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1.
Br J Radiol ; 94(1117): 20201041, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095671

RESUMO

OBJECTIVES: Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting. METHODS: A total of 468 metastatic/advanced NET patients (wide range of primary sites including CUP-NETs), who underwent at least two cycles of 177Lu-DOTATATE PRRT with available follow-up information, were included and analysed retrospectively in this study. In-house labelling of DOTATATE with 177Lu (direct route produced) was carried out in the hospital radiopharmacy and treatment administered in cycles (dose: 5.55 to 7.4 GBq per patient), at 10-12 weeks interval. The assessment of long-term outcome was undertaken under three broad headings: (a) Therapeutic response, (b) Survival outcome and (c) Toxicity assessment. The median point estimate with 95% CI for progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic covariates for association with PFS and OS was investigated by Cox proportional hazards model (univariate and multivariate Hazard Ratios) and with disease control rate (DCR) by Chi-square test, with significant P value defined as <0.05. RESULTS: Long-term outcome (follow-up ranging from 4 to 97.6 months; median period:46 months following first 177Lu-DOTATATE PRRT) results showed, (i) on symptomatic response evaluation scale, complete response (CR) in 214 patients (45.7%), partial response (PR) in 108 (23.1%), stable disease (SD) in 118 (25.2%), progressive disease (PD) in 28 (6%). (ii) Biochemical response evaluation showed CR in 52 (12%), PR in 172 (40%), SD in 161 (38%), and PD in 42 patients (10%). (iii) Molecular imaging response (by PERCIST criteria) showed CR in 29 (6%), PR in 116 (25%), SD in 267 (57%) and PD in 56 (12%) patients. (iv) On RECIST 1.1 criteria, CR was observed in 14 patients (3%), PR in 126 patients (27%), SD in 282 patients (60%) and PD in 46 patients (10%). The median PFS and OS were not reached at a median follow-up of 46 months. Observed PFS and OS at 7 years were 71.1% 95% CI (62.4-79.7%) and 79.4% 95% CI (71.4-86.9%) respectively. PFS was dependent on previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake, site of primary tumour, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake and number of PRRT cycles. The OS was dependent on baseline 68Ga-DOTATATE uptake, site of primary tumour, presence of bony metastatic disease, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for bony metastatic disease and number of PRRT cycles. Transient haematological toxicity of Grade 1, Grade 2, and Grade 3 was found in 8 (1.7%), 1 (0.2%) and one patient (0.2%), respectively. Nephrotoxicity of Grade 1, Grade 2, Grade 3, and Grade 4 were seen in 16 (3.5%), 3 (0.6%), 2 (0.4%) and one patient (0.2%), respectively. On a separate sub-analysis of 322 NET patients with progressive disease at the initiation point of PRRT, overall response rates (CR + PR + SD) were 93.5%, 88.5%, 89.1 and 87.9% on symptomatic, biochemical, RECIST 1.1 and PERCIST criteria and PFS and OS at 7 years 68.3% and 79.2%, respectively. CONCLUSIONS: The present results demonstrate that 177Lu-DOTATATE PRRT improved symptoms and biochemical markers substantially in most of the NET patients, with disease stabilisation on both anatomical and molecular imaging in majority and response in a sizeable fraction. Additionally, the therapeutic protocol with lesser dose per cycle (mean 5.92 GBq/cycle) and prolonged duration (over 5 cycles and 1.5 years) in a metastatic NET setting proved equally efficacious (with superior PFS and OS rates) and relatively better tolerated with minimal toxicity. ADVANCES IN KNOWLEDGE: The present work critically examines the long-term results, survival outcome and toxicity profile of the indigenous 177Lu-DOTATATE (produced through direct neutron activation of enriched 176Lu) in metastatic progressive NETs across a wide range of primary sites and malignancies. Such long-term outcome data establishes the favourable impact of PRRT in a wide patient base and also the therapeutic efficacy of the product.


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/secundário , Octreotida/análogos & derivados , Octreotida/análise , Compostos Organometálicos/uso terapêutico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos Retrospectivos , Análise de Sobrevida , Atenção Terciária à Saúde , Resultado do Tratamento , Adulto Jovem
2.
Clin Nucl Med ; 45(11): e493-e494, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32604119

RESUMO

The whole-body absolute quantification of Lu-DOTATATE therapy was achieved using a high-speed 360° CZT SPECT/CT system. Twelve high-resolution swelling detectors may be positioned close to patients, providing a high-count sensitivity that is particularly advantageous for the low-count rate conditions of Lu imaging. After initially validating Lu quantification on phantom, serial whole-body SPECT/CT acquisitions of only 20 minutes were obtained for a 70-year-old woman treated by Lu-DOTATATE injections for a metastatic recurrence of a pancreatic neuroendocrine tumor. The progressive decrease in tumor uptake between the consecutive Lu-DOTATATE injections could be quantified, and thereby the corresponding dosimetry changes could be estimated.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Imagem Corporal Total/instrumentação , Idoso , Estudos de Viabilidade , Feminino , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Imagens de Fantasmas , Radiometria
3.
Clin Nucl Med ; 45(9): e393-e399, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32604121

RESUMO

PURPOSE: Advanced inoperable/metastatic neuroendocrine tumors (NETs) pose a therapeutic challenge with limited treatment options. Peptide receptor radionuclide therapy (PRRT), being specific in targeting the somatostatin receptors, is a promising and viable option in this setting. In this study, we intended to evaluate the role of PRRT as the first-line systemic therapy in advanced inoperable/metastatic NETs. METHODS: Data of consecutive patients of advanced inoperable/metastatic NETs treated with first-line Lu-DOTATATE at our center, from September 2012 to August 2019, were collected and analyzed. RESULTS: Forty-five patients (median age, 50 years; range, 14-72 years) with treatment-naive advanced NETs received a median cumulative dose of 27 GBq (range, 13.3-41.3 GBq; over 2-7 cycles) Lu-DOTATATE and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Three patients were lost to follow-up, 2 had nonmeasurable lesions on CT, and hence, radiological response using Response Evaluation Criteria in Solid Tumors version 1.1 could be assessed in 40 patients. Twelve of 40 patients (30%) showed a partial response, whereas stable disease was observed in 22 of 40 patients (55%). Disease progression was limited to 6 of 40 patients (15%). Treatment-related adverse effects were minimal with grade 3/4 anemia, leukopenia, neutropenia, and hepatotoxicity observed in 2%, 2%, 4%, and 4% of the patients, respectively. Median progression-free survival was 48 months (95% confidence interval, 34.7-61.3 months). CONCLUSIONS: Our results indicate the efficacy and safety of first-line PRRT in advanced NETs. Future randomized trials, comparing PRRT and somatostatin analogs in treatment-naive patients, are required to identify the definite sequence of treatment options for these patients.


Assuntos
Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Receptores de Peptídeos/metabolismo , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/cirurgia , Octreotida/uso terapêutico , Intervalo Livre de Progressão , Adulto Jovem
4.
Clin Nucl Med ; 45(9): e400-e402, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32701804

RESUMO

Lu-DOTATATE is an effective treatment for inoperable metastatic well-differentiated pancreatic neuroendocrine tumors. There are no guidelines for patients with terminal renal failure. We present the case of a 74-year-old woman who received different lines of treatment: analogs of somatostatin, chemotherapy, a first series of peptide receptor radionuclide therapy (PRRT), and finally chemoembolization. Because of persistent hepatic progression, a safe and successful administration of 4 cycles of a second series of PRRT under hemodialysis was administered. Patient was in scintigraphic complete remission at 12 months with normal hematological parameters at 12 and 30 months after PRRT.


Assuntos
Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/uso terapêutico , Progressão da Doença , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Neoplasias Pancreáticas/radioterapia , Diálise Renal , Segurança , Idoso , Embolização Terapêutica , Feminino , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Neoplasias Pancreáticas/patologia , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(27): e21056, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629733

RESUMO

Primary nephrotic syndrome (PNS) is one of the most common primary glomerular diseases in children. Patients complicated nephrotic syndrome with pancreatic lesions are rarely reported, and the clinical manifestations in children are atypical. This study has observed the incidence, clinical types, and prognosis of acute pancreatitis (AP) in children with primary nephrotic syndrome, and analyzed its related factors, early diagnosis, and treatment.Seven children with PNS and AP in Shanghai Children's Hospital from January 2015 to December 2017 were reviewed. The clinical data including age, height, weight, body mass index (BMI), diet, biliary tract disease, PNS durations, drugs, proteinuria, creatinine, glucose, glycated hemoglobin, amylase and lipase, albumin, cholesterol, triglyceride, ultrasound, computerized tomography (CT), renal pathology and estimated glomerular filtration rate (eGFR) were retrospectively analyzed. All patients were followed for >2 years.Ten in 589 patients with PNS were detected pancreatic lesions by abdominal ultrasound. Seven were diagnosed as AP, which the incidence was 1.2%. Only 1 of 7 patients had elevated serum amylase. Lesions of pancreas were found by ultrasound and/or enhanced CT. Four of 7 patients had been treated with tacrolimus. All patients with AP were improved after octreotide acetate injection and supportive treatment. Only 1 patient suffered recurrent AP during the relapse of PNS 10 months later.AP in children with PNS is not common, and the clinical manifestations are not typical. Abdominal ultrasound and enhanced CT are of high value in diagnosis. The adverse effects of tacrolimus should be concerned. Early diagnosis and timely treatment can be helpful for a prognosis.


Assuntos
Rim/patologia , Síndrome Nefrótica/complicações , Síndrome Nefrótica/metabolismo , Pancreatite/metabolismo , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Masculino , Síndrome Nefrótica/diagnóstico por imagem , Síndrome Nefrótica/fisiopatologia , Octreotida/administração & dosagem , Octreotida/uso terapêutico , Pancreatite/diagnóstico por imagem , Pancreatite/tratamento farmacológico , Pancreatite/epidemiologia , Prognóstico , Recidiva , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico
6.
Clin Nucl Med ; 45(9): 714-715, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32657872

RESUMO

The efficacy of Lu-DOTATATE in large neuroendocrine tumors (NETs) is reduced because of the lower energy (Eßmax 0.497 MeV) and shorter range of Lu. The pure ß-emitter Y with its longer ß range is more effective in larger tumors. This should be balanced with the greater risk of Y-DOTATATE-related nephrotoxicity. Sequential duo-peptide receptor radionuclide therapy may result in a better response with minimal adverse effects in large-volume heterogeneous NETs. A 56-year-old man with large rectal NET liver metastases, treated with Y-DOTATATE and Lu-DOTATATE and sequential duo-peptide receptor radionuclide therapy, presented with post-Y-DOTATATE bremsstrahlung and PET/CT in comparison with Ga-DOTATATE PET/CT and Lu-DOTATATE scans.


Assuntos
Complexos de Coordenação/uso terapêutico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Receptores de Peptídeos/metabolismo , Carga Tumoral , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Octreotida/uso terapêutico , Carga Tumoral/efeitos da radiação
8.
Eur J Endocrinol ; 183(1): G17-G23, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32369770

RESUMO

Patients with pituitary tumours, ensuing hormonal abnormalities and mass effects are usually followed in multidisciplinary pituitary clinics and can represent a management challenge even during the times of non-pandemic. The COVID-19 pandemic has put on hold routine medical care for hundreds of millions of patients around the globe, while many pituitary patients' evaluations cannot be delayed for too long. Furthermore, the majority of patients with pituitary tumours have co-morbidities potentially impacting the course and management of COVID-19 (e.g. hypopituitarism, diabetes mellitus, hypertension, obesity and cardiovascular disease). Here, we summarize some of the diagnostic and management dilemmas encountered, and provide guidance on safe and as effective as possible delivery of care in the COVID-19 era. We also attempt to address how pituitary services should be remodelled in the event of similar crises, while maintaining or even improving patient outcomes. Regular review of these recommendations and further adjustments are needed, depending on the evolution of the COVID-19 pandemic status. We consider that the utilization of successful models of pituitary multidisciplinary care implemented during the COVID-19 pandemic should continue after the crisis is over by using the valuable and exceptional experience gained during these challenging times.


Assuntos
Adenoma/terapia , Antineoplásicos Hormonais/uso terapêutico , Infecções por Coronavirus , Agonistas de Dopamina/uso terapêutico , Procedimentos Neurocirúrgicos , Pandemias , Apoplexia Hipofisária/terapia , Neoplasias Hipofisárias/terapia , Pneumonia Viral , Adenoma/diagnóstico , Cabergolina/uso terapêutico , Gerenciamento Clínico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Apoplexia Hipofisária/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Guias de Prática Clínica como Assunto , Radioterapia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Telemedicina , Fatores de Tempo , Testes de Campo Visual
9.
Galicia clin ; 81(2): 54-56, abr. 2020. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-195199

RESUMO

Insulinomas are the most frequent etiology of hypoglycemia in a non-diabetic patient and the most common functional neuroendocrine tumors of the pancreas, with an annual incidence of about 4 cases per million. The majority of insulinomas are "well-differentiated endocrine tumors" or grade 1 tumors, as defined by World Health Organization. Most tumors are benign, solitary and occur sporadically. However, about 10% are associated with multiple endocrine neoplasia type 1 (MEN-1). Despite the majority being benign tumors, hypoglycemic symptoms caused by the hyperinsulinemia are frequently debilitating. Whipple triad (hypoglycemia, symptoms of hypoglycemia - either adrenergic or neuroglycopenic - and relief of these symptoms after administration of glucose) is usually present and should alert to the diagnosis.After the diagnosis is made, locating the tumor can be challenging because most tumors are small. Nonetheless, locating the tumor is crucial, once the only definite treatment is surgical excision. The majority of patients reach normalization of glucose levels after surgery. Incomplete resection leads to persistent symptoms and although uncommon in sporadic insulinomas, recurrence can be as high as 20% in patients with MEN-1 syndrome


No disponible


Assuntos
Humanos , Masculino , Adulto , Insulinoma/complicações , Insulinoma/diagnóstico por imagem , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico por imagem , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulinoma/cirurgia , Tumores Neuroendócrinos/cirurgia , Hipoglicemia/tratamento farmacológico , Octreotida/uso terapêutico , Diazóxido/uso terapêutico , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X
11.
J Cancer Res Clin Oncol ; 146(6): 1533-1543, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32281025

RESUMO

PURPOSE: To evaluate the efficacy of 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) radionuclide therapy in patients with inoperable or metastatic neuroendocrine tumours (NETs), (PROSPERO ID CRD42019130755). METHODS: All published clinical studies of NETs treated with 177Lu-DOTATATE were identified based on systematic searches in the PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov databases up to January 2019. Among these studies, only the reports evaluated with the "Response Evaluation Criteria in Solid Tumours (RECIST)" or "Southwest Oncology Group (SWOG)" criteria or both were included. We analysed the disease response rate (DRR) and disease control rate (DCR) of each group to evaluate the efficacy of 177Lu-DOTATATE. RESULTS: Fifteen studies were selected from 715 references. The pooled effect in the RECIST group (13 studies) was 27.58% (95% confidence interval (CI) 21.03-35.27%) for the DRR and 79.14% (95% CI 75.83-82.1%) for the DCR. In the SWOG criteria group (7 studies), the pooled effect was 20.59% (95% CI 10.89-35.51%) for the DRR and 78.28% (95% CI 74.39-81.72%) for the DCR. Therefore, the RECIST and SWOG groups showed similar DRRs and DCRs after177Lu-DOTATATE treatment, indicating that 177Lu-DOTATATE treatment has excellent efficacy with a control rate of approximately 78-79%. Moreover, adverse effects of 177Lu-DOTATATE were minimal, including fatigue, nausea, vomiting and hormonal disorders. CONCLUSIONS: For patients with inoperable or metastatic NETs, 177Lu-DOTATATE is an effective treatment with minimal side effects.


Assuntos
Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Metástase Neoplásica , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico
12.
Eur J Endocrinol ; 182(6): 583, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217809

RESUMO

Objective: In the Phase III PAOLA study (clinicaltrials.gov: NCT01137682), enrolled patients had uncontrolled acromegaly despite ≥6 months of octreotide/lanreotide treatment before study start. More patients achieved biochemical control with long-acting pasireotide versus continued treatment with octreotide/lanreotide (active control) at month 6. The current work assessed the extent of comorbidities at baseline and outcomes during a long-term extension. Design/methods: Patients receiving pasireotide 40 or 60 mg at core study end could continue on the same dose in an extension phase if biochemically controlled or receive pasireotide 60 mg if uncontrolled. Uncontrolled patients on active control were switched to pasireotide 40 mg, with the dose increased at week 16 of the extension if still uncontrolled (crossover group). Efficacy and safety are reported to 304 weeks (~5.8 years) for patients randomized to pasireotide (core + extension), and 268 weeks for patients in the crossover group (extension only). Results: Almost half (49.5%; 98/198) of patients had ≥3 comorbidities at core baseline. During the extension, 173 patients received pasireotide. Pasireotide effectively and consistently reduced GH and IGF-I levels for up to 5.8 years' treatment; 37.0% of patients achieved GH <1.0 µg/L and normal IGF-I at some point during the core or extension. Improvements were observed in key symptoms. The long-term safety profile was similar to that in the core study; 23/173 patients discontinued treatment because of adverse events. Conclusions: In this patient population with a high burden of comorbid illness, pasireotide was well tolerated and efficacious, providing prolonged maintenance of biochemical control and improving symptoms.


Assuntos
Acromegalia/tratamento farmacológico , Hormônios/administração & dosagem , Somatostatina/análogos & derivados , Fatores de Tempo , Acromegalia/sangue , Adulto , Estudos Cross-Over , Esquema de Medicação , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Prospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Resultado do Tratamento
13.
Clin Nucl Med ; 45(5): e232-e235, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32209879

RESUMO

Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Receptores de Somatostatina/metabolismo , Idoso , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Metástase Linfática , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Resultado do Tratamento
14.
Lancet Oncol ; 21(4): 561-570, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112737

RESUMO

BACKGROUND: In patients with metastatic neuroendocrine neoplasms, the liver is the most commonly affected organ and a crucial factor for prognosis and survival. Peptide receptor radionuclide therapy can prolong progression-free survival in these patients. Additional treatment of liver disease might further improve outcomes. We aimed to investigate the safety and efficacy of additional holmium-166 (166Ho) radioembolisation after peptide receptor radionuclide therapy in patients with metastatic liver neuroendocrine neoplasms. METHODS: The Holmium Embolization Particles for Arterial Radiotherapy Plus 177Lu-Dotatate in Salvage Neuroendocrine Tumour Patients (HEPAR PLuS) study was a single-centre, phase 2 study done at the University Medical Center Utrecht (Utrecht, Netherlands). Patients, aged at least 18 years, with histologically proven grade 1 or 2 neuroendocrine neoplasms of all origins, an Eastern Cooperative Oncology Group performance status of 0-2, and three or more measurable liver metastases according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria received 166Ho-radioembolisation within 20 weeks after four cycles of peptide receptor radionuclide therapy (lutetium-177-dotatate [177Lu-dotatate]). The primary endpoint was objective liver tumour response in the treated liver volume, defined as complete response (disappearance of all lesions) or partial response (≥30% decrease in the sum of the longest diameters of the target lesions, compared with baseline measurements), according to RECIST 1.1, analysed per protocol at 3 months. Safety was assessed in all patients who received treatment. This study is registered with ClinicalTrials.gov, NCT02067988. Recruitment is completed and long-term follow-up is ongoing. FINDINGS: From Oct 15, 2014, to Sept 12, 2018, 34 patients were assessed for eligibility. 31 patients received treatment and 30 (97%) patients were available for primary endpoint assessment and completed 6 months of follow-up. Three (9%) patients were excluded at screening and one (3%) patient was treated and died before the primary endpoint and was replaced. According to the per-protocol analysis 13 (43%; 95% CI 26-63) of 30 patients achieved an objective response in the treated volume. The most frequently reported Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 clinical and laboratory toxicities within 6 months included abdominal pain (three [10%] of 31 patients), increased γ-glutamyl transpeptidase (16 [54%]), and lymphocytopenia (seven [23%]). One (3%) fatal treatment-related serious adverse event occurred (radioembolisation-induced liver disease). Two (6%) patients had serious adverse events deemed to be unrelated to treatment (gastric ulcer and perforated cholecystitis). INTERPRETATION: 166Ho-radioembolisation, as an adjunct to peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm liver metastases, is safe and efficacious. Radioembolisation can be considered in patients with bulky liver disease, including after peptide receptor radionuclide therapy. A future randomised, controlled study should investigate the added benefit of this treatment on progression-free survival. FUNDING: None.


Assuntos
Embolização Terapêutica/métodos , Hólmio/uso terapêutico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Radioisótopos/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
15.
Clin Nucl Med ; 45(5): 374-376, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32149808

RESUMO

PRRT (peptide receptor radionuclide therapy) with Lu-DOTATATE for neuroendocrine tumor has some well-known adverse effects, concerning specially the bone marrow and kidneys. Hepatotoxicity has been rarely reported, and there are no data regarding hepatic steatosis secondary to PRRT. We reviewed upper abdomen CT and MRI and applied radiologic criteria for the diagnosis of hepatic steatosis on 62 patients treated between the years of 2010 and 2017. Two patients already showed radiologic signs of steatosis in the middle of the treatment and through follow-up all patients showed improvement of the steatosis.


Assuntos
Complexos de Coordenação/efeitos adversos , Fígado Gorduroso/etiologia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Radiofarmacêuticos/efeitos adversos , Complexos de Coordenação/uso terapêutico , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/uso terapêutico
16.
Medicine (Baltimore) ; 99(10): e19304, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150065

RESUMO

BACKGROUND: Somatostatin analog therapies showed great potential for patients suffering advanced neuroendocrine tumors (NETs). This study was aimed to evaluate the therapeutic efficacy of Lu-DOTATATE/DOTATOC (Lu-octreotate/octreotide) peptide receptor radionuclide therapy (PRRT) in advanced or inoperable NETs patients. METHODS: Pubmed, Web of Science, Embase and Cochrane Library were searched from 1950 to April 2019. Eligible studies should include randomized or nonrandomized controlled trials (RCTs)-based investigations of Lu-octreotate/octreotide PRRT for NETs. All these studies were assessed with Response Evaluation Criteria in Solid Tumors (RECIST), RECIST 1.1, Southwest Oncology Group (SWOG) criteria or World Health Organization (WHO) criteria. Disease response rates (DRRs) and disease control rates (DCRs) were calculated according to each response criteria group. DRRs were defined as the percentages of patients with complete response (CR) + partial response (PR), while DCRs represented the percentages of patients with CR+ PR+ stable disease (SD). The pooled proportions were calculated with either a fixed-effects model or a random-effects model depending on the test for heterogeneity. RESULTS: A total of 22 studies (1758 patients) were included in this meta-analysis: 8 studies with 478 patients met RECIST criteria, 10 studies with 1127 patients met RECIST 1.1 criteria, 5 studies with 459 patients met SWOG criteria, and 1 study with 40 patients met WHO criteria, and among these articles 1 study met both RECIST and RECIST 1.1 criteria and 1 met both RECIST 1.1 and SWOG criteria. The pooled DRRs were 33.0% (95% CI: 25.0%-42.0%, I = 65%), 35.0% (95% CI: 26.0%-45.0%, I = 91%) and 25.0% (95% CI: 14.0%-36.0%, I = 84%) according to RECIST, RECIST 1.1 and SWOG criteria, respectively. The pooled DCRs were 79.0% (95% CI: 75.0%-83.0%, I = 97%), 83.0% (95% CI: 78.0%-88.0%, I = 0) and 82.0% (95% CI: 75.0%-89.0%, I = 91%), respectively. CONCLUSION: In advanced NETs patients, DRRs and DCRs were significantly elevated after initial treatment with Lu-DOTATATE PRRT, which shows that this treatment would be beneficial and promising for advanced or inoperable NETs patients.


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/análogos & derivados , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/uso terapêutico , Compostos Radiofarmacêuticos/administração & dosagem , Critérios de Avaliação de Resposta em Tumores Sólidos
18.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 39(1): 31-34, ene.-feb. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-195944

RESUMO

Se realizó una PET/TC con 68Ga DOTANOC a un varón de 64 años con tumor neuroendocrino de grado III, para estadificación. La lesión pancreática, múltiples ganglios peripancreáticos y diversas metástasis de gran tamaño en ambos lóbulos hepáticos, se mostraron con captación intensa. Tras 3 ciclos de quimioterapia con cisplatino y etopósido, el tumor primario y las metástasis disminuyeron de tamaño, aunque se reveló una mayor captación en la PET/TC con 68Ga DOTANOC de seguimiento. Otra biopsia hepática reflejó un descenso significativo del índice de proliferación de Ki-67, del 35 al 1%. El paciente recibió 2 ciclos de terapia con radionúclidos de receptores peptídicos con 177Lu DOTANOC


A 64-year-old man with pancreatic grade III neuroendocrine carcinoma underwent 68Ga DOTANOC PET/CT scan for staging. The pancreatic lesion, multiple peripancreatic lymph nodes and multiple gross metastases in both hepatic lobes were revealed with intense uptake. After 3 cycles of chemotherapy containing cisplatin and etoposide the primary and metastatic lesions were decreased in size, however showing higher uptake on follow-up 68Ga DOTANOC PET/CT scan. Another biopsy from liver demonstrated a significant decrease in Ki-67 proliferation index from 35 to 1%. The patient received 2 cycles of peptide receptor-targeted radionuclide therapy with 177Lu DOTANOC


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Neuroendócrino , Neoplasias Hepáticas , Compostos Organometálicos , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X/métodos , Compostos Radiofarmacêuticos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/secundário , Desdiferenciação Celular , Proliferação de Células , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Antígeno Ki-67/análise , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Metástase Linfática/diagnóstico por imagem , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia
19.
JAMA Surg ; 155(4): 313-321, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101272

RESUMO

Importance: The operative scenarios with the highest postoperative pancreatic fistula (POPF) risk represent situations in which fistula prevention and mitigation strategies have the strongest potential to affect surgical outcomes after pancreaticoduodenectomy. Evidence from studies providing risk stratification is lacking. Objective: To investigate whether pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG), both with externalized transanastomotic stent, is the best reconstruction method for patients at high risk of POPF after pancreaticoduodenectomy. Design, Setting, and Participants: A single-center, phase 3, randomized clinical trial was conducted at the Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy, from July 12, 2017, through March 15, 2019, among adults undergoing elective pancreaticoduodenectomy and considered at high risk for pancreatic fistula after intraoperative assessment of the fistula risk score, some of whom were randomized to undergo PG or PJ. All analyses were performed on an intention-to-treat basis. Interventions: Intervention consisted of PJ or PG, both with externalized transanastomotic stent and octreotide omission. Main Outcomes and Measures: The primary end point was POPF. The secondary end points were Clavien-Dindo grade 3 or higher morbidity, postpancreatectomy hemorrhage, delayed gastric emptying, and average complication burden. Results: A total of 604 patients were screened for eligibility; 82 were at high risk for POPF (fistula risk score, 7-10), and 72 were randomized undergo PG (n = 36; 20 men and 16 women; median age, 65 years [interquartile range, 23-82]) or PJ (n = 36; 26 men and 10 women; median age, 63 years [interquartile range, 35-79]). There was no significant difference in the incidence of POPF between patients who underwent PG and patients who underwent PJ (18 [50.0%] vs 14 [38.9%]; P = .48), but for patients who developed a POPF, the mean (SD) average complication burden was lower for those who underwent PJ than for those who underwent PG (0.25 [0.13] vs 0.39 [0.17]; P = .04). The rates of postpancreatectomy hemorrhage (14 [38.9%] in the PG group vs 9 [25.0%] in the PJ group; P = .31) and delayed gastric emptying (16 [44.4%] in the PG group vs 18 [50.0%] in the PJ group; P = .81) were similar, but patients who underwent PG presented with a significantly higher incidence of Clavien-Dindo grade 3 or higher morbidity than those who underwent PJ (17 [47.2%] vs 8 [22.2%]; P = .047). Conclusions and Relevance: Among patients at the highest risk for POPF, those who underwent PG or PJ experienced similar rates of POPF. However, PG was associated with an increased incidence of Clavien-Dindo grade 3 or higher morbidity and with an increased average complication burden for the patients who developed a POPF. For patients at high risk for pancreatic fistula, PJ with the use of externalized stent and octreotide omission should be considered the most appropriate technical strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT03212196.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Gastrostomia/métodos , Octreotida/uso terapêutico , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Stents , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
World Neurosurg ; 138: 723-731, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32006738

RESUMO

We selected 992 patients who presented to our hospital for treatment and were diagnosed with a neuroendocrine tumor (NET) between January 1, 2008, and December 31, 2018, of whom 17 were diagnosed with primary hepatic neuroendocrine neoplasm. The clinical data were analyzed to study the clinical value of computed tomography (CT) and magnetic resonance imaging data in the diagnosis of the disease. Nine tumors (52.9%) were in the right lobe of the liver, and 9 tumors (52.9%) were single. On imaging, the arterial phase, venous phase, and delayed phase continued to be slightly enhanced, showing low-density change relative to the liver and no portal tumor thrombus formation. Four patients (23.5%) had distant metastases, including adrenal glands, portal interstitial lymph nodes, retroperitoneal lymph nodes, and the gallbladder and peritoneum. In terms of pathological grade, there were 3 cases of NET G2, 2 cases of NET G3, 10 cases of neuroendocrine carcinoma (NEC; including 2 cases of large-cell NEC and 3 cases of small-cell NEC), and 2 cases of hepatocellular carcinoma and small-cell NEC. Seven patients were treated with surgery alone, 4 patients were treated with transcatheter arterial chemoembolization (TACE), and 2 patients were treated with other therapies. Three patients were not treated with surgery and were treated with TACE, etoposide and cisplatin, and octreotide acetate. One patient was discharged automatically. The tumor density on CT images was lower than that of the liver parenchyma; medium-high enhancement was seen in the arterial enhancement phase, and continuous enhancement was seen in the venous phase, but the degree of enhancement was reduced, and rarely with portal tumor thrombosis. Currently, surgery is the main treatment method; however, postoperative combined TACE is superior to surgery in combination with microwave ablation, chemotherapy, and other treatments.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Neuroendócrino/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Técnicas de Ablação , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , Quimioembolização Terapêutica , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Octreotida/uso terapêutico , Tomografia Computadorizada por Raios X
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