Background Accurate quantification of iodine uptake is essential for performing pre-treatment dosimetry of ¹³¹I therapy after redifferentiation of radioiodine-refractory thyroid cancer. Standardized procedures for ¹²⁴I PET/CT-based dosimetry are currently lacking. We aim to evaluate the relation between ¹⁸F and ¹²⁴I imaging for two different PET/CT scanners, the effect of bias correction on recovery across scanners and investigate the impact of clinically-encountered background (BG)-to-lesion ratios on recovery correction. Methods Cylindrical and NEMA body phantoms were scanned following vendor-recommended ¹²⁴I acquisition using clinically representative activity concentrations (5.6–5.7 kBq/mL in cylindrical phantom, 45.1–59.2 kBq/mL in NEMA spheres) and BG-to-sphere ratios (∼1:125 to 1:infinity) using two digital PET/CT scanners (Philips Vereos and GE Healthcare Omni). Additionally, BG-to-sphere ratio ∼1:10 was acquired to compare ¹²⁴I to the EARL ¹⁸F standards 1 (EARL1). Calibration accuracy and recovery coefficients (RC_max, RC_mean) were compared between scanners with and without bias correction. Results ¹²⁴I recovery was ∼20% higher for the Omni compared to the Vereos, showing calibration accuracies of 1.12–1.15 vs. 0.94, and RC_mean reaching 0.86 vs. 0.69. After bias correction, RC_mean was comparable between scanners ('1%) but below the lower limits of EARL1. A single fit for recovery correction (R² = 0.97) was obtained for different BG-to-sphere ratios for both scanners as RC_mean was comparable (p ' 0.4). Conclusion Vendor-recommended ¹²⁴I acquisition and reconstruction leads to differences in quantification but can be compensated using a bias correction. Recovery correction is minimally affected by different BG-to-lesion ratios, suggesting that one RC curve is sufficient, simplifying ¹²⁴I calibration procedures in studies requiring ¹²⁴I quantification.

Background: Prior studies show that short-term treatment using tyrosine kinase inhibitors (TKIs) can reinduce radioiodine uptake and warrant ¹³¹I therapy in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). We aim to evaluate the potential of standard-of-care TKI lenvatinib to reinduce clinically meaningful radioiodine retention. Methods: Nine RAI-R DTC patients starting lenvatinib treatment for progressive advanced or metastatic disease, were included and underwent rhTSH-stimulated ¹²⁴I dosimetric procedures at baseline, week 6 (N=7) and week 12 (N=8). At all timepoints, the fraction of patients eligible for ¹³¹I therapy with a maximal activity of 7.4 GBq was assessed. Patients were considered eligible if at least one target lesion showed an expected mean absorbed dose ≥20 Gy. In total, 23 target lesions were segmented on¹²⁴I PET/CT images and their volumes estimated using low-dose CT images. Lesion size-specific recovery correction was applied to the measured mean activity concentration at each timepoint. Tumor dosimetry was performed using a mono-exponential fit and S-values from an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms (IDAC-Dose2.1). Mean absorbed lesion dose per administered activity (LDpA), 24h-uptake and residence time in target lesions were compared between time points. Results: By our definition, none of the patients were found eligible for ¹³¹I therapy at any timepoint. Lenvatinib-induced partial response was observed in 59% and 75% of target lesions at week 6 and 12, respectively. Median LDpA was 0.08 (IQR: 0.04-0.17), 0.18 (0.08-0.36) and 0.17 (0.09-0.37) Gy/GBq for week 0, 6 and 12, respectively (p=0.08). The 24h-uptake and residence time were comparable between timepoints (p>0.22). Conclusion: Redifferentiation of RAI-R DTC to reinduce radioiodine uptake to a level that warrants ¹³¹I therapy may not be established by short-term lenvatinib treatment. Multi-targeted TKIs may not be as potent as selective TKIs in reinducing clinically meaningful radioiodine retention.

Background and aims
Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment. However, ICIs may increase the immune response to non-tumor cells, possibly resulting in increased arterial inflammation, raising the risk of atherosclerotic events. Nevertheless, malignancies may induce a pro-inflammatory state and the association between ICIs and arterial inflammation remains to be clarified. This study aims to assess differences in increase in arterial inflammation between patients with advanced melanoma treated with ICIs compared to a control group without ICIs.

Methods
Patients with advanced melanoma who underwent [18F]FDG PET/CT scans at baseline, 6 months (T1) and 18 months (T2) were included in this retrospective observational study. Arterial inflammation was evaluated in eight segments by calculating the target-to-background ratio (TBR). The primary study outcome was the difference in increase in mean TBRmax between patients treated with and without ICIs.

Results
We included 132 patients of whom 72.7 % were treated with ICIs. After exclusion for the use of anti-inflammatory medication, patients treated with ICIs showed a significant increase in mean TBRmax between baseline and T1 from 1.29 ± 0.12 to 1.33 ± 0.13 (p = 0.017), while in the control group, no change in mean TBRmax (1.30 ± 0.12 to 1.28 ± 0.10, p = 0.22) was observed (p = 0.027). During longer follow-up, mean TBRmax remained stable in both groups. Arterial inflammation increased significantly after ICI therapy in patients without active inflammation (p < 0.001) and in patients without calcifications (p = 0.013).

Conclusions
A significant increase in arterial inflammation as measured on [18F]FDG PET/CT was observed in patients with advanced melanoma treated with ICIs only in the first six months after initiation of therapy, whereas no changes were observed in the control group. Moreover, arterial inflammation was mainly increased in patients without pre-existing inflammatory activity and with non-calcified lesions.

BACKGROUND: Adjuvant chemotherapy after curative resection for rectal cancer is the standard of care in several American and European guidelines. OBJECTIVE: The aim of this study was to examine the differences in health-related quality of life over time between patients with rectal cancer who were treated with adjuvant chemotherapy or observation. DESIGN: This is a randomized controlled phase III trial. SETTINGS: Health-related quality-of-life assessments were conducted in Dutch patients from 43 institutes. PATIENTS: Patients with stage II or III rectal cancer who underwent preoperative (chemo)radiotherapy followed by curative surgery (the SCRIPT trial) were included. INTERVENTIONS: Patients were randomly assigned to adjuvant capecitabine monotherapy for 8 cycles or observation. Health-related quality of life was assessed using the European Organization for Research and Treatment of Cancer C30 and CR38 questionnaires at 1 month after surgery (before the start of chemotherapy), and 3, 6, and 12 months after surgery. MAIN OUTCOME MEASURES: The primary outcome measure was the difference in quality of life at 6 months after surgery, just after completion of adjuvant chemotherapy for patients in the treatment group. Second, the difference in health-related quality of life at 12 months after surgery was examined. A statistically significant difference of 5 points was considered clinically relevant. RESULTS: Health-related quality-of-life results of 226 of 233 patients were available. At T3, overall quality of life (C30 summary score) was worse for patients treated with chemotherapy compared with observation (mean 82.3 versus 86.9, p = 0.006), but the difference was not clinically relevant. Patients treated with adjuvant chemotherapy reported clinically relevant worse physical functioning (mean 78.3 versus 87.0, p < 0.001) and more reports of fatigue and dyspnea (35.7 versus 21.0 and 17.1 versus 6.7, p < 0.001). All differences were resolved at 12 months postsurgery. LIMITATIONS: A selection of relatively fit patients willing to be randomly assigned may limit the generalizability of the results. CONCLUSIONS: Although inferior health-related quality of life was reported just after completion of adjuvant chemotherapy, no persistent deterioration in quality of life was detected. See Video Abstract at http://links.lww.com/DCR/A907.