International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients' pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called "theranostic" approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors' analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC.

Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 (90Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90Y-labeled spheres are available: glass (TheraSphere®) and resin (SIR-Spheres®) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.

Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma.

INTRODUCTION: The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. METHODS: A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. CONCLUSION: Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

Molecular response assessed by (68)Ga-DOTANOC and survival after (90)Y microsphere therapy in patients with liver metastases from neuroendocrine tumours.

PURPOSE: We investigated the prognostic role of (68)Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing (90)Y radioembolization ((90)Y-RE). METHODS: A group of 15 consecutive patients with unresectable NET liver metastases underwent (68)Ga-DOTANOC PET at baseline and 6 weeks after (90)Y-RE. Molecular response was defined as a reduction of >50% in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50% and nonresponders with ΔT/S <50%) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following (90)Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). RESULTS: A decrease in T/S ratio was seen in all patients on (68)Ga-DOTANOC PET scans performed after (90)Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. CONCLUSION: Molecular response assessed with (68)Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with (90)Y-RE.

An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland.

Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.

(18)F-FDG PET/CT imaging of massive portal vein tumor thrombosis from ileal adenocarcinoma.

A 72 years old patient was referred to us with ileal adenocarcinoma after surgical desection. Fluorine-18- fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) imaging showed massive portal vein, tumor thrombosis. Clinical examination and laboratory tests did not support the diagnosis of septic thrombus. To the best of our knowledge, this is the first reported case in the literature of a massive tumor thrombus in the right portal system from ileal carcinoma, detected by (18)F-FDG PET/CT.

The Prognostic Role of [18F]FDG PET/CT in Patients with Advanced Cutaneous Squamous Cell Carcinoma Submitted to Cemiplimab Immunotherapy: A Single-Center Retrospective Study.

Background: Baseline 2-deoxy-2[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography (PET)-derived parameters and 12-week metabolic response were investigated as prognostic factors in advanced cutaneous squamous cell carcinoma (cSCC) submitted to cemiplimab immunotherapy. Materials and Methods: Clinical records of 25 cSCC patients receiving cemiplimab, submitted to [18F]FDG positron emission tomography/computed tomography (PET/CT) at baseline and after ∼12 weeks, were retrospectively reviewed. The Kaplan-Meier (KM) method was applied to analyze differences in event-free survival (EFS), and Cox regression analysis was employed to identify the prognostic factors. Results: At the 12-week PET/CT evaluation, 16 patients (64%) were classified as responders (complete or partial response) and 9 (36%) as nonresponders ("unconfirmed progressive metabolic disease") according to immune PET Response Criteria in Solid Tumors (iPERCIST). By KM analysis, baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) significantly correlated with the EFS (p < 0.05). Furthermore, the KM analysis showed that the lack of metabolic response at 12 weeks was associated with meaningfully shorter EFS (7.2 ± 1 months in nonresponders vs. 20.3 ± 2.3 months in responders). In Cox multivariate analysis, metabolic response at 12 weeks remained the only predictor of the EFS (p < 0.05). Conclusions: Baseline tumor load (i.e., MTV and TLG) and metabolic response at 12 weeks may have a prognostic impact in cSCC patients treated with cemiplimab.

The Importance of Uncertainty Analysis and Traceable Measurements in Routine Quantitative 90Y-PET Molecular Radiotherapy: A Multicenter Experience.

Molecular Radiation Therapy (MRT) is a valid therapeutic option for a wide range of malignancies, such as neuroendocrine tumors and liver cancers. In its practice, it is generally acknowledged that there is a need to evaluate the influence of different factors affecting the accuracy of dose estimates and to define the actions necessary to maintain treatment uncertainties at acceptable levels. The present study addresses the problem of uncertainty propagation in 90Y-PET quantification. We assessed the quantitative accuracy in reference conditions of three PET scanners (namely, Siemens Biograph mCT, Siemens Biograph mCT flow, and GE Discovery DST) available at three different Italian Nuclear Medicine centers. Specific aspects of uncertainty within the quantification chain have been addressed, including the uncertainty in the calibration procedure. A framework based on the Guide to the Expression of Uncertainty in Measurement (GUM) approach is proposed for modeling the uncertainty in the quantification processes, and ultimately, an estimation of the uncertainty achievable in clinical conditions is reported.

[18F]FDG PET/CT in a Case of Mycosis Fungoides Showing an Unusual Adverse Reaction to Mogamulizumab: Correlation Between Imaging and Histological Findings.

A 73-year-old female patient, affected by mycosis fungoides (MF), discontinued mogamulizumab, after initial clinical benefit, due to the onset of generalized erythema. Follow-up positron emission computed tomography (PET/CTs) carried out at 3 weeks and 6 months after therapy discontinuation showed, with respect to baseline PET/CT scan, a progressively increasing number of hypermetabolic enlarged lymph nodes suspected for a neoplastic involvement, but with histology indicative of an inflammatory reaction. After sequential therapy with corticosteroids and methotrexate, a complete remission was registered at 18F-fluorodeoxyglucose ([18F]FDG) PET/CT performed at 12 months after mogamulizumab interruption. The case we describe highlights the usefulness of serial examinations with [18F]FDG PET/CT in an MF patient presenting an unusual adverse reaction to mogamulizumab.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

Management of a Patient With Metastatic Gastrointestinal Neuroendocrine Tumor and Meningioma Submitted to Peptide Receptor Radionuclide Therapy With 177 Lu-DOTATATE.

ABSTRACT: A 76-year-old woman affected by pancreatic neuroendocrine tumor previously subjected to surgery with progressive liver disease and a concomitant mild symptomatic meningioma of the left pontocerebellar angle underwent 4 cycles of peptide receptor radionuclide therapy with 177 Lu-DOTATATE. A prophylactic therapy with corticosteroids was carried out before each treatment cycle, and the neurosurgery unit was alerted in case of cerebral edema and related neurologic symptoms. A 68 Ga-DOTATOC PET/CT scan performed after the completion of the 4 cycles' treatment documented a hepatic partial response and a substantial stability of the brain mass. No neurological complications occurred during treatment and follow-up.

Digital PET/CT with 18F-FACBC in early castration-resistant prostate cancer: our preliminary results.

BACKGROUND: We assessed the role of digital PET/CT (dPET/CT) with 18F-FACBC in patients affected by castration-resistant prostate cancer with PSA levels ≤ 3 ng/mL (early CRPC), no lesions detectable at cross-sectional imaging (CIM) and bone scan (BS). METHODS: Clinical data of patients submitted to 18F-FACBC dPET/CT were retrospectively reviewed. PET/CT results were analyzed: lesions' number, location, and, in case of positive lymph nodes, largest node's short axis (i.e. SA) were annotated. According to PET/CT's results, patients with 18F-FACBC-avid lesions were further stratified into 1) unifocal; 2) oligometastatic (≤ 5 lesions); 3) disseminated (> 6 lesions). RESULTS: Twenty-four patients were enrolled. 18F-FACBC dPET/CT was positive in 21 out of 24 patients (87.5%). Thirteen patients (54.1%) showed recurrence in pelvic region, seven of whom with pelvic nodes' involvement, while eight cases (33.3%) presented 18F-FACBC-avid metastases to extra-pelvic nodes or bone. Average SA of PET-positive nodes resulted in 8.9 ± 3 mm. Patients were categorized as unifocal in four cases (26.6%), oligometastatic in 10 subjects (66.6%) and disseminated in 1 case (0.6%). PET/CT impacted on clinical management in 14 cases (58.3%). CONCLUSIONS: 18F-FACBC dPET/CT detected M1 status in 33.3% of early CRPC patients, significantly impacting on clinical management.

Cutaneous Squamous Cell Carcinoma Subjected to Anti PD-1 Immunotherapy: Monitoring Response Through Serial PET/CT Scans with 18F-FDG.

Background: The effectiveness of 18F-fluorodeoxyglucose (18F-FDG) positron emission computed tomography (PET/CT) for monitoring response to immunotherapy (IT) with cemiplimab in patients affected by cutaneous squamocellular carcinoma (cSCC) was investigated. Materials and Methods: Thirteen cSCC patients performed PET/CT at baseline (PET-1) and 3 months after IT (PET-2). According to immune PET Response Criteria in Solid Tumors (iPERCIST), patients showing progressive disease at PET-2 were classified as having "unconfirmed progressive metabolic disease" (uPMD) and were scheduled to perform a further PET/CT (PET-3) after 4 weeks. PET/CT's results were correlated with best clinical response (BCR) categorized, within 6 months from the start of IT, as clinical benefit (CB) or no clinical benefit (NCB) according to clinical follow-up. Results: At PET-2, 9 subjects (69.2%) showed metabolic response, whereas four (30.8%) were classified as uPMD. After 4 weeks, three uPMD patients were subjected to PET-3, which confirmed progressive disease in all cases, whereas 1 patient with uPMD did not undergo PET-3 due to clinical deterioration. All subjects with metabolic response at PET-2 were classified as having CB and continued IT in 8 out of 9 cases, whereas all patients with uPMD were categorized as NCB and discontinued IT. Conclusions: PET/CT, performed in cSCC patients after 3 months of cemiplimab, resulted capable to identify responders from nonresponders.

Cerebellar Metastases from Prostate Cancer Detected by PET/CT with 18F-Choline.

A 76-year-old male, previously submitted enucleation renal-cell carcinoma (pT1) and prostatectomy for prostate cancer (Gleason score 3+5, pT3b pN0 pMx), was submitted to positron emission/computed tomography (PET/CT) with 18F-choline for restaging due to raised levels of prostate-specific antigen. PET/CT scan showed increased tracer incorporation corresponding to bone metastases in the left ischio-pubic ramus, also revealing 2 areas of increased tracer uptake in the cerebellum, subsequently confirmed by brain magnetic resonance imaging. The patient was urgently submitted to neurosurgery. Post-operative histology was positive for brain metastases from prostate cancer.

Molecular and Metabolic Imaging of Castration-Resistant Prostate Cancer: State of Art and Future Prospects.

Prostate cancer (PCa) represents to be the most common tumor in male and one of the most relevant causes of death in the Western countries. Androgen deprivation therapy (ADT) constitutes a widely used approach in advanced PCa. When PCa progresses in spite of ADT and castrate levels of testosterone, the severe clinical condition termed as metastatic castration-resistant prostate cancer (mCRPC) takes place. The only approach to mCRPC has been represented by chemotherapy with taxanes for many years. Nevertheless, recently introduced treatments such as 2nd generation antiandrogens (i.e., enzalutamide and abiraterone), cell immunotherapy with sipuleucel-T or targeted alpha therapy with 223Ra-dichloride, have dramatically changed mCRPC prognosis. These novel therapies call for an unmet need for imaging biomarkers suitable for patients' pre-treatment stratification and response assessment. In this scenario, nuclear medicine can provide several metabolic and molecular probes for investigating pathological processes at a cellular and sub-cellular level. The aim of this paper is to review the most relevant findings of the literature published to date on this topic, giving particular emphasis on the pros and cons of each tracer and also covering future prospects for defining personalized therapeutic approaches.

Imaging Findings of 18F-Choline and 18F-DOPA PET/MRI in a Case of Glioblastoma Multiforme Pseudoprogression: Correlation with Clinical Outcome.

We describe the case of 74-year-old-male, previously treated with fronto-parietal craniotomy due to primary glioblastoma multiforme (GBM), followed by concurrent radiation therapy (RT) and temozolomide (TMZ) chemotherapy. Magnetic resonance imaging (MRI) of the brain, at 1 month after completing RT + TMZ, depicted partial response. Three months later, the patient was submitted to a further brain MRI, that resulted doubtful for therapy induced changes (i.e., pseudoprogression). The patient, who had been previously treated with prostatectomy for prostate cancer (PC), underwent a positron emission tomography/computed tomography (PET/CT) scan with 18F-choline for PC biochemical recurrence. 18F-choline whole body PET/CT resulted negative for PC relapse, while segmental brain PET, co-registered with MRI, demonstrated increased tracer uptake corresponding to tumor boundaries. In order to solve differential diagnosis between pseudoprogression and GBM recurrence, brain PET/CT with 18F-L-dihydroxy-phenil-alanine (18F-DOPA) was subsequently performed: fused axial PET/MRI images showed increased 18F-DOPA incorporation in the peri-tumoral edema, but not in tumor boundaries, consistent with the suspicion of GBM pseudoprogression, as then confirmed by clinical and radiological follow-up.

Somatostatin Receptor Targeted PET-Imaging for Diagnosis, Radiotherapy Planning and Theranostics of Meningiomas: A Systematic Review of the Literature.

The aims of the present systematic review are to: (1) assess the diagnostic performance of somatostatin receptor (SSR)targeted positron emission tomography (PET) with different tracers and devices in patients affected by meningiomas; and (2) to evaluate the theranostic applications of peptide receptor radionuclide therapy (PRRT) in meningiomas. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published from 2011 up to March 2022 in the English language with ≥10 enrolled patients were selected. Following our research strategy, 17 studies were included for the assessment. Fourteen studies encompassed 534 patients, harboring 733 meningiomas, submitted to SSR-targeted PET/CT (n = 10) or PET/MRI (n = 4) for de novo diagnosis, recurrence detection, or radiation therapy (RT) planning (endpoint 1), while 3 studies included 69 patients with therapy-refractory meningiomas submitted to PRRT (endpoint 2). A relevant variation in methodology was registered among diagnostic studies, since only a minority of them reported histopathology as a reference standard. PET, especially when performed through PET/MRI, resulted particularly useful for the detection of meningiomas located in the skull base (SB) or next to the falx cerebri, significantly influencing RT planning. As far as it concerns PRRT studies, stable disease was obtained in the 66.6% of the treated patients, being grade 1-2 hematological toxicity the most common side effect. Of note, the wide range of the administered activities, the various utilized radiopharmaceuticals (90Y-DOTATOC and/or 177Lu-DOTATATE), the lack of dosimetric studies hamper a clear definition of PRRT potential on meningiomas' management.