Caso clinico: Tumori Neuroendocrini

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Clinical case – NENs

Silvia Ortolani

UOC Oncologia Medica Azienda Ospedaliera Universitaria di Verona

 “New” entities: WD NETs, Ki67 > 20% (G3, WHO 2010)

 “New” drugs, potential applications : PRRT

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B.V., male, 53 y.

No relevant familial history nor relevant comorbidities.

✓ May 2014: persistent abdominal pain  US, CT, MR.

✓ Pancreatic FNAB: well differentiated PNET, Ki67 25% (G3, WHO 2010)

Solid mass in the body-tail of the pancreas (30x45x36 mm) with splenic vessels and spleno-mesenteric-portal confluence involvement. Suspicious peri-pancreatic, non-bulky nodes. No distant metatases. Locally advanced disease.

 CgA 598 ng/mL (> ULN), NSE 7.6 ng/mL, CEA 1.1 ng/mL, CA19.9 22.6 U/mL

 ⁶⁸Ga-DOTATOC-PET/CT: +++ (SUV max 83).¹⁸F-FDG-PET/CT: +++ (SUV max 10)

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Well differentiated PNET , Ki67 25% (G3 WHO, 2010):

….A CONTRADICTION?

1. SSA?

1. EVEROLIMUS?

2. SUNITINIB?

3. CHEMO?

AIOM Guidelines Neuroendocrine Neoplasms, v. 2015 Sorbye JR, Ann Oncol 2013;24: 152–60 Velayoudom-Cephise FL, Endocr Relat Cancer 2013;20(5):649-57 Heetfeld M, Endocr Relat Cancer 2015;22(4):657-64 Milione M, Neuroendocrinology 2016

1. Aim: radical surgery 2. Time: ...not now!

3. Outcome of interest: RR 4. Tool: ...???

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Treatment RR % mPFS mos mOS mos

SSA 3-5 nr (>12) nr

Chemo 15-40* 4-18 16-33

Everolimus 5 11.4 nr

Sunitinib 9.3 11.4 33

* Higher RR (40-70%) in NECs treated with CDDP-based CT CAP-TEM: RR up to 70% in a retrospective series of PNETs

 CDDP/CBDCA-VP16

 Other platinum-based doublets

 Alkylant + Antimetabolite

 Three-drugs combos

 Metronomic CT +/- BEVA

AIOM GL 2015: treatment options in PanNENs

Activity in PNENs

Activity in G2-G3 NETs RR up to 40%

Bajetta E, Cancer 1998;83(2):372-8 Kouvaraki MA, J Clin Oncol 2004;22(23):472-71 Turner NC, Br J Cancer 2010;102:1106-12 Bajetta E, Anticancer Res 2014;34:5657-60

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B.V., male, 53 y.

✓ May 2014: diagnosis.

✓ Jun  Oct 2014: CDDP-DTIC-CAPE x 3 + 3 cycles.

DWI Portal phase

Before:

After:

PR 1. Aim: radical surgery

2. Time: ...not yet!

3. Outcome of interest: RR 4. Tool: ...???

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Do we have other options to achieve tumour shrinkage?

ORR: 18.8-40%

(midgut, pancreas: +++)

AIOM guidelines Neuroendocrine Neoplasms, v. 2015 Bodei L, Eur J Nucl Med Mol Imaging 2003;30(2):207-16 Kwekkeboom DJ, J Clin Oncol 2008;26(13):2124-30 Kwekkeboom DJ, Endocr Relat Cancer 2010;17(1);R53-73 Sansovini M, Neuroendocrinology 2013;97(4):347-5 NETTER-1 trial, presented at ECCO/ESMO 2015, ASCO 2016 Van Vliet EI, Neuroendocrinology 2013;97:74-85 Van Vliet EI, J Nucl Med 2015;56:1647-53

“…new applications of PRRT may include the neoadjuvant use of PRRT for PNETs,

as suggested by a few case reports and retrospective series in which previously unresectable PNETs could be successfully

operated after PRRT”

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B.V., male, 53 y.

✓ May 2014: diagnosis.

✓ Jun  Oct 2014: CDDP-DTIC-CAPE x 3 + 3 cycles  PR.

✓ Jan  Jun 2015: experimental ¹⁷⁷Lu-DOTATATE-PRRT (4 cycles, 500 mCi)  “cold” SSA.

✓ October 2015: PR with resolution of the portal involvement. A short stenosis of the SMV remains, conditioning collateral vessels.

Surgery now?

Wait for best response?

mean: 12-15 mos (6.5-33.2)

Van Vliet EI, J Nucl Med 2015;56:1647-53

OCT 15 JAN 16 JAN 16 JUN 16

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Thank you

sil.ortolani6@gmail.com