Clinical value of negative 68Ga-PSMA PET/CT in the management of biochemical recurrent prostate cancer patients.

PURPOSE: To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR). METHODS: One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables. RESULTS: In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1-20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9-70.4) whereas the 24-month CRFS was 34.8% (range, 24-45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35-5.57] for subset 3 versus subset 1; HR of 2.08 [1.11-3.88] for subset 2 versus subset 1). CONCLUSION: 68Ga-PSMA PET/CT negativity in early BCR patients (PSA < 0.5 ng/mL) with low-grade primary prostate cancer (ISUP1 and 2) may support the exploration of a clinical surveillance approach in future prospective studies.

Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.

PET/CT and radiotherapy in gynecological cancer.

Molecular imaging, in particular, positron emission tomography (PET), has brought an additional dimension to management of patients with cancer and to radiation therapy planning. The combination of PET and computed tomography (CT) in a single system (PET/CT) to form an inherently fused anatomical and functional dataset has provided an imaging modality which could be used as the prime tool in the delineation of tumour volumes and the preparation of patient treatment plans, especially when integrated with virtual simulation. PET imaging (typically using ¹8F-FDG) can provide data on metabolically active tumour volumes. These functional data have the potential to modify treatment volumes and to guide treatment delivery to cells with particular metabolic characteristics. Depending on its sensitivity and specificity, ¹8F-FDG PET has been shown to influence the selection of target volumes also in gynecological cancer. The potential of such data from PET was recognized at an early stage and was integrated into the radiotherapy treatment for some gynecological malignancies. In particular ¹8F-FDG PET has been demonstrated to be useful in patients with cervical cancer candidate to radiotherapy; preliminary data suggest a potential use also in patients with endometrial cancer, uterine sarcoma and ovarian cancer. This paper reviews the state of the art of the integration of PET and PET/CT applications in radiotherapy, and the use of ¹8F-FDG PET in disease staging, patient selection, treatment planning and treatment evaluation in gynaecological malignancies, in particular in patients with cervical cancer, endometrial cancer, uterine sarcoma and ovarian cancer.

Non-FDG PET in the practice of oncology.

Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV) inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma) demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the therapeutic compound; 18F-FLT is a specific marker of cell proliferation and the most important field of application of FLT is lung cancer. Other tracers are used in PET utilized as markers of hypoxia inside big neoplastic masses include 18F-MISO, 64Cu-ATSM, 18F-EF5, which highlight the presence of hypoxic areas are useful for patients that must be treated with radiotherapy.

[Primary peritonitis in previously healthy children]. / Peritonitis primaria en niños sanos.

INTRODUCTION: Primary peritonitis occurs rarely in childhood, affecting mainly children with nephrosis or liver disease and only rarely occurring in previously healthy children. The aim of this case report is to describe the clinical features and natural course of primary peritonitis in six previously healthy children and to review the literature on the topic. MATERIAL AND METHOD: The clinical features and course of primary peritonitis in six previously healthy children are described. The diagnosis was made at laparotomy, which showed no intraabdominal findings, such as intestinal perforation. RESULTS: Presentation was acute and all the patients presented within 24 h of onset of symptoms. The most common presenting features were fever (100 %) and abdominal pain (100 %). Leucocytosis (> 15,000/mm3) was observed in four patients (66 %). Microorganisms were isolated from peritoneal fluid in four patients (Escherichia coli in two, Streptococcus pneumoniae in one and Gram-negative bacteria in one). Recovery was rapid and no postoperative complications were observed. CONCLUSION: Primary peritonitis in patients without underlying causes is clinically indistinguishable from acute appendicitis and diagnosis is usually made at surgery. The hallmarks of therapy are antibiotics and prompt exploratory laparotomy with appendectomy and the prognosis is good.

[Use of the pancreolauryl test in the diagnosis of exocrine pancreatic insufficiency. Preliminary results]. / Utilizzazione del pancreolauryl test nella diagnosi di insufficienza pancreatica esocrina. Risultati preliminari.

The Pancreolauryl Test (PLT), a tubeless test used to study exocrine pancreatic function, was performed in 18 patients (8 healthy controls and 10 patients with suspected chronic pancreatitis) to evaluate its sensitivity and clinical applicability. The sensitivity rate of PLT was 75%, the specificity 85.7%, the predictive value of a positive test 60% and of a negative test 92.3%. The PLT proved to be a non invasive, easy to perform test; besides it was acceptable to the patients, without collateral effects.