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.

Role of radiomic analysis of [18F]fluoromethylcholine PET/CT in predicting biochemical recurrence in a cohort of intermediate and high risk prostate cancer patients at initial staging.

AIM: To study the feasibility of radiomic analysis of baseline [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT) for the prediction of biochemical recurrence (BCR) in a cohort of intermediate and high-risk prostate cancer (PCa) patients. MATERIAL AND METHODS: Seventy-four patients were prospectively collected. We analyzed three prostate gland (PG) segmentations (i.e., PGwhole: whole PG; PG41%: prostate having standardized uptake value - SUV > 0.41*SUVmax; PG2.5: prostate having SUV > 2.5) together with three SUV discretization steps (i.e., 0.2, 0.4, and 0.6). For each segmentation/discretization step, we trained a logistic regression model to predict BCR using radiomic and/or clinical features. RESULTS: The median baseline prostate-specific antigen was 11 ng/mL, the Gleason score was > 7 for 54% of patients, and the clinical stage was T1/T2 for 89% and T3 for 9% of patients. The baseline clinical model achieved an area under the receiver operating characteristic curve (AUC) of 0.73. Performances improved when clinical data were combined with radiomic features, in particular for PG2.5 and 0.4 discretization, for which the median test AUC was 0.78. CONCLUSION: Radiomics reinforces clinical parameters in predicting BCR in intermediate and high-risk PCa patients. These first data strongly encourage further investigations on the use of radiomic analysis to identify patients at risk of BCR. CLINICAL RELEVANCE STATEMENT: The application of AI combined with radiomic analysis of [18F]fluoromethylcholine PET/CT images has proven to be a promising tool to stratify patients with intermediate or high-risk PCa in order to predict biochemical recurrence and tailor the best treatment options. KEY POINTS: • Stratification of patients with intermediate and high-risk prostate cancer at risk of biochemical recurrence before initial treatment would help determine the optimal curative strategy. • Artificial intelligence combined with radiomic analysis of [18F]fluorocholine PET/CT images allows prediction of biochemical recurrence, especially when radiomic features are complemented with patients' clinical information (highest median AUC of 0.78). • Radiomics reinforces the information of conventional clinical parameters (i.e., Gleason score and initial prostate-specific antigen level) in predicting biochemical recurrence.

Metastatic Adrenal PEComa: Case Report and Short Review of the Literature.

PEComa has become a widely accepted entity, and increased recognition has led to descriptions of this tumor in a wide variety of anatomic sites, including the adrenal gland. PEComa (perivascular epithelioid cell tumor) is a mesenchymal tumor composed of perivascular cells, and the most frequent sites of PEComas are the uterus and retroperitoneum. The incidence is <1 per 1,000,000 people. We report a case of adrenal metastatic PEComa in a 63-year-old man discovered by a spontaneous hematoma of the rectus abdominis. In our case, PEComa of the adrenal gland was a significant diagnostic dilemma as the morphologic and immunophenotypic features of this neoplasm may easily be confused with those of other more commonly encountered lesions.

Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications.

Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)-positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18F-DOPA-PET in 32/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated protein 1 and tankyrase 1 were upregulated, while beta-catenin, axin2, monocarboxylate transporter 8, and Frizzled 8 were downregulated. A positive relationship was found between 18F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of 18F-DOPA uptake correlating with LAT1 overexpression. We also demonstrated miR-375 overexpression and downregulated (Wnt) signaling and identified the Hippo pathway as a new potentially oncogenic feature of Pheo.

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.

Concomitant semi-quantitative and visual analysis improves the predictive value on treatment outcome of interim 18F-fluorodeoxyglucose/positron-emission tomography in advanced Hodgkin lymphoma.

BACKGROUND: Qualitative assessment using the Deauville five-point Scale (DS) is the gold standard for interim and end-of treatment positron-emission tomography (PET) interpretation in lymphoma. In the present study we assessed the reliability and the prognostic value of different semi- quantitative parameters in comparison with DS for interim PET (iPET) interpretation in Hodgkin lymphoma (HL). METHODS: A cohort of 82 out of 260 patients with advanced stage HL enrolled in the International Validation Study (IVS), scored as 3 to 5 by the expert panel was included in the present report. Two nuclear medicine physicians blinded to patient history, clinical data and treatment outcome reviewed independently the iPET using the following parameters: DS, SUVmax, SUVpeak of the most active lesion, Qmax (ratio of SUVmax of the lesion to liver SUVmax) and Qres (ratio of SUVpeak of the lesion to liver SUVmean). The optimal sensitivity, specificity, positive and negative predictive value to predict treatment outcome was calculated for all the above parameters with the receiver operator characteristics analysis. RESULTS: The prognostic value of all parameters were similar, the best cut-off value being 4 for DS (area under the curve [AUC], 0.81 95% CI: 0.72-0.90), 3.81 for SUVmax (AUC 0.82 95% CI: 0.73-0.91), 3.20 for SUVpeak (AUC 0.86 95% CI: 0.77-0.94), 1.07 for Qmax (AUC 0.84 95% CI: 0.75-0.93) and 1.38 for Qres (AUC 0.84 95% CI: 0.75-0.93). The reproducibility of different parameters was similar as the inter-observer variability measured with Cohen's kappa were 0.93 (95% CI: 0.84-1.01) for the DS, 0.88 (0.77-0.98) for SUVmax, 0.82 (0.70-0.95) for SUVpeak, 0.85 (0.74-0.97) for Qres and 0.78 (0.65-0.92) for Qmax. Due to the high specificity of SUVpeak (0.87) and to the good sensitivity of DS (0.86), upon the use of both parameters the positive predictive value increased from 0.65 of the DS alone to 0.79. When both parameters were positive in iPET, 3-years Failure-Free Survival (FFS) was significantly lower compared to patients whose iPET was interpreted with qualitative parameters only (DS 4 or 5): 21% vs. 35%. On the other hand, the FFS of patients with negative results was not significantly different (88% vs. 86%). CONCLUSIONS: In this study we demonstrated that, combining semi-quantitative parameters with SUVpeak to a pure qualitative interpretation key with DS, it is possible to increase the positive predictive value of iPET and to identify with higher precision the patients subset with a very dismal prognosis. However, these retrospective findings should be confirmed prospectively in a larger patient cohort.

The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale.

A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of 'interim' positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2-110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen's kappa 0.69-0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study.

WIDEN: A tool for medical image management in multicenter clinical trials.

Background It has been proposed that in clinical trials in which the therapeutic strategy is driven by functional imaging, central review of the images should be done in real time. Purpose We report our experience with a new tool for image exchange and review, called Web-Based Imaging Diagnosis by Expert Network (WIDEN), which we implemented for the HD0607 prospective multicenter Italian clinical trial in which Hodgkin lymphoma treatment was adapted based on results of an interim positron emission tomography (PET) scan performed after the first two cycles of chemotherapy. Methods We used WIDEN for general management of the clinical trial, site imaging qualification, image exchange, workflow control, blinded independent central review, inter-observer variability assessment, consensus creation, audit, and statistical analysis. Results As of February 2013, the interim PET was available for 512 patients; upon central review, 103 of the scans were judged to be positive and 409 to be negative. The median scan uploading and downloading times were 1 min, 25 s and 1 min, 55 s, respectively; the average and median times for diagnosis exchange were 47 h, 53 min and 37 h, 43 min, respectively. The binary concordance between pairs of reviewers (Cohen's kappa) ranged from 0.72 to 0.85. The 5-point scale concordance among all reviewers (Krippendorf's alpha) was 0.77. Conclusions WIDEN proved to be an effective tool for medical imaging exchange and online review. Data security, simplicity, feasibility, and prompt scan review were demonstrated. Central reviews were completed promptly.

Baseline prognostic predictors in classical Hodgkin Lymphoma: a retrospective, single-center analysis on patients treated with PET/CT-guided ABVD.

Introduction: The identification of baseline prognostic factors in Classical Hodgkin Lymphoma could help in tailoring a risk-based approach as the therapeutic landscape expands. Currently, the International Prognostic Score (IPS) represents the most used prediction tool in clinical practice, but other potential baseline risk predictors have been identified. Methods: We performed a retrospective analysis in a cohort of 274 patients treated with 18FDG-PET/CT-guided ABVD to assess the prognostic significance of the IPS risk factors, and to validate the impact of the peripheral blood lymphocyte to monocyte (LMR) and neutrophil to lymphocyte (NLR) ratios on prognosis definition. Results: Among the considered risk factors, stage IV disease (HR 1.83), leukocytosis (HR 2.28), anemia (HR 3.23) and low LMR (HR 2.01) significantly predicted PFS, whereas male sex (HR 2.93), stage IV disease (HR 3.00) and lymphopenia (HR 7.84) significantly predicted OS. A 4 variable and a 3 variable prognostic system was subsequently proposed for PFS and OS, respectively. In both cases, a stark decrease in the survival probability was documented as the score increased. Moreover, by selecting only the significant IPS items and considering a more recently proposed prognostic factor (LMR) we were able to better identify patients at higher risk of relapsing after PET/CT-guided ABVD. Discussion: Although the IPS was still able to identify a subgroup of high-risk patients within our cohort of individuals treated with PET/CT-guided ABVD, not all the risk factors that it considers were found to have an impact on survival times. Moreover, by selecting only the significant IPS items and considering a more recently proposed prognostic factor (LMR) we were able to better identify patients at higher risk of relapse, in an effort to contribute to the building of a modern risk prediction tool that can help guide treatment choices.

Evolution of the Diagnosis and Treatment of Primary Hyperparathyroidism.

This study aims to present the evolution of our center's approach to treating primary hyperparathyroidism (PHPT) from diagnosis to intraoperative interventions. We have also evaluated the intraoperative localization benefits of indocyanine green fluorescence angiography. This retrospective single-center study involved 296 patients who underwent parathyroidectomy for PHPT between January 2010 and December 2022. The preoperative diagnostic procedure included neck ultrasonography in all patients, [99mTc]Tc-MIBI scintigraphy in 278 patients, and, in 20 doubtful cases, [18F] fluorocholine positron emission tomography (PET) computed tomography (CT) was performed. Intraoperative PTH was measured in all cases. Indocyanine green has been administered intravenously since 2020 to guide surgical navigation using a fluorescence imaging system. The development of high precision diagnostic tools that can localize an abnormal parathyroid gland in combination with intra-operative PTH assay (ioPTH) enables the surgical treatment of PHPT patients with focused approaches and excellent results that are stackable with bilateral neck exploration (98% of surgical success). Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly and with minimal risk, especially when pre-operative localization has failed. When everything else fails, it is only an experienced surgeon who can resolve the situation.

Additional Value of PET and CT Image-Based Features in the Detection of Occult Lymph Node Metastases in Lung Cancer: A Systematic Review of the Literature.

Lung cancer represents the second most common malignancy worldwide and lymph node (LN) involvement serves as a crucial prognostic factor for tailoring treatment approaches. Invasive methods, such as mediastinoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), are employed for preoperative LN staging. Among the preoperative non-invasive diagnostic methods, computed tomography (CT) and, recently, positron emission tomography (PET)/CT with fluorine-18-fludeoxyglucose ([18F]FDG) are routinely recommended by several guidelines; however, they can both miss pathologically proven LN metastases, with an incidence up to 26% for patients staged with [18F]FDG PET/CT. These undetected metastases, known as occult LN metastases (OLMs), are usually cases of micro-metastasis or small LN metastasis (shortest radius below 10 mm). Hence, it is crucial to find novel approaches to increase their discovery rate. Radiomics is an emerging field that seeks to uncover and quantify the concealed information present in biomedical images by utilising machine or deep learning approaches. The extracted features can be integrated into predictive models, as numerous reports have emphasised their usefulness in the staging of lung cancer. However, there is a paucity of studies examining the detection of OLMs using quantitative features derived from images. Hence, the objective of this review was to investigate the potential application of PET- and/or CT-derived quantitative radiomic features for the identification of OLMs.

Prognostic value of myocardial perfusion scintigraphy in elderly patients with hypertension: a 10-year follow-up analysis.

PURPOSE: The aim of the study was to assess the role of myocardial perfusion scintigraphy (MPS) in the prediction of future cardiac events in elderly hypertensive patients and to investigate if its prognostic value is maintained during a 10-year follow-up period. METHODS: A total of 229 consecutive patients ≥ 65 years old (range 65-88 years) with arterial hypertension, who were referred to our institution for stress/rest (99m)Tc-sestamibi MPS between January 2000 and November 2001, were followed up for 10-12 years. Cardiac death, myocardial infarction and a coronary revascularization procedure were considered as events. Survival curves were computed by the Kaplan-Meier method. A stepwise Cox proportional hazards analysis was used to identify predictors of events. RESULTS: Follow-up was completed in 221 (96.5 %) patients; 26 patients experienced cardiac death, 29 myocardial infarction and 51 coronary revascularization. Annual event rates for cardiac death, cardiac death/myocardial infarction and cardiac death/myocardial infarction/coronary revascularization were, respectively, 0, 0.2 and 0.4 % for patients with a normal scan and 1.5, 3.0 and 5.3 % after an abnormal MPS. Event-free survival was significantly different according to extent and severity of perfusion defects (all p < 0.01). An increase in global chi-square in predicting cardiac events occurred when MPS data were added to pre-scan information (from 47.28 to 88.87; p < 0.001). CONCLUSION: MPS provides incremental prognostic information for the prediction of cardiac events in elderly patients with hypertension. Subjects with a normal scan have an excellent 10-year outcome, and the risk of experiencing a cardiac event increases with extension and severity of stress perfusion defect.

Detection of Unilateral Axillary Nodal Uptake Both at 68Ga-DOTATOC and 18F-FDG PET/CT After 1 Week From COVID-19 Vaccine.

ABSTRACT: Recently, vaccination against COVID-19 has gained wide diffusion, especially among vulnerable individuals, such as cancer patients. At the same time, patients have been undergoing PET/CT examinations after vaccination in an increasing number, and cases of false-positive axillary nodal uptake have been described, mostly at 18F-FDG PET. Here, we describe the case of both 68Ga-DOTATOC and 18F-FDG axillary nodal uptake in a young woman affected by a metastatic retroperitoneal paraganglioma.

Metastasis From Clear Cell Renal Cell Carcinoma Mimicking Well-Differentiated Pancreatic Neuroendocrine Tumor at 18F-FDG and 68Ga-DOTATOC PET/CT.

ABSTRACT: Dual-tracer PET/CT with both 18F-FDG and 68Ga-DOTA-conjugated peptides is currently used in clinical routine for characterizing pNET (pancreatic masses suspicious for neuroendocrine tumor). We describe here the case of a 81-year-old man with a pancreatic lesion showing high 68Ga-DOTATOC uptake and mild 18F-FDG avidity, thus suggesting a well-differentiated pNET, which resulted at endoscopic ultrasound-guided fine-needle aspiration to be a clear cell renal cell carcinoma metastasis. In fact, the patient had right nephrectomy for clear cell renal cell carcinoma 27 years earlier. This case puts light on the role of PET/CT with 68Ga-DOTATOC in imaging RCC, a field which deserves to be further explored.

Tumour markers and FDG PET/CT for prediction of disease relapse in patients with breast cancer.

PURPOSE: The aim of the study was to assess the role of CA 15.3, CT and positron emission tomography (PET)/CT in patients with breast cancer and suspected disease relapse after primary treatment. METHODS: We studied 111 consecutive patients (mean age 61 ± 12 years) with previous breast cancer, already treated and with clinical or biochemical suspicion of disease relapse. All patients underwent CT and (18)F-fluorodeoxyglucose (FDG) PET/CT. In all patients, the value of CA 15.3 was compared to PET/CT and CT. The final diagnosis of relapse was established by invasive and noninvasive follow-up and was compared with CA 15.3, CT and PET/CT results. Univariate and multivariate analyses were used to identify the independent predictors of disease relapse and receiver-operating characteristic (ROC) curve for the identification of optimal CA 15.3 cutoff. RESULTS: Of all patients, 40 (36%) showed an increased CA 15.3 value, CT was positive in 73 (66%), whereas at PET/CT imaging 64 (58%) showed positive findings for disease relapse. Of 40 patients with increased marker levels, 22 patients had positive CT and 30 positive PET/CT (55 vs 75%, p < 0.001). At the end of follow-up, recurrence occurred in 32 (29%) patients, 16 (50%) of whom showed high levels of CA 15.3. PET/CT predicted relapse in 26 (81%) patients, whereas CT correctly identified 23 (72%). At univariate analysis, recurrence was significantly associated with high CA 15.3 values (p < 0.05) and positive PET/CT (p < 0.005). At multivariable analysis only positive PET/CT remained an independent predictor of disease relapse (p < 0.05). ROC analysis showed an optimal cutoff point for CA 15.3 of 19.1 U/ml (AUC 0.65, p < 0.01) to individuate positive PET/CT. CONCLUSION: FDG PET/CT is more sensitive than CT and CA 15.3 in the evaluation of disease relapse. PET/CT might be considered a complementary imaging technique during follow-up in patients with breast cancer.

Additional Value of PET Radiomic Features for the Initial Staging of Prostate Cancer: A Systematic Review from the Literature.

We performed a systematic review of the literature to provide an overview of the application of PET radiomics for the prediction of the initial staging of prostate cancer (PCa), and to discuss the additional value of radiomic features over clinical data. The most relevant databases and web sources were interrogated by using the query "prostate AND radiomic* AND PET". English-language original articles published before July 2021 were considered. A total of 28 studies were screened for eligibility and 6 of them met the inclusion criteria and were, therefore, included for further analysis. All studies were based on human patients. The average number of patients included in the studies was 72 (range 52-101), and the average number of high-order features calculated per study was 167 (range 50-480). The radiotracers used were [68Ga]Ga-PSMA-11 (in four out of six studies), [18F]DCFPyL (one out of six studies), and [11C]Choline (one out of six studies). Considering the imaging modality, three out of six studies used a PET/CT scanner and the other half a PET/MRI tomograph. Heterogeneous results were reported regarding radiomic methods (e.g., segmentation modality) and considered features. The studies reported several predictive markers including first-, second-, and high-order features, such as "kurtosis", "grey-level uniformity", and "HLL wavelet mean", respectively, as well as PET-based metabolic parameters. The strengths and weaknesses of PET radiomics in this setting of disease will be largely discussed and a critical analysis of the available data will be reported. In our review, radiomic analysis proved to add useful information for lesion detection and the prediction of tumor grading of prostatic lesions, even when they were missed at visual qualitative assessment due to their small size; furthermore, PET radiomics could play a synergistic role with the mpMRI radiomic features in lesion evaluation. The most common limitations of the studies were the small sample size, retrospective design, lack of validation on external datasets, and unavailability of univocal cut-off values for the selected radiomic features.

Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143).

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC. METHODS: A retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens. RESULTS: 143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor. CONCLUSIONS: Autoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.

The role of 68Ga-DOTA derivatives PET-CT in patients with ectopic ACTH syndrome.

INTRODUCTION AND AIM: Ectopic ACTH secretion (EAS) is mostly secondary to thoracic/abdominal neuroendocrine tumours (NETs) or small cell-lung carcinoma (SCLC). We studied the diagnostic accuracy of CT with 68Ga-Dota derivatives (68Ga-SSTR) PET in localizing ACTH-secreting tumor in patients with EAS. MATERIALS AND METHODS: 68Ga-SSTR-PET/CT was performed and compared with the nearest enhanced CT in 18 cases (16 primary and 2 recurrent neoplasms). Unspecific, indeterminate and false-positive uptakes were assessed using conventional imaging, follow-up or histology. RESULTS: We diagnosed 13 thoracic (9 primary and 2 recurrent bronchial carcinoids, 2 SCLCs) and 1 abdominal (pancreatic NET) tumors. Eight ACTH-secreting tumors were promptly identified at EAS diagnosis ('overt', four pulmonary carcinoids with two recurrences and two SCLC); six EAS have been discovered during the subsequent follow-up ('covert', five bronchial carcinoids and one pancreatic NET). At the time of EAS diagnosis, imaging was able to correctly detect the ACTH-secreting tumour in 8/18 cases (6 new diagnosis and 2 recurrences). During the follow-up, six out of initially ten 'occult' cases became 'covert'. At last available follow-up, CT and 68Ga-SSTR-PET/CT were able to diagnose 11/18 and 12/18 ACTH-secreting tumours, respectively (11/14 and 12/14 considering only overt and covert cases, respectively). Four cases have never been localized by conventional or nuclear imaging ('occult EAS'), despite an average follow-up of 5 years. CONCLUSION: The 68Ga-SSTR-PET/CT is useful in localizing EAS, especially to enhance positive prediction of the suggestive CT lesions and to detect occult neoplasms.

A Case with Early Onset Alzheimer's Disease, Frontotemporal Hypometabolism, ApoE Genotype ɛ4/ɛ4 and C9ORF72 Intermediate Expansion: A Treviso Dementia (TREDEM) Registry Case Report.

We report the case of a woman firstly referred to our Memory Clinic at the age of 61, following the development of cognitive complaints and difficulties in sustained attention. The investigation that was performed showed: predominant executive dysfunctions at the neuropsychological evaluation, with mild, partial and stable involvement of the memory domain; cortical and subcortical atrophy with well-preserved hippocampal structures at MRI; marked fronto-temporal and moderate parietal hypometabolism from 18F-FDG PET study with a sparing of the posterior cingulate and precuneus; positivity of amyloid-ß at 18F-Flutemetamol PET; an hexanucleotide intermediate repeats expansion of C9ORF72 gene (12//38 repeats) and ApoE genotype ɛ4/ɛ4. The patient was diagnosed with probable early onset frontal variant of Alzheimer's disease (AD), presenting with a major executive function impairment. The lack of specific areas of brain atrophy, as well as the failure to meet the clinical criteria for any frontotemporal dementia, drove us to perform the aforementioned investigations, which yielded our final diagnosis. The present case highlights the need to take into consideration a diagnosis of frontal variant of AD when the metabolic and the clinical picture are somehow dissonant.