title: The efficacy of iodine-125 permanent brachytherapy versus intensity-modulated radiation for inoperable salivary gland malignancies: study protocol of a randomised controlled trial.
abstract: BACKGROUND
  Radiation therapy is the method of choice for subjects with inoperable salivary gland malignancies. I-125 brachytherapy, delivering a high radiation dose to a tumor but sparing surrounding normal tissues, is supposed to be ideal modality for the treatment of salivary gland malignancies. We designed a randomised controlled clinical trial to compare the efficacy of I-125 permanent brachytherapy (PBT) versus intensity-modulated radiation therapy (IMRT) for inoperable salivary gland malignancies.
  
  
  METHODS
  In this study, inclusion criteria are subjects with inoperable salivary gland malignancies, aged 18-80 years, have provided informed consent, with at least one measurable tumor focus, be able to survive ≥3 months, Karnofsky performance status ≥60, have adequate hematopoietic function of bone marrow, have normal liver and kidney function, and are willing to prevent pregnancy. Exclusion criteria include a history of radiation or chemotherapy, a history of other malignant tumors in the past 5 years, receiving other effective treatments, participating in other clinical trials, with circulatory metastasis, cognitive impairment, severe cardiovascular and cerebrovascular diseases, acute infection, uncontrolled systemic disease, history of interstitial lungdisease, and being pregnant or breast feeding. The study will be conducted as a clinical, prospective, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 90 subjects. Subjects with inoperable salivary gland malignancies are randomised to receive either I-125 PBT or IMRT, with stratification by tumor size and neck lymph node metastasis. Participants in both groups will be followed up at 2, 4, 6, 9, 12, 15, 18, 21 and 24 months after randomization. The primary outcome is local control rate of the primary site (based on imaging findings and clinical examination, RECIST criteria) in 1 year. Secondary outcomes are progression-free survival, overall survival, quality of life (QOL) measured with the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-H&N35) of Chinese version, and safety of treatment. Chi-squared test is used to compare the local control rates in both groups. The survival curves are estimated by the Kaplan-Meier method, and log-rank test is used to test the significant difference.
  
  
  CONCLUSIONS
  Only few observational studies have investigated the effect of I-125 PBT on inoperable salivary gland malignancies. To our knowledge, this is the first randomised controlled trial to investigate the efficacy of I-125 PBT for subjects with inoperable salivary gland malignancies, and will add to the knowledge base for the treatment of these subjects.
  
  
  BACKGROUND
  The study is registered to Clinical Trials.gov ( NCT02048254 ) on Jan 29, 2014.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Liu
authors.affiliation: Peking University Clinical Research Institute, Xueyuan Rd 38#, Haidian Dist, Beijing, 100191, PR China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Department of radiotherapy, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian Dist, Beijing, 100142, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Huang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Lv
authors.affiliation: Department of radiotherapy, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian Dist, Beijing, 100142, PR China.
authors.forename: Bao-Min
authors.initials: BM
authors.lastname: Zheng
authors.affiliation: Independent Consultant, New York, NY, USA.
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Reilly
authors.affiliation: Peking University Clinical Research Institute, Xueyuan Rd 38#, Haidian Dist, Beijing, 100191, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Yan
authors.affiliation: Peking University Clinical Research Institute, Xueyuan Rd 38#, Haidian Dist, Beijing, 100191, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.affiliation: Peking University Clinical Research Institute, Xueyuan Rd 38#, Haidian Dist, Beijing, 100191, PR China.
authors.forename: Yang-Feng
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun South St, Haidian Dist, Beijing, 100081, PR China. rszhang@126.com.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024221:Antineoplastic Protocols; D001918:Brachytherapy; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D050397:Radiotherapy, Intensity-Modulated; D012468:Salivary Gland Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes