Brachytherapy Alone Versus Whole Breast Radiotherapy After Breast Conserving Surgery: 5-year Results of a Phase I-II Study and Interim Findings of a Phase III Trial

Reviewer: Roberto Santiago, MD
OncoLink
Last Modified: October 9, 2002

Presenter: Csaba Polgar
Presenter's Affiliation: Department of Radiotherapy, National Institute of Oncology, Budapest, Hungary
Type of Session: Scientific

Background

Partial breast irradiation (PBI) has recently received alot of attention, especially since the FDA approval of a balloon-type brachytherapy applicator. This therapeutic approach is intended for highly selected patients with early invasive carcinoma of the breast with low-risk for local failure. There is limited data comparing the effectiveness of PBI to conventional BCT. This study tests the safety of PBI with interstitial HDR brachytherapy (HDR-BT) after breast conserving surgery (BCS) for T1 breast cancer in a phase I-II study, and to present the initial findings of a phase III trial comparing the efficacy of tumor bed irradiation (TBRT) alone with conventional whole breast radiotherapy (WBRT).

Materials and Methods

Forty-five prospectively selected patients with T1 N0-1a breast cancer undergoing BCS were enrolled into a phase I-II study of TBRT alone, using interstitial HDR implants.
HDR-BT consisting of seven fractions of 4.33 Gy (n = 8) or seven fractions of × 5.2 Gy given two per day (n = 37) was delivered to the tumor bed.
Based on the results of this phase I-II study, 222 additional patients were randomized to receive WBRT (50 Gy in fractions of 2 Gy) or TBRT alone.
Approximately 2/3 of the TBRT group consisted of patients treated with seven fractions of 5.2 Gy HDR-BT and 1/3 of patients treated with 50 Gy wide field electron irradiation in patients unsuitable for brachytherapy.
The eligibility criteria for both studies were: unifocal T1 disease, uninvolved margins of resection, no more than microscopic axillary node involvement, no grade 3 tumors, no in-situ carcinomas, no lobular carcinomas, and no EIC.
The two arms were well balanced.
Breast cancer related events and side effects were assessed. For late side effects only patients with a minimum follow-up of 20 months were evaluated.

Results

Phase I-II study: At a median follow-up of 66 months 2 (4.4%) local (all outside the tumor bed), 3 (6.7%) axillary, and 4 (8.9%) distant failures were observed. Three patients (6.7%) died of breast cancer.
Both local failures were salvaged with breast conserving surgery and whole breast radiotherapy.
The 6-year probability of cancer-specific (CSS), relapse-free (RFS) and local recurrence-free survival (LRFS) was 90.0%, 85.9% and 95.6%, respectively.
The cosmetic results were judged to be excellent in 44 out of 45 patients (97.8%). Severe (> G 2) skin sequalae or fibrosis was not found. Symptomatic fat necrosis occured in 2 (4.4%) patients.
Phase III study: At a median follow-up of 28 months, 1 patient in each arm has developed local recurrence, both of which were in the tumor bed. Both local failures were salvaged with breast conserving surgery and whole breast radiotherapy.
The 3-year probability of CSS, RFS and LRFS was 98%, 96% and 98% in the WBRT group and 100%, 94% and 98% in the TBRT group, respectively (p = NS).
There was no significant difference between the two treatment arms regarding the incidence of radiation side effects. There was one case of grade 3 fibrosis in the brachytherapy group. TBRT was significantly more cost effective than WBRT.
There was evidence of a learning curve for the brachytherapy procedure including the placement of more catheters per implant, bigger volume coverege by therapeutic doses, and better dose homogeneity as a function of time.

Author's Conclusions

Five-year results of our phase I-II study prove that sole HDR-BT of the tumor bed with careful patient selection and adequate quality assurance is a feasible alternative to WBRT.
At a median follow-up of 30 months in phase III study, HDR-BT alone is similar to WBRT with respect to skin and parenchymal side effects.

Clinical/Scientific Implications

Longer follow-up is required to draw a final conclusion regarding the difference in local control rate between the two treatment arms. Promising early results support further accrual into ongoing trials of this and similar approaches. There is a learning curve associate with this techniques probably requiring special training. This could be a reasonable approach for highly selected patients with limited access to conventional BCT practices.

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