title: Perineural Invasion Predicts for Distant Metastasis in Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation and Surgery.
abstract: OBJECTIVE
  The benefit of adjuvant chemotherapy in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and surgery is controversial. We examined the association of perineural invasion (PNI) with outcomes to determine whether PNI could be used to risk-stratify patients.
  
  
  METHODS
  We performed a retrospective study of 110 patients treated with nCRT and surgery for LARC at our institution from 2004 to 2011. Eighty-seven patients were identified in our final analysis. We evaluated the association of PNI with locoregional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival, using log-rank and Cox proportional hazard modeling.
  
  
  RESULTS
  Fourteen patients (16%) were PNI+ and 73 patients (84%) were PNI-. The median follow-up was 27 months (range, 0.9 to 84 mo). The median DMFS was 13.5 months for PNI+ and median not reached (>40 mo) for PNI- (P<0.0001). The median DFS was 13.5 months for PNI+ and 39.8 months for PNI- (P<0.0001). In a multivariate model including 7 pathologic variables, type of surgery, time to surgery from end of nCRT, and use of adjuvant chemotherapy, PNI remained a significant independent predictor of DMFS (hazard ratio 9.79; 95% confidence interval, 3.48-27.53; P<0.0001) and DFS (hazard ratio 5.72; 95% confidence interval, 2.2-14.9; P=0.0001).
  
  
  CONCLUSIONS
  For patients with LARC treated with nCRT, PNI found at the time of surgery is significantly associated with worse DMFS and DFS. Our data support testing the role of adjuvant chemotherapy in patients with PNI and perhaps other high-risk features.
authors.affiliation: Department of Radiation Oncology.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Chablani
authors.affiliation: Department of Radiation Oncology.
authors.forename: Phuong
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Center for Biostatistics.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Radiation Oncology.
authors.forename: Andrew
authors.initials: A
authors.lastname: Robinson
authors.affiliation: Department of Radiation Oncology.
authors.forename: Steve
authors.initials: S
authors.lastname: Walston
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: Christina
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.affiliation: Department of Radiation Oncology.
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Department of Radiation Oncology.
authors.forename: Evan
authors.initials: E
authors.lastname: Wuthrick
authors.affiliation: Department of Radiation Oncology.
authors.forename: Terence M
authors.initials: TM
authors.lastname: Williams
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059248:Chemoradiotherapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000473:pathology* / Q000628:therapy; D012007:Rectum / Q000601:surgery*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult