title: Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer.
abstract: OBJECTIVE
  Standard dose of external beam radiotherapy seems to be insufficient for satisfactory control of loco-regionally advanced cervical cancer. Aim of our study is to evaluate the outcome as well as early and chronic toxicities in patients with loco-regionally advanced cervical cancer, treated with dose escalated intensity modulated radiotherapy (IMRT) combined with cisplatin chemotherapy.
  
  
  METHODS
  Thirty-nine patients with cervical carcinoma FIGO stage IB2 - IVA were treated with curative intent between 2006 and 2010. The dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Primary tumors < 4 cm in diameter (n = 6; 15.4 %) received an external beam radiotherapy (EBRT) boost of 5.4 Gy, primary tumors > 4 cm in diameter (n = 33; 84.6 %) received an EBRT boost of 9 Gy. Patients with positive lymph nodes detected with (18)FDG-PET/CT (n = 22; 56.4 %) received a boost to a total dose of 59.4 - 64.8 Gy. The para-aortic region was included in the radiation volume in 8 (20.5 %) patients and in 5 (12.8 %) patients the para-aortic macroscopic lymph nodes received an EBRT boost. IMRT was followed with a 3D planned high dose rate intrauterine brachytherapy given to 36 (92.3 %) patients with a total dose ranging between 15-18 Gy in three fractions (single fraction: 4-6.5 Gy). Patients without contraindications (n = 31/79.5 %) received concomitantly a cisplatin-based chemotherapy (40 mg/kg) weekly. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0).
  
  
  RESULTS
  Mean overall survival for the entire cohort was 61.1 months (±3.5 months). Mean disease free survival was 47.2 months (±4.9 months) and loco-regional disease free survival was 55.2 months (±4.4 months). 65 % of patients developed radiotherapy associated acute toxicities grade 1, ca. 30 % developed toxicities grade 2 and just two (5.2 %) patients developed grade 3 toxicities, one acute diarrhea and one acute cystitis. 16 % of patients had chronic toxicities grade 1, 9 % grade 2 and one patient (2.6 %) toxicities grade 3 in the form of vaginal dryness.
  
  
  CONCLUSIONS
  Dose escalated IMRT appears to have a satisfactory outcome with regards to mean overall survival, disease free and loco-regional disease free survival, whereas the treatment-related toxicities remain reasonably low.
authors.affiliation: Department of Radiation Oncology, Bern University Hospital & University of Bern, Bern, Switzerland. nikola.cihoric@gmail.com.
authors.forename: Nikola
authors.initials: N
authors.lastname: Cihoric
authors.affiliation: Department of Radiation Oncology, Bern University Hospital & University of Bern, Bern, Switzerland. alexandros.tsikkinis@insel.ch.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tsikkinis
authors.affiliation: University of Bern, Institute for Pathology, Murtenstrasse 31, Bern, 3010, Switzerland. CTapia1@mdanderson.org.|Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Life Science Plaza, 2130 W. Holcombe, Blvd. Unit 2951, Houston, 77030, TX, USA. CTapia1@mdanderson.org.
authors.forename: Coya
authors.initials: C
authors.lastname: Tapia
authors.affiliation: Department of Radiation Oncology, Bern University Hospital & University of Bern, Bern, Switzerland. daniel.aebersold@insel.ch.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Aebersold
authors.affiliation: University of Bern, Institute for Pathology, Murtenstrasse 31, Bern, 3010, Switzerland. inti.zlobec@pathology.unibe.ch.
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.affiliation: Department of Radiation Oncology, Bern University Hospital & University of Bern, Bern, Switzerland. kristina.loessl@insel.ch.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lössl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods; D002277:Carcinoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin