Neuroendocrine tumors of the thymus

Primary neuroendocrine tumors of the thymus (NETTs) are rare and biologically very aggressive neoplasms, usually located in the anterior mediastinal space. They are more frequently observed in males, in their fourth/fifth decades of life. In 50% of cases, NETTs are associated with endocrinopaties [ Cushing's syndrome, acromegaly or Multiple Endocrine Neoplasia-1 (MEN-1) syndrome]. NETTs very often present with invasion of the surrounding mediastinal anatomical structures. Surgery, even in advanced stages, is the mainstay of treatment: a compete resection through a median sternotomy or a combined access (sternotomy + thoracotomy) should be always attempted. Induction chemotherapy (+/- radiotherapy) is usually administered in advanced neoplasms, with the aim to achieve tumor shinkage, increasing, therefore, the chance to obtain a complete resection. Postoperative radiotherapy (+/- chemotherapy) is administered in case of invasive lesions, or incomplete resections. NETTs long-term outcome is poor, even in case of completely resected tumors, due to high risk of recurrence or distant metastases development. Prognosis mainly depends on tumor stage, invasivity, completeness of resection, possible association with endocrinopaties and recurrence/distant metastases development

Early identification of residual disease after neuroendocrine tumor resection using a liquid biopsy multigenomic mRNA signature (NETest)

Introduction Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods This was a multicenter evaluation of surgically treated primary NETs (n = 153). Blood sampling was performed at day 0 and postoperative day (POD) 30. Follow-up included computed tomography/magnetic resonance imaging (CT/MRI), and messenger RNA (mRNA) quantification was performed by polymerase chain reaction (PCR; NETest score: 0–100; normal ≤20). Statistical analyses were performed using the Mann–Whitney U-test, Chi-square test, Kaplan–Meier survival, and area under the receiver operating characteristic curve (AUROC), as appropriate. Data are presented as mean ± standard deviation. Results The NET cohort (n = 153) included 57 patients with pancreatic cancer, 62 patients with small bowel cancer, 27 patients with lung cancer, 4 patients with duodenal cancer, and 3 patients with gastric cancer, while the surgical cohort comprised patients with R0 (n = 102) and R1 and R2 (n = 51) resection. The mean follow-up time was 14 months (range 3–68). The NETest was positive in 153/153 (100%) samples preoperatively (mean levels of 68 ± 28). In the R0 cohort, POD30 levels decreased from 62 ± 28 to 22 ± 20 (p 20 had image-identifiable recurrence. An NETest score of >20 predicted recurrence with 100% sensitivity and correlated with residual disease (Chi-square 17.1, p 20 predicted radiologically recurrent disease with 94% accuracy and 100% sensitivity. R0 resection appears to be ineffective in approximately 30% of patients. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management

Early Identification of Residual Disease After Neuroendocrine Tumor Resection Using a Liquid Biopsy Multigenomic mRNA Signature (NETest)

Introduction: Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods: This was a multicenter evaluation of surgically treated primary NETs (n = 153). Blood sampling was performed at day 0 and postoperative day (POD) 30. Follow-up included computed tomography/magnetic resonance imaging (CT/MRI), and messenger RNA (mRNA) quantification was performed by polymerase chain reaction (PCR; NETest score: 0–100; normal ≤20). Statistical analyses were performed using the Mann–Whitney U-test, Chi-square test, Kaplan–Meier survival, and area under the receiver operating characteristic curve (AUROC), as appropriate. Data are presented as mean ± standard deviation. Results: The NET cohort (n = 153) included 57 patients with pancreatic cancer, 62 patients with small bowel cancer, 27 patients with lung cancer, 4 patients with duodenal cancer, and 3 patients with gastric cancer, while the surgical cohort comprised patients with R0 (n = 102) and R1 and R2 (n = 51) resection. The mean follow-up time was 14 months (range 3–68). The NETest was positive in 153/153 (100%) samples preoperatively (mean levels of 68 ± 28). In the R0 cohort, POD30 levels decreased from 62 ± 28 to 22 ± 20 (p 20 had image-identifiable recurrence. An NETest score of >20 predicted recurrence with 100% sensitivity and correlated with residual disease (Chi-square 17.1, p 20 predicted radiologically recurrent disease with 94% accuracy and 100% sensitivity. R0 resection appears to be ineffective in approximately 30% of patients. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

Background: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript "liquid biopsy" (NETest) in BPC for diagnosis and monitoring of the disease status. Aim: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. Material and Methods: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. Results: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood. samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25-0.31). Conclusions: Elevated NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression

"Malattie dell’apparato respiratorio. Pneumologia e chirurgia toracica"

La tecnica tomografica permette di riconoscere con accuratezza la sede, le dimensioni, le porzioni anatomiche del polmone e le caratteristiche dei processi patologici. Esistono due tecniche di tomografia a emissione, quella a emissione di singolo fotone, la SPET, e quella a emissione di positroni, la PET (Tab. 7-11). Al fine di ottenere un'accurata diagnosi e una corretta interpretazione delle immagini scintigrafiche è diventato fondamentale disporre affianco alle immagini funzionali (SPET o PET) immagini di tipo morfologico (Rx, TC e RM). Inizialmente si è provveduto a effettuare fusioni di immagini provenienti da apparecchiature differenti e acquisite in tempi diversi mediante l'utilizzo di opportuni sistemi software. Attualmente si dispone però di sistemi hardware ibridi, ovvero un unico sistema con integrati SPET o PET e CT o più di recente SPET o PET e RM, in uno stesso gantry, con cui le immagini di due modalità vengono acquisite in un'unica sessione e co-registrate, senza che il paziente si muova dal lettino. Si ottengono così immagini multimodali, funzionali e morfologiche contemporaneamente. La utilizzazione di macchine SPECT/CT per ottenere contemporaneamente e durante un singolo esame sia le immagini di medicina nucleare (scintigrafie polmonari perfusive /ventilatorie) che la TC, rappresentano la migliore scelta tecnica per lo studio delle patologie polmonari. L'indagine che visualizza la distribuzione e la concentrazione del radiofarmaco nei due polmoni o nel torace viene definita scintigrafia statica. Le proiezioni possibili sono: anteriore, posteriore, laterali e oblique a 45° anteriore e posteriore. Se l'esame viene esteso all'intero corpo nelle due proiezioni, anteriore e posteriore, viene detto total body (IB) o whole body (WB). Le immagini WB sono utili nella stadiazione e ristadiazione di pazienti con patologie neoplastiche o infiammatorie con possibile disseminazione in varie sedi come anche nel ricercare patologie la cui sede di origine non è nota. Tale indagine WB rappresenta il primo step per guidare indagini su specifici distretti anatomici sede di patologie. Quando si acquisiscono immagini in sequenza sul torace è possibile ottenere la visualizzazione delle modificazioni spaziali della concentrazione del radiofarmaco nel tempo. Queste vengono definite scintigrafie dinamiche. Queste ultime sono caratterizzate dalla frequenza temporale, con cui vengono ottenute le immagini, e dal tempo di durata dell'esame (per esempio: 1 immagine ogni minuto per 60 minuti). Si può dire che nella maggioranza dei casi i radiofarmaci impiegati in pneumologia si distribuiscono nelle porzioni integre e normo-funzionanti del polmone, mentre nei processi patologici la loro concentrazione appare ridotta o assente. La lesione viene definita ipofissante, non fissante, fredda. Quando si utilizzano radiofarmaci con specifico tropismo per il tessuto patologico, la lesione accumula il radiofarmaco e si mette in evidenza come area Iperattiva o positiva. I radiofarmaci che permettono questo tipo di immagine sono detti indicatori positivi di lesione