Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2018

01-08-2018 | Gastrointestinal Oncology

Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is an Independent Predictor of Progression-Free Survival

Authors: Joel M. Baumgartner, MD, MAS, Victoria M. Raymond, MS, MBA, Richard B. Lanman, MD, Lisa Tran, MS, Kaitlyn J. Kelly, MD, Andrew M. Lowy, MD, Razelle Kurzrock, MD

Published in: Annals of Surgical Oncology | Issue 8/2018

Login to get access

Abstract

Background

Next-generation sequencing (NGS) is a useful tool for detecting genomic alterations in circulating tumor DNA (ctDNA). To date, most ctDNA tests have been performed on patients with widely metastatic disease. Patients with peritoneal carcinomatosis (metastases) present unique prognostic and therapeutic challenges. We therefore explored preoperative ctDNA in patients with peritoneal metastases undergoing surgery.

Methods

Patients referred for surgical resection of peritoneal metastases underwent preoperative blood-derived ctDNA analysis (clinical-grade NGS [68–73 genes]). ctDNA was quantified as the percentage of altered circulating cell-free DNA (% cfDNA).

Results

Eighty patients had ctDNA testing: 46 (57.5%) women; median age 55.5 years. The following diagnoses were included: 59 patients (73.8%), appendix cancer; 11 (13.8%), colorectal; five (6.3%), peritoneal mesothelioma; two (2.5%), small bowel; one (1.3%) each of cholangiocarcinoma, ovarian, and testicular cancer. Thirty-one patients (38.8%) had detectable preoperative ctDNA alterations, most frequently in the following genes: TP53 (25.8% of all alterations detected) and KRAS (11.3%). Among 15 patients with tissue DNA NGS, 33.3% also had ctDNA alterations (overall concordance = 96.7%). Patients with high ctDNA quantities (≥ 0.25% cfDNA, n = 25) had a shorter progression-free survival (PFS) than those with lower ctDNA quantities (n = 55; 7.8 vs. 15.0 months; hazard ratio 3.23, 95% confidence interval 1.43–7.28, p = 0.005 univariate, p = 0.044 multivariate).

Conclusions

A significant proportion of patients with peritoneal metastases referred for surgical intervention have detectable ctDNA alterations preoperatively. Patients with high levels of ctDNA have a worse prognosis independent of histologic grade.
Literature
1.
Schwaederle M, Zhao M, Lee JJ, et al. Impact of precision medicine in diverse cancers: a meta-analysis of Phase II clinical trials. J Clin Oncol. 2015;33(32):3817–25.CrossRefPubMedPubMedCentral
2.
Sinicrope FA, Okamoto K, Kasi PM, Kawakami H. Molecular biomarkers in the personalized treatment of colorectal cancer. Clin Gastroenterol Hepatol. 2016;14(5):651–8.CrossRefPubMedPubMedCentral
3.
Ghadimi BM, Jo P. Cancer gene profiling for response prediction. Methods Mol Biol (Clifton, N.J.). 2016;1381:163–79.
4.
Tsimberidou AM, Iskander NG, Hong DS, et al. Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res. 2012;18(22):6373-6383.CrossRefPubMedPubMedCentral
5.
Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92.CrossRefPubMedPubMedCentral
6.
Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90.CrossRefPubMed
7.
Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–38.
8.
Janku F, Angenendt P, Tsimberidou AM, et al. Actionable mutations in plasma cell-free DNA in patients with advanced cancers referred for experimental targeted therapies. Oncotarget. 2015;6(14):12809–21.CrossRefPubMedPubMedCentral
9.
10.
Husain H, Melnikova VO, Kosco K, et al. Monitoring daily dynamics of early tumor response to targeted therapy by detecting circulating tumor DNA in urine. Clin Cancer Res. 2017;23(16):4716–23.CrossRefPubMedPubMedCentral
11.
Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence - SEER 9 Regs Research Data, Nov 2013 Sub (1973–2011) ed. National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch 2013.
12.
Franko J, Shi Q, Goldman CD, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012;30(3):263–7.CrossRefPubMed
13.
Hasovits C, Clarke S. Pharmacokinetics and pharmacodynamics of intraperitoneal cancer chemotherapeutics. Clin Pharmacokinet. 2012;51(4):203–24.CrossRefPubMed
14.
Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449–56.CrossRefPubMed
15.
Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh HJ, 3rd. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116(16):3756–62.CrossRefPubMed
16.
Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.CrossRefPubMed
17.
Cashin PH, Mahteme H, Spang N, et al. Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: a randomised trial. Eur. J. Cancer (Oxford, England : 1990). 2016;53:155–62.
18.
van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230–40.CrossRefPubMed
19.
Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15(9):2426–32.CrossRefPubMed
20.
Pasqual EM, Bertozzi S, Bacchetti S, et al. Preoperative assessment of peritoneal carcinomatosis in patients undergoing hyperthermic intraperitoneal chemotherapy following cytoreductive surgery. Anticancer Res. 2014;34(5):2363–8.PubMed
21.
de Bree E, Koops W, Kroger R, van Ruth S, Witkamp AJ, Zoetmulder FA. Peritoneal carcinomatosis from colorectal or appendiceal origin: correlation of preoperative CT with intraoperative findings and evaluation of interobserver agreement. J Surg Oncol. 2004;86(2):64–73.CrossRefPubMed
22.
McMullen JRW, Selleck M, Wall NR, Senthil M. Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy. Oncotarget. 2017.
23.
Baumgartner JM, Tobin L, Heavey SF, Kelly KJ, Roeland EJ, Lowy AM. Predictors of progression in high-grade appendiceal or colorectal peritoneal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2015;22(5):1716–21.CrossRefPubMed
24.
Lanman RB, Mortimer SA, Zill OA, et al. Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS One. 2015;10(10):e0140712.CrossRefPubMedPubMedCentral
25.
Portilla AG, Shigeki K, Dario B, Marcello D. The intraoperative staging systems in the management of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):228–31.CrossRefPubMed
26.
Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224.
27.
Fang WL, Lan YT, Huang KH, et al. Clinical significance of circulating plasma DNA in gastric cancer. Int J Cancer. 2016;138(12):2974–83.CrossRefPubMed
28.
Schwaederle M, Chattopadhyay R, Kato S, et al. Genomic alterations in circulating tumor DNA from diverse cancer patients identified by next-generation sequencing. Cancer Res. 2017.
29.
Rivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 Tumor suppressor gene: important milestones at the various steps of tumorigenesis. Genes Cancer. 2011;2(4):466–74.CrossRef
30.
Schwaederle M, Husain H, Fanta PT, et al. Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay. Oncotarget. 2016;7(9):9707–17.CrossRefPubMedPubMedCentral
31.
Schwaederle MC, Patel SP, Husain H, et al. Utility of Genomic Assessment of Blood-Derived Circulating Tumor DNA (ctDNA) in Patients with Advanced Lung Adenocarcinoma. Clin Cancer Res. 2017;23(17):5101–11.CrossRefPubMedPubMedCentral
32.
Schwaederle M, Husain H, Fanta PT, et al. Use of liquid biopsies in clinical oncology: pilot experience in 168 patients. Clin Cancer Res. 2016;22(22):5497–505.CrossRefPubMed
33.
Austin F, Mavanur A, Sathaiah M, et al. Aggressive management of peritoneal carcinomatosis from mucinous appendiceal neoplasms. Ann Surg Oncol. 2012;19(5):1386–93.CrossRefPubMedPubMedCentral
34.
Genovese G, Kahler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–87.CrossRefPubMedPubMedCentral
35.
Kato S, Lippman SM, Flaherty KT, Kurzrock R. The conundrum of genetic “Drivers” in benign conditions. J Nat Cancer Inst. 2016;108(8).
Metadata
Title
Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is an Independent Predictor of Progression-Free Survival
Authors
Joel M. Baumgartner, MD, MAS
Victoria M. Raymond, MS, MBA
Richard B. Lanman, MD
Lisa Tran, MS
Kaitlyn J. Kelly, MD
Andrew M. Lowy, MD
Razelle Kurzrock, MD
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6561-z

Other articles of this Issue 8/2018

Annals of Surgical Oncology 8/2018 Go to the issue

Breast Oncology

Axillary Surgery for Early-Stage, Node-Positive Mastectomy Patients and the Use of Postmastectomy Chest Wall Radiation Therapy

Breast Oncology

Inhibition Mechanism of Acellular Dermal Matrix on Capsule Formation in Expander–Implant Breast Reconstruction After Postmastectomy Radiotherapy

Gastrointestinal Oncology

Current Management and Future Opportunities for Peritoneal Metastases

Hepatobiliary Tumors

RAS Mutation is Associated with Unsalvageable Recurrence Following Hepatectomy for Colorectal Cancer Liver Metastases

Breast Oncology

Routine Axillary Ultrasound for Patients with T1–T2 Breast Cancer Does Not Increase the Rate of Axillary Lymph Node Dissection Based on Predictive Modeling

Colorectal Cancer

Nationwide Heterogeneity in Hospital-Specific Probabilities of Rectal Cancer Understaging and Its Effects on Outcomes