A National Multicenter Study on overall survival in elderly metastatic castrate-resistant prostate cancer patients treated with Radium-223.

BACKGROUND: Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. AIMS: Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. METHODS: 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). RESULTS: 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. CONCLUSIONS: Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents.

Is whole body low dose CT still necessary in the era of 18F-FDG PET/CT for the assessment of bone disease in multiple myeloma patients?

OBJECTIVE: Whole body low dose computed tomography (WBLDCT) is the first-choice imaging modality to identify bone involvement in multiple myeloma (MM). Because the unenhanced LDCT co-registered to positron emission tomography (PET) (LDCT/PET) has similar technical characteristics to WBLDCT, we aimed to assess its reliability in the detection of bone disease, for employing fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT as unique multimodality imaging method in MM patients. SUBJECTS AND METHODS: Thirty three consecutive MM patients were prospectively enrolled and evaluated with WBLDCT to assess bone involvement. In addition, patients underwent 18F-FDG PET/CT using a disease-tailored optimized LDCT protocol. To compare both methods, skeletal anatomical regions were identified and a per-region and per-patient analysis were performed using Cohen's k test. Low dose computed tomography/PET sensitivity, specificity and accuracy were also calculated. RESULTS: The two imaging modalities resulted highly concordant considering both patient-based (k=0.841) and region-based analysis; some discrepancies were observed in dorsal spine (k=0.809) and thorax (k=0.756). Low dose computed tomography/PET sensitivity, specificity and accuracy were 89.4%, 98.3% and 93.5%, respectively. CONCLUSION: Low dose computed tomography co-registered PET has comparable performance to WBLDCT. If confirmed on a lager sample, these encouraging results suggest the possibility to use this multimodal hybrid imaging as the only method for MM evaluation, rather than both exams, providing both morphologic and metabolic information in one session with impact on patient compliance, health care spending and especially radiation exposure.

Typical and atypical PET/CT findings in non-cancerous conditions.

Nuclear Medicine multimodality imaging, such as positron emission tomography/computed tomography PET/CT, refers to metabolic tissue characteristics integrated with anatomical details. Fluorine-18-fluorodeoxyglucose (18F-FDG) is the most diffuse radiopharmaceutical and its application is spreading beyond the area of oncology. The causes of high 18F-FDG uptake that were once considered false positives have been identified and the new knowledge about them led to non-cancerous pathologies that can be studied by 18F-FDG PET/CT. This technique, due to the inflammatory cells high avidity of 18F-FDG, can be useful in studying a variety of inflammatory and infectious systemic conditions. Studies performed in patients with fever of unknown origin (FUO) indicate that 18F-FDG PET/CT offer a great advantage of detecting malignancy, inflammation and infection at the same time both in adults and children. Furthermore, the 18F-FDG PET/CT has proved useful in the study of specific organs such as the heart and brain that represent separate topics also for the development of new specific radiopharmaceuticals. In all the non-oncologic conditions 18F-FDG PET/CT imaging may offer an "all-in-one" procedure, thanks also to its panoramic whole-body acquisition, as an alternative to other diagnostic procedures, reducing the number of unnecessary investigations. The 18F-FDG PET/CT finding of the simultaneous presence of radiopharmaceutical uptake for multiple disease interconnect to different medical disciplines. It is important to describe unexpected occasional typical or atypical PET/CT findings to the growth of scientific and medical community; it can be the starting point to the enlargement of PET/CT indications for a better and wider comprehension of the human system. To recognize unexpected occasional findings is very important a well knowledge of many aspects: physiological biodistribution, diagnostic imaging instrumentations and techniques, pathological aspects of the different neoplastic diseases, patient story, such as previous therapy, and its comorbidity. An unexpected occasional finding can lead to suggest further tests or investigations in order to have a wider comprehension of patients' clinical situation and they are easily explainable when we have a physician's approach towards patient.

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol.

BACKGROUND: Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. METHODS/DESIGN: CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses' duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients' cetuximab-mediated ADCC and characterize the tumor microenvironment. DISCUSSION: The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results' interpretation as well as provide new insights in host-tumor interactions and cetuximab activity. TRIAL REGISTRATION: The CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number ( NCT03874062 ).

How often suspected pulmonary embolism is diagnosed and its main diagnostic characteristics, in an emergency nuclear medicine service? Four years experience.

OBJECTIVE: Acute pulmonary embolism (APE) is an emergency condition and its treatment must be immediate. Nevertheless, the diagnosis of APE is diffcult because its symptoms and risk factors are not specific. We present our 4 years experience on this subject. SUBJECTS AND METHODS: We retrospectively studied 2178 lung perfusion scintigraphies (LPS). Of them 1846 were performed to patients suspected for APE admitted to the emergency departments of the University Polyclinic of Bari and examined immediately by our Nuclear Medicine Department. Contingency tables and odds ratio (OR) were used to estimate the relation between symptoms, risk factors, D-dimers dosage, other imaging diagnostic tools and LPS results. RESULTS: Lung perfusion scintigraphy was positive for APE in 309/1846 (16.7%) patients which then were treated successfully. In 89.5% of these, 309 patients D-dimer dosage was previously examined and was increased in 97.7% of them, but was not predictive of APE (OR=1.04, P=1). Among all symptoms, a low diagnostic capacity was found for cough (OR=1.25, P=0.066) and for chest pain (OR=0.95, P=649). On the contrary, dyspnea was a significant symptom correlated with positive LPS (OR=1.78, P<0.001). The presence of risk factors was predictive of positive LPS and positively correlated with the number of positive 2 oglin lesions in LPS. x2loglin=6.472, P=0.011). Lung perfusion scintigraphy positive for APE were significantly associated with computed tomography pulmonary angiography and/or chest X-ray results (x =9.618, P=0.022). CONCLUSION: Lung perfusion scintigraphy could early diagnose APE in 16.7% of the cases (referred to our Nuclear Medicine Emergency Service) and exclude APE in 83.3% of these cases. Immediate treatment or release of these patients from the emergency department was thus possible. LPS has a key role in the early diagnosis but even more in exclusion of APE, optimizing the management of patients who do not require admission to intensive care. Our four-year and large-scale experience, based on clinical and resource optimization, support the need of Nuclear Medicine Units to perform LPS as emergency in on-call 24 hrs service.

Sickle cell diseases: What can nuclear medicine offer?

Sickle cell disease (SCD) is the best known haemoglobinopathy, caused by a mutation substituting valina for glutamic acid at position 6 of the beta-globin chain of adult hemoglobin A, resulting in hemoglobin S (HbS). The homozygous HbS disease (HbSS), an autosomal recessive disorder, is the most common form and the Mediterranean area, along with sub-Saharian African and India, have the highest prevalence (1%-15%). In particular, Sicily with a prevalence of 2%-5%, is among the most interested regions. However, migratory flows have led to a wider diffusion of the disease no longer confined to endemic areas. In Europe, the yearly estimate of affected births are 1,300 but more than 90% of children with SCD survive into adulthood thanks to screening programs and early available care; however, their lifespan remains shortened by two or three decades compared to general population. In Greece, the number of affected births surpassing 100,000 yearly and the total number of newborns carrying two deleterious genes, if no prevention measures are taken, is estimated to be about 120-130/year. Diagnosis of SCD is based on analysis of haemoglobin through protein electrophoresis or chromatography, that are cheap and widely available techniques, even if haemoglobin mass spectrometry and DNA analysis are techniques with high-throughput testing. Prenatal diagnosis is used in many European countries, so the number of affected newborns has significantly decreased during the last 3 years. Over the course of SCD, sickling process may cause acute and chronic abdominal pain due to vaso-occlusive crisis, bone pain often in long bones due to bone marrow infarction, chronic hemolytic anemia, splenic sequestration with rapid enlargement of the spleen, delayed sexual maturation and cholelithiasis, with important inter-indivuidual variability. Sickle hepatopathy reflects liver sickling process within hepatic sinusoids and includes gallstone disease, hepatic sequestration, hepatic sideroris, acute sickle cell hepatic crises (ASHC) and sickle cell intrahepatic cholestasis (SCIC). Clinically, it appears with fever, right upper quadrant pain, jaundice and increased serum liver function tests. These patients are repeatedly esposed to trasfused red cells that contributes to iron overload and may contribute to hepatic haemosiderosis. Increased bone turnover and resorption by osteoclasts and by marrow expansion due to activation of hematopoiesis. The hematopoietic system may expand physiologically. Computed tomography (CT) is an easily reproducible imaging method that allows the morphologic whole-body evaluation although with a high dose of radiation exposure and possible side effects from intravenous contrast media. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique without radiation chosen to image cholangiopathy and may be followed by the execution of endoscopic retrograde cholangiopancreatography (ERCP) in case of gallstone disease. Otherwise it can be helpful in identifying extramedullary hematopoiesis sites. Dual-energy X-rays absorptiometry (DEXA) is performed to evaluate deficit of bone mineral density (BMD), in which reduction of osteoblastic activity, high risk for necrosis may induce to fragility fractures. We recently had the experience of a typical case of a 56 years old Albanian woman with SCD, with jaundice after a long history of recurrent vaso-occlusive crisis. She was submitted to splenectomy and cholecystectomy 5 years before and since then she was treated with hydroxyurea. Hemocromatosis was excluded by genetic analysis. Hepatic biopsy (Pearl's stain) showed sinusoidal dilatation and diffuse iron accumulation in hepatocytes and Kupffer cells. Endo-hepatic jaundice was observed in MRCP images. It was interesting that DEXA examination was within normal range in both right proximal femur. This may probably be due to the presence of sclerotic lesions in the vertebrae, as was seen in the CT images. Technetium-99m-methylen bisphosphonate (99mTc-MDP) skeletal scintigraphy is a higly sensitive whole-body diagnostic nuclear medicine technique able to evaluate early bone metabolic changes. Multimodality SPET/CT allows to correlate scintigraphic findings with anatomical images with higher sensitivity and specificity. The higher uptake of 99mTc-MDP in SCD patients is due to the activation of hematopoetic system and relies on the osteoblastic response to bone resorption as in our patient. The 99mTc-MDP scan may be better than fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to show sclerotic lesions. Technetium-99m nanocolloids bone marrow scintigraphy (BMS) provides information about the assessment of the reticulum-endothelial system (RES), the whole-body distribution of functional red bone marrow and the presence and the extent of extramedullary hematopoiesis, especially in liver, spleen and bone marrow. Fluorine-18-FDG PET/CT completes the whole-body assessment with an integrated multimodal approach with high spatial resolution that evaluates the metabolic activity and the standardized uptake value (SUV) in SCD patients. Modern genetic diagnosis and gene treatment give promise for having fewer cases of SCD in the future.

Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study.

AIM: In this prospective multicenter real-life observational cohort study, we investigated the acceptance, adherence and safety of regorafenib, in the treatment of metastatic colorectal cancer patients. PATIENTS & METHODS: A total of 136 patients were recruited at six oncological hospital sites in southern Italy. The adherence to the treatment was measured with patient-completed medication diaries, physician interviews and pill counts. RESULTS: We found a statistically significant improvement of therapy adhesion by the acceptance questionnaire. The Eastern Cooperative Oncology Group performance status, the level of acceptance, the educational level and the concomitant usage of oral medications influenced the adherence to the treatment. CONCLUSION: Patients' level of education, concomitant other oral medications and patients' general clinical condition may influence the adherence to regorafenib.

Diabetes and Body Mass Index Are Associated with Neuropathy and Prognosis in Colon Cancer Patients Treated with Capecitabine and Oxaliplatin Adjuvant Chemotherapy.

BACKGROUND: There are few background data on the impact of clinical factors on neurotoxicity and prognosis in patients treated with adjuvant capecitabine and oxaliplatin (CAPOX) chemotherapy. METHODS: 102 stage II high-risk and stage III colorectal cancer patients were treated for 6 months with adjuvant CAPOX, then they were followed up. Associations between clinical variables, metabolic syndrome components, smoking and neurotoxicity were evaluated by the x03C7;2 test. The Kaplan-Meier product limit method was applied to graph disease-free survival (DFS). Univariate analysis was done with the log-rank test. Cox's proportional hazards regression was used to analyze the effect of several risk factors on DFS. RESULTS: Significant associations were found between diabetes (p < 0.001), BMI (p = 0.01) and the occurrence of chronic neurotoxicity. After a median follow-up of 46 months, 14 patients (13.7%) had suffered recurrence. An analysis of the prognostic factors for DFS showed that prognosis is unfavorable for patients with high lymph-nodal involvement (HR: 5.23, p = 0.0007), diabetes (HR: 4.86; p = 0.03) and a BMI ≥25 (HR: 3.69, p = 0.002). DISCUSSION: Common mediators in diabetes and obesity could be involved in peripheral neuropathy and in stimulating micro-metastases. Further studies are necessary to explain this interesting connection between diabetes, obesity and colon cancer.

Emerging Role of [18F]FLT PET/CT in Lymphoid Malignancies: A Review of Clinical Results.

Fluorine-18 fluorodeoxyglucose ([18F]FDG) is nowadays the leading positron emission tomography (PET) tracer for routine clinical work-ups in hematological malignancies; however, it is limited by false positive findings. Notably, false positives can occur in inflammatory and infective cases or in necrotic tumors that are infiltrated by macrophages and other inflammatory cells. In this context, 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been shown to be a promising imaging biomarker of hematological malignant cell proliferation. In this review, a total of 15 papers were reviewed to collect literature data regarding the clinical application of [18F]FLT PET/CT in hematological malignancies. This imaging modality seems to be a suitable tool for noninvasive assessment of tumor grading, also showing a correlation with Ki-67 immunostaining. Moreover, [18F]FLT PET/CT demonstrated high sensitivity in detecting aggressive lymphoma lesions, especially when applying a standardized uptake value (SUV) cutoff of 3. At baseline, the potential of [18F]FLT imaging as a predictive tool is demonstrated by the low tracer uptake in patients with a complete response. However, its use is limited in evaluating bone diseases due to its high physiological uptake in bone marrow. Interim [18F]FLT PET/CT (iFLT) has the potential to identify high-risk patients with greater precision than [18F]FDG PET/CT, optimizing risk-adapted therapy strategies. Moreover, [18F]FLT uptake showed a greater ability to differentiate tumor from inflammation compared to [18F]FDG, allowing the reduction of false-positive findings and making the first one a more selective tracer. Finally, FLT emerges as a superior independent predictor of PFS and OS compared to FDG and ensures a reliable early response assessment with greater accuracy and predictive value.

Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells.

The RAS/RAF/MEK/MAPK and the PTEN/PI3K/AKT/mTOR pathways are key regulators of proliferation and survival in human cancer cells. Selective inhibitors of different transducer molecules in these pathways have been developed as molecular targeted anti-cancer therapies. The in vitro and in vivo anti-tumor activity of pimasertib, a selective MEK 1/2 inhibitor, alone or in combination with a PI3K inhibitor (PI3Ki), a mTOR inhibitor (everolimus), or with multi-targeted kinase inhibitors (sorafenib and regorafenib), that block also BRAF and CRAF, were tested in a panel of eight human lung and colon cancer cell lines. Following pimasertib treatment, cancer cell lines were classified as pimasertib-sensitive (IC50 for cell growth inhibition of 0.001 µM) or pimasertib-resistant. Evaluation of basal gene expression profiles by microarrays identified several genes that were up-regulated in pimasertib-resistant cancer cells and that were involved in both RAS/RAF/MEK/MAPK and PTEN/PI3K/AKT/mTOR pathways. Therefore, a series of combination experiments with pimasertib and either PI3Ki, everolimus, sorafenib or regorafenib were conducted, demonstrating a synergistic effect in cell growth inhibition and induction of apoptosis with sustained blockade in MAPK- and AKT-dependent signaling pathways in pimasertib-resistant human colon carcinoma (HCT15) and lung adenocarcinoma (H1975) cells. Finally, in nude mice bearing established HCT15 and H1975 subcutaneous tumor xenografts, the combined treatment with pimasertib and BEZ235 (a dual PI3K/mTOR inhibitor) or with sorafenib caused significant tumor growth delays and increase in mice survival as compared to single agent treatment. These results suggest that dual blockade of MAPK and PI3K pathways could overcome intrinsic resistance to MEK inhibition.

Heterogeneous disease and intermittent treatment in metastatic colorectal cancer: A case report.

Background: Metastatic colorectal cancer is one of the most common causes of cancer death worldwide. RAS and BRAF mutational analyses are strongly recommended before beginning chemotherapy in the metastatic setting for their predictive role for the efficacy of anti-EGFR monoclonal antibodies. In most of cases, mutational status coincides between primary tumor and metastases. In RAS and BRAF wild-type patients treated with anti-EGFRs, after an induction treatment period, recent evidence supports the role of a maintenance treatment with fluoropyrimidines and anti-EGFRs. However, skin toxicity is the most described and limiting side-effect of maintenance. Moreover, it is described that the continuous administration of these monoclonal antibodies leads to an acquired resistance to anti-EGFRs, with subsequent treatment failure. Intermittent strategy with chemotherapy plus anti-EGFR may help maintain treatment efficacy, delaying resistance. Case presentation: In this case report, we describe the case of a RAS-BRAF wild-type elderly patient undergoing first-line chemotherapy with FOLFOX + panitumumab, reporting response of disease on all metastatic sites except for a node. This node, surgically removed, revealed host BRAF V600 mutant clones. After surgery, patient continued chemotherapy with a stop-and-go strategy continuing to benefit from the same drugs after 4 years since diagnosis, and continuing to achieve response when on treatment, avoiding unacceptable anti-EGFR toxicity. This patient, still alive after 6 years since the diagnosis, represents the case of a good synergy between molecular profiling of disease, surgery, and intermittent treatment.

ITA-IMMUNO-PET: The Role of [18F]FDG PET/CT for Assessing Response to Immunotherapy in Patients with Some Solid Tumors.

AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31-89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1-137) months, 113 (36.3%) patients had died. On Kaplan-Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory.

Can Baseline [18F]FDG PET/CT Predict Response to Immunotherapy After 6 Months and Overall Survival in Patients with Lung Cancer or Malignant Melanoma? A Multicenter Retrospective Study.

Aim: To assess the role of baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in predicting response to immunotherapy after 6 months and overall survival (OS) in patients with lung cancer (LC) or malignant melanoma (MM). Materials and Methods: Data from a multicenter, retrospective study conducted between March and November 2021 were analyzed. Patients >18 years old with a confirmed diagnosis of LC or MM, who underwent a baseline [18F]FDG-PET/CT within 1-2 months before starting immunotherapy and had a follow-up of at least 12 months were included. PET scans were examined visually and semiquantitatively by physicians at peripheral centers. The metabolic tumor burden (number of lesions with [18F]FDG-uptake) and other parameters were recorded. Clinical response was assessed at 3 and 6 months after starting immunotherapy, and OS was calculated as the time elapsing between the PET scan and death or latest follow-up. Results: The study concerned 177 patients with LC and 101 with MM. Baseline PET/CT was positive in primary or local recurrent lesions in 78.5% and 9.9% of cases, in local/distant lymph nodes in 71.8% and 36.6%, in distant metastases in 58.8% and 84%, respectively, in LC and in MM patients. Among patients with LC, [18F]FDG-uptake in primary/recurrent lung lesions was more often associated with no clinical response to immunotherapy after 6 months than in cases without any tracer uptake. After a mean 21 months, 46.5% of patients with LC and 37.1% with MM had died. A significant correlation emerged between the site/number of [18F]FDG foci and death among patients with LC, but not among those with MM. Conclusions: In patients with LC who are candidates for immunotherapy, baseline [18F]FDG-PET/CT can help to predict response to this therapy after 6 months, and to identify those with a poor prognosis based on their metabolic parameters. For patients with MM, there was only a weak correlation between baseline PET/CT parameters, response to therapy, and survival.

Intracranial Solitary Fibrous Tumor: A "New" Challenge for PET Radiopharmaceuticals.

Solitary fibrous tumor (SFT) of the central nervous system, previously named and classified with the term hemangiopericytoma (HPC), is rare and accounts for less than 1% of all intracranial tumors. Despite its benign nature, it has a malignant behavior due to the high rate of recurrence and distant metastasis, occurring in up to 50% of cases. Surgical resection of the tumor is the treatment of choice. Radiotherapy represents the gold standard in the case of post-surgery residual disease, relapse, and distant metastases. In this context, imaging plays a crucial role in identifying the personalized therapeutic decision for each patient. Although the referring imaging approach in SFT is morphologic, an emerging role of positron emission tomography (PET) has been reported in the literature. However, there is still a debate on which radiotracers have the best accuracy for studying these uncommon tumors because of the histological or biological heterogeneity of SFT.

[18F]Fluciclovine PET/CT Improves the Clinical Management of Early Recurrence Prostate Cancer Patients.

We investigated the [18F]Fluciclovine PET/CT reliability in the early detection of recurrent prostate cancer (PCa) and its impact on therapeutic decision making. We retrospectively analyzed 58 [18F]Fluciclovine PET/CT scans performed to identify early PCa recurrence. Detection rate (DR) and semiquantitative analysis were evaluated in relation to biochemical and clinical-histological features. Clinical follow-up data were collected and considered as gold standard to evaluate sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV). The impact of [18F]Fluciclovine PET/CT on clinical management was also assessed. Overall DR resulted as 66%, while DR was 53%, 28%, and 7% in prostate/bed, lymph nodes, and bone, respectively. DR significantly increased with higher PSA values (p = 0.009) and 0.45 ng/mL was identified as the optimal cut-off value. Moreover, SUVmax and SUVmean resulted significant parameters in interpreting malignant from benign findings. [18F]Fluciclovine PET/CT reached a sensitivity, specificity, PPV, NPV, and accuracy of 87.10%, 80.00%, 87.10%, 80.00%, and 84.31%, respectively. Therapeutic strategy was changed in 51% of patients. Our results support [18F]Fluciclovine PET/CT as a reliable tool for early restaging of PCa patients, especially for local recurrence detection, leading to a significant impact on clinical management. Semiquantitative analysis could improve specificity in interpreting malignant from benign lesions.

[18F]fluciclovine vs. [18F]fluorocholine Positron Emission Tomography/Computed Tomography: A Head-to-Head Comparison for Early Detection of Biochemical Recurrence in Prostate Cancer Patients.

Nowadays, there is still no consensus on the most accurate PET radiopharmaceutical to early detect prostate cancer (PCa) relapse. A tailored radiotracer choice based on a specific patient's profile could ensure prompt disease detection and an improvement in patients management. We aimed to compare the [18F]fluciclovine and [18F]fluorocholine PET/CT detection rate (DR) in PCa patients restaged for early biochemical recurrence (BCR), according to clinical and biochemical features. A cohort of 138 PCa patients with early BCR (mean age: 71 y, range: 50-87 y) were homogeneously randomized 1:1 to a [18F]fluciclovine or a [18F]fluorocholine PET/CT group. The respective PET/CT DR, according to per-patient and per-region analysis, and the impact of the biochemical, clinical, and histological parameters, were compared. The PSA cut-off values predictive of a positive scan were also calculated. Overall, the [18F]fluciclovine PET/CT DR was 64%, significantly higher than the [18F]fluorocholine PET/CT DR of 35% (p = 0.001). Similarly, in the per-region analysis, the [18F]fluciclovine PET/CT DR was 51% in the prostate region, significantly higher compared to 15% of [18F]fluorocholine (p < 0.0001). Furthermore, a statistically significant higher DR in per-patient and per-region (prostate/prostate bed) analysis was observed in the [18F]fluciclovine group for 0.5-1 ng/mL (p = 0.018, p = 0.049) and >1 ng/mL (p = 0.040, p < 0.0001) PSA values. A PSA of 0.45 ng/mL for [18F]fluciclovine and of 0.94 ng/mL for [18F]fluorocholine was identified as the optimal cut-off value in predicting a positive PET/CT scan. Our results demonstrated a better [18F]fluciclovine PET/CT DR compared to [18F]fluorocholine for restaging PCa patients in early BCR, particularly in the detection of locoregional recurrence. The significantly higher [18F]fluciclovine DR for low PSA values (PSA < 1 ng/mL) supports its use in this setting of patients.

Bayesian Network Analysis for Prediction of Unplanned Hospital Readmissions of Cancer Patients with Breakthrough Cancer Pain and Complex Care Needs.

BACKGROUND: Unplanned hospital readmissions (HRAs) are very common in cancer patients. These events can potentially impair the patients' health-related quality of life and increase cancer care costs. In this study, data-driven prediction models were developed for identifying patients at a higher risk for HRA. METHODS: A large dataset on cancer pain and additional data from clinical registries were used for conducting a Bayesian network analysis. A cohort of gastrointestinal cancer patients was selected. Logical and clinical relationships were a priori established to define and associate the considered variables including cancer type, body mass index (BMI), bone metastasis, serum albumin, nutritional support, breakthrough cancer pain (BTcP), and radiotherapy. RESULTS: The best model (Bayesian Information Criterion) demonstrated that, in the investigated setting, unplanned HRAs are directly related to nutritional support (p = 0.05) and radiotherapy. On the contrary, BTcP did not significantly affect HRAs. Nevertheless, the correlation between variables showed that when BMI ≥ 25 kg/m2, the spontaneous BTcP is more predictive for HRAs. CONCLUSIONS: Whilst not without limitations, a Bayesian model, combined with a careful selection of clinical variables, can represent a valid strategy for predicting unexpected HRA events in cancer patients. These findings could be useful for calibrating care interventions and implementing processes of resource allocation.

[The role of oropharyngoesophageal scintigraphy in the assessment of dysphagia in neurological patients.] / Ruolo dello studio scintigrafico del transito orofaringoesofageo nella valutazione della disfagia nei pazienti affetti da patologia neurologica.

PURPOSE: The aim of this study was to assess the role of oropharingoesophageal scintigraphy (OPES) in the management of neurological patients, investigating the clinical value of semiquantitative analysis. MATERIALS AND METHODS: We enrolled 39 neurological patients clinically evaluated and scored according to the Dysphagia Outcome Severity Scale (DOSS) scale who underwent fibrolaryngoscopic swallowing examination (FEES) and OPES using a 99mTc-nanocolloid-radioblabelled semiliquid bolus. We calculated the following semiquantitative parameters: Oral Transit Time (OTT), Pharyngeal Transit Time (PTT), Esophageal Transit Time (ETT), Retention Index (RI), and Esophageal Emptying Rate (EER10s). Differences in OPES semiquantitative parameters between patients classified according to the DOSS scale were performed using the nonparametric Mann-Whitney U test. Optimal semiquantitative parameters cut-off values that correlated with DOSS classification were investigated with ROC curves. The agreement between OPES, FEES and DOSS results was measured using Cohen's Kappa test (K). RESULTS: A significantly higher OTT (p=0.028), PTT (p=0.011) and ETT (p=0.030) and lower EER10s (p=0.016) values were identified. Moderate agreement resulted between OPES and DOSS results (k=0.429, 95%CI: 0.143-0.715, p=0.002). CONCLUSIONS: Our study revealed a significant correlation between clinical dysphagia graded using DOSS scale and semiquantitative parameters obtained by OPES evaluation. Despite reliable and reproducible OPES results, allowing an adequate study also of the esophageal phase, nowadays scintigraphic study remains an underestimated method to be considered in the diagnosis of dysphagia and related complications.

The Utility of Conventional Amino Acid PET Radiotracers in the Evaluation of Glioma Recurrence also in Comparison with MRI.

AIM: In this comprehensive review we present an update on the most relevant studies evaluating the utility of amino acid PET radiotracers for the evaluation of glioma recurrence as compared to magnetic resonance imaging (MRI). METHODS: A literature search extended until June 2020 on the PubMed/MEDLINE literature database was conducted using the terms "high-grade glioma", "glioblastoma", "brain tumors", "positron emission tomography", "PET", "amino acid PET", "[11C]methyl-l-methionine", "[18F]fluoroethyl-tyrosine", "[18F]fluoro-l-dihydroxy-phenylalanine", "MET", "FET", "DOPA", "magnetic resonance imaging", "MRI", "advanced MRI", "magnetic resonance spectroscopy", "perfusion-weighted imaging", "diffusion-weighted imaging", "MRS", "PWI", "DWI", "hybrid PET/MR", "glioma recurrence", "pseudoprogression", "PSP", "treatment-related change", and "radiation necrosis" alone and in combination. Only original articles edited in English and about humans with at least 10 patients were included. RESULTS: Forty-four articles were finally selected. Conventional amino acid PET tracers were demonstrated to be reliable diagnostic techniques in differentiating tumor recurrence thanks to their high uptake from tumor tissue and low background in normal grey matter, giving additional and early information to standard modalities. Among them, MET-PET seems to present the highest diagnostic value but its use is limited to on-site cyclotron facilities. [18F]labelled amino acids, such as FDOPA and FET, were developed to provide a more suitable PET tracer for routine clinical applications, and demonstrated similar diagnostic performance. When compared to the gold standard MRI, amino acid PET provides complementary and comparable information to standard modalities and seems to represent an essential tool in the differentiation between tumor recurrence and other entities such as pseudoprogression, radiation necrosis, and pseudoresponse. CONCLUSIONS: Despite the introduction of new advanced imaging techniques, the diagnosis of glioma recurrence remains challenging. In this scenario, the growing knowledge about imaging techniques and analysis, such as the combined PET/MRI and the application of artificial intelligence (AI) and machine learning (ML), could represent promising tools to face this difficult and debated clinical issue.

Heterogeneous Response to Immunotherapy in a Patient with Tonsillar Squamous Cell Carcinoma Assessed by 18F-FDG PET/CT.

Tonsillar carcinoma is the second most common malignancy of the head and neck region, with Squamous Cell Carcinoma (TSCC) as the most common histological type (>90%). For the advanced stage of TSCC, radiotherapy with or without platinum-based chemotherapy is the only therapeutic option. Immuno-checkpoint inhibitors (ICIs), in particular Nivolumab, considerably improves clinical management of these patients, but the response can be unpredictable. Difficulties can be encountered in evaluating response to immunotherapy, especially with morphological imaging, which can show an atypical response, such as pseudo-progression, leading to a premature discontinuation. Conversely, metabolic imaging can guide a more properly therapeutic decision. We present a case of a 71-year-old man affected by TSCC, treated with chemotherapy, radiotherapy, and Nivolumab as the last line of treatment. Pre- and post-immunotherapy 18F-FDG PET/CT showed an impressive response, avoiding early drug discontinuation and ensuring better management of this patient.