Skip to main content
Erschienen in:

30.10.2020 | Pancreatic Tumors

Clinical Implications of Pre- and Postoperative Circulating Tumor DNA in Patients with Resected Pancreatic Ductal Adenocarcinoma

verfasst von: Takuro Yamaguchi, MD, Kenichiro Uemura, MD, Yoshiaki Murakami, MD, Naru Kondo, MD, Naoya Nakagawa, MD, Kenjiro Okada, MD, Shingo Seo, MD, Eiso Hiyama, MD, Shinya Takahashi, MD, Taijiro Sueda, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 6/2021

Einloggen, um Zugang zu erhalten

Abstract

Background

The clinical implications of pre- and postoperative KRAS-mutated circulating tumor DNA (ctDNA) present in patients with pancreatic ductal adenocarcinoma (PDAC) have remained an unresolved issue. This study sought to investigate the clinical significance of pre- and postoperative ctDNA analyses and their impact on the prognosis of PDAC patients.

Methods

Digital droplet polymerase chain reaction detected ctDNA in pre- and postoperative plasma samples prospectively obtained from patients with resectable and borderline-resectable PDAC. Its associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. The patients were sorted according to the presence of pre- and postoperative ctDNA, and its ability to stratify prognosis was evaluated.

Results

The study analyzed 97 patients. Both pre- and postoperative ctDNA were detected in 9 patients, and neither was detected in 55 patients. Whereas 15 patients harbored only preoperative ctDNA, 18 patients had only postoperative ctDNA. The multivariate analysis showed that the presence of preoperative ctDNA was associated with poorer OS (P = 0.008) and that postoperative ctDNA was not associated with either RFS or OS. Survival did not differ significantly between the patients with a positive shift in ctDNA status and those without detectable pre- or postoperative ctDNA.

Conclusions

For the patients with PDAC, the presence of preoperative ctDNA was significantly associated poor OS, whereas postoperative ctDNA was not associated with poor survival. A positive change in ctDNA did not affect patients’ survival.
Literatur
1.
Zurück zum Zitat Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.CrossRef
2.
Zurück zum Zitat Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–87.CrossRef Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–87.CrossRef
3.
Zurück zum Zitat Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.CrossRef Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.CrossRef
4.
Zurück zum Zitat Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol. 2019;10:10–27.CrossRef Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol. 2019;10:10–27.CrossRef
5.
Zurück zum Zitat Sausen M, Phallen J, Adleff V, et al. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun. 2015;6:7686.CrossRef Sausen M, Phallen J, Adleff V, et al. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun. 2015;6:7686.CrossRef
6.
Zurück zum Zitat Biankin AV, Waddell N, Kassahn KS, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491:399–405.CrossRef Biankin AV, Waddell N, Kassahn KS, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491:399–405.CrossRef
7.
Zurück zum Zitat Uemura K, Hiyama E, Murakami Y, et al. Comparative analysis of K-ras point mutation, telomerase activity, and p53 overexpression in pancreatic tumours. Oncol Rep. 2003;10:277–83.PubMed Uemura K, Hiyama E, Murakami Y, et al. Comparative analysis of K-ras point mutation, telomerase activity, and p53 overexpression in pancreatic tumours. Oncol Rep. 2003;10:277–83.PubMed
8.
Zurück zum Zitat Rhim AD, Thege FI, Santana SM, et al. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology. 2014;146:647–51.CrossRef Rhim AD, Thege FI, Santana SM, et al. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology. 2014;146:647–51.CrossRef
9.
Zurück zum Zitat di Magliano MP, Logsdon CD. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology. 2013;144:1220–9.CrossRef di Magliano MP, Logsdon CD. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology. 2013;144:1220–9.CrossRef
10.
Zurück zum Zitat Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549–54.CrossRef Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549–54.CrossRef
11.
Zurück zum Zitat Kanda M, Matthaei H, Wu J, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology. 2012;142:730–733.e739. Kanda M, Matthaei H, Wu J, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology. 2012;142:730–733.e739.
12.
Zurück zum Zitat Bryant KL, Mancias JD, Kimmelman AC, Der CJ. KRAS: feeding pancreatic cancer proliferation. Trends Biochem Sci. 2014;39:91–100.CrossRef Bryant KL, Mancias JD, Kimmelman AC, Der CJ. KRAS: feeding pancreatic cancer proliferation. Trends Biochem Sci. 2014;39:91–100.CrossRef
13.
Zurück zum Zitat Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989;49:4682–9.PubMed Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989;49:4682–9.PubMed
14.
Zurück zum Zitat Mandel P, Metais P. Les acides nucléiques du plasma sanguin chez l'homme. C R Seances Soc Biol Fil. 1948;142:241–3.PubMed Mandel P, Metais P. Les acides nucléiques du plasma sanguin chez l'homme. C R Seances Soc Biol Fil. 1948;142:241–3.PubMed
15.
Zurück zum Zitat Riva F, Dronov OI, Khomenko DI, et al. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer. Mol Oncol. 2016;10:481–93.CrossRef Riva F, Dronov OI, Khomenko DI, et al. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer. Mol Oncol. 2016;10:481–93.CrossRef
16.
Zurück zum Zitat Hadano N, Murakami Y, Uemura K, et al. Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. Br J Cancer. 2016;115:59–65.CrossRef Hadano N, Murakami Y, Uemura K, et al. Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. Br J Cancer. 2016;115:59–65.CrossRef
17.
Zurück zum Zitat Del Re M, Vivaldi C, Rofi E, et al. Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer. Sci Rep. 2017;7:7931.CrossRef Del Re M, Vivaldi C, Rofi E, et al. Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer. Sci Rep. 2017;7:7931.CrossRef
18.
Zurück zum Zitat Yamada T, Nakamori S, Ohzato H, et al. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res. 1998;4:1527–32.PubMed Yamada T, Nakamori S, Ohzato H, et al. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res. 1998;4:1527–32.PubMed
19.
Zurück zum Zitat Uemura T, Hibi K, Kaneko T, et al. Detection of K-ras mutations in the plasma DNA of pancreatic cancer patients. J Gastroenterol. 2004;39:56–60.CrossRef Uemura T, Hibi K, Kaneko T, et al. Detection of K-ras mutations in the plasma DNA of pancreatic cancer patients. J Gastroenterol. 2004;39:56–60.CrossRef
20.
Zurück zum Zitat Overman DM, Jacobs JP, Prager RL, et al. Report from the Society of Thoracic Surgeons National Database Workforce: clarifying the definition of operative mortality. World J Pediatr Congenital Heart Surg. 2013;4:10–12.CrossRef Overman DM, Jacobs JP, Prager RL, et al. Report from the Society of Thoracic Surgeons National Database Workforce: clarifying the definition of operative mortality. World J Pediatr Congenital Heart Surg. 2013;4:10–12.CrossRef
21.
Zurück zum Zitat Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw. 2014;12:1083–93.CrossRef Tempero MA, Malafa MP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw. 2014;12:1083–93.CrossRef
22.
Zurück zum Zitat Murakami Y, Uemura K, Sudo T, et al. Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol. 2017;79:37–47.CrossRef Murakami Y, Uemura K, Sudo T, et al. Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol. 2017;79:37–47.CrossRef
23.
Zurück zum Zitat Kondo N, Murakami Y, Uemura K, et al. A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2017;79:775–81.CrossRef Kondo N, Murakami Y, Uemura K, et al. A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2017;79:775–81.CrossRef
24.
Zurück zum Zitat Murakami Y, Uemura K, Sudo T, et al. Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg. 2008;195:757–62.CrossRef Murakami Y, Uemura K, Sudo T, et al. Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg. 2008;195:757–62.CrossRef
25.
Zurück zum Zitat Murakami Y, Uemura K, Sudo T, et al. Long-term results of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic carcinoma. J Surg Oncol. 2012;106:174–80.CrossRef Murakami Y, Uemura K, Sudo T, et al. Long-term results of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic carcinoma. J Surg Oncol. 2012;106:174–80.CrossRef
26.
Zurück zum Zitat Sobin L, Gospodarowicz M, Wittekind C (eds). International Union Against Cancer (UICC): TNM Classification of Malignant Tumours. 7th ed. Wiley-Blackwell, New York, 2010. Sobin L, Gospodarowicz M, Wittekind C (eds). International Union Against Cancer (UICC): TNM Classification of Malignant Tumours. 7th ed. Wiley-Blackwell, New York, 2010.
27.
Zurück zum Zitat Grünewald K, Lyons J, Fröhlich A, et al. High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer. 1989;43:1037–41.CrossRef Grünewald K, Lyons J, Fröhlich A, et al. High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer. 1989;43:1037–41.CrossRef
28.
Zurück zum Zitat Kinugasa H, Nouso K, Miyahara K, et al. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. Cancer. 2015;121:2271–80.CrossRef Kinugasa H, Nouso K, Miyahara K, et al. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. Cancer. 2015;121:2271–80.CrossRef
29.
Zurück zum Zitat Cabel L, Proudhon C, Mariani P, et al. Circulating tumor cells and circulating tumor DNA: what surgical oncologists need to know? Eur J Surg Oncol. 2017;43:949–62.CrossRef Cabel L, Proudhon C, Mariani P, et al. Circulating tumor cells and circulating tumor DNA: what surgical oncologists need to know? Eur J Surg Oncol. 2017;43:949–62.CrossRef
30.
Zurück zum Zitat Pietrasz D, Pecuchet N, Garlan F, et al. Plasma-circulating tumor DNA in pancreatic cancer patients is a prognostic marker. Clin Cancer Res. 2017;23:116–23.CrossRef Pietrasz D, Pecuchet N, Garlan F, et al. Plasma-circulating tumor DNA in pancreatic cancer patients is a prognostic marker. Clin Cancer Res. 2017;23:116–23.CrossRef
31.
Zurück zum Zitat Gall TM, Jacob J, Frampton AE, et al. Reduced dissemination of circulating tumor cells with no-touch isolation surgical technique in patients with pancreatic cancer. JAMA Surg. 2014;149:482–5.CrossRef Gall TM, Jacob J, Frampton AE, et al. Reduced dissemination of circulating tumor cells with no-touch isolation surgical technique in patients with pancreatic cancer. JAMA Surg. 2014;149:482–5.CrossRef
32.
Zurück zum Zitat Nakano Y, Kitago M, Matsuda S, et al. KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study. Br J Cancer. 2018;118:662–9.CrossRef Nakano Y, Kitago M, Matsuda S, et al. KRAS mutations in cell-free DNA from preoperative and postoperative sera as a pancreatic cancer marker: a retrospective study. Br J Cancer. 2018;118:662–9.CrossRef
Metadaten
Titel
Clinical Implications of Pre- and Postoperative Circulating Tumor DNA in Patients with Resected Pancreatic Ductal Adenocarcinoma
verfasst von
Takuro Yamaguchi, MD
Kenichiro Uemura, MD
Yoshiaki Murakami, MD
Naru Kondo, MD
Naoya Nakagawa, MD
Kenjiro Okada, MD
Shingo Seo, MD
Eiso Hiyama, MD
Shinya Takahashi, MD
Taijiro Sueda, MD
Publikationsdatum
30.10.2020
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 6/2021
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-09278-9

Neu im Fachgebiet Chirurgie

Ab sofort gelten die neuen Verordnungsausnahmen für Lipidsenker

Freie Fahrt für Lipidsenker? Das nicht, doch mit niedrigerem Schwellenwert fürs Infarktrisiko und neuen Indikationen hat der G-BA die Verordnungs-Handbremse ein gutes Stück weit gelockert.

Appendizitis und Darminfarkt durch Blinddarm-Lipom

Eigentlich sind Lipome recht harmlos. Im Zäkum können sie jedoch erhebliche Komplikationen mit Darminfarkt und Appendizitis verursachen.

Gluteuslappen nach Rektumkarzinom-Op. schützt vor Abszessen

Die Wunddeckung mit einem autologen Rotationslappen nach Entfernung eines Rektumkarzinoms konnte in einer randomisierten Studie gegenüber dem primären Wundverschluss vor allem in einer Hinsicht punkten: Sie führte deutlich seltener zu präsakralen Abszessen.

MedTalk Leitlinie KOMPAKT: S3-Leitline zu peripheren Nervenverletzungen

  • Webinar | 10.02.2025 | 13:00

Über den Weg zur finalen Fassung der S3-Leitlinie "Versorgung peripherer Nervenverletzungen" sprechen Prof. Dr. Leila Harhaus-Wähner und Ressortleiter Dr. Gunter Freese im WebTalk Leitlinie KOMPAKT, einer neuen Webcast-Serie von SpringerMedizin passend zu Ihrem Fachmagazin Orthopädie und Unfallchirurgie Mitteilungen und Nachrichten. In dem kurzen Video geht es darum, was sich im Vergleich zur vorigen Fassung der Leitlinie geändert hat, welche Aspekte für die tägliche Praxis besonders wichtig sind und was jeder gemäß Leitlinie nun anders oder besser machen sollte.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.