title: Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.
abstract: Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Ailín C
authors.initials: AC
authors.lastname: Rogers
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Gibbons
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Hanly
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: John M P
authors.initials: JM
authors.lastname: Hyland
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: P Ronan
authors.initials: PR
authors.lastname: O'Connell
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Desmond C
authors.initials: DC
authors.lastname: Winter
authors.affiliation: 1] Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland [2] School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Kieran
authors.initials: K
authors.lastname: Sheahan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002454:Cell Differentiation; D002465:Cell Movement; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D009361:Neoplasm Invasiveness; D018579:Patient Selection; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome