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Abstract Metabolic alterations in cancers can be exploited for diagnostic, prognostic, and therapeutic purposes. This is exemplified by 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (FDG‐PET), an imaging tool that relies on enhanced glucose uptake by tumors for diagnosis and staging. By performing transcriptomic analysis of breast cancer (BC) samples from patients stratified by FDG‐PET, a 54‐gene signature (PETsign) is identified that recapitulates FDG uptake. PETsign is independently prognostic of clinical outcome in luminal BCs, the most common and heterogeneous BC molecular subtype, which requires improved stratification criteria to guide therapeutic decision‐making. The prognostic power of PETsign is stable across independent BC cohorts and disease stages including the earliest BC stage, arguing that PETsign is an ab initio metabolic signature. Transcriptomic and metabolomic analysis of BC cells reveals that PETsign predicts enhanced glycolytic dependence and reduced reliance on fatty acid oxidation. Moreover, coamplification of PETsign genes occurs frequently in BC arguing for their causal role in pathogenesis. CXCL8 and EGFR signaling pathways feature strongly in PETsign, and their activation in BC cells causes a shift toward a glycolytic phenotype. Thus, PETsign serves as a molecular surrogate for FDG‐PET that could inform clinical management strategies for BC patients.

Background: Since most endocrine glands express ACE-2 receptors and can be infected by SARS-CoV-2 virus, this retrospective multicentre observational study aims to assess the metabolic activity of thyroid and adrenal glands of COVID-19 patients by 18F-FDG PET/CT. Methods: We retrospectively evaluated the 18F-FDG PET/CT scans of COVID-19 patients admitted by three different centres, either in a low-intensity department or in the intensive care unit (ICU). A visual assessment and a semi-quantitative evaluation of areas of interest in thyroid and adrenal glands were performed by recording SUVmax and SUVmean. The 18F-FDG PET/CT uptake in COVID-19 patients was compared with those observed in normal age-matched controls. Results: Between March 2020 and March 2022, 33 patients from three different centres (twenty-eight patients in a low-intensity department and five patients in ICU), were studied by 18F-FDG PET/CT during active illness. Seven of them were also studied after clinical remission (3–6 months after disease onset). Thirty-six normal subjects were used as age-matched controls. In the thyroid gland, no statistically significant differences were observed between control subjects and COVID-19 patients at diagnosis. However, at the follow-up PET/CT study, we found a statistically higher SUVmax and SUVmean (p = 0.009 and p = 0.004, respectively) in the thyroid of COVID-19 patients. In adrenal glands, we observed lower SUVmax and SUVmean in COVID-19 patients at baseline compared to control subjects (p < 0.0001) and this finding did not normalize after clinical recovery (p = 0.0018 for SUVmax and p = 0.002 for SUV mean). Conclusions: In our series, we observed persistent low 18F-FDG uptake in adrenal glands of patients at diagnosis of COVID-19 and after recovery, suggesting a chronic hypofunction. By contrast, thyroid uptake was comparable to normal subjects at disease onset, but after recovery, a subgroup of patients showed an increased metabolism, thus possibly suggesting the onset of an inflammatory thyroiditis. Our results should alert clinicians to investigate the pituitary–adrenal axis and thyroid functionality at the time of infection and to monitor them after recovery.

Grade 3 (G3) neuroendocrine tumors (NETs) are a novel category among digestive neuroendocrine neoplasms, characterized by Ki-67 >20% and a well-differentiated morphology, presenting high intra-tumor heterogeneity. We aimed to explore the role of dual-tracer PET imaging (68Gallium (Ga)-DOTATOC and 18Fluorodeoxyglucose (FDG)) as overall survival (OS) predictor in NET G3 patients. We performed a retrospective analysis in NET G3 patients treated at our institution between 2003 and 2021. Accordingly, 30 NET G3 patients were analyzed. 68Ga-DOTA-TOC and 18F-FDG uptake were assessed by tumor/non-tumor (T-nonT) ratio. We reported a slightly better OS for patients with ≥75% concordance between 68Ga-DOTA-TOC and 18F-FDG PET/CT (p = 0.42). Among patients with discordant functional imaging, we reported a better 5-y OS rate for patients with a prevalent 68Ga-DOTATOC vs. 18F-FDG PET/CT (p = 0.016). In positive 18F-FDG PET/CT cases, we reported a better OS for p = 0.021). Among upfront-NET G3 patients with concordant exams, 5-y OS rate was 83.3% (95% CI: 27.3–97.5). Among patients with discordant exams, 5-y OS rate was 81.3% (52.5–93.5), 100% for those with prevalent receptor expression, and 50% (11.1–80.4) for those with prevalent 18F-FDG uptake. Our findings suggest that dual-tracer PET/CT can be considered as a predictor of patient outcome, able to stratify NET G3 patients with poorer prognosis.

Mediastinal lymph node enlargement is common in the follow-up of patients with previously treated malignancies. The aim of this study is to assess the role of endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) for cyto-histological evaluation of positron emission tomography with 18fluorodeoxyglucose (PET) positive mediastinal and hilar lymph nodes developed in patients with previous malignancies. All EBUS-TBNA cases performed from January 2012 to May 2016 were retrospective reviewed. Results of EBUS-TBNA in patients with mediastinal and/or hilar lymphadenopathies were analysed. Non-malignant cytopathologies were confirmed with surgical procedures or clinical and radiological follow-up. Among 1780 patients, 176 were included in the analysis. 103 of these (58.5%) had a diagnosis of tumour recurrence whereas 73 (41.5%) had a different diagnosis: 63 (35.8%) had a non-neoplastic diagnosis and 8 patients (4.6%) had a different cell type malignancy. Samples were false-negative in 5 (2.8%) out of 176 patients. The overall sensitivity, specificity, negative predicted value and diagnostic accuracy were 95.7% (95% CI 90.2–98.6%), 100% (95% CI 94.0–100%), 92.3% (95% CI 83.2–96.7%) and 97.2% (95% CI 93.5–98.8%), respectively. EBUS-TBNA demonstrated a pathological diagnosis different from the previous tumour in a large percentage of patients, confirming its strategic role in the management of patients with previously treated malignancies.

Radioembolization (RE) of liver cancer with 90Y-microspheres has been applied in the last two decades with notable responses and acceptable toxicity. Two types of microspheres are available, glass and resin, the main difference being the activity/sphere. Generally administered activities are established by empirical methods and differ for the two types. Treatment planning based on dosimetry is a prerogative of few centers, but has notably gained interest, with evidence of predictive power of dosimetry on toxicity, lesion response and overall survival (OS). Radiobiological correlations between absorbed doses and toxicity to organs at risk, and tumour response, have been obtained in many clinical studies. Dosimetry methods have evolved from the macroscopic approach at the organ level to voxel analysis, providing absorbed dose spatial distributions and Dose Volume Histograms –(DVH). The well known effects of the External Beam Radiation Therapy (EBRT), such as the volume effect, underlying disease influence, cumulative damage in parallel organs, different tolerability of retreatment, have been observed also in RE, identifying in EBRT a foremost reference to compare with. The radiobiological models Normal Tissue Complication Probability (NTCP) and Tumour Control Probability (TCP) and/or the style (DVH concepts) used in EBRT are introduced in RE. Moreover, attention has been paid to the intrinsic different activity distribution of resin and glass spheres at the microscopic scale, with dosimetric and radiobiological consequences. Dedicated studies and mathematical models have developed this issue and explain some clinical evidences –e.g. the shift of dose to higher toxicity thresholds using glass as compared to resin spheres. This paper offers a comprehensive review of the literature incident to dosimetry and radiobiological issues in RE, with the aim to summarize the results and to identify the most useful methods and information that should accompany future studies.

AbstractRadioimmunotherapy (RIT) with a commercially available brand of yttrium-90 (90Y)-ibritumomab-tiuxetan at the prescribed activity of 14.8 MBq/kg (0.4 mCi/kg) represents a complementary approach in the treatment of resistant/refractory B-cell non-Hodgkin's lymphoma. A trial based on higher activities is ongoing in our institute. In this paper, we report atypical pharmacokinetics and liver uptake in 2 patients. Before RIT, all patients underwent dosimetry with 111In-ibritumomab-tiuxetan. Imaging data were analyzed to obtain predicted absorbed doses to nontarget organs. Therapy was administered only if a 20-Gy-limit dose to normal organs (except red marrow) was guaranteed. Both patients we describe showed abnormal liver uptake, increasing for 6 days post injection. In patient 1, there was atypical biodistribution in whole-blood images at 16 hours, with a prevalent high liver uptake (45% at 20 hours). Injected activity (IA%) was above 40% at 26 hours in the liver and lower than 60% in the total body. In patient 2, early images showed regular biodistribution. Subsequent images showed progressive increase of liver uptake (above 25% of percent injected activity at 25 hours). Liver-absorbed doses of 51 and 53 Gy, respectively, would have resulted with the administration of the prescribed 56 MBq/kg. Following these dosimetric results, both patients did not receive the planned therapy. These findings support the recommendation to include dosimetry in high-dose RIT. [ABSTRACT FROM AUTHOR]