PRRT: identikit of the perfect patient

Albertelli, Manuela; Dotto, Andrea; Dato, Carla Di; Malandrino, Pasqualino; Modica, Roberta; Versari, Annibale; Colao, Annamaria; Ferone, Diego; Faggiano, Antongiulio; Nike,

doi:10.1007/s11154-020-09581-6

Cited by 17 publications

(10 citation statements)

References 77 publications

(241 reference statements)

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“…Unfortunately, the cardinality of the group studied in our work was too small to draw unequivocal conclusions as to whether the use of different PRRT types and schemes brings about the same results. Among many radiological and clinical features, only negative results of [18F]FDG PET/CT examination, histopathological grading ( 23 ), and to some extent the good SSTR expression on SRI ( 24 ) are widely known indicators of prognosis in NET patients. Nevertheless, none of those parameters are confirmed as factors influencing PRRT to be a neoadjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors

Opalińska¹,

Sowa‐Staszczak

Grochowska³

et al. 2021

Front. Oncol.

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IntroductionNeuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes.AimThis study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs.MethodsAmong the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment.ResultsNeoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved.ConclusionPRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.

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Section: Discussionmentioning

confidence: 99%

Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors

Opalińska¹,

Sowa‐Staszczak

Grochowska³

et al. 2021

Front. Oncol.

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“…In addition, PET derived parameters, such as the semiquantitative standardized uptake values (SUVs), have been widely studied as prognostic and predictive factors in NET patients treated with PRRT [7]. In several other malignancies, FDG-PET-derived metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which is the product of SUVmean × MTV, have shown a major role in prognosis and treatment monitoring compared to SUVs parameters [8].…”

Section: Introductionmentioning

confidence: 99%

Predictive and Prognostic Role of Pre-Therapy and Interim 68Ga-DOTATOC PET/CT Parameters in Metastatic Advanced Neuroendocrine Tumor Patients Treated with PRRT

Durmo

Filice

Fioroni

et al. 2022

Cancers

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Peptide receptor radionuclide therapy (PRRT) is an effective therapeutic option in patients with metastatic neuroendocrine tumor (NET). However, PRRT fails in about 15–30% of cases. Identification of biomarkers predicting the response to PRRT is essential for treatment tailoring. We aimed to evaluate the predictive and prognostic role of semiquantitative and volumetric parameters obtained from the 68Ga-DOTATOC PET/CT before therapy (bPET) and after two cycles of PRRT (iPET). A total of 46 patients were included in this retrospective analysis. The primary tumor was 78% gastroenteropancreatic (GEP), 13% broncho-pulmonary and 9% of unknown origin. 35 patients (76.1%) with stable disease or partial response after PRRT were classified as responders and 11 (23.9%) as non-responders. Logistic regression analysis identified that baseline total volume (bTV) was associated with therapy outcome (OR 1.17; 95%CI 1.02–1.32; p = 0.02). No significant association with PRRT response was observed for other variables. High bTV was confirmed as the only variable independently associated with OS (HR 12.76, 95%CI 1.53–107, p = 0.01). In conclusion, high bTV is a negative predictor for PRRT response and is associated with worse OS rates. Early iPET during PRRT apparently does not provide information useful to change the management of NET patients.

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“…Grading, expressed by Ki-67, is firmly considered a strong prognostic factor in NENs [ 9 , 49 ]. The literature reports an inverse correlation between Ki-67 and therapeutic outcomes in terms of overall survival and the disease control rate [ 38 , 49 , 50 , 51 ]. For these reasons, we expected to find a positive correlation between Ki-67 and ΔSUVmax increase on FDG PET/CT in our study.…”

Section: Discussionmentioning

confidence: 99%

Glucose Metabolism Modification Induced by Radioligand Therapy with [177Lu]Lu/[90Y]Y-DOTATOC in Advanced Neuroendocrine Neoplasms: A Prospective Pilot Study within FENET-2016 Trial

Urso

Panareo²,

Castello

et al. 2022

Pharmaceutics

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[18F]F-FDG (FDG) PET is emerging as a relevant diagnostic and prognostic tool in neuroendocrine neoplasms (NENs), as a simultaneous decrease in [68Ga]Ga-DOTA peptides and increase in FDG uptake (the “flip-flop” phenomenon) occurs during the natural history of these tumors. The aim of this study was to evaluate the variations on FDG PET in NEN patients treated with two different schemes of radioligand therapy (RLT) and to correlate them with clinical–pathologic variables. A prospective evaluation of 108 lesions in 56 patients (33 males and 23 females; median age, 64.5 years) affected by NENs of various primary origins (28 pancreatic, 13 gastrointestinal, 9 bronchial, 6 unknown primary (CUP-NENs) and 1 pheochromocytoma) and grades (median Ki-67 = 9%) was performed. The patients were treated with RLT within the phase II clinical trial FENET-2016 (CTID: NCT04790708). RLT was offered for 32 patients with the MONO scheme (five cycles of [177Lu]Lu-DOTATOC) and for 24 with the DUO scheme (three cycles of [177Lu]Lu-DOTATOC alternated with two cycles of [90Y]Y-DOTATOC). Variations in terms of the ΔSUVmax of a maximum of three target lesions per patient (58 for MONO and 50 for DUO RLT) were assessed between baseline and 3 months post-RLT FDG PET. In patients with negative baseline FDG PET, the three most relevant lesions on [68Ga]Ga-DOTA-peptide PET were assessed and matched on post-RLT FDG PET, to check for any possible changes in FDG avidity. Thirty-five patients (62.5%) had at least one pathological FDG uptake at the baseline scans, but the number was reduced to 29 (52%) after RLT. In the patients treated with DUO-scheme RLT, 20 out of 50 lesions were FDG positive before therapy, whereas only 14 were confirmed after RLT (p = 0.03). Moreover, none of the 30 FDG-negative lesions showed an increased FDG uptake after RLT. The lesions of patients with pancreatic and CUP-NENs treated with the DUO scheme demonstrated a significant reduction in ΔSUVmax in comparison to those treated with MONO RLT (p = 0.03 and p = 0.04, respectively). Moreover, we found a mild positive correlation between the grading and ΔSUVmax in patients treated with the MONO scheme (r = 0.39, p < 0.02), while no evidence was detected for patients treated with the DUO scheme. Our results suggest that RLT, mostly with the DUO scheme, could be effective in changing NEN lesions’ glycometabolism, in particular, in patients affected by pancreatic and CUP-NENs, regardless of their Ki-67 index. Probably, associating [90Y]Y-labelled peptides, which have high energy emission and a crossfire effect, and [177Lu]Lu ones, characterized by a longer half-life and a safer profile for organs at risk, might represent a valid option in FDG-positive NENs addressed to RLT. Further studies are needed to validate our preliminary findings. In our opinion, FDG PET/CT should represent a potent tool for fully assessing a patient’s disease characteristics, both before and after RLT.

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PRRT: identikit of the perfect patient

Cited by 17 publications

References 77 publications

Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors

Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors

Predictive and Prognostic Role of Pre-Therapy and Interim 68Ga-DOTATOC PET/CT Parameters in Metastatic Advanced Neuroendocrine Tumor Patients Treated with PRRT

Glucose Metabolism Modification Induced by Radioligand Therapy with [177Lu]Lu/[90Y]Y-DOTATOC in Advanced Neuroendocrine Neoplasms: A Prospective Pilot Study within FENET-2016 Trial

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