Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial.

Introduction: High total metabolic tumor volume (TMTV) measured on 18F-FDG PET/CT before R-CHOP has been shown to be significantly associated with inferior progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma. The REMARC study (NCT01122472) showed a significantly better progression-free survival (PFS) in 650 patients responding to R-CHOP treated with maintenance therapy with lenalidomide (LEN) versus placebo (PBO), but no difference in OS was observed. The aim was to analyze the prognostic impact of baseline TMTV together with biological profile. Methods: TMTV was computed on baseline PET/CT using the 41% SUVmax method. The optimal TMTV cut-off for PFS and OS was determined by Receiver Operating Curve and X-tile analyses and confirmed by a training validation method. A subset of patients (n = 192) was classified as GCB or non-GCB profile, and with MYC or BCL2 by FISH. Survival was estimated using Kaplan Meier (KM) curves. Analyses were performed on the evaluable population (n=301/650) and each arm, with 146 pts on PBO and 155 pts on LEN. Results: Clinical characteristics were similar to the overall population. After a median 5 years follow-up, 4y-PFS was 73% and 4y-OS was 85%. Median baseline TMTV was 238 cm3 (Q1-Q3;78,523). The optimal TMTV cut-off was 220 cm3 for PFS and OS. Patients with TMTV >220 vs ≤220 cm3 presented with worse ECOG performance status (ECOG ≥2: 21% vs 11.5%, p=0.029), higher Ann Arbor stage (stage III-IV: 94% vs 87%, p=0.043), more extra-nodal sites (>1: 63.5% vs 39%, p<0.001), more frequently elevated LDH (74% vs 45%, p<0.001), higher IPI (IPI 3-5: 85% vs 58%, p=10-3), and higher aaIPI (score 2-3: 74% vs 40%, p=10-3). In all evaluated patients, a significant impact of TMTV was observed for PFS (p=2.10-4) and OS (p=10-4). Patients with high TMTV>220 vs low TMTV≤220, had a 4-year PFS of 56% vs 82% and OS of 74% vs 92% respectively. This prognostic impact of a high baseline TMTV on PFS (HR=2.2; 95% CI, 1.4-3.5) and OS (HR=3.2; 95% CI, 1.5-6.6) was maintained in both PBO and LEN arms. As demonstrated in the original report, GCB/nonGCB profile had no significant impact on PFS and OS, regardless of TMTV. BCL2 impacted PFS and could be stratified by TMTV. MYC had no impact on PFS and OS. In multivariate analysis, baseline TMTV was the most powerful parameter associated with inferior PFS and OS, compared to aaIPI and treatment arm. Conclusion: TMTV measured on baseline PET/CT is the strongest prognosticator of outcome in DLBCL, even in patients in responding after R-CHOP. High TMTV at baseline was significantly associated with inferior PFS and OS in patients receiving either PBO or LEN. Keywords: diffuse large B-cell lymphoma (DLBCL); positron emission tomography (PET).

Baseline and interim functional imaging with PET effectively risk stratifies patients with peripheral T-cell lymphoma

Circulating Tumor DNA Predicts Time to First Treatment in Previously Untreated Follicular Lymphoma: Analysis from a Prospective Clonal Evolution Study

Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct prognostic value in follicular lymphoma

Simultaneous Assessment of Total Metabolic Tumor Volume and Intratumoral CD4+ T-Cell Infiltration Identifies Early Progression of Follicular Lymphoma on Watch-and-Wait Approach

The purpose of this study was to investigate the predictive value of tumor metabolic parameters in combination with secondary lymphoid metabolic parameters on positron emission tomography (PET)/computed tomography (CT) for immune checkpoint inhibitor (ICI) prognosis in advanced lung cancer. This study retrospectively included 125 patients who underwent 18F-fludeoxyglucose (FDG) PET/CT before ICI therapy, including 41 patients who underwent a second PET/CT scan during ICI treatment. The measured PET/CT parameters included tumor metabolism parameters [maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), total lesion glycolysis (TLG), and total metabolic tumor volume (TMTV)] and secondary lymphoid organ metabolism parameters [spleen-to-liver SUVmax ratio (SLR) and bone marrow-to-liver SUVmax ratio (BLR)]. The correlation of PET/CT metabolic parameters with early ICI treatment response, progression-free survival (PFS), and overall survival (OS) was analyzed. Within a median follow-up of 28.7 months, there were 44 responders and 81 non-responders. The median PFS was 8.6 months (95% confidence interval (CI): 5.872-11.328), and the median OS was 20.4 months (95% CI: 15.526-25.274). Pretreatment tumor metabolic parameters were not associated with early treatment responses. The high bone marrow metabolism (BLR &gt;1.03) was significantly associated with a shorter PFS (p = 0.008). Patients with a high TMTV (&gt;168 mL) and high spleen metabolism (SLR &gt;1.08) had poor OS (p = 0.019 and p = 0.018, respectively). Among the 41 patients who underwent a second PET/CT scan, the ΔSUVmax was significantly lower (p = 0.01) and the SLR was significantly higher (p = 0.0086) in the responders. Populations with low-risk characteristics (low TMTV, low SLR, and ΔSLR &gt; 0) had the longest survival times. High pretreatment TMTV and SLR are associated with poor OS, and increased spleen metabolism after ICI therapy predicts treatment benefit. This indicates that the combination of tumor and spleen metabolic parameters is a valuable prognostic strategy.

The Prognostic Value of MTV Is Retained in New Proposed SUV 4 Threshold: An International Comparison of Follicular and Hodgkin Patient Survival

Diffuse large B‐cell lymphoma (DLBCL) is the most frequent subtype of non‐Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using 18F‐FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18F‐FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin‐2 receptor (sIL‐2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL‐2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ≥150 cm3 or sIL‐2R ≥ 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ≥150 cm3 and sIL‐2R ≥1300 U/mL was significantly associated with worse 5‐year overall survival and event‐free survival. Importantly, each of sIL‐2R <1300 U/mL or TMTV <150 cm3 identified patients with favorable prognosis among NCCN‐IPI high‐intermediate and high‐risk group. Serum level of sIL‐2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by 18F‐FDG PET/CT that can predict treatment outcomes of patients with DLBCL.

BACKGROUND. Combined positron emission tomography/computed tomography (PET-CT) with [18F]fluorodeoxyglucose is an essential instrument of monitoring the response to chemotherapy in primary mediastinal (thymic) large B-cell lymphoma (PMBCL). Of outstanding interest is the interpretation of PET-CT findings with respect to the frequent persistence of large residual mediastinal tumor after the end of drug therapy in PMBCL patients. AIM. To assess the prognostic value of PET-CT findings at different treatment stages in patients with newly diagnosed PMBCL. MATERIALS &amp; METHODS. This study is based on the clinical data from 28 PMBCL patients (altogether, 131 patients are followed-up) who were treated with R-DA-EPOCH ± radiotherapy at the NN Blokhin National Medical Cancer Research Center from 2011 to 2024. The median age was 35 years (range 21–48 years), most patients were women (n = 23; 82 %). This group of patients was selected because of the availability of PET-CT data to be closely analyzed prior to treatment, after 3 cycles (interim PET-CT), and by the end of the drug stage. This paper focuses on the data of 20 PMBCL patients including not only Deauville criteria (DC) for response but also the following technically determinable volumetric parameters: total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), as well as standardized uptake values (SUVmax, SUVpeak, ΔSUVmax, ΔSUVpeak, and rSUVmax), maximum diameter (Dmax and ΔDmax), and products of perpendicular lesion diameters (PD, ΔPD). RESULTS. With a 23-month median follow-up, the 2-year progression-free survival (PFS) in the total group was 78.6 % whereas the 2-year overall survival was 100 %. Incomplete metabolic response (DC 4–5) was reported in 19 (68 %) patients by the interim PET-CT and in 15 (54 %) patients by the end-of-treatment PET-CT. At the same time, the prognosis in patients with DC 4 and DC 5 was markedly different, but the 2-year PFS in the groups with complete (DC 1–3) and partial (DC 4) metabolic response appeared to be identical and accounted for 85 %. Moreover, all patients with DC 5 showed disease progression after chemotherapy. In PMBCL, two volumetric parameters (TMTV and TLG) have a particularly high prognostic value: the 2-year PFS in the group with high and low TMTV was 40 % and 93 %, respectively, and with high and low TLG it was 57 % and 92 %, respectively. CONCLUSION. PET-negative status (DC 1–3) confirmed already by the interim analysis is a reliable factor for favorable prognosis in PMBCL. After completing drug therapy, a considerable proportion of patients show incomplete metabolic response (DC 4–5). However, long-term survival rates corresponding to DC 4 are noninferior to those in patients with DC 1–3, whereas in patients with DC 5, they are considerably worse. High TMTV and TLG values prior to chemotherapy are associated with unfavorable course of the disease.

Total metabolic tumor volume (TMTV) at baseline becomes a key biomarker in several lymphoma subtypes. Variability in segmentation methods such as 41%SUVmax and SUVmax > 4 has limited its clinical application. Additionally, immune-checkpoint-inhibitors introduced challenges in response assessment due to pseudoprogression, complicating the use of traditional metrics. This study investigates the prognostic impact of baseline- and residual-TMTV and introduces a novel personalized-liver-based-threshold (pTMTVliver) to enhance precision in patient stratification. We analyzed 91 patients with relapsed/refractory diffuse-large-B-cell lymphoma and follicular lymphoma from the GATA trial, comparing patient's outcome according to three segmentation methods: TMTV41%, TMTV4, and pTMTVliver. pTMTVliver used a threshold of 200%SUVmeanliver aligning with 125%SUVmaxliver to enhance standardization and reduce variability. Baseline-TMTV significantly influenced prognosis with higher TMTV correlating with shorter PFS and OS (p < 0.0001 for all methods). Residual-TMTV, particularly with pTMTVliver and TMTV4, stratified no-CMR patients with the lowest predictive errors and better predictive accuracy compared to TMTV41% Multivariate analyses confirmed residual-pTMTVliver as superior for prognostic performance for PFS (HR:5.10; C-index:0.724) and OS (HR:4.00; C-index:0.853) compared to TMTV4 and Deauville Score (DS). The DS alone did not fully capture the heterogeneity of outcomes of DS4-5 patients. Baseline- and residual-TMTV strongly influence prognosis and response in lymphoma patients. The novel personalized pTMTVliver method offers improved accuracy of patient stratification, particularly for those with DS4-5, providing more reliable risk assessment. Larger cohorts are needed to validate these findings and optimize residual-TMTV-based clinical applications.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare aggressive lymphoma characterized by a paucity of neoplastic B-cells and a majority of reactive T-cells with or without histiocytes. In the ‘Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas’ trial (clinicaltrials.gov NCT00554164; EudraCT 2006-001641-33), its frequency was less than 3%. While cancer cell content by quantitative histology was 10-times lower, baseline total metabolic tumor volume (TMTV) by 18-fluorodesoxyglucose positron emission tomography was 10-times higher in THRLBCL than in diffuse large B-cell lymphoma (DLBCL). When THRLBCL and DLBCL populations were matched for TMTV, the survival curves were superimposable. However, when the populations were matched for cancer cell volume by multiplying TMTV by cancer cell fraction, outcome in THRLBCL was worse than in DLBCL. Whether genetic differences between cancer cells, tumor-promoting properties of non-neoplastic cells, or both are responsible for inferior cancer cell volume-related outcome in THRLBCL, remains to be elucidated.

Grade 3B follicular lymphoma (G3BFL) is a rare lymphoma thought to sit on a continuum between low-grade FL and diffuse large B-cell lymphoma (DLBCL). The prognostic impact of quantitative positron emission tomography (PET) metrics such as total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUVmax) have been extensively analysed in FL and DLBCL, but G3BFL data are lacking. Here, we describe PET outcomes and radiomic characteristics in 46 G3BFL cases uniformly treated with R-CHOP (like) chemotherapy. Central semi-automated PET TMTV, TLG, and SUVmax analyses, using MIM software, were correlated with clinical outcomes and compared with published results in low-grade FL and DLBCL. In G3BFL, the end-of-treatment complete metabolic response was associated with improved progression-free survival (PFS; p = 0.002) and overall survival (OS; p = 0.04). G3BFL median TLG (1455) and SUVmax (16.50) sit between published values for low-grade FL (TLG: 1112, SUVmax: 11.3) and DLBCL (TLG: 3004, SUVmax: 24.35). No association between TMTV (>350 cm3) and survival was seen (PFS: p = 0.24; OS: p = 0.40). High SUVmax (>19.2) and TLG (>2760) both conferred inferior PFS but not OS (PFS: SUVmax p = 0.004; TLG p = 0.05). These data support the routine incorporation of PET radiomics at baseline and treatment response for G3BFL.

Simple SummaryWhile information about sociodemographic characteristics of Hodgkin lymphoma (HL) and their influence on outcomes remains elusive, the objective of this present study was to decipher the potential impact of social disparities on the disease features at diagnosis and to analyze how sociodemographic patient characteristics could impact HL outcomes. These findings suggest that some patient sociodemographic characteristics might impact access to medical care leading to a higher frequency of unfavorable presentations.Introduction: Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10–15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. Methods: This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events—SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data—marital status, living area, level of education, socio-professional category, and professional situation—were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. Results: Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0–2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area’s inhabitants and TMTV (R Pearson = −0.29, p = 0.0004) was observed. Conclusion: This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

In this prospective study, we investigated the correlation between prostate-specific antigen (PSA) levels in the blood of patients with prostate cancer in biochemical recurrence after radical treatment with the semiquantitative parameters standard uptake value maximum (SUV max ) and the total metabolic tumor volume (TMTV) in the metastatic foci depicted in 18F-prostate-specific membrane antigen (PSMA)-1007 and 18F-choline PET/computed tomography (CT) imaging. We prospectively examined 104 patients with biochemical relapse of prostate cancer after primary definitive treatment. All patients underwent one 18F-PSMA-1007 and one 18F-choline PET/CT examination in randomized order within a time frame of 10 days and were followed for at least 6 months (182 ± 10 days). The semiquantitative parameters of SUV max and metabolic tumor volume (MTV) of each neoplastic lesion in PET/CT imaging were calculated, and further summation of each MTV value was done to calculate the TMTV. According to the Spearman correlation analysis, a positive correlation was found between PSA levels and SUV max and TMTV scores in the metastatic foci of 18F-PSMA-1007 PET/CT ( r = 0.24 and 0.35, respectively; P < 0.05) and SUV max in the lesions of 18F-choline PET/CT ( r = 0.28; P < 0.0239). However, a positive but NS correlation was demonstrated between values of PSA and TMTV for each lesion in the 18F-choline PET/CT study ( r = 0.22; P = 0.0795). The detection rate of the different PSA levels with a cutoff of 1 ng/ml was higher for 18F-PSMA-1007 than 18F-choline. In biochemical relapse patients there is a positive correlation between PSA levels in the blood and the semiquantitative parameters SUV max and TMTV of the metastatic foci in the 18F-PSMA-1007 and 18F-Choline PET/CT imaging.

BackgroundChimeric antigen receptor (CAR) T-cell therapy has been proven to be an effective choice for patients with relapsed or refractory large B-cell lymphoma (LBCL). Early identification of patients who may have a poor prognosis and develop severe side effects is necessary. In this study, we aimed to assess the value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) parameters in predicting the prognosis and toxicity of CAR T therapy for children and young adults with LBCL.MethodsThis retrospective cohort study included patients with LBCL under 30 years of age who underwent 18F-FDG PET/CT at Beijing Friendship Hospital of Capital Medical University and Beijing GoBroad Boren Hospital before CAR T-cell infusion within 1 month. 18F-FDG PET/CT metabolic parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) were recorded. Clinical characteristics and laboratory indicators were also collected. The main endpoints were progression-free survival (PFS) and overall survival (OS) as estimated by the Kaplan-Meier method and log-rank test. We also assessed the relationship between these metabolic and clinical parameters and severe toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).ResultsForty-five patients were recruited. The median duration of the follow-up period was 13.9 months. Patients with an age-adjusted international prognostic index (aaIPI) 2–3 (P=0.014) and TMTV >101.4 mL (P=0.026) had a shorter PFS. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 2–3 (P=0.015) and TMTV >101.4 mL (P=0.011) had a shorter OS. Lactate dehydrogenase (LDH) > upper normal limit (UNL) (P=0.030) and TMTV >101.4 mL (P=0.042) were associated with grade 2–4 CRS, and C-reactive protein (CRP) > UNL (P=0.014) was associated with grade 2–4 ICANS.ConclusionsaaIPI and TMTV were independent risk factors for PFS, and ECOG score and TMTV had independent prognostic value for OS. Higher LDH and TMTV were associated with grade 2–4 CRS, and higher CRP was associated with more severe ICANS. Thus, integrating these metabolic parameters of 18F-FDG PET/CT and clinical-laboratory indicators can be valuable for managing children and young adults with B-cell lymphoma who have received CAR T-cell therapy.