title: Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.
abstract: BACKGROUND
  Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy.
  
  
  METHODS
  We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher's exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival.
  
  
  RESULTS
  A total of 132 patients met the inclusion criteria with a median age of 62 (range 36-80) and median follow-up of 28 months (range 4-128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p = 0.01) and close/positive margins (p < 0.01). Regional nodal failure was correlated with fewer LN assessed (p < 0.01) and larger pretreatment tumor size (p = 0.04). Patients with ≤13 LN evaluated had an inferior locoregional RFS versus patients with >13 LN evaluated (p = 0.003). Distant recurrence was correlated with higher pathologic nodal stage (p < 0.001), ulceration (p = 0.017), perineural invasion (p = 0.029), residual disease (p = 0.004), and higher post-treatment PET SUV max (p = 0.049). Patients with a pathologic complete response (OR 0.19, 95% CI 0.05-0.68) were less likely to experience distant recurrence.
  
  
  CONCLUSIONS
  Tumor and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients.
authors.affiliation: a Department of Radiation Oncology , Fox Chase Cancer Center , Philadelphia , PA , USA ;
authors.forename: Talha
authors.initials: T
authors.lastname: Shaikh
authors.affiliation: b Department of Radiation Oncology , Wayne State University , Detroit , MI , USA ;
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zaki
authors.affiliation: b Department of Radiation Oncology , Wayne State University , Detroit , MI , USA ;
authors.forename: Michael M
authors.initials: MM
authors.lastname: Dominello
authors.affiliation: c Department of Biostatistics , Fox Chase Cancer Center , Philadelphia , PA , USA ;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Handorf
authors.affiliation: d Department of Radiation Oncology , University of Pennsylvania , Chester , PA , USA ;
authors.forename: Andre A
authors.initials: AA
authors.lastname: Konski
authors.affiliation: e Department of Medical Oncology , Fox Chase Cancer Center , Philadelphia , PA , USA ;
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: f Department of Medical Oncology , Wayne State University , Detroit , MI , USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Shields
authors.affiliation: f Department of Medical Oncology , Wayne State University , Detroit , MI , USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Philip
authors.affiliation: a Department of Radiation Oncology , Fox Chase Cancer Center , Philadelphia , PA , USA ;
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Meyer
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D017211:Treatment Failure