Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

Performance evaluation of a new time of flight PET/CT scanner: Results of a multicenter study.

PURPOSE: The aim of this multicenter study was to evaluate the performance of the upgraded version of the Ingenuity TF PET/CT scanner, according to the NEMA NU-2 2012 standards. METHODS: Spatial resolution, sensitivity, count rate response, scatter fraction, image quality and accuracy were evaluated on three Ingenuity TF scanners installed in Italian hospitals. Furthermore, energy and timing resolution were measured. A detailed image quality phantom analysis was performed to evaluate the effect of different clinical reconstruction parameters, including the application of PSF correction. RESULTS: Results show an average spatial resolution of 4.7 mm and an average absolute system sensitivity of 7.9 cps/kBq. The average maximum NECR was 119.83 kcps at 20.67 kBq/ml, while the maximum true event rate was 322.62 kcps at the concentration of 24.51 kBq/ml. The average maximum bias below NECR peak was 12.58%. All the results of NEMA tests were in agreement with the values declared by the manufacturer. The estimated average energy and timing resolution were 10.83% and 536.2 ps, respectively. Image quality phantom analysis obtained with different reconstruction settings showed that PSF correction was the parameter that affected mainly on contrast recovery coefficient, while the iteration number and amplitude of Gaussian filter had no significant effect. Of relevance, the application of PSF correction never led to recovery coefficient values higher than 100% and to Gibbs or edge artifacts. CONCLUSIONS: The new Ingenuity TF model shows physical performance similar to other scanners of the latest generation for all standard NEMA NU2-2012 measurements.

PET-CT post therapy dosimetry in radioembolization with resin 90Y microspheres: Comparison with pre-treatment SPECT-CT 99mTc-MAA results.

Resin microspheres radioembolization is an effective treatment for liver tumors when the surgical option is not feasible. Doses delivered to tumor and normal liver can be assess in the pre-therapy phase by means of a 99mTc-MAA SPECT-CT simulation and after the treatment with 90Y PET-CT acquisition. The optimal therapeutic 90Y activity is determined on 99mTc-MAA SPECT-CT dose results in order to avoid healthy parenchyma toxicity and to effectively irradiate the tumor. The assumption of identical radiopharmaceutical distribution between simulation and verification is still under debate and literature data showed controversial results. In this study 10 HCC patient's dosimetry performed on 99mTc SPECT-CT and 90Y PET-CT were compared. Patients were selected when a good agreement between the pre and post-therapy distribution was observed in order to investigate the intrinsic dosimetric variations between the two imaging modalities. Mean doses (MIRD and Voxel approaches) showed a good correlation (Pearson's coefficient r > 0.90) both for tumor and normal liver. Dose Volume Histogram curves were compared with a good agreement particularly for normal liver (D50). Goal doses were achieved for 90% of patients. Bland-Altman analysis indicates lower variations for healthy parenchyma than for tumor (1.96 SD equal to 9.1 Gy and 68 Gy respectively) confirming the robustness of the dose-toxicity approach. PET-CT dosimetry well correlates with SPECT-CT doses (under assumption of same catheter position and 90Y activity). Better agreement was showed for 7/10 and 8/10 patients for T and NL respectively, confirming dosimetry as effective tool to optimize and individualize the treatment.

Calculation of tumour and normal tissue biological effective dose in 90Y liver radioembolization with different dosimetric methods.

PURPOSE: Radioembolization with 90Y microspheres is an effective treatment for unresectable liver tumours. Two types of microspheres are available: resin (SIR-Spheres®) and glass (Theraspheres®). The aim of this study is to compare biological effective dose (BED) values obtained with three different dosimetric methods. METHODS: 29 HCC patients were included in this study: 15 were treated with resin(mean injected activity 1.5GBq, range 0.8-2.7GBq) and 14 with glass microspheres (2.6GBq, range 1.3-4.1GBq). Average doses to tumours and normal liver tissues were calculated with AAPM, multi-compartmental MIRD and Voxel-based methods and consequently the BED values were obtained. Planar images were used for the AAPM method: 99mTc-MAA SPECT-CT attenuation and scatter corrected images (resin) and 99m Tc-MAA SPECT attenuation corrected (glass) were employed for the other two methods. RESULTS: Regardless of type of microspheres, both for tumours and normal liver tissues, no significant statistical differences were found between MIRD and Voxel for both doses and BED values. Conversely AAPM gave discordant results with respect to the other two methods (Mann-Whitney p-values⩽0.01). For resin spheres the calculated tumour-to-normal tissue ratios on planar images were on average 14 times greater than those obtained on SPECT-CT images, while they were 4 times greater on glass. A linear correlation was observed between MIRD and Voxel BEDs. CONCLUSIONS: The AAPM method appears to be less precise for absorbed dose and BED estimation, while MIRD and voxel based dosimetry are more confident each other.