Salvage Pelvic Lymph Node Dissection and Current State of Imaging for Recurrent Prostate Cancer: Does a Standard Exist?

PURPOSE OF REVIEW: We aim to evaluate the efficacy of salvage lymph node dissection (SLND) for nodal recurrent prostate cancer after primary treatment. We also provide a review of the diagnostic performance of next-generation sequencing (next-generation imaging (NGI)) radiotracers in the salvage setting. RECENT FINDINGS: Most studies evaluating SLND include a heterogeneous population with a small sample size and are retrospective in design. The 5-year clinical recurrence-free and cancer-specific survival following SLND are 26-52% and 57-89%, respectively, among prospective studies. NGI improves accuracy in detecting nodal recurrence compared to conventional CT, with PMSA PET-CT showing the most promise. However, limited studies exist comparing imaging modalities and performance is variable at low PSA values. SLND is a promising treatment option, but more prospective data are needed to determine the ideal surgical candidate and long-term oncologic outcomes. More studies comparing different NGI are needed to determine the best imaging modality in patients who may be candidates for salvage treatment.

PET/CT with (124)I-cG250: great potential and some open questions.

OBJECTIVE: A novel PET radiotracer, (124)I-cG250, is currently under clinical investigation to distinguish clear cell renal cell carcinoma from other benign and malignant renal masses. In this article, we will make suggestions on the data needed to maximize the use of this radiotracer. CONCLUSION: Although the published data are promising, further data are needed to assess the potential usefulness of this agent when dealing with indeterminate renal masses.

FDG PET in a Patient on a GLP-1 Agonist/Insulin Secretagogue.

ABSTRACT: With the increase in use of GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy, Rybelsus) in the population, nuclear medicine physicians should be aware of the possibility of nondiagnostic FDG PET scans due to these medications, which work partly by increasing insulin secretion. We demonstrate a case where a patient's use of such a medication presumptively led to muscular and myocardial uptake, complicating scan interpretation considerably. Clinicians should be aware of the presence of these drugs and their potential effect on biodistribution in FDG PET. Further study is needed to best understand the effects of these medications on FDG biodistribution.

PET/Computed Tomography Transformation of Oncology: Kidney and Urinary Tract Cancers.

Renal cell carcinoma (RCC) and urothelial carcinoma (UC) are two of the most common genitourinary malignancies. 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) can play an important role in the evaluation of patients with RCC and UC. In addition to the clinical utility of 18F-FDG PET to evaluate for metastatic RCC or UC, the shift in molecular imaging to focus on specific ligand-receptor interactions should provide novel diagnostic and therapeutic opportunities in genitourinary malignancies. In combination with the rise of artificial intelligence, our ability to derive imaging biomarkers that are associated with treatment selection, response assessment, and overall patient prognostication will only improve.

One institutions' experience with a true standard 15 mCi dose of I-131 for the treatment of Graves' disease.

INTRODUCTION: Currently, there is a lack of consensus on the fixed dosage of RAI to be administered for this purpose between the main guideline frameworks set forth by the American Thyroid Association (ATA), Society of Nuclear Medicine and Molecular Imaging (SNMMI), European Association of Nuclear Medicine (EANM) and the European Thyroid Association (ETA). In this retrospective study, we will investigate the effectiveness of using a standard dose of 15 mCi ±10% of RAI in the treatment of Graves'. METHODS: A retrospective chart review was conducted for the period between 1 May 2014 and 2 September 2020, to identify patients diagnosed with hyperthyroidism due to Graves' disease. The patients were grouped based on outcome and assessed for the efficacy of the dosage of 15 mCi ±10% of RAI in a successful treatment. RESULTS: Sixty-seven patients were identified that met the inclusion criteria between 1 May 2014 and 2 September 2020. Of the 67 RAI ablations; 60 patients became hypothyroid [60/67, (89.55%)], 2 euthyroid [2/67, (2.99%)] and 5 remained hyperthyroid [5/67, (7.46%)]. CONCLUSIONS: For the treatment of Graves' disease, the use of a standard low dose of 15 mCi ±10% has a high success rate without additional measurements or calculations beyond a standard planar image and 24-h uptake %. The adoption of a standard low dose of 15 mCi of I-131 across institutional guidelines would streamline dosage questions and eliminate the need to determine the weight of the thyroid for calculations in all RAI treatments for hyperthyroidism caused by Graves' disease.

Incidental findings on a Tc99m-SESTAMIBI parathyroid scan post COVID-19 vaccination.

We present a case of abnormal findings on a Tc99m-Sestamibi parathyroid scan, post COVID-19 vaccination. The patient is a 48-year-old female presenting for evaluation of hyperparathyroidism who received the mRNA-1273 Moderna (ModernaTX, Inc.) vaccine seven days prior to the scan. The patient is right hand dominant and reported no traumatic events, inflammation, infection, or extraneous use of the left arm. The patient did report "soreness" of the extremity starting approximately 24 hours post injection which continued to the time of the study.

Incidental renal masses on SPECT/CT and PET/CT.

While the presence of incidental breast and lung masses on cardiac scans is well known, renal masses are often incidentally discovered as well on cardiac examinations, some of which are malignant. We searched the electronic medical record system over the past 18 years, since the system was installed, for patients with a cardiac rubidium-82 (82Rb) rubidium PET/CT or technetium-99m (99mTc) sestamibi SPECT/CT performed within 1 year of a renal-protocol CT or MR. Each PET/CT or SPECT/CT was examined for presence of a renal lesion on the attenuation-correction CT images. We found 43 SPECT/CT and 18 PET/CT studies which fit the desired criteria. Of these, 7 SPECT/CT studies and 2 PET/CT studies demonstrated the renal mass on at least one of the two sets of CT images (rest or stress); if not visible, most commonly the tumor was either out of the field of view or had already been removed. Of these, 6 SPECT/CT and 2 PET/CT studies demonstrated a malignancy. Cardiac SPECT/CT and PET/CT images demonstrate incidental renal masses with a non-negligible frequency, and CT images should be carefully examined.

Rubidium Uptake in Chest Tumors on PET/CT.

Background Chest tumors are often found incidentally on cardiac scans; we aimed to describe the findings of rubidium (Rb) in incidentally discovered extracardiac tumors. Materials and Methods We reviewed a database of cardiac Rb scans performed over a period of 11 years and identified those with a previously unsuspected malignancy seen on the plane of section. We then measured maximum standard uptake value for each of the tumors, as well as background lung, liver, mediastinum, and body wall. In cases where fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) was available, we compared Rb results with FDG PET/CT. Results We identified 63 patients meeting criteria including full visualization of a tumor of at least 1.0 cm with no prior treatment. Of these patients, 17 had breast, 36 had lung, and 10 had miscellaneous other tumors. We selected patients with either breast or lung tumors for further analysis. Overall uptake was relatively stable between rest and stress but lower than FDG PET/CT; it was generally low and similar to blood pool. There was a small but statistically significant correlation between estrogen receptor positivity and Rb uptake in breast tumors. There was a stable pattern of uptake in background tissues, with liver being greater than mediastinal blood pool, which in turn was more avid than lung, which was more avid than subcutaneous body wall tissues. Lung showed a noticeable tendency toward increased uptake in dependent regions, likely reflecting low-level atelectasis. Conclusion Uptake was stable between rest and stress but low relative to FDG PET/CT; some correlations with receptors suggest it may be useful in molecular imaging.

Non-small cell lung cancer: prognostic importance of positive FDG PET findings in the mediastinum for patients with N0-N1 disease at pathologic analysis.

PURPOSE: To assess the prognostic implications of mediastinal positron emission tomographic (PET) findings in patients undergoing curative resection of non-small cell lung cancer (NSCLC) who have histologically negative mediastinal lymph nodes (LNs), with the hypothesis that positive findings at PET are prognostic even in patients with negative histologic findings in the LNs. MATERIALS AND METHODS: Records of patients with a preoperative PET undergoing curative surgery, without adjuvant radiation, for pathologic T1-3N0-1 NSCLC at the University of North Carolina between 2000 and 2006 were reviewed as an institutional review board-approved HIPAA-compliant retrospective study. Ninety patients were evaluable (all histologically negative in mediastinum; 44 with both mediastinoscopy and surgery); 13 patients had positive mediastinal PET findings, and 77 had negative mediastinal PET findings. Local-regional and distant failure rates in patients with and those without mediastinal abnormalities at preoperative PET were compared by using logistic regression and log-rank tests. RESULTS: Median follow-up was 54.3 months (range, 1-99 months). There were higher rates of local-regional (P = .001) and distant (P < .001) failure as well as death (P = .001) in patients with postive PET findings than in patients with negative findings. In multivariable analysis (adjusting for other prognostic factors), positive PET findings in the mediastinum remained prognostic for distant failure (P < .001, hazard ratio = 6.9) and were marginally prognostic for local-regional failure (P = .093, hazard ratio = 1.9). CONCLUSION: Positive findings at preoperative PET in the mediastinum appear to have prognostic implications despite the mediastinal LNs being histologically negative. The high rate of local-regional and distant failure suggests that postoperative radiation therapy and/or chemotherapy may be particularly helpful in patients with positive mediastinal findings at preoperative PET.

Patterns of Recurrence, Detection Rates, and Impact of 18-F Fluciclovine PET/CT on the Management of Men With Recurrent Prostate Cancer.

OBJECTIVE: To evaluate the characteristics of FACBC PET/CT in detecting recurrent prostate cancer after radiation or prostatectomy. The secondary aim was to determine the impact of FACBC PET/CT on radiation treatment recommendations in men with biochemical recurrence postprostatectomy. METHODS: This is a single center retrospective study of men who underwent an FACBC PET/CT for rising PSA after definitive prostate cancer therapy. Detection rates in men with recurrence following any definitive treatment were compared at different PSA levels and anatomical sites. Radiotherapy treatment recommendations for patients postprostatectomy based on conventional imaging findings were compared to recommendations based on FACBC PET/CT findings. RESULTS: A total of 103 men underwent imaging with FACBC PET/CT. 74.8% (77) had lesions consistent with sites of prostate cancer recurrence. At PSA thresholds of <1, 1-2, and >2 ng/mL lesions were detected in 35.5%, 63.6%, and 95.2% of patients respectively (P <.001). The most common site of recurrence was outside of the pelvis (37). Detection of extraprostatic or extrapelvic recurrence was observed in 45.5% of men in the PSA tertile <1ng/mL. FACBC PET/CT results led to changes to the recommended radiotherapy treatment plan in 44.1% (15/34) of men with recurrence following radical prostatectomy. CONCLUSION: FACBC PET/CT demonstrated increased detection of recurrent prostate cancer with increasing PSA levels. Most recurrences were found outside the pelvis. Results of FACBC PET/CT changed radiotherapy management decisions in men treated with prostatectomy, supporting its use in localizing sites of disease recurrence in men with prostate cancer.

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

INTRODUCTION: Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear. PATIENTS AND METHODS: This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms. RESULTS: A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59-2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11-3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45). CONCLUSION: Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis.

Correction: A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

[This corrects the article DOI: 10.1371/journal.pone.0253021.].

Use of yttrium-90 microspheres in patients with advanced hepatocellular carcinoma and portal vein thrombosis.

PURPOSE: Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options because of increased disease burden and diminished hepatic perfusion. Yttrium-90 ((90)Y) microspheres may be better tolerated than chemoembolization in these patients. The present study reviews the safety and efficacy of (90)Y microspheres in HCC with major PVT. MATERIALS AND METHODS: A retrospective review of HCC with main (n = 10) or first-branch (n = 12) PVT treated with (90)Y microspheres (N = 22) was conducted. Cancer of the Liver Italian Program (CLIP) scores ranged from 2 to 5, with 18% of patients having a score of 4 or greater. Imaging response at 8-12 was based on Response Evaluation Criteria In Solid Tumors. Overall survival (OS) was estimated by the Kaplan-Meier method. RESULTS: A total of 32 microsphere treatments (26 glass, six resin) were administered to 22 patients. Common grade 1/2 toxicities included abdominal pain (38%), nausea (28%), and fatigue (22%). Four posttreatment hospitalizations occurred, all less than 48 hours in duration. One death occurred 10 days after therapy. The partial response rate was 8% and progressive disease was seen in 42% of patients. Stable disease was achieved in 50% of treatments. Median OS was 7 months from initial treatment. Patients with Child-Pugh class A disease had a median OS of 7.7 months; those with class B/C disease had an OS of 2.7 months (P = .01). Median OS for patients with CLIP scores of 2/3 was 7 months, versus 1.3 months for those with scores of 4/5 (P = .04). CONCLUSIONS: Yttrium-90 microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. The median OS of 7 months is promising and warrants further study versus systemic therapy.

Detectable size of melanoma metastases to brain on PET/CT.

OBJECTIVE: We aimed to determine at what size melanoma metastases become detectable by PET/CT. METHODS: We reviewed a total of 293 whole-body PET/CT studies performed on 212 patients for staging of melanoma where there was an MRI within a month of the PET/CT. MR and PET/CT were reviewed independently by separate readers. RESULTS: PET/CT revealed an overall incidental true-positive rate of 1% on a per-patient basis, consistent with other studies, with 'hot' lesions (more avid than brain parenchyma) visible at smaller sizes than 'cold' lesions. CONCLUSIONS: PET/CT can detect metastatic melanoma lesions over about 2 cm in size, with hot lesions generally visible at smaller sizes.

Outcome of radioiodine therapy in thyroid cancer patients with recent contrasted computed tomography.

OBJECTIVE: To document the outcome of radioiodine therapy (RIT) in differentiated thyroid cancer (DTC) patients with recent contrasted computed tomography (CCT). METHODS: Eighteen patients with DTC and recent thyroidectomy who underwent RIT within 90 days after a CCT were included. Disease status following RIT and whether the expected response to RIT was achieved were documented. Disease status was classified into one of three categories based on the patient's thyroglobuline level, radioiodine scan (RIS), and other imaging modalities: no evidence of disease (NED), microscopic residual disease (MRD), or gross residual disease (GRD). Expected response to RIT was based on the overall interpretation of the referring physicians of follow up thyroglobuline values, RIS findings and clinical assessment as reflected in progress notes. Follow-up stimulated thyroglobuline and (or) RIS was performed on average 10.8 months after RIT (median 12 months). The last progress note reviewed was on average 33.3 months after RIT (median 31 months). RESULTS: There were 12 patients with NED, two with MRD and four with GRD. Expected response to RIT was achieved in 17 patients. In one patient, the effectiveness of RIT could not be determined. CONCLUSION: RIT in postthyroidectomy setting can be successfully performed within 90 days after CCT. Further research is needed to confirm our findings.

Visual and semiquantitative analysis of 82Rb uptake in malignant tumors on PET/CT: first systematic analysis.

OBJECTIVE: The objective of this study was to analyze the uptake of rubidium in malignant tumors. PARTICIPANTS AND METHODS: Sixteen malignant lesions were included. Two radiologists compared each lesion to four references (subcutaneous fat, lung, mediastinal blood pool, and liver) at rest and stress and scored as 1-4. Maximum standardized uptake value (SUV) in each lesion and four references, as well as ratios of lesion SUV to SUV of each of the references, were calculated at rest and stress. We assessed an agreement for scores of reader 1 versus reader 2 (inter-reader) at rest and stress, scores at rest versus stress (intrapatient) for reader 1 and reader 2, and lesion SUV and respective ratios at rest and stress using paired t-test and Bland-Altman analyses. RESULTS: Fifteen (94%) out of 16 lesions had a score of 3 or 4 at rest or stress or both by at least one reviewer. We did not find evidence of inter-reader bias at rest or stress or intrapatient (rest vs. stress) bias for either reader. SUV ranged from 1.0 to 8.1 at rest and from 0.7 to 6.7 at stress. There was an excellent agreement between ratios of lesion SUV to lung SUV at rest versus stress. On the extreme, there was a poor agreement between ratios of lesion SUV to liver SUV at rest versus stress. Otherwise, the agreement was good for the majority of the results, and moderate for a few others. CONCLUSION: Malignant tumors can be readily depicted and quantified on rubidium PET/CT. Further research is needed.

A pilot study of early 18F-FDG PET to evaluate the effectiveness of radiofrequency ablation of liver metastases.

OBJECTIVE: The objective of our study was to collect pilot data about the use of FDG PET within hours after radiofrequency ablation (RFA) of liver metastases. CONCLUSION: Total photopenia on early PET can potentially be regarded as a macroscopic tumor-free margin; focal uptake can be regarded as macroscopic residual tumor.

Sensitivity of FDG PET, GLUT1 expression and proliferative index in bronchioloalveolar lung cancer.

OBJECTIVE: To estimate the sensitivity of [F] fluorodeoxyglucose (FDG) positron emission tomography (PET) and to assess the expression of glucose transporter 1 (GLUT1) and proliferative index (PI) in bronchioloalveolar lung cancer (BAC). METHODS: Twenty-four patients with resected BAC underwent preoperative PET between October 1996 and February 2003. The surgical specimens were re-examined, and 18 patients who fulfilled the 1999 WHO definition for BAC were included in the study. The PET images were reviewed in order to determine the positive (PET+) and negative (PET-) tumours on PET. The pathology slides were stained with antibodies to GLUT1 and Proliferating cell nuclear antigen (PCNA) in order to determine GLUT1 expression and PI, respectively. RESULTS: There were 13 cases of PET+ BAC (sensitivity, 72%; confidence interval, 52-93%); seven of them were GLUT1+ cases and six were GLUT1-. The stromal cell PI was significantly higher in GLUT1+ BAC compared to GLUT- BAC (50.9+/-17.1 vs. 33.2+/-14.2, P=0.0286), and higher in PET+ BAC compared to PET- BAC (45.5+/-15.3 vs. 29.6+/-19.6, P=0.0854). CONCLUSION: After applying the 1999 WHO criteria, the sensitivity of PET for detecting BAC is still relatively low. Other glucose transporters such as GLUT3 likely play a role in FDG uptake in BAC. GLUT1+ or PET+ BAC tumours have a higher stromal cell PI when compared to GLUT1- BAC or PET- BAC tumours, respectively.

Frequency of high blood glucose prior to FDG PET.

PURPOSE: To assess the frequency of blood glucose level higher than 150 mg/dL in non-diabetic patients presenting for FDG PET. METHODS: We reviewed the electronic medical record (EMR) of all lymphoma patients who had at least one FDG PET/CT from July 1, 2014 through June 30, 2015. We extracted the blood glucose level at the time of the FDG PET during this 1-year time period and any previous PET scans these patients had. Patients' diabetic status was determined from EMR. RESULTS: One hundred seventeen patients with 574 scans were included: 91 non-diabetic with 429 scans and 26 diabetic patients with 145 scans. Blood glucose level ranged from 44 to 259 mg/dL: 44 to 144 mg/dL in non-diabetic patients and 73 to 259 mg/dL in diabetic patients. There was no non-diabetic patient with a glucose level higher than 150 mg/dL at any occasion. Only one scan was performed with 144 mg/dL of glucose. All other scans were performed with a glucose level less than 140 mg/dL. There were nine diabetic patients with glucose level less than 150 mg/dL prior to all of their scans and 17 diabetic patients with a glucose level higher than 150 mg/dL prior to PET at least on one occasion. CONCLUSIONS: In all non-diabetic patients, blood glucose level was below the lower limit of the recommended range prior to all their FDG PET scans while this was not the case in diabetic patients. We conclude that measuring blood glucose level prior to FDG PET may be limited to diabetic patients.

Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell-Renal-Cell-Carcinoma: Proof-of-Concept Study.

Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone.