The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients.

PURPOSE: To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine 131I therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by 124I PET. METHODS: Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUVmax > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-124I to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers ("predictors") such as SUVmax and activity in microcurie per gram, from a single imaging timepoint. RESULTS: In the 169 lesions (in 15 patients) that received 131I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUVmax was the best predictor of lesion radiation dose and permitted calculation of the 131I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals. CONCLUSIONS: Based on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint 124I-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement 124I-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center. TRIAL REGISTRATION: NCT04462471, Registered July 8, 2020. NCT03647358, Registered Aug 27, 2018.

Improving risk stratification of indeterminate adnexal masses on MRI: What imaging features help predict malignancy in O-RADS MRI 4 lesions?

PURPOSE: Ovarian-Adnexal Reporting and Data System (O-RADS) MRI uses a 5-point scale to establish malignancy risk in sonographically-indeterminate adnexal masses. The management of O-RADS MRI score 4 lesions is challenging, as the prevalence of malignancy is widely variable (5-90%). We assessed imaging features that may sub-stratify O-RADS MRI 4 lesions into malignant and benign subgroups. METHOD: Retrospective single-institution study of women with O-RADS MRI score of 4 adnexal masses between April 2021-August 2022. Imaging findings were assessed independently by 2 radiologists according to the O-RADS lexicon white paper. MRI and clinical findingswere compared between malignant and benign adnexal masses, and inter-reader agreement was calculated. RESULTS: Seventy-four women (median age 52 years, IQR 36-61) were included. On pathology, 41 (55.4%) adnexal masses were malignant. Patients with malignant masses were younger (p = 0.02) with higher CA-125 levels (p = 0.03). Size of solid tissue was greater in malignant masses (p = 0.01-0.04). Papillary projections and larger solid portion were more common in malignant lesions; irregular septations and predominantly solid composition were more frequent in benign lesions (p < 0.01). Solid tissue of malignant lesions was more often hyperintense on T2-weighted and diffusion-weighted imaging (p ≤ 0.03). Other imaging findings were not significantly different (p = 0.09-0.77). Inter-reader agreement was excellent-good for most features (ICC = 0. 662-0.950; k = 0. 650-0.860). CONCLUSION: Various MRI and clinical features differed between malignant and benign O-RADS MRI score 4 adnexal masses. O-RADS MRI 4 lesions may be sub-stratified (high vs low risk) based on solid tissue characteristics and CA-125 levels.

124I-PET/CT-Guided Diagnosis and Personalized Treatment of Metastatic Papillary Thyroid Cancer to the Pancreas.

ABSTRACT: Metastasis to the pancreas from differentiated thyroid carcinoma is rare. A new pancreatic lesion was identified on surveillance imaging of a man with metastatic papillary thyroid carcinoma 7 years after initial diagnosis. Imaging with 124I-PET/CT was performed to noninvasively confirm metastatic thyroid cancer and provide prospective dosimetry to guide selection of a safe and effective administered activity of 131I. This case demonstrates the emerging role of 124I-PET/CT as a useful diagnostic scan, pretherapy scan, and dosimetric tool to deliver personalized therapy for patients with metastatic thyroid cancer.

Radiomics Biomarkers Correlate with CD8 Expression and Predict Immune Signatures in Melanoma Patients.

Treatment for metastatic melanoma includes targeted and/or immunotherapy. Although many patients respond, only a subset has complete response. As late-stage patients often have multiple tumors in difficult access sites, non-invasive techniques are necessary for the development of predictive/prognostic biomarkers. PET/CT scans from 52 patients with stage III/IV melanoma were assessed and CT image parameters were evaluated as prognostic biomarkers. Analysis indicated patients with high standard deviation or high mean of positive pixels (MPP) had worse progression-free survival (P = 0.00047 and P = 0.0014, respectively) and worse overall survival (P = 0.0223 and P = 0.0465, respectively). Whole-exome sequencing showed high MPP was associated with BRAF mutation status (P = 0.0389). RNA-sequencing indicated patients with immune "cold" signatures had worse survival, which was associated with CT biomarker, MPP4 (P = 0.0284). Multiplex immunofluorescence confirmed a correlation between CD8 expression and image biomarkers (P = 0.0028). IMPLICATIONS: CT parameters have the potential to be cost-effective biomarkers of survival in melanoma, and reflect the tumor immune-microenvironment. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/950/F1.large.jpg.

Microglial responses around intrinsic CNS neurons are correlated with axonal regeneration.

BACKGROUND: Microglia/macrophages and lymphocytes (T-cells) accumulate around motor and primary sensory neurons that are regenerating axons but there is little or no microglial activation or T-cell accumulation around axotomised intrinsic CNS neurons, which do not normally regenerate axons. We aimed to establish whether there was an inflammatory response around the perikarya of CNS neurons that were induced to regenerate axons through a peripheral nerve graft. RESULTS: When neurons of the thalamic reticular nucleus (TRN) and red nucleus were induced to regenerate axons along peripheral nerve grafts, a marked microglial response was found around their cell bodies, including the partial enwrapping of some regenerating neurons. T-cells were found amongst regenerating TRN neurons but not rubrospinal neurons. Axotomy alone or insertion of freeze-killed nerve grafts did not induce a similar perineuronal inflammation. Nerve grafts in the corticospinal tracts did not induce axonal regeneration or a microglial or T-cell response in the motor cortex. CONCLUSIONS: These results strengthen the evidence that perineuronal microglial accumulation (but not T-cell accumulation) is involved in axonal regeneration by intrinsic CNS and other neurons.