High-dose whole abdominal and pelvic irradiation for treatment of ovarian carcinoma: long-term toxicity and outcomes.
OBJECTIVE
To evaluate the role of high-dose whole abdominal and pelvic irradiation (WART) in the treatment of epithelial ovarian carcinoma.


METHODS
A retrospective review was performed on 71 patients with Stage I-III ovarian carcinoma who were treated with WART using an open field technique after total abdominal hysterectomy and bilateral oophorectomy with or without omentectomy. Whole abdominal doses greater than typically recommended were used in a series of patients to enhance local control and to decrease abdominal recurrence. None of the patients had received chemotherapy before RT. Thirty-one patients received Alkeran or cyclophosphamide and two received cisplatin-based chemotherapy after WART. The median whole abdominal dose was 36 Gy (range 9-45.5), delivered in a median of 30 fractions (range 8-46). A pelvic boost was delivered using AP-PA fields during whole abdominal RT to a total midline pelvic dose of 200 cGy/d. The median pelvic dose was 51 Gy (range 16-59). The right lobe and a portion of the left lobe of the liver were shielded with custom blocks at a median dose of 25 Gy (range 9-41). The kidneys were shielded either AP-PA or PA from the first day of RT. The median dose to the kidneys was 19 Gy (range 4-30).


RESULTS
The 5-year overall survival rate was 93%, 48%, and 29% for Stage I, II, and III patients, respectively. On multivariate analysis, stage and the extent of residual disease were independent prognostic factors. The 5- and 10-year overall survival rate for the 46 patients in the intermediate-risk group was 61% and 54%, respectively. For this group, a total abdominal dose of > or /=36 Gy was associated with a longer overall survival independent of stage, grade, and the amount of residual disease. This was most likely due to a significant reduction in the incidence of abdominal recurrence in patients receiving >36 Gy to the whole abdomen (18% vs. 49%, p = 0.006). Multivariate analysis revealed that grade (p = 0.023) and abdominal dose (p = 0.018) were independent factors influencing the rate of abdominal recurrence. Pelvic recurrence was rare as a first site of failure (6%). Twenty-one percent (n = 15) of the patients developed Grade 3 or 4 (Radiation Therapy Oncology Group [RTOG] criteria) chronic small or large bowel toxicity. Eleven percent of all patients had a small bowel obstruction requiring surgery. A whole abdominal dose >30 Gy and a pelvic dose >50 Gy were associated with a significant increase in small bowel obstruction (p = 0.01) independent of other factors. Chronic Grade 3 or 4 (Common Toxicity Criteria) anemia, thrombocytopenia, and leukopenia were seen in 7%, 1%, and 4% of the patients, respectively. Transient liver enzyme elevation was common (62%). Two patients had Grade 3 (RTOG) hepatic toxicity. Grade 3 or 4 renal toxicity (RTOG) was observed in 4%, and 2 patients (3%) were diagnosed with pelvic insufficiency fractures that were managed conservatively.


CONCLUSIONS
Survival after RT for ovarian carcinoma rivals that achieved with systemic chemotherapy. The results of this study suggest a possible dose-control relationship between the whole abdominal dose and the risk of abdominal recurrence; however, a higher rate of small bowel obstruction was observed when greater abdominal doses and greater pelvic doses were combined. Careful attention to balancing toxicity and efficacy is imperative if RT is to have a future role in the treatment of this disease.
Firat
Selim
S
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Murray
Kevin
K
Erickson
Beth
B
D000005:Abdomen / Q000528:radiation effects; D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000401:mortality* / Q000532:radiotherapy* / Q000601:surgery; D010388:Pelvis / Q000528:radiation effects; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology