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A Delay in Adjuvant Therapy Is Associated With Worse Prognosis Only in Patients With Transitional Circulating Tumor Cells After Resection of Pancreatic Ductal Adenocarcinoma.
Javed, Ammar A; Floortje van Oosten, Anne; Habib, Joseph R; Hasanain, Alina; Kinny-Köster, Benedict; Gemenetzis, Georgios; Groot, Vincent P; Ding, Ding; Cameron, John L; Lafaro, Kelly J; Burns, William R; Burkhart, Richard A; Yu, Jun; He, Jin; Wolfgang, Christopher L.
Afiliação
  • Javed AA; Department of Surgery, New York University Langone Hospital, New York City, NY.
  • Floortje van Oosten A; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Habib JR; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Hasanain A; Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht University, The Netherlands.
  • Kinny-Köster B; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Gemenetzis G; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Groot VP; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Ding D; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Cameron JL; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Lafaro KJ; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Burns WR; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell, Manhasset, NY.
  • Burkhart RA; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Yu J; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • He J; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Wolfgang CL; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD.
Ann Surg ; 277(6): 866-872, 2023 06 01.
Article em En | MEDLINE | ID: mdl-36111839
OBJECTIVES: The aim of the study was to assess the association of circulating tumor cells (CTCs) with survival as a biomarker in pancreatic ductal adenocarcinoma (PDAC) within the context of a delay in the initiation of adjuvant therapy. BACKGROUND: Outcomes in patients with PDAC remain poor and are driven by aggressive systemic disease. Although systemic therapies improve survival in resected patients, factors such as a delay in the initiation of adjuvant therapy are associated with worse outcomes. CTCs have previously been shown to be predictive of survival. METHODS: A retrospective study was performed on PDAC patients enrolled in the prospective CircuLating tUmor cellS in pancreaTic cancER trial (NCT02974764) on CTC-dynamics at the Johns Hopkins Hospital. CTCs were isolated based on size (isolation by size of epithelial tumor cells; Rarecells) and counted and characterized by subtype using immunofluorescence. The preoperative and postoperative blood samples were used to identify 2 CTC types: epithelial CTCs (eCTCs), expressing pancytokeratin, and transitional CTCs (trCTCs), expressing both pancytokeratin and vimentin. Patients who received adjuvant therapy were compared with those who did not. A delay in the receipt of adjuvant therapy was defined as the initiation of therapy ≥8 weeks after surgical resection. Clinicopathologic features, CTCs characteristics, and outcomes were analyzed. RESULTS: Of 101 patients included in the study, 43 (42.5%) experienced a delay in initiation and 20 (19.8%) did not receive adjuvant therapy. On multivariable analysis, the presence of trCTCs ( P =0.002) and the absence of adjuvant therapy ( P =0.032) were associated with worse recurrence-free survival (RFS). Postoperative trCTC were associated with poorer RFS, both in patients with a delay in initiation (12.4 vs 17.9 mo, P =0.004) or no administration of adjuvant chemotherapy (3.4 vs NR, P =0.016). However, it was not associated with RFS in patients with timely initiation of adjuvant chemotherapy ( P =0.293). CONCLUSIONS: Postoperative trCTCs positivity is associated with poorer RFS only in patients who either experience a delay in initiation or no receipt of adjuvant therapy. This study suggests that a delay in the initiation of adjuvant therapy could potentially provide residual systemic disease (trCTCs) a window of opportunity to recover from the surgical insult. Future studies are required to validate these findings and explore the underlying mechanisms involved.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Células Neoplásicas Circulantes Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Células Neoplásicas Circulantes Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article