title: Two fractions of high-dose-rate brachytherapy in the management of cervix cancer: clinical experience with and without chemotherapy.
abstract: OBJECTIVE
  In recent years, high-dose-rate brachytherapy has become popular in the management of carcinoma of the uterine cervix, because it eliminates many of the problems associated with low-dose-rate brachytherapy. However, the optimum time-dose-fractionation remains controversial. Two fractions of high-dose-rate brachytherapy are convenient for patients, but most radiation oncologists in the United States do not use them, because of fear that they could lead to excessive rectal or bladder toxicity. Here we present our experience, which suggests that a two-fraction regimen is indeed safe and effective.
  
  
  METHODS
  We treated 49 patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by external beam radiation therapy (EBRT), plus two fractions of high-dose-rate brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3-10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty patients (61%) also received irradiation to the para-aortic lymph nodes to a dose of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median: 10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy (cisplatin 20 mg/m(2)/day for 5 days) during the first and fourth weeks of EBRT and once after the second high-dose-rate brachytherapy application. Chemotherapy was not assigned in a randomized fashion. The use of chemotherapy increased during the time period spanned by this study as increasing evidence supporting the use of chemotherapy began to appear.
  
  
  RESULTS
  The observed survival rates after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving patients have been followed up for a median of 3 years (range: 2-6 years). Eight of the 49 patients suffered local failures. Among patients treated without chemotherapy, the 3-year local control rate was 77%; it was 88% among those receiving chemotherapy. There have been no regional failures. Four patients developed distant metastases. At 3 years, 91% of the patients in each group were free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade 4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2 and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late toxicity was 5%, with or without chemotherapy.
  
  
  CONCLUSIONS
  Our experience suggests that two fractions of high-dose-rate brachytherapy are safe and effective in the management of cervix cancer, even in conjunction with concomitant cisplatin. The fears that the use of two fractions would lead to excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a low complication rate are discussed.
authors.affiliation: Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210 Street, Bronx, NY 10461, USA.
authors.forename: Brij M
authors.initials: BM
authors.lastname: Sood
authors.forename: Giridhar
authors.initials: G
authors.lastname: Gorla
authors.forename: Sajel
authors.initials: S
authors.lastname: Gupta
authors.forename: Madhur
authors.initials: M
authors.lastname: Garg
authors.forename: Shivaji
authors.initials: S
authors.lastname: Deore
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Runowicz
authors.forename: Abbie L
authors.initials: AL
authors.lastname: Fields
authors.forename: Gary L
authors.initials: GL
authors.lastname: Goldberg
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Anderson
authors.forename: Bhadrasain
authors.initials: B
authors.lastname: Vikram
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D001743:Urinary Bladder; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D002945:Cisplatin