The Vegf Pathway in Patients with Pancreatic Neuroendocrine Tumors: Efficacy of Everolimus by Baseline Marker Level, and Prognostic and Predictive Effect Analyses from Radiant-3

Yao, James C.; Shah, Manisha H.; Panneerselvam, Ashok; Stergiopoulos, Sotirios; Chen, D.; Ito, Takayoshi; Pavel, Marianne; Faivre, S.; Niccoli, Patricia; Raoul, Jean-Luc; Bang, Yung Jue; Borbath, Ivan; Huang, Xin; Patyna, Shem; Chao, Richard C.; Raymond, Éric; Wiedenmann, Bertram; Capdevila, Jaume; Herder, Wouter W. de; Metzer, C.; Salazar, Renato; Hörsch, Dieter; Öberg, Kjell; Grande, E.; Castellano, Daniel; García‐Carbonero, Rocío; Teulé, Alexandre; Durán, Ignacio; Fuster, José Luís; Sevilla, Isabel; Escudero, P.; Sastre, Javier; Casanovas, Oriol; Ortega, Luís; Earl, Julie; Díez, Juan J.; Velasco, G. De; Longo, Francesca; Navarro, Alejandro; Pachón, Vanessa; Carrato, Alfredo; Craig, Jonathan C.; Cheung, Matthew C.; Law, Calvin; Singh, Simron; Seitz, Jean‐François; Smith, David J.; O’Toole, Dermot; Lepère, Céline; Dromain, Clarisse; Gorana, A.; Mitry, Emmanuel; Ducreux, Michel; Walter, Thomas; Baudin, Éric; Kurtz, James; Ruszniewski, Philippe; Bengrine-Lefèvre, Léïla; Cadiot, G.; Dominguez-Tinajero, Sophie; Kraemer, S; Meyer, Tim; Caplin, Martyn; Reed, Nicholas; Qian, Wendi; Lao-Sirieix, S.; Armstrong, G.; Valle, Juan W.; Tablot, D.; Cunningham, David; Corrie, Pippa; Claringbold, Phillip G.; Turner, J. Harvey; Dreyer, Chantal; Hentic, Olivia; Zappa, M.; Hammel, Pascal; Benameur, M.; Mateescu, Cristian; O’Connor, Juan Manuel; Belli, Susana; Pesce, Verónica; Bestani, Claudia; Mendez, G.; Dominichini, E.; Cabanne, A.; López, Gonzalo; Marmissolle, F.; Roca, Elisa; Alonso, Vicente; Antón-Aparicio, Luis; Fonseca, Paula; Reina, Juan José; Manzano, José Luís; Alonso-Jara, J.; Alfonso, Pilar; Leyden, John; Jones, S C Bowen; Foster, L. Bryant; Mansoor, Wasat; Hubner, Richard A; Chakrabarty, Bipasha; Mohamed, Zareen; Pinato, David J.; Sharma, R.; Papadaki, Chara; Pentheroudakis, George; Ruiperez, Andrés Cervantes; Lagoudaki, Eleni; Petrakis, Dimitrios; Souglakos, John; Braun, E; Georgoulias, Vasilis; Mavroudis, D.; Pavlidis, Nicholas; Shimoi, Tatsunori; Sasaki, Ei; Kudo, Masashi; Shimoyama, Tatsu; Omuro, Yasushi; Okamoto, Ryuichi; Maeda, Yasunari; Sasaki, Takanori; Маркович, А. А.; Емельянова, Г. С.; Gorbounova, Vera; Bruzgin, V.; Орел, Н Ф

doi:10.1093/annonc/mds405

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, new potentially specific biomarkers of tumor responses to antiangiogenic therapies, e.g., plasma levels of placental growth factor, vascular endothelial growth factor (VEGF), or the soluble forms of its receptor (sVEGFR-1 and -2), have been studied in patients with various malignancies. For NETs, those biomarkers were evaluated only in a post hoc analysis of the RADIANT-3 trial, in which their baseline levels were not predictive of everolimus efficacy, despite their prognostic value (Yao et al 2012b). Further investigation is warranted to determine whether early decreases in those markers during treatment could be predictive of better outcomes, particularly for patients treated with agents targeting the VEGF pathway, like bevacizumab.…”

Section: Biological Markers Tumor Progression and Therapeutic Respomentioning

confidence: 99%

Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Mestier¹,

Dromain²,

d’Assignies³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies.

show abstract

Section: Biological Markers Tumor Progression and Therapeutic Respomentioning

confidence: 99%

Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Mestier¹,

Dromain²,

d’Assignies³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Elevated baseline levels of neuron-specific enolase (NSE) and chromogranin A (CgA) were shown to be prognostic for poor survival in pNETs under everolimus [ 1 , 37 ]. In our study cohort, DADCmin correlated better with OS than baseline CgA, while there was no significant correlation with pretherapeutic NSE levels, which might be explained by a small sample size.…”

Section: Discussionmentioning

confidence: 99%

Treatment Assessment of pNET and NELM after Everolimus by Quantitative MRI Parameters

et al. 2022

View full text Add to dashboard Cite

Assessment of treatment response to targeted therapies such as everolimus is difficult, especially in slow-growing tumors such as NETs. In this retrospective study, 17 patients with pancreatic neuroendocrine tumors (pNETs) and hepatic metastases (NELMs) (42 target lesions) who received everolimus were analyzed. Intralesional signal intensities (SI) of non-contrast T1w, T2w and DCE imaging, and apparent diffusion coefficients (ADCmean and ADCmin) of DWI, were measured on baseline and first follow-up MRI after everolimus initiation. Response assessment was categorized according to progression-free survival (PFS), with responders (R) showing a PFS of ≥11 months. ADCmin of NELMs decreased in Rs whereas it increased in non-responders (NR). Percentual changes of ADCmin and ADCmean differed significantly between response groups (p < 0.03). By contrast, ADC of the pNETs tended to increase in Rs, while there was no change in NRs. Tumor-to-liver (T/L) ratio of T1 SI of NELMs increased in Rs and decreased in NRs, and percentual changes differed significantly between response groups (p < 0.02). T1 SI of the pNETs tended to decrease in Rs and increase in Ns. The quotient of pretherapeutic and posttherapeutic ADCmin values (DADCmin) and length of everolimus treatment showed significant association with PFS in univariable Cox analysis. In conclusion, quantitative MRI, especially DWI, seems to allow treatment assessment of pNETs with NELMs under everolimus. Interestingly, the responding NELMs showed decreasing ADC values, and there might be an opposite effect on ADC and T1 SI between NELMs and pNETs.

show abstract

“…As previously described for TKIs markers, midgut NENs and PNENs overexpress VEGF and its receptors (Christofori et al 1995, Terris et al 1998, La Rosa et al 2003. In the RADIANT-III trial, a significantly progressive reduction in VEGFR-2 was observed after treatment with everolimus (Yao et al 2012), but the specific clinical relevance and applicability in NENs must still be determined.…”

Section: Molecular Biomarkers For Mtor Pathway Inhibitorsmentioning

confidence: 93%

“…Immunohistochemical and molecular expression of VEGFR-1/-2 has been reported in over 50% of GEP-NENs (La Rosa et al 2003, Angelescu et al 2013) without being directly related to tumor malignancy (La Rosa et al 2003). Some relations between VEGFR and patient outcome have been described; specifically, low VEGFR-1 levels have been related to longer PFS (Yao et al 2012), high baseline VEGFR-2 levels to decreased OS in PNENs (Zurita et al 2015) and low VEGFR-3 levels to longer PFS/OS in carcinoid patients (Zurita et al 2015). Increased VEGF concentrations accompanied by decreased VEGFR-2 and VEGFR-3 levels have been reported after treatment with sunitinib (Deprimo et al 2007), but their levels returned to baseline during the off-treatment period (Zurita et al 2015).…”

Section: Vascular Endothelial Growth Factor Receptormentioning

confidence: 99%

Neuroendocrine neoplasms: current and potential diagnostic, predictive and prognostic markers

Herrera‐Martínez

Hofland

Moreno

et al. 2019

Endocrine-Related Cancer

View full text Add to dashboard Cite

Some biomarkers for functioning and non-functioning neuroendocrine neoplasms (NENs) are currently available. Despite their application in clinical practice, results should be interpreted cautiously. Considering the variable sensitivity and specificity of these parameters, there is an unmet need for novel biomarkers to improve diagnosis and predict patient outcome. Nowadays, several new biomarkers are being evaluated and may become future tools for the management of NENs. These biomarkers include (1) peptides and growth factors; (2) DNA and RNA markers based on genomics analysis, for example, the so-called NET test, which has been developed for analyzing gene transcripts in circulating blood; (3) circulating tumor/endothelial/progenitor cells or cell-free tumor DNA, which represent minimally invasive methods that would provide additional information for monitoring treatment response and (4) improved imaging techniques with novel radiolabeled somatostatin analogs or peptides. Below we summarize some future directions in the development of novel diagnostic and predictive/prognostic biomarkers in NENs. This review is focused on circulating and selected tissue markers.

show abstract

The Vegf Pathway in Patients with Pancreatic Neuroendocrine Tumors: Efficacy of Everolimus by Baseline Marker Level, and Prognostic and Predictive Effect Analyses from Radiant-3

Cited by 3 publications

References 0 publications

Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art

Treatment Assessment of pNET and NELM after Everolimus by Quantitative MRI Parameters

Neuroendocrine neoplasms: current and potential diagnostic, predictive and prognostic markers

Contact Info

Product

Resources

About