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PSM

PSM Abstract Session 1

12: The Landscape of Circulating Tumor DNA (ctDNA) in Appendiceal Adenocarcinoma (AA)

Saturday, February 17, 2024
9:55 AM - 10:05 AM AST
Location: Miramar I & II

    Abstract Presenter(s)

  • Michael G. White, MD, M.Sc.

    Assistant Professor
    Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston TX, USA
    Houston, Texas, United States

    • Submitter(s)

  • Michael G. White, MD, M.Sc.

    Assistant Professor
    Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston TX, USA
    Houston, Texas, United States

    • Author(s)

  • Michael G. White, MD, M.Sc.

    Assistant Professor
    Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston TX, USA
    Houston, Texas, United States

  • MZ

    Mohammad Zeineddine, MD

    Resident
    Cleveland Clinic Akron General Hospital, United States

  • EF

    Eleanor Fallon, MD

    Complex general surgical oncology fellow
    University of Texas MD Anderson Cancer Center, United States

  • FZ

    Fadl Zeineddine, MD

    Research Fellow
    The University of Texas MD Anderson Cancer Center, United States

  • JD

    Julia Dansby, MD

    Fellow
    The University of Texas MD Anderson Cancer Center, United States

  • SC

    Saikat Chowdhury, PhD

    Research Fellow
    The University of Texas MD Anderson Cancer Center, United States

  • NH

    Nicholas Hornstein, MD, PhD

    Fellow
    The University of Texas MD Anderson Cancer Center, United States

  • YA

    Yousef Abdelrahman, MD

    Research Fellow
    The University of Texas MD Anderson Cancer Center, United States

  • MY

    Mahmoud Yousef, MD

    Research Fellow
    The University of Texas MD Anderson Cancer Center, United States

  • Neal Bhutiani, M.D.

    Fellow, Colorectal Surgery
    Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston TX, USA
    Houston, Texas, United States

  • YG

    Yue Gu, n/a

    Graduate Research Assistant
    The University of Texas MD Anderson Cancer Center, United States

  • KR

    Kanwal Raghav, MBBS, MD

    Associate Professor
    The University of Texas MD Anderson Cancer Center, United States

  • SK

    Scott Kopetz, MD, PhD

    Professor
    The University of Texas MD Anderson Cancer Center, United States

  • AU

    Abhineet Uppal, M.D.

    Assistant Professor
    Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston TX, USA, United States

  • Beth A. Helmink, M.D. Ph.D. (she/her/hers)

    Assistant Professor
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX, USA
    Houston, Texas, United States

  • MT

    Melissa Taggart, MD

    Professor
    The University of Texas MD Anderson Cancer Center, United States

  • Tim Newhook, MD

    Assistant Professor
    The University of Texas MD Anderson Cancer Center

  • KF

    Keith F. Fournier, MD

    Associate Professor
    Division of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, United States, United States

  • LD

    Leylah Drubosky, n/a

    Director of Medical Strategy
    Guardant Health, United States

  • John Paul Shen, MD (he/him/his)

    Assistant Professor
    The University of Texas MD Anderson Cancer Center, Texas, United States

Disclosure(s):
Michael G. White, MD, M.Sc.: No financial relationships to disclose
John Paul Shen, MD: BostonGene: Research Grant (Ongoing); Celsius Therapeutics: Research Grant (Terminated, January 2, 2024); Engine Biosciences: Advisor (Ongoing); NaDeNo Nanosciences: Advisor (Ongoing)
Introduction: AA is a rare cancer that rarely metastasizes hematogenously. Preliminary studies in AA have shown low rates of ctDNA positivity. Here we present the landscape of somatic alterations detected via ctDNA in AA from 713 patients with AA along with a single institution subset to assess survival implications of detectable ctDNA and identify clinical, pathologic, or molecular features associated with ctDNA positivity.


Methods: Plasma samples from 713 patients with AA were profiled with a plasma-based NGS assay (Guardant Health), performed as part of routine clinical care. Separately a cohort of 183 blood samples from 168 patients treated at our institution were profiled with a CLIA approved 70-gene, plasma-based NGS assay with clinical data extracted retrospectively using the Palantir-Foundry software system and manual chart review. Paired tumor sequencing was available for 47 patients.


Results: Of 713 plasma samples studied, 532 (75%) had ≥1 circulating somatic alteration(s) detected. The most frequent alterations occurred in TP53 (34.4%), KRAS (21.4%), ATM (13.1%), APC (8.6%) and GNAS (8.3%). This ctDNA mutational profile was distinct from that noted in 1,281 patients with colorectal cancer in whom the same assay was applied (Figure 1). TP53 had the highest mutational frequency in both blood (46%) and tumor (64%). Within AA, several genes co-occurred within the same tumor: TP53 and KRAS; KRAS and APC; KRAS and PIK3CA; TP53 and APC; KRAS and GNAS; among others (p< 0.001; q< 0.001). Of 153 plasma samples from our institution, 121 were evaluated in the setting of radiographically apparent metastatic disease which had a 37% somatic alteration detection rate, a similar detection rate of 40% (19/47) in 47 patients who had their ctDNA tests performed with no radiographic evidence of disease. ctDNA positivity increased with tumor grade 12/49 (24.5%), 17/44 (38.6%), and 29/60 (48.3%) for well-, moderate-, and poorly-differentiated tumors, respectively. When paired tissue and blood were available, the positive concordance of the assay was 20%, less than the concordance in 274 metastatic CRC patients (288/581=49.6%). ctDNA positivity was associated with a shorter overall survival (HR=2.34, p=0.04).


Conclusions: In patients with AA, the presence of detectable ctDNA is associated with shorter overall survival. The positive concordance of ctDNA with tumor sequence in metastatic AA is overall markedly lower than CRC, with detection more likely in high-grade tumors and higher positive concordance in tumors containing TP53 mutation. Further work is needed to incorporate this prognostic marker into clinical algorithms.

Learning Objectives:

  • Upon completion, participant will be able to describe differences in the unique tumoral and circulating mutational profiles of appendiceal and colorectal adenocarcinomas.
  • Upon completion, participant will be able to list factors associated with ctDNA positivity in appendiceal adenocarcinoma.
  • Upon completion, participant will be able to describe the impact of ctDNA positivity on survival in appendiceal adenocarcinoma.