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B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). Here, we describe the case of a patient with MM who was enrolled in the CARTITUDE-1 trial ( NCT03548207 ) and who developed a progressive movement disorder with features of parkinsonism approximately 3 months after ciltacabtagene autoleucel BCMA-targeted CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We show BCMA expression on neurons and astrocytes in the patient’s basal ganglia. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting that this might be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade 3 or higher parkinsonism on the phase 2 ciltacabtagene autoleucel trial and of grade 3 parkinsonism in the idecabtagene vicleucel package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies. A progressive movement disorder in a patient with multiple myeloma treated with anti-BCMA CAR-T cells that might have been related to on-target activity in the brain supports prospective neurologic monitoring after BCMA-targeting therapies.

Inhibition of mitogen-activated protein kinase resulted in an increase in expression of the sodium–iodide symporter in 12 of 20 patients, 8 of whom had sufficient uptake to warrant treatment with radioiodine. Five patients had a response, and 3 had stable disease. Metastatic disease is the most frequent cause of death related to thyroid cancer. 1 Radioiodine (iodine-131) remains a mainstay of therapy for patients with metastatic thyroid cancer of follicular origin (i.e., papillary thyroid cancer or follicular thyroid cancer). Unfortunately, many patients have tumors that do not concentrate iodine, resulting in radioiodine resistance and a poor prognosis (the 10-year survival rate among patients with metastatic thyroid cancer that retains radioiodine avidity is approximately 60%, whereas it is only 10% if the metastases are refractory to radioiodine therapy). 2 Several trials have evaluated strategies to “redifferentiate” metastatic thyroid cancers and render them responsive to . . .

PurposeThe 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.Methods25 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.Results18 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.ConclusionsPET/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.

PurposeTo assess the diagnostic performance of FDG-PET/MRI for the preoperative diagnosis and staging of peritoneal carcinomatosis (PC) using surgical Sugarbaker’s PC index (PCI) as the reference in a multireader pilot study.MethodsFourteen adult patients (M/F: 3/11, mean age: 57 ± 12 year) with PC were prospectively included in this single-center study. Patients underwent FDG-PET/MRI prior to surgery (mean delay: 14 d, range: 1–63 d). Images were reviewed independently by 2 abdominal radiologists and 2 nuclear medicine physicians. The radiologists assessed contrast-enhanced abdominal MR images, while the nuclear medicine physicians assessed PET images fused with T2-weighted images. The abdomen was divided in 13 regions, scored from 0 to 3. A hybrid FDG-PET/MRI radiological PCI was created by combining the study data. Radiological PCI was compared to the surgical PCI on a per-patient and per-region basis. Inter-reader agreement was evaluated.ResultsMean surgical PCI was 10 ± 8 (range: 0–24). Inter-reader agreement was almost perfect for all sets for radiologic PCI (Kappa: 0.81–0.98). PCI scores for all reading sets significantly correlated with the surgical PCI score (r range: 0.57–0.74, p range: < 0.001–0.003). Pooled per-patient sensitivity, specificity, and accuracy were 75%/50%/71.4% for MRI, 66.7%/50%/64.3% for FDG-PET, and 91.7%/50%/85.7% for FDG-PET/MRI, without significant difference (p value range 0.13–1). FDG-PET/MRI achieved 100% sensitivity and 100% specificity for a cutoff PCI of 20. Per-region sensitivity and accuracy were lower: 37%/61.8% for MRI, 17.8%/64.3% for FDG-PET, and 52.7%/60.4% for FDG-PET/MRI, with significantly higher sensitivity for FDG-PET/MRI. Per-region specificity was higher for FDG-PET (95%) compared to MRI (78.4%) and FDG-PET/MRI (66.5%).ConclusionFDG-PET/MRI achieved an excellent diagnostic accuracy per-patient and weaker performance per-region for detection of PC. The added value of PET/MRI compared to MRI and FDG-PET remains to be determined.

B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). We describe the case of a MM patient, enrolled in the CARTITUDE-1 trial (NCT03548207), who developed a progressive movement disorder with features of parkinsonism approximately three months after BCMA-targeted ciltacabtagene autoleucel CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We demonstrate BCMA expression on neurons and astrocytes in the basal ganglia of the patient. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting this may be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade ≥3 parkinsonism on the phase 2 cilta-cel trial and of grade 3 parkinsonism in the idecabtagene vicleucel (ide-cel) package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies.

We propose a standardized approach to quantitative molecular imaging (MI) in cancer patients with multiple lesions. Twenty patients with castration-resistant prostate cancer underwent (18)F-FDG and (18)F-16β-fluoro-5-dihydrotestosterone ((18)F-FDHT) PET/CT scans. Using a 5-point confidence scale, 2 readers interpreted coregistered scan sets on a workstation. Two hundred three sites per scan (specified in a lexicon) were reviewed. (18)F-FDG-positive lesion bookmarks were propagated onto (18)F-FDHT studies and then manually accepted or rejected. Discordance-positive (18)F-FDHT lesions were similarly bookmarked. Lesional SUV(max) was recorded. Tracer- and tissue-specific background correction factors were calculated via receiver-operating-characteristic analysis of 65 scan sets. Readers agreed on more than 99% of (18)F-FDG- and (18)F-FDHT-negative sites. Positive-site agreement was 83% and 85%, respectively. Consensus-lesion maximum standardized uptake value (SUV(max)) was highly reproducible (concordance correlation coefficient > 0.98). Receiver-operating-characteristic curves yielded 4 correction factors (SUV(max) 1.8-2.6). A novel scatterplot (Larson-Fox-Gonen plot) depicted tumor burden and change in SUV(max) for response assessments. Multilesion molecular imaging is optimized with a 5-step approach incorporating a confidence scale, site lexicon, semiautomated PET software, background correction, and Larson-Fox-Gonen graphing.

We propose a standardized approach to quantitative molecular imaging (MI) in cancer patients with multiple lesions.