ABSTRACT:The phase 2 ALYCANTE trial aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axicabtagene ciloleucel (axi-cel) infusion as a primary end point in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (ASCT). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls. This study reports the health-related quality of life (HRQoL) results as a secondary end point. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) cancer-specific questionnaire, the Quality of Life Questionnaire high-grade non-Hodgkin lymphoma 29 (QLQ-NHL-HG29) , and the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) generic questionnaire at baseline and 1, 3, 6, and 12 months after axi-cel infusion. Among the 62 patients included, 60 (97%) completed a baseline and at least 1 postbaseline HRQoL assessment. At 1 month infusion, adjusted mean change in HRQoL scores from baseline showed a clinically significant deterioration (greater than the clinical threshold) in physical, role, social functioning, and fatigue. However, all HRQoL dimensions recovered by 3 months after infusion and remained stable or continued to improve by 12 months. In an exploratory analysis, adjusted mean change in HRQoL score from baseline in ALYCANTE was similar to or better than in ASCT-eligible patients who received axi-cel in the phase 3 ZUMA-7 trial. Finally, the global health status and fatigue scores of the ALYCANTE population improved to levels comparable to the general French population of similar age by 3 months after infusion. These findings indicate that axi-cel improves HRQoL regardless of transplant eligibility, supporting its use across a broad patient population. This trial was registered at www.clinicaltrials.gov as #NCT04531046.

Abstract: This study aimed to assess the prognostic value of medullary total metabolic tumor volume (mTMTV) derived from fluorodeoxyglucose–positron emission tomography/computed tomography ([18F]FDG-PET/CT) compared with conventional PET-derived features and biological/chromosomal abnormalities in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab for induction/consolidation and/or maintenance and enrolled in CASSIOPET, a companion study of CASSIOPEIA, with long-term follow-up. Automated bone/liver CT–based segmentation were applied to the baseline [18F]FDG-PET images, with mTMTV being defined using the median liver background as the cut-off, including focal lesions and diffuse bone marrow (BM) involvement. Both univariate/multivariate Cox and machine learning (ML)–based survival models were performed. A total of 195 patients were included, 81% of them PET-positive. Multivariate analysis demonstrated independent prognostic value of mTMTV for progression-free survival (PFS) (P < .001) and overall survival (OS) (P < .001), complementary to Revised International Staging System (R-ISS) (P = .008 and P < .001, respectively). The ML model confirmed these findings, achieving concordance index of 0.609 and 0.659 and identifying mTMTV as the most informative feature for PFS and OS. Adding R-ISS, BM maximum standardized uptake value (SUVmax) and anemia to mTMTV accounted for >60% of the ML model explanation for PFS and adding R-ISS, the number of focal lesions and BM SUVmax for >60% of the model for OS. Combining R-ISS and mTMTV enabled the creation of 2 new-risk subgroups. In conclusion, this prospective study demonstrated the prognostic relevance of [18F]FDG-PET/CT–based parameters in the initial workup of patients with NDMM in the era of anti-CD38–based therapy. mTMTV was found to have strong independent prognostic value, complementary to R-ISS and refining risk stratification. This trial was registered at www.clinicaltrials.gov as #NCT02541383.

BACKGROUND:In light-chain (AL) amyloidosis, liver involvement is defined using arbitrary criteria such as hepatomegaly or elevated Alkaline Phosphatase (ALP). We aimed to determine its prevalence and to characterize its phenotype and prognostic impact. METHODS:This study included 200 patients with AL amyloidosis. Liver involvement was defined by MRI/CT hepatomegaly and/or elevated ALP. Liver phenotyping included early-phase 99mTc-HMDP bone scintigraphy (BS), and histological analysis (n = 12). Predictors of liver involvement were identified using logistic regression. Unsupervised clustering analysis was performed to identify distinct patterns of liver involvement. RESULTS:Liver involvement was identified in 71 patients (35%) and was independently associated with digestive and renal amyloidosis, liver uptake and increased vena cava diameter. Clustering analysis identified three phenotypes: a cardiac cluster, characterized by severe cardiac failure and congestive hepatopathy associated with elevated bilirubin; a hepatic cluster, marked by multivisceral amyloidosis, elevated γGT and ALP, in which liver involvement reflected amyloid deposition; an intermediate cluster with milder abnormalities and better prognosis. Histological findings supported this. Sixty-month survival was 32%, 44% and 54% in the cardiac, hepatic and intermediate clusters, respectively. CONCLUSION:Liver involvement in AL amyloidosis is due to both amyloid deposition and cardiac congestion. Clustering analysis revealed distinct liver patterns with different prognoses.

Background 18F-florbetaben positron emission tomography (PET) is reported to detect i) cardiac amyloidosis (CA), particularly AL (light chain) forms, and ii) sites of extracardiac AL-amyloid infiltrates. Objectives The purpose of this study was to identify CA and differentiate AL-CA from ATTR-CA (transthyretin) by evaluating cardiac and multi-organ involvement with whole-body 18F-florbetaben PET. Methods Multicentric study of 61 patients with left ventricular hypertrophy due to AL-CA (n = 25), ATTR-CA (n = 25), and aortic stenosis (n = 11, controls). A 20-minute whole-body PET was preceded by a 10-minute dynamic cardiac PET recording started during 18F-florbetaben injection. Results Tracer uptake was significantly increased in whole-body PET of CA patients compared to controls, with AL-CA patients, in particular, exhibiting increased uptake in myocardium, lung, and spleen, and decreased uptake in blood, salivary glands, skeletal muscle, and liver. Among cardiac parameters, the myocardial/blood standardized uptake value (SUV)max ratio from whole-body PET best differentiated AL-CA from ATTR-CA, with 90% (55/61) of patients identified correctly (kappa value: 0.819) using SUVmax ratio thresholds of 2-to-4 for ATTR-CA and >4 for AL-CA. When combining cardiac with extracardiac PET variables, the selected multivariate predictors were myocardial uptake volume and the lung and salivary gland SUVmean. Thresholds of myocardial uptake volume >10 mL for CA and lung/salivary gland SUVmean >0.285 for AL-CA correctly identified 93% (57/61) of patients (kappa value: 0.871). PET variables improved the overall prediction provided by the bone scan Perugini score (P < 0.001). Conclusions Whole-body 18F-florbetaben PET identifies CA and differentiates AL-CA from ATTR-CA. These distinctions are strengthened by combining assessments of cardiac and multi-organ involvement.

AIMS:Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience delayed diagnosis, which may detrimentally impact clinical outcomes. This study aimed to assess the frequency of use of planar scintigraphy with and without single-photon emission computed tomography (SPECT) in patients with hypertrophic cardiomyopathy (HCM) screened for ATTR-CM in the TTRACK study. Variability in readings based on different readers, tests and radiotracers used in cardiac nuclear imaging, and differences in echocardiogram findings between patients with and without ATTR-CM were explored. METHODS:Patients aged ≥50 years with HCM (left-ventricular wall thickness ≥15 mm without an identified cause) underwent diagnostic technetium-99m [99mTc]Tc-DPD [3,3-diphosphono-1,2-propanodicarboxylic acid], -PYP [pyrophosphate] and -HMDP [hydroxymethylene diphosphonate]-labelled planar bone scintigraphy with or without SPECT. Cardiac-versus-bone uptake on images was visually graded (Perugini, 0-3) by onsite and central readers (discrepancies resolved by consensus). Patients with grade 1-3 cardiac uptake underwent monoclonal protein testing. RESULTS:Of 766 eligible patients (mean age ± standard deviation, 72.3 ± 10.6 years, 69.6% male), 691 (90.2%) had planar imaging alone and 75 (9.8%) planar plus SPECT imaging. Cardiac uptake was observed on imaging in 245 patients (32.0%); grades 1, 2 and 3 were assigned in 37 (4.8%), 34 (4.4%) and 174 (22.7%), respectively. Initial cardiac uptake grading for planar scintigraphy by onsite readers was strongly concordant with consensus decisions [κ coefficient, 0.84 (95% confidence interval 0.81-0.88)]. Grading for planar versus SPECT imaging was very strongly concordant [0.93 (95% confidence interval 0.86-1.00)]; discordant findings were only observed with [99mTc]Tc-PYP. Compared with patients with no cardiac uptake, patients with ATTR-CM had a lower mean left ventricular (LV) ejection fraction (55.7% vs. 61.4%; P < 0.001), higher mean LV mass index (179.0 vs. 155.6 g/m2; P < 0.01), a higher rate of preserved apical strain (73.4% vs. 57.9%; P < 0.05) and differences in hypertrophic pattern (P < 0.001), such as a higher rate of concentric hypertrophic pattern (77.5% vs. 38.8%;). Clinical overlap between patients with ATTR-CM and those without cardiac uptake was high. CONCLUSIONS:In this real-world study, a high level of concordance was seen in cardiac uptake grading on planar versus SPECT imaging, with discordant findings only observed with [99mTc]Tc-PYP. The findings support the use of these imaging tools to facilitate ATTR-CM screening in clinical practice. Further studies should investigate differences across tracers used in ATTR-CM screening. NCT03842163.

ABSTRACT:The GAINED study was a randomized phase 3 trial comparing obinutuzumab (G) with rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, and prednisone, combined with either vindesine or bleomycin) or CHOP14 (cyclophosphamide, doxorubicin, vincristine, and prednisone, administered on a 14-day schedule) induction, followed by positron emission tomography (PET)-guided consolidation. This post hoc analysis aimed to detail the outcomes of patients with primary mediastinal B-cell lymphoma (PMBL), verified through expert pathological review and the use of gene expression profiling (GEP) and next-generation sequencing. Of 620 centrally reviewed patients, 138 (22.3%) confirmed PMBL cases were analyzed. Baseline characteristics included a median age of 33.5 years, 63.8% female, 55.1% stage III to IV, 90.6% elevated lactate dehydrogenase, 87.6% Eastern Cooperative Oncology Group performance status score of 0 to 1, 62.3% extranodal involvement, 52.6% age-adjusted International Prognostic Index (aaIPI) of 2% to 3%, and 53.6% bulk (>10 cm). Induction regimens were R/G-CHOP14 (56.9%) and R/G-ACVBP (43.1%). Postinduction treatments, based on interim PET results, included: standard consolidation chemotherapy (59.8%) if change in maximum standardized uptake value (ΔSUVmax) of >66% after cycle 2 and >70% after cycle 4 (PET2-/4-), intensive treatment and autologous transplantation (26.8%) if PET2+/4-, and salvage therapy (13.4%) if PET4+ (ΔSUVmax of ≤70%). Among patients with GEP data (n = 107), 38 (35.5%) were PDL1high/PDL2high. Key somatic mutations data (n = 87) included SOCS1 (70.1%), B2M (56.3%), STAT6 (49.4%), TNFAIP3 (47.1%), GNA13 (39.1%), CIITA (37.9%), CD58 (36.8%), and TP53 (29.9%). After a median follow-up of 39.5 months, 2-year progression-free survival (PFS) and overall survival (OS) rates were 86.2% and 93.2%, respectively. In a multivariate model including bulk, aaIPI, and ΔSUVmax PET2/PET4, only bulk and ΔSUVmax PET4 of ≤70% were associated with shorter PFS (hazard ratio, 4.39 [95% confidence interval (CI), 1.28-15.11] and 4.95 [95% CI, 1.71-14.3], respectively), whereas none were associated with OS. The ΔSUVmax-based interim PET4 response emerged as the strongest predictor of patient outcomes in this selected clinical trial population. This trial was registered at www.ClinicalTrials.gov as #NCT01659099.

ABSTRACT:The CASSIOPEIA trial demonstrated superior progression-free survival (PFS) with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (D-VTd) induction/consolidation, and with daratumumab maintenance vs observation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The companion study, CASSIOPET, assessed the prognostic value of premaintenance (PM) positron emission tomography (PET)/computed tomography (CT) response, based on the standardized Deauville score on PFS and overall survival (OS), in addition to bone marrow (BM) minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) at 10-5 level. PM PET/CT was available for 225 patients: 112 patients treated with daratumumab after D-VTd (59) or bortezomib, thalidomide, and dexamethasone (VTd; 53), and 113 patients followed by observation after D-VTd (56) or VTd (57). At PM, 92% of the 175 baseline PET-positive patients achieved PET negativity, with a longer PFS in univariate analysis (P = .019) and a major trend of prolonged OS (P = .056). In univariate analysis, patients who achieved both PET and MFC negativity were found to have a better PFS (P < .0001) than those who had at least 1 positive result. In daratumumab-treated patients, PM PET negativity was associated with prolonged PFS and OS in univariate analysis (P = .0023 and P = .033, respectively), and double MFC and PET negativity was independently associated with PFS by multivariate analysis (P = .0006). This study confirms the prognostic relevance of a PM PET response in patients with NDMM treated with daratumumab in addition to MRD detection by MFC at the BM level. This trial was registered at ww.clinicaltrials.gov as #NCT02541383.

BACKGROUND:We explored sex differences in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and determined survival and prognostic factors. METHODS:In a retrospective cohort study at a reference centre in France from 1 January 2008 to 31 December 2022, multiple regression analyses, supervised clustering, Cox models, and a Kaplan-Meier analysis were used to compare women and men in each age quartile (Q1: ≤77 years; Q2: 78-82; Q3: 83-86; Q4 > 86). RESULTS:We included 1062 patients with ATTRwt-CM (180 women, 16%). The women had a higher median [IQR] left ventricular ejection fraction (LVEF; 52% [45-60] vs. 50 [43-58] in men) and a thinner interventricular septum. 12% of women and 4.1% of men had a septum thickness <12 mm (p = 0.004). The women in Q1 had lower LVEF and global longitudinal strain values and a higher prevalence of a septum <12 mm (15.8%, vs 2.0% in men) than men and older women (Q2-Q3-Q4). Women had a greater risk of sudden death than men (13.8% vs. 4.6%, respectively; odds ratio [95% confidence interval]: 3.24 [1.56-6.64]; p = 0.001). CONCLUSIONS:In women, the ATTRwt-CM phenotype and prognosis are related to age at diagnosis. Decreasing the septum thickness cut-off would increase the frequency of ATTR-CM diagnosis in women.

Patients with follicular lymphoma who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at end of induction (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase 3 trial with both available serum samples for ctDNA testing and PET images at randomization and at EOI (week 24) was investigated. Twelve percent were POD24. ctDNA was analyzed using a customized 130-kilobase capture panel, with phased variant (PV) enriched regions representing 39% of the panel. ctDNA was detected in 140 patients (99.3%) at baseline. To optimize specificity, only PVs, found in 124 patients (88%), were considered for ctDNA MRD assessment at EOI. Median progression-free survival (PFS) from EOI was not reached (NR) for the 112 patients with undetected ctDNA at EOI vs 17.7 months (95% confidence interval [CI], 1.4 to NR) for patients with positive ctDNA (MRD+) (P = .0038). Similarly, median PFS was NR for the 104 patients with undetected disease on PET at EOI vs 28.3 months (95% CI, 2.9 to NR; P = .0002) for patients with PET positivity. Both tests had a negative predictive value (NPV) of >90% for POD24. The positive predictive value was 58.3% for ctDNA MRD and 45% for PET but increased to 85.7% when both parameters were combined, without alteration of NPV. These data show that the combination of PET response and ctDNA MRD at EOI allows an early prediction of POD24, which may lead to a preemptive treatment decision. This trial was registered at www.clinicaltrials.govas # NCT01650701.

Introduction: The GAINED study (NCT01659099) was a randomized phase 3 trial comparing obinutuzumab (G) to rituximab (R) plus ACVBP or CHOP14 induction, followed by PET-guided consolidation. No significant survival differences were found between the arms (Le Gouill et al. 2021). This post-hoc analysis aimed to detail the outcomes of primary mediastinal B-cell lymphoma (PMBL) patients included in the trial, verified through expert pathological review and the use of a molecular gene-expression profiling-based (GEP) classifier. Methods: Conducted by LYSA across 99 centers in Belgium and France from 2012 to 2015, the GAINED study had the following key inclusion criteria : patients aged 18-60 years, CD20+ diffuse large B-cell lymphoma (DLBCL) according to the 2008 WHO classification, aaIPI ≥1, and eligibility for autologous stem cell transplant (ASCT). Patients with a ΔSUVmax >66% after cycle 2 and >70% after cycle 4 (PET2−/4−) received standard consolidation chemotherapy, while those with PET2+/4− received intensive treatment with ASCT. PET4+ patients (ΔSUVmax ≤70%) were given salvage therapy. We here focused on clinical characteristics, treatment responses, and outcomes, incorporating metabolic tumor volume (MTV, fixed SUV4 method) and biological data including cell-free DNA (cfDNA) and soluble PDL1 (sPDL1) levels, mutational landscape (custom targeted NGS panel), and GEP (LymphoSign test). Primary endpoints included were progression-free survival (PFS) and overall survival (OS). False discovery rate correction was applied for multiple testing. Results: Of the initial 670 patients, 138 (20.6%) confirmed PMBL cases were analyzed. Baseline characteristics included a median age of 33.5 years, 63.8% female, 55.1% stage III-IV, 90.6% elevated LDH, 87% ECOG 0-1, 62.3% extranodal involvement, 52.2% aaIPI 2-3, 50.7% MTV ≥360 cm³, and 53.6% with bulky (>10cm) mediastinal masses. Induction regimens were R/G-CHOP14 (56.5%) and R/G-ACVBP (42.8%). Post-induction treatments, based on interim PET (iPET) results, included: consolidation chemotherapy (55.1%), ASCT (24.6%), and salvage therapy (12.3%). After a median follow-up of 39.5 months, 2-year PFS and OS rates were 86.2%, and 93.2%. PET2−/4− had superior PFS (p<0.001) but similar OS (p=0.123) compared to PET2+/4− and PET4+ patients; the 2-year PFS and OS were: 93.5% vs 82.4% vs 58.8% and 96% vs 90.9% vs 85.6% respectively. ACVBP plus ASCT (n=38) and CHOP14 plus ASCT (n=38) had similar 2-year PFS and OS: 94.6% vs 92.1% and 97.1% vs 94.7%. ACVBP plus sequential consolidation chemotherapy and CHOP14 8 cycles had also comparable 2-year PFS and OS: 81.8% vs 82.6% and 90.9% vs 90.9%. Among patients with GEP data (n=107), 38 (35.5%) were PDL1high/PDL2high. Key somatic mutations data (n=87) included SOCS1 (70.1%), B2M (56.3%), STAT6 (49.4%), TNFAIP3 (47.1%), GNA13 (39.1%), CIITA (37.9%), CD58 (36.8%), and TP53 (29.9%). Univariate analysis highlighted that bulky mass (HR 4.37 [95%CI: 1.48-12.92]), stage III-IV (HR 4.06 [1.38-12.01]), and PET4+ (HR 3.18 [1.07-9.48]) were associated with shorter PFS, whereas PET2- and ΔSUVmax PET4 (continuous variable) where associated with longer PFS (HR=0.48 [0.16-1.44] and 0.26 [0.15-0.43], respectively). Additionally, stage III-IV (HR 9.9 [1.28-76.57]) was linked to shorter OS, whereas ΔSUVmax PET4 was associated with longer OS (HR=0.36 [0.21-0.62]). None of the other factors assessed (aaIPI, induction chemotherapy regimen, R or G, cfDNA and sPDL1 level, PDL1high/PDL2high status, B2M,CD58, TP53 alterations, MTV) were significantly associated with outcomes. Finally, in multivariate models, bulky mass adjusted on aaIPI remained significantly associated with inferior PFS (HR 3.84 [1.11-13.27], p=0.034). When MTV and ΔSUVmax PET2 and PET4 were also included, only ΔSUVmax PET4 was associated with longer PFS (HR=0.21 [0.08-0.55], p=0.001) and OS (HR=0.46 [0.23-0.93], p=0.032). Conclusion: This analysis highlights the strong representation, distinct characteristics and excellent outcomes of PMBL patients in the GAINED trial, emphasizing the importance of expert histopathological and molecular characterization for accurate diagnosis. The iPET response, especially ΔSUVmax PET4, emerged as the primary predictor of outcomes in this selected clinical trial population. Tailoring consolidation treatments based on iPET results may have mitigated the impact of baseline adverse characteristics.

Diffuse Large B-cell Lymphoma (DLBCL) is a lymphatic cancer of steadily growing incidence. Its diagnostic and follow-up rely on the analysis of clinical biomarkers and 18F-Fluorodeoxyglucose (FDG)-PET/CT images. In this context, we target the problem of assisting in the early identification of high-risk DLBCL patients from both images and tabular clinical data. We propose a solution based on a graph neural network model, capable of simultaneously modeling the variable number of lesions across patients, and fusing information from both data modalities and over lesions. Given the distributed nature of DLBCL lesions, we represent the PET image of each patient as an attributed lesion graph. Such lesion-graphs keep all relevant image information while offering a compact tradeoff between the characterization of full images and single lesions. We also design a cross-attention module to fuse the image attributes with clinical indicators, which is particularly challenging given the large difference in dimensionality and prognostic strength of each modality. To this end, we propose several cross-attention configurations, discuss the implications of each design, and experimentally compare their performances. The last module fuses the updated attributes across lesions and makes a probabilistic prediction of the patient's 2-year progression-free survival (PFS). We carry out the experimental validation of our proposed framework on a prospective multicentric dataset of 545 patients. Experimental results show our framework effectively integrates the multi-lesion image information improving over a model relying only on the most prognostic clinical data. The analysis further shows the interpretable properties inherent to our graph-based design, which enables tracing the decision back to the most important lesions and features.

AbstractAimsTransthyretin cardiac amyloidosis (ATTR‐CM) may be an underestimated cause of heart failure among geriatric patients and represent a unique phenotype and prognostic profile.Methods and resultsThis retrospective, observational, cohort study characterizes cardiac and extracardiac disorders at diagnosis and assesses prognosis among ATTR‐CM patients based on age (geriatric vs. non‐geriatric) and amyloidosis subtype (wild type, ATTRwt and hereditary, ATTRv). In total, 943 patients with ATTR‐CM were included, of which 306 had ATTRv and 637 had ATTRwt. Among these, 331 (35.1%) were non‐geriatric (<75 years), and 612 (64.9%) were geriatric (≥75 years). The population exhibited conduction abnormalities, atrial fibrillation and ischaemic heart disease that progressively deteriorated with age. Among ATTRwt patients, peripheral neuropathy, neurovegetative symptoms, and hearing loss were present across all age groups, but reports of carpal tunnel symptoms or surgery decreased with age. Conversely, among ATTRv patients, reports of extracardiac symptoms increased with age and Val122ILe mutation was highly prevalent among geriatric patients. The 3‐year survival was higher among non‐geriatric ATTR‐CM patients (76%) than geriatric patients (55%) and predictors of 3‐year mortality differed. Notably, predictors identified among geriatric patients were alkaline phosphatase (ALP) (HR = 1.004, 95% CI: [0.001–1.100)], troponin T hs (HR = 1.005, 95% CI: [1.001–1.120)] and tricuspid insufficiency (HR = 1.194, 95% CI: [1.02–1.230)]. Whereas, among non‐geriatric patients, NT‐proBNP (HR = 1.002, 95% CI: [1.02–1.04], global longitudinal strain (HR = 0.95, 95% CI: [0.922–0.989], and glomerular filtration rate (HR = 0.984, 95% CI: [0.968–1.00) were identified. We propose a 3‐stage prognostic staging system combining troponin T hs (≥44 ng/L) and ALP levels (≥119 UI/L). In the geriatric population, this model discriminated survival more precisely than the National Amyloidosis Centre staging, particularly for classifying between stage 1 (82%), stage 2 (50%) and stage 3 (32%) for ATTRv and ATTRwt.ConclusionsThese diagnostic and prognostic indicators, along with ATTR subtype, highlight the distinct characteristics of this important, geriatric ATTR‐CM patient group. Recognizing these mortality markers can be valuable for geriatricians to improve the prognostic quality management of geriatric patients with ATTR‐CM.

Background Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. Methods and Results We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09–3.64]; ATTRv: SRR, 3.41; 95%CI [1.64–4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25–14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56–1.14]; ATTRv: SRR, 1.27; 95%CI [0.85–1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71–4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42–1.19]; P =0.19). Conclusions Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

The results of the GA in Newly Diagnosed Diffuse Large B-Cell Lymphoma (GAINED) study demonstrated the success of an 18F-FDG PET-driven approach to allow early identification-for intensification therapy-of diffuse large B-cell lymphoma patients with a high risk of relapse. Besides, some works have reported the prognostic value of baseline PET radiomics features (RFs). This work investigated the added value of such biomarkers on survival of patients involved in the GAINED protocol. Methods: Conventional PET features and RFs were computed from 18F-FDG PET at baseline and extracted using different volume definitions (patient level, largest lesion, and hottest lesion). Clinical features and the consolidation treatment information were also considered in the model. Two machine-learning pipelines were trained with 80% of patients and tested on the remaining 20%. The training was repeated 100 times to highlight the test set variability. For the 2-y progression-free survival (PFS) outcome, the pipeline included a data augmentation and an elastic net logistic regression model. Results for different feature groups were compared using the mean area under the curve (AUC). For the survival outcome, the pipeline included a Cox univariate model to select the features. Then, the model included a split between high- and low-risk patients using the median of a regression score based on the coefficients of a penalized Cox multivariate approach. The log-rank test P values over the 100 loops were compared with a Wilcoxon signed-ranked test. Results: In total, 545 patients were included for the 2-y PFS classification and 561 for survival analysis. Clinical features alone, consolidation features alone, conventional PET features, and RFs extracted at patient level achieved an AUC of, respectively, 0.65 ± 0.07, 0.64 ± 0.06, 0.60 ± 0.07, and 0.62 ± 0.07 (0.62 ± 0.07 for the largest lesion and 0.54 ± 0.07 for the hottest). Combining clinical features with the consolidation features led to the best AUC (0.72 ± 0.06). Adding conventional PET features or RFs did not improve the results. For survival, the log-rank P values of the model involving clinical and consolidation features together were significantly smaller than all combined-feature groups (P < 0.007). Conclusion: The results showed that a concatenation of multimodal features coupled with a simple machine-learning model does not seem to improve the results in terms of 2-y PFS classification and PFS prediction for patient treated according to the GAINED protocol.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The primary analysis of the Ro-CHOP phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT01796002 ) established that romidepsin (Ro) plus cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) did not yield an increased efficacy compared with CHOP alone as first-line treatment of peripheral T-cell lymphoma. We report the planned final analysis 5 years after the last patient enrolled. With a median follow-up of 6 years, median progression-free survival (PFS) was 12.0 months compared with 10.2 months (hazard ratio [HR], 0.79 [95% CI, 0.62 to 1.005]; P = .054), while median overall survival was 62.2 months (35.7-86.6 months) and 43.8 months (30.1-70.2 months; HR, 0.88 [95% CI, 0.68 to 1.14]; P = .324) in the Ro-CHOP and CHOP arms, respectively. In an exploratory analysis, the median PFS in the centrally reviewed follicular helper T-cell lymphoma subgroup was significantly longer in the Ro-CHOP arm (19.5 v 10.6 months, HR, 0.703 [95% CI, 0.502 to 0.985]; P = .039). Second-line treatments were given to 251 patients with a median PFS2 and OS2 after relapse or progression of 3.3 months and 11.5 months, respectively. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005).

Introduction and aim: Simultaneous positron emission tomography/magnetic resonance imaging (PET-MRI) combines the high sensitivity of PET with the high specificity of MRI and is a tool for the assessment of gastroenteropancreatic neuroendocrine neoplasms (G-NENs). However, it remains poorly evaluated with no clear recommendations in current guidelines. Thus, we evaluated the prognostic impact of PET-MRI in G-NEN patients. Methods: From June 2017 to December 2021, 71 G-NEN patients underwent whole-body PET-MRI for staging and/or follow-up purposes. A whole-body emission scan with 18F-6-fluoro-L-dihydroxyphenylalanine (18FDOPA, n = 30), 18F-fluoro-2-deoxy-D-glucose (18FDG, n = 21), or 68Ga-(DOTA(0)-Phe(1)-Tyr(3))-octreotide (68Ga-DOTATOC, n = 20) with the simultaneous acquisition of a T1-Dixon sequence and diffusion-weighed imaging (DWI), followed by a dedicated step of MRI sequences with a Gadolinium contrast was performed. The patients underwent PET-MRI every 6–12 months during the follow-up period until death. Over this period, 50 patients with two or more PET-MRI were evaluated. Results: The mean age was 61 [extremes, 31–92] years. At the baseline, PET-MRI provided new information in 12 cases (17%) as compared to conventional imaging: there were more metastases in eight, an undescribed location (myocardia) in two, and an unknown primary location in two cases. G grading at the baseline influenced overall survival. During the follow-up (7–381 months, mean 194), clinical and therapy managements were influenced by PET-MRI in three (6%) patients due to new metastases findings when neither overall, nor disease-free survivals in these two subgroups (n = 12 vs. n = 59), were different. Conclusion: Our study suggests that using PET/MRI with the appropriate radiotracer improves the diagnostic performance with no benefit on survival. Further studies are warranted to evaluate the cost-effectiveness of this procedure.