Cut-off Values Of Metabolic Tumor Volume Research Articles

Merits of 18F-FDG PET/CT metabolic tumor volume for prediction of occult axillary lymph node metastasis in luminal early breast cancer patients with clinical and radiologically negative axilla

Abstract Background To see if pre-treatment 18F-FDG PET/CT metabolic tumor volume (MTV) might predict occult axillary lymph node metastases (ALNM) in luminal early breast cancer (BC) with negative axilla on clinical examination, radiological studies, and conventional 18F-FDG PET/CT interpretation. Methods Out of 330 consecutive patients with early BC who were referred for preoperative staging, only 110 female patients with luminal early BC who had biopsy-proven axillary lymph node (ALN) status and negative axilla on clinical examination, radiological studies, and conventional 18F-FDG PET/CT interpretation, were eligible for analysis. Maximum standardized uptake value (SUVmax), SUVmean, MTV, total lesion glycolysis (TLG), and clinicopathological features were determined. Via ROC analysis, we determined the optimal cutoff values for SUVmax, SUVmean, MTV, and TLG of the primary tumor to predict ALNM. Univariate and multivariate regression analyses were performed to identify the most potent PET metabolic parameters to predict ALNM. Results Pathologic ALNM was identified in 29.1% of cases; 40.6% of them had lymphovascular invasion (LVI) compared to 9% of the ALN-negative group (P < 0.0001). The median MTV of tumors with ALNM was significantly higher than that of the ALN-negative group (P = 0.049). The best cutoff value of MTV was > 4.83. In univariate analysis, MTV (P = 0.005) and LVI (P < 0.0001) were significantly associated with ALNM, and in multivariate analysis, both MTV (P = 0.002) and LVI (P < 0.0001) were confirmed to be independent predictors for ALNM. Conclusions In early luminal BC with clinically and radiologically negative axilla, including negative conventional interpretation of PET/CT, the inclusion of MTV has an added value in predicting ALNM.

Volume-based 18F-FDG PET/CT predicts prognosis and outcome of active surveillance for intra-abdominal desmoid tumor.

Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.

Metabolic Tumor Volume from Baseline PET/CT Improves Stratification in the High IPI Risk Patients with Diffuse Large B‐Cell Lymphoma

Background: In the rituximab era, the international prognostic index (IPI) risk stratification was not enough to predict outcome in patients with diffuse large B cell lymphoma (DLBCL). Previous studies showed the Metabolic tumor volume（MTV） from baseline [ 18F]FDG PET/CT could be used to predict outcome. In this study, we evaluated the prognostic value of IPI and MTV in DLBCL patients. Patients and methods: A total of 262 de novo DLBCL patients who were treated with the R-like chemotherapy were retrospectively analyzed in this study. The IPI and MTV were compared to the Overall Survival (OS) and Progression Free Survival (PFS). Results: The MTV is better than TLG and SUVmax for predicting disease progression. The cutoff value of MTV was 444 cm 3. Patients with high MTV showed inferior OS and PFS ( p &amp;lt; 0.001, respectively). Although the IPI remains predictive it distinguishes only 2 risk groups, rather than the 4 groups originally described. Further analysis showed high MTV could identify a subgroup of patients with extremely inferior OS and PFS in high IPI risk patients ( p = 0.0089 and p= 0.024, respectively). Multivariate analysis revealed that high MTV is a significant poor prognostic factor for both OS (HR 3.168[1.81-5.56], p &amp;lt;0.001) and PFS (HR 2.637 [1.51-3.71], p &amp;lt;0.001). Conclusions: Our study suggests that MTV from baseline PET/CT is an important prognostic factor in DLBCL patients, allowing the identification of an inferior outcome subgroup in high-risk patients, which may help to guide treatment in clinical trial.

Prognostic role of metabolic 18F-FDG PET/CT parameters and hematological prognostic indicators in patients with colorectal cancer.

The aim of this study is to evaluate the role of preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) parameters, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), hematologic prognostic indicators in patients with colorectal cancer (CRC) in terms of predicting prognosis. One hundred and one patients who had undergone 18F-FDG PET/CT for initial staging were evaluated retrospectively. Patient data including pathologic stage at presentation, histology, tumor location, and overall survival (OS) were analyzed. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), serum carcinoembryonic antigen (CEA) (ng/mL), CA-125 (cancer antigen 125) (U/mL), and CA19-9 (U/mL) levels, which were obtained within 2 weeks of the PET/CT examination, were used for hematological data. The TNM Classification of Malignant Tumors stage and PET/CT parameters, including SUVmax, MTV, and TLG, were found to be correlated with survival rate in univariate analysis (P < 0.05). All hematological markers excluding PLR were also significantly associated with survival time. Receiver operating characteristics (ROC) analysis revealed that the optimal SUVmax cutoff value for predicting survival time in patients with CRC was >17.9 (Area under curve (AUC) = 0.625; P < 0.05). The calculated sensitivity and specificity values for this cutoff were 60% and 65.7%, respectively. To predict the survival time in these patients, the optimal MTV cutoff value was >34.29 (AUC = 0.775; P < 0.001; sensitivity = 85%; specificity = 62.3%). The optimal TLG cutoff value for predicting survival time was >270.4 (AUC = 0.790; P < 0.001; sensitivity = 77.5%; specificity = 68.9%). FDG PET/CT metabolical parameters are useful for predicting the prognosis in patients with CRC. High preoperative NLR and high tumor markers were also shown to be negative independent prognostic factors in these patients.

P017: The role of baseline bulk and dissemination measures as predictors of progression in advanced Hodgkin lymphoma

Figure 1: Probability of progression-free survival by baseline MTV (A) and Dmax (B) Introduction: Numerous clinical and FDG-PET/CT-associated models were proposed to predict treatment failure in Hodgkin’s lymphoma (HL). Baseline quantitative FDG-PET metrics are emerging biomarkers showing promising prognostic value. We retrospectively analysed the impact of tumour bulk and dissemination as measured by assessing Metabolic Tumor Volume (MTV) and D max - the distance between the furthest lesions identified by FDG-PET/CT - on the probability of progression in HL patients in clinical stages II to IV. Methods: Baseline FDG-PET/CT data of 117 patients with newly diagnosed HL from the PLRG-11 study was analysed and MTV was assessed by manual segmentation with the volume of interest (VOI) threshold of 41%SUVmax and Dmax was calculated by measuring the diameter between centroids of VOIs with SUVmax above SUVmax of the liver located furthest apart. The Median follow-up was months. The distance was measured in 3-dimensional space using Euclidean geometry. The cut-off values of MTV and Dmax were calculated with the maximally selected rank statistic method. Results: MTV cut-off value for progression-free survival (PFS) prediction was 214 ml with PPV 0,516 and NPV of 0.848 and for Dmax was 10 cm with PPV 0.291 and NPV of 1.0. In the cohort of 69 patients with negative interim PET/CT performed post-second cycle of ABVD PFS event was reported in 0% and 17% patients with Dmax below and above 10 cm, respectively and in 6% and 36% of patients with MTV below and above threshold value of 214 ml, respectively. Conclusion: Bulk and dissemination assessments in baseline PET/CT in Hodgkin lymphoma stage II-IV patients may help identify a population of patients with an especially good prognosis.

The Role of Metabolic Volumetric Parameters in Predicting Malignancy in Incidental Thyroid Nodules Detected in 18F-FDG PET/CT Scans

Objectives:The metabolic activities of tumors can be calculated volumetrically during positron emission tomography/computed tomography (PET/CT) imaging using metabolic tumor volume (MTV) and total lesion glycolysis (TLG). This study aimed to evaluate the roles of MTV and TLG in predicting the malignancy risk of incidental thyroid nodules detected by PET/CT imaging.Methods:Active metabolic areas of each section were manually drawn by region of interest to calculate the MTV of nodules, and all obtained values were then summed. TLG, the product of mean standardized uptake value and MTV, was calculated by multiplying two values. All participants underwent thyroid ultrasonography imaging. All nodules were divided into risk classes according to the European Thyroid Image Reporting and Data System (EU-TIRADS) that was developed by the European Thyroid Association. The American Thyroid Association Guidelines were used to determine which thyroid nodules would undergo thyroid fine-needle biopsy (FNAB). Results were classified according to the Bethesda scoring system.Results:TLG levels were significantly higher in malignant or malignant-suspicious nodules than in benign nodules (p=0.013). Although MTV levels were high in malignant or malignant-suspicious nodules than in benign and non-diagnostic nodules, it was statistically insignificant at limit values (p=0.079). Areas under curve (AUC) were 0.726 (p=0.005) and AUC: 0.668 (p=0.039) for TLG and MTV, respectively. The 2.3 g cut-off value of TLG has a sensitivity of 85.7% and specificity of 59.0%. The 1.7 mL cut-off value of MTV has a sensitivity of 78.6% and specificity of 60.4%.Conclusion:We believe that TLG evaluation will be useful in predicting high-risk malignancy or malignancy suspicion based on EU-TIRADS risk classification of incidental thyroid nodules detected in PET/CT images. We believe that unnecessary thyroid FNABs can be avoided for thyroid incidental nodules if such relation and cut-off values are determined and that it will be useful in hastening the operation of the necessary patients.

Predictive Value of Occult Metastasis and Survival Significance of Metabolic Tumor Volume Determined by PET-CT in cT1-2N0 Squamous Cell Carcinoma of the Tongue.

ObjectivesOur goal was to analyze the possibility of using metabolic tumor volume (MTV) to predict occult cervical metastasis and survival in cT1-2N0 squamous cell carcinoma (SCC) of the tongue.MethodsData on the primary tumor MTV and cervical node status as determined by the maximum standardized uptake value were retrieved. The sensitivity and specificity in predicting occult metastasis were calculated with a fourfold table. Associations between occult metastasis and clinicopathological variables were evaluated by univariate and multivariate analyses. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS).ResultsA total of 24 (20.3%) of 118 patients had occult metastasis. An MTV cutoff value of 4.3 cm3 showed a sensitivity of 50.0% and a specificity of 76.6% in predicting occult metastasis. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT1 tumors were 66.6 and 89.8%, respectively, with values of 83.3 and 67.3%, respectively, when combined with the MTV. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT2 tumors were 72.2 and 82.2%, respectively, with values of 88.9 and 57.8%, respectively, when combined with the MTV. Patients with MTV ≥4.3 cm3 had a higher occult metastasis rate than patients with MTV <4.3 cm3. The 5-year LRC and DSS rates were 86 and 94%, respectively, in patients with MTV <4.3 cm3 and 54 and 72%, respectively, in patients with MTV ≥4.3 cm3. Both differences were found to be significant in univariate and multivariate analyses.ConclusionsMTV ≥4.3 cm3 was associated with an increased probability of occult metastasis and lower LRC and DSS rates in early-stage SCC of the tongue.

High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma

AbstractHigh metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.

Abstract P3-08-30: Low levels of metabolic tumor volume at baseline significantly associated with longer progression-free survival in patients with locally advanced or metastatic breast cancer treated with endocrine therapies

Abstract Background Endocrine therapy is an essential treatment choice for patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative locally advanced and metastatic breast cancers. Although patients with non-visceral metastasis or with favorable efficacy induced by prior endocrine therapy, are reported to be associated with a longer duration of endocrine therapy, predictive markers have yet to be established. In general, breast cancers with low proliferative activity and small tumor burden seem to obtain favorable efficacy induced by endocrine therapy. Metabolic tumor volume (MTV) on fluorodeoxyglucose-positron emission tomography (FDG-PET) examination measures uptake activity of glucose in tumor cells, which represents tumor aggressiveness, and tumor volume. Thus, using MTV as a metabolic parameter for both proliferative activity and tumor burden, we evaluated the predictive usefulness of MTV for treatment efficacy of endocrine therapy.MethodA total of 83 patients treated with endocrine therapy for locally advanced and metastatic breast cancers, treated with an aromatase inhibitor (AI; n=39) or fulvestrant (Ful; n=44), examined by FDG-PET before start of treatment, were constitutively recruited in this retrospective study. The treatment lines were as follows; 1st, n=46; 2nd, n=22; 3rdor more, n=15. The maximum value of the standard uptake value (SUV, regional radioactivity concentration (Bq/mL)/injected dose (Bq)/patient weight (g)) in the volume of interest (VOI) was defined as the SUVmax. Total volume of voxels of ≥40% of the SUVmax in the VOI was defined as the MTV. The cut-off value of MTV was defined at 45 and the relationships between MTV and progression-free survival (PFS) was calculated.ResultsPFS of patients treated with Ful (median, 19.0 months) was marginally favorable than those with AI (median, 9.8 months; p=0.084). In all participants, PFS of patients with low levels of MTV (n=29; median, 23.6 months) was significantly longer than those with high levels (n=54; median, 10.0 months; p=0.0124). The association between low levels of MTV and longer PFS was significantly (p=0.0369) and marginally (p=0.0715) recognized in Ful and AI, respectively. Similarly, association between MTV and PFS seems to be consistent in subgroups in visceral or non-visceral metastasis, de novo or recurrence, and treatment lines.Discussion and conclusionIn the present study, we demonstrated that low levels of MTV at baseline are significantly associated with longer PFS for patients treated with AI or Ful. MTV seems to be a predictor for the efficacy of endocrine therapy by evaluating both tumor aggressiveness and tumor volume. This data may be useful in selecting patients who could benefit from endocrine therapy with non-invasive method. Citation Format: Reiko Fukui, Tomoko Higuchi, Yukie Fujimoto, Atsushi Sata, Ayako Bun, Hiromi Ozawa, Hiromi Ozawa, Yoshimasa Miyagawa, Michiko Imamura, Kazuhiro Kitajima, Yasuo Miyoshi. Low levels of metabolic tumor volume at baseline significantly associated with longer progression-free survival in patients with locally advanced or metastatic breast cancer treated with endocrine therapies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-30.

Prognostic value of pretreatment (18)F-FDG PET-CT metabolic parameters in patients with advanced extranodal NK/T cell lymphoma

Objective: To investigate the prognostic values of the maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated from pretreatment (18)F-fluorodeoxy glucose ((18)F-FDG) PET-CT results of patients with advanced extranodal NK/T cell lymphoma (ENKTL). Methods: The clinic data, follow-up data and pretreatment (18)F-FDG PET-CT data of 45 patients with ENKTL of stage Ⅳ were collected. The optimal cutoff value of progression-free survival (PFS) of SUV(max), MTV and TLG were analyzed by using receiver-operating characteristic (ROC) curve. The Kaplan-Meier method, Log-rank test and COX proportional hazards model were used for survival analysis, univariate analysis and multivariate analysis, respectively. Results: The median SUV(max), MTV and TLG of 45 ENKTL patients were 17.98, 70.18 and 755.42, respectively. ROC curve showed that the area under the curve (AUC) of SUV(max), MTV and TLG were 0.504 (P=0.970), 0.868 (P<0.001) and 0.848 (P=0.001), respectively. The value of SUV(max) was too small to fit for calculating the cutoff value of AUC. The cutoff value of MTV was 42.54 (sensitivity =78.1% and specificity =84.6%), and the cutoff value of TLG was 435.15 (sensitivity=75.0% and specificity =76.9%). Univariate analysis showed that lactate dehydrogenase (LDH) level, epstein-barr virus (EBV)-DNA, Eastern Cooperative Oncology Group (ECOG) score, bone marrow, Korean prognostic index (KPI), MTV, TLG were significantly related with PFS (all P<0.05), and lactate dehydrogenase (LDH) level, EBV-DNA, ECOG score, primary tumor location, KPI, MTV, TLG were significantly related with overall survival (OS) (all P<0.05). Multivariate analysis showed that KPI, MTV and TLG were independent prognostic predictors of PFS and OS (all P<0.05). Conclusions: MTV and TLG of pretreatment (18)F-FDG PET-CT are independent prognostic factors for PFS and OS of patients with advanced ENKTL. MTV and TLG may be more fit for evaluating the prognosis of ENKTL patients than SUV(max).

Validation of metabolic tumor volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery

Despite the promise of metabolic tumor volume (MTV) as a risk-stratifying marker, the retrospective design of the initial study limits its generalizability. Therefore, this study sought to validate MTV as a prognostic factor for oral cavity squamous cell carcinoma (OCSCC) treated with primary surgery within an independent data set. The validation data set consisted of 42 patients diagnosed with OCSCC between 2008 and 2012. The original cohort consisted of 80 patients. MTV and SUVmax were calculated for the primary tumor and nodal metastasis separately, as well as combined. Before statistical analysis, MTV and SUVmax values were divided into intertertile thirds to allow for intergroup survival analysis. Validation analysis was conducted on the validation data set alone. Data from both cohorts were then combined (n=122) to increase statistical power. An increase in combined MTV of 17.5cm(3) was associated with statistically significant increase in risk of disease recurrence (HR=19.2, p<0.001) and death (HR=9.2, p<0.05). Combined SUVmax failed to predict overall (HR=1.0, p>0.05) and disease-free survival (HR=1.0, p>0.05). Increase in the MTV of the primary tumor was associated with an increase in the risk of disease recurrence (HR=21.7, p=0.0001) and risk of death (HR=7.0, p=0.0001), while increase in the MTV of the locoregional neck metastasis was not (p>0.05). An MTV cutoff value of greater than 10.2cm(3) was found to significantly affect survival. Due to the reproducibility of MTV findings, this study validates MTV as an independent prognostic factor for OCSCC treated with primary surgery.

Metabolic tumor volume by positron emission tomography/computed tomography as a clinical parameter to determine therapeutic modality for early stage Hodgkin's lymphoma

Recent studies have shown that metabolic tumor volume (MTV) by positron emission tomography/computed tomography (PET/CT) is an important prognostic parameter in patients with non-Hodgkin's lymphoma. However, it is unknown whether doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone in early stage Hodgkin's lymphoma would lead to similar disease control as combined modality therapy (CMT) using MTV by PET/CT. One hundred and twenty-seven patients with early stage Hodgkin's lymphoma who underwent PET/CT at diagnosis were enrolled. The MTV was delineated on PET/CT by the area ≥SUV(max), 2.5 (standardized uptake value [SUV]). Sixty-six patients received six cycles of ABVD only. The other 61 patients received CMT (involved-field radiotherapy after 4-6 cycles of ABVD). The calculated MTV cut-off value was 198 cm(3) . Clinical outcomes were compared according to several prognostic factors (i.e. age ≥50 years, male, performance status ≥2, stage II, B symptoms, ≥4 involved sites, extranodal site, large mediastinal mass, CMT, elevated erythrocyte sedimentation rate and high MTV). Older age (progression-free survival [PFS], P = 0.003; overall survival [OS], P = 0.007), B symptoms (PFS, P = 0.006; OS, P = 0.036) and high MTV (PFS, P = 0.008; OS, P = 0.007) were significant independent prognostic factors. Survival of two high MTV groups treated with ABVD only and CMT were lower than the low MTV groups (PFS, P < 0.012; OS, P < 0.045). ABVD alone was sufficient to control disease in those with low MTV status. However, survival was poor, even if the CMT was assigned a high MTV status. The MTV would be helpful for deciding the therapeutic modality in patients with early stage Hodgkin's lymphoma.