Poblacions amb alt risc de càncer de pàncrees. Quin seguiment hem de fer?

Transcription

1 Poblacions amb alt risc de càncer de pàncrees. Quin seguiment hem de fer? T. Macarulla Hospital Vall d Hebrón Actualització en patologia pancreàtica Societat catalana de pàncrees-scpanc 4 Octubre 2016

2 PANCREATIC CANCER High mortality cases/year in Spain Overall survival at 5 years: <5% Less than 1cm with curative resection:100% Stage I: 58% Stage IIb:17% Curative resection: 10-15% 4-16% have a familial pancreatic cancer. Ariyama J, Nippon Risho 1986; Klein AP, Cancer 2001.

3 Projecting Cancer Incidence and Deaths to 2030 Rahib et al, Cancer Res 2014

4 Why is this disease so aggressive? No early symptoms No screening program Very early invasion and metastases Chemo-resistant (sanctuary?) Debilitating cytokines mediated symptoms

5 How can we improve these results? Surgical resection the only potentially curative treatment. Improvement in resectability requires detection of PDAC at an early stage. Selective screening of individuals at high risk for PDAC might lead to early detection of PDAC or detection of precursor lesions allowing curative surgical treatment.

6 Normal duct PanIN Ia PanIN Ib PanIN II PanIN III Cancer MCN low grade Normal duct Intermediate grade High grade IPMN low grade

7 PANCREATIC CANCER Casos esporádicos <45 años 3% Hereditary syndromes 5-15% Cáncer de páncreas familiar Otros síndromes hereditarios Casos esporádicos Mediana edad 72 años 82% Chanjuan Shi et al. Arch Pathol Lab Med

8 To asses: -Type of mutation -DM -Nº family members -Smoking history

9 RR 132 RR 9-47 RR 62 RR 8 RR 3-10

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11 The International Cancer of the Pancreas Screening (CAPS) Consortium Screening of pancreatic cancer: who? Not general population screening (low incidence) Selected patients: 3 relative affected (1 st, 2 d, 3 st degree) 2 relative affected (1st degree) Peutz-Jeghers syndrome BRCA-2, PALB2, and p16 mutations and 1st or 2d degree relative with PC Hereditary pancreatitis Lynch syndrome and one 1st degree with PC Canto M, Gut 2012

12 No consensus: Screening of pancreatic cancer Age to initiate screening (familiar PC, median age 68) Stop surveillance Need for EUS fine-needle aspiration to evaluate cysts Optimal screening modalities and intervals for follow-up imaging Which screening abnormalities were of sufficient concern to for surgery to be recommended. Canto M, Gut 2012

13 EUS and MRI are considered the most accurate tolos for pancreatic imaging and do not involve ionising radiation

14 Screening of pancreatic cancer: When should surgery be performed? Screening should be offered to individuals who are candidate form surgery (agree 75%) Pancreatic resections should be performed at high-volumen speciality centres (agree 100%) Determinig when surgery is required is difficult and best individualised after multidisciplinary assessment. Little consensus about which lesions detected by screening required surgery. Canto M, Gut 2012

15 Aim of the study: To asses if surveillance lead to detection of early-stage PDAC or to the detection of relevant PRLs and to evaluate if the program leads to improvement in prognosis. Three centers in Europe. N 407; 178 CDKN2A mutation carriers, 214 FPC, 19 BRCA1/2 or PALB2 mutations Median age 42.8 y (27-81), median duration of follow up 2.8 y. Screening: Annual MRI and/or endoscopic ultrasound

16 CDKN2A/p16 -Leiden mutation carriers: PDAC was detected in 13 (7.3%) of 178 mutation carriers.9 patients underwent surgery; resection rate: 75%. 5y OS was 24% (sporadic PDAC 4-7%). 14.6% a cystic lesion was found, 1% underwent surgery. FPC: Two (0.9%) had pancreatic tumor; one advanced PDAC, one early neuroendocrine tumor. 13 (6.1%) underwent surgical resection for PRL, 1,9% rellevant. BRCA1/2 or PALBB2 mutation carriers: One SIA PDAC in BRCA2 mutation carrier. Two patient underwent surgery for cystic lesions. Vasen et al, J Clin Oncol 2016

17 Conclusions: Surveillance of CDKN2A/p16-Leiden carriers was relatively successful, detecting most PDAC s at resectable stage, and improve prognosis. Whether surveillance of FPC families meets this goal is still questionable, and main effect seems to be prevention of PDAC by removal of PRL s. Without control group, it is difficult to determine the effects of the surveillance program on PDAC outcome. Vasen et al, J Clin Oncol 2016

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19 Bibliografia recomanada: Rahib L, Dmith B, Aizenberg R, et al. Projecting Cancer Incidence and deaths to 2013: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74(11): Canto M, Harinck F, Hruban R, et al. International cancer of the pancreas screening consortium Summit on the management of patients with increased risk for familiar pancreatic cancer. Gut 2012;0:1-9. Vasen H, Ibrahim I, Guillem-Ponce C, et al. Benefit of survillance for pancreatic cancer in high-risk individuals: Outcome of long-term prospective follow-up studies from three european expert centers. J Clin Oncol 2016;34: Brentnall T. Progress in the earlier detection of pancreatic cancer. J Clin Oncol 2016;34:1973.