Malene Grubbe Hildebrandt

Background: Adjuvant anti-PD-1 therapy improves recurrence-free survival (RFS) in high-risk melanoma, but many patients experience adverse events. 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography with computed tomography [¹⁸F]FDG-PET/CT has been proposed to identify biomarkers that may predict outcome of treatment. Objectives: The aim of this register-based study was to investigate the prognostic value of immune-related adverse events (irAEs), spleen-to-liver ratio (SLR), and bone marrow-to-liver ratio (BLR), detected by [¹⁸F]FDG-PET/CT. Methods: This retrospective, register-based cohort study included 122 patients with radically resected stage III–IV melanoma treated with adjuvant anti-PD-1. Patient data were extracted from a Danish register, and measurements for SLR and BLR were made using an AI model. Cox regression models were made on irAEs and BLR to assess associations with RFS and overall survival (OS). Results: Over half of the patients experienced recurrence, and one quarter died during follow-up of 4 ¾ years. Seventy-four percent exhibited at least one PET-detected irAE. This study found no association between irAEs and OS. Regarding RFS, our findings suggest an increased risk of recurrence for the presence of irAEs within the first 1.5 years of follow-up (HR: 2.93, CI: 1.10–7.84, p = 0.032). BLR and SLR were not associated with RFS or OS in multivariable models. Conclusions: This study did not confirm the findings of a positive association between irAEs and survival found in previous studies. PET-detected irAEs were common in the study population, but did not predict OS, while early-onset irAEs were linked to increased recurrence risk. Neither SLR nor BLR demonstrated prognostic value. Further research is needed to clarify the clinical utility of PET-derived biomarkers, especially in the adjuvant setting.

Purpose: The PET Response Criteria in Solid Tumours (PERCIST) 1.0 provides a standardized framework for evaluating treatment response using [ ¹⁸ F]fluorodeoxyglucose ([ ¹⁸ F]FDG) positron emission tomography – computed tomography (PET-CT), but its clinical use is hindered by manual complexity. This study presents coPERCIST, an artificial intelligence (AI)-assisted module integrated into the RECOMIA platform that semi-automates and streamlines PERCIST analysis. Methods: coPERCIST performs organ segmentation and automates key steps of the PERCIST workflow, including background activity quantification, lesion detection, SULpeak calculation, and longitudinal lesion comparison. A novel image alignment method using organ-specific transformations and uncertainty estimation enables accurate lesion tracking over time. The system was evaluated in 58 oncological patients, each with two PET-CT scans. Up to three measurable lesions per patient were analysed. Results: The AI-suggested liver and aorta volume of interest for threshold calculation were correct in all baseline and follow-up studies. Follow-up studies were classified as progressive metabolic disease (PMD) in 38 cases, stable metabolic disease (SMD) in 16, and partial metabolic response (PMR) in 4. Of 130 lesions evaluated, anatomical alignment was accurate in all cases, and pairwise SULpeak quantification was accurate in 95%. Pairwise SULpeak quantification failed in seven lesion pairs due to proximity to other lesions or misclassified physiological uptake. Review time was less than one minute for most cases. Conclusion: This study demonstrates the feasibility of AI-assisted PERCIST evaluation for [ ¹⁸ F]FDG PET-CT, showing promising accuracy. coPERCIST offers potential for reproducible response assessment and supports future multicentre validation. It is freely available to researchers via the RECOMIA platform.

Positron emission tomography–computed tomography (PET-CT) is recommended for response evaluation in aggressive large B-cell lymphoma (LBCL) but cannot detect minimal residual disease (MRD). Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for real-time disease monitoring. This study evaluated longitudinal ctDNA monitoring as an MRD marker in LBCL. In this prospective, single-center study, 14 newly diagnosed patients with LBCL receiving first-line immunochemotherapy underwent frequent longitudinal blood sampling. A 53-gene targeted sequencing panel quantified ctDNA and evaluated its kinetics, correlating it with clinical parameters and PET-CT, including total metabolic tumor volume (TMTV) calculated using artificial intelligence–based analysis via RECOMIA. Baseline ctDNA was detected in 11 of 14 patients (79%) with a median variant allele frequency of 6.88% (interquartile range, 1.19%-10.20%). ctDNA levels correlated significantly with TMTV (ρ = 0.90; P < .0001) and lactate dehydrogenase. ctDNA kinetics, including after 1 treatment cycle, mirrored PET-CT metabolic changes and identified relapsing or refractory patients. This study demonstrates ctDNA-based MRD monitoring in LBCL using a fixed targeted assay with an analytical sensitivity of at least 10−3. The kinetics of ctDNA reflects the clinical course and PET-CT findings, underscoring its complementary potential to PET-CT.

Background/Objectives: The SENTIREC-endo study identified a safe sentinel lymph node mapping algorithm combined with PET-positive node dissection, matching radical pelvic and paraaortic lymphadenectomy in high-risk endometrial cancer. The present study evaluated the diagnostic accuracy of FDG-PET/CT for lymph node metastases in the same population based on location, size, and Standardised Uptake Value (SUV), in addition to assessing interrater agreement across three Danish centres. Methods: This prospective multicentre study included women with high-risk endometrial cancer from the Danish SENTIREC study database (2017–2023). All patients underwent preoperative FDG-PET/CT. Diagnostic accuracy was evaluated against a pathology-confirmed reference standard. Interrater agreement was evaluated between trained specialists in Nuclear Medicine. Results: Among 227 patients, 52 patients (23%) had lymph node metastases. FDG-PET/CT identified lymph node metastases with 56% sensitivity (95% CI: 42–68) and 91% specificity (95% CI: 86–94). Positive and negative predictive values were 64% and 87%, respectively. Specificity for paraaortic nodes was high (97%), though sensitivity remained limited (56%). Lymph node size and SUVmax had moderate diagnostic value (AUC-ROC ~0.7). Interrater proportion of agreement was 95% and Cohen’s Kappa κ = 0.84 (95% CI: 0.73–0.94), the latter of which was ‘almost perfect’. Conclusions: FDG-PET/CT had limited sensitivity in lymph node staging in high-risk EC, and the diagnostic accuracy of FDG-PET/CT remains complementary to the sentinel node procedure. Due to its high specificity and strong interrater reliability, FDG-PET/CT is recommended for clinical implementation in combination with the sensitive sentinel node biopsy for the targeted dissection of PET-positive lymph nodes, particularly in paraaortic regions.

Nuclear medicine imaging for prostate cancer has advanced significantly over the past decade. A survey is presented in this review. PSMA-PET/CT is a new highly accurate method that has been introduced, but bone scans and bone-PET continue to be widely applied. PSMA-PET/CT still lacks sufficient patient outcome data to be recommended for treatment allocation when used for primary staging. However, the literature and clinical guidelines support its use at the stage of biochemical recurrence. In Denmark, the use of nuclear medicine examinations for prostate cancer aligns with clinical guideline recommendations.

The study aimed to compare the metastatic pattern of breast cancer and the intermodality proportion of agreement between [¹⁸F]FDG-PET/CT and CE-CT. Women with metastatic breast cancer (MBC) were enrolled prospectively and underwent a combined [¹⁸F]FDG-PET/CT and CE-CT scan to diagnose MBC. Experienced nuclear medicine and radiology physicians evaluated the scans blinded to the opposite scan results. Descriptive statistics were applied, and the intermodality proportion of agreement was used to compare [¹⁸F]FDG-PET/CT and CE-CT. In total, 76 women with verified MBC were enrolled in the study. The reported number of site-specific metastases for [¹⁸F]FDG-PET/CT vs. CE-CT was 53 (69.7%) vs. 44 (57.9%) for bone lesions, 31 (40.8%) vs. 43 (56.6%) for lung lesions, and 16 (21.1%) vs. 23 (30.3%) for liver lesions, respectively. The proportion of agreement between imaging modalities was 76.3% (95% CI 65.2–85.3) for bone lesions; 82.9% (95% CI 72.5–90.6) for liver lesions; 57.9% (95% CI 46.0–69.1) for lung lesions; and 59.2% (95% CI 47.3–70.4) for lymph nodes. In conclusion, bone and distant lymph node metastases were reported more often by [¹⁸F]FDG-PET/CT than CE-CT, while liver and lung metastases were reported more often by CE-CT than [¹⁸F]FDG-PET/CT. Agreement between scans was highest for bone and liver lesions and lowest for lymph node metastases.

We evaluated the cost-effectiveness of 2-[¹⁸F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[¹⁸F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007–2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[¹⁸F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[¹⁸F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[¹⁸F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[¹⁸F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[¹⁸F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer.

We investigated the impact of 2-[18F]FDG-PET/CT on detection rate (DR) of the primary tumor and survival in patients with suspected cancer of unknown primary tumor (CUP), comparing it to the conventional diagnostic imaging method, CT. Patients who received a tentative CUP diagnosis at Odense University Hospital from 2014–2017 were included. Patients receiving a 2-[18F]FDG-PET/CT were assigned to the 2-[18F]FDG-PET/CT group and patients receiving a CT only to the CT group. DR was calculated as the proportion of true positive findings of 2-[18F]FDG-PET/CT and CT scans, separately, using biopsy of the primary tumor, autopsy, or clinical decision as reference standard. Survival analyses included Kaplan–Meier estimates and Cox proportional hazards regression adjusted for age, sex, treatment, and propensity score. We included 193 patients. Of these, 159 were in the 2-[18F]FDG-PET/CT group and 34 were in the CT group. DR was 36.5% in the 2-[18F]FDG-PET/CT group and 17.6% in the CT group, respectively (p = 0.012). Median survival was 7.4 (95% CI 0.4–98.7) months in the 2-[18F]FDG-PET/CT group and 3.8 (95% CI 0.2–98.1) in the CT group. Survival analysis showed a crude hazard ratio of 0.63 (p = 0.024) and an adjusted hazard ratio of 0.68 (p = 0.087) for the 2-[18F]FDG-PET/CT group compared with CT. This study found a significantly higher DR of the primary tumor in suspected CUP patients using 2-[18F]FDG-PET/CT compared with patients receiving only CT, with possible immense clinical importance. No significant difference in survival was found, although a possible tendency towards longer survival in the 2-[18F]FDG-PET/CT group was observed.