Plasmacytoma and Amyloid Lymphadenopathy, FDG, and Fluorocholine.

ABSTRACT: A 56-year-old man with thoracal mass suspected of solitary plasmacytoma was referred for 18F-FDG PET-CT scan. His PET-CT revealed FDG-avid rib mass and cervical lesion at level 2. He also underwent 18F-fluorocholine (FCH) PET-CT to evaluate possible metastatic spread of the disease. FCH PET-CT showed increased uptake at the rib mass, while the cervical lesion was not FCH-avid. Biopsies confirmed rib lesion was a solitary plasmacytoma; however, the cervical lesion was an amyloid deposited lymph node. This case showed FCH PET-CT is a valuable companion of FDG scan for the evaluation of plasma cell dyscrasias with a better specificity.

Theranostics of Thyroid Cancer.

Molecular imaging is pivotal in evaluating and managing patients with different thyroid cancer histotypes. The existing, pathology-based, risk stratification systems can be usefully refined, by incorporating tumor-specific molecular and molecular imaging biomarkers with theranostic value, allowing patient-specific treatment decisions. Molecular imaging with different radioactive iodine isotopes (ie, I131, I123, I124) is a central component of differentiated carcinoma (DTC)'s risk stratification while [18F]F-fluorodeoxyglucose ([18F]FDG) PET/CT is interrogated about disease aggressiveness and presence of distant metastases. Moreover, it is particularly useful to assess and risk-stratify patients with radioiodine-refractory DTC, poorly differentiated, and anaplastic thyroid cancers. [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT is the most specific and accurate molecular imaging procedure for patients with medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells. In addition, [18F]FDG PET/CT can be used in patients with more aggressive clinical or biochemical (ie, serum markers levels and kinetics) MTC phenotypes. In addition to conventional radioiodine therapy for DTC, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC. Moreover, peptide receptor theranostics showed promising results in patients with advanced and metastatic radioiodine-refractory DTC and MTC, respectively. The current appropriate role and future perspectives of molecular imaging and theranostics in thyroid cancer are discussed in our present review.

Integrated Diagnostics of Thyroid Nodules.

Thyroid nodules are common findings, particularly in iodine-deficient regions. Our paper aims to revise different diagnostic tools available in clinical thyroidology and propose their rational integration. We will elaborate on the pros and cons of thyroid ultrasound (US) and its scoring systems, thyroid scintigraphy, fine-needle aspiration cytology (FNAC), molecular imaging, and artificial intelligence (AI). Ultrasonographic scoring systems can help differentiate between benign and malignant nodules. Depending on the constellation or number of suspicious ultrasound features, a FNAC is recommended. However, hyperfunctioning thyroid nodules are presumed to exclude malignancy with a very high negative predictive value (NPV). Particularly in regions where iodine supply is low, most hyperfunctioning thyroid nodules are seen in patients with normal thyroid-stimulating hormone (TSH) levels. Thyroid scintigraphy is essential for the detection of these nodules. Among non-toxic thyroid nodules, a careful application of US risk stratification systems is pivotal to exclude inappropriate FNAC and guide the procedure on suspicious ones. However, almost one-third of cytology examinations are rendered as indeterminate, requiring "diagnostic surgery" to provide a definitive diagnosis. 99mTc-methoxy-isobutyl-isonitrile ([99mTc]Tc-MIBI) and [18F]fluoro-deoxy-glucose ([18F]FDG) molecular imaging can spare those patients from unnecessary surgeries. The clinical value of AI in the evaluation of thyroid nodules needs to be determined.

Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [18F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC.

Unexpected Axillary Lymph Node Uptake During Lower-Limb Lymphoscintigraphy in a Case With Vulvar Lymphangioma Circumscriptum.

ABSTRACT: Lymphoscintigraphy is a safe, minimally invasive, and well-established imaging modality for evaluating lymphatic drainage in patients with suspected lymphedema. We report a case of an 8-year-old girl with lymphangioma circumscriptum of the labium majora. She was referred to lymphoscintigraphy for swelling of the lower extremities. Scintigraphy showed widespread dermal backflow at bilateral lower limbs, aberrant uptake in the abdominal lymph nodes, and unexpected uptake in the right axillary lymph nodes.

Pretest PSA and Restaging PSMA PET/CT Predict Survival in Biochemically Recurrent Prostate Cancer.

BACKGROUND: A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. METHODS: A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA threshold and restaging PSMA PET/CT. A Cox regression analysis of OS was carried out to detect significant clinical characteristics. RESULTS: In the cohort, 271 patients had a pretest PSA of <0.5 ng/mL and 945 patients had higher PSA values. The restaging PSMA PET/CT was positive for 834 patients and negative for 369. Of 1203 patients, 133 (11%) died, including 19 of the 369 (5%) patients without positive sites on the restaging PSMA PET/CT, 82 of the 711 (12%) with 1-5 positive sites, and 32 of the 123 (26%) with >5 positive sites. In the Cox regression analysis, four variables significantly predicted OS: treatment center, International Society of Urologic Pathology (ISUP) grade, pretest PSA threshold, and the grouping of positive sites on the restaging PSMA PET/CT. CONCLUSIONS: The pretest PSA and PSMA PET/CT were important for the OS of the BCR patients. The findings argue for the new BCR risk model and serve as framework for ongoing trials.

Value of Dynamic 18F-FDG PET/CT in Predicting the Success of Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer: A Prospective Study.

Objectives: This prospective study was planned to compare the predictive value of dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in locally advanced breast cancer patients (LABC) receiving neoadjuvant chemotherapy (NAC). Methods: Twenty seven patients with LABC [median age: 47, (26-66)] underwent a dynamic 18F-FDG PET study at baseline, and after 2-3 cycles of (NAC) were included (interim). Maximum standardized uptake value (SUVmax) values and SUV ratios for the 2nd, 5th, 10th, and 30th minutes and dynamic curve slope (SL) values and SL ratios were measured using 18F-FDG dynamic data. In addition, the values of SUVmean (2minSUVmean), SULpeak (2minSULpeak), metabolic volume (2minVol), and total lesion glycolysis (2minTLG) were measured for the first 2 min. Percent changes between baseline and interim studies were calculated and compared with the pathological results as the pathological complete response (PCR) or the pathological non-complete response (non-PCR). Receiver operating characteristic curves were obtained to calculate the area under the curve to predict PCR. Optimal threshold values were calculated to discriminate between PCR and non-PCR groups. Results: Baseline study SUV 30 (p=0.044), SUV 30/2 (p=0.041), SUV 30/5 (p=0.049), SUV 30/10 (p=0.021), SL 30/2 (p=0.029) and SL 30/5 (p=0.027) values were statistically significant different between PCR and non-PCR groups. The percentage changes of 2minVol between PCR and non-PCR groups were statistically significant. For the threshold value of -67.6% change in 2minVol, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.2%, 77.8%, 63.6%, 93.3%, and 80.7%, respectively (area under the curve: 0.826, p=0.009). Conclusion: Semiquantitative parameters for dynamic 18F-FDG PET can predict PCR. % changes in 2minVol can identify non-responding patients better than other parameters.

Prognostic factors of overall and prostate-specific antigen-progression-free survival in metastatic castration-resistant prostate cancer patients treated with 177 Lu-PSMA-617. A single-center prospective observational study.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is characterized by heterogeneity among patients as well as therapy responses due to diverse genetic, epigenetic differences, and resistance mechanisms. At this stage of the disease, therapy modalities should be individualized in light of the patients' clinical state, symptoms, and genetic characteristics. In this prospective study, we aimed to evaluate the outcome of patients with mCRPC treated with 177 Lutetium labeled PSMA-617 therapy (PSMA-RLT), as well as baseline and therapy-related parameters associated with survival. METHODS: This prospective study included 52 patients who received two to six cycles of PSMA-RLT. Primary endpoints were overall survival (OS) and prostate-specific antigen (PSA)-progression-free survival (PFS). 18 F-Fluorodeoxyglucose (FDG) and 68 Ga-PSMA (PSMA) Positron Emission Tomography/Computer Tomography (PET/CT) scans were performed for a comprehensive assessment of tumor burden and heterogeneity. Biochemical, imaging, clinical, and therapy-related parameters were analyzed with the Kaplan-Meier, log-rank, and Cox regression analyses to predict OS and PFS. RESULTS: Median OS and PSA-PFS were 17.7 (95% confidence interval [CI]: 15.2-20.2) and 6.6 months (95% CI: 4.5-8.8), respectively. Primary resistance to PSMA-RLT (hazard ratio [HR]: 12.57, 95% CI: 2.4-65.2, p: 0.003), <30% PSA response rate after first cycle of PSMA-RLT (HR: 1.016, 95% CI: 1.006-1.03, p: 0.003), FDG > PSMA disease (HR: 4.9, 95% CI: 1.19-20.62, p: 0.03), PSA doubling time (PSA DT) of ≤2.4 months (HR: 15.7, 95% CI: 3.7-66.4, p: <0.0001), and low hemoglobin levels (HR: 0.59, 95% CI: 0.41-0.83, p: 0.003) were correlated with poor OS in the multivariate analysis. Bone scintigraphy > PSMA disease (HR: 5.6; 95% CI: 1.8-17, p: 0.002) and high C-reactive protein (HR: 1.4, 95% CI: 1.1-1.7, p: 0.001) were significant predictive biomarkers for PFS in the multivariate analysis. CONCLUSION: PSA response rate and pattern to PSMA-RLT are the most important predictors of survival in patients receiving PSMA-RLT. Being a strong predictive biomarker, combined FDG and PSMA PET can be helpful for the decision of PSMA-RLT eligibility.

Correction: von Eyben et al. A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis. Cancers 2022, 14, 5461.

In the original publication [...].

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Diagnostic Performance of 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) for Risk Stratification of Hypofunctioning Thyroid Nodules: A European Multicenter Study.

99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: -19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

Role of indocyanine green combined with radiotracer-Technetium 99 m in neck surgery for primary and recurrent head and neck cancer: preliminary results of a tertiary cancer center.

PURPOSE: Neck dissection (ND), whether therapeutic or elective, is an essential component of the treatment of head and neck squamous cell carcinoma (HNSCC). Due to altered anatomy and fibrosis caused by initial treatments, surgeons face challenges during salvage ND. A combination of Technetium-99 m and indocyanine green (ICG) previously used in the sentinel lymph node (SLN) biopsy for oral cavity cancers, may be useful in different types of neck surgeries. We aimed to show the additional advantage of this combination in detecting HNSCC and thyroid cancer recurrences, as well as individual lymphatic drainage in elective ND. METHODS: We retrospectively reviewed medical records of patients, underwent neck surgery guided with ICG and Tc-99 m, in Hacettepe University Hospital between June 2018 and December 2020. In a total of 28 patients, intraoperative gamma probes were paired with near infrared (NIR) cameras. Patients are divided into two groups: neck surgery with recurrent occult lesion localization (NS- ROLL) (n: 14) and ND with SLN screening (ND-SLNS) (n: 14). RESULTS: Among all 14 patients in NS-ROLL group, recurrent diseases, hidden behind tissues were 100% successfully localized. In ND-SLNS group, 238 lymph nodes were harvested, metastasis rate was 31.3% (10/32) in sentinel nodes. SLNS revealed 100% accuracy in detecting metastasis in clinically N0 neck (10/238). Contralateral lymphatic drainage was observed in three patients (lateral-sided oral cavity SCC). In two patients (floor of mouth), three sentinel nodes were detected by NIR only. CONCLUSION: The use of ICG-radiotracer provides additional value in disease removal for both primary and recurrent tumors of the head and neck.

68Ga-DOTATATE PET/CT in Pituitary Carcinoma.

ABSTRACT: A 47-year-old woman with atypical pituitary adenoma was referred to the neurosurgery department due to recent back pain. She had multiple transsphenoidal surgery, stereotactic body radiation, and 177Lu-DOTATATE therapy. Her spinal MRI showed multiple spinal masses. The patient underwent 68Ga-DOTATATE PET/CT to confirm the metastatic spread of the disease. PET/CT images showed increased uptake at the local recurrent tumor site and spinal metastases confirmed by biopsy to pituitary carcinoma. Our case presents the role of 68Ga-DOTATATE PET/CT in patients with pituitary carcinoma.

Clinical parameters and nomograms for predicting lymph node metastasis detected with 68 Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy.

BACKGROUND: Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients. MATERIALS AND METHODS: The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves. RESULTS: A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF. CONCLUSION: The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning.