Role of 18F-FCH PET/CT in Detecting Recurrences of Prostate Cancer After Curative Treatments.

Objectives: To evaluate the role of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) in prostate cancer (PC) patients with biochemical recurrence who were submitted to different curative treatments. Methods: Seventy-five patients with PC who underwent 18F-FCH PET/CT for biochemical recurrence were retrospectively analyzed to distinguish patients who were submitted only to prostatectomy (PR group), only to radiotherapy (RT) on prostate with curative intent (RT group), and to both (PR + RT group). Correlations between 18F-FCH PET/CT and outcome and between prostate-specific antigen (PSA) values and sites and the number of metastases were analyzed. The performance of 18F-FCH PET/CT in relation to the PSA value and of maximum standardized uptake value (SUVmax) value in relation to patient outcome were assessed by receiver operating characteristic (ROC) curves. Results: 18F-FCH PET/CT relapses mostly involved lymph nodes, bones, and prostate bed. K-cohen test showed moderate agreement with the outcome in the whole population and in the PR group, whereas in the RT group it was perfect and in PR + RT fair. A statistically significant difference in PSA values was observed in the presence of lymph node metastases and with multiple metastases. ROC curves showed PSA cut-off values of 1.96 ng/dL, 1.95, 1.81, and 2.96, respectively, in the whole population, PR, RT and PR + RT group. SUVmax cut-off values of 3.75, 3.45, and 4.7 were described in the whole population, PR group, and PR + RT group. Conclusion: The study confirms that 18F-FCH PET/CT is still valid in PC patients with suspected biochemical recurrence. Therefore, we can affirm that it still makes sense to perform it both with high PSA values and with lower values when prostate-specific membrane antigen tracers are not available.

Impact of the COVID-19 Pandemic on Radiotherapy Supply.

BACKGROUND: The impetuous entrance of the COVID-19 pandemic in Italy in March 2020, after the onset and diffusion in China, found the health system widely unfit to face the large amount of infected patients. The matter of this investigation was to evaluate how pandemic fear and guidelines for limiting the diffusion of SARS-CoV-2 virus could have impacted the regular supply of radiotherapy (RT) and the outcome of the treatments. MATERIALS AND METHODS: From March 9, 2020, to May 29, 2020, a register has been established to record patients that cancelled or postponed the RT appointment. The reasons were as follows: (1) patients whose appointments were postponed by the staff according to national guidelines; (2) patients who asked themselves to postpone the appointment; (3) patients who interrupted the treatment for causes directly or indirectly related to the pandemic; (4) patients who cancelled their care path. RESULTS: A total number of 277 patients started regular RT, and 384 respected their computed tomography (CT) simulation appointment, but 60 of them had alteration of their therapeutic pathway. Among these, 18 cancelled their appointment. 42 patients asked to postpone their procedure. Twenty-seven out of 42 adduced directly or indirectly SARS-CoV-2 infection-related reasons. CONCLUSIONS: The COVID-19 pandemic affected the regular RT delivery to oncologic patients, owing to the delay or cancellation of procedures with the likely effect to observe worsening of local disease control and reduced survival rates in the future.

Somatostatin Receptors in Merkel-Cell Carcinoma: A Therapeutic Opportunity Using Somatostatin Analog Alone or in Association With Checkpoint Inhibitors Immunotherapy. A Case Report.

Background: Merkel-cell carcinoma (MCC) is a rare, highly aggressive skin cancer typically involving elderly people. Surgery is usually the first treatment for primary tumor. In adjuvant setting, radiotherapy is effective in reducing local recurrence and in improving overall survival. Regarding advanced disease, systemic chemotherapy ended up disappointing results whereas antiPD1/antiPD-L1 immunotherapy recently gave relevant clinical benefits. Interestingly, about the half of MCC patients expresses high somatostatin receptors (SRs) to possibly represent a target for the therapeutic use of somatostatin analogs (SSAs). Nevertheless, SSAs have been little studied in MCC and cases treated with SSAs in association with checkpoint inhibitor immunotherapy have not been published yet. Case Report: We report the case of a 73-year-old man affected by metastatic MCC of right arm previously treated with surgery and adjuvant radio and chemotherapy. Three years later the patient presented loco-regional relapse involving lateral-cervical, mediastinal, and submandibular lymph nodes with high value of chromogranin A and neuron specific enolase. Due to the high expression of SRs at octreoscan and immunoistochemistry, patient started octreotide 30 mg i.m. every 28 days with a good control of disease for about 2 years. A widespread progression of disease was reported afterwards. The patient started the antiPD-L1 avelumab immunotherapy, only recently available in Italy, while still taking SSA. The patient showed an impressive regression of the disease after only four cycles of avelumab until complete remission. Conclusions: SSA could be a valid therapeutic option in patients with MCC with high SR expression. When combined with PD-1/PD-L1 immune-checkpoint inhibition, SSA is likely to enhance antiproliferative activity. Our case report provides the rationale to conduct a prospective trial and translational research to verify the efficacy and safety of combined SSA and checkpoint inhibitors for advanced MCC.

Dyspnea in Patients Receiving Radical Radiotherapy for Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND AND PURPOSE: Dyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry. MATERIAL AND METHODS: Eighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters. RESULTS: The median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment. CONCLUSIONS: Worsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits.

Lung Perfusion Imaging in Tetralogy of Fallot: A Case Report

Congenital heart diseases, such as tetralogy of fallot (TOF), are the most common human birth defects that may cause pulmonary diseases. Lung perfusion scintigraphy (LPS) has an important role in evaluating pulmonary involvement in patients with these defects, both as part of the diagnostic work-up and for follow-up to guide best therapeutic strategy. Herein, we report a 10-year-old female patient with TOF who underwent LPS two years after cardiac surgery. The scan showed hypoperfusion of the left respect to the right lung and abnormal uptake of Tc-99m-macroaggregated albumin in the kidneys and spleen, revealing the presence of a right-to-left shunt, and the necessity for further cardiac surgery. This case is a demonstrative example of the usefulness of LPS in patients with TOF, allowing an accurate evaluation of the best therapeutic strategy with the benefits of low radiation exposure, lack of side effects, reproducibility, management ease and good patient compliance.

Extralymphatic Disease Is an Independent Prognostic Factor in Hodgkin Lymphoma.

PURPOSE: To identify the characteristics and outcomes of patients with extralymphatic Hodgkin lymphoma. PATIENTS AND METHODS: We performed a retrospective single-institution study of 341 cases comprising 207 male (61%) and 134 female (39%) subjects with a median follow-up of 44 months. RESULTS: Fifty-five patients (16%) had extralymphatic disease. The sites were lung in 29 patients (44%), bone in 22 (33%), liver in 12 (18%), and kidney in 3 (5%). In 46 patients (86%) only one organ was involved, while in 7 patients (13%) extralymphatic disease was present in 2 sites and in 2 patients (3%) in 3 sites. The extralymphatic disease group had a poorer prognosis than the lymphatic disease group. Complete remission rates in the extralymphatic and lymphatic patient subsets were 65% and 82% (P = .043), respectively. CONCLUSION: Extralymphatic disease in patients with Hodgkin lymphoma is a rare occurrence (16%) associated with poor clinical outcome.

Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson's disease.

Coffee may interfere with the dopaminergic transmission, and this action would possibly enhance motor activity and exert an antidyskinetic effect in Parkinson's disease (PD). This study aimed to see whether coffee habit could be associated with change in striatal dopamine active transporter (DAT)-single photon emission computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well as smoking habit was collected at the time of imaging acquisition. The Unified Parkinson's Disease Rating Scale part III was used to evaluate disease severity. On multivariable analysis, chronic coffee consumption was not associated with any significant change in striatal uptake of the radionuclide. However, the number of years patients drunk coffee was correlated with a significant increase in age at PD onset (p < 0.001). Confirming a previous report, current cigarette smoking was associated with a reduction of radionuclide uptake in putamen and caudate (p < 0.001).

Role of WB-MR/DWIBS compared to (18)F-FDG PET/CT in the therapy response assessment of lymphoma.

INTRODUCTION: This study prospectively evaluated whole-body magnetic resonance/diffusion-weighted imaging with body signal suppression (WB-MR/DWIBS) reliability compared to (18)F-FDG PET/CT in the treatment response assessment of classic Hodgkin lymphomas (HL) and aggressive non-Hodgkin lymphomas (aNHL). MATERIALS AND METHODS: Twenty-seven consecutive patients were prospectively enrolled at the time of diagnosis. Eighteen (11 HL and seven aNHL) were considered for the analysis. They received chemo/radiotherapy as induction and completed post-treatment evaluation performing both (18)F-FDG PET/CT and WB-MR/DWIBS. The revised response criteria for malignant lymphomas were used to assess the response to treatment. We evaluated the agreement between the two methods by Cohen's K test. Post-therapy WB-MR/DWIBS sensitivity, specificity, PPV, NPV and accuracy were then calculated, considering the 12 months of follow-up period as the gold standard. RESULTS: By using an evaluation on a lesion-by-lesion basis, WB-MR/DWIBS and (18)F-FDG PET/CT showed an overall good agreement (K = 0.796, 95% IC = 0.651-0.941), especially in the evaluation of the nodal basins in aNHL (K = 0.937, 95% IC = 0.814-1). In reference to the revised response criteria for malignant lymphomas, the two methods showed a good agreement (K = 0.824, 95% IC = 0.493-1). Post-therapy sensitivity, specificity, PPV, NPV and accuracy of WB-MR/DWIBS were 43, 91, 75, 71 and 72%, respectively. CONCLUSION: WB-MR/DWIBS seems to be an appropriate method for the post-treatment assessment of patients affected by HL and aNHL. The small discrepancies between the two methods found within HL could be due to the biological and metabolic behavior of this group of diseases. Larger prospective studies are necessary to better define the role of WB-MR/DWIBS in this setting of patients.

Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [(64)Cu]CuCl2. To evaluate the potential theranostic role of [(64)Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [(64)Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

Whole body magnetic resonance with diffusion weighted sequence with body signal suppression compared to (18)F-FDG PET/CT in newly diagnosed lymphoma.

Lymphomas are a heterogeneous group of lymphoid malignancies, which can be broadly divided into non-Hodgkin Lymphomas (NHL) and Hodgkin lymphoma (HL) that display different patterns of biological behavior and response to treatment. Their incidence is still increasing and for this reason they require a lot of effort in scientific research. The management of both NHL and HL follows well-established guidelines based on the initial staging assessment. Therefore an accurate staging is the basis for the selection of an appropriate therapeutic approach in order to prevent over or under treatment as well as to minimize morbidity related to the radio-chemotherapy regimens given. (18)F-FDG-PET is currently regarded as the reference standard imaging modality in the staging of the majority of lymphoma type, for evaluation of distribution of the disease by providing both functional and anatomic information in a single whole body examination. In particular its role is established in HL and high-grade NHL, confirmed also in Follicular Lymphoma, but its impact on the other histotypes remains to be demonstrated. Among the diagnostic tools currently available for a bio-molecular imaging assessment, of great interest is the Whole Body-Magnetic Resonance with DWIBS sequence (WB-MR/DWIBS), an emerging and promising functional whole body imaging modality to evaluate oncologic and non-oncologic lesions, resulting in images that remarkably resemble (18)F-FDG PET/CT studies. In our research study we evaluated the role of WB-MR/DWIBS, compared with (18)F-FDG-PET/CT in the initial staging of lymphomas, considering its impact on the management of these patients and how it could influence the therapeutic choice. We prospectively enrolled 27 consecutive patients with newly diagnosed lymphoma (13 HL, 14 NHL) histologically proven, who underwent (18)F-FDG-PET/CT and WB-MR/DWIBS (coronal T1-weighted, coronal STIR, axial sequences DWIBS) within 10 days from the diagnosis and before start the treatment. We evaluated the overall agreement between the two methods, the general agreement in evaluating both nodal and extra-nodal involvement and a specific site agreement according to lymph nodal basins or extra-nodal sites involvement. The agreement between the two diagnostic tools in relation to histological types (HL/NHL) and in relation to indolent and aggressive forms, within NHL histotypes, as well as in relation to the Ann Arbor stage was also evaluated. We also analyzed the role of WB-MRI/DWIBS and (18)F-FDG-PET/CT in bone marrow involvement detection by calculating their sensitivity and specificity, with bone marrow biopsy as the reference standard, and comparing them with McNemar test. A total of 85 lesions, nodal (74) and extra-nodal (11), were detected by (18)F-FDG-PET/CT. WB-MRI/DWIBS showed a total of 91 sites involved, (81) nodal and (13) extra-nodal lesions. The overall agreement between the two imaging modalities was very good (k=0.815; IC:0.739-0.890); however considering histotypes, the agreement comes down to good in evaluating NHL for both nodal and extra-nodal involvement (k=0.763, IC: 0.627-0.898; k=0.629, IC:-0.021-1.278). Considering indolent or aggressive forms the agreement between WB-MR/DWIBS and (18)F-FDG PET/CT findings was very good in aggressive forms while it appeared to be lower in indolent forms. Sensitivity and specificity of WB-MRI/DWIBS and (18)F-FDG PET/CT in bone marrow involvement detection were respectively: 100%and 100% vs. 50% and 96%. The switch from (18)F-FDG PET/CT to WB-MR/DWIBS in the AA Staging System resulted in an over-staging in 1/27 patient. The two methods were concordant in the staging in 26/27 patients (96%). In conclusion, our initial results show a good overall agreement between the two diagnostic tools. (18)F-FDG-PET/CT remains the gold standard for lymphoma staging, however WB-MRI/DWIBS can be useful in histotypes not (18)F-FDG-avid or in the evaluation of "critical" organs for (18)F-FDG PET/CT. The integrated information provided by metabolic and tissutal functional imaging can be complementary to assist hematologic decision of tailored patient's treatment.

Useful diagnostic biometabolic data obtained by PET/CT and MR fusion imaging using open source software.

In the last decade numerous attempts were considered to co-register and integrate different imaging data. Like PET/CT the integration of PET to MR showed great interest. PET/MR scanners are recently tested on different distrectual or systemic pathologies. Unfortunately PET/MR scanners are expensive and diagnostic protocols are still under studies and investigations. Nuclear Medicine imaging highlights functional and biometabolic information but has poor anatomic details. The aim of this study is to integrate MR and PET data to produce distrectual or whole body fused images acquired from different scanners even in different days. We propose an offline method to fuse PET with MR data using an open-source software that has to be inexpensive, reproducible and capable to exchange data over the network. We also evaluate global quality, alignment quality, and diagnostic confidence of fused PET-MR images. We selected PET/CT studies performed in our Nuclear Medicine unit, MR studies provided by patients on DICOM CD media or network received. We used Osirix 5.7 open source version. We aligned CT slices with the first MR slice, pointed and marked for co-registration using MR-T1 sequence and CT as reference and fused with PET to produce a PET-MR image. A total of 100 PET/CT studies were fused with the following MR studies: 20 head, 15 thorax, 24 abdomen, 31 pelvis, 10 whole body. An interval of no more than 15 days between PET and MR was the inclusion criteria. PET/CT, MR and fused studies were evaluated by two experienced radiologist and two experienced nuclear medicine physicians. Each one filled a five point based evaluation scoring scheme based on image quality, image artifacts, segmentation errors, fusion misalignment and diagnostic confidence. Our fusion method showed best results for head, thorax and pelvic districts in terms of global quality, alignment quality and diagnostic confidence,while for the abdomen and pelvis alignement quality and global quality resulted poor due to internal organs filling variation and time shifting beetwen examinations. PET/CT images with time of flight reconstruction and real attenuation correction were combined with anatomical detailed MRI images. We used Osirix, an image processing Open Source Software dedicated to DICOM images. No additional costs, to buy and upgrade proprietary software are required for combining data. No high technology or very expensive PET/MR scanner, that requires dedicated shielded room spaces and personnel to be employed or to be trained, are needed. Our method allows to share patient PET/MR fused data with different medical staff using dedicated networks. The proposed method may be applied to every MR sequence (MR-DWI and MR-STIR, magnet enhanced sequences) to characterize soft tissue alterations and improve discrimination diseases. It can be applied not only to PET with MR but virtually to every DICOM study.

Radiometabolic treatment of bone-metastasizing cancer: from 186rhenium to 223radium.

Skeletal metastases occur in many patients with different kinds of malignant tumors, especially in advance stage of breast cancer (in 47%-85% of patients), prostate cancer (33-85%), and lung cancer (32%-60%). The management of painful skeletal metastases is complicated and should be carried out by a multidisciplinary approach including conventional analgesics, antitumor therapy (chemo- and hormone therapy), osteoclast-inhibitory agents (bisphosphonates), corticosteroids, external-beam radiotherapy, surgery, and nuclear medicine therapy. The nuclear medicine therapy for palliation of pain from bone metastases is a systemic radionuclide therapy based on the use of radiopharmaceuticals. In several studies the efficacy of bone-seeking radiopharmaceuticals have been demonstrated in terms of pain reduction from diffuse skeletal metastases. In this review, we will summarize the current literature on bone-seeking radiopharmaceuticals for the treatment of painful bone metastases (Phosphorus-32, Strontium-89, Rhenium-186, Rhenium-188, Samarium-153, and Radium-223) and the combination therapy with biphosphonates and chemotherapy.

(18)F-FDG positron emission tomography/computed tomography and (99m)Tc-MDP skeletal scintigraphy in a case of Erdheim-Chester disease.

Erdheim-Chester disease (ECD), first described by Jakob Erdheim and William Chester in 1930, is a rare form of non-Langerhan's cell histiocytosis with unknown aetiology, is charaterized by systemic xanthogranulomatous infiltrative disease. To date, about 350 cases of ECD have been described in the medical literature. The typical ECD diagnostic triad is bone pain, diabetes insipidus and bilateral exophthalmos. A 24 years old man came at our attention for polydipsia with nocturnal and diurnal polyuria, anorexia, febrile episodes (38(o)C), and arthromyalgia especially in the knees. Physical examination showed bilateral periorbital xanthelasma. Blood exams showed increase of plasma osmolarity, haematocrit, sodium and urea and decrease of potassium. Urine exams showed just decreased urine specific gravity, (1.001;normal range: 1.010-1.030) suggestive for central diabetes insipidus (CDI). Brain magnetic resonance with gadolinium enhancement showed the presence of multiple hyperintense lesions expecially in neurohypophysis (swollen and with markedly contrast enhancement). All these data raised the suspision of neurosarcoidosis, so a chest and abdomen contrast enhancement computed tomography was performed, which didn't show abnormalities, making less possible the diagnosis of sarcoidosis. Two weeks later, whole-body (from head to pelvis) plus lower limbs 18-fluorine-labelled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed. Uptake of (18)F-FDG was observed in the upper portion of the midbrain area (SUV(max) 7.1) and the pituitary gland (SUV(max) 7.3), and diffuse bone marrow uptake of (18)F-FDG in the proximal epiphysis and metaphysis of both humeri and thigh bones (SUV(max) 6.5), shoulder blades, pelvis bones and the L2 vertebral body (SUV(max) 3.9). This (18)F-FDG PET/CT confirmed the presence of brain lesion seen in MRI , the absence of visceral lesions, but also showed the presence of an atypical bone uptake of (18)F-FDG, leading to the suspision of ECD. A technetium-99m-methyl-diphosphonate skeletal scintigraphy ((99m)Tc-MDP) scan showed diffuse uptake of the radiopharmaceutical, in the diaphysis of long bones and in the left portion of the body and the spinous process of L2. Considering the difficulties of an osteomedullary or brain biopsy, biopsy was performed on a right anterior thoracic cutaneous xanthelasma. Histology showed lipid-laden histiocytes (CD1a-, CD68+, S-100 protein -) with small nuclei, Touton giant, lymphocytic infiltrates, eosinophils and fibrosis, ECD gold standard patterns as reported in literature. The patient was discharged with the diagnosis of ECD with central nervous system (CNS) manifestations, and treatment started. The diagnosis can be lead by the most charateristic bone findings of symmetrical osteosclerosis of the long bones, especially the lower limbs (tibia and fibula), involving metaphyses and diaphyses but sparing epiphyses. The typical pattern of osteoscerosis of the long bones reflects increased osteoblastic activity. About half of all ECD patients may experience extraskeletal manifestations, including CNS. Visceral involvement in ECD is not specific, and this enforces the diagnostic value of skeletal imaging findings. Furthermore xanthomas can be found at any location on the skin, especially the eyelids as in our patient. For visceral involvement, CT is most useful, while MRI is more sensitive for CNS lesions. Involvement of CNS may be frequently revealed clinically by diabetes insipidus. Few case reports have shown that (18)F-FDG PET/CT scanning could be useful in assessing the extension of ECD lesions. Both radiography and (99m)Tc-MDP skeletal scintigraphy may reveal osteosclerosis of the long bones, which is a typical finding in ECD. The typical bone pattern of (18)F-FDG PET/CT scan is specific for ECD and (99m)Tc-MDP skeletal scintigraphy may be performed in patients in whom initial (18)F-FDG PET/CT scans present the possibility of ECD diagnosis. Others reported that (18)F-FDG PET/CT scans had good sensitivity (66.7%) and specificity (92.3%) as compared with MRI of the CNS involvement or lesions. In conclusion, the (18)F-FDG PET/CT scan and the (99m)Tc-MDP scan depicted many of the most relevant lesions of ECD for the initial assessment of ECD in our patient.