title: Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients-Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group.
abstract: OBJECTIVE
  The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique.
  
  
  METHODS
  A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique.
  
  
  RESULTS
  A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT.
  
  
  CONCLUSIONS
  The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.
authors: Department of Radiation Oncology, University of Cologne Medical Faculty, Cologne, Germany. Electronic address: simone.marnitz-schulze@uk-koeln.de.
authors: Simone
authors: S
authors: Marnitz
authors: Institute for Clinical Epidemiology and Applied Biostatistics, Eberhard-Karls-Universität Tübingen, Tübingen, Germany.
authors: Peter
authors: P
authors: Martus
authors: Department of Advanced Operative and Oncologic Gynecology, Asklepios Clinics, Hamburg, Germany.
authors: Christhardt
authors: C
authors: Köhler
authors: Department of Radiation Oncology, University of Cologne Medical Faculty, Cologne, Germany.
authors: Carmen
authors: C
authors: Stromberger
authors: Department of Radiation Oncology, University Hospital Greifswald, Greifswald, Germany.
authors: Elke
authors: E
authors: Asse
authors: Department of Gynecology and Obstetrics, University Hospital Cologne, Cologne, Germany.
authors: Peter
authors: P
authors: Mallmann
authors: Department of Radiation Oncology, University of Mainz, Mainz, Germany.
authors: Heinz
authors: H
authors: Schmidberger
authors: Department of Radiation Oncology, Hospital de Cãncer de Barretos, Barretos, Brazil.
authors: Renato José
authors: RJ
authors: Affonso Júnior
authors: Department of Clinical Oncology, Hospital de Cãncer de Barretos, Barretos, Brazil.
authors: João Soares
authors: JS
authors: Nunes
authors: Department of Gynecology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Jalid
authors: J
authors: Sehouli
authors: Department of Radiation Oncology, University of Cologne Medical Faculty, Cologne, Germany.
authors: Volker
authors: V
authors: Budach
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001918:Brachytherapy / Q000009:adverse effects; D016190:Carboplatin / Q000627:therapeutic use; D018196:Carcinoma, Adenosquamous / Q000401:mortality / Q000523:psychology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006176:Gynecology; D006801:Humans; D008197:Lymph Node Excision / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011446:Prospective Studies; D018787:Radiation Oncology; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin