Staging and response assessment of melanoma is a challenging radiological task as the tumor entity is characterized by atypical metastatic phenotypes and response patterns. Radiologists should scrutinize diagnostic images for unusual metastatic sites, including, e.g., gastrointestinal, endobronchial, or splenic metastases. Routine imaging modalities must include body CT or PET/CT staging and brain MRI. Response assessment is complicated by pseudoprogression and dissociated response, which radiologists must identify and communicate with the treating physicians. Criteria-based reporting with immune-adapted response criteria, such as iRECIST, should be used. The abundant use of checkpoint inhibitor therapy should make radiologists aware of immune-related adverse events, which must be detected early. In addition, imaging professionals must carefully identify potential side effects that mimic progression, in particular sarcoid-like reactions with newly developed mediastinal and hilar lymphadenopathy, as this will ensure that progressive disease is not overcalled. Additionally, radiologists should be aware of the emerging field of intratumoral immunotherapy, which can result in local inflammatory changes at injection sites that may also mimic progression. For this, a dedicated adaptation of the response criteria may be applied with itRECIST.

Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024–2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. 81 patients (median age 68, interquartile range 64–75) were included. Algorithm results were benign (48.1

Imaging-based staging is a key component of renal cell carcinoma (RCC) management, yet anatomic labels alone do not fully capture tumor biology. This review highlights key aspects of RCC staging using computed tomography (CT) and magnetic resonance imaging (MRI), compares their use across major guidelines, and explores how integrating imaging-based prognostic markers can refine preoperative risk assessment. We summarize the pragmatic use of multiphase CT and MRI for T-staging, highlight pitfalls, and outline indications for chest and ancillary imaging based on American Urological Association, European Association of Urology, and National Comprehensive Cancer Network guidelines. We also discuss imaging-based prognostic biomarkers, including central non-enhancement and enhancement heterogeneity, diffusion metrics, and radiomic signatures, and we describe how they correlate with outcomes such as tumor grade, stage, molecular features, and survival. In addition, we dive into future directions, focusing on the potential integration of advanced technologies (e.g., photon-counting detector CT, [89Zr] Zr-deferoxamine (DFO)-girentuximab positron emission tomography/CT), integration with liquid biopsy, and development of standardized reporting systems focusing on cancer likelihood and aggressiveness (e.g., Kidney Imaging Reporting and Data System). By bridging staging descriptors with prognostic phenotypes, we aim to standardize reports, better inform management, and improve decision-making for patients with RCC.

INTRODUCTION:Focal dose intensification strategies targeting the dominant intra-prostatic lesion (DIL) improve outcomes of patients with prostate cancer. The purpose was to determine whether the 6-month multiparametric (mp)MRI response of the DIL is associated with post-treatment prostate-specific antigen (PSA) kinetics after MRI linear accelerator (LINAC) guided stereotactic body radiotherapy (SBRT) with focal dose intensification. METHODS:Retrospective, single-center study including 72 patients with localized prostate cancer treated with MRI-LINAC SBRT with focal dose intensification and without androgen deprivation therapy. Patients were followed up at 6 months after SBRT with mpMRI and PSA. mpMRI complete response (CR) was defined as no residual lesion on diffusion-weighted imaging and dynamic contrast-enhanced MRI. This was correlated with PSA responses including PSA reduction (%), PSA reduction ≥ 50.0% (PSA50), and PSA ≤ 1.0 ng/mL. RESULTS:mpMRI CR was achieved in 37 patients (51.4%) at 6 months. Patients with mpMRI CR had greater PSA reduction (81.8% vs 66.1%, p < 0.001), and more commonly had PSA50 (100.0% vs 82.9%, p = 0.010) and PSA ≤ 1.0 ng/mL (45.9% vs 11.4%, p = 0.001) compared to those without mpMRI CR. In 10 patients without 6-month mpMRI CR but had further MRI follow-up (median 13 months), DILs either further decreased in size (30.0%) or resolved (70.0%). CONCLUSION:Initial 6-month mpMRI response correlates with PSA kinetics, which is associated with important clinical outcomes. mpMRI can be used for post-SBRT evaluation to gauge local tumor response of the DIL, where most recurrences occur.

PURPOSE OF THE REPORT:To determine the prevalence, etiology, and clinical significance of incidental focal small bowel FDG uptake in patients undergoing PET/CT for staging of non-small bowel cancers. MATERIAL AND METHODS:Retrospective review of consecutive FDG PET/CT examinations obtained for cancer staging with incidental focal small bowel radiotracer uptake was performed. Exclusion criteria included known small bowel pathology or insufficient reference standard. Imaging findings assessed included lesion location, number, CT correlate, SUV max , and presence of metastases outside the bowel. Clinical data included age, sex, cancer clinical setting, origin, and stage. Focal small bowel FDG uptake etiology (benign vs. metastatic) was determined by composite reference standard (histopathology, clinical, and imaging follow-up). Statistical analyses included Wilcoxon rank-sum test, Pearson's χ 2 test, Fisher exact test, and ROC curve analyses. RESULTS:In a review of 147,516 PET/CT examinations, incidental focal small bowel FDG uptake was rare, with a prevalence of 0.1% (88/147,516). Most cases were metastatic, 60.2% (53/88), most commonly spread from lymphoma [32.1% (17/53)] and melanoma [30.2% (16/53)]. Metastatic lesions were evenly distributed throughout the ileum [47.2% (25/53)] and jejunum [39.6% (21/53)]. Metastatic focal small bowel FDG uptake was associated with presence of other sites of distant metastases, higher SUV max , and presence of a CT correlate ( P <0.01). CONCLUSIONS:Incidental focal small bowel FDG uptake is rare. Most small bowel hypermetabolic foci are metastatic and are predominantly encountered with melanoma and lymphoma. Multiple imaging and clinical factors helped differentiate between benign and metastatic focal small bowel FDG uptake.

To assess the performance of 68Ga-PSMA PET/CT in detecting biochemically recurrent prostate cancer and evaluate associations of PET imaging findings with alterations on genomic profiling. 68Ga-PSMA PET/CT scans of 603 prostate cancer patients with biochemical recurrence or persistently elevated PSA and without known metastatic disease were retrospectively included (mean PSA 1.0 ng/mL; range, 0.08-5). All scans were analysed for presence of recurrence by two experienced nuclear medicine physicians independently; discrepancies were resolved by an additional expert reader. A subset of patients (n = 239) had undergone tumour genetic profiling using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay. PET positivity and positive predictive value, inter-reader agreement, as well as associations between patient characteristics, location of recurrence, time to PET confirmed biochemical recurrence (PCBR), SUVmax, and most frequent gene alterations were investigated. The overall recurrence detection rate of 68Ga-PSMA PET/CT was 59.2

Background Magnetic field inhomogeneities are challenging for ultrahigh-field (UHF) MRI, and may affect segmentation algorithm performance. We therefore investigated the impact of different segmentation techniques on radiomic features extracted from UHF MRI of the brain. Materials and Methods We analyzed 21 MP2RAGE datasets with 0.63 mm3 isotropic resolution obtained at 7 Tesla. Radiomic features (histogram, texture, and shape) from the cerebral gray and white matter, basal ganglia, ventricles, cerebellum, and brainstem were extracted using three segmentation techniques: the deep-learning algorithm Cerebrum-7T; the Freesurfer-v7 algorithm; and the Nighres algorithm. Principal components (PCs) were calculated for histogram and texture features, and intraclass correlation coefficients (ICC) were used to compare radiomic feature values and PCs to those obtained with a reference standard including human expert correction. Results For histogram PCs, exemplary median ICCs for Cerebrum-7T, Freesurfer-v7, and Nighres were 0.99, 0.42, and 0.11 for the gray matter; and 0.84, 0.25, and 0.43 for basal ganglia. For texture PCs, median ICCs for Cerebrum-7T, Freesurfer-v7, and Nighres were 0.95, 0.21, and 0.15 for the gray matter; and 0.70, 0.36, and 0.023 for basal ganglia. For shape features, median ICCs for Cerebrum-7T, FreeSurfer-v7, and Nighres were 0.99, 0.91, and 0.36 for the gray matter; and 0.89, 0.90, and 0.13 for basal ganglia. Conclusions Radiomic features on UHF MRI of the brain show substantial variability depending on the segmentation method. Segmentation tools tailored for the use with UHF data, such as the deep-learning algorithm Cerebrum-7T, may be needed for adequate reproducibility of radiomic features at 7 Tesla.

Disease progression is a substantial challenge in patients with non-Hodgkin lymphoma (NHL) undergoing chimeric antigen receptor T cell (CAR-T) therapy. Here we present InflaMix (INFLAmmation MIXture Model), an unsupervised quantitative model integrating 14 pre-CAR-T infusion laboratory and cytokine measures capturing inflammation and end-organ function. Developed using a cohort of 149 patients with NHL, InflaMix revealed an inflammatory signature associated with a high risk of CAR-T treatment failure, including increased hazard of death or relapse (hazard ratio, 2.98; 95% confidence interval, 1.60–4.91; P < 0.001). Three independent cohorts comprising 688 patients with NHL from diverse treatment centers were used to validate our approach. InflaMix consistently and reproducibly identified patients with a higher likelihood of disease relapse and mortality, and it provided supplementary predictive value beyond established prognostic markers, including tumor burden. Moreover, InflaMix exhibited robust performance in cases with missing data, maintaining accuracy when considering only six readily available laboratory measures. These findings show that InflaMix is a valuable tool for point-of-care clinical decision-making in patients with NHL undergoing CAR-T therapy. A preinfusion circulatory inflammation biomarker-based signature predicts the likelihood of treatment failure in patients with non-Hodgkin lymphoma who were treated with CAR-T cell therapy, with an inflammatory cluster assignment being prognostic of clinical response and survival outcomes.

An increasing number of patients with prostate cancer (PCa) undergo assessment with magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This offers comprehensive multimodality staging but can lead to discrepancies. The objective was to assess the rates and types of discordance between MRI and PSMA-PET/CT for primary PCa assessment. Consecutive men diagnosed with intermediate and high-risk PCa who underwent MRI and PSMA-PET/CT in 2021–2023 were retrospectively included. MRI and PSMA-PET/CT were interpreted using PI-RADS v2.1 and PRIMARY scores. Discordances between the two imaging modalities were categorized as “minor” (larger or additional lesion seen on one modality) or “major” (positive on only one modality or different index lesions between MRI and PSMA-PET/CT) and reconciled using radical prostatectomy or biopsy specimens. Three hundred and nine men (median age 69 years, interquartile range (IQR) 64–75) were included. Most had Gleason Grade Group ≥ 3 PCa (70.9

Imaging is used for lymphoma detection, Ann Arbor/Lugano staging, and treatment response assessment. [18F]FDG PET/CT should be used for most lymphomas, including Hodgkin lymphoma, aggressive/high-grade Non-Hodgkin lymphomas (NHL) such as diffuse large B-cell lymphoma, and many indolent/low-grade NHLs such as follicular lymphoma. Apart from these routinely FDG-avid lymphomas, some indolent NHLs, such as marginal zone lymphoma, are variably FDG-avid; here, [18F]FDG PET/CT is an alternative to contrast-enhanced CT at baseline and may be used for treatment response assessment if the lymphoma was FDG-avid at baseline. Only small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) should exclusively undergo CT at baseline and follow-up unless transformation to high-grade lymphoma is suspected. While [18F]FDG PET/CT is sufficient to rule out bone marrow involvement in Hodgkin lymphoma, biopsy may be needed in other lymphomas. The 5-point (Deauville) score for [18F]FDG PET that uses the liver and blood pool uptake as references should be used to assess treatment response in all FDG-avid lymphomas; post-treatment FDG uptake ≤ liver uptake is considered complete response. In all other lymphomas, CT should be used to determine changes in lesion size; for complete response, resolution of all extranodal manifestations, and for lymph nodes, long-axis decrease to ≤ 1.5 cm are required.

PURPOSE We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities. METHODS In this first-in-human, phase I, dose escalation and expansion clinical trial, patients with relapsed or refractory large B-cell lymphoma received 19(T2)28z-1XX CAR T cells at four dose levels (DLs), ranging from 25 to 200 × 10 6 . RESULTS Twenty-eight patients underwent apheresis and received CAR T cells. Sixteen and 12 patients were treated in the dose escalation and expansion cohorts, respectively. The overall response rate (ORR) was 82% and complete response (CR) rate was 71% in the entire cohort. The lowest dose of 25 × 10 6 was selected for dose expansion. In 16 patients treated at this DL, 88% achieved ORR and 75% CR. With the median follow‐up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond 12 months. In all cohorts, grade ≥3 cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome rates were low at 4% and 7%, respectively. 1XX CAR T-cell products contain a higher proportion of CD8 T cells with memory features, and CAR T-cell persistence has been detected beyond 1-2 years in patients with ongoing remission. CONCLUSION The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses with favorable toxicity profiles and may benefit the treatment of other hematologic malignancies, solid tumors, and autoimmunity.

To develop a tool for the clinical hybrid imaging workflow which combines morphologic and functional measurements. And to quantify the number of clicks saved per positron emission tomography/computed tomography (PET/CT) interpretation. A tool was developed where a volume of interest (VOI) is automatically created around line distance measurements. VOI statistics for both PET and CT component, and line distances are generated and displayed. Usage data for the first two months after introduction of the tool was analyzed. Eleven radiologists and nuclear medicine physicians used the tool in 364 PET/CTs. In 19

The role of extranodal (EN) sites as potential sanctuary regions resistant to CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) remains unclear. To investigate this, we retrospectively analyzed 283 adults treated with commercial CD19 CAR-T therapy, assessing 958 PET-CT scans across four time points: pre-apheresis, pre-lymphodepletion, best response, and relapse. EN involvement prior to CAR-T therapy was common (76%). Outcomes for patients with exclusive EN disease were similar to those with nodal (ND) disease alone; however, patients with concomitant EN and ND disease (EN + ND) had lower complete response rates and shorter progression-free survival. Site-specific outcomes varied: lungs/pleura/pericardium and gastrointestinal/peritoneum involvement had the lowest local response rates (48% and 51%, respectively). Notably, the risk of same-site relapse was highest in the lungs/pleura/pericardium (hazard ratio [HR] 7.8) and gastrointestinal/peritoneum (HR 5.97). Among patients relapsing after CAR-T, two-year overall survival rates from time of relapse were significantly lower in those with EN relapse (23% for exclusive EN; 25% for EN + ND) compared to exclusive ND relapse (64%; p = 0.008). These findings underscore the high prevalence of EN disease in CAR-T recipients and its site-specific impact on outcomes, highlighting the need for organ-targeted strategies to enhance treatment efficacy.

Prostate-specific membrane antigen (PSMA)-PET/CT has become integral to management of prostate cancer; however, PSMA-avid rib lesions pose a diagnostic challenge. This study investigated clinicopathological and imaging findings that predict metastatic etiology of PSMA-avid rib lesions. Consecutive patients with prostate cancer that underwent PET/CT with [18F]F-DCFPyL in 2021–2023 for newly diagnosed intermediate-/high-risk prostate cancer or recurrent/metastatic disease and had PSMA-avid rib lesions were included. Imaging findings assessed were: lesion number, PSMA expression (maximum standard uptake value (SUVmax), miPSMA score), CT features (sclerotic, lucent, fracture, no correlate), other sites of metastases, and primary tumor findings. A composite reference standard for rib lesion etiology (metastatic vs non-metastatic) based on histopathology, serial imaging, and clinical assessment was used. One hundred and seventy-five men (median 71 years, IQR 65–77) with PSMA-avid rib lesions were included; 47/175 (26.9

While CD19-directed CAR T-cell therapy represents a transformative immunotherapy for relapsed/refractory large B-cell lymphoma (r/r LBCL), more than 50% of patients ultimately progress or relapse. Recently, the International Metabolic Prognostic Index (IMPI) – incorporating age, stage, and metabolic tumor volume (MTV) – was shown to improve prognostication for LBCL frontline treatment. Here, we examine its utility to predict toxicity and survival in CAR-T recipients. This multicenter observational study spanning six international sites included 504 patients with available 18FDG-PET/CT imaging at last response assessment prior to lymphodepletion. Optimal CAR-adapted MTV thresholds were identified in a development cohort (n = 256) and incorporated into a CAR-T-specific IMPI (“CAR-IMPI”). The prognostic performance of CAR-IMPI was validated in an independent cohort (n = 248). CAR-IMPI risk categories, defined by the median (1.35) and terciles (1.07, 1.58), demonstrated significant discrimination for progression-free survival (PFS; p < 0.0001) and overall survival (OS; p < 0.0001) in both cohorts. Multivariate Cox regression confirmed CAR-IMPI as an independent predictor of survival, accounting for pre-lymphodepletion LDH and CRP, performance status, treatment center, and CAR-T product. Patients in the CAR-IMPI high-risk category experienced increased severity of CRS and ICANS, and higher rates of intensive care unit (ICU) admissions. In an exploratory analysis, combining CAR-IMPI with established indices of high-risk systemic inflammation (CAR-HEMATOTOX, InflaMix) further enhanced survival stratification. The CAR-IMPI may provide a potent and validated PET-based tool for risk stratification of clinical outcomes in patients with r/r LBCL receiving CD19 CAR-T therapy. Our data highlight the utility of combining clinical and radiological modalities, with implications for patient selection and the anticipated level-of-care for toxicity management.

To explore pragmatic approaches integrating MRI and PSMA-PET/CT for evaluating extraprostatic extension (EPE) of prostate cancer (PCa). Consecutive patients with newly-diagnosed PCa that underwent multiparametric MRI and PSMA-PET/CT, followed by radical prostatectomy in 2021–2024 were included. Imaging parameters assessed on both modalities were: size, length of capsular contact (LCC), Likert scales (MRI EPE grade/PSMA Likert scale), PI-RADS/PRIMARY scores, and SUVmax. Three pragmatic integrated approaches were tested: (1) Integration of Likert scales (positive if either or both MRI and PSMA-PET/CT were positive); (2) P score (framework combining PI-RADS + PRIMARY); and (3) combining MRI morphological information with PSMA-PET/CT functional information (upgrading suspicion of lesions with LCC below cutoff if SUVmax>12). Diagnostic performance was tested with receiver operating characteristic (ROC) curves and compared using DeLong and McNemar tests. 67 men (median age, 66 years) with EPE in 76.1

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71

Supplementary Table S1. Systemic bridging regimens.