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Purpose: Artificial intelligence can reduce the time used by physicians on radiological assessments. For 18 F-fluorodeoxyglucose-avid lymphomas, obtaining complete metabolic response (CMR) by end of treatment is prognostic., Methods: Here, we present a deep learning-based algorithm for fully automated treatment response assessments according to the Lugano 2014 classification. The proposed four-stage method, trained on a multicountry clinical trial (ClinicalTrials.gov identifier: NCT01287741) and tested in three independent multicenter and multicountry test sets on different non-Hodgkin lymphoma subtypes and different lines of treatment (ClinicalTrials.gov identifiers NCT02257567, NCT02500407; 20% holdout in ClinicalTrials.gov identifier NCT01287741), outputs the detected lesions at baseline and follow-up to enable focused radiologist review., Results: The method's response assessment achieved high agreement with the adjudicated radiologic responses (eg, agreement for overall response assessment of 93%, 87%, and 85% in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, respectively) similar to inter-radiologist agreement and was strongly prognostic of outcomes with a trend toward higher accuracy for death risk than adjudicated radiologic responses (hazard ratio for end of treatment by-model CMR of 0.123, 0.054, and 0.205 in ClinicalTrials.gov identifiers NCT01287741, NCT02500407, and NCT02257567, compared with, respectively, 0.226, 0.292, and 0.272 for CMR by the adjudicated responses). Furthermore, a radiologist review of the algorithm's assessments was conducted. The radiologist median review time was 1.38 minutes/assessment, and no statistically significant differences were observed in the level of agreement of the radiologist with the model's response compared with the level of agreement of the radiologist with the adjudicated responses., Conclusion: These results suggest that the proposed method can be incorporated into radiologic response assessment workflows in cancer imaging for significant time savings and with performance similar to trained medical experts.

The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed. Landmark analyses of progression-free survival (PFS) and overall survival (OS) by end of treatment (EOT) and end of induction (EOI) response status according to RECIL 2017 and Lugano 2014 criteria, and prognostic value of response at EOT/EOI were also compared. Overall, 1333 patients were included from GOYA and 502 from GALLIUM. Complete response (CR) status according to RECIL 2017 criteria showed high concordance with complete metabolic response (CMR) status by Lugano 2014 criteria in both GOYA (92.5%) and GALLIUM (92.4%). EOT and EOI CR/CMR status by both criteria was highly prognostic for PFS in GOYA (RECIL 2017 [CR]: hazard ratio [HR], 0.35 [95% confidence interval [CI] 0.26-0.46]; Lugano 2014 [CMR]: HR, 0.35 [95% CI 0.26-0.48]; both p  < .0001) and GALLIUM (RECIL 2017 [CR]: HR, 0.35 [95% CI 0.23-0.53]; Lugano 2014 [CMR]: HR, 0.21 [95% CI 0.14-0.31]; both p  < .0001). In conclusion, response categorization by RECIL 2017 is similar to that by Lugano 2014 criteria, with high concordance observed. Both were prognostic for PFS and OS., Competing Interests: Lale Kostakoglu is a consultant at F. Hoffmann‐La Roche Ltd, Genentech, Inc. and reports consulting and honoraria fees from F. Hoffmann‐La Roche Ltd. Maurizio Martelli has served on a consulting and advisory board and speaker's bureau for F. Hoffmann‐La Roche Ltd, Janssen, Novartis, Gilead Sciences and Sandoz; and reports travel, accommodations and other expenses from F. Hoffmann‐La Roche Ltd. Laurie H. Sehn reports research funding from F. Hoffmann‐La Roche Ltd and Genentech, Inc. and consulting and honoraria fees from F. Hoffmann‐La Roche Ltd, Genentech, Inc., AbbVie, Amgen, Apobiologix, Acerta, AstraZeneca, Celgene, Gilead Sciences, Janssen, Kite Pharma, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Takeda, Teva, TG Therapeutics and Verastem. Andrew Davies reports research funding from F. Hoffmann‐La Roche Ltd and Genentech, Inc, AstraZeneca/Acerta Pharma, MSD and consulting and honoraria fees from F. Hoffmann‐La Roche Ltd, Genentech, Inc., AbbVie, Acerta/AstraZeneca, Celgene, Genmab, Gilead Sciences, Kite Pharma and Incyte. Marek Trněný reports honoraria and consulting fees from Janssen, Gilead Sciences, Bristol‐Meyers Squibb, Amgen, AbbVie, Takeda, F. Hoffmann‐La Roche Ltd, MorphoSys and Incyte; consulting for Celgene; and travel, accommodation and other expenses from AbbVie, Gilead Sciences, Bristol‐Meyers Squibb, Takeda, F. Hoffmann‐La Roche Ltd and Janssen. Michael Herold reports a consultancy/advisory role with Celgene, Gilead and F. Hoffmann‐La Roche Ltd and research funding from F. Hoffmann‐La Roche Ltd. Umberto Vitolo reports a consulting or advisory role for Janssen, Celgene, Juno Therapeutics, Kite Pharma, Genmab and Incyte; speaker's bureau fees from F. Hoffmann‐La Roche Ltd, Janssen, Celgene, Gilead Sciences, Servier and AbbVie; research funding from Celgene; and travel, accommodations or other expenses from Celgene, F. Hoffmann‐La Roche Ltd and AbbVie. Wolfgang Hiddemann reports honoraria from F. Hoffmann‐La Roche Ltd, Janssen, Gilead Sciences and Celgene; a consulting/advisory role for F. Hoffman‐La Roche Ltd, Janssen and Gilead Sciences; speakers’ bureau for F. Hoffmann‐La Roche Ltd, Janssen and Gilead Sciences; research funding from F. Hoffmann‐La Roche Ltd, Janssen and Bayer; and travel expenses/accommodation from F. Hoffmann‐La Roche Ltd, Janssen and Gilead Sciences. Judith Trotman reports research funding from F. Hoffmann‐La Roche Ltd, BMS, BeiGene, Pharmacyclics, Janssen and Cellectar. Andrea Knapp is employed by and has equity ownership interests in F. Hoffmann‐La Roche Ltd. Federico Mattiello is an employee of F. Hoffmann‐La Roche Ltd. Tina G. Nielsen is an employee and stockholder of F. Hoffmann‐La Roche Ltd. Deniz Sahin is an employee and stockholder of F. Hoffmann‐La Roche Ltd. Gila Sellam is an employee and stockholder of F. Hoffmann‐La Roche Ltd. Carol Ward is an employee and stockholder of F. Hoffmann‐La Roche Ltd. Anas Younes is employed by and has stock and other ownership interests in AstraZeneca; has received honoraria from Merck, F. Hoffmann‐La Roche Ltd, Takeda, Janssen, AbbVie, Curis and Epizyme; reports a consulting or advisory role with Bio‐Path Holdings Inc, Xynomic Pharma, Epizyme, F. Hoffmann‐La Roche Ltd, Celgene and HCM; has received research funding from Janssen, Curis, F. Hoffmann‐La Roche Ltd, Genentech, Inc., Merck, Bristol‐Myers Squibb, Syndax; and other relationship with AstraZeneca., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease., Methods: Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation., Results: Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04)., Conclusion: Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.

Aggressive large B-cell lymphoma (LBCL) has variable outcomes. Current prognostic tools use factors for risk stratification that inadequately identify patients at high risk of refractory disease or relapse before initial treatment. A model associating 2 risk factors, total metabolic tumor volume (TMTV) >220 cm3 (determined by fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography) and performance status (PS) ≥2, identified as prognostic in 301 older patients in the REMARC trial (#NCT01122472), was validated in 2174 patients of all ages treated in 2 clinical trials, PETAL (Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas; N = 510) and GOYA (N = 1315), and in real-world clinics (N = 349) across Europe and the United States. Three risk categories, low (no factors), intermediate (1 risk factor), and high (2 risk factors), significantly discriminated outcome in most of the series. Patients with 2 risk factors had worse outcomes than patients with no risk factors in the PETAL, GOYA, and real-world series. Patients with intermediate risk also had significantly worse outcomes than patients with no risk factors. The TMTV/Eastern Cooperative Oncology Group-PS combination outperformed the International Prognostic Index with a positive C-index for progression-free survival and overall survival in most series. The combination of high TMTV > 220 cm3 and ECOG-PS ≥ 2 is a simple clinical model to identify aggressive LBCL risk categories before treatment. This combination addresses the unmet need to better predict before treatment initiation for aggressive LBCL the patients likely to benefit the most or not at all from therapy., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

This study's focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint.

Background: Current radiological assessments of 18 fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment., Methods: Our aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422)., Results: Our AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31-2.67) vs 1.38 (95% CI: 0.98-1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37-3.40) vs 1.40 (95% CI: 0.90-2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%., Conclusion: Our tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients., Trial Registration: Registered clinicaltrials.gov number: NCT01287741., (© 2022. The Author(s).)

Introduction: A good response to initial therapy is key to maximizing survival in patients with diffuse large B-cell lymphoma (DLBCL), but patients with chemorefractory disease and early progression have poor outcomes., Patients and Methods: Data from the GOYA study in patients with DLBCL who received first-line rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were analyzed. Positron emission tomography/computed tomography (PET/CT)-derived characteristics associated with total metabolic tumor volume (TMTV) and clinical risk factors for primary chemorefractory disease and disease progression within 12 months (POD12) were explored., Results: Of those patients fulfilling the criteria for analysis, 108/1126 (10%) were primary chemorefractory and 147/1106 (13%) had POD12. Primary chemorefractory and POD12 status were strongly associated with reduced overall survival. After multivariable analysis of clinical and imaging-based risk factors by backward elimination, only very high TMTV (quartile [Q] 1 vs. Q4 odds ratio [OR]: 0.45; P = .006) and serum albumin levels (low vs. normal OR of 1.86; P = .004) were associated with primary chemorefractoriness. After additionally accounting for BCL2/MYC translocation in a subset of patients, TMTV and BCL2/MYC double-hit status remained as significant predictors of primary chemorefractoriness (Q1 vs. Q4 OR: 0.32, P = .01 and double-hit vs. no-hit OR of 4.47, P = .02, respectively). Risk factors including very high TMTV, high sum of the product of the longest diameters (SPD), geographic region (Asia), short time since diagnosis, extranodal involvement and low serum albumin were retained for POD12., Conclusion: PET-derived TMTV has prognostic value in identifying patients at risk of early treatment failure., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Complete metabolic response (CMR) on PET/CT was the sole independent predictor of overall survival in the PET substudy of the phase III GALLIUM trial (NCT01332968) in first-line treatment of high-tumor-burden follicular lymphoma. The aim of this analysis was to further investigate the outcome of patients not achieving CMR. Methods: Two international experts rereviewed PET/CT scans from patients failing to achieve CMR assessed by the Independent Review Committee masked otherwise to committee results. Metabolic response category and Deauville score were assigned. Progression-free survival (PFS) was investigator-assessed with contrast-enhanced CT. Kaplan-Meier methodology was used to estimate landmark PFS and time to next treatment from end of induction by Deauville score. Patients who experienced CT-based progressive disease at the end of induction were excluded. Results: Fifty-four patients were reviewed. Six had CMR, 37 had a partial metabolic response, 2 had no metabolic response, and 9 had progressive metabolic disease. Patients were reassigned to CMR because 18 F-FDG uptake was considered inflammatory ( n  = 2), was considered incidental neoplasia ( n  = 2), or was visually close to liver uptake but quantitatively lower ( n  = 2). There was a trend for shorter PFS and time to next treatment for patients with a Deauville score of 5 than a score of 4. High-grade mesenteric uptake at the end of induction was common, occurring in 20 patients with non-CMR, 14 of whom achieved CMR at all other sites. Only 3 of 14 (21%) patients with mesenteric uptake as the only site of disease experienced progression or death within 24 mo, whereas 4 of 6 patients (67%) with mesenteric and additional sites of 18 F-FDG-avid disease experienced progression or death within 24 mo. All patients with early progression had measurable disease on contrast-enhanced CT at 18 F-FDG-avid sites at the end of induction. Conclusion: After induction immunochemotherapy, CMR was assigned after reassessment in some patients, in whom increased 18 F-FDG uptake was considered due to inflammation or incidental neoplasia rather than to lymphoma. Quantitative assessment to confirm the visual impression of residual uptake in lesions is suggested. Isolated mesenteric 18 F-FDG uptake is likely a common false-positive finding at the end of induction and does not warrant changes in clinical management or disease surveillance unless there is measurable disease on contrast-enhanced CT or clinical suspicion of active disease., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

This retrospective analysis of the phase III GOYA study investigated the prognostic value of baseline metabolic tumor volume parameters and maximum standardized uptake values for overall and progression-free survival (PFS) in treatment-naïve diffuse large B-cell lymphoma. Baseline total metabolic tumor volume (determined for tumors >1 mL using a threshold of 1.5 times the mean liver standardized uptake value +2 standard deviations), total lesion glycolysis, and maximum standardized uptake value positron emission tomography data were dichotomized based on receiver operating characteristic analysis and divided into quartiles by baseline population distribution. Of 1,418 enrolled patients, 1,305 had a baseline positron emission tomography scan with detectable lesions. Optimal cut-offs were 366 cm3 for total metabolic tumor volume and 3,004 g for total lesion glycolysis. High total metabolic tumor volume and total lesion glycolysis predicted poorer PFS, with associations retained after adjustment for baseline and disease characteristics (high total metabolic tumor volume hazard ratio: 1.71, 95% confidence interval [CI]: 1.35- 2.18; total lesion glycolysis hazard ratio: 1.46; 95% CI: 1.15-1.86). Total metabolic tumor volume was prognostic for PFS in subgroups with International Prognostic Index scores 0-2 and 3-5, and those with different cell-of-origin subtypes. Maximum standardized uptake value had no prognostic value in this setting. High total metabolic tumor volume associated with high International Prognostic Index or non-germinal center B-cell classification identified the highest-risk cohort for unfavorable prognosis. In conclusion, baseline total metabolic tumor volume and total lesion glycolysis are independent predictors of PFS in patients with diffuse large B-cell lymphoma after first-line immunochemotherapy.

Image texture analysis (radiomics) uses radiographic images to quantify characteristics that may identify tumour heterogeneity and associated patient outcomes. Using fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT)-derived data, including quantitative metrics, image texture analysis and other clinical risk factors, we aimed to develop a prognostic model that predicts survival in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) from GOYA (NCT01287741). Image texture features and clinical risk factors were combined into a random forest model and compared with the international prognostic index (IPI) for DLBCL based on progression-free survival (PFS) and overall survival (OS) predictions. Baseline FDG-PET scans were available for 1263 patients, 832 patients of these were cell-of-origin (COO)-evaluable. Patients were stratified by IPI or radiomics features plus clinical risk factors into low-, intermediate- and high-risk groups. The random forest model with COO subgroups identified a clearer high-risk population (45% 2-year PFS [95% confidence interval (CI) 40%-52%]; 65% 2-year OS [95% CI 59%-71%]) than the IPI (58% 2-year PFS [95% CI 50%-67%]; 69% 2-year OS [95% CI 62%-77%]). This study confirms that standard clinical risk factors can be combined with PET-derived image texture features to provide an improved prognostic model predicting survival in untreated DLBCL., Competing Interests: LK is a consultant at F. Hoffmann‐La Roche Ltd, Genentech, Inc., and reports travel, accommodations and other expenses to F. Hoffmann‐La Roche Ltd. LAP reports equity ownership in Precision Sensing LLC. UV reports a consulting or advisory role for Janssen, Celgene, Juno Therapeutics and Kite Pharma; speaker's bureau fees from F. Hoffmann‐La Roche Ltd, Janssen, Celgene, Gilead Sciences, Servier and AbbVie; research funding from Celgene; and travel, accommodations or other expenses from Celgene, F. Hoffmann‐La Roche Ltd and AbbVie. MM has served on a consulting and advisory board and speaker's bureau for F. Hoffmann‐La Roche Ltd, Janssen, Novartis, Gilead Sciences and Sandoz; and reports travel, accommodations and other expenses from F. Hoffmann‐La Roche Ltd. LHS reports research funding from F. Hoffmann‐La Roche Ltd and Genentech, Inc. and consulting and honoraria fees from F. Hoffmann‐La Roche Ltd, Genentech, Inc., AbbVie, Amgen, Apobiologix, Acerta, AstraZeneca, Celgene, Gilead Sciences, Janssen, Kite Pharma, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Takeda, Teva, TG Therapeutics and Verastem. MT reports honoraria and consulting fees from Janssen, Gilead Sciences, Bristol‐Meyers Squibb, Amgen, AbbVie, Takeda, F. Hoffmann‐La Roche Ltd, MorphoSys and Incyte; consulting for Celgene; and travel, accommodation and other expenses from AbbVie, Gilead Sciences, Bristol‐Meyers Squibb, Takeda, F. Hoffmann‐La Roche Ltd and Janssen. TGN is an employee and stockholder of F. Hoffmann‐La Roche Ltd. CRB is an employee of Genentech, Inc. and stockholder of F. Hoffmann‐La Roche Ltd. DS is an employee and stockholder of F. Hoffmann‐La Roche Ltd. CL is an employee of Genentech, Inc. TCE‐G is a former employee of F. Hoffmann‐La Roche Ltd and reports speaker fees for AbbVie. FM is an employee of F. Hoffmann‐La Roche Ltd. SC reports research funding from F. Hoffmann‐La Roche Ltd. and honoraria fees from Sirtex Medical. FD, PB and PEK have declared no conflict of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [ 18 F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [ 18 F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [ 18 F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI., (© 2020. The Author(s).)

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim-18F-FDG-PET, hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-cell lymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determine the optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL. Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects of timing and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using ΔSUVmax, respectively. ΔSUVmax identified a larger proportion of poor responders than DS5 did. For all criteria, the negative predictive value was >80%, and positive predictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3 discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs, 2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOP therapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Good response at I-PET2 is suggested for de-escalation trials, and poor response using ΔSUVmax at I-PET4 is suggested for randomized trials that are evaluating new therapies., (© 2021 by The American Society of Hematology.)

Purpose: Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell-like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL., Patients and Methods: Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS)., Results: Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell-like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1., Conclusion: In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL., Competing Interests: Grzegorz S. NowakowskiConsulting or Advisory Role: Celgene/BMS, MorphoSys, Genentech, Roche Selvita, Debiopharm Group, Kite/Gilead, Karyopharm TherapeuticsResearch Funding: Celgene/BMS, NanoString Technologies, MorphoSys Roche, Seattle Genetics Fangxin HongConsulting or Advisory Role: Merck Sharp & Dohme David W. ScottConsulting or Advisory Role: Celgene/BMS, Janssen, AbbVie, AstraZenecaResearch Funding: Janssen, Roche/Genentech, NanoString TechnologiesPatents, Royalties, Other Intellectual Property: Named inventor on a pending patent describing gene expression profiling in prognostication in classical Hodgkin lymphoma, As a member of the LLMPP I am potentially a named inventor on a pending patent on the use of gene expression profiling to assign cell-of-origin in diffuse large B-cell lymphoma, I am a named inventor on a pending patent on the use of gene expression profiling to determine the proliferation signature in mantle cell lymphoma, Named inventor on a pending patent describing using gene expression profiling to identify molecular subtypes of GCB-DLBCL Rebecca L. KingResearch Funding: Celgene/BMS Thomas M. HabermannConsulting or Advisory Role: Celgene/BMS, Kite/Gilead Nina Wagner-JohnstonConsulting or Advisory Role: ADC Therapeutics, Bayer, Regeneron, Calibr, Verastem, Gilead SciencesResearch Funding: Merck, Novartis/Pfizer, Genentech, Astex Pharmaceuticals, Juno Therapeutics, Regeneron, Acerta Pharma, ADC Therapeutics Carla CasuloHonoraria: Gilead SciencesResearch Funding: Celgene/BMS, Verastem, Gilead SciencesTravel, Accommodations, Expenses: Gilead Sciences, Roche James L. WadeEmployment: Johnson & JohnsonStock and Other Ownership Interests: Celgene/BMS, Abbott, GlaxoSmithKline, Johnson & Johnson, NovartisConsulting or Advisory Role: New Century Health Jonathon B. CohenConsulting or Advisory Role: Celgene/BMS, Seattle Genetics, Abbvie, Janssen, Loxo, Kite/Gilead, AstraZeneca, Cellectar, Aptitude MedicalResearch Funding: Bristol-Myers Squibb, Janssen, Novartis, Takeda, AI Therapeutics, Genentech, ASH, Lymphoma Research Foundation, Loxo, Bioinvent, AstraZeneca Nadia KhanHonoraria: JanssenConsulting or Advisory Role: IncyteResearch Funding: Bristol-Myers Squibb Jennifer E. AmengualHonoraria: Janssen, Daiichi Sankyo, Karyopharm TherapeuticsResearch Funding: Appia PharmaceuticalsTravel, Accommodations, Expenses: Epizyme John P. LeonardConsulting or Advisory Role: Celgene/BMS, Bristol-Myers Squibb, Gilead Sciences, Epizyme, Bayer, Genentech/Roche, ADC Therapeutics, MEI Pharma, AstraZeneca, Merck, Morphosys, Nordic Nanovector, Karyopharm Therapeutics, Sutter Medical Group, Miltenyi Biotec, Regeneron, Bayer, Akcea Therapeutics, Sandoz, Nordic Nanovector, Genmab, Abbvie, IncyteResearch Funding: Research Funding: Celgene/BMS, Alliance for Clinical Trials in Oncology, Takeda, Pfizer, National Cancer Institute, Janssen Oncology, EpizymeTravel, Accommodations, Expenses: BeiGene Jonathan W. FriedbergConsulting or Advisory Role: Astellas Pharma, NovartisResearch Funding: Seattle GeneticsPatents, Royalties, Other Intellectual Property: Patient on bone marrow microenvironment signals Lale KostakogluConsulting or Advisory Role: Roche/Genentech Brad S. KahlConsulting or Advisory Role: Celgene/BMS, Juno Therapeutics, Abbvie, Pharmacyclics, Acerta Pharma, ADC Therapeutics, Pharmacyclics, Genentech, Roche, AstraZeneca, BeiGene, Bayer, MEI Pharma, TG Therapeutics, Kite/Gilead, MorphoSys, JanssenResearch Funding: Genentech, Acerta Pharma, ADC Therapeutics, Celgene/BMSTravel, Accommodations, Expenses: Celgene/BMS, Juno Therapeutics, Genentech/Roche, Abbvie, Millennium, Seattle Genetics Thomas E. WitzigConsulting or Advisory Role: Karyopharm Therapeutics, Abbvie/Genentech, Seattle Genetics, Celgene/BMS, Incyte, Epizyme, Cellectar, Tessa Therapeutics, Portola Pharmaceuticals, MorphoSys, ADC TherapeuticsResearch Funding: Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm TherapeuticsPatents, Royalties, Other Intellectual Property: T.E.W. is co-inventor on a patent application filed by Mayo Clinic and pending on the combination of CRM1 inhibitors with salicylates.No other potential conflicts of interest were reported.

GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)-based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP. Patients received a mandatory fluoro-2-deoxy-d-glucose-PET/computed tomography scan at baseline and end of treatment. After a median follow-up of 29 months, the numbers of independent review committee-assessed PFS and OS events in the entire cohort were 416 (29.3%) and 252 (17.8%), respectively. End-of-treatment PET CR was highly prognostic for PFS and OS according to Lugano 2014 criteria (PFS: hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.19-0.38; P < .0001; OS: HR, 0.12; 95% CI, 0.08-0.17; P < .0001), irrespective of international prognostic index score and cell of origin. In conclusion, the results from this prospectively acquired large cohort corroborated previously published data from smaller sample sizes showing that end-of-treatment PET CR is an independent predictor of PFS and OS and a promising prognostic marker in DLBCL. Long-term survival analysis confirmed the robustness of these data over time. Additional meta-analyses including other prospective studies are necessary to support the substitution of PET CR for PFS as an effective and practical surrogate end point. This trial was registered at www.clinicaltrials.gov as #NCT01287741., (© 2021 by The American Society of Hematology.)

Segmentation of lymphoma lesions in FDG PET/CT images is critical in both assessing individual lesions and quantifying patient disease burden. Simple thresholding methods remain common despite the large heterogeneity in lymphoma lesion location, size, and contrast. Here, we assess 11 automated PET segmentation methods for their use in two scenarios: individual lesion segmentation and patient-level disease quantification in lymphoma. Lesions on 18 F-FDG PET/CT scans of 90 lymphoma patients were contoured by a nuclear medicine physician. Thresholding, active contours, clustering, adaptive region-growing, and convolutional neural network (CNN) methods were implemented on all physician-identified lesions. Lesion-level segmentation was evaluated using multiple segmentation performance metrics (Dice, Hausdorff Distance). Patient-level quantification of total disease burden (SUV total ) and metabolic tumor volume (MTV) was assessed using Spearman's correlation coefficients between the segmentation output and physician contours. Lesion segmentation and patient quantification performance was compared to inter-physician agreement in a subset of 20 patients segmented by a second nuclear medicine physician. In total, 1223 lesions with median tumor-to-background ratio of 4.0 and volume of 1.8 cm 3 , were evaluated. When assessed for lesion segmentation, a 3D CNN, DeepMedic, achieved the highest performance across all evaluation metrics. DeepMedic, clustering methods, and an iterative threshold method had lesion-level segmentation performance comparable to the degree of inter-physician agreement. For patient-level SUV total and MTV quantification, all methods except 40% and 50% SUV max and adaptive region-growing achieved a performance that was similar the agreement of the two physicians. Multiple methods, including a 3D CNN, clustering, and an iterative threshold method, achieved both good lesion-level segmentation and patient-level quantification performance in a population of 90 lymphoma patients. These methods are thus recommended over thresholding methods such as 40% and 50% SUV max , which were consistently found to be significantly outside the limits defined by inter-physician agreement.

Purpose: To automatically detect lymph nodes involved in lymphoma on fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET/CT images using convolutional neural networks (CNNs)., Materials and Methods: In this retrospective study, baseline disease of 90 patients with lymphoma was segmented on 18 F-FDG PET/CT images (acquired between 2005 and 2011) by a nuclear medicine physician. An ensemble of three-dimensional patch-based, multiresolution pathway CNNs was trained using fivefold cross-validation. Performance was assessed using the true-positive rate (TPR) and number of false-positive (FP) findings. CNN performance was compared with agreement between physicians by comparing the annotations of a second nuclear medicine physician to the first reader in 20 of the patients. Patient TPR was compared using Wilcoxon signed rank tests., Results: Across all 90 patients, a range of 0-61 nodes per patient was detected. At an average of four FP findings per patient, the method achieved a TPR of 85% (923 of 1087 nodes). Performance varied widely across patients (TPR range, 33%-100%; FP range, 0-21 findings). In the 20 patients labeled by both physicians, a range of 1-49 nodes per patient was detected and labeled. The second reader identified 96% (210 of 219) of nodes with an additional 3.7 per patient compared with the first reader. In the same 20 patients, the CNN achieved a 90% (197 of 219) TPR at 3.7 FP findings per patient., Conclusion: An ensemble of three-dimensional CNNs detected lymph nodes at a performance nearly comparable to differences between two physicians' annotations. This preliminary study is a first step toward automated PET/CT assessment for lymphoma.© RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: A.J.W. Activities related to the present article: disclosed money paid to institution for research support by GE Healthcare. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. M.W.K. disclosed no relevant relationships. S.B.P. disclosed no relevant relationships. M.H. disclosed no relevant relationships. R.J. Activities related to the present article: disclosed grant money paid to institution by the National Cancer Institute, in part supported by the UW Carbone Cancer Center. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed patent issued by WARF and patent pending with AIQ Solutions. L.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money paid for consultancy by Roche, Genentech. Other relationships: disclosed no relevant relationships. T.J.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: institution receives research support from GE Healthcare., (2020 by the Radiological Society of North America, Inc.)

As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.

The utility of posttreatment bone marrow biopsy (BMB) histology to confirm complete response (CR) in lymphoma clinical trials is in question. We retrospectively evaluated the impact of BMB on response assessment in immunochemotherapy-treated patients with previously untreated follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the phase 3 Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM; NCT01332968) and A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA; NCT01287741) trials, respectively. Baseline BMB was performed in all patients, with repeat BMBs in patients with a CR by computed tomography (CT) at end of induction (EOI) and a positive BMB at baseline, to confirm response. Positron emission tomography imaging was also used in some patients to assess EOI response (Lugano 2014 criteria). Among patients with an EOI CR by CT in GALLIUM and GOYA, 2.8% and 4.1%, respectively, had a BMB-altered response. These results suggest that postinduction BMB histology has minimal impact on radiographically (CT)-defined responses in both FL and DLBCL patients. In GALLIUM and GOYA, respectively, 4.7% of FL patients and 7.1% of DLBCL patients had a repeat BMB result that altered response assessment when applying Lugano 2014 criteria, indicating that bone marrow evaluation appears to add little value to response assessment in FL; however, its evaluation may still have merit in DLBCL., (© 2020 by The American Society of Hematology.)

Lymphoma is a potentially curable disease; however, the clinical challenge lies in further improvement of outcomes. PET with fludeoxyglucose is an effective imaging tool. PET-derived quantitative metrics have raised significant interest to be used as a prognostic factor to complement clinical parameters for treatment decisions. The most optimized use of these quantitative PET metrics, however, will be possible with the standardization of imaging procedures. In this article, we review the technical and methodological considerations related to PET-derived quantitative metrics, and the relevant published data to emphasize the potential value of these metrics in patient prognosis and treatment response in lymphoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

"PET imaging with fluorodeoxyglucose (FDG), integrated with PET/computed tomography (FDG-PET/CT), is an effective management tool of diffuse large B-cell lymphoma (DLBCL). The results of end-of-treatment (EOT) FDG-PET/CT are more accurate for detection of active disease with residual masses on CT. Complete response defined by EOT FDG-PET/CT (PET-CR) correlates with long-term outcome of patients. Treatment efficacy is determined using EOT PET/CT rather than progression-free survival (PFS) for clinical trials assessing novel drugs. If the correlation of EOT PET/CT with PFS is further proven in large studies and meta-analyses, EOT PET-CR could serve as an expedited novel endpoint replacing PFS.", (Copyright © 2019 Elsevier Inc. All rights reserved.)

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity 131 I-meta-iodobenzylguanidine (HSA 131 I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA 131 I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131 I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131 I-MIBG, 17 (25%; 95% confidence interval, 16%-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9-49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA 131 I-MIBG. Conclusion: HSA 131 I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: The prospective, multicenter LOCATE (F Fluciclovine [FACBC] PET/CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent., Materials and Methods: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other., Results: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%)., Conclusions: F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.

Objective: The aim of our study was to compare yttrium -90 ( 90 Y) dosimetry obtained from pre-therapy 99m Tc-macroaggregated albumin (MAA) SPECT/CT versus post-therapy PET/MRI imaging among patients with primary or metastatic hepatic tumors., Materials and Methods: Prior to 90 Y radioembolization (RE), 32 patients underwent a scan using MAA mimicking 90 Y distribution. After RE with 90 Y microspheres, the patients were imaged on a PET/MRI system. Reconstructed images were transferred to a common platform and used to calculate 90 Y dosimetry. The Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between dosimetry values., Results: For MAA and PET/MRI modalities, the mean liver doses for all 32 subjects were 43.0 ± 20.9 Gy and 46.5 ± 22.7 Gy, respectively, with a mean difference of 3.4 ± 6.2 Gy. The repeatibility coefficient was 12.1 (27.0% of the mean). The Spearman rank correlation coefficient was high (ρ = 0.92). Although, there was a substantial difference in the maximum doses to the liver between the modalities, the mean liver doses were relatively close, with a difference of 24.0% or less., Conclusions: The two main contributors to the difference between dosimetry calculations using MAA versus 90 Y PET/MRI can be attributed to the changes in catheter positioning as well as the liver ROIs used for the calculations. In spite of these differences, our results demonstrate that the dosimetry values obtained from pre-therapy MAA SPECT/CT scans and PET/MRI post-therapy 90 Y studies were not significantly different., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: The purpose of the study was to assess the feasibility and diagnostic performance of FDG-PET/MR imaging compared to PET/CT for staging of patients with a gynecological malignancy., Methods: 25 patients with a gynecological malignancy were prospectively enrolled into this pilot study. Patients underwent sequential full-body PET/CT and PET/MR of the abdomen and pelvis after administration of a single dose of F-18 FDG. PET/MRI and PET/CT images were independently reviewed by two expert radiologists. Readers were blinded to the results of the other imaging procedures. Clinical and pathologic information was abstracted from medical charts., Results: 18 patients were included in the final analysis with a median age of 62 years (range 31-88). 61% of patients (11/18) had cervical cancer, while the remaining patients had endometrial cancer. PET/MRI as compared to PET/CT detected all primary tumors, 7/7 patients with regional lymph nodes, and 1/1 patient with an abdominal metastasis. Two patients had additional lymph nodes outside of the abdominopelvic cavity detected on PET/CT that were not seen on PET/MRI, whereas 6 patients had parametrial invasion and one patient had invasion of the bladder seen on PET/MRI not detected on PET/CT. Five cervical cancer patients had discordant clinical vs. radiographic staging based on PET/MRI detection of soft tissue involvement. Management changed for two patients who had clinical stage IB1 and radiographic stage IIB cervical cancer., Conclusions: PET/MRI is feasible and has at least comparable diagnostic ability to PET/CT for identification of primary cervical and endometrial tumors and regional metastases. PET/MRI may be superior to PET/CT for initial radiographic assessment of cervical cancers.

Purpose: To assess the feasibility of using CT to correct specific uptake values (SUVs) for fluorodeoxyglucose (FDG) in patients with nonsolid nodules., Methods: Patients with FDG-PET/CT and thin-section CT were included in this pilot study. Thirty-five adenocarcinomas manifesting as nonsolid nodules were classified into two groups; 90-100% and 1-89% lepidic component. SUVmax was corrected based on the CT determination of the proportion of soft tissue component within the cancer (SUVatt)., Results: Both SUVmax and SUVatt increased as the percentage of the lepidic component decreased. SUVmax and SUVatt were significantly different between the groups., Conclusion: Extent of invasiveness of nonsolid cancers (as a marker of aggressiveness) can potentially be quantified by PET/CT using a correction method that accounts for the proportion of soft tissue within the tumor., (Copyright © 2018. Published by Elsevier Inc.)

A negative interim positron emission tomography/computerized tomography (PET/CT) after 1 to 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with newly diagnosed, nonbulky stage I or II Hodgkin lymphoma (HL) predicts a low relapse rate. This phase 2 trial was designed to determine if a population of patients with early-stage disease can be treated with short-course ABVD without radiation therapy (RT) on the basis of a negative interim PET/CT, thereby limiting the risks of treatment. Between 15 May 2010 and 21 February 2013, 164 previously untreated patients with nonbulky stage I/II HL were enrolled, and 149 were included in the final analysis. Patients received 2 cycles of ABVD followed by PET. Deauville scores 1 to 3 were negative (≤ liver uptake) based on central review. PET - patients received 2 more cycles of ABVD, and PET + patients received 2 cycles of dose-intense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus 3060-cGy involved-field RT. The primary objective was to determine 3-year progression-free survival (PFS) for the PET - group. One hundred thirty-five patients (91%) were interim PET - , and 14 patients (9%) were PET + With median follow-up time of 3.8 years, the estimated 3-year PFS was 91% for the PET - group and 66% for the PET + group (hazard ratio, 3.84; 95% confidence interval, 1.50-9.84; P = .011). There was 1 death as a result of suicide. Four cycles of ABVD resulted in durable remissions for a majority of patients with early-stage nonbulky HL and a negative interim PET. This trial was registered at www.clinicaltrials.gov as #NCT01132807., (© 2018 by The American Society of Hematology.)

Background: The aim of our study was to compare 90 Y dosimetry obtained from PET/MRI versus PET/CT post-therapy imaging among patients with primary or metastatic hepatic tumors. First, a water-filled Jaszczak phantom containing fillable sphere with 90 Y-chloride was acquired on both the PET/CT and PET/MRI systems, in order to check the cross-calibration of the modalities. Following selective internal radiation therapy (SIRT) with 90 Y microspheres, 32 patients were imaged on a PET/CT system, immediately followed by a PET/MRI study. Reconstructed images were transferred to a common platform and used to calculate 90 Y dosimetry. A Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between the dosimetry values., Results: The phantom study showed that both modalities were calibrated with less than 1% error. The mean liver doses for the 32 subjects calculated from PET/CT and PET/MRI were 51.6 ± 24.7 Gy and 46.5 ± 22.7 Gy, respectively, with a mean difference of 5.1 ± 5.0 Gy. The repeatability coefficient was 9.0 (18.5% of the mean). The Spearman rank correlation coefficient was very high, ρ = 0.97. Although the maximum dose to the liver can be significantly different (up to 40%), mean liver doses from each modalities were relatively close, with a difference of 18.5% or less., Conclusions: The two main contributors to the difference in 90 Y dosimetry calculations using PET/CT versus PET/MRI can be attributed to the differences in regions of interest (ROIs) and differences attributed to attenuation correction. Due to the superior soft-tissue contrast of MRI, liver contours are usually better seen than in CT images. However, PET/CT provides better quantification of PET images, due to better attenuation correction. In spite of these differences, our results demonstrate that the dosimetry values obtained from PET/MRI and PET/CT in post-therapy 90 Y studies were similar.

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Sorensen has been an employee of Siemens Medical Solutions from 2011-2016, and is currently a board member of IMRIS (includes equity stake). He also has two patents assigned to MGH (US patent # 8,698,496 and US patent # 7,512,435). Dr. Andronesi has one patent (US patent #8,698,496). Dr. Schmainda has an ownership interest in Imaging Biometrics LLC. Dr. Barboriak is a member of the GE Medical systems Neuro MRI Advisory Committee. Dr. Mankoff is an advisory for GE Healthcare. Dr. Ratai is a member on the advisory board for BrainSpec, Inc. Erin Greco is currently employed at Novartis Institutes for BioMedical Research, Cambridge, MA, United States. All other authors declare no conflicts of interest. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Background/aim: Current guidelines derived from a pre-human papilloma virus (HPV) era in oropharyngeal cancer do not recommend routine surveillance imaging. We aimed to analyze the method of recurrence detection in HPV+ disease to determine a role for follow-up imaging., Patients and Methods: All HPV+ and HPV- oropharyngeal cancer patients treated at our institution from 2005-2016 with biopsy-proven recurrence were identified and their method of recurrence detection was analyzed., Results: A total of 16 HPV+ oropharyngeal cancer patients were identified to have recurrence, 12 (75%) of which experienced distant recurrence and 13 (81.3%) were detected asymptomatically with imaging at a median time of 19.7 months after initial treatment and verifying no residual disease. Twelve (75%) detections were with PET-CT. While HPV- patients (17 patients) also have a high rate of asymptomatic detection (16 patients, 94.1%), their 3-year post-recurrence survival was significantly lower at 6.5% compared to 83.6% for the HPV+ group (p<0.01)., Conclusion: In HPV+ patients, a large proportion of failures are asymptomatic distant metastases, which occur beyond 6 months following treatment completion, and are detected with whole body imaging alone. In light of long term post-recurrence survival observed, this preliminary data suggests that routine surveillance imaging should be further studied for HPV+ disease., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although visual assessment using the Deauville criteria is strongly recommended by guidelines for treatment response monitoring in all FDG-avid lymphoma histologies, the high rate of false-positives and concerns about interobserver variability have motivated the development of quantitative tools to facilitate objective measurement of tumor response in both routine and clinical trial settings. Imaging studies using functional quantitative measures play a significant role in profiling oncologic processes. These quantitative metrics allow for objective end points in multicenter clinical trials. However, the standardization of imaging procedures including image acquisition parameters, reconstruction and analytic measures, and validation of these methods are essential to enable an individualized treatment approach. A robust quality control program associated with the inclusion of proper scanner calibration, cross-calibration with dose calibrators and across other scanners is required for accurate quantitative measurements. In this section, we will review the technical and methodological considerations related to PET-derived quantitative metrics and the relevant published data to emphasize the potential value of these metrics in the prediction of patient prognosis in lymphoma., (Copyright © 2017. Published by Elsevier Inc.)

Amyloid positron emission tomography (PET) imaging with florbetapir 18 F ( 18 F-AV-45) allows in vivo assessment of cerebral amyloid load and can be used in the evaluation of progression of Alzheimer's disease (AD) and other dementias associated with b-amyloid. However, cortical amyloid deposition can occur in healthy cases, as well as in patients with AD and quantification of cortical amyloid burden can improve the 18 F-AV-45 PET imaging evaluations. The quantification is mostly performed by cortical-to-cerebellum standardized uptake value ratio (SUVr). The aim of our study was to compare two methods for SUVr calculations in amyloid florbetapir 18 F PET brain imaging. In amyloid florbetapir 18 F PET brain imaging study, we imaged 42 cases with the mean age of 72.6 ± 9.9 (mean ± standard deviation). They were imaged on different PET/computed tomography systems with 369.0 ± 34.2 kBq of 18 F florbetapir. Data were reconstructed using the vendor's reconstruction software. Corresponding magnetic resonance imaging (MRI) data were retrieved, and matched PET and MRI data were transferred to a common platform. Two methods were used for the calculation of the ratio of cortical-to-cerebellar signal (SUVr). One method was based on the MIM Software Inc., Version 6.4 software and only uses PET data. The second approach used the PMOD Neuro tool (version 3.5). This approach utilizes PET and corresponding MRI data (preferably T1-weighted) for better brain segmentation. For all the 42 cases, the average SUVr values for MIM and PMOD applications were 1.24 ± 0.26 and 1.22 ± 0.25, respectively, with a mean difference of 0.02 ± 0.15. The repeatability coefficient was 0.15 (12.3% of the mean). The Spearman's rank correlation coefficient was very high, r = 0.96. For amyloid-negative cases, the average SUVr values were lower than all group SUVr average values, 0.96 ± 0.07 and 1.00 ± 0.09, for MIM and PMOD applications, respectively. A mean difference was 0.04 ± 0.12, the repeatability coefficient was 0.12 (12.9% of the mean) and the Spearman's rank correlation coefficient was modest, r = 0.55. For amyloid-positive patients, the average SUVr values were higher than the same all group values, 1.34 ± 0.16 and 1.35 ± 0.20, respectively, with a mean difference of 0.01 ± 0.16. The repeatability coefficient was 0.16 (11.9% of the mean). The Spearman's rank correlation coefficient was high, r = 0.93. Our results indicated that the SUVr values derived using MIM and PMOD Neuro are effectively interchangeable and well correlated. However, PET template-based quantification (MIM approach) is clinically friendlier and easier to use. MRI template-based quantification (PMOD Neuro) better delineates different regions of the brain, can be used with any tracer, and therefore is more suitable for research., Competing Interests: There are no conflicts of interest.

18 F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to 18 F-fluciclovine could interpret 18 F-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. Methods: 18 F-Fluciclovine PET/CT images ( n = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of 18 F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Results: Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate region; and 83.3%, 75.0%, and 83.3% in the extraprostatic region for readers 1, 2, and 3, respectively. Concordance between the BIE and the onsite reader exceeded 75% for each reader at the lesion, region, and subject levels. Conclusion: Specific training in the use of standardized interpretation methodology for assessment of 18 F-fluciclovine PET/CT images enables naïve readers to achieve acceptable diagnostic performance and reproducibility when staging recurrent prostate cancer., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

An exploratory analysis of 75 follicular lymphoma patients treated with obinutuzumab or rituximab induction therapy (IT) for 4 weeks in the phase II GAUSS study aimed to determine whether positron emission tomography (PET) results could predict progression-free survival (PFS) and tumor response. The proportion of patients with a PFS event (progression or death) was higher in those who were PET-positive after IT (assessed using Deauville five-point scale criteria; 35/52, 67%) than PET-negative (5/20, 25%); the hazard ratio for progression or death was 0.25 (95%CI: 0.01-0.64; p = 0.0018). A significant association was also found when PET results were assessed using International Harmonization Project and European Organisation for Research and Treatment of Cancer criteria. Change between baseline and end of IT in values of standardized uptake value and other PET parameters were associated with PFS and response. Validation of these results in prospective studies of larger cohorts is warranted.

Introduction: The successful management of infected pelvic pressure ulcer patients (PPUP) depends on the distinction between infections limited to soft tissue (STI) and those with underlying osteomyelitis (OM), which can be difficult to determine clinically. Dual-isotope (DI) comprehensive imaging has excellent accuracy in localizing diabetic foot infection and differentiating OM from STI with SPECT/CT utilization. In this study, we assess the accuracy and confidence of the different DI SPECT/CT imaging steps in PPUP with confirmed diagnoses., Patients and Methods: Pelvic flow and blood pool imaging were followed by labeled white blood cell reinjection and Tc-99m hydroxymethylene-diphosphonate bone (bone scan) and In-111-leukocytes (white blood cell scan) DI planar and SPECT/CT (step 1) acquisitions. Tc-99m sulfur colloid (bone marrow scan)/WBCS SPECT/CT (step 2) images were obtained on the following day. DI step 1 planar, step 1 SPECT/CT, step 2 SPECT/CT, and combined step 1/step 2 SPECT/CT were reviewed separately for diagnosis and diagnosis confidence. The final diagnosis was confirmed by culture/pathology in 21 patients and clinical/imaging follow-up in 12 patients., Results: There were 19 OM patients, three STI patients, and 11 patients with no infection. The final diagnosis agreement to DI combined step 1/step 2 SPECT/CT was higher than DI step 2 or step 1 SPECT/CT alone, or DI step 1 planar, as assessed by λ and error reduction %, respectively. Combined DI step 1/step 2 SPECT/CT was more sensitive than DI step 2 SPECT/CT and more specific than DI step 1 SPECT/CT, and showed higher diagnostic confidence than both imaging techniques., Conclusion: DI SPECT/CT is highly useful in evaluating PPUP with suspected infection. DI step 1 is more sensitive, whereas step 2 is more specific. Both step 1 and step 2 DI SPECT/CT images are needed to accurately and confidently assess for infection and distinguish OM from STI, which are crucial for optimal management.

Interim positron emission tomography (PET)/CT has shown encouraging results when used as a prognostic tool early in the course of treatment of advanced Hodgkin lymphoma, allowing for a reduction in treatment for patients with favorable characteristics, while suggesting a benefit from changing therapy for those with a positive scan. For patients with limited disease, a negative scan allows for a decrease in treatment; however, the benefits for those patients whose scans are positive are less certain. Here we critically analyze the role of PET/CT in the early assessment of Hodgkin lymphoma. In Part 2, we will review the role of interim PET/CT in diffuse large B-cell lymphoma (DLBCL), and also explore the question of whether new approaches to quantitative assessment improve the prognostic value of interim PET scans in both Hodgkin lymphoma and DLBCL.

In Part 1, we reviewed the role of interim positron emission tomography (PET)/CT scans in Hodgkin lymphoma. In advanced Hodgkin lymphoma, interim PET is a useful prognostic tool that can be used to implement risk-adapted therapy with potential benefits for both patients who have negative interim scans and those whose scans are positive. Interim PET/CT has not shown as encouraging results in diffuse large B-cell lymphoma (DLBCL), with the exception of germinal center B-cell DLBCL. Thus, quantitative methods of interpreting interim PET scans have been pursued in an effort to improve their predictive value. Early results using the change in maximal standardized uptake value between baseline and interim PET (ΔSUVmax) to quantitatively interpret interim PET scans in DLBCL patients showed promise, but later results were contradictory. Thus, there is not firm evidence of a prognostic value for interim PET interpreted using either visual or ΔSUVmax-based analysis in patients with DLBCL. Nor are there data to support altering treatment in DLBCL on the basis of an interim PET scan. More sophisticated methods of quantitative interpretation of interim PET, using metabolic tumor volume and tumor lesion glycolysis measurements, have been investigated in both Hodgkin lymphoma and DLBCL. Although to date studies of these approaches have been small and heterogeneous, they do provide some support for the potential of a PET-derived volumetric approach to discriminate between risk groups better than ΔSUVmax; this remains to be proven in well-designed large-scale studies.

Interim and end-of-treatment PET/CT have become central to the evaluation of Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical decision making by providing an overview of available data on the diagnostic and prognostic value of PET/CT imaging for response assessment and pretransplant evaluation in lymphoma. The relative strengths and limitations of these techniques in various disease subtypes and clinical scenarios are explored, along with their current standards for reporting and latest developments. Particular attention is given to response-adapted therapy, which is emerging as a cornerstone of clinical management., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Lymphoid malignancies are a heterogeneous group of tumors that have distinctive clinical and biological behaviors. The increasing prevalence of disease reflects both treatment advances and the fact that some of these tumors are indolent. The ability to determine treatment needs at diagnosis remains problematic for some of the tumors, such as in follicular lymphomas. Major clinical advances will likely depend on precision oncology that will enable identification of specific disease entities, prognostic determination at diagnosis, and identification of precise therapeutic targets and essential pathways. However, refinement in diagnostic evaluation is an evolving science. The ability to determine prognosis at diagnosis is variable, and for many of the lymphoid malignancies prognosis can only be made after initial treatment. Clinical trials that aim to evaluate specific features of these diseases are required in order to advance clinical practice that meaningfully addresses this important public health challenge. Herein, we describe the process and general recommendation from the National Cancer Institute (NCI) clinical trials planning meeting in November 2014 to address clinical trial design and biomarker proposals in the context of NCI-supported lymphoma clinical trials in the National Clinical Trials Network., (Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.)

Purpose: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma., Experimental Design: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (k trans ) as well as 18 F-Fluoromisonidazole ( 18 F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival., Results: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18 F-FMISO SUV peak (P = 0.048), mean k trans (P = 0.024), and median k trans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median k trans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUV peak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year., Conclusions: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18 F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR., Competing Interests: Dr. Sorensen reports stock ownership and employment with Siemens and patents/royalties/intellectual property with General Electric. Dr Schmainda reports ownership interest in Imaging Biometrics LLC. All other authors report no conflict of interest., (©2016 American Association for Cancer Research.)

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [ 18 F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [ 18 F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [ 18 F]florbetapir was negative for amyloidosis. The [ 18 F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [ 18 F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [ 18 F]T807/AV1451 retention requires postmortem correlation, our data suggest that [ 18 F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

Purpose: Positron emission tomography (PET) imaging of yttrium-90 in the liver post radioembolization has been shown useful for personalized dosimetry calculations and evaluation of extrahepatic deposition. The purpose of this study was to quantify the benefits of several MR-based data correction approaches offered by using a combined PET/MR system to improve Y-90 PET imaging. In particular, the feasibility of motion and partial volume corrections were investigated in a controlled phantom study., Methods: The ACR phantom was filled with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast of 10:1 between the hot cylinders and the background. Y-90 PET motion correction through motion estimates from MR navigators was evaluated by using a custom-built motion stage that simulated realistic amplitudes of respiration-induced liver motion. Finally, the feasibility of an MR-based partial volume correction method was evaluated using a wavelet decomposition approach., Results: Motion resulted in a large (∼40%) loss of contrast recovery for the 8 mm cylinder in the phantom, but was corrected for after MR-based motion correction was applied. Partial volume correction improved contrast recovery by 13% for the 8 mm cylinder., Conclusions: MR-based data correction improves Y-90 PET imaging on simultaneous PET/MR systems. Assessment of these methods must be studied further in the clinical setting.

The effectiveness of cancer therapy, both in individual patients and across populations, requires a systematic and reproducible method for evaluating response to treatment. Early efforts to meet this need resulted in the creation of numerous guidelines for quantifying posttherapy changes in disease extent, both anatomically and metabolically. Over the past few years, criteria for disease response classification have been developed for specific cancer histologies. To date, the spectrum of disease broadly referred to as lymphoma is perhaps the most common for which disease response classification is used. This review article provides an overview of the existing response assessment criteria for lymphoma and highlights their respective methodologies and validities. Concerns over the technical complexity and arbitrary thresholds of many of these criteria, which have impeded the long-standing endeavor of standardizing response assessment, are also discussed., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Dual imaging with both contrast enhanced CT scan and PET-CT is recommended for evaluation of lymphoma. We compared the performance in identification and size measurements of involved lymph nodes in FDG-avid lymphomas on the low dose non-contrast enhanced CT of a PET-CT scan with those on a diagnostic contrast enhanced CT scan. The size of FDG-avid lymph nodes was measured in both the short and long axis on both the low dose non-contrast CT of the PET-CT and the contrast enhanced CT by two independent readers. A total of 307 FGD avid lymph nodes were identified in 52 patients. There was no statistically significant differences in the measured size of the nodes on the non-contrast and contrast enhanced scans (p=0.21). Baseline staging and restaging of FDG-avid lymphomas can be performed with one test, PET-CT, without an accompanying contrast enhanced CT scan, with no effect on the measured nodal size.