Baseline Total Lesion Glycolysis Research Articles

A preliminary investigation of the relationship between 18F-FDG PET/CT metabolic parameters and prognosis in angioimmunoblastic T-cell lymphoma.

The goal of the study was to determine the prognostic significance of metabolic parameters in baseline 18F-FDG PET/CT images obtained from patients with angioimmunoblastic T-cell lymphoma (AITL). Forty patients with pathologically diagnosed AITL who had baseline 18F-FDG PET/CT between May 2014 and May 2021 were assessed as part of this study. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and total metabolic tumor volume (TMTV) were obtained and analyzed. In addition, many relevant features were evaluated, including sex, age, staging, International Prognostic Index (IPI), prediction index for T-cell lymphoma (PIT), Ki-67, and so on. Estimates of progression-free survival (PFS) and overall survival (OS) were determined using the log-rank test and Kaplan-Meier. The median follow-up was 30.2 months (interquartile range 9.82-43.03). Throughout the follow-up period, 29 (72.5%) deaths occurred and 22 (55.0%) patients made progress. The rates for 2- and 3-year PFS were 43.6% and 26.4%, respectively. The 3- and 5-year OS were 42.6% and 21.5%. For TMTV, TLG, and SUVmax, the cut-off values were 87.0 cm3, 711.1, and 15.8, respectively. Poorer PFS and OS were substantially correlated with high SUVmax and TLG. An increased TMTV suggested a shorter OS. TLG performed independently as OS predictors in multivariate analysis. The risk score for predicting the prognosis of AITL includes the TMTV, TLG, SUVmax, and IPI scores, with 4.5 for TMTV, 2 for TLG, 1.5 for IPI scores, and 1 for SUVmax. Three risk categories of patients with AITL had 3-year OS rates of 100.0%, 43.3%, and 25.0%, respectively. Baseline TLG was a strong predictor of OS. Here a new prognostic scoring system for AITL based on the clinical indicators and PET/CT metabolic parameters was constructed, which might make stratification of prognosis easy and also help to individualize treatment.

Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy is potentially associated with treatment-related toxicities mainly consisting of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B-cell lymphoma patients treated with CAR-T. Twenty-one refractory DLCBLs underwent whole-body and brain [18 F]-fluorodeoxyglucose (FDG) PET before and 30days after treatment with CAR-T. Five patients did not develop inflammatory-related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post-CAR-T brain FDG-PET were compared with a local controls dataset to identify hypometabolic patterns both at single-patient and group levels (p<.05 after correction for family-wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG-PET and compared between patients' subgroups (t-test). ICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (p<.003 FWE-corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (p<.002 FWE-corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (p<.002 FWE-corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (p<.02). Patients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine-induced inflammation.

Abstract P6-01-42: BASELINE 18FDG-PET METABOLIC TUMOUR VOLUME (MTV) AS A POTENTIAL PREDICTIVE FACTOR OF RESPONSE TO METRONOMIC CHEMOTHERAPY (mCHT) IN HR+/HER2- METASTATIC BREAST CANCER (MBC) PATIENTS (pts). PRELIMINARY RESULTS OF THE METRO-PET STUDY

Abstract Background: MBC is an incurable disease and chemotherapy (CHT) represents one option of treatment upfront, in TNBC pts, or at failure of an endocrine therapy + targeted agents in HR+ ones. mCHT was extensively studied in different types of ABC pts and is largely used in clinical practice. 18FDG-PET is often used as a tool for disease staging at baseline and for disease restaging during treatment. Different quantitative and semi-quantitative 18FDG-PET parameters have been investigated as predictive and prognostic biomarkers in NSCLC and other tumours. Aim of the present study is to evaluate the role of baseline SUVmax , global SUVmean, SUVpeak, Metabolic Tumour Volume (MTV) and Total Lesion Glycolysis (TLG) as predictive factors of response to mCHT. Patients and Methods: We identified 36 MBC pts treated with mCHT between 2014 and 2021, with at least two separate 18FDG-PET evaluations. Patients and biological tumour characteristics, previous treatments, site of relapse as well as quantitative pre-treatment 18FDG-PET parameters have been collected. Tumour response was assessed using PERCIST Criteria. Median and mean ± SD 18FDG-PET parameters have been reported according to the type of response. Complete and Partial responses have been grouped together with Stable Disease. Results: Median age was 69 (33-82). Luminal pts were 25 (67.6%), TNBC pts were 16.2%); most were heavily pre-treated for their metastatic disease (≥ 3 lines: 14, 37.8%) and presented ≥ 3 metastatic sites (14, 37.8%). All pts received mCHT, 26 (70.3%) as combination therapy (VRL+CAPE or VRL+CAPE+CTX), or single agent (VRL, 11). Bone was the commonest metastatic site (62.2%). ORR was 43.2%; 7 pts had SD (18.9%), the remaining developed PD (37.8%). Similar values have been observed between the 2 groups in terms of SUVmax , global SUVmean and SUVpeak,. Mean MTV was higher in responder (n=22) vs non responder (n=14) pts, as TLG. Details are reported in Table 1. Conclusions: High mean baseline MTV and TLG seem to be related to response to mCHT in MBC pts. Our observation is in contrast to what is described for other cancer types, especially NSCLC, and for standard neoadjuvant treatment of BC. Considering the peculiar mechanisms of action of mCHT, our preliminary findings warrant further exploration in a larger series of BC pts. Table 1 Baseline 18FDG-PET uptake values in responder and non responder patients Citation Format: Marco Meazza Prina, Irene Gotuzzo, Marina Elena Cazzaniga, Elisabetta De Bernardi, Pietro Cafaro, Serena Capici, Viola Cogliati, Francesca Fulvia Pepe, Federica Cicchiello, Francesca Riva, Nicoletta Cordani, Maria Grazia Cerrito, Elia Anna Turolla, Claudio Landoni, Federica Elisei, Cinzia Crivellaro, Leonardo Virdone, Lavinia Monaco, Alessandro Guidi, Luca Guerra. BASELINE 18FDG-PET METABOLIC TUMOUR VOLUME (MTV) AS A POTENTIAL PREDICTIVE FACTOR OF RESPONSE TO METRONOMIC CHEMOTHERAPY (mCHT) IN HR+/HER2- METASTATIC BREAST CANCER (MBC) PATIENTS (pts). PRELIMINARY RESULTS OF THE METRO-PET STUDY [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-42.

Automated analysis of FDG-PET/CT imaging to monitor heterogeneous disease response in metastatic castration-resistant prostate cancer.

251 Background: The heterogeneity of individual sites of disease in prostate cancer is well recognized and increases over time as the therapies administered promote divergent evolution. In clinical practice, this is often depicted in radiology reports as a mixed response, wherein some lesions improve and others progress or emerge, for which individualizing management is challenging. The problem is exacerbated in patients with high volume disease by the inability to concisely and effectively assess overall disease status which may mask the presence of emerging resistance that could benefit from early intervention and/or a change in therapy. Methods: Thirty-one sets of serial baseline and on-treatment FDG-PET/CT images done for the clinical management of patients with progressing mCRPC were analyzed using TRAQinform IQ software (AIQ Solutions). Individual regions of interest (ROI) identified and tracked across imaging time-points were analyzed for a range of features. The univariate prognostic weight of each feature was assessed with Cox regression models. Imaging features from single timepoints, heterogeneity of response features, and PSA values/dynamics were input into the separate TRAQinform Profile software, which was calculated to predict either time on treatment or overall survival using 3-fold cross-validation of a random survival forest. Individual case reviews were performed on select patients including TRAQinform IQ analytics, PSA trends, radiology reports, and physician notes to evaluate the potential additive benefit of the TRAQinform IQ output. Results: In general, imaging features were more strongly correlated with overall survival than PSA dynamics. After iterative feature selection, only imaging features were selected for TRAQinform Profile scores. In the case of predicting OS, the most important features were baseline total lesion glycolysis (TLG), and the number of new/progressing lesions. Patients with high TRAQinform Profile scores had shorter median survival times than those with low scores (630 vs 1326 days, p&lt;0.01, c-index = 0.744). Of particular value was the finding that the software could identify indicators of oligo-progression for which directed radiotherapy could be considered. Also detected were early indications of widespread disease progression represented as changes in total SUV uptake and TRAQinform Profile scores, which could indicate that the patient was no longer benefitting from treatment and a change in therapy was needed. Conclusions: In pilot analysis, the TRAQinform Profile scores generated from baseline and early on-treatment FDG-PET images had treatment-agnostic prognostic value in mCRPC. Further validation is on-going. The TRAQinform IQ software can aid in identifying the presence of resistant lesions in the setting of otherwise grossly stable disease as determined by the treating physician.

P004: Advanced stage classical Hodgkin lymphoma (cHL) patients with a positive interim-PET (PET-2) Deauville score (DS) 5 after 2 ABVD cycles: A pooled analysis of individual patient data of three multicenter trials

Background: PET-2 is widely adopted to select patients (pt) with advanced-stage cHL, who might benefit from intensifying or de-escalating therapy. Improved PFS has been reported in PET-2 positive pt switched from ABVD to escalated BEACOPP (eBEACOPP) compared to historical controls continuing ABVD. Nevertheless, pt with a PET-2 Deauville score (DS) 5 have a dismal prognosis, with PFS from 35% to 50% at 3 years despite treatment intensification. Aim of Study: To refine outcome prediction, we conducted a pooled analysis of individual pt data from 3 multicenter trials: HD0607 GITIL/FIL, RATHL and SWOG S0816 focusing on pt with PET-2 DS 5 after ABVD who had intensified treatment with eBEACOPP or BEACOPP-14. Methods: The prognostic value of clinical characteristics, laboratory parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) at diagnosis was evaluated. MTV was calculated with an automatic software segmentation using SUV 4.0 threshold in each pt. Predictive factors of PFS measured from the date of PET-2 until progression, relapse, death from any cause or last follow-up, and overall survival (OS) were analyzed using Cox regression. Baseline characteristics and PET MTV/TLG of pt who failed vs those who achieved CR with intensified treatment were compared. Results: Among 2231 pt with available PET scans for review, 136 (6%) PET-2 DS 5 pt were included in the study: M 72, F 64, median age 34 yrs, Nodular Sclerosis 71%, stage IIB/III/IV 29%/ 22% /49%, B symptoms 72%, IPS >3: 31%; bulky 22%; neutrophil/lymphocyte ratio > 6: 61%. At baseline median MTV and TLG were 243 cm3 (range, 1.6–4266) and 1476cm3 (range, 7.3–29386). After a median follow-up of 41 months, 3-yr PFS and OS were 32% (95% CI, 25–42) and 82% (95% CI, 75–89), respectively. In univariate analysis no clinical or laboratory parameter nor MTV was significantly associated with PFS, whereas age ≥ 45 years, median numbers of leukocytes, lymphocytes and monocytes were significantly associated with OS. Using a threshold of 192 cm3 for MTV calculated by Youden index, 3-year PFS and OS were 35% and 87% vs 34% and 79% for pt with low vs high MTV (p=ns). Conclusions: Pt with PET-2 DS 5 after ABVD receiving intensified treatment have similar outcomes to refractory disease with only 32% 3-yr PFS. No factors measured at diagnosis were able to detect the later failures within the DS 5 cohort. Nevertheless, pt receiving PET-guided treatment intensification can benefit from a prolonged OS.

High baseline total lesion glycolysis predicts early progression of disease within 24months in patients with high-tumor-burden follicular lymphoma.

Despite the introduction of rituximab-containing regimens, approximately 20% of patients with follicular lymphoma (FL) still experience progression of disease within 24months (POD24) and have poor overall survival. Therefore, a more accurate risk assessment tool is required. We investigated the predictive value of two new volume-based parameters determined from baseline 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), baseline total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), in 45 patients with high-tumor-burden FL who underwent baseline PET/CT. We observed that high TMTV, high TLG, and poor initial treatment response (less than complete [metabolic] response [non-CR/CMR] at the end of induction therapy) independently predicted poor PFS. Notably, POD24-positive patients were more common in the high-TLG group than in the high-TMTV group, which suggests that TLG is a stronger predictor of outcomes than TMTV. Combining baseline TLG and initial treatment response showed that patients with both high TLG and non-CR/CMR experienced significantly poorer outcomes, with a 2year PFS of 0% (hazard ratio 60.39, P = 0.000002). This combination had 56% sensitivity and 100% specificity for detecting patients who would experience POD24. Baseline TLG and initial treatment response can precisely identify patients at high risk of POD24.

The association of FDG PET/CT and NaF PET/CT with survival outcomes in patients (pts) with metastatic genitourinary malignancies (mGU) treated with cabozantinib + nivolumab +/- ipilimumab (CaboNivo +/- Ipi).

452 Background: This study determined the association of functional imaging parameters obtained on FDG PET/CT and NaF PET/CT with OS for pts with mGU malignancies treated on a phase I study with CaboNivo +/- Ipi. Methods: Pts on this phase I study underwent sequential (1-hour apart) FDG PET/CT and NaF PET/CT imaging at baseline and at first-restaging (8 weeks follow up). Scan semi-quantitative parameters measures included: maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for FDG and MTV for NaF. Total lesion number was captured for all scans. The association of imaging parameters and survival was determined with Kaplan-Meier curves. Baseline values and percent change values were calculated. Results: 81 pts were included in the analysis. 67 (83%) were males; Median age was 63 (range 25-86); Histologically, 30 pts had urothelial carcinoma, 15 clear cell renal cell carcinoma, 9 germ cell tumors, 8 urachal/adenocarcinoma, 8 prostate cancer, 3 penile cancer, 3 squamous cell carcinoma, 3 renal medullary carcinoma, and 2 small cell (1 bladder, 1 prostate). All 81 had a baseline FDG PET scan, 78 pts received baseline NaF PET scans; 66 received both FDG PET and NaF PET baseline and follow up scans. 957 total lesions were detected on FDG PET across all histologies, 87 liver (9%), 252 lung (26%), 152 bone (16%), 411 lymph node (43%), and 55 other visceral metastases (6%). 414 total lesions were detected on NaF imaging. Low vs high baseline FDG MTV (31 vs 11 months, p = 0.0002), TLG (30 vs 11 months, p = 0.0004), Lesion number (49 vs 15 months, p = 0.0005), and SUVmax (25 vs 12 months, p = 0.025), FDG lesion number decrease or no change vs increase (24 vs 12 months, p = 0.0068), and low vs high baseline NaF MTV (26 vs 16 months, p = 0.007), and lesion number (26 vs 16 months, p = 0.007) showed the strongest associations with OS. A multivariable Cox analysis demonstrated that baseline FDG MTV (HR = 2.87, 95% CI 1.62-5.08, p = 0.0003) and FDG lesion number percent change (HR = 2.71, 95% CI 1.40-5.24, p = 0.0031) were jointly associated with OS. Conclusions: Baseline functional imaging parameters and percent change seen on follow imaging with FDG PET and NaF PET are prognostic in mGU pts treated with CaboNivo +/- ipi. Additional parameters and histologic subsets will be presented.

2-[18F]FDG PET in the Management of Radioiodine Refractory Differentiated Thyroid Cancer in the Era of Thyrosin-Kinases Inhibitors: A Real-Life Retrospective Study.

Purpose To evaluate the role of 2-[18F]FDGPET/CT in the follow-up of radioiodine refractory thyroid cancer (RR-TC). Methods Forty-six 2-[18F]FDGPET/CT scans from 14 RR-TC patients were considered. Thyroid function tests: thyroglobulin (Tg), levothyroxine (LT4), and tyrosine-kinases inhibitors (TKIs) assumptions were recorded. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from each scan and correlated with clinical parameters and the overall survival (OS). Results Baseline TLG and MTV predicted OS (p = 0.027 and p = 0.035), and negative correlation with OS was also confirmed when the same parameters were measured in follow-up scans (p = 0.015 and p = 0.021). Tg also correlated with the OS; (p = 0.014; p = 0.019 and p = 0.009). However, TLG and MTV were not significantly correlated with Tg levels. MTV and TLG variation in time were reduced during TKI therapy (p = 0.045 and p = 0.013). Conclusions 2-[18F]FDGPET/CT confirmed its prognostic role at the first assessment and during the follow-up of RR-TC patients. 2-[18F]FDGPET/CT parameters seem at least partially independent from Tg. TKI therapy resulted in a measurable effect on the variation of 2-[18F]FDGPET/CT parameters over time.

The role of pre-treatment and mid-treatment 18F-FDG PET/CT imaging in evaluating prognosis of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)

BackgroundIt has been reported the prognostic value of MTV in predicting the disease prognosis of peripheral T-cell lymphoma (PTCL) through pre-treatment PET/CT imaging. However, these are limited data on pretreatment evaluation and prognosis assessments of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). This study aimed to determine the prognostic values of pre-treatment and mid-treatment total metabolic tumor volume (MTV), total lesion glycolysis (TLG), and Deauville 5-Point Scale (D-5PS) in accessing the prognosis of PTCL-NOS.MethodsA retrospective analysis was conducted in 31 patients with pathologically diagnosed PTCL-NOS. These patients have undergone positron emission PET/CT scanning before and during chemotherapy. Follow-ups were also done to investigate the 2-year progression-free survival (PFS) and Overall Survival (OS) of these patients. During {}^{18}F-fluorodeoxyglucose ({}^{18}F-FDG) PET/CT scans, the MTV and TLG were recorded. Meanwhile, bigtriangleupMTV and bigtriangleupTLG were calculated. Furthermore, the receiver operating characteristic (ROC) curve was employed to classify and to define the threshold values. On the other hand, the mid-chemotherapy assessment and staging of these 31 patients were done by utilizing D-5PS. Subsequently, based on the D-5PS scores obtained, these patients were grouped into two categories: a group of patients with a score of <4 and another group with ge4 points. For these two groups of patients, the survival analysis was done by Kaplan–Meier analysis and a multivariate COX regression model. Moreover, Pearson’s chi-square test (chi ^{2} test) and Spearman rank correlation coefficient were used to comparing the collected data, respectively.ResultsDuring the 2-year follow-up period, 15 out of the 31 patients experienced disease progression. The optimal threshold values for both baseline MTV and TLG were 158.16 cm^{3} and 677.40.Additionally, the difference in 2-year PFS between the progressive and non-progressive groups was statistically significant (chi ^{2}=8.193, P=0.004<0.05; chi ^{2}=8.872, P=0.003<0.05), significant between-group difference was detected for MTV and for TLG (chi ^{2}=6.494, P=0.011<0.05; chi ^{2}=4.687, P=0.03<0.05). On the other hand, when these patients were classified into two groups according to the mid-chemotherapy Deauville score of <4 and ge4, the statistical difference of 2-year PFS between these two groups was significant, too (chi ^{2}=14.966, P=0.001<0.05),but there is no significant between-group difference in OS (chi ^{2}=3.337, P=0.068<0.05). COX analysis revealed that D-5PS are the independent factors influencing PFS, while MTV is the independent influencing factor of OS.ConclusionThe baseline total MTV obtained by PET/CT scanning, and D-5PS are crucial prognostic factors in evaluating the prognosis of PTCL-NOS.

Individualised dosimetry and safety of SIRT for intrahepatic cholangiocarcinoma

BackgroundThe aim of this study was to investigate the safety and efficacy of selective internal radiation therapy (SIRT) with 90Y resin microspheres for the treatment of Intrahepatic Cholangiocarcinoma (ICC). A total of 23 SIRT procedures from 18 ICC subjects were analysed to determine a lesion-based dose/response relationship with absorbed dose measures from 90Y PET and metabolic response as measured on [18F]FDG PET. Average absorbed dose (Davg), minimum dose to 70% of the volume (D70), volume receiving at least 50 Gy (V50), biological effective dose (BED) and equivalent uniform dose (EUD), were compared to changes in metabolic volume, maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Dose to normal liver was assessed with changes in liver uptake rate as measured with [99mTc]mebrofenin scintigraphy for a cohort of 20 subjects with primary liver malignancy (12 ICC, 8 hepatocellular carcinoma (HCC)).ResultsThirty-four lesions were included in the analysis. A relationship was found between metabolic response and both Davg and EUD similar to that seen previously in metastatic colorectal cancer (mCRC), albeit trending towards a lower response plateau. Both dose and SUV coefficient of variation within the lesion (CoVdose and CoVSUV), baseline TLG and EUD were found to be mildly significant predictors of response. No strong correlation was seen between normal liver dose and change in [99mTc]mebrofenin liver uptake rate; low baseline uptake rate was not indicative of declining function following SIRT, and no subjects dropped into the ‘poor liver function’ category.ConclusionsICC lesions follow a similar dose–response trend as mCRC, however, despite high lesion doses a full metabolic response was rarely seen. The CoV of lesion dose may have a significant bearing on response, and EUD correlated more tightly with metabolic response compared to Davg. SIRT in primary liver malignancy appears safe in terms of not inducing a clinically significant decline in liver function, and poor baseline uptake rate is not predictive of a reduction in function post SIRT.

Prognostic Value of Baseline and Interim Total Metabolic Tumour Volume and Total Lesion Glycolysis Measured on 18f-FDG PET/CT in Patients with Follicular Lymphoma

Objective: To investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) scans.Subjects and methods: The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET/CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5 and 3.0 thresholding method respectively. Furthermore, 24 interim PET/CT scans of the patients were researched. For interim scans, we recorded the changes in TMTV and TLG, which were defined as ΔTMTV3.0 and ΔTLG3.0.Results: Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Most patients (40/48, 83.3%) received immunochemotherapy with rituximab, cyclophosphamide, epirubicin, vindesine and prednisone (R-CHOP) and 3 patients received radiotherapy while the other 5 patients didn't receive treatment due to no indications. Median follow-up is 35 months (range, 16-98 months). ROC curve analysis showed that the optimal cut-off values for SUVmax, TMTV2.0, TMTV2.5, TMTV3.0, TLG2.0, TLG2.5 and TLG3.0 of 7.0 (sensitivity 85.7%; specificity 46.3%; AUC (areas under the curve) 0.650; P=0.141), 505.5 (sensitivity 85.7%; specificity 63.4%; AUC 0.774; P <0.001), 391.2 (sensitivity 85.7%; specificity 65.9%; AUC 0.777; P <0.001), 476.4 (sensitivity 85.7%; specificity 78.0%; AUC 0.760; P=0.003), 3259.7 (sensitivity 71.4%; specificity 75.6%; AUC 0.763; P=0.002), 3080.0 (sensitivity 71.4%; specificity 78.0%; AUC 0.770; P=0.001) and 2676.9 (sensitivity 71.4%; specificity 78.0%; AUC 0.760; P=0.003) (Table 1). Taking sensitivity, specificity and AUC into consideration, we selected TMTV3.0 and TLG3.0 for further analyses. By univariate analysis, we found that BM involvement, FLIPI2 score of 3-5, TLG3.0>2676.9 and TMTV3.0>476.4 were both significantly associated with inferior PFS and OS in our cohort. On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (HR=5.406, 95%CI: 1.326-22.040; P=0.019 and HR=6.502, 95%CI: 1.079-39.182; P=0.042) and overall survival (OS) (HR=4.111, 95%CI: 1.125-15.027; P=0.033 and HR=5. 885, 95%CI: 1.014-34.148; P=0.049) (Table 2). ROC curve analysis showed the optimal cut-off values for ΔTMTV3.0and ΔTLG3.0 were 66.3% (sensitivity 85.7%; specificity 63.4%; AUC 0.774; P <0.001) and 64.5% (sensitivity 85.7%; specificity 65.9%; AUC 0.777; P <0.001). Kaplan-Meier PFS and OS curves for the ΔTMTV3.0 (66.3%) and ΔTLG3.0 (64.5%) using the optimal cut-off value are shown in Figure 1.Conclusion: Baseline TMTV and TLG are strong predictors of PFS and OS in FL. Furthermore, interim TMTV (ΔTMTV>66.3%) and TLG (ΔTLG>64.5%) reduction are valuable tools for early treatment response assessment in FL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prediction of Pretreatment 18F-FDG-PET/CT Parameters on the Outcome of First-Line Therapy in Patients with Metastatic Breast Cancer.

Objective18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) can provide prognostic information, especially 18F-FDG uptake has been proven to be a predictor for the prognosis of various tumors. Nevertheless, the prognosis of other PET parameters in the metastatic setting remains unclear. This study was aimed at investigating pretreatment parameters based on 18F-FDG-PET/CT so as to estimate the progression-free survival (PFS) of metastatic breast cancer (MBC) patients receiving first-line treatment.MethodsMBC patients who underwent a whole-body 18F-FDG-PET/CT prior to first-line therapy were enrolled. The heterogeneity parameter of PET/CT was analyzed, including heterogeneity index (HI) and general parameters (metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax) and mean SUV (SUVmean). PFS was used to evaluate the treatment outcome. Kaplan–Meier method was adopted to carry out survival analysis and Log rank test was conducted to make a comparison.ResultsA total of 177 MBC patients were selected, in which 68 were in De novo stage IV. Thirty patients were human epidermal growth factor receptor 2 (HER2)-positive, 60 patients were triple-negative, and 87 patients were hormone receptor (HR)-positive and HER2-negative. In the whole population, patients with high baseline SUVmax, SUVmean, MTV, TLG or HI were associated with lower PFS (P=0.028, 0.005, 0.017, 0.026 and 0.035, respectively). Among the patients in De novo stage IV, those with high HI at baseline had significantly shorter PFS (P=0.001). In HR+/HER2- and HER2+ subgroups, only baseline HI showed the predictive value of PFS (P=0.023 and 0.049, respectively). In the triple-negative subgroup, high baseline SUVmax, MTV or TLG showed the predictive value of worse PFS (P=0.030, 0.011 and 0.023, respectively).ConclusionPretreatment 18F-FDG-PET/CT parameters show the predictive value of PFS in MBC patients receiving first-line treatment. However, predictive PET/CT parameters might be different in patients with different molecular subtypes and De novo stage IV.

Baseline Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on 18F-FDG PET-CT Predict Outcomes in T-Cell Lymphoblastic Lymphoma.

PurposeThere is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL.Materials and MethodsThirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test.ResultsThe optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001).ConclusionBaseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.

Will Baseline Total Lesion Glycolysis Play a Role in Improving the Prognostic Value of the NCCN-IPI in Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated With the R-CHOP Regimen?

The aim was to explore whether baseline total lesion glycolysis (TLG) can improve the prognostic value of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients treated with an R-CHOP-like regimen. Ninety-four PG-DLBCL patients who underwent baseline PET/CT between July 2010 and May 2019 were included in this retrospective study. FDG-avid lesions in each patient were segmented to calculate the SUVmax, total metabolic tumor volume (TMTV), and TLG. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate prognosis. During the follow-up period of 5 to 108 months (35.3 ± 23.5 months), high TLG and a high NCCN-IPI were significantly associated with poor PFS and OS. Total lesion glycolysis and the NCCN-IPI were independent predictors of PFS and OS. Patients were stratified into 3 groups according to the combination of TLG and the NCCN-IPI for PFS (P < 0.001) and OS (P < 0.001): high-risk group (TLG > 1159.1 and NCCN-IPI 4-8) (PFS and OS, 57.7% and 61.5%, respectively, n = 42), intermediate-risk group (TLG > 1159.1 or NCCN-IPI 4-8) (PFS and OS, both 76.9%, n = 26), and low-risk group (TLG ≤ 1159.1 and NCCN-IPI 0-3) (PFS and OS, 97.6% and 100.0%, respectively, n = 26). Both TLG and the NCCN-IPI are independent predictors of PG-DLBCL patient survival. Moreover, the combination of TLG and the NCCN-IPI improved patient risk stratification and might help personalize therapeutic regimens.

The contribution of metabolic parameters of FDG PET/CT prior and during therapy of adult patients with lymphomas.

Lymphomas are the most common hematological malignancies and are further distinguished in Hodgkin lymphoma (HL) and non-Hodgkin (NHL). For staging purposes and for assessing response to treatment, the Lugano classification is currently used, both for HL and NHL patients, whereas for the assessment of prognosis, several prognostic systems exist, such as the international prognostic index (IPI) and revised-IPI for diffuse large B cell lymphomas, follicular lymphoma IPI (FLIPI)-1 and 2 for follicular lymphomas, and the international prognostic score for advanced HL. The aim of this systematic review was to determine the significance of the metabolic FDG PET/CT parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in monitoring therapeutic interventions and prognostic outcome of patients with HL and NHL. We performed a systematic search on the literature and selection of articles concerning treatment evaluation, response and survival in association with MTV and TLG in patients with lymphomas. Our review documented that in most studies, baseline MTV and TLG were predictive of treatment response, progression-free survival (PFS) and overall survival (OS) for both HL and NHL patients. There were conflicting results for the value of interim determination of MTV and TLG. Our conclusion was that combination of baseline MTV and TLG parameters with prognostic scoring systems, such as IPI, or FLIPI-1 and -2, will add additional predictive power for response and prognosis in lymphoma patients.

Role of 18F-FDG PET-derived parameters for predicting complete response to chemoradiotherapy in squamous cell anal carcinoma.

We aimed to evaluate the accuracy of metabolic parameters, calculated on pretreatment positron emission computed tomography (PET/CT) with fluorodeoxyglucose (F-FDG), for predicting complete response to chemoradiotherapy (CRT) of patients affected by squamous cell anal carcinoma (SCAC). Clinical records of 20 patients affected by SCAC and treated with CRT were retrospectively evaluated. F-FDG PET/CT was performed at time 0 (baseline) and time 1 (12 weeks after CRT). The following parameters were extracted from PET at time 0: standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Response was assessed according to PET response criteria in solid tumors and classified as complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD). Receiver operating characteristic analysis was performed to analyze the predictive value of each PET-derived parameter on CMR. Sixteen patients were finally enrolled. All presented increased F-FDG uptake in the primary tumor and 11 (68.7%) also showed metastatic lymph nodes. At PET/CT performed at time 1, 11 subjects (68.7%) presented CMR, three (18.7%) had PMR and the remaining two (12.5%) showed PMD (i.e. hepatic metastases). Among baseline PET-derived parameters, both MTV and TLG efficiently predicted response to CRT with an area under the curve of 0.9 (cutoff 62.3 cm, sensitivity 80%, specificity 100%, P = <0.0001) and 0.87 (cutoff 654.1 g, sensitivity 80%, specificity 100%, P = 0.004), respectively. Among PET-derived parameters, both MTV and TLG presented a high predictive value on subjects' outcome after CRT.

Baseline total lesion glycolysis combined with interim positron emission tomography-computed tomography is a robust predictor of outcome in patients with peripheral T-cell lymphoma.

BackgroundPeripheral T‐cell lymphoma (PTCL) represents a heterogeneous and rare subgroup of aggressive lymphomas that generally demonstrate poor clinical outcomes with conventional treatment. Since the prognosis of PTCL is heterogeneous, more accurate risk assessment, and risk‐adapted treatment strategies are required. In this study, we examined whether interim positron emission tomography (iPET)‐computed tomography (PET/CT) results can be combined with baseline volume‐based metabolic assessments including total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) for risk stratification in PTCL.MethodsThe data of 63 patients with nodal PTCL, who had analyzable baseline PET/CT and iPET, were retrospectively reviewed. We calculated the baseline TMTV and TLG values. All iPET responses were analyzed using the Deauville 5‐point scale.ResultsOn univariate analysis, a prognostic index for PTCL (PIT) higher than 2 (hazard ratio [HR], 2.03; P = .026), high TMTV (>389 cm3; HR, 2.24; P = .01), high TLG (>875; HR, 3.77; P = .0005), and positive iPET (HR, 2.18; P = .009) were significantly associated with poorer progression‐free survival (PFS). On multivariate analysis, only high TLG and positive iPET independently predicted both poorer overall survival (OS) and PFS. A model combining TLG and iPET showed that patients with low TLG and negative iPET had superior outcomes, with a 5‐year PFS and OS of 72% and 90%, respectively. Conversely, both 5‐year PFS and OS for those with high TLG and positive iPET were 0%.ConclusionsIn summary, TLG combined with iPET predicted survival in PTCL more accurately. This information may help in the development of risk‐adapted treatment strategies for PTCL.

Predictive value of positron emission tomography for the prognosis of immune checkpoint inhibitors (ICIs) in malignant tumors.

This study aimed at investigating the value of applying positron emission tomography (PET) to early predict the effect of immune checkpoint inhibitors (ICIs) in malignant tumors. Electronic databases MEDLINE/PubMed, EMBASE, and Cochrane Library were searched to identify relevant trials. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The results were analyzed utilizing Stata 12.0 statistical software. Subgroup analyses were implemented based on primarytumors, study designs, continents, type of ICIs, evaluationindex of PET, and evaluated PET timing. Fifteen studies incorporating 664 individuals were eligible. Compared with PET nonresponse group, PET response group displayed a significantly prolonged PFS (HR 0.27, 95% CI [0.16, 0.44]; P < 0.001) and OS (HR 0.56, 95% CI [0.48, 0.65]; P < 0.001). Analogical outcomes were obtained in subgroup analyses of PFS in non-small cell lung cancer, prospective, America, ipilimumab, nivolumab/pembrolizumab combined ipilimumab, PET Response Criteria in Solid Tumors (PERCIST), baseline PET and early PET timing arms without heterogeneity; so did OS in melanoma, retrospective, Europe, America, ipilimumab, nivolumab/pembrolizumab, PERCIST, baseline metabolic tissue volume, baseline standard uptake value, and baseline total lesion glycolysis, baseline PET timing, early PET timing and late PET timing arms. Our study demonstrated that PET was a promising approach to early predict the prognosis of ICIs for malignancies.

Baseline Total Lesion Glycolysis Combined with Interim PET/CT Is a Robust Predictor of Outcome in Patients with Peripheral T-Cell Lymphoma

Background: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the initial staging and monitoring of the response in patients with malignant lymphomas, including peripheral T-cell lymphoma (PTCL). FDG PET/CT performed during a course of chemotherapy (interim PET, iPET) indicates early response and has been found to have prognostic value in various lymphoma subtypes. In addition to early treatment response, baseline characteristics including tumor burden and metabolic activity also significantly impact outcomes. Recently, volume-based metabolic assessments using PET/CT, including the total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), have emerged as new assessment tools. In this study, we investigated the predictive value of baseline TMTV and TLG in PTCL, and ascertained whether iPET response can be combined with these parameters to improve risk stratification. Methods: Patients with confirmed PTCL treated at Kameda Medical Center were retrospectively analyzed. The inclusion criteria included: a confirmed histological diagnosis of PTCL; pretreatment PET/CT and iPET evaluation; and anthracycline-based chemotherapy as first-line treatment. TMTV was defined as the volume of lymphoma visualized on PET/CT with a standardized uptake value (SUV) greater than or equal to the fixed absolute threshold of 2.5. TLG was calculated as the sum of the product of the average SUV (SUVmean) and MTV of all lesions. The computer-aided analyses of the PET/CT images for TMTV and TLG calculations were performed using an open-source software application Metavol (Hokkaido University, Sapporo, Japan). All iPET scans were defined as PET/CT scans performed after 2-4 cycles of chemotherapy. Response on iPET was assessed using the Deauville 5-point scale, with a score of 4-5 reflecting positivity. Results: Of the 107 patients with PTCL in our lymphoma cohort, we excluded adult T-cell leukemia/lymphoma, extranodal NK/T cell lymphoma, and cutaneous T-cell lymphoma, due to the different treatment strategies. Finally, 63 patients were enrolled in this study, including 30 with PTCL not otherwise specified (PTCL-NOS), 28 with angioimmunoblastic T-cell lymphoma (AITL), 4 with ALK-negative anaplastic large cell lymphoma (ALCL), and one with ALK-positive ALCL. The median age was 73 (range: 46-88) years. The majority of patients were treated with CHOP or CHOP-like chemotherapy. Consolidation therapy with stem cell transplantation was performed only in seven patients (11%) as our patients had a relatively higher age. After a median follow-up period of 35 months, the 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 30% and 51%, respectively. First, we assessed the prognostic value of the TMTV and TLG. The median baseline TMTV and TLG values were 423 cm3 (range, 21-3012 cm3) and 1980 (range, 56-21400), respectively. The optimal cutoff values determined using ROC curve analysis were 389 cm3 for TMTV and 875 for TLG. A high baseline TMTV was associated with worse PFS (hazard ration [HR], 2.244; 95% confidence interval [CI], 1.195-4.212; P = .01) and OS (HR, 3.358; 95% CI, 1.502-7.503; P = .002). Moreover, high baseline TLG were highly predictive of worse PFS (HR, 3.767; 95% CI, 1.666-8.517; P = .0005) and OS (HR, 4.722; 95% CI, 2.032-10.97; P &lt;.0001) (Figure 1). Next, we confirmed the prognostic value of the iPET findings. The iPET results were negative in 38 of 63 (60%) cases. In the univariate analysis, iPET positivity was predictive of worse PFS (HR, 2.177; 95% CI, 1.203-3.940; P = .009) and OS (HR, 4.931; 95% CI, 2.395-10.15; P &lt;.0001) (Figure 2). In the multivariate analysis testing TLG or TMTV with iPET results and PIT scores, only high TLG and positive iPET independently predicted both worse OS and PFS. Thus, we constructed a prognostic model combining the baseline TLG and iPET results. This model showed that patients with low baseline TLG values and negative iPET results had superior outcomes, with 5-year PFS of 72% and 5-year OS of 90% (Figure 3). While 5-year PFS and OS for those with high TLG and positive iPET were both 0%. Conclusion: Baseline TLG and iPET results are both independent prognostic factors in PTCL. Furthermore, TLG combined with iPET more accurately predicted survival in PTCL. This information may help the development of a risk-adapted treatment strategy for patients with PTCL. Disclosures Takahashi: Novartis Pharmaceuticals: Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; Chug Pharmaceuticals: Research Funding; Otsuka Pharmaceutical: Research Funding, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding, Speakers Bureau; Eisai Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Speakers Bureau; Asahi Kasei Pharma: Research Funding; Ono Pharmaceutical: Research Funding. Matsue:Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Novartis Pharma K.K: Honoraria; Ono Pharmaceutical: Honoraria.

A better prediction of progression-free survival in diffuse large B-cell lymphoma by a prognostic model consisting of baseline TLG and %ΔSUVmax.

In the era of rituximab, the International Prognostic Index (IPI) has been inefficient in initial risk stratification for patients with R‐CHOP‐treated diffuse large B‐cell lymphoma (DLBCL). To estimate the predictive values of PET/CT quantitative parameters and three prognostic models consisting of baseline and interim parameters for three‐year progression‐free survival (PFS), we conducted an analysis of 85 patients in China with DLBCL underwent baseline and interim PET/CT scans and treated at the Department of Hematology of Peking University Third Hospital from November 2012 to November 2017. The PET/CT parameters, viz. the baseline and interim values of standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), and their rates of change, were analyzed by a receiver operating characteristics curve, Kaplan‐Meier analysis, and log‐rank test. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI) was also included in the multivariate Cox hazards model. Owing to the strong correlation between TMTV and TLG at baseline and interim (Pearson's correlation coefficient, r = 0.823, P‐value = 0.000, and 0.988, P‐value = 0.000, respectively), only TLG was included in the multivariate Cox hazards model, where TLG0 > 1036.61 g and %ΔSUVmax < 86.02% showed predictive value independently (HR = 10.42, 95% CI 2.35‐46.30, P = 0.002, and HR = 4.86, 95% CI 1.27‐18.54, P = 0.021, respectively). Replacing TLG in the equation, TMTV0 and TMTV1 both showed significantly predictive abilities like TLG (HR = 8.22, 95% CI 1.86‐32.24, P = 0.005, and HR = 2.96, 95% CI 1.16‐7.54, P = 0.023, respectively). After dichotomy, NCCN‐IPI also gave a significant performance (P = 0.035 and P = 0.010, respectively, in TLG and TMTV models). The baseline variables, that is, TMTV0, TLG0 and dichotomized NCCN‐IPI, and the interim variables TMTV1 and %ΔSUVmax, presented independent prognostic value for PFS. In prognostic model 2 (TLG0 + %ΔSUVmax), the group with TLG0 > 1036.61 g and %ΔSUVmax < 86.02% recognized 19 (82.6%) of the relapse or progression events, which showed the best screening ability among three models consisting of baseline and interim PET/CT parameters.