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.

Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer's disease.

PURPOSE: To compare the incremental diagnostic value of amyloid-PET and CSF (Aß42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. METHODS: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. RESULTS: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. CONCLUSIONS: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. TRIAL REGISTRATION: EudraCT no.: 2014-005389-31.

GEMOX: An Active Regimen for the Treatment of Luminal and Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

BACKGROUND: Pretreated metastatic breast cancer (MBC) remains a formidable challenge with unmet needs both in terms of prolonged survival and quality-of-life-related issues. METHODS: We collected data from 27 MBC patients treated with gemcitabine and oxaliplatin (GEMOX) at our institution between June 2009 and April 2015. The patients were heavily pretreated, and all had previously been exposed to anthracyclines and taxanes. RESULTS: We achieved a complete response in 1 patient (4%), a partial response in 7 patients (26%) and stable disease in 12 patients (44%), while 6 patients (22%) experienced progressive disease. The response of 1 patient (4%) could not be evaluated because she interrupted her treatment during the first cycle due to a major reaction to oxaliplatin. We observed grade 4 hypertransaminasaemia in only 1 patient (4%) and grade 2 neuropathy in 16 patients (59%). Grade 3 leuconeutropenia was observed in 5 patients (18%). The median progression-free survival was 5.9 months and the median overall survival was 9.6 months. CONCLUSIONS: GEMOX is an efficient and well-tolerated salvage regimen for MBC patients.

The importance of a correct positioning of the heart using IQ-SPECT system with multifocal collimators in myocardial perfusion imaging: a phantom study.

BACKGROUND: We have recently validated a quarter-time protocol in Myocardial Perfusion Imaging named IQ-SPECT, whose basic principle is to implement a multifocal collimator; However, in clinical practice, it may sometimes be difficult to center the heart in the region of highest magnification of the multifocal collimators (the so-called sweet spot). We therefore aimed to evaluate whether a heart mispositioning may affect results in MPI. METHODS: We simulated a rest study with an anthropomorphic phantom with an in vivo distribution of 400 MBq [(99m)Tc]tetrofosmin, with and without a transmural defect (TD). For each set of images, we performed 5 acquisitions, one with a correct centering and with other 4 degrees of mispositioning. Raw data and reconstructed images were evaluated qualitatively and quantitatively, including no corrections, correction for attenuation, for scatter or for both. We assessed polar plot uniformity, LV wall thickness, and TD and cavity contrast. RESULTS: Images obtained either with a correct heart centering or with mild misposition showed no differences, both qualitatively and quantitatively. Those obtained with major mispositioning differed in uniformity and TD contrast depending on correction parameters. CONCLUSION: This is the first study investigating how a heart mispositioning can affect diagnostic accuracy with IQ-SPECT system. Mild-to-moderate mispositioning (≤2.5 cm) is unlikely to significantly affect results.

Final results of a phase 2A study for the treatment of metastatic neuroendocrine tumors with a fixed activity of 90Y-DOTA-D-Phe1-Tyr3 octreotide.

BACKGROUND: The objective of this study was to assess the efficacy of (90)Y-DOTA-D-Phe1-Tyr3 octreotide ((90)Y-DOTATOC) therapy with a fixed activity of 2.56 GigaBequerels bimonthly in patients with advanced stage, well differentiated neuroendocrine carcinomas. METHODS: In total, 38 patients were enrolled in this phase 2A protocol. All patients had gastroenteropancreatic neuroendocrine tumors in sharp clinical and radiologic progression despite previous surgery, chemotherapy, and biotherapy. Their survival rate after therapy with (90)Y-DOTATOC was compared with a chronologic control group of patients who had received biotherapy and chemotherapy and with results from a previous similar study. The progression-free survival rate after peptide receptor radionuclide therapy with (90)Y-DOTATOC was determined for all patients until they had documented disease progression according to Response Criteria in Solid Tumors, tumor-related death, or censoring. RESULTS: Seventeen patients (43.6%) had a partial response, 10 patients (25.6%) had stable disease, and 11 patients (28.2%) had progressive disease. A statistically significant difference was observed (P < .001) between the response to (90)Y-DOTATOC treatment and the response to biotherapy with somatostatin analogs and chemotherapy and also between the current results and the results from a previous similar study (P < .05). At the time of the current evaluation with ongoing follow-up for 30 patients, the median progression-free survival was 22.3 months. CONCLUSIONS: The results from this phase 2 study indicated that the treatment of metastatic neuroendocrine tumors with fixed (90)Y-DOTATOC activity is useful and safe.

Clinical and prognostic 18F-FDG PET/CT role in recurrent vulvar cancer: a multicentric experience.

PURPOSE: The aim of this retrospective multicentric study was to investigate the diagnostic performance, the prognostic value and the impact of 18F-FDG PET/CT on treatment decision-making in patients with suspected recurrent vulvar cancer (VC). MATERIALS AND METHODS: Sixty-three patients affected by VC performed 18F-FDG-PET/CT for restaging purposes in case of suspected clinical and/or radiological recurrence. Histopatology results if available and/or clinical-imaging follow-up for at least 12 months were considered as reference standard. The diagnostic accuracy and the clinical impact of 18F-FDG PET/CT were investigated. Progression free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier curves. RESULTS: Fifty-two (82.5%) PET/CT showed the presence of recurrence, while the remaining 11 (17.5%) were negative. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT were 100% (95%CI 93-100%), 92% (95%CI 62-100%), 98% (95%CI 89-99%), 100% and 98% (95%CI 92-100%). A relevant impact of 18F-FDG PET/CT imaging was registered in 28 cases: in 12 cases moving from local therapy to chemotherapy due to the recognition of disseminate localizations; in 10 showing the site of recurrence in presence of negative conventional imaging, and in 6 cases confirming to be true negative and avoiding unnecessary therapies. Beside advanced age and HPV status, a positive restaging 18F-FDG PET/CT scan was significantly correlated with shorter PFS and OS compared to negative scan (p < 0.001). CONCLUSIONS: 18F-FDG PET/CT demonstrated to be an accurate tool in the assessing of recurrent VC with high sensitivity and specificity and with a significant impact on clinical decision-making. Restaging 18F-FDG PET/CT findings were associated with survival.

Delayed PET/CT of Pericardial Synovial Sarcoma.

ABSTRACT: Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma. When considering mediastinal or pericardial mass, a delayed PET/CT may improve lesion-to-background contrast by reducing blood pool activity.

Penile Metastasis From Prostate Cancer Detected by 18F-Fluorocholine PET/CT.

F-Fluorocholine (F-FCH) PET/CT is widely used to study patients affected by prostate cancer. F-FCH PET/CT is suitable for the detection of pelvic and abdominal nodal and skeletal metastases. Indeed, F-FCH PET/CT sensitivity for other organs, such as the liver and the urinary tract, is lowered by the radiopharmaceutical urinary washout and intense liver uptake. Herein, we report the case of a patient affected by oligometastatic prostate cancer in good clinical condition treated with total androgen blockade. F-FCH PET/CT showed a diffuse and intense uptake in the shaft of the penis, which was an evidence of a rare penile metastasis.

Drug-Related Pneumonitis in Cancer Treatment during the COVID-19 Era.

Interstitial lung disease is recognized as a group of diseases with a different etiopathogenesis characterized by chronic lung inflammation with the accumulation of inflammatory cells, lymphocytes and macrophages, and the consequent release of proinflammatory cytokines. Various degrees of pulmonary fibrosis can be associated with this inflammatory condition. Interstitial lung disease related to oncological drugs is a relevant problem in clinical practice. The etiopathogenetic mechanisms underlying this adverse event are not completely known but can be partly explained by the mechanism of action of the drug involved. Therefore, knowledge of the relevance of this potentially fatal adverse event supported by the reported safety data of pivotal studies becomes fundamental in the management of patients. The prompt diagnosis of drug-related pneumonia and the consequent differential diagnosis with other forms of pneumonia allow a rapid suspension of treatment and the establishment of an immunosuppressive treatment if necessary. In the context of the health emergency related to SARS CoV2 infection and COVID-19-related interstitial lung disease, such knowledge holds decisive relevance in the conscious choice of cancer treatments. Our intent was to describe the oncological drugs most correlated with this adverse event by reporting, where possible, the percentages of insurgency in pivotal studies to provide an overview and therefore promote greater awareness of this important toxicity related to oncological treatment.

SARS-CoV-2-related encephalitis with prominent parkinsonism: clinical and FDG-PET correlates in two patients.

Considering the similarities with other pandemics due to respiratory virus infections and subsequent development of neurological disorders (e.g. encephalitis lethargica after the 1918 influenza), there is growing concern about a possible new wave of neurological complications following the worldwide spread of SARS-CoV-2. However, data on COVID-19-related encephalitis and movement disorders are still limited. Herein, we describe the clinical and neuroimaging (FDG-PET/CT, MRI and DaT-SPECT) findings of two patients with COVID-19-related encephalopathy who developed prominent parkinsonism. None of the patients had previous history of parkinsonian signs/symptoms, and none had prodromal features of Parkinson's disease (hyposmia or RBD). Both developed a rapidly progressive form of atypical parkinsonism along with distinctive features suggestive of encephalitis. A possible immune-mediated etiology was suggested in Patient 2 by the presence of CSF-restricted oligoclonal bands, but none of the patients responded favorably to immunotherapy. Interestingly, FDG-PET/CT findings were similar in both cases and reminiscent of those observed in post-encephalitic parkinsonism, with cortical hypo-metabolism associated with hyper-metabolism in the brainstem, mesial temporal lobes, and basal ganglia. Patient's FDG-PET/CT findings were validated by performing a Statistical Parametric Mapping analysis and comparing the results with a cohort of healthy controls (n = 48). Cerebrum cortical thickness map was obtained in Patient 1 from MRI examinations to evaluate the structural correlates of the metabolic alterations detected with FDG-PET/CT. Hypermetabolic areas correlated with brain regions showing increased cortical thickness, suggesting their involvement during the inflammatory process. Overall, these observations suggest that SARS-CoV-2 infection may trigger an encephalitis with prominent parkinsonism and distinctive brain metabolic alterations.

Delirium in Patients with SARS-CoV-2 Infection: A Multicenter Study.

OBJECTIVES: The aims of this study are to report the prevalence of delirium on admission to the unit in patients hospitalized with SARS-CoV-2 infection, to identify the factors associated with delirium, and to evaluate the association between delirium and in-hospital mortality. DESIGN: Multicenter observational cohort study. SETTINGS: Acute medical units in four Italian hospitals. PARTICIPANTS: A total of 516 patients (median age 78 years) admitted to the participating centers with SARS-CoV-2 infection from February 22 to May 17, 2020. MEASUREMENTS: Comprehensive medical assessment with detailed history, physical examinations, functional status, laboratory and imaging procedures. On admission, delirium was determined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria, 4AT, m-Richmond Agitation Sedation Scale, or clinical impression depending on the site. The primary outcomes were delirium rates and in-hospital mortality. RESULTS: Overall, 73 (14.1%, 95% confidence interval (CI) = 11.0-17.3%) patients presented delirium on admission. Factors significantly associated with delirium were dementia (odds ratio, OR = 4.66, 95% CI = 2.03-10.69), the number of chronic diseases (OR = 1.20, 95% CI = 1.03; 1.40), and chest X-ray or CT opacity (OR = 3.29, 95% CI = 1.12-9.64 and 3.35, 95% CI = 1.07-10.47, for multiple or bilateral opacities and single opacity vs no opacity, respectively). There were 148 (33.4%) in-hospital deaths in the no-delirium group and 43 (58.9%) in the delirium group (P-value assessed using the Gray test <.001). As assessed by a multivariable Cox model, patients with delirium on admission showed an almost twofold increased hazard ratio for in-hospital mortality with respect to patients without delirium (hazard ratio = 1.88, 95% CI = 1.25-2.83). CONCLUSION: Delirium is prevalent and associated with in-hospital mortality among older patients hospitalized with SARS-CoV-2 infection.

Dural Metastases of Advanced Prostate Cancer Detected by 18F-Fluorocholine.

Prostate cancer with extensive dural metastases is very rare, with only few cases described in the literature. We report one such case of a 74-year-old man with advanced prostate cancer, and in relatively good clinical condition. The patient returned with complaints of headache and diplopia. Fluorocholine (18F) chloride (18F-FCH) is an analog of choline in which a hydrogen atom has been replaced by fluorine (18F). After crossing the cell membrane by a carrier-mediated mechanism, choline is phosphorylated by choline kinase to produce phosphorylcholine. 18F-FCH positron emission tomography-computed tomography (PET/CT) is widely used to stage and restage patients affected by prostate cancer with good sensitivity. 18F-FCH PET/CT showed disease progression with the onset of multiple skull lesions. Numerous suspicious dural hypermetabolic lesions indicating neoplastic involvement were detected along the fronto-parietal convexities, in the left fronto-orbital region and right lateral wall of the orbit, concerning for metastases in these regions. A contrast-enhanced computed tomography (CECT) scan was performed which showed corresponding enhancing tissue which correlated with the PET findings. The final imaging diagnosis was osteo-dural metastases from prostate cancer associated with poor outcome. Awareness of this pattern of metastases may be of clinical relevance in order to avoid unnecessary invasive diagnostic procedures in groups of patients with a dismal prognosis.

Big data, observational research and P-value: a recipe for false-positive findings? A study of simulated and real prospective cohorts.

BACKGROUND: An increasing number of observational studies combine large sample sizes with low participation rates, which could lead to standard inference failing to control the false-discovery rate. We investigated if the 'empirical calibration of P-value' method (EPCV), reliant on negative controls, can preserve type I error in the context of survival analysis. METHODS: We used simulated cohort studies with 50% participation rate and two different selection bias mechanisms, and a real-life application on predictors of cancer mortality using data from four population-based cohorts in Northern Italy (n = 6976 men and women aged 25-74 years at baseline and 17 years of median follow-up). RESULTS: Type I error for the standard Cox model was above the 5% nominal level in 15 out of 16 simulated settings; for n = 10 000, the chances of a null association with hazard ratio = 1.05 having a P-value < 0.05 were 42.5%. Conversely, EPCV with 10 negative controls preserved the 5% nominal level in all the simulation settings, reducing bias in the point estimate by 80-90% when its main assumption was verified. In the real case, 15 out of 21 (71%) blood markers with no association with cancer mortality according to literature had a P-value < 0.05 in age- and gender-adjusted Cox models. After calibration, only 1 (4.8%) remained statistically significant. CONCLUSIONS: In the analyses of large observational studies prone to selection bias, the use of empirical distribution to calibrate P-values can substantially reduce the number of trivial results needing further screening for relevance and external validity.

Cutaneous Adnexal Carcinoma with Apocrine Differentiation: A Challenging Diagnosis and Personalized Treatment with mTOR Inhibitor in a Very Rare Disease.

Cutaneous adnexal carcinoma with apocrine differentiation is a rare neoplasm arising from cutaneous adnexa, especially of the head and neck and trunk region. Because of its rarity, the diagnosis is challenging and often impossible to distinguish from metastatic cutaneous adenocarcinoma of the breast. The standard of care remains surgery for resectable disease. To date, univocal guidelines for metastatic disease are lacking, particularly regarding systemic therapy. We report a clinical case of a patient diagnosed with cutaneous adnexal adenocarcinoma with apocrine differentiation of the left axilla with lymph node and bone metastasis. We started with carboplatin and paclitaxel chemotherapy regimen, with good response. After progression, we performed a next-generation sequencing analysis (by the Foundation One CDx test) to identify genomic alteration in cancer-related genes. We found PIK3CA and KRAS mutations. Due to this result, the patient started a second-line treatment with a personalized therapy including an mTOR inhibitor, everolimus, and, to date, he is still under treatment. To our knowledge, this is the first case of a patient responding both to chemotherapy and to a personalized treatment with an mTOR inhibitor. It is important to support the value of genomic screening in this rare neoplasm.

A patient with medullary thyroid carcinoma and right ventricular cardiac metastasis treated by (90)Y-Dotatoc.

Medullary thyroid carcinoma (MTC) is rare derived from C cells of the thyroid gland and represents approximately 5% of all thyroid carcinomas. We report a case of a 74 years old male with MTC, diagnosed in 2002 and treated with total thyroidectomy and lymphadenectomy. A metastatic lesion was diagnosed on the right ventricle by indium-111-octreoscan, fluorine-18-fluorodeoxyglucose-positron emission tomography/computerized tomography, echocardiography, magnetic resonance imaging, high resolution computed tomography and was confirmed by histopathology. We present the results of treatment of this patient with yttrium-90-DOTA-tyr(3)-octreotide.

18F-Fluorocholine Uptake by a Head and Neck Meningeal Inflammatory Pseudotumor.

F-Fluoro-ethyl-choline (F-FCH) PET/CT is widely used to study patients affected by prostate cancer. However, F-FCH may be taken-up by other neoplastic diseases, infections, and non-infective inflammatory processes. While this behavior may be an opportunity to study different diseases, on the other hand, this condition brings with it the source of error in the evaluation of the images. Here we present the case of a meningeal inflammatory pseudotumor evidenced by F-FCH.

Diagnosis of Mixed Adenoneuroendocrine Carcinoma (MANEC) after Neoadjuvant Chemotherapy for Pancreatic and Gastric Adenocarcinoma: Two Case Reports and a Review of the Literature.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract involving both epithelial and neuroendocrine (NE) components, each of which represents at least 30% of the tumor. Because of the low frequency of this histotype, only a few cases have been described. In this report we discuss two cases treated with neoadjuvant chemotherapy: a pancreatic adenocarcinoma and a gastric adenocarcinoma. The histopathological specimens examined after surgery showed an additional NE component with a possible indication of the MANEC histotype. We hypothesize two possible explanations: tumor NE cells are more chemo-resistant than adenocarcinoma cells, and cytotoxic injury induces NE differentiation in tumor cells. The clinical significance and prognostic value of endocrine differentiation, however, remain controversial issues.

Early-Stage Supraglottic "In Situ" Squamous Cell Carcinoma of the Larynx Incidentally Detected by 18F-Fluorocholine PET/CT.

F-fluorocholine (F-FCH) PET/CT is widely used to study patients affected by prostate cancer. Despite its specificity, however, F-FCH may be taken up by other neoplasms such as multiple myeloma, lymphomas, lung, bladder, and colon cancer; brain tumors; and renal and hepatocellular carcinoma. This is due to its ability to evaluate the cell proliferation, which is typical of neoplastic cells. While this behavior may be an opportunity to image more neoplasms, on the other hand it could represent a source of error in the evaluation of the images. Here we present the case of a laryngeal squamous cell carcinoma detected by F-FCH.