The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study).

PURPOSE: To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). PATIENTS AND METHODS: Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. RESULTS: Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). CONCLUSIONS: The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.

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.

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.

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.

18F-FDG PET/CT in therapy response and in predicting responders or non-responders in malignant pleural mesothelioma patients, by using semi-quantitative mRECIST and EORTC criteria.

OBJECTIVE: To evaluate the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in therapy response assessment according modified response evaluating criteria of solid tumors (mRECIST) and the predictive role of volume-based semi-quantitative parameters in patients with malignant pleural mesothelioma (MPM). Furthermore modified RECIST criteria for MPM mRECIST and the European Organization for Research and Treatment of Cancer (EORTC) criteria were compared and the predictive role of 18F-FDG PET/CT in the post-therapy outcome. SUBJECTS AND METHODS: Thirty five selected patients with MPM underwent 18F-FDG PET/CT scan at baseline (1) and after therapy (2). Semi-quantitative 18F-FDG PET/CT parameters were collected for each scan and also differences (Δ) ΔSUVmax, ΔSUVav, ΔMTV, ΔTLG, response index (RI)max% and RIav% were evaluated. Radiologic response to therapy was assessed by using the mRECIST and EORTC. RESULTS: The correlation between response to therapy assessed by EORTC and mRECIST criteria was moderate (K=0.418; 95%CI:0099-0736). According to mRECIST, statistical differences between responders and non-responders were significant in the analysis of semi-quantitative parameters. According mRECIST criteria, all parameters defined a good area under the curve (AUC) but the better AUC resulted for ΔMTV (cut-off≤11.3, sensitivity=91.3%, specificity=91.7%) and ΔTLG (cut-off≤59.1, sensitivity=82.6%, specificity=100%). Kaplan-Meier curves between responders and non-responders did not show statistically significant differences. CONCLUSION: The semi-quantitative analysis of 18F-FDG PET/CT has an important role in MPM therapy response assessment and has a predictive role in distinguishing responders and non-responders.

Tyrosine-Kinase Inhibitors Therapies with Mainly Anti-Angiogenic Activity in Advanced Renal Cell Carcinoma: Value of PET/CT in Response Evaluation.

Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib. As anti-angiogenic agents, TKIs interfere the loop, being able to inhibit tumor proliferation. TKIs are now available treatments for advanced RCC, which demonstrated to improve overall survival and/or progression free survival. Their effects can be detectable early on Positron Emission Tomography/Computed Tomography (PET/CT) by change in 18F-fluoro-2-deoxy-2-d-glucose (18F-FDG) uptake, the main radiotracer used to date, as a strong indicator of biological response. 18F-FDG PET/CT demonstrated an ability to predict and monitor disease progression, allowing an early and reliable identification of responders, and could be used for image-guided optimization and "personalization" of anti-angiogenic regimens. New radiotracers for biometabolic imaging are currently under investigation, which exploit the other pathways involved in the cancer process, including cellular proliferation, aerobic metabolism, cell membrane synthesis, hypoxia and amino acid transport, as well as the angiogenic process, but they require further studies.

Increased and normalized uptake of 18F-FDG in a case of bone periprosthetic infection treated by antibiotics.

We report the case of a 69 years old man with left hip prosthesis, who presented clinical, biochemical and imaging signs of periprosthetic infection treated with linezolid, an antibacterial agent of the oxazolidinone class. Two weeks after this treatment, a fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan showed increased uptake in the skeleton and also increased uptake in several focal areas in the spine and near the prosthesis and the surgical wound on the left gluteus medius. Bone marrow biopsy was negative; meanwhile the antibiotic therapy, after four weeks of treatment was stopped due to red blood cells and platelets toxicity. Six weeks later, the patient developed high fever again and in order to revaluate the periprosthetic inflammation, he was resubmitted to 18F-FDG PET/CT which showed normal 18F-FDG uptake in the whole skeleton, including the prosthesis and the subcutaneous wound. Some focal areas of increased uptake in the lumbar spine were still detected. In the next 4 weeks the patient was under a "watch and wait" follow-up in a steady state. IN CONCLUSION: In the case we report, since we found no otnt focal areas in the lumbar spine where due to age-related bone deformities including some Schmorl's nodes. The inflammation in the bone prosthesis and the subcutaneous wound responded almost totally to the antibiotic treatment we applied.

Role of (18)F-FDG PET/CT in the evaluation of response to antibiotic therapy in patients affected by infectious spondylodiscitis.

OBJECTIVE: Spondylodiscitis is characterized by infection involving the intervertebral disc and adjacent vertebrae. It can occur anywhere in the vertebral column but more commonly involves lumbar spine. Our aim was to evaluate the usefulness of (18)F-FDG PET/CT to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis and to compare the role of (18)F-FDG PET/CT and MRI in post-treatment evaluation. MATERIALS AND METHODS: 15 patients (12M, 3F), with mean age 65±13 years old, with typical clinical symptoms of Infectious Spondylodiscitis (pain, fever and increase of inflammatory indexes) and confirmed by blood culture or vertebral biopsy underwent within three day-interval a (18)F-FDG PET/CT and Magnetic Resonance (MR) at "baseline" and after antibiotic therapy. Semiquantitative parameters at (18)F-FDG PET/CT "baseline" SUVmax1, MTV1 and TLG1 and after therapy SUVmax2, MTV2 and TLG2 of involved vertebrae were calculated. Follow-up period of at least three months was available for all patients. T-student test for paired groups was performed to compare baseline and after therapy (18)F-FDG PET/CT semiquantitative parameters. RESULTS: According to (18)F-FDG PET/CT parameters all patients showed a response to antibiotic therapy. All patients were positive at "baseline" MRI of the spine, while at follow-up, 7/15 patients showed MR signs of infection and were considered "positive" and 8/15 showed resolution of infectious condition and, therefore they were considered "negative". A statistical significant difference between (18)F-FDG PET/CT "baseline" and after antibiotic therapy was found for all semiquantitative parameters: SUVmax (t=5.8, P=0.01); MTV (t=5.17, P=0.001); TLG (t=5,26, P=0,001). The comparison between the "baseline" and "after treatment" (18)F-FDG semiquantitative parameters showed a significant reduction of all parameters. This reduction was relevant also in patients with positive post-treatment MRI. This can be probably related to the tissue remodeling in the very immediate phase post-treatment, resulted positive at MRI and negative at (18)F-FDG PET/CT. Clinical follow-up of at least three months confirmed these results. CONCLUSIONS: (18)F-FDG PET/CT is useful to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis. (18)F-FDG PET/CT semiquantitative parameters provide critical diagnostic information of the infectious process. (18)F-FDG PET/CT should be considered as first-line exam in the early post-treatment evaluation of spondylodiscitis while MR should be preferred for delayed assessment.

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study.

BACKGROUND/AIM: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. METHODS: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. RESULTS: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12-14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052-1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040-1.068, p < 0.001). CONCLUSIONS: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

[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.

Ultrasound evaluation of ductal carcinoma in situ of the breast.

PURPOSE: To assess the role of ultrasound (US) in detecting and characterizing ductal carcinoma in situ (DCIS) of the breast and to investigate the correlation between ultrasonographic and biological features of DCIS. METHODS: In total, 171 patients (mean age 44; range 39-62) with 178 lesions were retrospectively evaluated by two independent radiologists searching for US mass or non-mass lesions. Immunohistochemistry analysis was performed to determine estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. The US detection rate and pattern distribution among the lesion types were evaluated. The χ2 test was used to evaluate the correlation between the US findings and the biological factors. Statistical significance was indicated by p values < 0.05. Inter-observer agreement was calculated by Kohen's k test. RESULTS: US detected 35% (63/178) of all lesions. Fifty-two (83%) lesions were classified as mass lesions, and 11 (17%) as non-mass lesions (p < 0.0001). Among the mass lesions, the most common shape was irregular (79%; p < 0.0001), with 45 (87%) lesions having indistinct margins. Hypoechogenicity was the most common echo pattern (49 cases, 94%; p < 0.0001). Microcalcifications were found in 23 cases (37%; p = 0.004) and were associated with mass lesions in 15 cases (65%) and with non-mass lesions in 8 cases (35%) (p = 0.21). An almost perfect inter-observer agreement (k = 0.87) was obtained between the two radiologists. A significant ER expression was found in mass lesions (83%; p < 0.0001), with no significant PR (p = 0.89) or HER2 expression (p = 0.81). Among the lesions with microcalcifications, only 7 out of 23 cases (30%) were positive for HER2 (p = 0.09). CONCLUSION: DCIS represents a heterogeneous pathological process with variable US appearance (mass-like, non-mass-like, or occult). The most common US finding is represented by mass-type, hypoechogenic lesions with indistinct margins. A significant ER expression exists among mass-type lesions, while microcalcifications seem not to be associated with HER2 expression.

Radium-223 in mCPRC patients: a large real-life Italian multicenter study.

BACKGROUND: Radium-223 is a targeted alpha-particles therapy approved for the treatment of mCRPC patients with symptomatic bone metastases. To our knowledge we account for the largest cohort of mCRPC patients subjected to Radium-223 treatment in our country. We aim to describe in a real-life setting the largest cohort of mCRPC patients treated with Radium-223 ever taken into consideration. METHODS: Four hundred and thirty consecutive mCRPC patients were enrolled. Clinical data have been collected at baseline and at the end of the Radium-223 treatment. Furthermore, the overall survival(OS) of our population has been provided. RESULTS: One hundred fifty-seven patients (36.5%) were still alive at the time of data analysis. A mean number of 4.95±1.6 cycles of Radium-223 was reached by our cohort. 265 patients (61.6%) completed the whole six cycles regimen. The mean follow-up period from the first cycle of Radium-223 to the date of the analysis was 12.7 months. The analysis of patients Annual Incidence Rate (AIR) in relation to the number of Radium-223 cycles received depicting a clear advantage for those patients who completed the whole six administrations planned, with an AIR (AIR=0.32) of much lesser value compared to those that have performed five cycles (AIR =0.98). 165 patients (38.4%) dropped out of treatment for death or disease progression. CONCLUSIONS: This study offers a cross-section of the clinical performance of Radium-223 treatment in a real-world context, confirming on a large scale the effectiveness of Radium-223 in improving the OS and quality of life, along with the preservation of an excellent safety profile.

Prognostic Value of the BIO-Ra Score in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 after the European Medicines Agency Restricted Use: Secondary Investigations of the Multicentric BIO-Ra Study.

The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value.

Synergism Between Immunotherapy and Radiotherapy in Esophageal Cancer: An Overview of Current Knowledge and Future Perspectives.

Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. Immunotherapy is a promising therapeutic approach that is currently highly investigated in association to standard therapies, including RT, with the aim to improve patients' outcomes. Materials and Methods: A PubMed search was performed with the following keywords in all fields: "esophageal cancer" and "radiotherapy" and "radiation" and "immunotherapy" and "PD-1" and "PD L1." For an overview of ongoing trials, an additional search on ClinicalTrials.gov website was performed using the keywords "esophageal cancer" and "immunotherapy" and "PD-L1" and "CTLA-4" and "radiation" and "radiotherapy." Emerging data from preclinical and clinical studies are suggesting a synergistic effect between immunotherapy and RT. With the aim to update the knowledge of this synergistic immune-mediated antitumor activity and discuss current challenges, the authors summarize published data concerning the basic mechanisms and the effectiveness and tolerance of the combination between immunotherapy and RT for patients with EC, followed by an overview of ongoing clinical trial. Conclusions: Published results encourage the use of personalized therapeutic approaches for EC patients in the future; results from ongoing studies will help to identify the optimal strategies for patient selection and treatment response evaluation.

Diagnostic Value of the Early Heart-to-Mediastinum Count Ratio in Cardiac 123I-mIBG Imaging for Parkinson's Disease.

BACKGROUND: Early diagnosis of Parkinson's disease (PD) is of primary importance. The delayed (3-4 h after injection) Iodine-123-Metaiodobenzylguanidine (123I-mIBG) scintigraphy has been proven to be effective in early differential diagnosis for Lewy body disease. But early imaging (15-30 min after injection) has only been marginally studied for its possible diagnostic role. In this prospective study, a threshold for the early Heart-to-Mediastinum (H/M) count ratio has been investigated, obtaining a diagnostic accuracy analogous to conventional, delayed imaging. METHODS: One hundred and eight patients with suspected Parkinson's disease (PD) were acquired after 15 and 240 minutes from the injection of 150-185 MBq of 123I-mIBG. The early and late H/M (He/Me and Hl/Ml) were evaluated by drawing Region-of-Interests on the heart and the upper half of the mediastinum. Optimal threshold (Youden index) and overall predictive performance were determined by receiver operating characteristic curve, classifying tentatively patients having an Hl/Ml lower than 1.6 as suffering from PD. RESULTS: He/Me was not significantly different from Hl/Ml (p-value=0.835). The Area-under-curve was 0.935 (95%CI: 0.845-1.000). The He/Me optimal threshold was 1.66, with sensitivity, specificity, and diagnostic accuracy of 95.5%, 85.7 and 90.7% respectively. CONCLUSION: The He/Me Ratio is almost as accurate as the widely used delayed 123I-mIBG imaging, reducing the burden of delayed imaging but preserving the diagnostic accuracy of the method. Moreover the differential diagnosis in Parkinson's disease can be made in just 25 minutes against the 4 hours currently needed, lowering costs of the healthcare system and improving patients compliance.

Early Predictive Response to Multi-Tyrosine Kinase Inhibitors in Advanced Refractory Radioactive-Iodine Differentiated Thyroid Cancer: A New Challenge for [18F]FDG PET/CT.

Differentiated thyroid cancer (DTC) represents the most common thyroid cancer histotype. Generally, it exhibits a good prognosis after conventional treatments; nevertheless, about 20% of patients can develop a local recurrence and/or distant metastasis. In one-third of advanced DTC, the metastatic lesions lose the ability to take up iodine and become radioactive iodine-refractory (RAI-R) DTC. In this set of patients, the possibility to perform localized treatments should always be taken into consideration before the initiation of systemic therapy. In the last decade, some multi-tyrosine kinase inhibitor (MKI) drugs were approved for advanced DTC, impacting on patient's survival rate, but at the same time, these therapies have been associated with several adverse events. In this clinical context, the role of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in the early treatment response to these innovative therapies was investigated, in order to assess the potentiality of this diagnostic tool in the early recognition of non-responders, avoiding unnecessary therapy. Herein, we aimed to present a critical overview about the reliability of [18F]FDG PET/CT in the early predictive response to MKIs in advanced differentiated thyroid cancer.

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

AIM: The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. METHODS: In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [18F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [18F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. RESULTS: Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. CONCLUSIONS: Currently, [18F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40336-021-00445-w.

18F-Fluorocholine PET/CT, Tc-99m-MIBI and TC-99m-MDP SPECT/CT in Tertiary Hyperparathyroidism with Renal Osteodystrophy.

Tertiary hyperparathyroidism (HPT) is a metabolic disorder characterized by the semi-autonomous hypersecretion of parathyroid hormone (PTH), leading to hypercalcemia. It can be the end result of persistent secondary hyperparathyroidism and is most commonly observed in patients with long-standing chronic kidney disease (CKD) and often after renal transplantation. Untreated HPT can lead to progressive bone disease, fibrocystic osteitis, and soft-tissue calcifications, along with other severe complications. In the 2009 Kidney Disease Improving Global Outcomes (KDIGO) guidelines, CKD-Mineral and Bone Disorder (CKD-MBD) is used to describe the broader clinical syndrome encompassing mineral, bone, and calcific cardiovascular abnormalities that develop as a complication of CKD. We report a 62-year-old female with a severe HPT evolved from advanced chronic kidney disease (stage 5D, KDIGO). Patient was evaluated with multimodality nuclear medicine functional imaging to assess hyperfunctioning parathyroid glands and bone lesions. Tc-99m-methoxyisobutylisonitrile (MIBI) dual-phase scintigraphy, Tc-99m-methylenediphosphonate (MDP) bone scan and 18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) were performed before surgery.