Pancreatic Cancer Screening in a Population at High Risk

Обзор

Pancreatic cancer is one of the diseases with the worst prognosis, which is mainly due to the initial asymptomatic prognosis. Unfortunately, the incidence of this disease in the Czech Republic is still increasing. In a certain proportion of patients, it is possible to predict the disease, e.g. due to family burdens. Regular follow-up of such individuals is the subject of the SCREPAN study: "Pancreatic Cancer Screening in High-Risk Persons".

Подробное описание

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the worst prognosis. Mortality in this disease is almost equal to the incidence. In the Czech Republic, the incidence of this cancer has an upward trend, in 2017, 21.2 new cases per 100,000 people were reported, which represents a more than double increase compared to the data from the 1970s.

Pancreatic cancer is associated with an extremely poor prognosis for several reasons. It is usually diagnosed at an advanced stage, which is often due to the asymptomatic course of the disease or non-specific symptoms, the lack of sensitive and specific tumor markers, and difficult diagnosis by imaging methods in the early stages. Five-year survival, regardless of clinical stage, is between 7-9%.

Resectable disease is diagnosed in only 10% of patients, in which the 5-year survival rate is 37 %, locally advanced unresectable disease is detected in about 30 % of patients with a 5-year survival of 12 %, and metastatic disease is found in about 60 % of patients, with a 5-year survival rate of only around 3 %.

The poor prognosis of this disease is also due to the limited possibilities of screening and curative intervention for a short "lead time" in rapidly metastatic disease.

Pancreatic cancer screening is not suitable for the non-selected population. On the contrary, it is important for individuals with a high risk of developing this disease. In these subjects, early diagnosis during screening demonstrated a higher number of curative resections and longer survival.

Вмешательства

• Процедура endoscopic ultrasonography
  endoscopic ultrasonography - frequency defined by arm
• Процедура magnetic resonance
  magnetic resonance - frequency defined by arm
• Диагностический тест laboratory examination
  hematology, biochemistry, Na+, K+, Cl-, Ca2+, bilirubin, ALT, AST, GGT, ALP, lactate dehydrogenase, creatinine, urea, fasting glycemia, HbA1c, alpha-amylase, LPS, albumin, total protein, CA19-9, CEA

Первичные конечные точки

• Number of participants with newly diagnosed pancreatic ductal adenocarcinoma [Срок оценки: From date of subject enrollment annualy in determined examinations according to the protocol schedule until the date of PDAC diagnosis or up to 60 months of subject participation in the study]

Вторичные конечные точки (3)

• Methods yield comparison [Срок оценки: through study completion, an average of 1 year]
• Screening methods cost-effectiveness [Срок оценки: through study completion, an average of 1 year]
• KRAS mutation status evaluation [Срок оценки: From the date of subject enrollment annualy in determined examinations according to the protocol schedule until the date of PDAC diagnosis or up to 60 months of subject participation in the study]

Критерии участия

Критерии включения

• willing to participate in the study
• age 18+
• arms specific criteria:

A:

• chronic pancreatic disease in the context of cystic fibrosis or chronic pancreatitis
• age 50+

B1:

• confirmed Peutz-Jegherson syndrome (mutSTK11) + age over 35 years or 10 years earlier than pancreatic ductal adenocarcinoma was diagnosed in the youngest family member
• familial melanoma syndrome (mutCDKN2A) + age over 40 years or 10 years before pancreatic ductal adenocarcinoma was diagnosed in the youngest family member
• confirmed hereditary pancreatitis (mutPRSS1) + age over 40 years or 20 years after the first attack

B2:

• confirmed diagnosis of hereditary syndrome (Lynch syndrome /mutMLH1, mutMSH2, mutMSH6, mutPMS2, mutEPCAM/, HBOC /mutBRCA1, mutBRCA2, mutPALB2, mutATM/, familial adenomatous polyposis /mutAPC/, Li-Fraumeni syndrome /mutTP53/)
• at least one relative with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis at the same time (Grade I or II relative)
• age over 50 years, or 10 years before the pancreatic ductal adenocarcinoma was diagnosed in the youngest relative - which comes first

C:

• positive family anamnesis of pancreatic ductal adenocarcinoma without hereditary syndrome context
• age 50+ or 10 years earlier than the youngest relative with pancreatic ductal adenocarcinoma - screening is recommended for all first-degree relatives of affected family members

Критерии исключения

• Inability to undergo radical curative surgery for a pancreatic tumor.
• Inability to undergo scheduled imaging examinations.
• Incurable malignant cancer.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Скрининг

Центры проведения

Чехия · 1 центр

• Masaryk Memorial Cancer Institute — Brno

Публикации

• Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, Nio Y, Schulick RS, Bassi C, Kluijt I, Levy MJ, Chak A, Fockens P, Goggins M, Bruno M; International Cancer of Pancreas Screening (CAPS) Consortium. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar;62(3):339-47. doi: PMID 23135763
• Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 Feb;110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. Epub 2015 Feb 3. PMID 25645574
• Stoffel EM, McKernin SE, Brand R, Canto M, Goggins M, Moravek C, Nagarajan A, Petersen GM, Simeone DM, Yurgelun M, Khorana AA. Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion. J Clin Oncol. 2019 Jan 10;37(2):153-164. doi: 10.1200/JCO.18.01489. Epub 2018 Nov 20. PMID 30457921
• Abe T, Blackford AL, Tamura K, Ford M, McCormick P, Chuidian M, Almario JA, Borges M, Lennon AM, Shin EJ, Klein AP, Hruban RH, Canto MI, Goggins M. Deleterious Germline Mutations Are a Risk Factor for Neoplastic Progression Among High-Risk Individuals Undergoing Pancreatic Surveillance. J Clin Oncol. 2019 May 1;37(13):1070-1080. doi: 10.1200/JCO.18.01512. Epub 2019 Mar 18. PMID 30883245
• Bartsch DK, Slater EP, Carrato A, Ibrahim IS, Guillen-Ponce C, Vasen HF, Matthai E, Earl J, Jendryschek FS, Figiel J, Steinkamp M, Ramaswamy A, Vazquez-Sequeiros E, Munoz-Beltran M, Montans J, Mocci E, Bonsing BA, Wasser M, Kloppel G, Langer P, Fendrich V, Gress TM. Refinement of screening for familial pancreatic cancer. Gut. 2016 Aug;65(8):1314-21. doi: 10.1136/gutjnl-2015-311098. Epub 2016 May 2 PMID 27222532
• Harinck F, Konings IC, Kluijt I, Poley JW, van Hooft JE, van Dullemen HM, Nio CY, Krak NC, Hermans JJ, Aalfs CM, Wagner A, Sijmons RH, Biermann K, van Eijck CH, Gouma DJ, Dijkgraaf MG, Fockens P, Bruno MJ; Dutch research group on pancreatic cancer surveillance in high-risk individuals. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high- PMID 25986944
• Corral JE, Das A, Bruno MJ, Wallace MB. Cost-effectiveness of Pancreatic Cancer Surveillance in High-Risk Individuals: An Economic Analysis. Pancreas. 2019 Apr;48(4):526-536. doi: 10.1097/MPA.0000000000001268. PMID 30946242
• Vasen H, Ibrahim I, Ponce CG, Slater EP, Matthai E, Carrato A, Earl J, Robbers K, van Mil AM, Potjer T, Bonsing BA, de Vos Tot Nederveen Cappel WH, Bergman W, Wasser M, Morreau H, Kloppel G, Schicker C, Steinkamp M, Figiel J, Esposito I, Mocci E, Vazquez-Sequeiros E, Sanjuanbenito A, Munoz-Beltran M, Montans J, Langer P, Fendrich V, Bartsch DK. Benefit of Surveillance for Pancreatic Cancer in High PMID 27114589

Идентификаторы

NCT: NCT06330441 · MOU-2021-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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