title: A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458).
abstract: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC.
  
  
  
  A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT.
  
  
  
  Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached).
  
  
  
  The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.
authors.affiliation: Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Walid L
authors.initials: WL
authors.lastname: Shaib
authors.affiliation: Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Natalyn
authors.initials: N
authors.lastname: Hawk
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cassidy
authors.affiliation: Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Edith
authors.initials: E
authors.lastname: Brutcher
authors.affiliation: Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: David
authors.initials: D
authors.lastname: Kooby
authors.affiliation: Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Sarmiento
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Jerome
authors.initials: J
authors.lastname: Landry
authors.affiliation: Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. Electronic address: bassel.el-rayes@emoryhealthcare.org.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000628:therapy*; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology*; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods*; D018714:Radiotherapy, Adjuvant / Q000379:methods; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin