Mohit Kasibhatla MD, Presenter: Nothing to Disclose

Robert Clough BS, Abstract Co-Author: Nothing to Disclose

James R. Oleson MD, Abstract Co-Author: Nothing to Disclose

Gustavo S. Montana MD, Abstract Co-Author: Nothing to Disclose

Kim Light CMD, Abstract Co-Author: Nothing to Disclose

Ellen Jones MD, PhD, Abstract Co-Author: Nothing to Disclose

Purpose/Objective: To determine clinical and dosimetric predictors of severe GI toxicity in patients undergoing EBRT and interstitial brachytherapy for primary or recurrent gynecological malignancies. Materials/Methods: A retrospective review of 36 patients treated at DUMC from 1989-2001 for non-metastatic primary or recurrent gynecological malignancies was performed. All patients received EBRT followed by interstitial brachytherapy. Patients with severe GI toxicities, including small bowel obstruction requiring surgery (SBO) and recto-vaginal fistula, were identified by chart review. Variables investigated as possible predictors of toxicity included age, prior hysterectomy, primary vs. recurrent disease, chemotherapy use as well as characteristics of EBRT and interstitial brachytherapy including total tumor and rectal doses. The difference in crude rates of severe GI toxicity between patient subgroups was analyzed using Fisher's exact test. The Duke University IRB approved this investigation. Results: The median patient age was 54 years (range 33-84). Sixteen patients had a hysterectomy prior to radiotherapy. There were 22 patients with cervical cancer, 10 patients with vaginal carcinoma, two patients with endometrial carcinoma and two patients with vulvar carcinoma. Seventeen patients had advanced stage (III/IV) primary carcinoma and 11 patients had recurrent carcinoma. Squamous cell carcinoma was the predominant histology (28 pts). All patients received pelvic EBRT with 6 or 15 MV photons using 2 (13 pts) or 4 fields (23 pts) to a median total dose of 45 Gy (range 30-50.4 Gy) in 180-200 cGy/fraction. Chemotherapy was used in 21 patients either prior to or concurrent with external beam radiotherapy. Agents used included cisplatin , 5-FU and hydroxyurea. Iridium 192 low dose rate interstitial brachytherapy was used in all patients (median strength 0.55 mCi/seed) two weeks after EBRT. A median of 23 strands (range 6-40 strands) and 193 seeds (range 45-524 seeds) were used. A Syed template was used in 17 patients and 19 patients had a custom designed template. The median dose delivered to the tumor volume, rectum and bladder by interstitial brachytherapy was 27 Gy (range 14-45 Gy), 21 Gy (range 11-41 Gy) and 21 Gy (range 11-44 Gy), respectively. The median total dose of EBRT + interstitial brachytherapy to the tumor, rectum and bladder was 72 Gy, 66 Gy and 66 Gy, respectively. At a median follow-up of 19 months for all patients (range 5-125 months), local failure occurred in 17 patients (46%) with 13 patients alive and free of disease (35%). There were 6 patients (17%) who developed severe GI toxicities including recto-vaginal fistula (3 pts) and SBO (3 pts). None of these events were related to recurrent disease. Rectal isodose data was available in 24 patients. Three of five patients who received a combined EBRT + interstitial brachytherapy dose of >=76 Gy to the rectum developed recto-vaginal fistula compared with no recto-vaginal fistulas in 19 patients who received a total rectal dose below 76 Gy (60% vs 0%, p= 0.005). Three of the four patients who had prior hysterectomy and were treated with EBRT using 2 fields developed SBO compared with no SBO events in 32 patients treated with either 4 fields after hysterectomy or 2-4 fields without hysterectomy (75% vs 0%, p<0.0007). No other clinical or dosimetric variable predicted for severe GI toxicity. Conclusions: To minimize the risk of recto-vaginal fistula in patients who receive EBRT + interstitial brachytherapy for primary or recurrent gynecological malignancies, the total rectal dose should be <76 Gy. Patients who have had a hysterectomy prior to EBRT should be treated with 4 fields to decrease irradiated small bowel volume and thereby lower risk of SBO.

Kasibhatla, M, Clough, R, Oleson, J, Montana, G, Light, K, Jones, E, Predictors of Severe Gastro Intestinal (GI) Toxicity after External Beam Radiotherapy (EBRT) and Interstitial Brachytherapy for Primary or Recurrent Gynecological Malignancies.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4417816.html