title: Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation.
abstract: OBJECTIVE
  To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent.
  
  
  METHODS
  A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest.
  
  
  RESULTS
  Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis.
  
  
  CONCLUSIONS
  Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas. Electronic address: skrishnan@mdanderson.org.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas.
authors.forename: Awalpreet S
authors.initials: AS
authors.lastname: Chadha
authors.affiliation: Department of Radiation Physics, The University of Texas, Houston, Texas.
authors.forename: Yelin
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Arvind
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas.
authors.forename: Prajnan
authors.initials: P
authors.lastname: Das
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Minsky
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas.
authors.forename: Usama
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Delclos
authors.affiliation: Department of Radiation Physics, The University of Texas, Houston, Texas; Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas.
authors.forename: Gabriel O
authors.initials: GO
authors.lastname: Sawakuchi
authors.affiliation: Department of Radiation Physics, The University of Texas, Houston, Texas.
authors.forename: Sam
authors.initials: S
authors.lastname: Beddar
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Katz
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Milind M
authors.initials: MM
authors.lastname: Javle
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Radiation Oncology, The University of Texas, Houston, Texas.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Crane
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D062485:Breath Holding; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011859:Radiography; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden / Q000528:radiation effects