI for monitoring early response to bevacizumab in children with recurrent brain tumors

Noninvasively predicting early response to therapy in recurrent pediatric brain tumors provides a challenge. 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) PET/MRI has not been previously studied as a tool to evaluate early response to antiangiogenic therapy in children. The purpose of this study was to evaluate the safety and feasibility of using 18F-FDOPA PET/MRI to assess response to bevacizumab in children with relapsed brain tumors. Six patients with recurrent gliomas (5 low-grade, 1 high-grade) planned to undergo treatment with bevacizumab were enrolled. 18F-FDOPA PET/MRI scans were obtained prior to and 4 weeks following the start of treatment, and these were compared with the clinical response determined at the 3-month MRI. The primary PET measure was metabolic tumor volume (MTV) at 10 to 15 min after 18F-FDOPA injection. For each tumor, the MTV was determined by manually defining initial tumor volumes of interest (VOI) and then applying a 1.5-fold threshold relative to the mean standardized uptake value (SUV) of a VOI in the frontal lobe contralateral to the tumor. 18F-FDOPA PET/MRI was well tolerated by all patients. All tumors were well visualized with 18F-FDOPA on the initial study, with peak tumor uptake occurring approximately 10 min after injection. Maximum and mean SUVs as well as tumor-to-brain ratios were not predictors of response at 3 months. Changes in MTVs after therapy ranged from 23% to 98% (n = 5). There is a trend towards the percent MTV change seen on the 4-week scan correlating with progression-free survival. 18F-FDOPA PET/MRI was well tolerated in pediatric patients and merits further investigation as an early predictor of response to therapy.