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This thesis evaluated the potential of quantitative PET biomarkers at baseline before treatment and response during treatment using the interim PET in DLBCL patients. The aim is to facilitate selection of high risk patients to ultimately improve outcome due to early treatment modifications and identification of low risk patients to allow treatment de escalation. The main findings were that radiomics features at baseline were predictive of 2-year survival without progression, regardless of the applied segmentation method to delineate the lesions and the applied radiomics feature and/or lesion selection. Moreover, adding radiomics features significantly improves prediction of outcome in DLBCL patients compared to currently used risk scores such as the IPI score, leading to better upfront selection of high risk and low risk patients. An interim PET after 2-4 cycles of treatment is able to differentiate between good and poor responders, and especially the negative predictive value of an I PET is high. It is cost effective to reduce treatment based on a negative interim PET after 2 cycles using the Deauville score. With respect to the optimal response criterion, the ΔSUVmax criterion seems to be the best trade off between sensitivity and positive predictive value. Concluding, PET biomarkers can play a pivotal role in personalizing treatment and management of DLBCL patients and in future lymphoma research.

This thesis evaluated the potential of quantitative PET biomarkers at baseline before treatment and response during treatment using the interim PET in DLBCL patients. The aim is to facilitate selection of high risk patients to ultimately improve outcome due to early treatment modifications and identification of low risk patients to allow treatment de escalation. The main findings were that radiomics features at baseline were predictive of 2-year survival without progression, regardless of the applied segmentation method to delineate the lesions and the applied radiomics feature and/or lesion selection. Moreover, adding radiomics features significantly improves prediction of outcome in DLBCL patients compared to currently used risk scores such as the IPI score, leading to better upfront selection of high risk and low risk patients. An interim PET after 2-4 cycles of treatment is able to differentiate between good and poor responders, and especially the negative predictive value of an I PET is high. It is cost effective to reduce treatment based on a negative interim PET after 2 cycles using the Deauville score. With respect to the optimal response criterion, the ΔSUVmax criterion seems to be the best trade off between sensitivity and positive predictive value. Concluding, PET biomarkers can play a pivotal role in personalizing treatment and management of DLBCL patients and in future lymphoma research.

Our objective was to develop version 1.0 of a novel framework for response evaluation criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) and a composite response classification that combines responses by prostate-specific antigen (PSA) measurements and by RECIP 1.0 (PSA + RECIP). Methods: This was an international multicenter, retrospective study. One hundred twenty-four men with metastatic castration-specific prostate cancer (mCRPC) who underwent 177Lu-PSMA therapy and received PSMA PET/CT at baseline and at an interim time point of 12 wk were included. Pairs of baseline interim PET/CT scans were interpreted by consensus among 3 masked readers for appearance of new lesions. Tumor lesions were segmented, and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which included classifications of complete response (RECIP-CR: absence of any PSMA-ligand uptake on interim PET/CT), partial response (RECIP-PR: decline ≥ 30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥ 20% in PSMA-VOL and appearance of new lesions), and stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 wk by Prostate Cancer Working Group Criteria 3 were recorded. PSA + RECIP results were defined as response (PSA decline ≥ 50% or RECIP-PR/CR) or progression (PSA increase ≥ 25% or RECIP-PD). The study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). The secondary outcome measure was the prognostic accuracy (C-index) of PSA + RECIP versus PSA responses. Results: Patients with RECIP-PD (n = 39; 8.3 mo) had a shorter OS than patients with stable disease (RECIP-SD) (n = 47; 13.1 mo; P < 0.001) or RECIP-PR (n = 38; 21.7 mo; P < 0.001). In identifying responders and progressors, PSA + RECIP had C-indices superior to those of PSA only: 0.65 versus 0.62 (P = 0.028) and 0.66 versus 0.63 (P = 0.044), respectively. Conclusion: PSMA PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor early efficacy of 177Lu-PSMA in men with mCRPC. PSA + RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.

Diffuse large B-cell lymphoma is treated with anti-CD 20 and multi-drug chemotherapy for cure. Positron emission tomography (PET) scans are performed at end of treatment (EOT) to assess response. EOT Deauville scores (DS) are equivocal for treatment response in some situations, requiring physicians to determine the need for further investigations or treatment. Studies have suggested the delta maximum standardised uptake value (ΔSUVmax) to be superior to DS for assessment of metabolic response at interim PET, although its use at EOT PET, especially in cases of equivocal response, has yet to be established. We investigated whether ΔSUVmax could better discriminate prognosis than DS 3 or 4 at EOT. ΔSUVmax did not outperform DS. Combination of DS 3 and International Prognostic Index (IPI)

Purpose To investigate the prognostic value of interim PET (PETi) in adult HL patients, comparing visual with semiquantitative analysis. Material and methods Retrospective analysis of Hodgkin's lymphoma (HL) patients diagnosed between 2012 and 2016 in the Onco-hematology Department of Instituto Portugues de Oncologia – Porto (median follow-up: 46.5 months [2.6–66.4]). Fifty-eight patients with available PET at diagnosis (PET0) and PETi data were included. PETi scans were analyzed according to Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value [SUVmax], peak SUV [SUVpeak], metabolic tumour volume [MTV] and total lesion glycolysis index [TLG] between PETi and PET0 were computed using ROC analysis. Visual and semiquantitative data were compared with each other in the prediction of patient outcomes. Results Semiquantitative analysis obtained a higher sensitivity for persistent/relapsed disease compared to the 5-PS (70% vs. 10%, respectively), but lower specificity. It also demonstrated better predictive performance for response to first-line therapy (negative predictive value >92%). The positive predictive value was similar for all five measurements. At 60 months of follow-up, there was a significant difference between the progression free survival (PFS) curves of patients with positive and negative PETi according to ΔSUVmax (56.9% vs. 88.0%, p Discussion PETi interpretation according to a semiquantitative approach appears to discriminate HL patients better than the visual 5-PS analysis. This could allow better detection of persistent or early relapsed disease, while a negative PETi result could support de-escalating therapy intensity.

18-fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET) and mainly combined with computed tomography (CT), abbreviated as FDG PET/CT is a useful and accurate tool for staging and restaging in locally advanced breast cancer. In daily practice static images are prepared during the PET/CT examinations. However, despite the success of static PET and PET/CT imaging, the role of precise quantification of FDG-uptake – measured by dynamic acquisition – is ambiguous in the staging and management of different malignancies. In this case report, we described our experience with staging, interim and restaging dynamic PET/CT examinations of a woman suffering from breast cancer. Based on the described case we concluded that dynamic PET/CT is suitable for accurate quantification of FDG-uptake in primary breast tumors. However, performing dynamic PET/CT examinations is time-consuming, therefore, it is important to define the group of patients where their use is with the most favourable benefit/risk ratio. Furthermore, using of interim PET/CT scan is recommended in cases with clinically controversial baseline tests. Based on literature in vivo biomarkers of the dynamic PET/CT are predictive of more favourable tumor response and longer disease-free survival, as confirmed by our own results.

The positron emission tomography (PET) could predict the prognosis of DLBCL patients, but the exact procedure on interim PET (iPET) to determine chemoresistant patients remains elusive.We retrospectively analyzed 593 newly diagnosed DLBCL patients uniformly treated with R-CHOP regimen. Among them, 352 patients diagnosed from August 2010 to December 2016 were included in the test cohort and 241 patients diagnosed from January 2017 to December 2019 were included in the validation cohort. The iPET was evaluated with Deauville criteria and ΔSUVmax method. The reduction of maximal SUV between baseline and after 4 cycles of chemotherapy were defined as ΔSUVmax. The survival functions were depicted using the Kaplan-Meier method and compared with the log-rank test.Patients with iPET Deauville 4 had heterogeneous outcome and end of treatment complete response rates (eCRR). Combined Deauville with ΔSUVmax method, we proposed a modified-Deauville model: patients with Deauville 4 and ΔSUVmax70%, as well as those with Deauville 1-3, were reclassified into the modified-Deauville negative group, while patients with Deauville 4 and ΔSUVmax ≤ 70%, as well as those with Deauville 5, into the modified-Deauville positive group. In the test cohort, 3-year PFS, OS and eCRR of modified-Deauville negative group were 80.2%, 89.9% and 91.8%, significantly higher than those of positive group (12.5%, 27.3% and 29.2%,The modified-Deauville model could better distinguish DLBCL patients with poor response to chemotherapy. Accordingly, these patients could be recognized early and provided with alternative therapeutic agents, which might improve the clinical outcome of refractory DLBCL patients.

Objective. Assessment of the role of positron emission tomography (PET) in the diagnosis and treatment of B‑cell lymphoproliferative disorders (B-LPD) in Russian real‑world clinical practice from 2014 to 2017.Materials and Methods. The EQUILIBRIUM, a post marketing multicenter study, included 1000 patients aged 21 to 91 years with a verified diagnosis of B‑cell non‑Hodgkin»s lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL) who received at least 4 cycles of rituximab‑containing therapy with Acellbia®. The main method for the assessment of the disease dissemination, the size and location of the lesions was computed tomography, which was used in 76.2 % of patients. PET was performed in 324 (32.4 %) patients: in 152 (47 %) cases during initial diagnosis, PET during treatment in 102 (31 %) patients and — in the vast majority, i. e. 310 (96 %) patients — after completion of induction chemo‑immunotherapy. Results. According to the results of interim PET, complete remission was achieved in 44 (43 %) of 102 patients, partial remission — in 53 (52 %) cases, stabilization of the disease was observed in 5 (5 %) patients, and no cases of progression among patients who underwent interim PET was detected. The main evidence of the final PET assessment efficacy was the achievement of complete remission (CR) in 235 (75.8 %) cases; partial remission (PR) was observed in only 61 (19.7 %) patients, and disease progression was reported in 14 (4.5 %) of cases. The median follow‑up was 15 months (range from 1 to 42 months). As expected, the median overall survival (OS) as well as the median event‑free survival (EFS) has not been reached for this period of time. There was a statistically significant effect of the results of interim PET on event‑free survival (p = 0.07661) without a significant effect on overall survival (p = 0.69868). The depth of response recorded during the final PET scan turned out to be a prognostically significant factor for both EFS and OS (p = 0.00000).Conclusion. Positron emission tomography is a modern and effective method for diagnosing and assessing the efficacy of therapy in B‑cell lymphoproliferative disorders, which is used for only 1 / 3 of patients in a real‑world clinical practice. Nevertheless, the role of this method in assessing the effectiveness of therapy is beyond doubt.

The lead author with clinical stage I malignant pleural mesothelioma, epithelioid type, highly programmed cell death ligand 1 (PD-L1) positive, and BAP1 negative, experienced a prompt and exceptionally favorable response to pembrolizumab monotherapy. After cessation of treatment due to immune-related endocrinopathies, complete metabolic response on interim PET/CT scan was achieved. Two years after initial diagnosis, unifocal tumor reactivation was addressed with successful pembrolizumab monotherapy rechallenge. Immunotherapy, typically not used as frontline treatment for malignant pleural mesothelioma, may provide an effective and durable response for some patients. Based on this single case study, epithelioid type tumors with strongly positive PD-L1 and BAP1-negative immunohistochemical markers may be well suited for treatment with immune checkpoint inhibitors such as pembrolizumab.

Objective Identification of imaging prognostic parameters for early therapy personalisation to reduce treatment-related morbidity in paediatric Hodgkin lymphoma (HL). Our aim was to evaluate quantitative markers from baseline 2-[F]fluoro-2-deoxy-D-glucose PET/CT as prognostic factors for treatment outcomes. Another goal was assessing the prognostic value of Deauville score at interim PET/CT. Methods Twenty-one patients were prospectively enrolled. Median age was 12 years (range 6-17); 13 were female. Patients underwent PET/CT for disease staging (bPET), at the end of two cycles of chemotherapy (iPET) and after chemotherapy. A total of 173 lesions were segmented from bPET. We calculated 51 texture features for each lesion. Total metabolic tumour volume and total lesion glycolysis from bPET were calculated for response prediction at iPET. Univariate and multivariate analyses were used for optimal cut-off values to separate responders at iPET according to the Deauville score. Results We identified four texture features as possible independent predictors of treatment outcomes at iPET. The areas under the ROC for univariate analysis were 0.89 (95% CI, 0.75-1), 0.82 (95% CI, 0.64-1), 0.79 (95% CI, 0.59-0.99) and 0.89 (95% CI, 0.75-1). The survival curves for patients assigned Deauville scores 1, 2, 3 and X were different from those assigned a score 4, with 4-year progression free-survival (PFS) rates of 85 versus 29%, respectively (P = 0.05). Conclusions We found four textural features as candidates for predicting early response to chemotherapy in paediatric patients with HL. The Deauville score at iPET was useful for differentiating PFS rates.

Purpose MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients. Methods Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. Results MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8–94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%). Conclusion MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. Trial registration number and date of registration HOVON-84: EudraCT: 2006–005,174-42, retrospectively registered 01–08-2008. HOVON-130: EudraCT: 2014–002,654-39, registered 26–01-2015

In first-line treatment of Hodgkin lymphoma (HL), Deauville scores 1-3 define complete metabolic remission. Interim 18F-FDG PET is also used for relapse-treatment adaptation; however, PET response criteria are not validated for relapse treatment. Methods: We performed a pairwise comparative analysis of early response to first- and second-line treatments in 127 patients with classic HL who experienced relapse. The patients participated in the prospective, multicenter EuroNet-PHL-C1 study. Residual uptake was measured retrospectively using the qPET method, a validated semiautomatic quantitative extension of the Deauville score. Empiric cumulative distribution functions of the qPET values were used to systematically analyze the response to first- and second-line treatments. Results: Individual patients responded variably to first- and second-line treatments. However, the empiric cumulative distribution functions of the qPET values from all patients were nearly superimposable. Conclusion: The findings support that first- and second-line treatments in HL do not require different response criteria.

Hodgkin lymphoma (HL) has a bimodal age distribution curve, with a second peak in people aged more than 60 years. Interim PET/CT (iPET/CT) is highly predictive for PFS and OS in young HL, but it has not been sufficiently studied in the elderly. In this retrospective dual-center study, 82 patients with HL and aged 65 or more who performed iPET/CT were included. At iPET/CT, 60 patients had a complete metabolic response, 18 partial responses, and 4 progressions of disease. Baseline PET/CT metabolic features were not significantly correlated with the metabolic response at interim. In patients with interim complete metabolic response, PFS and OS were significantly longer than in patients without complete response(

Background Peripheral 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. Methods The 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. Results On 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%. Conclusions In 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., Recently, volume‐based positron emission tomography‐computed tomography (PET/CT) assessments such as total metabolic tumor volume (TMTV) and tumor lesion glycolysis (TLG) have been reported to be useful prognostic indicators for various cancers. In this study, we found that baseline TLG has stronger prognostic potential than baseline TMTV, and interim PET/CT response can be combined with TLG to improve risk stratification in peripheral T‐cell lymphoma.

Introduction: Positron-emission tomography (PET)/computerized tomography (CT) with 18F-fludeoxyglucose (FDG) has been come into use for risk assessment of Hodgkin lymphoma (HL) patients in recent years. The aim of our study is to evaluate the reliability of interim PET results according to Deauville score (DS), and also to compared PET findings with tumor reduction on CT. Methods: Forty-two HL patients (median 39, range 19-75 y, 27 M, 15 F) were retrospectively evaluated with pre, interim and post-treatment PET/CT imaging. PET/CT imaging was obtained 60 min after the intravenous administration of 3.7-5.2 MBq/kg 18F-FDG. Results: The negative predictive value of the interim PET was 89%. Four (10.5%) of the 38 interim PET-negative patients became post-treatment PET-positive. According to CT, 15 patients were in complete remission (CR), 27 (64.6%) patients were in partial remission (PR) or stable disease (SD). Conclusion: The negative predictive value of interim PET was not satisfactory considering the treatment rate of over 80% of HL. Additionally, high rate of interim PET-negative patients’ conversion to PET-positive post-treatment state was considered as unexpected.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immunochemotherapy after 2 cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying 2 different methods of interpretation: the Deauville visual 5-point scale (5-PS) and a change in SUV (ΔSUV) by semiquantitative evaluation. Methods: In total, 145 patients with newly diagnosed DLBCL underwent pretreatment PET and PET-2 assessment. PET-2 was classified according to both 5-PS and percentage ΔSUV. Receiver-operating-characteristic analysis was performed to compare the accuracy of the 2 methods for predicting progression-free survival. Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET-) groups and compared. Results: Both with 5-PS and with ΔSUV-based evaluations, significant differences were found between the progression-free survival of iPET- and iPET+ patient groups (P < 0.001). Visually, the best negative predictive value (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if the Deauville score was 4-5 (89% and 59%, respectively). Using the 66% ΔSUV cutoff reported previously, NPV and PPV were 80% and 76%, respectively. ΔSUV at the 48.9% cutoff, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). The 5-PS and a semiquantitative ΔSUV of less than 48.9% for each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100%, respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL patients, iPET had good prognostic value interpreted either visually or semiquantitatively. We determined that the most effective ΔSUV cutoff was 48.9% and that when combined with 5-PS assessment, a positive PET-2 result was highly predictive of treatment failure.cases, and MRI in 92.5% of cases; no false negative cases were observed. These results suggest the use of PET/CT as a unique diagnostic imaging tool after CCRT, to correctly assess residual and progression disease.

Purpose Prognostic evaluation using interim positron emission tomography/computed tomography (interim PET/CT; I-PET) remains controversial. For any predictor, the prognosis of patients around its cutoff value is most uncertain. If the patients around the cutoff value could be subdivided by another factor, like the international prognostic index (IPI), it may improve the predictive power of I-PET. The combination of I-PET and IPI for risk stratification of patients was explored in this study. Patients and methods One hundred and eleven diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP therapy were included retrospectively, 59 of whom underwent PET/CT after three or four cycles of treatment (I-PET). Fifty-two patients underwent PET/CT after five or six cycles of treatment (end of treatment; E-PET). Results When Deauville 5-point scale (5-DS) scores of 4-5 were classified as a positive scan (denoted by DS [score 4]), there was no significant difference in progression-free survival (PFS) between I-PET positive and negative patients (P=0.151). Further, patients with 5-DS score 3 and high IPI were stratified into I-PET positive-, whereas those with 5-DS score 3 and low IPI were classified into I-PET negative scan groups. Under this stratification, there was a significant difference in PFS between I-PET positive and negative patients (P=0.001). The sensitivity, positive predictive value, and negative predictive value for 2-year PFS for the combination score were higher than DS (score 4) alone (66.7% vs 33.3%, 50.0%vs 37.5%, 93.6% vs 88.2%) whereas specificity was almost the same (90.0% vs 88.0%). Conclusion Subdivision of patients with 5-DS score 3 by IPI improved prognostic prediction accuracy. The IPI adds strength to 5-DS in I-PET to detect patients with good or poor prognosis. Compared with other combinations of I-PET and IPI, dividing the patients around the cutoff value of 5-DS by IPI was easily accepted by clinicians and allowed them to decide on further treatment practically.

Objectives A diverse intratumoral T‐cell receptor (TCR) repertoire is associated with improved survival in diffuse large B‐cell lymphoma (DLBCL) treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy. We explored the impact of intratumoral TCR repertoire on interim PET (iPET) done after four cycles of R‐CHOP, the relationships between intratumoral and circulating repertoire, and the phenotypes of expanded clonotypes. Methods We sequenced the third complementarity‐determining region of TCRβ in tumor samples, blood at pre‐therapy and after four cycles of R‐CHOP in 35 patients enrolled in ALLGNHL21 trial in high‐risk DLBCL. We correlated the TCR diversity metrics with iPET status, gene expression profiles and HLA‐class I genotypes. We then sequenced the FACS‐sorted peripheral blood T cells in six patients, and pentamer‐sorted EBV‐specific CD8+ T cells in one patient from this cohort. Results Compared with iPET− patients, the intratumoral TCR repertoire in iPET+ patients was characterised by higher cumulative frequency of abundant clonotypes and higher productive clonality. There was a variable overlap between circulating and intratumoral repertoires, with the dominant intratumoral clonotypes more likely to be detected in the blood. The majority of shared clonotypes were CD8+ PD‐1HI T cells, and CD8+ T cells had the largest clonal expansions in tumor and blood. In a patient with EBV+ DLBCL, EBV‐specific intratumoral clonotypes were trackable in the blood. Conclusion This study demonstrates that clonally expanded intratumoral TCR repertoires are associated with iPET+ and that the blood can be used to track tumor‐associated antigen‐specific clonotypes. These findings assist the rationale design and therapeutic monitoring of immunotherapeutic strategies in DLBCL., In a cohort of high‐risk diffuse large B‐cell lymphoma patients enrolled in phase 2 clinical trial, clonally expanded intratumoral TCR repertoires were associated with a positive interim PET scans. Abundant intratumoral clonotypes were identified in peripheral blood at baseline and during chemoimmunotherapy.

Purpose The role of interim 18F‐FDG PET/CT (iPET/CT) in diffuse large B‐cell lymphoma (DLBCL) remains controversial. The purpose of this study was to assess the prognostic value of iPET/CT in patients with newly diagnosed DLBCL according to visual and semiquantitative interpretation methods. Methods A total of 129 newly diagnosed DLBCL patients with baseline PET/CT data were retrospectively screened. The iPET/CT findings were evaluated by the Deauville 5‐point scale (DS) and ΔSUVmax. Furthermore, the reduction in SUVmax incorporated with tumor size (ΔSUVmax*ΔSLD) was calculated. The optimal cutoff values of ΔSUVmax and ΔSUVmax*ΔSLD were determined by receiver operating characteristic (ROC) analysis. Kaplan‐Meier analysis was applied to test for the influence of prognostic values. Univariate and multivariate analyses were conducted to examine the potential independent impacts of iPET/CT. Results Seventy‐seven patients with PET/CT images acquired both at baseline and after four cycles of chemotherapy were finally enrolled. The optimal cutoff values for ΔSUVmax and ΔSUVmax*ΔSLD were 74% and 30%, respectively. After a median follow‐up of 23 months, iPET/CT findings were significant predictors of PFS and OS whenever iPET/CT was interpreted by DS, ΔSUVmax, or ΔSUVmax*ΔSLD methods. ΔSUVmax‐based methods were more accurate than those based on DS. The IPI, DS, ΔSUVmax, and ΔSUVmax*ΔSLD were predictive in univariate analyses. However, in the multivariate analysis, only IPI and ΔSUVmax remained independent predictors of PFS and OS. Conclusions Interim PET/CT may help to identify DLBCL patients with different prognoses. ΔSUVmax analysis shows the best accuracy and the strongest predictive value among these three methods. ΔSUVmax*ΔSLD may be a promising parameter to interpret iPET/CT images, reflecting both the changes in tumor size and metabolic activity.

Treating patients with DLBCL remains a challenge, as the response to first-line immunochemotherapy is somewhat unpredictable. The International Prognostic Index (IPI) is one of the most widely used methods for assessing prognosis. Interim PET/CT (iPET/CT) can play an important role in the early identification of 'non-responder' patients before the end of treatment examination. In this study, we retrospectively analyzed 104 newly diagnosed DLBCL patients treated with R-CHOP-like regimens who underwent iPET/CT imaging during therapy. There was a significant difference in 2-year OS between patients with negative iPET/CT and those with positive iPET/CT. Patients who had positive iPET/CT showed inferior 2-year PFS compared to those with negative iPET/CT. According to IPI, there was a statistically significant difference in 2-year OS and PFS between patients in the lower and higher risk groups. However, these patients can be further subdivided according to iPET/CT. The iPET/CT results in the present study clearly separate good- and poor-prognosis patients according to differences in 2-year OS, both in the lower and higher IPI risk groups. These results are in agreement with those of previous studies that demonstrated that iPET/CT has high negative predictive value, clearly identifying good-prognosis patients even within the poor-prognosis IPI group.

In diffuse large B-cell lymphoma, early assessment of treatment response by 18F-FDG PET may trigger treatment modification. Reliable identification of good and poor responders is important. We compared 3 competing methods of interim PET evaluation. Methods: Images from 449 patients participating in the "PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas" trial were reanalyzed by applying the visual Deauville score and the SUV-based qPET (q = quantitative) and ΔSUVmax scales to interim PET scans performed after 2 cycles of chemotherapy. qPET relates residual lymphoma 18F-FDG uptake to physiologic liver uptake, converting the ordinal Deauville scale into a continuous scale and permitting a direct comparison with the continuous ΔSUVmax scale, which is based on SUVmax changes between baseline and interim scans. Positive and negative predictive values were calculated for progression-free survival. Results: When established thresholds were used to distinguish between good and poor responders (visual Deauville score 1-3 vs. 4-5; ΔSUVmax > 66% vs. ≤ 66%), the positive predictive value was significantly lower with Deauville than ΔSUVmax (38.4% vs. 56.6%; P = 0.03). qPET and ΔSUVmax were strongly correlated on the log scale (Pearson r = 0.75). When plotted along corresponding percentiles, the positive predictive value curves for qPET and ΔSUVmax were superimposable, with low values up to the 85th percentile and a steep rise thereafter. The recommended threshold of 66% SUVmax reduction for the identification of poor responders was equivalent to qPET = 2.26, corresponding to score 5 on the visual Deauville scale. The negative predictive value curves were also superimposable but remained flat between 80% and 70%. Conclusion: Continuous scales are better suited for interim PET-based outcome prediction than the ordinal Deauville scale. qPET and ΔSUVmax essentially carry the same information. The proportion of poor-risk patients identified is less than 15%.

The value of interim 18F-FDG PET/CT (iPET)-guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the change-in-SUV max (DSUV max) approach-2 methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas trial, iPET scans of 596 patients originally evaluated using the DSUV max method were available for post hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the ΔSUV max approach is characterized as a relative reduction of the SUV max between baseline and iPET staging of less than or equal to 66%. We investigated the 2 methods' correlation and concordance by Spearman rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the prespecified cutoffs. Time-dependent receiver-operating-characteristic curve analysis provided information on the methods' respective discrimination performance. Results: Deauville score and DSUV max approach differed in their iPET-based prognosis. The ΔSUV max approach outperformed the Deauville score in terms of discrimination performance-most likely because of a high number of false-positive decisions by the Deauville score. Cutoff-independent discrimination performance remained low for both methods, but cutoff-related analyses showed promising results. Both favored the ΔSUV max approach, for example, for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval, 2.22-4.46) for ΔSUV max and 1.70 (95% confidence interval, 1.29-2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cutoff of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The ΔSUV max criterion of a relative reduction in SUV max of less than or equal to 66% should be considered as an alternative.

5066 Background: The aim of this analysis was to evaluate the prognostic value of interim PSMA PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA and to develop a novel framework for Response Evaluation Criteria In PSMA-imaging (RECIP). Methods: This was an explorative, multicenter, retrospective study; 124 men with mCRPC who underwent 177Lu-PSMA treatment and received PSMA-PET/CT at baseline (bPET) and at interim after two cycles of treatment (iPET) met the eligibility criteria and were included in this analysis. The primary endpoint was overall survival (OS). Pairs of bPET and iPET were interpreted by three independent readers for appearance of new lesions. Whole-body tumor lesions were segmented using qPSMA software and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Changes in PSMA-VOL on iPET relative to bPET were calculated. After being tested separately for associations with OS, appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP. Results: The median OS was 13.5 months (95%CI, 11.6-15.4). Appearance of at least one new lesion on iPET was observed in 73 (59%) patients and was associated with poor OS (hazard ratio [HR] 2.23; 95%CI, 1.51-3.28; P 177Lu-PSMA. Validation of these findings in clinical trials is warranted.