title: Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy.
abstract: BACKGROUND
  Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival.
  
  
  METHODS
  We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan-Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax).
  
  
  RESULTS
  Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients.
  
  
  CONCLUSIONS
  Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC.
authors.affiliation: a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.|b Department of Radiation Oncology , University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center , Miami , Florida , USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Mellon
authors.affiliation: a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Jin
authors.affiliation: a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Frakes
authors.affiliation: c Department of Pathology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.affiliation: a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Tobin J
authors.initials: TJ
authors.lastname: Strom
authors.affiliation: d Gastrointestinal Tumor Program , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Springett
authors.affiliation: d Gastrointestinal Tumor Program , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Mokenge P
authors.initials: MP
authors.lastname: Malafa
authors.affiliation: e Department of Radiation Oncology , Florida Hospital Cancer Institute , Orlando , Florida , USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shridhar
authors.affiliation: d Gastrointestinal Tumor Program , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hodul
authors.affiliation: a Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida , USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hoffe
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D011379:Prognosis; D016634:Radiosurgery; D016019:Survival Analysis; D016896:Treatment Outcome