Impact of radioiodine therapy on recurrence and survival outcomes in intermediate-risk papillary thyroid carcinoma -A systematic review and meta-analysis.

OBJECTIVE: The utility of radioiodine (RAI) therapy in intermediate-risk papillary thyroid carcinoma (PTC) remains a topic of ongoing discussion. This systematic review and meta-analysis aimed to consolidate existing evidence on the impact of postoperative RAI therapy on recurrence and survival outcomes in intermediate-risk PTC. METHODS: A literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles from January 2008 to March 2023 were included. Odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis. RESULTS: Eleven articles comprising 56,266 intermediate-risk PTC patients were included. 41,530 (73.8%) patients underwent postoperative RAI therapy, while 14,736 (26.2%) patients were kept on no-RAI (NOI) follow-up. No significant reduction in rates of structural disease recurrence was noted with RAI therapy in comparison to NOI follow-up (pooled univariate OR, 0.73, 95% confidence interval [CI], 0.29-1.87, I2 = 75%). RAI therapy was not a significant predictor of better recurrence-free survival (pooled multivariate HR, 0.21; 95% CI, 0.01-3.74, I2 = 94%). Interestingly, RAI therapy was associated with an overall survival benefit compared to NOI follow-up (pooled multivariate HR, 0.63; 95% CI, 0.48-0.82, I2 = 79%). CONCLUSIONS: This meta-analysis did not establish a conclusive benefit of RAI therapy in preventing structural disease recurrence or improving recurrence-free survival in intermediate-risk PTC. However, these results need to be interpreted with caution owing to significant heterogeneity in the existing literature. A prospective, randomised clinical trial is the need of the hour to better understand the effect of RAI therapy on long-term outcomes.

Radioiodine versus no radioiodine outcomes in low-risk differentiated thyroid cancers: A propensity-score matched analysis.

OBJECTIVE: The 2015 American Thyroid Association guidelines recommend against radioiodine (RAI) ablation for patients with low-risk papillary microcarcinoma. However, its role in other low-risk differentiated thyroid cancer (DTC) patients remains controversial. Here, we compare long-term outcomes with RAI versus no-RAI in a large cohort comprising all low-risk DTCs. METHODS: Patients with low-risk, histologically-proven DTC post-thyroidectomy, treated with RAI or kept on follow-up without RAI, between 1990 and 2019 were included. The main outcomes included recurrence rate and recurrence-free survival (RFS), and were validated by propensity-score matching analysis. RESULTS: Of the 2074 low-risk DTC patients (median age: 35 years), 1686 patients underwent RAI-ablation (RAI group), while 388 patients underwent no-RAI follow-up (NOI group). Over a median follow-up of 8 years (range: 3-29), the recurrence rates were similar between the RAI and NOI groups (2.0% vs. 3.3%, p = .161). The 5- and 10-year RFS probabilities were 99.2% and 97.4%, respectively in RAI group versus 98.4% and 96.2%, respectively, in NOI group (p = .055). Subgroup regression analyses showed that patients with age <55 years (p = .044), male sex (p = .015), papillary histology (p = .043), pT3a tumours (p = .049) and postoperative thyroglobulin ≥5 ng/mL (p = .002) had significantly better RFS with RAI compared to NOI follow-up. Propensity-score matching generated 776 matched pairs with no significantly different outcomes between the two groups. CONCLUSIONS: In low-risk DTC patients post-thyroidectomy, RAI ablation does not confer significant survival advantage over no-RAI follow-up. Further studies are required to demonstrate any long-term benefit with RAI, specifically in patients with tumour size >4 cm and elevated postoperative thyroglobulin.

Positron Emission Tomography/Computed Tomography in Thyroid Cancer: An Updated Review.

PET/computed tomography (CT) is a valuable hybrid imaging modality for the evaluation of thyroid cancer, potentially impacting management decisions. 18F-fluorodeoxyglucose (FDG) PET/CT has proven utility for recurrence evaluation in differentiated thyroid cancer (DTC) patients having thyroglobulin elevation with negative iodine scintigraphy. Aggressive histologic subtypes such as anaplastic thyroid cancer shower higher FDG uptake. 18F-FDOPA is the preferred PET tracer for medullary thyroid cancer. Fibroblast activation protein inhibitor and arginylglycylaspartic acid -based radiotracers have emerged as promising PET agents for radioiodine refractory DTC patients with the potential for theranostic application.

Utility of PSMA-PET derived volumetric parameters in initial risk stratification and prediction of prostate cancer metastasis - a head-to-head comparison of the radiotracers 18F-PSMA-1007 and 68Ga-PSMA-11.

OBJECTIVE: This study aimed to explore and compare the utility of baseline 18F-PSMA-1007 and 68Ga-PSMA-11 PET/computed tomography (CT) derived volumetric parameters in initial risk stratification and prediction of prostate cancer (PCa) metastasis. METHODS: Forty treatment-naïve, biopsy-proven intermediate-/high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68Ga-PSMA-11 and 18F-PSMA-1007 (within 2 weeks). The maximum and mean standardized uptake values (SUVmax and SUVmean) of primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) were measured. RESULTS: PSMA-TVp and TL-PSMAp (with both radiotracers) mostly exhibited moderate-to-strong correlation with Gleason score, serum prostate-specific antigen level and clinical tumor stage (Spearman ρ = 0.361-0.783, P-values ≤0.022). Primary tumor SUVmax values were similar across initial risk categories. PSMA-TVp and TL-PSMAp, however, were significantly higher in high-risk PCa compared to intermediate-risk PCa (P-values ≤0.001). Receiver operating characteristic (ROC) curve analysis revealed that F-PSMA-TVp, Ga-PSMA-TVp, F-TL-PSMAp, and Ga-TL-PSMAp (optimal cutoff values of 20.9, 23.4, 142.5, and 144.8, respectively) could effectively differentiate high-risk from intermediate-risk PCa [area under the ROC curve (AUCs) 0.859-0.898, P-values <0.001] with high sensitivity (~68.8-75%) and excellent specificity (100%). PSMA-TVp and TL-PSMAp (with both radiotracers) could predict presence of regional and extraregional nodal metastasis (AUCs 0.703-0.801, P-values ≤0.03) with moderate sensitivity (~47.8-70.6%) and excellent specificity (~82.6-94.1%). CONCLUSION: Our results suggest that baseline PSMA-PET primary tumor volumetric parameters provide a noninvasive, objective, and accurate index for initial risk stratification and can predict presence of regional and extraregional nodal metastasis in PCa patients. Larger studies are warranted to evaluate their incremental role over conventional parameters.

Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: Actinium-225-DOTATATE and Combined Therapies.

The role of lutetium-177-DOTATATE in advanced well-differentiated gastro-entero-pancreatic neuroendocrine tumors is well established. However, there is a scope for improving treatment outcomes. Actinium-225-DOTATATE is a form of targeted alpha therapy (TAT) that results in more efficient tumor cell killing owing to the substantially higher linear energy transfer of alpha particles. Systemic TAT is also safe given that the shorter path length of the alpha particles spares the surrounding healthy tissue and results in relatively fewer adverse events. Combination therapies with radiosensitizing and other chemotherapeutic agents have also gained popularity, especially in the setting of higher grade and fluorodeoxyglucose-avid tumors.

FAPI PET/CT Imaging-An Updated Review.

Despite revolutionizing the field of oncological imaging, Positron Emission Tomography (PET) with [18F]Fluorodeoxyglucose (FDG) as its workhorse is limited by a lack of specificity and low sensitivity in certain tumor subtypes. Fibroblast activation protein (FAP), a type II transmembrane glycoprotein, is expressed by cancer-associated fibroblasts (CAFs) that form a major component of the tumor stroma. FAP holds the promise to be a pan-cancer target, owing to its selective over-expression in a vast majority of neoplasms, particularly epithelial cancers. Several radiolabeled FAP inhibitors (FAPI) have been developed for molecular imaging and potential theranostic applications. Preliminary data on FAPI PET/CT remains encouraging, with extensive multi-disciplinary clinical research currently underway. This review summarizes the existing literature on FAPI PET/CT imaging with an emphasis on diagnostic applications, comparison with FDG, pitfalls, and future directions.

Perirenal Fascia - an Uncommon Site of Metastases in Prostate Cancer Detected on 68Ga-PSMA-11 PET/CT.

Prostate-specific membrane antigen (PSMA) PET/CT is being increasingly utilized as a hybrid imaging modality for the evaluation of prostate cancer (PCa). We report a case of a 50-year-old man with biopsy-proven high-risk PCa in which multiple tracer avid perirenal fascia deposits were identified on 68Ga-PSMA-11 PET/CT, in addition to multi-focal prostatic primary, extensive nodal, and skeletal metastases. This case highlights that perirenal fascia is an uncommon metastatic site in PCa.

Utility of 18F-FDG PET/CT in Assessment of Disease Extent and Response to Treatment in Xanthoma Disseminatum.

The clinical utility of 18F-FDG PET/CT is being increasingly recognized in histiocytic disorders. We report the case of a 23-y-old woman who presented with slowly progressive, yellowish-brown papules, plaques, and nodules over her face and flexures. Besides the multiple cutaneous lesions, lesions of the brain, stomach, gallbladder, and marrow were additionally revealed by baseline 18F-FDG PET/CT. Skin biopsy and the overall clinical picture were consistent with xanthoma disseminatum. Subsequent PET/CT after cladribine therapy revealed a decrease in the extent and metabolic activity of most lesions, suggestive of a favorable response. This case report highlights the potential role of 18F-FDG PET/CT in the accurate assessment of disease extent and posttreatment response in rare histiocytic disorders.

Comparison of 18 F-PSMA-1007 PET/CT With 68 Ga-PSMA-11 PET/CT for Initial Staging in Intermediate- and High-Risk Prostate Cancer.

PURPOSE: This study aimed to compare 18 F-PSMA-1007 PET/CT with 68 Ga-PSMA-11 PET/CT for initial staging in intermediate- and high-risk prostate cancer (PCa) patients. METHODS: Forty treatment-naive, biopsy-proven, intermediate- or high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68 Ga-PSMA-11 and 18 F-PSMA-1007 (within 2 weeks). Assessment of both set of images included delineating number and characteristics of lesions, measurement of tracer uptake (SUV max ), miPSMA scoring, and PET-based stage categorization. RESULTS: Intraprostatic lesions were detected in all patients by both tracers with concordant PET-based T stage. Median SUV max of the dominant PSMA-positive prostatic lesions was not significantly different with 18 F-PSMA-1007 and 68 Ga-PSMA-11 (19.9 vs 19.4, P = 0.127, n = 40). Prostatic miPSMA scores were similar in 31/40 (77.5%) patients with both tracers (weighted κ = 0.71). In 23/40 (57.5%) patients, regional lymph nodes (n = 171) were detected by both tracers. Few additional PET-positive regional lymph nodes (n = 3) were exclusively detected by 18 F-PSMA in 2 patients without altering PET-based N stage. Extraregional lymph nodes (n = 123 in 17/40 patients) and visceral metastatic lesions (n = 18 in 3/40 patients) were detected concordantly by both tracers. PET-positive marrow based and skeletal metastases (n = 71) were detected in 14/40 (35%) patients by both tracers. Few additional marrow and skeletal lesions (n = 7) were exclusively detected on 18 F-PSMA-1007 in 5/14 patients, potentially upstaging PET-based M stage in 2/5 patients. Both radiotracers showed excellent interreader agreement for region-wise detection of lesions. CONCLUSIONS: Our results suggest that 18 F-PSMA-1007 PET/CT is comparable to 68 Ga-PSMA-11 PET/CT in detecting primary and metastatic lesions of PCa.

[68 Ga]Ga-PSMA-11 Small Bowel Uptake in Crohn's Disease: Revisiting the "Non-specificity" of PSMA Ligands.

The rapidly evolving clinical utility of prostate-specific membrane antigen (PSMA) PET/CT as an imaging modality for prostate cancer (PCa) has brought to the forefront a multitude of non-prostatic diseases also exhibiting PSMA radioligand uptake. We report a case of a 71-year-old male with PCa who underwent PSMA PET/CT for recurrence evaluation. The scan demonstrated [68 Ga]Ga-PSMA-11 uptake in the distal ileum. Retrospective enquiry revealed that the patient was a known case of Crohn's disease. This case highlights an uncommon finding of PSMA radioligand uptake in the distal small bowel (non-prostatic benign pathological uptake) in a patient with known Crohn's disease, which may be misinterpreted in the evaluation of PCa.

68Ga-PSMA-11 uptake in tracheal mucus plug - a potential pitfall.

Prostate-specific membrane antigen (PSMA) PET/CT is a well-acclaimed imaging modality for prostate cancer (PCa). However, many reports have highlighted PSMA radioligand uptake in a variety of benign tumors and lesions. We report a case of PCa in which 68 Ga-PSMA-11 uptake was noted in the tracheal lumen. However, 18F-PSMA-1007 PET/CT was done on a subsequent day, which demonstrated no abnormal radiotracer uptake or morphological lesion within the tracheal lumen. This case highlights an uncommon finding of PSMA ligand uptake in a tracheal mucus plug (non-prostatic benign uptake), which may be misinterpreted as a false-positive finding.

Incidental Muscle Uptake of 177Lu-DOTATATE in Peripheral Vascular Disease.

Somatostatin receptor (SSTR)-based imaging and therapy has emerged as well-established modality in neuroendocrine tumors. However, its role in inflammation imaging is still evolving. We present a 48-year-old male with metastatic neuroendocrine tumor who underwent lutetium-177-based somatostatin receptor-based therapy. The post-therapy scan showed a focal tracer uptake in the left calf muscle in addition to the expected tracer uptake at the primary and metastatic sites. Further, cross-sectional imaging and biochemical investigations revealed peripheral vascular disease (PVD). The incidental tracer uptake in the calf on post-therapy scan potentiates the role of somatostatin receptor scintigraphy in identifying macrophage-specific inflammatory reactions.

Orbital and brain metastases on 68Ga-PSMA PET/CT in a patient with prostate carcinoma refractory to 177Lu-PSMA and 225Ac-PSMA therapy.

We present a case of metastatic prostate cancer with rare metastases involving the brain and orbit, in addition to liver, skeletal and nodal metastases. The patient had undergone prior hormonal therapy and chemotherapy and had disease progression despite 2 cycles of 177Lu-Prostate specific membrane antigen (177Lu-PSMA) based radioligand therapy. He had a partial response after 2 cycles of 225Ac-PSMA based targeted alpha therapy, as demonstrated on the 68Ga-PSMA PET/CT study. However, the patient had disease progression at the end of 4 cycles of 225Ac-PSMA therapy, evident by rising prostate specific antigen levels and imaging findings. The end of treatment 68Ga-PSMA PET/CT showed additional sites of metastases in the orbit and brain apart from overall disease progression. These are rare sites of distant spread in prostate cancer and require urgent evaluation and local treatment to prevent potential complications. The importance of detection of metastatic sites in closed cavities is because of the requirement for urgent intervention to avoid compression related complications.