Modlin IM, Drozdov I, Alaimo D, Callahan S, Teixeira N, Bodei L, Kidd M

A critical requirement in neuroendocrine tumor (NET) management is a blood biomarker test that is sensitive, specific and reproducible. We evaluated the NETest detect tumors, compared it with chromogranin A (CgA) and examined the confounding effect of proton pump inhibitors (PPIs), which cause falsely elevated CgA levels. NETest...

Modlin IM, Kidd M, Aslanian H, Bodei L, Drozdov I

A critical requirement in neuroendocrine tumor (NET) management is a sensitive, specific and reproducible blood biomarker test. We evaluated the NETest versus chromogranin A (CgA), pancreastatin (PST) and neurokinin A (NKA). NETest was >92% accurate. CgA was 76% accurate, PST 63% accurate and NKA 39% accurate...

Modlin IM, Kidd M, Bodei L, Drozdov I, Aslanian H

This study demonstrates that a blood-based multianalyte NET gene transcript measurement of well-differentiated small intestinal and pancreatic neuroendocrine tumor disease is sensitive (94-98%) and specific and outperforms the current monoanalyte diagnostic strategy of plasma CgA (52%) measurement...

Pęczkowska M, Cwikla J, Kidd M, Lewczuk A, Kolasinska-Ćwikła A, Niec D, Michałowska I, Prejbisz A, Januszewicz A, Chiarelli J, Bodei L, Modlin I

Paragangliomas and pheochromocytomas (PPGLs) exhibit variable malignancy, which is difficult to determine by histopathology, amine measurements or tissue genetic analyses. We evaluated the NETest as a diagnostic and prognostic for these tumors. Circulating NET transcript analysis is positive (100% diagnostic) in well-differentiated...

Kidd M, Modlin IM, Drozdov I, Aslanian H, Bodei L, Matar S, Chung KM

No effective blood biomarker exists to detect and clinically manage bronchopulmonary (BP) neuroendocrine tumors (NET). We the blood-based 51 NET-specific transcript set for diagnosis and monitoring and evaluated clinical performance metrics in BPNETs. All 51 genes were identified in BPNET transcriptomes, tumor samples...

Filosso PL, Kidd M, Roffinella M, et al

The management of bronchopulmonary neuroendocrine tumors (BPNETs) is difficult, since imaging, histology and bio-markers have a limited value in diagnosis, predicting outcome and defining therapeutic efficacy. We evaluated a NET multi gene blood test (NETest) to diagnose BPNETs, assess disease status and evaluate surgical resection...

Pavel M, Jann H, Prasad V, Drozdov I, Modlin IM, Kidd M

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...

Pęczkowska M, Cwikla J, Kidd M, Lewczuk A, Kolasinska-Ćwikła A, Niec D, Michałowska I, Prejbisz A, Januszewicz A, Chiarelli J, Bodei L, Modlin I

Spider plot identifying the changes from baseline. All three patients who continued to progress or developed progressive disease (arrows) exhibited a positive change in the NETest score. This who were stable or underwent curative surgery demonstrated a decrease in scores...

Liu E, Paulson S, Gulati A, Freudman J, Grosh W, Kafer S, Wickremesinghe PC, Salem RR, Bodei L

Clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. The NETest was evaluate for management of neuroendocrine tumor disease (NETs) in a real-world study (USA registry (RegisterNET: NCT02270567). The NETest was the only feature linked to PFS (OR: 6.1, p<0.0001)...

Ćwikła JB, Bodei L, Cwikla A, Sankowski A, Alaimo D, Modlin IM, Kidd M

Early and precise delineation of therapeutic responses are key issues in neuroendocrine neoplasm/tumor management. Imaging is currently used but exhibits limitations in sensitivity and specificity. The utility of biomarkers is unclear. We evaluated the NETest in somatostatin analog-treated GEP-NETs and compared it to CgA as a monitor...

Bodei L, Kidd M, Modlin IM, Severi S, Drozdov I, Nicolini S, Kwekkeboom DJ, Krenning EP, Baum RP, Paganelli G

We evalutated the NETest prior to PRRT, during therapy and at 3 and 6 months after therapy in 54 177Lu-treated GEP-NET. The NETest accurately correlated with standard morphologic and functional imaging and therefore with treatment response and outcome of therapy.

Pavel M, Jann H, Prasad V, Drozdov I, Modlin IM, Kidd M

Time prior to disease progression identified by imaging. A rise in NETest >70% occurred a median 1.62 years before imaging confirmation of tumor progression (failure of therapy). A rise in NETest >80% occurred a median 0.76 years before imaging confirmation of tumor progression (failure of therapy).

Liu E, Paulson S, Gulati A, Freudman J, Grosh W, Kafer S, Wickremesinghe PC, Salem RR, Bodei L

Relationship between NETest score and clinical management
A. In the watch-and-wait cohort, a low score was associated with in no treatment intervention in 93%. A high score led to a treatment intervention in 83%.
B. In the treatment cohort, a low score was associated with no change in treatment in...

Modlin IM, Frilling AF, Salem RR, Alaimo D, Drymousis P, Wasan HS, Callahan S, Faiz O, Weng L, Teixeira NS, Bodei L, Drozdov I, Kidd M

Surgery significantly reduced NETest levels consistent with removal of the source of the circulating gene expression.

In those with surgical cures (NED – no evidence of disease), elevated levels after surgery predicted disease recurrence...

Filosso PL, Kidd M, Roffinella M, Lewczuk A, Chung KM, Kolasinska-Cwikla A, Cwikla J, Lowczak A, Doboszynska A, Malczewska A, Catalano M, Zunino V, Boita M, Arvat E, Cristofori R, Guerrera F, Oliaro A, Tesselaar M, Buikhuisen W, Kos-Kudla B, Papotti M, Bodei L, Drozdov I, Modlin I

Current biomarkers used in BPNET management are single analytes and have a low utility, e.g., CgA (Chromogranin A) or NSE (neuron specific enolase). Histology and imaging have a high clinical utility. Imaging is especially useful in assessing disease evolution over time. Monoanalytes have minimal utility in assessing surgical...

Bodei L, Kidd M, Modlin IM, Severi S, Drozdov I, Nicolini S, Kwekkeboom DJ, Krenning EP, Baum RP, Paganelli G.

We developed a complementary diagnostic based on circulating gene expression measurements (Ome index) and grading which can be used to predict response to PRRT. The accuracy of this Prediction Quotient in this discovery cohort of 54 NETs was 94%...

Kidd M, Modlin IM

Patients with neuroendocrine tumors are increasingly treated with peptide receptor radionuclide therapy. However, somatostatin receptor expression evaluation cannot predict who will respond to therapy. Additional criteria to identity which patients are most likely to respond and those who will develop radiation-associated sequelae...

Bodei L, Kidd MS, Singh A, van der Zwan WA, Severi S, Drozdov IA, Cwikla J, Baum RP, Kwekkeboom DJ, Paganelli G, Krenning EP, Modlin IM

We validated the PRRT Prediction Quotient (PPQ) as a complementary diagnostic in two different PRRT cohorts. The accuracy of this Prediction Quotient in the validation cohorts was 95%. It was significantly more predictive and of more clinical better than either grade (70%) or elevated chromogranin A (50%). Other parameters like SUVmax and FDG...