Federica Matteucci

Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours

PurposeThe prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after 177Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs.MethodsWe retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7xa0GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index ≤2xa0%, 19 patients), and those with grade 2 tumour (Ki-67 index >3xa0% to <20xa0%, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET−).ResultsFDG PET was positive in 57xa0% of patients with grade 1 NET and in 66xa0% of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95xa0% and 79xa0%, respectively (Pu2009=u20090.232). In PET− and PET+ patients, the DC rates were 100xa0% and 76xa0% (Pu2009=u20090.020) with a PFS of 32 and 20xa0months, respectively (Pu2009=u20090.033). Of the PET+ patients with grade 1 NET, 91xa0% showed disease control, whereas about one in three PET+ patients with grade 2 NET (32xa0%) progressed after Lu-PRRT (DC rate 68xa0%).ConclusionThese results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET− patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32xa0% of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT.

18F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

PurposeWe investigated the role of 18F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.MethodsThe study group comprised 36 patients with a median age of 72xa0years (range 48–90xa0years) who were treated with enzalutamide 160xa0mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3–6xa0weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).ResultsAt a median follow-up of 24.2xa0months (range 1.8–27.3xa0months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50xa0% was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3xa0months in advance of CT in 12 of 18 patients (66xa0%) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2xa0months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (pu2009=u20090.0005 and pu2009=u20090.029, respectively), whereas decrease in PSA level alone was predictive of OS (pu2009=u20090.007).ConclusionThis is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study.

PurposeWe evaluated the activity and safety profile of 177Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs).MethodsForty-three patients with radiological tumor progression at baseline and a positive Octreoscan® completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8xa0GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve.ResultsTwenty-five (58xa0%) patients were treated with a “standard” Lu-PRRT full dosage (FD) of 25.7xa0GBq (range 22.2-27.8), while the remaining 18 patients (42xa0%) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4xa0GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7xa0%) cases and stable disease (SD) in 33 (77xa0%), with a disease control rate (DCR) of 84xa0%. Median response duration was 25xa0months (range 7-50). Median progression-free survival (PFS) was 36xa0months (95xa0% CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT.ConclusionLu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84xa0% DCR (95xa0% CI 73-95) that lasted for 25xa0months and a PFS of 36xa0months. Both activities of 27.8xa0GBq and 18.5xa0GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity.

FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy.

Purpose: Talc pleurodesis (TP) is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F FDG PET/CT) response evaluation in malignant pleural mesothelioma (MPM) patients treated with TP and chemotherapy. Methods: Patients with histologically confirmed MPM underwent TP and FDG PET/CT staging and restaging after 3-4 courses of chemotherapy. All patients fasted and received a dose of 5.18 MBq 18F-FDG per kilogram of body weight. Whole-body emission scans were acquired with and without Ordered Subset Expectation Maximization (OSEM) iterative reconstruction algorithm. Results: From January 2004 to March 2010, 8 patients with biopsy confirmed MPM (7 epithelial, 1 biphasic), with a median age of 65 years (range: 54-77), were evaluated. Median follow-up was 31 months (range: 4-44). After TP treatment, there was a mean interval of 14 days (range: 9-22) and 125 days (range: 76-162) between FDG PET/CT staging and restaging. According to modified RECIST and EORTC criteria, there was a concordance between the radiologic and metabolic SUVmean and SUVmax responses in 6 (75%) and 3 (37.5%) patients, respectively. Conclusion: TP produces an increased FDG PET uptake which may interfere with the post-chemotherapy disease evaluation. In our case series, the metabolic response measured by SUVmean seems to be in better agreement with the radiologic response compared to the SUVmax.

Biomarkers and Molecular Imaging as Predictors of Response to Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

Standard treatment of patients with locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Tumor regression after NCRT varies substantially among individuals and pathological complete response is a known prognostic factor for LARC. The identification of a predictive model for response to chemoradiotherapy would help clinicians to identify patients who would probably benefit from multimodal treatment and to perform an early assessment of individual prognosis. Carcinoembryonic antigen has proven to be a good predictor of response in several clinical trials. Other widely studied predictive models in LARC include molecular biomarkers, analyzed at various levels and by different techniques, and molecular imaging, in particular magnetic resonance imaging and positron emission tomography/computed tomography. Although none of the studied markers have been approved in clinical practice, their evaluation in larger, prospective trials and in combined predictive models could be of use to define tailored therapeutic strategies.

Erratum to: 18F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide [Eur J Nucl Med Mol Imaging, DOI 10.1007/s00259-015-3042-5]

We investigated the role of 18F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. The study group comprised 36 patients with a median age of 72xa0years (range 48–90xa0years) who were treated with enzalutamide 160xa0mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3–6xa0weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 24.2xa0months (range 1.8–27.3xa0months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50xa0% was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3xa0months in advance of CT in 12 of 18 patients (66xa0%) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2xa0months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (pu2009=u20090.0005 and pu2009=u20090.029, respectively), whereas decrease in PSA level alone was predictive of OS (pu2009=u20090.007). This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response to enzalutamide in mCRPC patients.

Radiation dosimetry of 18F-flurocholine PET/CT studies in prostate cancer patients

PURPOSEnWe aimed to evaluate the Equivalent Doses (HTs) to highly exposed organs as well as the Effective Dose (ED) for (18)F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients.nnnMETHODSnFifty patients were administered with (18)F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered (18)F-fluorocholine and CT scan, respectively, and the (18)F-fluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure.nnnRESULTSnThe calculated (18)F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/300 MBq and 6.7 mSv, respectively. The (18)F-fluorocholine HTs to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the (18)F-fluorocholine did.nnnCONCLUSIONSnFor (18)F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered (18)F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures.

FDG PET/CT in autoimmune pancreatitis.

A 72-year-old male patient was admitted to the Emergency Room with acute jaundice in the absence of other clinical symptoms. Laboratory data demonstrated direct hyperbilirubinaemia related to an obstruction in the biliary tree. Endoscopic retrograde cholangiopancreatography was planned and a stent was placed in the common bile duct (e, yellow arrow) with progressive resolution of the jaundice. A biopsy of the ampulla of Vater was performed and was nega-

Development of sentinel node localization and ROLL in breast cancer in Europe

The concept of a precise region in which to find the lymph nodes that drain the lymph directly from the primary tumor site can be traced back to a century ago to the observations of Jamieson and Dobson who described how cancer cells spread from cancer of the stomach in a single lymph node, which they called the “primary gland”. However, Cabanas was the first in 1977 to realize the importance of this concept in clinical studies following lymphography performed in patients with penile cancer. Thanks to Morton’s studies on melanoma in 1992, we began to understand the potential impact of the sentinel lymph node (SN) on the surgical treatment of this type of cancer. The use of a vital dye (blue dye) administered subdermally in the region surrounding the melanoma lesion led to the identification of the sentinel node, and the vital dye technique was subsequently applied to other types of solid tumors, e.g. breast, vulva. However, difficulties in using this technique in anatomical regions with deep lymphatic vessels, e.g. axilla, led to the development of lymphoscintigraphy, started by Alex and Krag in 1993 on melanoma and breast cancer and optimized by our group at European Institute of Oncology (IEO) in Milan in 1996. Today, lymphoscintigraphy is still considered as the most reliable method for the detection of the SN. In 1996, a new method for the localization of non-palpable breast lesion called radioguided occult lesion localization (ROLL) was also developed at IEO. Retrospective and prospective studies have since shown that the ROLL procedure permits the easy and accurate surgical removal of non-palpable breast lesions, overcoming the limitations of previous techniques such as the wire-guided localization. The purpose of this paper is to describe the evolution of SN biopsy and radioguided surgery in the management of breast cancer. We also include a review of the literature on the clinical scenarios in which SN biopsy in breast cancer is currently used, with particular reference to controversies and future prospects.

Early response assessment and bone flare phenomenon on 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in patients (pts) with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone acetate.

134 Background: In this prospective study, in patients with CRPC previously treated with docetaxel, we evaluated prostate specific antigen (PSA) and FCH-PET/CT for early response assessment to abiraterone acetate, and assessed frequency of early FCH-PET/CT discordant with PSA and clinical response.nnnMETHODSnTwenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was repeated after 4-6 weeks and a CT scan was done after 3 months of abiraterone acetate. FCH-PET/CT bone flare was defined as the combination, after 3 months of therapy, of an interpreting radiologists report indicating progressive disease (PD) in context of a ≥50% decline in PSA, no PD at 3-month CT scan, with FCH-PET/CT improvement or stability 2-3 months later.nnnRESULTSnThree of 29 patients treated with abiraterone acetate did not perform the follow-up FCH-PET/CT due to rapidly PD with a decline in performance status. Of the remaining 26 patients, 4 are still undergoing early response evaluation. Twenty two pts, median age was 71 yrs (range, 57-86 yrs) were evaluable for this analysis. A ≥50% PSA decline was observed in 15/22 (68%) evaluable pts. Undetectable PSA levels (≤0.1 ng/mL) occurred in one case. Early FCH PET/CT response assessment was as follows: complete response (n=2, 9%), partial response (n=7, 32%), stable disease (n=3, 14%), PD (n=10, 45%), but in 4 of 10 pts with PD a bone flare phenomenon on FCH PET/CT was observed. PSA decline ≥50% and FCH PET/CT response correlated in 19 of 22 pts (86%).nnnCONCLUSIONSnDiscordant findings between serologic PSA response and increases in early FCH-PET/CT bone lesion intensity are reported here for the first time in CRPC. Further investigation is needed to clarify the confounding effect of FCH-PET/CT bone flare on patient management and interpretation of results.