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1.
J Neuroendocrinol ; : e13060, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34825753

RESUMO

BACKGROUND: This European Neuroendocrine Tumor Society (ENETS) Expert Consensus document aims to provide practical guidance and standardization for echocardiography in the screening and follow-up of carcinoid heart disease (CHD) in patients with a neuroendocrine tumour (NET) and carcinoid syndrome. METHODS: NET experts within the ENETS Carcinoid Heart Disease Task Force reviewed both general reporting guidelines and specialized scoring systems for transthoracic echocardiography (TTE) in CHD. Based on this review, a dedicated template report was designed by the multidisciplinary working group of cardiologists, oncologists, endocrinologists, gastroenterologists, surgeons and radiologists. RESULTS: We propose a Synoptic Reporting of Echocardiography in Carcinoid Heart Disease which represents an agreed peer reviewed proforma to capture information at the time of referral and enable a detailed outcome of CHD assessment. This includes a systematic and detailed list of structures to evaluate data to capture at the time of reporting of TTE. CONCLUSIONS: Adherence to these reporting guidelines aims to promote homogeneous and detailed evaluation of CHD to secure accurate assessment and allow comparison of studies performed intra- and inter-individually. These guidelines could also facilitate CHD assessment as part of prospective clinical trials to enable standardization of the findings seen in response to therapy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34379772

RESUMO

CONTEXT: Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors. OBJECTIVE: Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) PET/CT in patients with metastatic MTC, and to determine their eligibility for peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively identified patients with metastatic MTC who had 68Ga-DOTA-SSA PET/CT at five centers. We collected characteristics on contrast-enhanced CT, 68Ga-DOTA-SSA and 18F-FDG PET/CT. The efficacy of PRRT was explored in a subgroup of patients. Kaplan-Meier analysis was used to estimate time to treatment failure (TTF) and overall survival (OS). RESULTS: Seventy-one patients were included (10 local recurrence, 61 distant disease). Of the patients with distant disease, 16 (26%) had ≥50% of disease sites with tracer avidity greater than background liver, including 10 (10/61, 16%) with >90%. In 19 patients with contemporaneous contrast-enhanced CT, no disease regions were independently identified on 68Ga-DOTA-SSA PET/CT. Thirty-five patients had an 18F-FDG PET/CT, with 18F-FDG positive/ 68Ga-DOTA-SSA negative metastases identified in 15 (43%). Twenty-one patients had PRRT with a median TTF of 14 months (95%CI 8-25) and a median OS of 63 months (95%CI 21-not reached). Of the entire cohort, the median OS was 323 months (95%CI 152-not reached). Predictors of poorer overall survival included a short calcitonin doubling-time (≤24 months), strong 18F-FDG avidity and age ≥60 years. CONCLUSIONS: The prevalence of high tumour avidity on 68Ga-DOTA-SSA PET/CT is low in the setting of metastatic MTC; nevertheless, PRRT may still be a viable treatment option in select patients.

4.
EJNMMI Phys ; 8(1): 63, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436698

RESUMO

BACKGROUND: Following each cycle of peptide receptor radionuclide therapy (PRRT), absorbed doses by tumors and normal organs are typically calculated from three quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) studies acquired at t1 = 24 h, t2 = 96 h, t3 = 168 h after the first cycle of treatment and from a single study at t1 after the subsequent cycles. In the present study, we have assessed the feasibility of a single SPECT/CT study after each PRRT cycle using a trained multiple linear regression (MLR) model for absorbed dose calculation and have evaluated its impact on patient management. Quantitative [177Lu]-DOTA-TATE SPECT/CT data after PRRT of seventy-two consecutive metastatic neuroendocrine tumors patients were retrospectively evaluated. A set of 40 consecutive studies was used to train the MLR model. The two independent variables of the model included the time of imaging after administration of the treatment and the radiopharmaceutical activity concentration in a given  organ/tumor. The dependent variable was the dose absorbed by the organ/tumor obtained with the standard protocol. For bone marrow dosimetry, the independent variables included the time of imaging, and the blood and remainder of the body activity concentration. The model was evaluated in 32 consecutive patients. Absorbed doses were assessed for kidneys, bone marrow, liver, spleen and tumor sites. RESULTS: There was no difference in management decisions, whether PRRT can be safely continued or not because unsafe absorbed dose to risk organs between the standard and the MLR model-based protocol using a single SPECT/CT study performed at t3 = 168 h after the first cycle and at t1 = 24 h after the subsequent cycles. Cumulative absorbed doses were obtained with mean relative differences of - 0.5% ± 5.4%, 1.6% ± 15.1%, - 6.2% ± 7.3%, - 5.5% ± 5.8% and 2.9% ± 12.7% for kidneys, bone marrow, liver, spleen and tumors, respectively (Pearson's r correlation coefficient 0.99, 0.91, 0.99, 0.99 and 0.97, respectively). CONCLUSION: Dosimetry calculations using a MLR model with a single SPECT/CT study are in good agreement with the standard protocol, while avoiding the use of dosimetry software and enabling improved patient comfort and reduced scanner and staff time.

5.
Eur J Cancer ; 154: 246-252, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298375

RESUMO

BACKGROUND: Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. MATERIAL AND METHODS: This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. RESULTS: Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. CONCLUSIONS: Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.


Assuntos
COVID-19/terapia , Carcinoma Neuroendócrino/terapia , Saúde Global , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/imunologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Harefuah ; 160(7): 419-424, 2021 07.
Artigo em Hebraico | MEDLINE | ID: mdl-34263567

RESUMO

AIMS: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. METHODS: A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed. RESULTS: When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p < 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles. CONCLUSIONS: Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients. DISCUSSION: The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.


Assuntos
Tumores Neuroendócrinos , Exposição à Radiação , Humanos , Tumores Neuroendócrinos/radioterapia , Radioisótopos , Radiometria , Estudos Retrospectivos
7.
Endocrine ; 74(2): 421-429, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34120313

RESUMO

PURPOSE: Type III gastric neuroendocrine neoplasms (g-NENs) have historically been regarded as aggressive tumours, hence current guidelines advocate radical surgery with lymph node dissection. Data on the roles of endoscopic or less extensive surgical resections are more limited. The aim of our study is to evaluate the clinicopathological features and long-term outcomes of patients undergoing endoscopic or limited surgical resection for localised grade 1 or 2 type III g-NENs when compared to radical surgery. METHODS: Retrospective analysis of all patients diagnosed with a localised grade 1 or 2 type III g-NENs across six tertiary NEN centers between 2006 and 2019. RESULTS: Forty-five patients were diagnosed with a potentially resectable grade 1 or 2 type III g-NEN of whom 36 underwent either endoscopic or surgical resection. No statistically significant differences were found between the three resection groups in terms of patient age, tumour location, grade or size. Only tumour size was found to be significantly associated with poor clinical outcome (p = 0.012) and ROC curve analysis identified tumour size >10 mm as a negative predictor (AUC:0.8030, p = 0.0021). Tumours >10 mm were also more likely to be associated with lymph node metastases on imaging and histology (p = 0.039 and p = 0.026 respectively). CONCLUSIONS: Localised grade 1 or 2 type III g-NENs had a good prognosis in this series. Tumour size >10 mm was the most significant prognostic factor affecting patient outcome. Endoscopic resection or limited surgical resection is feasible and safe in small type III g-NENs which demonstrate favourable grade 1/2, well differentiated histology.


Assuntos
Tumores Neuroendócrinos , Neoplasias Gástricas , Humanos , Metástase Linfática , Tumores Neuroendócrinos/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
8.
J Nucl Med ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049983

RESUMO

To assess the efficacy and safety of 177Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET). Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with 177Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and 68Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of 177Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5. Results: Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment 68Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of 177Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available 68Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and 68Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on 68Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia. Conclusion: In patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.

9.
Curr Treat Options Oncol ; 22(4): 28, 2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33641079

RESUMO

OPINION STATEMENT: DIPNECH is caused by an idiopathic proliferation of pulmonary neuroendocrine cells which can lead to bronchiolitis and multifocal lung neuroendocrine tumors. Patients often present with chronic cough and dyspnea. Larger NETs may develop malignant potential. Somatostatin analogs can palliate chronic symptoms, particularly cough. Surgical resection can be considered for relatively large (e.g. >1 cm), progressive tumors.

10.
EJNMMI Phys ; 8(1): 13, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580359

RESUMO

BACKGROUND: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter ß controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68Ga-DOTATATE (68Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of ß and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: ß = 300-1100; 1.0 min/bp: ß = 600-1400 and 0.5 min/bp: ß = 800-2200). An additional analysis adding ß values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. RESULTS: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using ß = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUVmax of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for ß values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. CONCLUSION: 68Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUVmax and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with ß = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.

11.
Rev Endocr Metab Disord ; 22(3): 553-561, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33443717

RESUMO

Carcinoid heart disease (CHD) is a paraneoplastic cardiac manifestation occurring in patients with carcinoid syndrome (CS) and advanced neuroendocrine malignancy. In about 20-40% of patients with CS, chronic exposure to tumor-released circulating vasoactive peptides typically results in right-sided valvular fibrosis leading to valve dysfunction and right heart failure. CHD remains a significant cause of morbidity and mortality. The management of patients with CHD is complex, as both the systemic malignant disease and the heart involvement have to be addressed. Early diagnosis and timely surgical intervention in selected patients are of utmost importance and offer a survival benefit. In patients with advanced carcinoid heart disease, valve replacement surgery is the most effective option to alleviate cardiac symptoms and contribute to survival outcomes. A collaboration of a multidisciplinary team in centers with experience is required to provide optimal patient management. Here, we review the current literature regarding CHD presentation, pathophysiology, diagnostic tools, and available treatment strategies.

12.
Endocrine ; 72(1): 279-286, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33175321

RESUMO

PURPOSE: Neuroendocrine neoplasms (NENs) differ in their biological behavior and growth potential in a way that can be predicted using histological classification and grading systems. A subset of pancreatic NENs (pNENs) may develop a more aggressive phenotype during the course of the disease, associated with an increase in the Ki-67 proliferation index (PI). The purpose of the study was to present the clinical characteristics of these patients. METHODS: Using re-biopsy of growing lesions, we investigated the increase in Ki-67 PI sufficient to change initial grading (G). RESULTS: Of 264 patients with well differentiated (WD) pNENs who showed progressive disease during follow-up, 15 (6%) exhibited an increase in Ki-67 PI at a median time 36.8 (9.3-255.8) months. All neoplasms had WD-morphology: five had G1 (Ki-67 median value 1%), nine G2 (median value 5%), one G3 (25%) grades. Upon change of Ki-67 PI, 3 patients had G2 (8%) and 12 G3 (57.5%) NENs, while all retained their WD-morphology. At last follow-up, eight patients were alive with a median overall survival (OS) of 52.5 (9.5-264.3) months. Μedian OS was shorter in patients who had a change in Ki-67 PI before 36 months compared to those who had a change of Ki-67 PI at a later stage (27.5 95%CI: 11.88-43.06 vs. 120.87 95%CI: 96.05-145.69; log-rank p = 0.018). CONCLUSIONS: During the course of their disease, 6% patients with progressive pNENs develop an increase in Ki-67 PI resulting in an increase in grading status while maintaining their morphology. This process is associated with worse OS when it occurs at an early stage.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Testes Diagnósticos de Rotina , Humanos , Antígeno Ki-67 , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Prognóstico
13.
J Bone Miner Res ; 36(1): 100-109, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32780883

RESUMO

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic and pituitary tumors, and is due to mutations in the coding region of the MEN1 gene, which encodes menin. We investigated a family with identical twins that had MEN1, with different MEN1 tumors. DNA sequence analysis of the MEN1 coding region had not identified any abnormalities and we hypothesized that deletions and mutations involving the untranslated regions may be involved. Informed consent and venous blood samples were obtained from five family members. Sanger DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses were performed using leukocyte DNA. This revealed a heterozygous 596bp deletion (Δ596bp) between nucleotides -1087 and -492 upstream of the translation start site, located within the MEN1 5' untranslated region (UTR), and includes the core promoter and multiple cis-regulatory regions. To investigate the effects of this 5'UTR deletion on MEN1 promoter activity, we generated luciferase reporter constructs, containing either wild-type 842bp or mutant 246bp MEN1 promoter, and transfected them into human embryonic kidney HEK293 and pancreatic neuroendocrine tumor BON-1 cells. This revealed the Δ596bp mutation to result in significant reductions by 37-fold (p < 0.0001) and 16-fold (p < 0.0001) in luciferase expression in HEK293 and BON-1 cells, respectively, compared to wild-type. The effects of this 5'UTR deletion on MEN1 transcription and translation were assessed using qRT-PCR and Western blot analyses, respectively, of mRNA and protein lysates obtained from Epstein-Barr-virus transformed lymphoblastoid cells derived from affected and unaffected individuals. This demonstrated the Δ596bp mutation to result in significant reductions of 84% (p < 0.05) and 88% (p < 0.05) in MEN1 mRNA and menin protein, respectively, compared to unaffected individuals. Thus, our results report the first germline MEN1 5'UTR mutation and highlight the importance of investigating UTRs in MEN1 patients who do not have coding region mutations. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Assuntos
Neoplasia Endócrina Múltipla Tipo 1 , Regiões 5' não Traduzidas/genética , Sequência de Bases , Células HEK293 , Humanos , Neoplasia Endócrina Múltipla Tipo 1/genética , Proteínas Proto-Oncogênicas , Análise de Sequência de DNA
14.
Eur J Cancer ; 144: 200-214, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33370645

RESUMO

Neuroendocrine neoplasms (NENs) are a heterogeneous family of uncommon tumours with challenging diagnosis, clinical management and unique needs that almost always requires a multidisciplinary approach. In the absence of guidance from the scientific literature, along with the rapidly changing data available on the effect of COVID-19, we report how 12 high-volume NEN centres of expertise in 10 countries at different stages of the evolving COVID-19 global pandemic along with members of international neuroendocrine cancer patient societies have suggested to preserve high standards of care for patients with NENs. We review the multidisciplinary management of neuroendocrine neoplasms during the COVID-19 pandemic, and we suggest potential strategies to reduce risk and aid multidisciplinary treatment decision-making. By sharing our joint experiences, we aim to generate recommendations for proceeding to other institutions facing the same challenges.


Assuntos
COVID-19 , Tumor Carcinoide/terapia , Neoplasias Gastrointestinais/terapia , Oncologia/normas , Neoplasias Pancreáticas/terapia , Neoplasias Torácicas/terapia , Tumor Carcinoide/diagnóstico , Consenso , Neoplasias Gastrointestinais/diagnóstico , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Torácicas/diagnóstico
15.
Endocrine ; 70(1): 178-186, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524502

RESUMO

BACKGROUND/AIMS: Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL). METHODS: Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis' validation. RESULTS: We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p = 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n = 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08-1] vs 0.83[0.4-1], respectively; p = 0.929). Among patients with WD-ANEN impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group. CONCLUSIONS: WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs <20 mm is challenged.


Assuntos
Neoplasias do Apêndice , Tumores Neuroendócrinos , Qualidade de Vida , Neoplasias do Apêndice/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/cirurgia , Inquéritos e Questionários
16.
Endocr Relat Cancer ; 27(9): R345-R355, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32590358

RESUMO

Neuroendocrine neoplasms (NENs) occur usually as sporadic tumours; however, rarely, they may arise in the context of a hereditary syndrome, such as multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterised by the combined development of pancreatic NENs (pNENs) together with parathyroid and anterior pituitary tumours. The therapeutic decision for sporadic pNENs patients is multi-disciplinary and complex: based on the grade and stage of the tumor, various options (and their combinations) are considered, such as surgical excision (either curative or for debulking aims), biological drugs (somatostatin analogues), targeted therapies (mTOR inhibitors or tyrosine kinases (TK)/receptors inhibitors), peptide receptor radioligand therapy (PRRT), chemotherapy, and liver-directed therapies. However, treatment of MEN1-related NENs' patients is even more challenging, as these tumours are usually multifocal with co-existing foci of heterogeneous biology and malignant potential, rendering them more resistant to the conventional therapies used in their sporadic counterparts, and therefore associated with a poorer prognosis. Moreover, clinical data using standard therapeutic options in MEN1-related NENs are scarce. Recent preclinical studies have identified potentially new targeted therapeutic options for treating MEN1-associated NENs, such as epigenetic modulators, Wnt pathway-targeting ß-catenin antagonists, Ras signalling modulators, Akt/mTOR signalling modulators, novel somatostatin receptors analogues, anti-angiogenic drugs, as well as MEN1 gene replacement therapy. The present review aims to summarize these novel therapeutic opportunities for NENs developing in the context of MEN1 syndrome, with an emphasis on pancreatic NENs, as they are the most frequent ones studied in MEN1-NENs models to date; moreover, due to the recent shifting nomenclature of 'pituitary adenomas' to 'pituitary neuroendocrine neoplasms', relevant data on MEN1-pituitary tumours, when appropriate, are briefly described.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Feminino , Humanos , Masculino
17.
Eur J Surg Oncol ; 46(11): 2023-2028, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32389525

RESUMO

INTRODUCTION: The lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC. MATERIALS AND METHODS: A retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated. RESULTS: Study population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005). CONCLUSIONS: This study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.


Assuntos
Carcinoma Neuroendócrino/patologia , Linfonodos/patologia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Adulto , Fatores Etários , Idoso , Calcitonina/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Carga Tumoral
19.
Endocr Relat Cancer ; 27(7): R267-R280, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32449694

RESUMO

Incidence of neuroendocrine neoplasia (NEN) is increasing, as is use of health-related quality of life (HRQoL) measurement in clinical trials. Following development of validated questionnaires, HRQoL is widely used to assess outcomes. This review is intended for healthcare professionals and is based on a selection of data published in the last decade. HRQoL is on par with other clinical endpoints such as performance status. Assessments in clinical trials have been particularly useful for monitoring the symptom burden of NEN, for the effects of treatments on patients' lives, and have provided new data allied to the usual clinical endpoints. QoL expressed as quality-adjusted life years (QALYs) have become the most important primary outcome to establish cost-effectiveness in health economic evaluation. From looking at clinical trials over the last 10 years, we see that the quality of HRQoL evidence reported in published studies has improved and, in general, recent studies are likely to be more methodologically robust. Assessment of HRQoL in clinical trials is likely to become a standard part of clinical practice in NEN, as in other cancers. However, clear methods for calculating the clinical meaningfulness of changes in scores are needed. Other limitations of HRQoL measurement include lack of specificity to certain symptom sets and ease of completion and administration. An international group taking a lead on developing HRQoL research specifically in NEN patients is needed to address limitations of the evidence base. In order for greater weight to be placed on HRQoL data, agreement on optimal, validated scoring systems is needed.


Assuntos
Tumores Neuroendócrinos/psicologia , Qualidade de Vida/psicologia , Humanos
20.
J Nucl Med ; 61(9): 1326-1330, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32005769

RESUMO

Esthesioneuroblastoma is rare, with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in esthesioneuroblastoma from 2 referral centers. Methods: Using PRRT databases at 2 European Neuroendocrine Tumor Society Centers of Excellence, cases were sought between 2004 and 2018 of patients who had PRRT with recurrent or metastatic esthesioneuroblastoma deemed unsuitable for further conventional therapies. Evaluations of survival and of response using a composite reference standard were performed. Results: Of 7 patients, 4 had partial response, 2 had disease stabilization, and one had early progression. Possible side effects include worsening cerebrospinal fluid leaks. Median progression-free survival was 17 mo (range, 0-30 mo), and median overall survival was 32 mo (range, 4-53 mo). Conclusion: PRRT shows promising efficacy and moderate survival duration in unresectable locally advanced or metastatic esthesioneuroblastoma warranting larger cohort studies incorporating measures of quality of life.


Assuntos
Estesioneuroblastoma Olfatório/radioterapia , Receptores de Peptídeos/metabolismo , Adulto , Idoso , Estesioneuroblastoma Olfatório/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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