Plasma Chromogranin A Response to Octreotide Test: Prognostic Value for Clinical Outcome in Endocrine Digestive Tumors

Massironi, Sara; Conte, Dario; Sciola, V.; Spampatti, Matilde Pia; Ciafardini, C.; Valenti, L.; Rossi, Roberta; Peracchi, M.

doi:10.1038/ajg.2010.154

Cited by 55 publications

(37 citation statements)

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“…A variety of metrics have been assessed to evaluate the use of these markers. For example, a 30% decrease in CgA (from pretreatment levels) is considered predictive of SSA efficacy [38], while an increase in three consecutive measurements is considered to anticipate relapse after midgut surgery [39]. Some authors proposed that alterations of ≥25% in CgA may have good sensitivities (>75%) and specificities (>85%) for predicting disease events [33] while others suggested that levels twice the ULN (∼300 µg/l or 300 ng/ml) [32] or higher (≥600) [40] are effective predictors of disease progression.…”

Section: Discussionmentioning

confidence: 99%

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

et al. 2016

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Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical evaluation and imaging are limited due to the lack of sensitivity and disease indolence. We assessed the NETest as a predictive and prognostic marker of progression in a long-term follow-up study. Methods: GEP-NETs (n = 34) followed for a median 4 years (2.2-5.4) were evaluated. WHO tumor grade/stage grade 1: n = 17, grade 2: n = 14, grade 3: n = 1 (for 2, no grade was available); 31 (91%) were stage IV. Baseline and longitudinal imaging and blood biomarkers were available in all, and progression was defined per standard clinical protocols (RECIST 1.0). The NETest was measured by quantitative PCR of blood and multianalyte algorithmic analysis (disease activity scaled 0-100% with low <40% and high activity risk cutoffs >80%); chromogranin A (CgA) was measured by radioimmunoassay (normal <150 µg/l); progression-free survival (PFS) was analyzed by Cox proportional-hazard regression and Kaplan-Meier analysis. Results: At baseline, 100% were NETest positive, and CgA was elevated in 50%. The only baseline variable (Cox modeling) associated with PFS was NETest (hazard ratio = 1.022, 95% confidence interval = 1.005-1.04; p < 0.012). Using Kaplan-Meier analyses, the baseline NETest (>80%) was significantly associated (p = 0.01) with disease progression (median PFS 0.68 vs. 2.78 years with <40% levels). The NETest was more informative (96%) than CgA changes (>25%) in consistently predicting disease alterations (40%, p < 2 × 10^-5, χ² = 18). The NETest had an earlier time point change than imaging (1.02 ± 0.15 years). Baseline NETest levels >40% in stable disease were 100% prognostic of disease progression versus CgA (χ² = 5, p < 0.03). Baseline NETest values <40% accurately (100%) predicted stability over 5 years (p = 0.05, χ² = 3.8 vs. CgA). Conclusion: The NETest correlated with a well-differentiated GEP-NET clinical status. The NETest has predictive and prognostic utility for GEP-NETs identifying clinically actionable alterations ∼1 year before image-based evidence of progression.

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Section: Discussionmentioning

confidence: 99%

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

et al. 2016

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“…However, these results need confirmation in further prospective studies, validation in different settings such as digestive endocrine tumors (carcinoids) as well as testing with other treatment options such as peptide receptor radionuclide therapy and chemotherapy. Recent data from our own institution demonstrated that a ≥30% decrease in plasma CgA levels after acute octreotide administration has prognostic relevance for GEP-NEN patients as it allows discriminating between patients more likely to respond to chronic somatostatin analogue treatment and those likely to be unresponsive [17]. Accordingly, determining plasma CgA levels may be helpful in diagnosing NENs in a more precise way and can be relevant in delineating the prognosis by predicting disease recurrence, disease outcome and treatment effectiveness [18].…”

Section: Introductionmentioning

confidence: 99%

Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

et al. 2014

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Background/Aims: Plasma chromogranin A (CgA) is the most widely used biochemical biomarker in the diagnostic workup and follow-up of gastroenteropancreatic neuroendo- crine neoplasms (GEP-NENs). Herein, we assessed the clinical utility of CgA in diagnosing and monitoring a large series of GEP-NENs. Patients and Methods: A total of 181 GEP-NEN patients (87 males, 94 females) with pancreatic (n = 81) and gastrointestinal neoplasms (n = 100) were included; 99 patients had grade (G)1 NENs (Ki-67 ≤2%), 57 G2 NENs (Ki-67 3-20%) and 25 G3 NENs (Ki-67 >20%); 81 patients had tumor-node-metastasis (TNM) stage I, 14 stage II, 17 stage III and 69 stage IV cancer. For every patient, CgA values were assessed at diagnosis and during follow-up. Results: At diagnosis, the CgA values were above the upper reference limit in 148 patients (82%); the median CgA levels were significantly higher in functioning than in nonfunctioning tumors (295 vs. 43 U/l; p = 0.0001) as well as significantly higher in patients with metastases than in those without metastases (324.5 vs. 42 U/l; p = 0.0001). In logistic regression analysis, baseline CgA levels were significantly associated with Ki-67 index (p < 0.0001) and TNM stage (p < 0.0001) independently of the age and sex of the patient and the primary site of the tumor. The overall 5- and 10-year survival rates were 74 and 64.5%, respectively. A low Ki-67 index, the type of treatment and an early CgA decrease after treatment were positively correlated with the survival rate. After radical surgery, 15/95 patients relapsed, and an increase in CgA values anticipated the clinical and objective disease recurrence after a period of 9-12 months. Conclusions: In GEP-NENs, plasma CgA has a significant prognostic relevance.

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“…Высокий уровень ХГ-А чаще наблю-дается при НЭО средних отделов (midgut) ЖКТ, особенно при метастазах в печень, а также при нефункционирующих опухолях поджелудочной железы [44,45]. Следует от-метить, что повышение ХГ-А отмечается у пациентов, получающих терапию ингибито-рами протонной помпы, страдающих хрони-ческим атрофическим гастритом, почечной недостаточностью, застойной сердечной не-достаточностью и циррозом печени.…”

Section: лабораторные тестыunclassified

Radionuclide imaging and therapy in patients with neuroendocrine tumors

et al. 2018

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Нейроэндокринные опухоли представляют собой гетерогенную группу опухолей, возникающих из энтерохром-аффинных клеток диффузной нейроэндокринной системы и встречающихся в 0,5% случаев всех новообразований. За последние годы отмечается значительный рост заболеваемости нейроэндокринными опухолями, что безуслов-но связано с усовершенствованием методов их диагностики. Однако, несмотря на значительные успехи в изучении биологических и молекулярных механизмов поведения данной группы заболеваний, формирование единого алго-ритма диагностики и лечения нейроэндокринных опухолей остается затруднительным и по сей день. Лечение нейроэндокринных опухолей во многом зависит от их функционального статуса и стадии заболевания. Наиболее предпочтительным подходом в лечении локализованных форм нейроэндокринных опухолей остается хирургиче-ский. В то же время для больных с распространенными процессами, характеризующимися наличием отдаленных метастазов, на сегодняшний день доступен широкий спектр терапевтических стратегий. Среди них можно выде-лить контроль над синдромами, ассоциированными с гиперсекрецией тех или иных гормонов, выполнение цито-редуктивных вмешательств, системную химиотерапию, применение аналогов соматостатина, а также радиотар-гетную терапию. Однако алгоритм выбора того или иного терапевтического подхода в современной клинической практике у разнородной группы больных с нейроэндокринными опухолями требует дальнейшего обсуждения. Ключевые слова: нейроэндокринные опухоли, радионуклидная диагностика, радиотаргетная терапия, аналоги соматостатина, октреотид, онкология, радиология.Neuroendocrine tumors (NETs) are heterogeneous group of the tumors that arise from the enterochromaffin cells of the diffuse neuroendocrine system and occurr in 0.5% of all neoplasms. Recently there has been a significant increase in the incidence of neuroendocrine tumors, which is undoubtedly associated with the improvement of diagnostic methods. However, despite significant success in studying the biological and molecular mechanisms of its behavior, a single algorithm for the diagnosis and treatment of neuroendocrine tumors remains unclear today. Treatment of neuroendocrine tumors largely depends on their functional status and the stage of the disease. While the treatment of localized NETs is surgical resection, varieties of therapeutic options are available for patients with advanced NETs. These include medical control of excess hormone levels and associated symptoms, cytoreductive surgery for patients with advanced disease, systemic chemotherapy, somatostatin analogues, and peptide receptor-targeted radionuclide therapy. However, the right choice of the therapeutic approach in current clinical practice in heterogeneous group of patients with neuroendocrine tumors requires further discussion.

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Plasma Chromogranin A Response to Octreotide Test: Prognostic Value for Clinical Outcome in Endocrine Digestive Tumors

Abstract: In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.

Cited by 55 publications

References 39 publications

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

Radionuclide imaging and therapy in patients with neuroendocrine tumors

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