Peptide Receptor Radionuclide Therapy (PRRT) in a Patient Affected by Metastatic Breast Cancer with Neuroendocrine Differentiation.
Ontology highlight
ABSTRACT: Background
Breast cancer (BC) is the most frequent cancer in European women with nearly 30% of the patients eventually developing metastases. Neuroendocrine differentiation is a rare event, but overexpression of somatostatin receptors in BC has been reported in many studies.Case report
A patient with liver metastases from BC was treated with peptide receptor radionuclide therapy (PRRT). Computed tomography scan and biochemical examinations showed a clear response to radionuclide therapy.Conclusion
PRRT may be useful in metastatic BC patients.
SUBMITTER: Savelli G
PROVIDER: S-EPMC3518936 | biostudies-literature | 2012 Oct
REPOSITORIES: biostudies-literature
Publications
Peptide Receptor Radionuclide Therapy (PRRT) in a Patient Affected by Metastatic Breast Cancer with Neuroendocrine Differentiation.
Savelli Giordano G Zaniboni Alberto A Bertagna Francesco F Bosio Giovanni G Nisa Lutfun L Rodella Carlo C Biasiotto Giorgio G Bettinsoli Giovanni G Migliorati Elena E Peli Alessia A Falchi Roberta R Giuffrida Francesca F Giubbini Raffaele R
Breast care (Basel, Switzerland) 20121001 5
<h4>Background</h4>Breast cancer (BC) is the most frequent cancer in European women with nearly 30% of the patients eventually developing metastases. Neuroendocrine differentiation is a rare event, but overexpression of somatostatin receptors in BC has been reported in many studies.<h4>Case report</h4>A patient with liver metastases from BC was treated with peptide receptor radionuclide therapy (PRRT). Computed tomography scan and biochemical examinations showed a clear response to radionuclide ...[more]
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Project description:Rationale: Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumors (NETs) has been explored for more than two decades, but there are only limited data on the treatment of NETs of unknown primary site (CUP-NETs). This study aimed to analyze the long-term outcome, efficacy, and safety of PRRT in patients with CUP-NETs. Methods: Patients with pathologically confirmed metastatic CUP-NET who received lutetium-177 (177Lu) and/or yttrium-90 (90Y) labeled somatostatin analogs between March 2001 and March 2019 were retrospectively reviewed; those patients were referred as cCUP-NETs (clinical CUP-NETs). Eighty-one patients had unknown primary tumors even after [68Ga]Ga-SSTR and [18F]FDG PET/CT and were classified as pCUP-NETs (PET CUP-NETs). Treatment response was assessed according to RECIST 1.1 and PERCIST. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis, and adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: A total of 575 PRRT cycles were administered to 156 patients (76 men and 80 women) evaluable for analysis: these patients were monitored for a median period of 92.3 mo (range, 4.0-169.1 mo). The disease control rate was 41.4% (43.4%) by RECIST and 40.2% (40.8%) by PERCIST in cCUP-NENs (pCUP-NETs). The objective response rate (ORR) with PRRT was 29.4% and 32.2% in cCUP-NENs and pCUP-NETs, respectively. The median PFS and OS for the entire cohort were 17.4 mo (95% confidence interval [95% CI], 11.4-23.4) and 67.4 mo (95% CI, 47.2-87.2) for all patients, respectively. The median OS for G3 tumors was significantly lower (15 mo) than for patients with G1 NET (85.5 mo), G2 (71.7 mo), and for patients with unknown grade (63.3 mo) NETs (P = 0.186, HR: 10.6, 95% CI: 3.87, 28.97, P = 0.09). PRRT was well tolerated by all patients. During treatment and long-term follow-up, CTCAE grade 3 and grade 4 thrombocytopenia and leukocytopenia were observed in only 3 patients (1.9%); there was no evidence of renal or hepatic toxicity. Conclusion: In a large cohort of patients with advanced CUP-NETs treated with PRRT in a real-world scenario and followed up to 14 years after the commencement, PRRT has demonstrated favorable and clinically significant efficacy and survival with minimal and acceptable side effects. Our results indicate that PRRT is a well-tolerated and effective treatment option for patients with metastatic CUP-NETs expressing somatostatin receptors.
| S-EPMC10750196 | biostudies-literature
Project description:Neuroendocrine neoplasms (NENs) are tumors originating from neuroendocrine cells distributed throughout the human body. With an increasing incidence over the past few decades, they represent a highly heterogeneous group of neoplasms, mostly expressing somatostatin receptors (SSTRs) on their cell surface. Peptide receptor radionuclide therapy (PRRT) has emerged as a crucial strategy for treating advanced, unresectable neuroendocrine tumors by administering radiolabeled somatostatin analogs intravenously to target SSTRs. This article will focus on the multidisciplinary theranostic approach, treatment effectiveness (such as response rates and symptom relief), patient outcomes, and toxicity profile of PRRT for NEN patients. We will review the most significant studies, such as the phase III NETTER-1 trial, and discuss promising new radiopharmaceuticals, including alpha-emitting radionuclide-labeled somatostatin analogs and SSTR antagonists.
| S-EPMC10251822 | biostudies-literature
Project description:BackgroundMetastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression.AimTo describe the characteristics and outcomes of patients with ECS treated with PRRT.MethodsSingle-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006 to 2023.ResultsPatients were aged 17-75 (female n = 6). The primary site was the pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one had a previous BA). A median of 34.4 GBq of [177Lu]Lu-DOTA-octreotate was given. [90Y]Y-DOTA-octreotate (one patient) and [111In]In-octreotide (one patient) were also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within 1 week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5-6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [18F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), and one had a partial metabolic response. PFS was 3-208 months. Two patients progressed at the first follow-up. The longest ECS remission and CMR continues at >17 years.ConclusionPRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.
| S-EPMC11623253 | biostudies-literature
Project description:Purpose177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate.MethodsA retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals).ResultsMedian follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively.ConclusionHigh burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT.Trial registrationClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.
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Project description:Dosimetry during peptide receptor radionuclide therapy (PRRT) has mainly focused on normal organs and less on the tumors. The absorbed dose in one target tumor per patient and several response related factors were assessed in 23 pancreatic neuroendocrine neoplasms (P-NENs) and 25 small-intestinal NEN (SI-NENs) during PRRT with 177Lu-DOTATATE. The total administered activity per patient was (mean ± standard error of mean (SEM) 31.8 ± 1.9 GBq for P-NENs and 36 ± 1.94 GBq for SI-NENs. The absorbed tumor dose was 143.5 ± 2 Gy in P-NENs, 168.2 ± 2 Gy in SI-NENs. For both NEN types, a dose-response relationship was found between the absorbed dose and tumor shrinkage, which was more pronounced in P-NENs. A significant drop in the absorbed dose per cycle was shown during the course of PRRT. Tumor vascularization was higher in P-NENs than in SI-NENs at baseline but equal post-PRRT. The time to progression (RECIST 1.1) was similar for patients with P-NEN (mean ± SEM 30 ± 1 months) and SI-NEN (33 ± 1 months). In conclusion, a dose response relationship was established for both P-NENs and SI-NENs and a significant drop in the absorbed dose per cycle was shown during the course of PRRT, which warrants further investigation to understand the factors impacting PRRT to improve personalized treatment protocol design.
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Project description:BackgroundPeptide receptor radionuclide therapy (PRRT) is an approved treatment modality for gastroenteropancreatic neuroendocrine tumours (GEP NETs), Although Phase III randomised clinical trial data is not available for NETs of other site of origin, in practice, PRRT is used more widely in clinical practice, based on its mechanism of targeting the somatostatin receptor. Use of PRRT for lung (bronchial) NET, specifically typical and atypical carcinoid (TC, AC), has been reported only in small retrospective case series. This multicentre study adds to the evidence regarding utility of PRRT for lung NETs.Materials and methodsA retrospective chart review of patients with TC and AC who received 177Lu-dotatate PRRT between January 2002 and June 2019 in six hospitals across Australia was undertaken. Data regarding demographics, efficacy and toxicity was evaluated at each site by the treating clinician.ResultsForty-eight patients (32 AC, 15 TC, 1 unclassified) received a median of four 177Lu-dotatate treatments. There was a median of one prior line of systemic treatment (range: 0-3). The response rate to 177Lu-dotatate was 33%, with a median overall survival of 49 months (range of 3-91), at a median follow up of 33 months. This compares favourably with GEP NET. Overall toxicity was recorded as modest.Conclusions177Lu-dotatate PRRT in patients with lung NETs is used in real world practice, where it appears well-tolerated with some efficacy. Further evidence could be obtained through a global prospective clinical or registry trial.
| S-EPMC7343632 | biostudies-literature
Project description:Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included 177Lu (n = 142) and 90Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.
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| S-EPMC9390818 | biostudies-literature
Project description:Purpose To evaluate the predictive value of 7-week apparent diffusion coefficient change from baseline (ADCratio7w) at whole-body diffusion-weighted MRI (WB-DWI MRI) after one peptide receptor radionuclide therapy (PRRT) cycle to predict outcome in patients with metastatic neuroendocrine tumor (mNET). Materials and Methods From April 2009 to May 2012, participants in a prospective clinical trial investigating yttrium 90-DOTA Phe1-Tyr3-octreotide (DOTATOC) treatment for mNET (EudraCT no. 2008-007965-22) underwent WB-DWI MRI and gallium 68 (68Ga)-DOTATOC PET/CT before and 7 weeks after one PRRT cycle. ADCratio7w response was compared with the 7-week Response Evaluation Criteria in Solid Tumors version 1.1 and 68Ga-DOTATOC PET/CT quantitative responses to predict overall survival (OS) and progression-free survival (PFS) with Cox regression analysis. Results Forty participants were analyzed (mean age, 60 years ± 11 [SD]; 21 men). Median PFS and OS were 10.5 months (range, 2-36 months) and 18 months (range, 3-81 months), respectively. Survival analysis showed significantly positive effects on PFS by age (hazard ratio [HR] = 0.96, P = .007), tumor grade (HR = 2.84, P = .006), Ki-67 index (HR = 1.05, P = .01), ADCratio7w of the least-responding lesion (ADCratio7w-least) (HR = 0.94, P < .001), and baseline mean standardized uptake values (SUVmean) (HR = 0.89, P = .02), with ADCratio7w-least and SUVmean remaining significant in multivariable analysis (P < .001, P = .02, respectively). There were significantly positive effects on OS by pretreatment lesion volume (HR = 1.004, P = .004), tumor grade (HR = 2.14, P = .04), Ki-67 index (HR = 1.05, P = .01), and ADCratio7w-least (HR = 0.97, P < .001), with pretreatment volume and ADCratio7w-least remaining significant at multivariable analysis (P = .005, P = .002, respectively). Conclusion The ADCratio7w after start of PRRT for mNET was an independent predictor of patient outcome. Keywords: MR-Diffusion-Weighted Imaging, Radionuclide Therapy, Whole-Body Imaging, Metastases, Tumor Response, Treatment Effects EudraCT no. 2008-007965-22 © RSNA, 2022.
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