TUMORES NEUROENDOCRINOS. Miguel Navarro. Salamanca
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1 TUMORES NEUROENDOCRINOS Miguel Navarro. Salamanca
2 Introduction to Neuroendocrine Tumours (NETs) NETs are relatively RARE At least 40 different entities are described arising in different organs. Different terminologies have also caused confusion.
3 Most NETs 70% are non functional
4 Diagnostic challenges in NET Wide variety of clinical presentations Late presentation Over 60% of NETs are advanced at the time of diagnosis The median survival for patients with advanced NET is 33 months
5 Incidence Trends of NETs Dasari A et al. JAMA Oncol. April 2017
6 NETs Are Second Most Prevalent Gastrointestinal Tumor Median survival Localized 203 months Regional 114 months Distant 39 months
7 Confusion Caused by the Term Carcinoid Oberndorfer coined the term karzinoide in This term implies that these tumours are benign; this is an unfortunate misnomer for the majority of NET. NET have malignant potential and metastasize, generally to the liver.
8 Histologic classification
9 Treatment challenges in NET One Treatment Does Not Fit All
10 Treatment challenges in NET
11
12 Somatostatin Analogues AAS
13 Telotristat. A Tryptophan Hydroxylase (TPH) Inhibitor to treat carcinoid syndrome diarrhea Indicated for carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy
14 Telotristat Patients who received telotristat etiprate also experienced a lower frequency of flushing episodes and less intense abdominal pain compared to placebo, though these differences did not reach statistical significance.
15 Where does telotristat fit in? Active in controlling diarrhea from carcinoid syndrome. Does it have QOL benefits beyond diarrhea control? Flushing? Abdominal pain? Is there a role in prevention of carcinoid heart disease?
16
17 New options in NETs
18 Treatment challenges in NET cancers in slow motion WATCHFUL WAITING
19 Somatostatin Analogues AAS
20 PROMID Trial
21 CLARINET Trial
22 Somatostatin Analogues AAS Previous restrictions on the use of AAS in non functioning tumors are no longer justified. Favorable side effects profile. Appropriate 1st line agents in most well-differenciated NETs. Early antitumor therapy
23 Indications for cytotoxic chemotherapy
24 QT en NETS
25 Newer chemotherapy regimens have demonstrated acceptable toxicity in advanced NET
26 Cap/Tem Example of response Baseline Maximal response
27 Targeting NETs
28 Targeting NETs
29 Targeting NETs
30
31 AAS
32 Targeting NETS
33 Targeting NETS There are several biological agents being evaluated. Pazopanib (Votrient) Cabozantinib (Cabometyx) Axitinib (Inlyta) Lenvatinib (Lenvima)
34 Radionuclide Therapy Theranostics-Diagnosis and Therapy
35
36 n engl j med 376;2 nejm.org January 12, 2017
37 Number of deaths: LU-Dotate: 14 Control: 26 Estimated risk of death 60% lower n engl j med 376;2 nejm.org January 12, 2017
38 Case Report 58 yo m. Large cell Neuroendocrine carcinoma. Surgery. Stage Ib Cisplatin-Vp16 (Ady) Liver- Bone Mtx Carboplatin-Vp16, Lanreotide, Everolimus,Pazopanib,TMZ-Cap Topotecan ECOG -2. Oxycontin 60 mg/12 h plus oxinorm ECOG-0, weight gain 20 KG, no opioids PRRT
39 Case Report Progression If patient had responded to the first few rounds of Lutathera and then the tumors start to grow again, it can be given safely for a second time? 5 round of Lutathera May/18
40 Where does PRRT fit in? Phase 3 randomized data only in midgut NETs. Early phase data suggesting higher response rates in non-midgut NETs COMPETE trial. Somatostatin-receptor (SSTR) expression is strong predictive marker. Consider as 2nd line therapy in patients with strong SSTR expression. Advantages: Limited treatment course (4x), exceptionally long-pfs, low toxicity Are there long-term risks to consider?
41 Inmunotherapy NETs do not have many mutations. Merkel cell carcinoma (MCC). Rare and aggressive neuroendocrine tumor of the skin. MCC incidence is higher in immunocompromised populations. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultravioletradiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. CarboVp16 Rt - Avelumab
42 Ongoing clinical trials
43 Take Home Messages Nets are not rare. Consider patient and tumor characteristic. Increasing number of treatment options Octeotride / Lanreotide Telotristat Sunitinib / Everolimus Temozolomide. PPRT Exciting Decade in Neuroendocrine Tumor Treatment
44 Muchas gracias
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