title: Safety and efficacy of stereotactic body radiation therapy combined with S-1 simultaneously followed by sequential S-1 as an initial treatment for locally advanced pancreatic cancer (SILAPANC) trial: study design and rationale of a phase II clinical trial.
abstract: Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine. Additionally, stereotactic body radiation therapy with Cyberknife could provide better efficacy than conventional radiotherapy in pancreatic cancer. Therefore, Cyberknife with S-1 simultaneously followed by sequential S-1 as an initial treatment may bring about favourable outcomes but needs further studies.
  
  
  
  The S-1 as an initial treatment for locally advanced pancreatic cancer (SILAPANC) trial is a prospective, single-centre, one armed ongoing study. 190 eligible patients are required to initially receive Cyberknife with 1 cycle of S-1 simultaneously. After the concurrent chemoradiotherapy, 2 or 3 cycles of S-1 are sequentially given. Doses and fractions depend on the locations and volumes of tumours and the adjacent organs at risk. S-1 is taken orally, 2 times a day, at a dose of 80 mg/m2for 28 days, followed by a 14-day interval. The primary objectives are overall survival and 1-year, 2-year, 3-year, 4-year and 5-year overall survival rates. The secondary objectives are cancer-specific survival, progression-free survival, time to progression, local control rates, clinical benefit rates, radiation-induced acute and late toxicities, adverse effects of chemotherapy and quality of life of patients. Besides, variables most predictive of prognosis would be identified via multivariate methods.
  
  
  
  Approvals have been granted by the Changhai Hospital Ethics Committee (CHEC-2016-032-01). The results will be disseminated in peer-reviewed journals and at conferences.
  
  
  
  NCT02704143; Pre-results.
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ju
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Shuiwang
authors.initials: S
authors.lastname: Qing
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Yangsen
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China.
authors.forename: Huojun
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods; D018572:Disease-Free Survival; D004338:Drug Combinations; D006801:Humans; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011788:Quality of Life; D016634:Radiosurgery / Q000009:adverse effects; D012107:Research Design; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid