Impa c t of dia g nosis with Pa nc re a tic Ne uroe ndoc rine T - PowerPoint PPT Presentation

14 th Inte rna tiona l VHL Me dic a l Re se a rc h Symposium Impa c t of dia g nosis with Pa nc re a tic Ne uroe ndoc rine T umors on Morta lity in Pa tie nts with Von Hippe l- L inda u Dise a se L ia t Arnon, MSc , Re ut Ha lpe rin, MD PhD, Amit T irosh, MD VHL Clinic a l Ca re Ce nte r, Ne uroe ndoc rine T umors Se rvic e , Division of E ndoc rinolog y, Dia be te s a nd Me ta bolism, She ba Me dic a l c e nte r, T e l Ha shome r, Isra e l

• Orig ina te from ne uroe ndoc rine c e lls L ung NE T Pa nc re a tic NE T Ga stro inte stina l NE T • T he inc ide nc e of NE Tha s inc re a se d VHL VHL Sporadic Sporadic related OR related • Most PNE Ta re spora dic PNET PNET PNET PNET • T he y c a n a lso de ve lop a s pa rt of inhe rite d syndrome s, suc h a s von Hippe l- L inda u (VHL ).

Ga rc ia -Ca rb o ne ro e t al ., 2016, Bla nsfie ld e t al. , 2007, K ra uss e t a l., 2018, I g a ra shi e t a l., 2014

68 Ga-DOTATATE PET/CT • Pre va le nc e : 8-17% (somatostatin receptor-based imaging) • Me dia n a g e a t onse t: 34y (14-55) • Surve illa nc e - Size (g e notype ) • Ma na g e me nt is ma inly surg ic a l Bla nsfie ld e t al. , 2007, I g a ra shi e t al. , 2014, L o nse r e t al., 2003, T iro sh e t al., 2017, Krauss e t al., 2018

• L e a ding c o ntrib uto rs fo r VHLmo rb idity a nd mo rta lity:  Ce ntra l ne rvo us syste m he ma ng io b la sto ma (HB)  Cle a r c e ll re na l c e ll c a rc ino ma (RCC) Wha t is the impa c t of dia g nosis with PNE T on the ove ra ll morta lity in • pa tie nts with VHL ? L o nse re t al., 2003

• Re trospe c tive study , b a se d o n the Surve illanc e , E pide mio lo g y and E nd Re sults (SE E R) da ta b a se . • Pa tie nts : Dia g no se d with RCC, PNE T , HB a nd/ o r PPGL  “I nte rna tio na l Crite ria ” • VHL dia g nosis:  “Da nish Crite ria ” Univa ria te a na lysis with surviva l a na lysis b y K a pla n-Me ie r c urve s, • Ana lysis: Multiva ria b le a na lysis using the Co x pro po rtio na l re g re ssio n. Bind e rup, M. L . M. e t al. (2017)

Spora dic p va lue VHL n 170 16,174 Me a n a g e 46.6 63.9 <0.001 (SD) (17.0) (11.3) RCC 164 15,620 <0.001 PNE T 91 419 <0.001 HB 83 75 <0.001 PPGL 7 60 <0.001 SD, sta nd a rd d e via tio n; RCC, re na l c e ll c a rc ino ma ; PNET , pa nc re a tic ne uro e nd o c rine tumo r; HB, he ma ng io b la sto ma ; PPGL , phe o c hro mo c yto ma / pa ra g a nglio ma

Spora dic VHL p va lue n=91 n=419 Ag e a t dia g no sis me a n 54.0±14.0 60.2±13.0 <0.001 (SD) Ma le se x n(%) 48 (52.7) 229 (54.7) 0.8 Me ta sta tic PNE T n(%) 32 (45.7) 217 (57.9) 0.08 0.007 Dia me te r n(%) <10 mm 10 (16.9) 27 (9.2) 11-29 mm 31 (52.5) 114 (38.6) >30 mm 18 (30.5) 154 (52.2) SD, sta nd a rd d e via tio n; PNET , pa nc re a tic ne uro e nd o c rine tumo r;

• Hig he r ACM risk in pa tie nts with VHLa nd PNE Tvs. tho se witho ut PNE T . Pa tie nts with VHL -re la te d PNET • ha d lo we r ACM risk c o mpa re to pa tie nts with spo ra dic PNE T

All PNE T Spora dic PNE T VHL - re la te d PNE T T with dia me te r ≥ 30 vs. A tre nd fo r hig he r risk fo r ACM wa s fo und in pa tie nts ha rb o ring PNE <30 mm (p=0.06 a nd p=0.1 in pa tie nts with spo ra dic a nd VHL -re la te d PNE T , re spe c tive ly).

Sta g e Gra de • Hig he r ACM risk in pa tie nts with Simila r tre nd o f hig he r ACM risk with • spo ra dic a dva nc e d PNET , with a simila r hig he r g ra de s in VHL -re la te d a nd tre nd a mo ng pa tie nts with a dva nc e d spo ra dic PNE T VHL -re la te d PNE T . However, is PNET diagnosis an independent risk factor for ACM in VHL?

• Dia g no sis with PNE T wa s no t a sso c ia te d with inc re a se d fo r ACM (HR 0.42, 95% CI 0.12-1.5, p=0.18). • An inc re a se d risk fo r ACM wa s de te c te d a mo ng pa tie nts with me ta sta tic PNE T (HR 3.71, 95% CI1.4-9.8, p=0.008).

Doe s PNE T dia g nosis a ffe c t ACM in pa tie nts with VHL ? Adva nc e d PNE T L o c a lize d PNE T Hig he r ACM risk in pa tie nts with • Ha s no inde pe nde nt impa c t o n ACM in • a dva nc e d PNE T pa tie nts with VHL . Impo rta nc e o f surve illa nc e fo r e a rly • Co mple x e ffe c t o f multiple VHL -re la te d • . de te c tio n o f hig h-risk PNE T tumo rs o n ACM. Do pa tie nts with spora dic a nd VHL re la te d PNE T diffe r in ACM risk? Dia me te r Gra de Sta g e VHL -re la te d PNE T spo ra dic PNE T . ACM

• Unde re stima tio n o f VHL po pula tio n (SE E R da ta b a se ) • So me o f the va ria b le s ha ve missing va lue s • No da ta o n VHL g e no type • No lo ng itudina l da ta o n tumo r size dyna mic s

T surve illa nc e in VHL ma y a ffe c t ACM b y re duc ing the ra te o f me ta sta tic • PNE dise a se . • T he impa c t of e a rly de te c tion of hig h- risk PNE T o n ACM sho uld b e inve stig a te d in future studie s. • Ca re g ive r- pa tie nt re la tions ma y a ssist in time ly e xe c utio n o f the VHL A g uide line s fo r o ptima l sc re e ning .

14 th Inte rna tiona l VHL Me dic a l Re se a rc h Symposium L ia t.a rnon@she ba .he a lth.g ov.il