title: Prevalence of bone marrow micrometastases in esophagogastric cancer patients with and without neoadjuvant chemoradiotherapy.
abstract: BACKGROUND
  Bone marrow micrometastases are present in a high proportion of patients undergoing curative resection for esophagogastric cancer. The incorporation of preoperative systemic therapies into these patients' treatment is widely practiced. This study investigates the effect of neoadjuvant chemoradiotherapy (CRT) on the incidence of micrometastases and the viability of detected tumor cells.
  
  
  METHODS
  Rib bone marrow was obtained from patients (n = 106) in three centers, who were selected for potentially curative resection. Patients received neoadjuvant CRT plus surgery (n = 55), or surgery alone (n = 51). To detect micrometastases, mononuclear cells were isolated from fresh marrow and immediately stained immunohistochemically with an anti-cytokeratin-18 antibody using the APAAP technique. Tumor cell viability was assessed by immunohistochemical staining of marrow cell cultures for cytokeratin-positive cells.
  
  
  RESULTS
  Micrometastases were detected in fresh marrow in 42% (23/55) of patients who received neoadjuvant CRT plus surgery, and in 67% (34/51) of patients treated with surgery alone. Viable tumor cells were demonstrated in 10 of 18 marrow cultures from CRT plus surgery cases. In this patient subset, combination of results of staining fresh and cultured marrow significantly increased micromet detection to 78%.
  
  
  CONCLUSIONS
  A significant proportion of patients with esophagogastric cancer have disseminated viable tumor cells at time of surgery, irrespective of pre-operative treatment. The use of marrow culture in parallel with fresh marrow staining may increase the detection of micrometastases. The persistence of tumor cells resistant to systemic therapy may explain why these regimens fail in a majority of patients.
authors.affiliation: Cork Cancer Research Centre, National University of Ireland, Cork, Dublin, Ireland. geraldc@iol.ie
authors.forename: Paul
authors.initials: P
authors.lastname: Ryan
authors.forename: Seán
authors.initials: S
authors.lastname: McCarthy
authors.forename: Jacquie
authors.initials: J
authors.lastname: Kelly
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Collins
authors.forename: Colum
authors.initials: C
authors.lastname: Dunne
authors.forename: Liam
authors.initials: L
authors.lastname: Grogan
authors.forename: Oscar
authors.initials: O
authors.lastname: Breathnach
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.forename: P Declan
authors.initials: PD
authors.lastname: Carey
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Walsh
authors.forename: Gerald C
authors.initials: GC
authors.lastname: O'Sullivan
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary* / Q000628:therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019046:Bone Marrow Neoplasms / Q000453:epidemiology / Q000556:secondary* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000556:secondary* / Q000628:therapy; D002470:Cell Survival / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D015995:Prevalence; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D013274:Stomach Neoplasms / Q000473:pathology* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents