Targeted Therapies in the Management of Well-Differentiated Digestive and Lung Neuroendocrine Neoplasms
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Skin Cancer (T Ito, Section Editor)
Targeted Therapies in the Management of Well-Differentiated Digestive and Lung Neuroendocrine Neoplasms Namrata Vijayvergia, MD1,* Arvind Dasari, MD, MS2 Address *,1 Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA Email: [email protected] 2 Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
* Springer Science+Business Media, LLC, part of Springer Nature 2020
This article is part of the Topical Collection on Skin Cancer Keywords Targeted therapy I NETs I Neuroendocrine I Recent advances
Opinion statement Ongoing advances in our understanding of neuroendocrine tumor (NET) biology, genetics, and immunology, will continue to expand the availability of targeted therapies, thus improving the outcomes of patients. Well-differentiated neuroendocrine tumors (NETs) are grouped into pancreatic and non-pancreatic NETs (includes GI and thoracic NETs) for treatment considerations (Fig. 1). For panNETs, initial therapy is driven by the need of radiographic response, and targeted agents are typically reserved for second and third line based on the toxicity profile. Treatment options for non-pancreatic NETs are also expanding and while SSAs are the typical first-line option, everolimus and PRRT both remain approved therapies for future lines, and VEGF TKIs are showing promising results in research settings. Sequencing these agents and best time to incorporate peptide receptor radio therapy into the management algorithm remains an unmet need.
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Introduction Neuroendocrine neoplasms (NENs) are rare diverse cancers; they have recently gained significant interest as a result of their increased incidence: the age-adjusted incidence has increased over six times in the last four decades (1.09 per 100,000 in 1973 to 6.98 per 100,000 by 2012), per a recent SEER data analysis [1•]. The majority originate in the gastrointestinal tract (55%) and bronchopulmonary system (30%) [1•]. Because of their indolent course, they are often diagnosed at an advanced stage, particularly if they are localized in the small intestine or pancreas [2]. While most NENs are relatively slow growing; their histologic grade and differentiation are closely correlated with their clinical behavior. NEN classification
systems are based on proliferative indices and continue to evolve [3, 4] (Table 1). For instance, the recent WHO Digestive NEN classification system subdivides G3 tumors into poorly differentiated neuroendocrine carcinomas and well-differentiated, high-grade neuroendocrine tumors (NETs); their differences are highlighted in Table 1 [5, 6••]. At the same time, evidence-based medicine has changed the treatment landscape in the last decade. This review summarizes the established treatment options for well-differentiated, advanced gastrointestinal, pancreatic, and lung NETs, with a focus on targeted therapies, recent efforts to improve out
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