title: Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study.
abstract: OBJECTIVE
  This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.
  
  
  METHODS
  In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m2/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).
  
  
  RESULTS
  Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).
  
  
  CONCLUSIONS
  Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Sang Myung
authors.initials: SM
authors.lastname: Woo
authors.affiliation: Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Biometric Research Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Goyang, Korea.
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.affiliation: College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors.forename: Kyong-Ah
authors.initials: KA
authors.lastname: Yoon
authors.affiliation: Biometric Research Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Goyang, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Park
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Sang-Jae
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Sung-Sik
authors.initials: SS
authors.lastname: Han
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Hong
authors.affiliation: Molecular Imaging and Therapy Branch, Research Institute National Cancer Center, Goyang, Korea.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Emergency Department, National Cancer Center, Goyang, Korea.
authors.forename: Hae
authors.initials: H
authors.lastname: Moon
authors.affiliation: Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.|Department of Laboratory Medicine, Center for Diagnostic Oncology, National Cancer Center, Goyang, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Cisplatin; Gemcitabine; Pancreatic neoplasms; Radiotherapy