03 | Pancreatic cancer burden in Italian CDKN2a-positive families followed for up to 25 years
Eleonora Allavena1|2, Bruna Dalmasso2, Andrea Gambino2, Francesca Barbero2, Irene Vanni2, Cansu Gorgun1, Francesco Spagnolo2|4, Enrica Tanda3, Andrea Boutros3, William Bruno1|2, Lorenza Pastorino1|2, Paola Ghiorzo1|2 | 1Department of Internal Medicine and Medical Specialties - DiMI, University of Genoa; 2Cancer Genetics Unit, IRCCS Ospedale Policlinico San Martino, Genoa; 3Medical Oncology Unit, IRCCS Ospedale Policlinico San Martino, Genoa; 4Department of Surgical and Diagnostic Integrated Sciences, University of Genoa, Genoa, Italy.
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Background: Pancreatic cancer (PC) risk in CDKN2A pathogenic variant (PV) carriers is among the highest (more than twice that of BRCA1/2), with a standardized incidence ratio (SIR) of 20 and cumulative incidence of 20% by age 70 in the Dutch cohort (median age 60). These data are currently considered for surveillance protocols, which showed promising results in CDKN2A PV carriers. Prospective, lifetime and variant-specific estimates are missing in the Italian population, in which retrospective risk estimates conducted in a small number of families and with limited follow-up, were <10%.
Methods: We assessed SIR and cumulative incidence of PC in CDKN2A PV carriers and first-degree relatives from 202 families, followed for >20 years, not yet included in formal surveillance protocols.
Results: PC was reported in 66/202 families (32.67%, median age at diagnosis 66, IQR 62-74). When only considering melanoma families for which pancreatic cancer was not determinant as selection criteria, SIR was 23.08 [CI 17.13-30.43]. Cumulative incidence was <1% by age 60 and >10% after 87. After including all CDKN2A-positive families, SIR rose to 34.63 [CI 27.46-43.09]. Cumulative incidence, which remained below 1% until age 52, increased to 10% at 70 and 19% after 90 (Figure 1). PC surveillance within melanoma follow-up (N=38) resulted in the diagnosis of 1 resectable PC, 4 IPMN and 1 pancreatic neuroendocrine tumor, compared to 7 advanced and 1 resectable PC in 190 cases without surveillance.
Conclusions: In our cohort SIR at least as high as Dutch estimates, whereas cumulative incidence reaches comparable rates at older age of diagnosis of PC cases. Taking into consideration regional-specific risk and age of onset can help optimize PC screening strategies in high-risk individuals, in order to optimize efficacy, patient compliance and sustainability.
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