International Benchmark for Total Metabolic Tumor Volume Measurement in Baseline 18F-FDG PET/CT of Lymphoma Patients: A Milestone Toward Clinical Implementation.

Total metabolic tumor volume (TMTV) is prognostic in lymphoma. However, cutoff values for risk stratification vary markedly, according to the tumor delineation method used. We aimed to create a standardized TMTV benchmark dataset allowing TMTV to be tested and applied as a reproducible biomarker. Methods: Sixty baseline 18F-FDG PET/CT scans were identified with a range of disease distributions (20 follicular, 20 Hodgkin, and 20 diffuse large B-cell lymphoma). TMTV was measured by 12 nuclear medicine experts, each analyzing 20 cases split across subtypes, with each case processed by 3-4 readers. LIFEx or ACCURATE software was chosen according to reader preference. Analysis was performed stepwise: TMTV1 with automated preselection of lesions using an SUV of at least 4 and a volume of at least 3 cm3 with single-click removal of physiologic uptake; TMTV2 with additional removal of reactive bone marrow and spleen with single clicks; TMTV3 with manual editing to remove other physiologic uptake, if required; and TMTV4 with optional addition of lesions using mouse clicks with an SUV of at least 4 (no volume threshold). Results: The final TMTV (TMTV4) ranged from 8 to 2,288 cm3, showing excellent agreement among all readers in 87% of cases (52/60) with a difference of less than 10% or less than 10 cm3 In 70% of the cases, TMTV4 equaled TMTV1, requiring no additional reader interaction. Differences in the TMTV4 were exclusively related to reader interpretation of lesion inclusion or physiologic high-uptake region removal, not to the choice of software. For 5 cases, large TMTV differences (>25%) were due to disagreement about inclusion of diffuse splenic uptake. Conclusion: The proposed segmentation method enabled highly reproducible TMTV measurements, with minimal reader interaction in 70% of the patients. The inclusion or exclusion of diffuse splenic uptake requires definition of specific criteria according to lymphoma subtype. The publicly available proposed benchmark allows comparison of study results and could serve as a reference to test improvements using other segmentation approaches.

Improvements and future perspective in diagnostic tools for neuroendocrine neoplasms.

INTRODUCTION: Neuroendocrine neoplasms (NENs) represent a complex group of tumors arising from neuroendocrine cells, characterized by heterogeneous behavior and challenging diagnostics. Despite advancements in medical technology, NENs present a major challenge in early detection, often leading to delayed diagnosis and variable outcomes. This review aims to provide an in-depth analysis of current diagnostic methods as well as the evolving and future directions of diagnostic strategies for NENs. AREA COVERED: The review extensively covers the evolution of diagnostic tools for NENs, from traditional imaging and biochemical tests to advanced genomic profiling and next-generation sequencing. The emerging role of technologies such as artificial intelligence, machine learning, and liquid biopsies could improve diagnostic precision, as could the integration of imaging modalities such as positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrids and innovative radiotracers. EXPERT OPINION: Despite progress, there is still a significant gap in the early diagnosis of NENs. Bridging this diagnostic gap and integrating advanced technologies and precision medicine are crucial to improving patient outcomes. However, challenges such as low clinical awareness, limited possibility of noninvasive diagnostic tools and funding limitations for rare diseases like NENs are acknowledged.

End of induction [18F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

PURPOSE: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. METHODS: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). RESULTS: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). CONCLUSION: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.

Progressive multifocal leukoencephalopathy in multiple myeloma: a case report of a patient with SARS-CoV-2 infection and an updated systematic literature review.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2, previously known as JCV) in immunosuppressed individuals. Few cases of PML have been described in multiple myeloma (MM) patients. METHODS: We described a case of PML in a patient with MM with fatal worsening that occurred during SARS-CoV-2 infection. We also performed a literature review to update the 16 cases series of MM patients with PML already collected until April 2020. RESULTS: A 79-year-old female patient with refractory IgA lambda MM in Pomalidomide- Cyclophosphamide-Dexamethasone regimen developed gradual lower limbs and left arm paresis along with a decreased consciousness 3.5 years after the MM diagnosis. Symptoms developed shortly after the recognition of hypogammaglobulinemia. After SARS-CoV-2 infection, her neurological status quickly worsened until she deceased. MRI features and JCV-positive PCR on CSF confirmed the PML diagnosis. Our literature review adds sixteen clinical cases of PML in MM published between May 2020 and March 2023 to the 16 cases already collected in the previously published review by Koutsavlis. DISCUSSION: PML has been increasingly described in MM patients. It remains questionable if the HPyV-2 reactivation is determined by the severity of MM itself, by the effect of drugs or by a combination of both. SARS-CoV-2 infection may have a role in worsening PML in affected patients.

18F-FDG PET/CT Maximum Tumor Dissemination (Dmax) in Lymphoma: A New Prognostic Factor?

Recently, several studies introduced the potential prognostic usefulness of maximum tumor dissemination (Dmax) measured by 2-deoxy-2-fluorine-18-fluoro-D-glucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Dmax is a simple three-dimensional feature that represents the maximal distance between the two farthest hypermetabolic PET lesions. A comprehensive computer literature search of PubMed/MEDLINE, Embase, and Cochrane libraries was conducted, including articles indexed up to 28 February 2023. Ultimately, 19 studies analyzing the value of 18F-FDG PET/CT Dmax in patients with lymphomas were included. Despite their heterogeneity, most studies showed a significant prognostic role of Dmax in predicting progression-free survival (PFS) and overall survival (OS). Some articles showed that the combination of Dmax with other metabolic features, such as MTV and interim PET response, proved to better stratify the risk of relapse or death. However, some methodological open questions need to be clarified before introducing Dmax into clinical practice.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

Intrahepatic cholangiocarcinoma (iCCA) is recognized as the second most frequently diagnosed liver malignancy, following closely after hepatocellular carcinoma. Its incidence has seen a global upsurge in the past several years. Unfortunately, due to the lack of well-defined risk factors and limited diagnostic tools, iCCA is often diagnosed at an advanced stage, resulting in a poor prognosis. While surgery is the only potentially curative option, it is rarely feasible. Currently, there are ongoing investigations into various treatment approaches for unresectable iCCA, including conventional chemotherapies, targeted therapies, immunotherapies, and locoregional treatments. This study aims to explore the role of transarterial radioembolization (TARE) in the treatment of unresectable iCCA and provide a comprehensive review. The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA, with a median overall survival (OS) of 14.9 months in the study cohort. Studies on TARE for unresectable iCCA, both as a first-line treatment (as a neo-adjuvant down-staging strategy) and as adjuvant therapy, have reported varying median response rates (ranging from 34% to 86%) and median OS (12-16 mo). These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies. Most studies have identified tumor burden, portal vein involvement, and the patient's performance status as key prognostic factors. Furthermore, a phase 2 trial evaluated the combination of TARE and chemotherapy (cisplatin-gemcitabine) as a first-line therapy for locally advanced unresectable iCCA. The results showed promising outcomes, including a median OS of 22 mo and a 22% achievement in down-staging the tumor. In conclusion, TARE represents a viable treatment option for unresectable iCCA, and its combination with systemic chemotherapy has shown promising results. However, it is important to consider treatment-independent factors that can influence prognosis. Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

The "digital biopsy" in non-small cell lung cancer (NSCLC): a pilot study to predict the PD-L1 status from radiomics features of [18F]FDG PET/CT.

PURPOSE: The present pilot study investigates the putative role of radiomics from [18F]FDG PET/CT scans to predict PD-L1 expression status in non-small cell lung cancer (NSCLC) patients. METHODS: In a retrospective cohort of 265 patients with biopsy-proven NSCLC, 86 with available PD-L1 immunohistochemical (IHC) assessment and [18F]FDG PET/CT scans have been selected to find putative metabolic markers that predict PD-L1 status (< 1%, 1-49%, and ≥ 50% as per tumor proportion score, clone 22C3). Metabolic parameters have been extracted from three different PET/CT scanners (Discovery 600, Discovery IQ, and Discovery MI) and radiomics features were computed with IBSI compliant algorithms on the original image and on images filtered with LLL and HHH coif1 wavelet, obtaining 527 features per tumor. Univariate and multivariate analysis have been performed to compare PD-L1 expression status and selected radiomic features. RESULTS: Of the 86 analyzed cases, 46 (53%) were negative for PD-L1 IHC, 13 (15%) showed low PD-L1 expression (1-49%), and 27 (31%) were strong expressors (≥ 50%). Maximum standardized uptake value (SUVmax) demonstrated a significant ability to discriminate strong expressor cases at univariate analysis (p = 0.032), but failed to discriminate PD-L1 positive patients (PD-L1 ≥ 1%). Three radiomics features appeared the ablest to discriminate strong expressors: (1) a feature representing the average high frequency lesion content in a spherical VOI (p = 0.009); (2) a feature assessing the correlation between adjacent voxels on the high frequency lesion content (p = 0.004); (3) a feature that emphasizes the presence of small zones with similar grey levels inside the lesion (p = 0.003). The tri-variate linear discriminant model combining the three features achieved a sensitivity of 81% and a specificity of 82% in the test. The ability of radiomics to predict PD-L1 positive patients was instead scarce. CONCLUSIONS: Our data indicate a possible role of the [18F]FDG PET radiomics in predicting strong PD-L1 expression; these preliminary data need to be confirmed on larger or single-scanner series.

Validity of cingulate-precuneus-temporo-parietal hypometabolism for single-subject diagnosis of biomarker-proven atypical variants of Alzheimer's Disease.

The aim of our study was to establish empirically to what extent reduced glucose uptake in the precuneus, posterior cingulate and/or temporo-parietal cortex (PCTP), which is thought to indicate brain amyloidosis in patients with dementia or MCI due to Alzheimer's Disease (AD), permits to distinguish amyloid-positive from amyloid-negative patients with non-classical AD phenotypes at the single-case level. We enrolled 127 neurodegenerative patients with cognitive impairment and a positive (n. 63) or negative (n. 64) amyloid marker (cerebrospinal fluid or amy-PET). Three rating methods of FDG-PET scan were applied: purely qualitative visual interpretation of uptake images (VIUI), and visual reading assisted by a semi-automated and semi-quantitative tool: INLAB, provided by the Italian National Research Council, or Cortex ID Suite, marketed by GE Healthcare. Fourteen scans (11.0%) patients remained unclassified by VIUI or INLAB procedures, therefore, validity values were computed on the remaining 113 cases. The three rating approaches showed good total accuracy (77-78%), good to optimal sensitivity (81-93%), but poorer specificity (62-75%). VIUI showed the highest sensitivity and the lowest specificity, and also the highest proportion of unclassified cases. Cases with asymmetric temporo-parietal hypometabolism and a progressive aphasia or corticobasal clinical profile, in particular, tended to be rated as AD-like, even if biomarkers indicated non-amyloid pathology. Our findings provide formal support to the value of PCTP hypometabolism for single-level diagnosis of amyloid pathophysiology in atypical AD, but also highlight the risk of qualitative assessment to misclassify patients with non-AD PPA or CBS underpinned by asymmetric temporo-parietal hypometabolism.

Clinical Application of a High Sensitivity BGO PET/CT Scanner: Effects of Acquisition Protocols and Reconstruction Parameters on Lesions Quantification.

AIMS: The aim of this retrospective study was to investigate SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm. BACKGROUND: SUVmax and SUVpeak are influenced by technical factors as count statistics and reconstruction algorithms. OBJECTIVE: To fulfill the aim, we evaluated the SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm (ordered - subset expectation maximization plus point spread function option - OSEM+PSF, regularized Bayesian Penalized Likelihood - BPL) in a 5 - rings BGO PET/CT scanner. METHODS: Discovery IQ scanner (GE Healthcare, Milwaukee, Wisconsin, US) was used for list mode acquisition of 25 FDG patients, 12 injected with 3.7 MBq/kg (Standard Dose protocol - SD) and 13 injected with 1.8 MBq/kg (Low Dose protocol - LD). Each acquisition was reconstructed at different time/FOV with both OSEM+PSF algorithm and BPL using seven different beta factors. SUVs were calculated in 70 lesions and analysed in function of time/FOV and Beta. Image quality was evaluated as a coefficient of variation of the liver (CV - liver). RESULTS: SUVs were not considerably affected by time/FOV. However, SUVs were influenced by beta: differences were higher in small lesions (37% for SUVmax, 15% for SUVpeak) compared to larger ones (14% and 6%). CV - liver ranged from 6% with Beta-500 (LD and SD) to 13% with Beta- 200 (LD). CV - liver of BPL with Beta-350 (optimized for clinical practice in our institution) in LD was lower than CV - liver of OSEM+PSF in SD. CONCLUSION: When a high sensitivity 5 - rings BGO PET/CT scanner is used with the same reconstruction algorithm, quantification by means of SUVmax and SUVpeak is a robust standard compared to the activity and scan duration. However, both SUVs and image quality are influenced by reconstruction algorithms and the related parameters should be considered to obtain the best compromise between detectability, quantification, and noise.

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study.

PURPOSE: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS: Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). CONCLUSION: A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience.

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume-wMTV, total lesion glycolysis-wTLG, higher standardized uptake volume maximum and mean-SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

Temporal lobe dysfunction in late-onset epilepsy of unknown origin.

OBJECTIVE: Epilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU. METHODS: We selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment. RESULTS: Twenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%). SIGNIFICANCE: Late-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

COVID-19-related encephalopathy presenting with aphasia resolving following tocilizumab treatment.

Encephalopathy is emerging as a recurrent complication of COVID-19 yet remains poorly characterized. We report the case of a middle-aged woman with COVID-19-related encephalopathy presenting as expressive aphasia and inattentiveness, subsequently progressing to agitation and marked confusion. Brain MRI and CSF analysis were unremarkable, while EEG showed slowing with frontal sharp waves. Neuropsychiatric symptoms resolved following treatment with tocilizumab. CNS involvement in COVID-19 may present as a subacute encephalopathy characterized by prominent frontal lobe dysfunction, with language disturbances as first neurological manifestation. Future studies should further investigate the role of tocilizumab in treating COVID-19-related encephalopathy.

Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial.

PURPOSE: To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS: Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS: Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION: cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Respiratory Gating and the Performance of PET/CT in Pulmonary Lesions.

BACKGROUND: Motion artifacts related to the patient's breathing can be the cause of underestimation of the lesion uptake and can lead to missing of small lung lesions. The respiratory gating (RG) technology has demonstrated a significant increase in image quality. OBJECTIVE: The aim of this paper was to evaluate the advantages of RG technique on PET/CT performance in lung lesions. The impact of 4D-PET/CT on diagnosis (metabolic characterization), staging and re-staging lung cancer was also assessed, including its application for radiotherapy planning. Finally, new technologies for respiratory motion management were also discussed. METHODS: A comprehensive electronic search of the literature was performed by using Medline database (PubMed) searching "PET/CT", "gated" and "lung". Original articles, review articles, and editorials published in the last 10 years were selected, included and critically reviewed in order to select relevant articles. RESULTS: Many papers compared Standardized Uptake Value (SUV) in gated and ungated PET studies showing an increase in SUV of gated images, particularly for the small lesions located in medium and lower lung. In addition, other features as Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) and textural-features presented differences when obtained from gated and ungated PET acquisitions. Besides the increase in quantification, gating techniques can determine an increase in the diagnostic accuracy of PET/CT. Gated PET/CT was evaluated for lung cancer staging, therapy response assessment and for radiation therapy planning. CONCLUSION: New technologies able to track the motion of organs lesion directly from raw PET data, can reduce or definitively solve problems (i.e.: extended acquisition time, radiation exposure) currently limiting the use of gated PET/CT in clinical routine.

Combining positron emission tomography/computed tomography, radiomics, and sentinel lymph node mapping for nodal staging of endometrial cancer patients.

OBJECTIVE: To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS: From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). RESULTS: In Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%). CONCLUSIONS: PET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.