Mutation of K-RAS, CDKN2A, SMAD4 and TP53 in Pancreatic Cancer: Role of Liquid Biopsy in Preoperative Diagnosis

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Brief Title

Mutation of K-RAS, CDKN2A, SMAD4 and TP53 in Pancreatic Cancer: Role of Liquid Biopsy in Preoperative Diagnosis

Official Title

Mutation of K-RAS, CDKN2A, SMAD4 and TP53 in Pancreatic Cancer: Role of Liquid Biopsy in Preoperative Diagnosis

Brief Summary

      Pancreatic cancers represent a challenge for the multidisciplinal team. A patient-tailored
      treatment plan requires an accurate preoperative staging. Currently more than 40% of patient
      taken to the OR are actually unresectable and another 40% will shortly recur with dismal
      prognosis.

      Among patients that meet upfront surgery some would have benefit of a neoadjuvant treatment
      and vice versa. Accuracy of preoperative staging is of primary importance in treatment
      decisional making. Due to its location, invasive preoperative diagnostic tests on pancreatic
      cancer are expensive and risky. Liquid biopsy provides a non-invasive signature of the tumor.
      Analyzing mutations on cell-free nucleic acids gives translational information on tumor
      biology and therefore on its clinic-pathological features and likely on its progression. This
      study would be the first -in our knowledge- analyzing the relationship of a pattern of 4
      major genes involved in pancreatic cancer progression on liquid biopsy and the time to
      recurrence and T-stage, with particular attention to vascular invasion. A properly staged
      patient provides a better resource allocation, an optimal treatment plan and improves
      patient's outcomes.
    

Detailed Description

      BACKGROUND Pancreatic cancer is the 4th cancer-related cause of death in Western countries
      and it is expected to become the 2nd leading cause of death by 2030 [1]. Approximately 80% of
      patients are unresectable at diagnosis [2] including a 41.4% of patients found unresectable
      at exploratory laparoscopy/tomy [3]. Moreover up to 38% of eventually resected patients will
      need a vascular resection in order to achieve a radical pancreatectomy [4], just over half of
      which because of a histological invasion [2]. Last but not least, successfully resected
      patients will recur within 12 months in more than 40% of cases with dismal prognosis [5].
      Those early recurrent patients will show local spread or metastatic disease within 12 months
      with a post-recurrence survival and overall survival more than halved compared to patients
      recurring beyond one year from resection [5]. Laparotomy may be therefore useless in such
      patients. In this setting neoadjuvant treatment plays a key-role. It has the potential
      advantages to deliver systemic therapy to all patients with an increased efficacy of radio-
      and chemotherapies distributed in a virgin field, identify patients with aggressive tumor
      biology that could recur shortly after surgery and thus would not benefit form an operation.
      Moreover neoadjuvant therapy could downstage the tumor avoiding major vessels resections,
      decrease positive margins resections and decrease post-operative pancreatic fistulas [6].
      Unfortunately imaging is no longer reliable in predicting resectability after neoadjuvant
      treatment [7]. The total mean direct cost of a patient with a resectable disease is $134,700,
      while for metastatic or unresectable patients this cost is $49,000-65,300 [8]. A properly
      staged patient provides a better resource allocation.

      Liquid biopsy provides an non-invasive signature of the tumor, it is based circulating
      genetic material coming from cellular turnover and thus especially from the tumor [9].
      Analyzing mutations on cell-free nucleic acids gives translational information on tumor
      biology and therefore on its clinico-pathological features and likely on its progression.
      Pancreatic cancer progression has long been studied. What is clear is that activating K-RAS
      mutations are an early event in most lesions, followed by inactivating mutations in CDKN2A,
      TP53 and SMAD4 [10]. Those 4 mountain genes are predictive of progression pattern in an
      autoptic study: patients with 2 or less genes mutations were more likely to develop
      oligometastatic failure and to harbor earlier disease stage at diagnosis compared to those
      with 3 or more mutated genes [11]. K-RAS mutations have been associated to a worse overall
      survival in particular when found in peripheral blood by liquid biopsy [12]. CDKN2A mutations
      have been associated to lymphatic invasion and widespread metastatic recurrence [13]. TP53
      mutations have been associated to poor differentiation and locoregional recurrence [13].
      Finally SMAD4 mutations have been associated to portal vein invasion, perineural invasion and
      lymph vessel invasion [14]. Besides evidences on those mountain genes there is a growing body
      of evidence of several stage and prognosis predictors: MET protein over expression
      significantly correlated with increased TNM stage and worsened survival [15]; EDIL3
      expression was significantly up-regulated in PDAC in both cell lines and clinical specimens
      and correlated with patients' TNM stage, T classification and overall survival times [16];
      BRCA1/BRCA2 mutation predict significantly shorter disease-free and overall survival [17];
      High RAB27A expression was significantly associated with vascular invasion and tumor stage
      [18].

      Those data have been validated on samples of the tumor and thus usually on specimens since
      only 53,3% of ultrasound guided biopsies provides enough material for histopathology and/or
      immunohistochemistry [19]. Recent evidences show that pancreatic cancer is one of the 4
      cancers, along with colorectal, gastroesophageal and breast cancer, in which detectable ctDNA
      levels are present either in localized either in metastatic stages [20]. As seen in previous
      studies, the concordance between plasma and primary tumor mutations is as high as 100% in
      pancreatic cancer [9, 21].

      The study of those mutations on liquid biopsy would provide non-invasive informations on
      preoperative staging and pattern progression and therefore a more accurate therapeutic
      planning.

      AIM OF THE PROJECT This study is a pilot study. Genomic data will be described along with the
      clinical features of the disease for each patient.

      The primary objective of this study is to evaluate the relationship of mutations of the main
      genes responsible for pancreatic cancer progression (K-RAS, CDKN2A, SMAD4 and TP53) along
      with others related to stage and prognosis (MET, BRCA1/BRCA2, EDIL3 and RAB27A) detected on
      peripheral blood and time to progression and vascular invasion in patients undergoing
      pancreatectomy. Other outcomes of interest will be clinicopathological and operative features
      such as operative time, type of vascular resection, clinical stage, pathological T-, N- and
      M-stage, margin status and overall-survival.

      MATERIALS AND METHOD Patients with non-metastatic PaC undergoing pancreatic resection will be
      enrolled from surgery departments of a multi center international web. Blood samples in EDTA
      will be centrifugated at 2300 rpm for 10min twice. Liquid biopsies will be preoperatively
      collected and stored at -80°. An protected anonymous multi parametric database will be filled
      with all relevant patient's and disease's informations (sex, birth date, comorbidities, BMI,
      lab tests, imaging clinical stage, operation time, operation type, ICU stay, Dindo-Clavien
      post-operative morbidity, pathological stage, TNM, Grading, ajcc 8th stage, perineural,
      vascular and lymphatic invasion, resection margins, disease free survival, overall survival)
      and K-RAS, CDKN2A, SMAD4, TP53, MET, BRCA1/BRCA2, RAB27A and EDIL3 somatic genetic mutations
      on liquid biopsy with Next Generation Sequencing (NGS).

      Recruitment will be multicentric: AOU sant'andrea di Roma, Policlinico Universitario Gemelli
      di Roma, St Vincent University Hospital Dublino, Policlinico Universitario di Modena.

      STATISTICAL ANALYSIS Assessment of relationship among gene mutations and vascular invasion
      will be performed by means of logistic regression models. An overall score will be prepared
      based on rounding of estimated log-odds ratios and its performance evaluated by means of ROC
      curves and C-statistic.

      An evaluation of the conditional association will also be performed by means of multivariable
      logistic regression models, which will be selected by minimizing the Akaike Information
      Criterion.

      To assess secondary outcomes we will also use Cox regression models in a similar fashion.

      To the best of our knowledge, there is information in the literature regarding the frequency
      of vascular invasion in pancreatectomies with vascular resection (56.7%), and about mutations
      of the genes of interest in pancreatic ductal adenocarcinoma (the lowest mutated allele
      frequency being 30% for CDKN2A). Since there is no previous hypothesis on the relationship
      among genes and vascular invasion, and since this study simply involves the analysis of a
      small amount of blood posing no additional risk for the patient, we decided to perform a
      pilot study based on 50 patients. A fully planned and adequately powered study will be then
      conducted on the basis of the results of this pilot study. The sample size of 50 is deemed
      small enough (considering, as stated, the no additional risk and no use of invasive
      techniques) but large enough to guarantee that the final contingency table is not sparse. All
      analyses will be conducted with the R software.

      CONCLUSIONS Non-metastatic PaC represent a challenge in staging and prognosis definition. A
      patient tailored treatment requires an accurate preoperative staging. Up to now more than 40%
      of patients thought to be resectable exit the operating room unresected and another 40% of
      resected patients recur within one year. Among patients who are offered a surgery, some would
      benefit of a neoadjuvant treatment and some others of palliative treatments. This is why a
      reliable preoperative staging is essential in therapeutic decisional making. Invasive
      diagnostic tests of the pancreas are expensive and risky due to its central retroperitoneal
      location. Liquid biopsy offers a non invasive tumor characterization. This study will be the
      first analyzing the relationship of the four major genes, along with 5 other prognostic
      genes, involved in pancreatic cancer genesis and progression and T stage with special
      attention to early recurrence and vascular invasion, by liquid biopsy. This will result in a
      better resource allocation, treatment planning and patients outcomes.

      REFERENCES

        1. Cancer Res. 2014; 74: 2913-2921

        2. Ann Surg Oncol. 2016 Jun;23(6):2028-37

        3. Cochrane Database Syst Rev. 2016 Jul 6;7:CD009323

        4. J Gastrointest Surg 2004 Dec;8(8):935-49

        5. Ann Surg 2018 Mar 23 Epub ahead of print.

        6. J Gastrointest Oncol. 2015 Aug;6(4):418-29.

        7. Ann Surg. 2017 Dec 7. doi: 10.1097/SLA.0000000000002600. [Epub ahead of print]

        8. Cancer. 2012 Oct 15;118(20):5132-9

        9. Science 2018 Feb 23:359(6378):926-930.

       10. Oncogene. 2013 Nov 7;32(45):5253-60.

       11. Clin Cancer Res 2012 Nov 15;18(22):6229-47.

       12. Cancer 2015 Jul 1;121(13):2271-80.

       13. Ann Surg 2013 Aug;258(2):336-46.

       14. Pancreas 2015 May;44(4):660-4.

       15. World J Gastroenterol 2014 Jul 14;20(26):8458-70.

       16. Oncotarget 2016 Jan 26;7(4):4226-40.

       17. J Am Coll Surg 2018 Apr;226(4):630-637.

       18. Med Oncol (2015) 32:372.

       19. Gastrointest Endosc. 2016 Oct;84(4):670-8.

       20. Sci Transl Med 2014 Feb 19;6(224):224ra24.

       21. Proc Natl Acad Sci U S A 2017 Sep 19;114(38):10202-10207.
    


Study Type

Observational


Primary Outcome

Vascular Invasion

Secondary Outcome

 Overall Survival

Condition

Pancreatic Cancer

Intervention

Liquid Biopsy

Study Arms / Comparison Groups

 Non metastatic pancreatic cancer
Description:  patients with biopsy or fnac proven ductal adenocarcinoma without any systemic metastatic spread at preoperative imaging

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

50

Start Date

January 23, 2019

Completion Date

January 2020

Primary Completion Date

November 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Non metastatic Pancreatic Cancer

        Exclusion Criteria:

          -  <18y
      

Gender

All

Ages

18 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

Giovanni Ramacciato, MD, FACS, +393470409876, [email protected]

Location Countries

Ireland

Location Countries

Ireland

Administrative Informations


NCT ID

NCT03524677

Organization ID

17_D'Angelo


Responsible Party

Principal Investigator

Study Sponsor

University of Roma La Sapienza

Collaborators

 Azienda Ospedaliero, Universitaria Pisana

Study Sponsor

Giovanni Ramacciato, MD, FACS, Study Chair, Sapieza University of Rome (IT)


Verification Date

January 2019