(18)F-Fluorodeoxyglucose positron emission tomography/ computed tomography (PET/CT) is a highly accurate staging method in classical Hodgkin lymphoma (cHL). We retrospectively compared the staging results obtained in two large cohorts of patients with cHL diagnosed before (n = 324) and after (n = 406) the introduction of PET/CT staging in a retrospective study. In PET/CT staged patients, stage I disease was less frequent (16% vs. 27%, p < 0.001) while stage IV disease was more frequent (17% vs. 10%, p = 0.02). Imaging-detected skeletal involvement was recognized more often in PET/CT staged patients (17% vs. 2%, p < 0.001), and the presence of focal skeletal PET/CT lesions was associated with higher risk of progression (hazard ratio [HR] 1.96, 95% confidence interval [CI]: 1.14-3.36). The German Hodgkin Study Group (GHSG) risk classification (early, intermediate, advanced disease) predicted outcome in PET/CT staged patients. In conclusion, PET/CT led to higher disease stages, and the more frequently diagnosed skeletal lesions may be an adverse prognostic factor.

Purpose: The aim of this phase II trial (NCT02965001) was to evaluate the prognostic value of urokinase-type plasminogen activator receptor (uPAR)-PET/CT with the novel ligand ⁶⁸Ga-NOTA-AE105 in head and neck cancer and compare it to ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Materials and Methods: Patients with head and neck squamous cell carcinoma (HNSCC) referred to curatively intended radiotherapy were eligible and prospectively included in this phase II study. A ⁶⁸Ga-uPAR- and ¹⁸F-FDG-PET/CT were performed before initiation of curatively intended radiotherapy and maximum standardized uptake values (SUV_max) of the primary tumor was measured on both PET/CTs by two independent readers. Relapse-free survival (RFS) and overall survival (OS) were calculated and optimal cut-off values were established for ⁶⁸Ga-uPAR- and ¹⁸F-FDG-PET independently and compared using log rank and Kaplan-Meier statistics, and univariate and multivariate analysis in Cox proportional hazards model. Results: A total of 57 patients were included and followed for a median of 33.8 months (range 2.30-47.2). The median SUV_max of the primary tumors were 2.98 (range 1.94-5.24) for ⁶⁸Ga-uPAR and 15.7 (range 4.24-45.5) for ¹⁸F-FDG. The optimal cut-off points for ⁶⁸Ga-NOTA-AE105 SUV_max in the primary tumor was 2.63 for RFS and 2.66 for OS. A high uptake of ⁶⁸Ga-NOTA-AE105 (SUV_max above cut-off) was significantly associated with poor RFS and OS (log-rank P = 0.012 and P = 0.022). ⁶⁸Ga-NOTA-AE105-uptake in the primary tumor was significantly associated with poor RFS in univariate analysis (HR=8.53 (95% confidence interval (CI) 1.12-64.7), P = 0.038) and borderline associated with OS (HR=7.44 (95% CI 0.98-56.4), P = 0.052). For ¹⁸F-FDG-PET, the optimal cut-off points were 22.7 for RFS and 22.9 for OS. ¹⁸F-FDG SUV_max above cut-off was significantly associated with reduced RFS (log-rank P = 0.012) and OS (log-rank P = 0.000). ¹⁸F-FDG-uptake was significantly associated with reduced RFS and OS in univariate analysis (HR=3.27; 95% CI 1.237-8.66), P = 0.017) and (HR=7.10; 95% CI 2.60-19.4), p<0.001). In a multivariate analysis including ⁶⁸Ga-uPAR SUV_max, ¹⁸F-FDG SUV_max, Tumor, Node and Metastasis (TNM) stage and p16 status, only ⁶⁸Ga-uPAR SUV_max remained significant (HR 8.51 (95%CI 1.08-66.9), P = 0.042) for RFS. For OS, only TNM stage and ¹⁸F-FDG remained significant. Conclusion: The current phase II clinical trial showed promising results for the use of ⁶⁸Ga-uPAR-PET SUV_max in the primary tumor to predict RFS in HNSCC patients referred to curatively intended radiotherapy when compared to ¹⁸F-FDG-PET, TNM stage and p16 status. ⁶⁸Ga-uPAR-PET could potentially become valuable for identification of patients suited for de-escalation of treatment and risk stratified follow-up schemes.

The prognostic value of metabolic tumor burden parameters obtained from ¹⁸F-FDG PET/CT imaging was evaluated in this retrospective national multicenter study of patients with metastatic posterior uveal melanoma (PUM) and compared to the largest diameter of the largest metastatic lesion (LDLM) and the American Joint Committee on Cancer (AJCC) staging system. The Maximal Standard Uptake Value (SUV_max), Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) were obtained in 106 patients. Higher values of SUV_max (p = 0.007, log-rank), MTV (p < 0.001, log-rank), and TLG (p < 0.001, long-rank) were associated with shorter survival. The three parameters were also independent predictors in the multivariate Cox model, while the AJCC staging turned insignificant. Time-dependent positive predictive value (PPV) analysis and Receiver Operating Characteristics (ROC) curves showed that MTV (Area Under the Curve (AUC) = 0.78), TLG (AUC = 0.78), and LDLM (AUC = 0.76) were good predictors of 1-year survival. For the subset of 97 patients with liver metastases, the corresponding regional measurements in the liver tended to be even better predictors. In conclusion, MTV and TLG were found to be better predictors of survival in metastatic PUM than the AJCC staging system, but when LDLM was used as a continuous variable it showed an equally good prediction of 1-year survival.

Background/Objectives: Identifying treatment failure at earlier time points to could spare cancer patients from ineffective treatment and side effects. In this study, circulating tumor DNA (ctDNA) and [¹⁸F]FDG-PET/CT were investigated during the first cycle of anticancer therapy in patients with advanced non-small cell lung cancer (NSCLC) to explore their potential for early response evaluation. Methods: Patients with advanced NSCLC receiving first-line therapy with immune checkpoint inhibitors and/or chemotherapy were included. CtDNA and [¹⁸F]FDG-PET/CT assessments were conducted before treatment and at weeks 1 and 3 during the first cycle of therapy. ctDNA quantification was performed using a targeted next-generation sequencing (NGS) panel, and the least favorable change in any mutated allele frequency at a given time was used for analysis. [¹⁸F]FDG-PET/CT was quantified using sumSUL_peak and metabolic tumor volume (MTV_4.0). Early changes in ctDNA levels and [¹⁸F]FDG-PET parameters were compared with final treatment response, measured by RECIST after 12 weeks, as well as progression-free survival and overall survival. Results: Of the sixteen included patients, eight were non-responders. ctDNA mutations were detected in baseline blood samples in eight patients. Changes in ctDNA level, MTV_4.0, and sumSUL_peak at week 3 indicated response in 7 out of 8 patients, 13 out of 15 patients, and 9 out of 15 patients, respectively. At week 3, no false increases were seen with ctDNA and MTV_4.0. Conclusions: These results suggest that early changes in ctDNA and [¹⁸F]FDG-PET/CT at 3 weeks of treatment could be used to early assess treatment response. Increased levels of ctDNA and MTV_4.0 at week 3 were only observed in patients with treatment failure.

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.