title: Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2).
abstract: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer.
  
  
  
  We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life.
  
  
  
  From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ2P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25).
  
  
  
  IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California. Electronic address: lmell@ucsd.edu.
authors.forename: Loren K
authors.initials: LK
authors.lastname: Mell
authors.affiliation: Department of Oncology and Radiotherapy, University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Sirák
authors.affiliation: Xijing Hospital, Xian, China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wei
authors.affiliation: Marie Sklodowska Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Tarnawski
authors.affiliation: Tata Memorial Centre, Parel, Mumbai, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Mahantshetty
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Catheryn M
authors.initials: CM
authors.lastname: Yashar
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McHale
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Xu
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Gordon
authors.initials: G
authors.lastname: Honerkamp-Smith
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Ruben
authors.initials: R
authors.lastname: Carmona
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Mary
authors.initials: M
authors.lastname: Wright
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Casey W
authors.initials: CW
authors.lastname: Williamson
authors.affiliation: Department of Oncology and Radiotherapy, University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Linda
authors.initials: L
authors.lastname: Kasaová
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Washington University, St Louis, Missouri.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kry
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Walter
authors.initials: W
authors.lastname: Bosch
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: William
authors.initials: W
authors.lastname: Straube
authors.affiliation: Washington University, St Louis, Missouri.
authors.forename: Julie
authors.initials: J
authors.lastname: Schwarz
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lowenstein
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Steve B
authors.initials: SB
authors.lastname: Jiang
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Cheryl C
authors.initials: CC
authors.lastname: Saenz
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Steve
authors.initials: S
authors.lastname: Plaxe
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: John
authors.initials: J
authors.lastname: Einck
authors.affiliation: Kaiser Permanente Medical Center, San Diego, California.
authors.forename: Chonlakiet
authors.initials: C
authors.lastname: Khorprasert
authors.affiliation: Chulalongkorn Hospital, Bangkok, Thailand.
authors.forename: Paul
authors.initials: P
authors.lastname: Koonings
authors.affiliation: Chulalongkorn Hospital, Bangkok, Thailand.
authors.forename: Terry
authors.initials: T
authors.lastname: Harrison
authors.affiliation: Xijing Hospital, Xian, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California.
authors.forename: A J
authors.initials: AJ
authors.lastname: Mundt
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow; D001918:Brachytherapy / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009503:Neutropenia / Q000453:epidemiology / Q000517:prevention & control*; D059351:Organ Sparing Treatments / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin