This article outlines how France reorganised itself to meet the growing demand for radioligand therapy (RLT) in patients with prostate cancer following VISION trial's success in 2021. A national RLT network has progressively established itself as a key structure on which administrative bodies, scientific societies, policymakers, and industry partners can rely. By identifying existing gaps between supply and demand, the RLT network is now positioned to support nuclear medicine departments in implementing RLT, thereby expanding patient access to this innovative therapeutic approach and responding to the increasing demand in prostate cancer as well as other cancers.

CAR T-cell therapy has changed the management of relapsed/refractory (R/R) Diffuse large B-cell lymphoma (DLBCL). Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (PET/CT) plays a central role in lymphoma response assessment, but its prognostic use remains insufficiently standardized in this setting. Patients from the French DESCAR-T registry treated in third line or beyond with commercial anti-CD19 CAR T-cells in real-life, and having centrally reviewed PET/CT before infusion, and at one month (M1) or three months (M3) post-infusion were included. For each visit, Total Metabolic Tumor Volume (TMTV) and SUVmax were measured. Deauville score (DS) and response according to 2014 Lugano classification were registered on follow-up PET/CT. Optimal TMTV cut-offs at baseline, M1 and M3 follow-up for progression-free survival (PFS) and overall survival (OS) and the prognostic impact of DS at M1 and M3 were determined. A total of 212 R/R DLBCL patients were analysed. Baseline median SUVmax was 16.4 and median TMTV 41.3 cm3. A baseline TMTV cut-off of 30 cm3 significantly stratified patients for PFS and OS, in both univariate and multivariate analysis, along with LDH. Complete metabolic response (DS 1–3) at M1 was significantly associated with better PFS M1 and OS M1 than DS4-5 (for PFS M1: median of 21.8 vs 1.8 vs months; p < 0.0001; for OS M1: median not reached versus median of 6.3 months; p < 0.0001). DS5 identified patients with the worst outcomes (for PFS M1: median of 0.1 month and for OS M1: median of 4.5 months). Similarly, at M3 DS1-3 was associated with a better outcome than DS4-5, and patients with DS5 had the worst outcome. In patients without complete metabolic response residual TMTV provided additional prognostic value. Baseline TMTV and metabolic response assessed by DS, together with residual TMTV on follow-up PET/CT, are strong prognostic biomarkers in R/R DLBCL patients treated with anti-CD19 CAR T-cells.

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.

504 Background: This study evaluated the effectiveness, quality-of-life, safety, and dosimetry of Y90 glass microspheres for the treatment of primary and colorectal liver metastasis in a real-world clinical setting. Herein, we present the final data for patients with hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [iCCA]. Methods: All patients treated with Y90 glass microspheres (TheraSphere) between 2019 and 2024 who agreed to data collection were included from 34 French institutions. Duration of follow-up and overall survival (OS) were assessed by reverse Kaplan-Meier (KM) and KM analysis, respectively. Toxicity was assessed using CTCAE v5. Pre/post-treatment dosimetry was re-assessed by central read using activity determined by the site. Results: In total, 1196 patients with PLC (989 HCC; 207 iCCA) were included. Of the HCC patients, 35.3% had portal vein thrombosis; 13.3%, 18.9%, 57.9%, and 5.8% were BCLC A, B, C, D, respectively. Among iCCA patients, 56.5% were ECOG 0; 31.9% had associated liver fibrosis or cirrhosis. At least one prior treatment was reported in 39% of PLC patients (systemic, n=194; locoregional [LRT], n=289; surgery, n=72). Personalized multicompartment dosimetry was used for 73% of patients and selective treatment administration was used for 55%. By central assessment, pretreatment mean absorbed dose to total perfused tumor was 422.1 Gy in HCC and 357.2 Gy in iCCA. Median OS [95%CI] was 21.8 months (M) [20.1 – 23.3] for HCC and 21.9M [18.2 – 24.3] for iCCA. iCCA patients treated with TARE as a first-line treatment had longer OS (23.3M) compared to patients treated as a second-line treatment (11.4M). More than half of PLC patients had subsequent treatment (54%). PLC patients who had post-Y90 surgery (12%) had the greatest OS benefit. In HCC, median OS was 48.6M with subsequent surgery (n=112), 23.3M with subsequent LRT or systemic treatment (n=424), and 14.8M with no further treatment (n=396). In iCCA, median OS was not reached in patients with subsequent surgery (n=27), 21.3M for patients with subsequent LRT or systemic treatment (n=90), and 17.4M for patients without subsequent treatment (n=76). Among all patients, 93 experienced adverse events (AEs; n=134), 88 had serious AEs (n=114), and 45 patients had related/possibly related serious treatment-emergent AEs (3.8%). Conclusions: Results from this large prospective real-world study using contemporary TARE treatment highlight its critical role as an integral component in the continuum of care for patients with PLC. In most cases, patients received personalized treatment, resulting in meaningful survival, and an acceptable adverse event profile. Importantly, TARE followed by surgery resulted in survival outcomes rarely observed in this population of patients typically not eligible for surgery. Clinical trial information: NCT04069468 .

Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) has transformed the management of metastatic castration-resistant prostate cancer. Early-access programs conducted before full regulatory approval provide important real-world evidence complementing clinical trials. Across heterogeneous and often heavily pretreated populations, lutetium-177 PSMA-617 demonstrated consistent clinical benefit, with a tolerable safety profile. Key predictors of poorer outcomes include low PSMA expression, discordant imaging phenotypes, liver metastases, and impaired performance status. These programs refined patient selection and response assessment, highlighting the value of PSMA positron emission tomography over prostate-specific antigen alone, and informed strategies such as extended treatment and dosimetry-guided care. They also enabled early evaluation of α-emitter therapies. PATIENT SUMMARY: Recent years have seen the approval of radioligand therapy (RLT) for patients with advanced metastatic prostate cancer. Our mini review focuses on results in early-access programs. These findings support the effectiveness and manageable safety of RLT in routine practice, including in more complex cases that are often excluded from trials.

[68Ga]Ga-PentixaFor, a CXCR4-targeted PET tracer, has shown potential in multiple myeloma. However, [68Ga]Ga-PentixaFor-PET/CT acquisition protocols lack standardization. This is a prospective ancillary study to the PentiMyelo trial aimed to determine the optimal acquisition time for [68Ga]Ga-PentixaFor-PET. Twenty multiple myeloma patients underwent [68Ga]Ga-PentixaFor-PET/CT at 60 min post-injection, with additional acquisitions at 30, 40, 50 min (Group 1) or 75, 85, 95 min (Group 2). Semi-quantitative metrics including SUV, tumor-to-background ratios and image noise — assessed by the coefficient of variation, were systematically analyzed. Physiological liver, spleen and mediastinal blood-pool uptakes decreased over time while image noise increased. A total of 343 lesions were detected (316 in Group 1, 27 in Group 2). Neither earlier nor later acquisition time affected the positivity of [68Ga]Ga-PentixaFor-PET, which was positive in 10 of 20 patients (5 in Group 1 and 5 in Group 2). In Group 1, tumor-to-background ratio was significantly higher at 60 min; in Group 2, tumor-to-background ratio remained stable. An acquisition time of 60 min post-injection provided optimal lesion contrast, supporting its adoption as the standard imaging time point for [68Ga]Ga-PentixaFor-PET/CT. Name of the registry: ClinicalTrials.gov. Trial registration number: NCT04561492. Date of registration: 17 September 2020. URL of trial registry record: https://clinicaltrials.gov/study/NCT04561492. This imaging sub-study is ancillary to the PentiMyelo prospective trial registered under the identifier NCT04561492.

Background: Accurate phenotyping of cancer lesions is critical for guiding targeted therapies. In multiple myeloma (MM), CD38 is a validated biomarker and a major therapeutic target. However, a companion diagnostic tool is still lacking. This study aimed to evaluate the potential of a copper-64-labeled anti-CD38 single-domain antibody (sdAb or nanobody), WF121, for immuno-PET (Positron Emission Tomography) imaging of CD38 expression in vivo in a preclinical model of MM. The nanobody’s binding affinity and specificity were assessed by flow cytometry using CD38 + MM1S and CD38⁻ U266 cell lines. Its internalization profile was evaluated by confocal microscopy. WF121 nanobody was conjugated to the NOTA (1,4,7-Triazacyclononane-1,4,7-triacetic acid) chelator through lysine residues and radiolabeled with copper-64. In vivo PET imaging was performed in C.B-17/IcrHanHsd-Prkdc-scid mice bearing subcutaneous MM1S or U266 xenografts. MM1S-grafted mice underwent dynamic scans (0–2h post-injection) and static acquisitions at 1, 2 and 24h. U266-grafted mice were imaged at 1, 2 and 24h. Ex vivo biodistribution analyses were conducted at 2 h and 24 h for MM1S, and at 24 h for U266. Autoradiography was performed on excised tumors and kidneys for high-resolution localization of radiotracer uptake. Results: Flow cytometry showed selective binding of WF121 to CD38 + MM1S cells, with no binding to CD38⁻ U266 cells, while confocal microscopy revealed predominantly membrane-associated WF121 with partial internalization into the cytoplasm. 64 Cu-NOTA-WF121 demonstrated favorable in vivo behavior, with specific and high-contrast uptake in CD38 + MM1S tumors, low background uptake in CD38 − U266 models, and predominantly renal clearance. Autoradiography confirmed homogenous tumor uptake and highlighted WF121 accumulation pattern in the renal cortex. Conclusion: This study provides the first preclinical evidence that a 64 Cu-labeled anti-CD38 nanobody enables effective early and delayed immuno-PET imaging of CD38 expression in MM. These findings support the potential of nanobody-based radiotracers for non-invasive phenotyping and patient stratification in CD38 targeted therapies.

Background:Selective Internal Radiation Therapy with yttrium-90 (Y90) has been used for decades, yet guideline recommendations remain inconsistent. High-quality real-world data is needed to guide practice. The objectives of this study were to evaluate effectiveness, safety, and patient quality of life (QoL) with TheraSphere™ treatment in real-world clinical practice, and to identify clinical and dosimetric factors associated with survival. Methods:PROACTIF was a prospective, open label, non-interventional, all-comers cohort study that recruited patients who received Y90 glass microspheres (TheraSphere™) per local standard of care across 34 French sites (January 2019-January 2024). Co-primary endpoints were overall survival (OS) and QoL. Secondary endpoints included safety, conversion to surgery, and factors associated with OS. OS and time-to-deterioration in QoL (Functional Assessment of Cancer Therapy-Hepatobiliary) were assessed by Kaplan-Meier analysis. Adverse events were descriptively summarized using Common Terminology Criteria for Adverse Events, version 5. Trial registration: ClinicalTrials.gov Identifier, NCT04069468. Findings:Amongst 989 HCC patients, 13·3%/18·9%/57·9%/5·8% were Barcelona Clinic Liver Cancer (BCLC) A/B/C/D, respectively; 35·3% had portal-vein tumor thrombosis (PVT); 74·4% were treated using multicompartment dosimetry, and 53·6% with selective Y90 administration. Mean index lesion dose was 435·4 Gy. For all patients, median OS (mOS) [95% CI] was 21·8 months (M) [20·1-23·3]. mOS was 27·0 M [20·7-31·4] for BCLC B, 21·1 M [18·0-22·8] for BCLC C; 23·1 M [21·6-27·0] without PVT, 24·8 M [19·3-30·3] for patients with Vp1/Vp2; 16·8 M mOS for patients with a pretreatment absorbed dose to the index lesion <200 Gy versus 26·0 M with ≥200 Gy (p < 0·001); 19·7 M for <400 Gy and 30·7 M for ≥400 Gy (p < 0·001). After Y90, 106/989 (10·7%) underwent curative-intent surgery, resulting in a mOS of 48·6 M [40·6-not evaluable], versus 20·1 M [17·7-21·7] without surgery. Median time-to-deterioration in QoL was 10·6 M [9·6-11·7]. Serious adverse events occurred in 7·5% patients; serious treatment-related events in 3·7%. Interpretation:In this large real-world cohort, treatment with Y90 glass microspheres demonstrated favorable effectiveness and safety with meaningful outcomes, especially in PVT patients and following subsequent surgery. PROACTIF showed a strong dose-survival relationship as demonstrated in previous studies, and highlights the potential of a tumor absorbed dose ≥400 Gy to further increase survival. These findings support dosimetry-guided Y90 across all BCLC stages, and should inform future guideline recommendations. Funding:Boston Scientific Corporation.

Manual segmentation of prostate cancer metastases on PSMA PET/CT and SPECT/CT is time-consuming and poorly scalable, particularly in highly metastatic patients. This study evaluated nnU-Net–based automatic segmentation models trained on PET and SPECT either separately or jointly and assessed whether PET-derived information can improve SPECT lesion segmentation. Seventy-three patients with metastatic castration-resistant prostate cancer treated with ¹⁷⁷Lu-PSMA were retrospectively included: 48 from the Henri Becquerel Cancer Center (HBCC) and 25 from Nantes University Hospital (NUH). For each patient, ⁶⁸Ga-PSMA PET/CT and ¹⁷⁷Lu-PSMA SPECT/CT were acquired before and during the first treatment cycle respectively. All images were manually segmented by four nuclear medicine physicians in consensus. Four nnU-Net models were trained: M1 (PET/CT only), M2 (SPECT/CT only), M3 (joint PET/CT+SPECT/CT, unimodal input at inference), and M4 (SPECT/CT with PET/CT segmentation as a priori input). Models were first trained and internally validated on HBCC data, then retrained on the full HBCC cohort and externally validated on NUH data. For PET/CT segmentation, M1 and M3 achieved comparable performance. M1 reached DSCs of 0.83 ± 0.19 (internal) and 0.76 ± 0.22 (external), while M3 achieved 0.83 ± 0.16 (internal) and 0.77 ± 0.21 (external). For SPECT/CT, the PET-guided model M4 (DSC: 0.63 ± 0.24 internal; 0.78 ± 0.14 external; PPV: 0.65 ± 0.26 internal; 0.75 ± 0.23 external) provided the best results. Compared with the SPECT-only model M2 (DSC: 0.61 ± 0.26 internal; 0.70 ± 0.25 external; PPV: 0.63 ± 0.25 internal; 0.71 ± 0.24 external), M4 showed no statistically significant difference in internal validation (DSC p = 0.35), while being statistically significant in external validation (DSC p = 0.014). The nnU-Net framework enables accurate lesion segmentation on both ⁶⁸Ga-PSMA PET/CT and ¹⁷⁷Lu-PSMA SPECT/CT. While PET-only and joint PET+SPECT models perform similarly on PET images, incorporating PET-derived segmentations as prior information tends to improve SPECT/CT lesion segmentation. This PET-guided SPECT segmentation strategy leverages the higher spatial resolution of PET and represents a key step towards fully automated extraction of volumetric and dosimetric biomarkers for personalized prostate cancer treatment.

Abstract Purpose Therapeutic administration of 90Y-loaded microspheres is routinely used for primary and secondary liver tumours. For activity-based therapeutic prescription the activity must be within 10% of the intended activity. Previous studies reported significant discrepancies between manufacturer-declared vial activities and both experimental and Monte-Carlo assessments, greater than 10%, for resin/glass 90Y-microspheres. The objective of this work was to investigate whether these discrepancies were also seen in patients. Methods We analysed patient 90Y-PET reconstructions (99 glass and 15 resin microspheres) from 4 different institutions and 4 different systems. We considered tail-fitting background scaling (TFBS) and absolute scaling (ABS), for scatter correction. Residuals after therapeutic injection were measured. Eighty-one patients were imaged with PET/CT and 33 with PET/MR. The PET measured activity (APET) was assessed in the whole liver. The ratio APET/Acalibrator was calculated for each patient, where Acalibrator was the injected activity measured by the dose calibrator corrected for residual and lung shunt. Results Quantification ratio between calibrators and PET was significantly different from 1, regardless of the scatter correction used. In glass microspheres, the mean APET/CT/Acalibrator was 0.84 ± 0.06 for TFBS and 0.90 ± 0.06 for ABS (0.66 ± 0.09 and 0.76 ± 0.07 for (APET/MR/Acalibrator)). The mean APET/CT/Acalibrator ratio for resin microspheres was 1.16 ± 0.09 for TFBS and 1.30 ± 0.12 for ABS. Conclusions We observed in patients similar activity discrepancies as reported for vials, with a relative difference of 44 ± 16% between glass and resin 90Y-loaded microspheres. In 90Y hepatic radioembolization, the 10% accuracy prerequisite on knowing the administered therapeutic activity is then unlikely to be met.

Contexte L’étude Vision a montré que le [177Lu]Lu-PSMA-617 ajouté au standard de traitement prolongeait la survie sans progression (SSP) radiographique et la survie globale chez les patients (pts) atteints de cancer de la prostate résistant à la castration métastatique (CPRCm) TEP-PSMA positive. Les autorités françaises ont accordé une autorisation d’accès précoce au [177Lu]Lu-PSMA-617 dans cette indication. Méthodes Les pts CPRCm PSMA positif ayant reçu≥1 chimiothérapie à base de taxane et≥1 hormonothérapie dite de nouvelle génération (HTNG) ont été inclus. Le [177Lu]Lu-PSMA-617 a été administré jusqu’à 6 cycles (7,4 GBq) toutes les 6 semaines. Les caractéristiques des pts et la tolérance sont décrites pour l’ensemble de la population. L’efficacité a été analysée chez les pts inclus la 1re année. L’évaluation du grade des événements indésirables (EI) n’a pas été réalisée. Résultats Du 01/12/2021 au 30/06/2023, 945 pts ont été inclus et 535 ont été analysés pour l’efficacité. Au moment de la clôture des données, 474 pts étaient encore sous traitement et 471 avaient arrêté le traitement en raison d’une progression de la maladie (50,5 %), de la survenue d’un EI (7,2 %) ou d’un décès (7,4 %). 124 pts (26,3 %) ont bénéficié des 6 cures. Les caractéristiques de la population étaient : âge médian 73,2 (44–92) ans ; ECOG 0–1 : 86,3 % ; sites métastatiques : os 93,8 % ; ganglions lymphatiques : 62,4 % ; foie : 10,7 % ; traitement antérieur par taxane : 97,1 %, dont 61,6 %>1 ; traitement antérieur par HTNG : 100 % dont 66,6 %>1 (médiane : 2). Traitement concomitant par HTNG : 26,8 %. À propos des résultats d’efficacité, la meilleure réponse à l’imagerie a été évaluée à la discrétion des investigateurs : 1,2 % de RC, 35,7 % de RP et 26,7 % de maladie stable. Le PSA a diminué chez 68,1 % des pts avec un délai médian de 1,22 (0,1–9,6) mois. 12,8 % (n=121) des pts ont déclaré≥1 EI lié au traitement, dont 99 pts avec≥1 EI grave. Trois décès liés au traitement ont été rapportés. Les EI les plus rapportés étaient : thrombocytopénie (5,4 % des pts) et anémie (5,0 % des pts). Conclusion Dans cette cohorte « en vie réelle » de CPRCm traités par [177Lu]Lu-PSMA-617, comparativement à Vision, les pts sont plus lourdement prétraités, ont reçu moins de traitements par HTNG en concomitant et sont plus nombreux à avoir reçu>1 chimiothérapie par taxanes. La tolérance du [177Lu]Lu-PSMA-617 reste favorable. Les inclusions étant toujours en cours, des résultats actualisés seront présentés.

PET has become an indispensable tool in medical imaging, providing critical insight into disease prognosis and treatment response. This review article aims to examine the multifaceted role of PET quantification by (1) providing an overview of the routinely used quantitative metrics and their limitations; (2) reporting how these metrics are being tested in clinical research to improve prognosis, highlighting both their potential benefits and the most promising applications; (3) defining current therapeutic assessment criteria in hemato-oncology with adaptations to innovative treatments and novel tracers; and (4) exploring advanced quantification techniques to harness large-scale data for more accurate prognostic modeling.

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.

This study compared the prognostic value of total metabolic tumor volume (TMTV) in lymphoma measured with the recently proposed SUV4.0 segmentation threshold versus the 41

89Zr is emerging as a popular positron-emitting radionuclide for imaging; however, its 909 keV gamma emission presents shielding challenges, and radiation exposure safety guidelines for healthcare professionals working with the radionuclide have not been well-established. To guide assessment of the radiation risk and necessary safety guidelines, we present laboratory dose rate measurements of 89Zr syringes and vials, and dose rates measurements made during the ZIRCON clinical trial ([89Zr]Zr-girentuximab) to evaluate healthcare provider exposure during administration, imaging, and surgical procedures. The maximum dose rate from a vial with no shielding was 0.334 µSv/h/MBq, and the minimum dose rate with 66 mm lead shielding was 0.004 µSv/h/MBq. The controlled spill measured 0.52 µSv/h/MBq. Dose rates 1 m from patients who received [89Zr]Zr-girentuximab had an average of 3.90 µSv/h at imaging. During surgery, waste measured below background levels, and a bed assistant 0.8 m from the patient received a 5 µSv/h whole-body dose rate. The excised kidney measured 6 µSv/h at 5 cm. Our results demonstrate low radiation exposure levels associated with 89Zr handling and exposure to the patient. With potential integration of 89Zr into clinical practice, appropriate radiation safety guidelines are needed. Dose rate measurements can help guide development of best practices and site-specific protocols. Clinical trial number: not applicable for this study; ZIRCON trial number NCT03849118, registered on 19 February 2019.