Targeted α-therapy in non-prostate malignancies.

Progress in unraveling the complex biology of cancer, novel developments in radiochemistry, and availability of relevant α-emitters for targeted therapy have provided innovative approaches to precision cancer management. The approval of 223Ra dichloride for treatment of men with osseous metastatic castrate-resistant prostate cancer unleashed targeted α-therapy as a safe and effective cancer management strategy. While there is currently active research on new α-therapy regimens for prostate cancer based on the prostate-specific membrane antigen, there is emerging development of radiopharmaceutical therapy with a range of biological targets and α-emitting radioisotopes for malignancies other than the prostate cancer. This article provides a brief review of preclinical and first-in-human studies of targeted α-therapy in the cancers of brain, breast, lung, gastrointestinal, pancreas, ovary, and the urinary bladder. The data on leukemia, melanoma, myeloma, and neuroendocrine tumors will also be presented. It is anticipated that with further research the emerging role of targeted α-therapy in cancer management will be defined and validated.

EANM guideline on the role of 2-[18F]FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA).

In most patients with ovarian carcinoma, the diagnosis is reached when the disease is long past the initial stages, presenting already an advanced stage, and they usually have a very bad prognosis. Cytoreductive or debulking surgical procedures, platinum-based chemotherapy and targeted agents are key therapeutic elements. However, around 7 out of 10 patients present recurrent disease within 36 months from the initial diagnosis. The metastatic spread in ovarian cancer follows three pathways: contiguous dissemination across the peritoneum, dissemination through the lymphatic drainage and, although less importantly in this case, through the bloodstream. Radiological imaging, including ultrasound, CT and MRI, are the main imaging techniques in which management decisions are supported, CT being considered the best available technique for presurgical evaluation and staging purposes. Regarding 2-[18F]FDG PET/CT, the evidence available in the literature demonstrates efficacy in primary detection, disease staging and establishing the prognosis and especially for relapse detection. There is limited evidence when considering the evaluation of therapeutic response. This guideline summarizes the level of evidence and grade of recommendation for the clinical indications of 2-[18F]FDG PET/CT in each disease stage of ovarian carcinoma.

Machine learning-based differentiation between multiple sclerosis and glioma WHO II°-IV° using O-(2-[18F] fluoroethyl)-L-tyrosine positron emission tomography.

INTRODUCTION: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°. METHODS: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance. RESULTS: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm. CONCLUSIONS: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.

Uncovering Lymphatic Transport Abnormalities in Patients with Primary Lipedema.

BACKGROUND: Although lipedema is often clinically distinguished from lymphedema, there is considerable overlap between the two entities. The purpose of this study was to evaluate lymphoscintigraphic findings in patients with lipedema to better characterize lymphatic flow in this patient population. METHODS: Patients with lipedema receiving lymphoscintigraphy between January 2015 and October 2017 were included. Patient demographics, clinical characteristics, and lymphoscintigraphic findings were extracted. Klienhan's transport index (TI) was utilized to assess lymphatic flow in patient's lower extremities (LEs).Scores ranged from 0 to 45, with values > 10 denoting pathologic lymphatic transport. RESULTS: A total of 19 total patients with lipedema underwent lymphoscintigraphic evaluation. Mean age was 54.8 years and mean body mass index was 35.9 kg/m2. Severity of lipedema was classified as stage 1 in five patients (26.3%), stage 2 in four patients (21.1%), stage 3 in four patients (21.1%), and stage 4 in six patients (31.6%). The mean TI for all extremities was 12.5; 24 (63.2%) LEs had a pathologic TI, including 7 LEs with stage 1 (29.2%), 3 LEs with stage 2 (12.5%), 6 LEs with stage 3 (25.0%), and 8 LEs with stage 4 lipedema (33.3%). The mean TI was significantly greater for extremities with severe (stage 3/4) lipedema than those with mild or moderate (stage 1/2) lipedema (15.1 vs. 9.7, p = 0.049). Mean difference in TI scores between each LE for individual patients was 6.43 (standard deviation +7.96). CONCLUSION: Our results suggest that patients with lipedema have impaired lymphatic transport, and more severe lipedema may be associated with greater lymphatic transport abnormalities.

Earlier Diagnosis of Subcentimeter Lung Cancers Is Not Self-Evidently Beneficial: Personal Experience.

OBJECTIVE. The purpose of this article is to point out the potential harms related to overdiagnosis of subcentimeter lung cancers. CONCLUSION. Reich and Kim's argument for reconsidering the seeking and treatment of subcentimeter pulmonary nodules is challengeable on the basis of individualized patient results.

Aberrant right subclavian artery ("arteria lusoria") without the known associated nerve anomaly: an "anomaly of the anomaly"? A clinical case and review of the literature.

The "non-recurrent" course of the inferior laryngeal nerve (ILN) is an anatomical variant which must be borne in mind during thyroid surgery. The "non-recurrent" course of the ILN on the right side is associated with the aberrant right subclavian artery (arteria lusoria), and, on the left, is described in situs viscerum inversus. We present a case in which the "arteria lusoria" was not associated with the non-recurrent right ILN. The aims of this paper are to report this "anomaly of the anomaly" to surgeons who may be unaware of it on the one hand and on the other to emphasize that this is the only case so far reported in the literature. Moreover we proposed to explain embryologically these unexpected findings.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.

Sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma: current status and unresolved challenges.

Because imaging with ultrasound, computed tomography, magnetic resonance imaging or positron emission tomography is unreliable for preoperative lymph node staging of early-stage oral and oropharyngeal squamous cell carcinoma (OSCC), elective neck dissection has been typically performed. The targeted sampling of sentinel lymph nodes (SLN) identified by lymphoscintigraphy and detected by gamma probe has become an effective alternative for the selection of patients for regional nodal resection. With careful consideration to technique, high SLN detection rates have been reported. Advanced techniques including intraoperative handheld gamma camera imaging and freehand single photon emission computed tomography (SPECT) are expected to increase surgical confidence in these procedures. This review gives an update on SLN biopsy in patients with OSCC including clinical standards and controversial aspects.

EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma.

PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized melanoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with melanoma. METHODS: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, national nuclear medicine societies, the European Society of Surgical Oncology (ESSO) and the European Association for Research and Treatment of Cancer (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). CONCLUSION: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of melanoma patients.

Value of (18)F-FDG PET for Predicting Response to Neoadjuvant Therapy in Rectal Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the predictive value of (18)F-FDG PET/ CT for pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. MATERIALS AND METHODS: A systematic search was performed (PubMed and Cochrane databases) for potentially relevant studies up to January 2014. Pooled sensitivity and specificity were calculated. The AUCs of the global cohort and for "major response," "complete response," "only PET after chemoradiotherapy," "ad interim PET," "major response excluding ad interim studies," "complete response excluding ad interim studies," "response index (RI)," "posttreatment maximum standardized uptake value (SUV(max) post)," "visual response analysis (VRA)," "percentage reduction of the total lesion glycolysis (ΔTLG)," and "percentage reduction of the metabolic tumor volume (ΔMTV)" were analyzed. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% CI were calculated. RESULTS: Thirty-four of 131 (26%) initial articles met the inclusion criteria. Those articles included 1526 patients. PET/CT showed good pooled accuracy both in the global cohort (pooled sensitivity, 73%; pooled specificity, 77%; pooled AUC, 0.83) and for subgroups. Pooled accuracy was similar for early PET restaging and at 1 and 2 weeks after beginning chemoradiotherapy (pooled sensitivity, 84%; pooled specificity, 81%; pooled AUC, 0.89). The major response group showed similar sensitivity to the complete response group (74% and 71%, respectively). RI, SUV(max), and VRA were the most frequent parameters used. Pooled RI and SUV(max) postcutoff values were 63% and 4.4. Pooled time to PET during and after chemoradiotherapy was 1.5 and 6.5 weeks, respectively. CONCLUSION: This meta-analysis supports the use of FDG PET for restaging locally advanced rectal cancer.

High resolution MRI evaluation of meniscal volume and anthropometric correlations.

The purpose of this study was to digitally determine meniscal volumes, and compare them with linear and surface area anthropometric measurements to evaluate these measurements for meniscal allograft sizing. Eighteen subjects (10 male and 8 female; mean age 37.5 years) underwent 3.0 T knee magnetic resonance imaging (MRI) of the dominant leg. The following morphometric measurements were evaluated: medial meniscal volume (MMV), lateral meniscal volume (LMV), tibial plateau width (TPW), width of the femoral condyles (WFC), and tibial plateau surface area (TPSA). MMV and LMV were compared to TPW, WFC, and TPSA. Meniscal volume and TPW were correlated to height and body-mass index (BMI) and stratified by gender. Statistical analysis included coefficient of determination (r(2)) between MRI-based MMV, LMV, TPW, TPSA, WFC, height, BMI, and gender. Significance was set at the P = 0.05 level. The mean MMV was 2275 mm(3) and the mean LMV was 2102 mm(3). TPW correlated well with meniscal volumes (r(2) > 0.62). WFC and TPSA correlated with meniscal volumes in the range of 0.40 < r(2) < 0.61. Height, BMI, and gender correlated poorly with total meniscal volume and TPW with values of r(2) < 0.44. Medial and lateral menisci have statistically similar volumes. TPW had the greatest utility for volumetric meniscal sizing. MRI-based TPW can be considered as a statistically accurate measurement for determining meniscal volumes and meniscal size.

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

PSMA Radioligand Therapy in Prostate Cancer: Where Are We and Where Are We Heading?

ABSTRACT: Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific membrane antigen agents has been proven beneficial in certain clinical indications. In this review, we describe management of prostate cancer patients according to current guidelines, especially focusing on the available clinical evidence for prostate-specific membrane antigen radioligand therapy.

Role of ¹8F-choline PET/CT in suspicion of relapse following definitive radiotherapy for prostate cancer.

PURPOSE: The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of ¹8F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread. METHODS: ¹8F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51-84 years) with prostate cancer (mean Gleason score 6.4, range 5-8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1-49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0 < PSA ≤ 2.0 ng/ml (11 patients), 2.0 < PSA ≤ 4.0 ng/ml (16 patients), 4.0 < PSA ≤ 6.0 ng/ml (9 patients) and PSA > 6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread. RESULTS: The overall PDR of ¹8F-CH PET/CT was 80.4% (37/46 patients), increasing with the increase of trigger PSA. PDR of ¹8F-CH PET/CT is not influenced by ADT (p = 0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6%). The majority of the patients (59%, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22% of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19% (7/37 patients) showed both local and distant (lymph node and bone) spread. CONCLUSION: ¹8F-CH PET/CT showed a high overall detection rate (80%), proportional to the trigger PSA (both for local and distant relapse) not influenced by ADT. ¹8F-CH PET/CT is proposed as a first-line imaging procedure in restaging prostate cancer patients primarily treated with radiotherapy.

Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy.

PURPOSE: The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. METHODS: Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). RESULTS: SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm(3), 23.4 cm(3), 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. CONCLUSION: FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.

Measuring bone mineral density with fat-water MRI: comparison with computed tomography.

PURPOSE: To develop a method for measuring bone mineral density (BMD) with MRI, and to validate this method against quantitative computed tomography (QCT). MATERIALS AND METHODS: A mathematical relationship between signal intensities from proton-density-weighted in-phase images generated by multi-fat-peak T2*-IDEAL MRI and BMD was derived using a set of calibration standards constructed from various concentrations of hydroxyapatite in water. Using these standards, the relationship between hydroxyapatite concentration and MRI signal intensity was examined. A T2*-IDEAL protocol was performed on the patella of 5 volunteers and the signal model was used to compute BMD of all voxels of the patella. The BMD data were validated by obtaining QCT scans of the same patella, computing QCT BMD of all voxels, and comparing the MRI and QCT BMD data by performing linear regression analysis on a voxel-by-voxel basis. RESULTS: A strong linear correlation between hydroxyapatite concentration of the calibration standards and MRI signal intensities was observed (r = 0.98; P < 0.01). In the patella, BMD measurements (N = 28796 voxels) from the MRI signal model were significantly correlated with those from QCT (r = 0.82; P < 0.001; slope = 1.02; and intercept = -0.26). CONCLUSION: A standardized phantom consisting of hydroxyapatite and water can be used to accurately quantify BMD in vivo using MRI.

How do reviewers affect the final outcome? Comparison of the quality of peer review and relative acceptance rates of submitted manuscripts.

OBJECTIVE: The purpose of this study was to clarify how peer reviewers affect the relative rate of acceptance of manuscripts submitted to AJR: American Journal of Roentgenology. MATERIALS AND METHODS: Manuscript peer reviews for AJR are evaluated and rated by the journal editors on a scale from 1 (lowest) to 4 (highest). These scores are subjective; they are not based on well-defined criteria and are not specifically defined other than as review quality. We obtained all peer review performance scores for the six main types of manuscripts received by AJR as initial submissions (as opposed to revisions) over 5 years and categorized the manuscripts into four groups based on the peer review performance score (not the manuscript rating). Statistical analysis included evaluation of differences in the relative acceptance rates of the manuscripts among the four groups. RESULTS: The relative acceptance rates of manuscripts in the lower review performance score groups (scores 1, 2, and 3) were significantly higher than those of the highest review score group (score 4) for Original Research (p=0.036, p<0.0001, p<0.0001) and Pictorial Essay (all p<0.0001, except for score 3) manuscripts. CONCLUSION: There was correlation between the quality of peer review performance and the relative acceptance rate of the manuscripts. It is important for AJR to retain highly rated reviewers to maintain its high publishing standards.