Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Riechelmann, Rachel P.; Weschenfelder, Rui; Costa, Frederico; Andrade, Alexander de; Osvaldt, Alessandro Bersch; Quidute, Ana Rosa Pinto; Santos, A. Dos; Hoff, Ana Amelia O.; Gumz, Brenda Pires; Buchpiguel, Carlos Alberto; Pereira, Bruno; Lourenço, Delmar M.; Filho, Duílio Reis da Rocha; Fonseca, Eduardo A.; Mello, Eduardo Linhares Riello de; Makdissi, Fábio F.; Waechter, Fábio Luiz; Carnevale, Francisco César; Filho, George Coura; Paulo, Gustavo Andrade de; Girotto, Gustavo; Neto, João Batista de Andrade; Glasberg, João; Casali-da-Rocha, José Claudio; Rêgo, Juliana Florinda M.; Meirelles, Luciana Rodrigues de; Hajjar, Ludhmila Abrahão; Menezes, Marcos Roberto de; Bronstein, Marcello D.; Sapienza, Marcelo Tatit; Fragoso, Maria Candida Barisson Villares; Pereira, Maria Adelaide Albergaria; Barros, Milton; Forones, Nora Manoukian; Amaral, Paulo Cezar Galvão do; Medeiros, Raphael Salles Scortegagna de; Araújo, Raphael L. C.; Bezerra, Régis Otaviano França; Peixoto, Renata D’Alpino; Aguiar, Samuel; Ribeiro, Ulysses; Pfiffer, Tatiana; Hoff, Paulo M.; Coutinho, Anelisa K.

doi:10.3332/ecancer.2017.716

Cited by 16 publications

(23 citation statements)

References 130 publications

(182 reference statements)

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“…The optimal medical management of asymptomatic, unresectable NETs is controversial , in part because a substantial proportion of patients can remain progression free—even without treatment—for months or even years. For this reason, many authors and clinical guidelines recommend active surveillance in asymptomatic patients with low‐grade, nonfunctional tumors. However, this approach has an important drawback: the unpredictable clinical course of these tumors, which tend to progress, even when the biological characteristics of the tumor are favorable .…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Randomized Clinical Trials Comparing Active Treatment with Placebo in Metastatic Neuroendocrine Tumors

et al. 2019

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Background. Most guidelines still recommend active surveillance for patients with asymptomatic, unresectable neuroendocrine tumors (NETs). However, recent findings from several randomized placebo-controlled trials suggest that most patients would benefit from active treatment. We conducted a metaanalysis of pooled outcomes from clinical trials in which an active treatment arm was compared with placebo to determine whether active treatment provides a survival advantage. Materials and Methods. This meta-analysis evaluated six trials that compared a medication with placebo in patients with an asymptomatic, metastatic NET. The trials were heterogenous with regard to the active medication (octreotide, lanreotide, sunitinib, everolimus, Lu-Dotatate) and tumor localizations (gastrointestinal, pancreas, lung). Overall survival (OS) and progression-free survival (PFS) for the placebo and active treatment arms were obtained from individual trial data and combined to obtain pooled outcomes. Results. The individual trials all reported significantly better PFS outcomes for active treatment. The pooled data confirmed this advantage. At months 3, 6, 12, 18, and 24, pooled PFS rates for the placebo and treatment arms, respectively, were 92.9% versus 96.9%; 54.3% versus 83.7%; 35.5% versus 68.5%; 25.1% versus 54.7%; and 17.7% versus 61.0%. OS was also higher in the active treatment groups. At months 6, 12, 24, 36, 48, and 60, OS rates (placebo vs. active treatment), respectively, were 88.1% versus 93.4%; 84.1% versus 86.2%; 67.4% versus 76%; 56.6% versus 64.4%; 49.9% versus 61.0%; and 41.7% versus 45.9%. Conclusion. This meta-analysis confirms findings from recent clinical trials indicating that active treatment yields better survival outcomes than placebo. Importantly, these findings were obtained across a wide range of patient profiles and diverse medical treatments for metastatic NETs. Given the lack of reliable prognostic factors to determine a priori which patients are unlikely to benefit from active treatment, these findings support early treatment in most patients. The Oncologist 2019;24:e1315-e1320 Implications for Practice: Although most guidelines still recommend active surveillance for patients diagnosed with metastatic neuroendocrine tumors, the results of this meta-analysis, together with recent data from key clinical trials, suggest that most patients could benefit from upfront active treatment. However, more data are needed to confirm this.

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Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Randomized Clinical Trials Comparing Active Treatment with Placebo in Metastatic Neuroendocrine Tumors

et al. 2019

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“…However, there is no evidence that treating CS delays the onset of valvular damage. When CHD is installed, surgical valve replacement is the only effective therapy, although associated with high morbi-mortality [ 5 , 6 ]. Pharmacological and nonpharmacological treatments for right heart dysfunction, such as salt and water restrictions, diuretics and digitalis drugs, are used as symptomatic strategies.…”

Section: Introductionmentioning

confidence: 99%

“…Pharmacological and nonpharmacological treatments for right heart dysfunction, such as salt and water restrictions, diuretics and digitalis drugs, are used as symptomatic strategies. The diagnosis of CHD is made by an echocardiographic evaluation with Doppler [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

High tumour burden, delayed diagnosis and history of cardiovascular disease may be associated with carcinoid heart disease

Alves

Mesquita

Silva

et al. 2018

ecancer

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BackgroundPatients with carcinoid syndrome (CS) may present carcinoid heart disease (CHD) but prognostic factors are not entirely understood.Patients and MethodsRetrospective study of patients with metastatic neuroendocrine tumours (NETs) and CS and/or abnormal 24-hour-urinary 5-hydroxiindolacetic acid. CHD was defined as moderate to severe tricuspid or pulmonary regurgitation in the echocardiogram.ResultsThe frequency of CHD among 42 patients was 38% (95% confidence interval [CI]: 23%–54%). CHD was associated with higher volume of liver metastases (odds ratio [OR] 13.86, 95% CI: 2.57–74.68, p = 0.002). Time from CS symptoms to NET diagnosis was borderline significant (p = 0.08). When CHD was defined as at least mild tricuspide regurgitation, the frequency of CHD was 45% and it was associated with cardiovascular comorbidities (OR: 6.58, 95% CI: 1.09; 39.78, p = 0.040).ConclusionCHD was frequent among patients with CS, significantly associated with high liver tumour burden, and likely linked to the history of cardiovascular disease and longer time of CS.

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“…by their prognosis, considering histopathological features and proliferative index (Riechelmann et al, 2017). According to the current classification of WHO and ENETS (European Society of Neuroendocrine Tumor), the NET-G1 type neuroendocrine tumor would have a mitotic count of <2 by 2 mm2 (in a 40x magnification) and a Ki-67 (proliferative index) <2%.…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine Neoplasm in Cecal Appendix: A Case Report

Feitosa

Rodrigues

Felix

et al. 2019

AIMJ

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Although neuroendocrine neoplasms are relatively uncommon entities, the appendix is a site with relatively frequent emergence of this pathology and its precise diagnosis and clinical management have been a challenge for practitioners. This paper aims to present and discuss a case report of neuroendocrine neoplasia in the appendix of a patient with acute abdomen who underwent appendectomy. A 46-year-old man referred to the Emergency Department complaining of abdominal pain in the right iliac fossa and signs of peritoneal irritation. After diagnosis of acute appendicitis, the patient underwent appendectomy. In a macroscopic analysis, an area of 1.9 cm long, hardened, irregular and yellowish shapes was noted in the distal third of the appendix. Histopathological analysis showed neoplasia consisting of invasive islands of monotonous rounded epithelioid cells, large areas of necrosis, high mitotic activity, neural and angiolymphatic invasion and extension to adipose tissue compatible with invasion of the mesoappendix. Circumferential resection was compromised, suggesting the persistence of neoplasia in the patient even after the surgical approach, which would probably recommend the need for surgical approach. Therefore, the importance of sending collected materials for anatomopathological analysis is emphasized, since it helps in the clinical evaluation, in the etiological diagnosis, guides the medical conduct in the evolution of the case, as well as assisting in family mourning in cases of mortality.Keywords: Neuroendocrine tumor, Appendix, Histopathological analysis.

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Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Cited by 16 publications

References 130 publications

Meta-Analysis of Randomized Clinical Trials Comparing Active Treatment with Placebo in Metastatic Neuroendocrine Tumors

Meta-Analysis of Randomized Clinical Trials Comparing Active Treatment with Placebo in Metastatic Neuroendocrine Tumors

High tumour burden, delayed diagnosis and history of cardiovascular disease may be associated with carcinoid heart disease

Neuroendocrine Neoplasm in Cecal Appendix: A Case Report

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