Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the underlying reasons for these differences remain poorly understood. Potential contributors include hormonal influences, sex-specific risk factors, and treatment disparities. Understanding these differences is critical for optimizing personalized treatment strategies. Methods: We conducted a retrospective analysis of patients with gliomas from a neuro-oncological database, with a primary focus on GB cases. Variables collected included sex, age, tumor type, molecular biomarker, and treatment modalities. The primary objective was to assess sex-based differences in tumor characteristics and outcomes, while the secondary objective was to identify predictors of time to progression and mortality. Results: The cohort comprised 125 GB, 48 astrocytomas, and 16 oligodendrogliomas, with no significant sex-based differences in age or tumor type distribution. Among GB patients, multifocality was more prevalent in females (14% vs. 8%; p = 0.01); also, EGFR amplification was more frequent in females (25.5% vs. 52.5%; p = 0.007). Males received chemotherapy (80% vs. 63%; p = 0.04) and radiotherapy (84% vs. 67%; p = 0.03) more frequently than females. Survival was positively associated with MGMT methylation (p = 0.002) and negatively associated with TERT mutation (p = 0.01). Multivariable analysis identified TERT mutation as a predictor of increased mortality (HR = 4.1; 95% CI: 1.2–14; p = 0.025), while multifocality predicted both mortality (HR = 2.3; 95% CI: 1.3–3.9; p = 0.003) and reduced time to progression (HR = 3.3; 95% CI: 1.02–10.6; p = 0.04). Conclusions: This study underscores the importance of sex and molecular profiling in GB management, revealing distinct patterns in tumor characteristics and treatment administration between males and females. Our findings advocate for the integration of sex-specific considerations and molecular profiling into clinical decision-making to improve outcomes for GB patients.

Background: Peptide receptor radionuclide therapy (PRRT) could be a therapeutic option for patients with advanced, recurrent or progressing meningiomas overexpressing somatostatin receptors. The aim of this study is to perform an updated meta-analysis to establish the disease control rate of PRRT in these patients. Methods: A comprehensive literature search of studies on PRRT in patients with advanced, recurrent or progressing meningioma was carried out. Four different databases (PubMed/MEDLINE, EMBASE, Cochrane library, Google Scholar) were screened until April 2025. Only original articles about PRRT in advanced, progressive or refractory meningiomas were selected. Case reports were excluded. Three review authors independently performed the literature search, the article selection and the data extraction. Main findings of eligible studies were summarized and a proportion meta-analysis on the disease control rate was carried out using a random-effects model. Results: In total, 18 studies (269 patients) published from 2006 to 2025 were included in the analysis. In most of the included studies, PRRT was performed using [177Lu]Lu-DOTATATE. The pooled disease control rate was 67.7% (95% confidence interval values: 59.6–75.7%). PRRT was well-tolerated in most patients with advanced, recurrent or progressive meningioma. Moderate statistical heterogeneity was found in the meta-analysis (I-square: 53%). Conclusions: PRRT is an effective and well-tolerated treatment in patients with advanced, progressive or recurrent meningiomas, showing a significant disease control rate (in about two-thirds of patients). Even if well-designed clinical trials are needed to corroborate these findings, evidence-based data seem to support the clinical use of PRRT for this indication.

Here, we describe the case of a 74-year-old male patient with a high-risk prostate carcinoma who underwent positron-emission tomography/computed tomography (PET/CT) with [68Ga]Ga-prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) for staging. [68Ga]Ga-PSMA-11 PET/CT detected an extensive area of increased tracer uptake at the prostatic level, involving both lobes. Additionally, a rounded lesion approximately 4 cm in diameter was identified in the celiac region adjacent to the stomach, exhibiting moderate tracer uptake. Based on these imaging findings, the patient underwent radiation therapy applied to the prostate and pelvis and a biopsy of the suspected lesion adjacent to the stomach, which was positive for Siewert type III gastroesophageal junction adenocarcinoma (HER2-negative, PDL-1 60%). This case demonstrates the importance of not overlooking incidental tracer uptakes in PSMA PET/CT imaging in the stomach, as they could represent neoplastic lesions.

Background: Incidental brain imaging findings could be clinically relevant, and advancements in molecular imaging could lead to their more frequent identification. The aim of this review is to establish the prevalence and clinical significance of brain incidentalomas at PET (BIPs) using radiotracers other than [18F]FDG. Methods: A comprehensive literature search of studies about BIPs was carried out. Four different databases (PubMed/MEDLINE, EMBASE, the Cochrane library, and Google Scholar) were screened up to December 2024. Only original articles about BIPs using radiotracers other than [18F]FDG were selected. A proportion meta-analysis of the prevalence of BIPs was carried out using a random-effects model. Results: Fourteen studies were included in the review, using somatostatin receptor (SSTR) PET (n = 6), radiolabeled choline PET (n = 5), prostate-specific membrane antigen (PSMA) ligands PET (n = 1), [18F]Fluciclovine PET (n = 1), and [18F]FDOPA PET (n = 1). The pooled prevalence of BIPs was 4.6% for SSTR PET, 1.1% for choline PET, 1.2% for PSMA ligands PET, 2.5% for [18F]Fluciclovine PET, and 3.9% for [18F]FDOPA PET. When BIPs were further evaluated using MRI, meningiomas were the most frequent lesions detected, but both benign and malignant lesions could be incidentally diagnosed. Conclusions: BIPs using radiotracers other than [18F]FDG are not rare, in particular at SSTR PET, further justifying the extension of PET scans to the brain when radiotracers other than [18F]FDG are used. When detected, a BIP should be further evaluated using brain MRI. Both benign and malignant lesions could be incidentally detected in the brain. Further studies are warranted to better clarify the clinical impact of BIP detection.

With the emergence of targeted therapies and immunotherapy, various cellular pathways are utilized to improve tumor control and patient survival. In patients receiving these new agents, radiotherapy is commonly applied with both radical and palliative intent. Combining radiotherapy with targeted therapies or immunotherapy may improve treatment outcomes, but may also lead to increased toxicity. High-quality toxicity data and evidence-based guidelines regarding combined therapy are very limited. The present framework, developed by ESMO and ESTRO, explores the main biological effects and interaction mechanisms of radiotherapy combined with targeted agents or immunotherapy. It addresses general clinical factors to take into consideration when deciding on whether and/or how to combine radiotherapy with these agents. Furthermore, it provides pragmatic, biological mechanism-based, clinical considerations for combining radiotherapy with various targeted agents or immunotherapy.

Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence.

BackgroundSeveral recent studies have proposed the possible application of positron emission tomography/computed tomography (PET/CT) administering radiolabelled fibroblast-activation protein (FAP) inhibitors for various forms of thyroid cancer (TC), including differentiated TC (DTC), and medullary TC (MTC).MethodsThe authors conducted an extensive literature search of original studies examining the effectiveness of FAP-guided PET/CT in patients with TC. The papers included were original publications exploring the use of FAP-targeted molecular imaging in restaging metastatic DTC and MTC patients.ResultsA total of 6 studies concerning the diagnostic yield of FAP-targeted PET/CT in TC (274 patients, of which 247 DTC and 27 MTC) were included in this systematic review. The included articles reported high values of FAP-targeted PET/CT detection rates in TC, ranging from 81 to 100% in different anatomical sites and overall superior to the comparative imaging method.ConclusionAlthough there are promising results, the existing literature on the diagnostic accuracy of FAP-guided PET in this context is still quite limited. To thoroughly evaluate its potential significance in TC patients, it is needed to conduct prospective randomized multicentric trials.

We present the case of a 60-year-old male with recurrent atypical meningioma in the right parietal lobe, previously treated with surgery and radiation therapy. Magnetic resonance imaging (MRI) performed 5 years after radiation therapy suggested a possible recurrence. A somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) scan with Gallium-68 DOTATATE was performed to confirm this suspicion. SR-PET/CT confirmed the presence of recurrent meningioma, showing a novel “rosary sign” with multiple adjacent areas of focal tracer uptake along the resection margins of the previous surgical site in the right parietal region. This novel imaging pattern improved diagnostic accuracy by detailing disease extent and identifying additional lesions not visible via MRI. Given the failure of prior treatments and high SR expression, peptide receptor radionuclide therapy (PRRT) was proposed as a therapeutic option for the patient.

Imaging has a pivotal role in neuro-oncology for the management of primary and secondary brain tumors [...].

Several studies have examined the use of positron emission tomography (PET) using [Ga-68]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients.

Several studies have examined the use of positron emission tomography (PET) using [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients.

Background: The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings. Methods: A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values. Results: Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7–1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men. Conclusions: The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted.

Background: 18F-Fluciclovine ([18F]FACBC) has been recently proposed as a synthetic radiolabeled amino acid for positron emission tomography (PET) imaging in patients with brain neoplasms. Our aim is to evaluate the diagnostic performance of [18F]FACBC PET in high-grade glioma (HGG) patients, taking into account the literature data. Methods: A comprehensive literature search was performed. We included original articles evaluating [18F]FACBC PET in the detection of HGG before therapy and for the suspicion of tumor recurrence. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and diagnostic odds ratios (DOR), including 95% confidence intervals (95% CI), were measured. Statistical heterogeneity and publication bias were also assessed. Results: ten studies were included in the review and eight in the meta-analysis (113 patients). Regarding the identification of HGG, the sensitivity of [18F]FACBC PET ranged between 85.7% and 100%, with a pooled estimate of 92.9% (95% CI: 84.4–96.9%), while the specificity ranged from 50% to 100%, with a pooled estimate of 70.7% (95% CI: 47.5–86.5%). The pooled LR+, LR−, and DOR of [18F]FACBC PET were 2.5, 0.14, and 37, respectively. No significant statistical heterogeneity or publication bias were found. Conclusions: evidence-based data demonstrate the good diagnostic accuracy of [18F]FACBC PET for HGG detection. Due to the still limited data, further studies are warranted to confirm the promising role of [18F]FACBC PET in this context.

Paraneoplastic autoimmune disorders (PAD) are a group of autoimmune diseases associated with neoplasms. Several evidence-based articles (systematic reviews and meta-analyses) have reported data about the role of positron emission tomography (PET) and related hybrid modalities (e.g., PET/CT) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in patients with PAD. We performed an umbrella review of published systematic reviews and meta-analyses in this setting to provide an evidence-based summary and suggestions for further studies. Several databases were searched to find systematic reviews and meta-analysis on [18F]FDG PET/CT in PAD. Evidence-based data support the use of [18F]FDG PET/CT in patients with suspected PAD for investigating an underlying malignancy even if it is still unclear whether [18F]FDG PET/CT should be performed after negative/inconclusive conventional imaging or as part of the initial workup of PAD.

Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3–99.9%), specificity 91.2% (95% CI: 68.4–98.1%), LR+ 4.5 (95% CI: 2.2–9.3), LR− 0.07 (95% CI: 0.04–0.15), and DOR 70.1 (95% CI: 19.6–250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

Several recent studies comparing radiolabeled fibroblast activation protein inhibitors (FAPI) and fluorine-18 fluorodeoxyglucose ([18F]F-FDG) as positron emission tomography (PET) radiotracers in oncology have been published. The aim of this systematic review is to perform an updated evidence-based summary about the comparison of these PET radiotracers in oncology to better address further research in this setting. Studies or subsets of studies comparing radiolabeled FAPI and [18F]F-FDG as PET radiotracers in oncology were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until August 2021. Literature data about the comparison of [18F]F-FDG and radiolabeled FAPI are rapidly increasing. Overall, taking into account radiotracer uptake and tumor-to-background uptake ratio, compared to [18F]F-FDG PET, an equal or higher detection of primary tumors and/or metastatic lesions was usually demonstrated by using radiolabeled FAPI PET. In particular, the cancer entities with better detection rate of tumor lesions by using radiolabeled FAPI PET, compared to [18F]F-FDG PET, were gastrointestinal tumors, liver tumors, breast cancer and nasopharyngeal carcinoma. Further comparison studies are needed to better evaluate the best field of application of radiolabeled FAPI PET.

Recently, several articles reported incidental findings at 2-[18F]FDG PET/CT in patients who have received COVID-19 vaccinations, including hypermetabolic axillary lymph nodes (HALNs) ipsilateral to the COVID-19 vaccine injection site which may cause diagnostic dilemmas. The aim of our work was to calculate the prevalence of this finding. A comprehensive computer literature search of PubMed/MEDLINE, Embase, and Cochrane library databases was performed to identify recently published articles that investigated the prevalence of HALNs detected by 2-[18F]FDG PET/CT after COVID-19 vaccination. Pooled prevalence of this finding was calculated through a meta-analytic approach. Nine recently published articles including 2354 patients undergoing 2-[18F]FDG PET/CT after recent COVID-19 vaccination have been included in the systematic review. Overall, HALNs ipsilateral to the vaccine injection site were frequent findings mainly due to vaccine-related immune response in most of the cases. The pooled prevalence of HALNs after COVID-19 vaccination was 37% (95% confidence interval: 27–47%) but with significant heterogeneity among the included studies. Physicians must be aware and recognize the significant frequency of HALNs at 2-[18F]FDG PET/CT related to immune response to vaccine injection. Larger studies are needed to confirm the findings of this systematic review and meta-analysis.

ABSTRACT A 76-year-old woman underwent 99mTcO4- thyroid scintigraphy to clarify thyrotoxicosis. In addition to suppressed thyroid uptake, an atypical tracer accumulation appeared on already know pulmonary adenocarcinoma in the left lung upper lobe. Surgical pathology was reviewed confirming the diagnosis of lung adenocarcinoma with focal mucins production and excluding a misdiagnosed differentiated thyroid carcinoma metastasis.

BACKGROUND:Several meta-analyses have reported quantitative data about the diagnostic performance, the prognostic value, the impact on management and the safety of positron emission tomography (PET) including related hybrid modalities (PET/CT or PET/MRI) using different radiopharmaceuticals in patients with neuroendocrine neoplasms. We performed an umbrella review of published meta-analyses to provide an evidence-based summary.METHODS:A comprehensive literature search of meta-analyses listed in PubMed/MEDLINE and Cochrane Library databases was carried out (last search date: 30 June 2021).RESULTS:Thirty-four published meta-analyses were selected and summarized. About the diagnostic performance: 68Ga-SSA PET yields high diagnostic performance in patients with NETs and PGL; 18F-FDOPA PET yields good diagnostic performance in patients with intestinal NETs, PGL, NB, being the best available PET method in detecting rMTC; 68Ga-exendin-4 PET has good diagnostic accuracy in detecting insulinomas; 18F-FDG PET has good diagnostic performance in detecting aggressive neuroendocrine neoplasms. About the prognostic value: 68Ga-SSA PET has a recognized prognostic value in well-differentiated NETs, whereas 18F-FDG PET has a recognized prognostic value in aggressive neuroendocrine neoplasms. A significant clinical impact of 68Ga-SSA PET and related hybrid modalities in patients with NETs was demonstrated. There are no major toxicities or safety issues related to the use of PET radiopharmaceuticals in patients with neuroendocrine neoplasms.CONCLUSIONS:Evidence-based data support the use of PET with different radiopharmaceuticals in patients with neuroendocrine neoplasms with specific indications for each radiopharmaceutical.