Locoregional irradiation for inflammatory breast cancer: Effectiveness of dose escalation in decreasing recurrence

Purpose: To evaluate the effect of radiation dose escalation on locoregiona l control, overall survival, and long-term complication in patients with in flammatory breast cancer. Patients and Methods: From September 1977 to December 1993, 115 patients wi th nonmetastatic inflammatory breast cancer were treated with curative inte nt at The University of Texas M. D. Anderson Cancer Center. The usual seque nce of multimodal treatment consisted of induction FAC or FACVP chemotherap y, mastectomy (if the tumor was operable), further chemotherapy, and radiat ion therapy to the chest wall and draining lymphatics. Sixty-one patients t reated from September 1977 to September 1985 received a maximal radiation d ose of 60 Gy to the chest wall and 45-50 Gy to the regional lymph nodes, 22 treated once a day at 2 Gy per fraction, and 35 were treated b.i.d. (32 af ter mastectomy and all chemotherapy was completed, and 2 immediately after mastectomy; one patient had distant metastases discovered during b.i.d. irr adiation, and treatment was stopped). Four additional patients received pre operative radiation with standard fractionation. Based on the analysis of t he failure patterns of the patients, the dose was increased for the b.i.d. patients in the new series, with 51 Gy delivered to the chest wall and regi onal nodes, followed by a 15-Gy boost to the chest wall with electrons. Fro m January 1986 to December 1993, 39 patients were treated b.i.d. to this hi gher dose after mastectomy and all the chemotherapy was completed; and 8 ad ditional patients received preoperative irradiation with b.i.d. fractionati on to 51 Gy. During this period, another 7 patients were treated using stan dard daily doses of 2 Gy per fraction to a total of 60 Gy, either because t hey had a complete response or minimal residual disease at mastectomy or be cause their work schedule did not permit the b.i.d. regimen. Comparison was made between the groups for locoregional control, disease-free and overall survival, and complication rates. Results: The median follow-up time was 5.7 years (range, 1.8-17.6 years). F or the entire patient group, the 5- and 10-year local control rates mere 73 .2% and 67.1%, respectively. The 5- and 10-year disease-free survival rates were 32.0% and 28.8%, respectively, and the overall survival rates for the entire group were 40.5% and 31.3%, respectively. To evaluate the effective ness of dose escalation, a specific comparison of patients who received b.i .d. radiation after mastectomy and completion of adjuvant chemotherapy was performed. There were 32 patients treated b.i.d. to 60 Gy in the old series versus 39 patients treated b.i.d. to 66 Gy in the new series. There was an significant improvement in the rate of locoregional control for the b.i.d. patients for the old vs. new series, from 57.8% to 84.3% and from 57.8% to 77.0% (p = 0.028) at 5 and 10 years, respectively. Chemotherapy regimens d id not change significantly during this time period. Long-term complication s of radiation, such as arm edema more than 3 cm (7 patients), rib fracture (10 patients), severe chest wall fibrosis (4 patients), and symptomatic pn eumonitis (5 patients), were comparable in the two groups, indicating that the dose escalation did not result in increased morbidity. Significant diff erences in the rates of locoregional control (p = 0.03) and overall surviva l (p = 0.03), and a trend of better disease-free survival (p = 0.06) were a lso observed that favored the recently treated patients receiving the highe r doses of irradiation. Conclusion: Twice-daily postmastectomy radiation to a total of 66 Gy for pa tients with inflammatory breast cancer resulted in improved locoregional co ntrol, disease free survival, and overall survival, and was well tolerated. (C) 2000 Elsevier Science Inc.