Accelerated Partial Breast Irradiation (APBI): An Analysis of Variables Associated with Late Toxicity after HDR Interstitial Brachytherapy

Reviewer: Voika BarAd, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 17, 2005

Presenter: S. Kaufman
Presenter's Affiliation: Radiation Oncology, Tufts/ Brown Universities, Boston, MA, Radiation Oncology, Virginia Commonwealth University, Richmond, VA
Type of Session: Scientific

Background

There is currently limited data regarding late tissue toxicity and long-term cosmetic results with APBI.
This study offers a detailed analysis of the variables associated with late tissue effects in patients treated with high dose rate (HDR) interstitial brachytherapy APBI. The reported findings reflect a large study population with relatively long follow-up.

Materials and Methods

75 patients with stage I/II invasive ductal carcinoma breast cancer who underwent lumpectomy were enrolled
Eligible patients had T1-2, N0-1 (< 4 positive lymph nodes), M0 tumors of nonlobular histology, negative surgical margins, no extracapsular nodal extension, and a negative post-excision mammogram.
All patients underwent surgical excision and post-operative irradiation via HDR brachytherapy implant.
The planning treatment volume (PTV) for the implant was defined as the excision cavity plus 2-cm margins.
The treatment was delivered with a high-activity Ir-192 source at 3.4 Gy/ fraction BID for 5 consecutive days, to a total dose of 34 Gy.
The dosimetric analysis was performed with 3-D post-implant dose and volume reconstructions.
All patients were evaluated at 3-6 month intervals and assessed using a standardized cosmetic rating scale.

Results

The median follow-up of all patients was 73 months.
The cosmetic outcome at last follow-up was rated as excellent, good, and fair/poor in 67%, 24%, and 9% respectively.
The suboptimal cosmetic outcome was significantly associated with implant volume, as well as the volume of tissue encompassed by the 150% and 200% isodose lines. Suboptimal cosmetic outcome was inversely associated with the dose homogeneity index.
Late skin toxicity, rated in order of increasing severity as grade 0, 1, and 2, occurred in 78%, 18%, and 4%, respectively.
The risk of grade 1 and 2 skin toxicity was significantly associated with the volume of tissue encompassed by the 150% and 200% isodose lines, and inversely associated with the dose homogeneity index ( DHI 0.77 vs 0.71).
Late subcutaneous toxicity was rated as grade 0, 1, 2, 3, or 4, and occurred in 54%, 15%, 12.5%, 5.6% and 12.5%, respectively.
The risk of grade 0 or 1 late subcutaneous toxicity vs grade 3 or 4 late subcutaneous toxicity was significantly associated with a lower value of the dose homogeneity index (DHI 0.77 vs 0.73)
Dose hotspots, as reflected in the 150% and 200% isodose lines, were significantly associated with the risk of fat necrosis.
The use of Adriamycin-based chemotherapy after APBI was found to be associated with a significant increase in the incidence of higher-grade skin toxicity as well as a higher risk of fat necrosis and suboptimal cosmetic outcome.
Patient age, volume of resection, extent of axillary surgery, a history of diabetes, and the use of Tamoxifen were all found to NOT be statistically significantly associated with either outcome or later normal tissue complications.

Author's Conclusions

The cosmetic outcome was significantly associated with the implant volume, with the volume of tissue encompassed by the 150% and 200% isodose lines, with the dose- homogeneity index, and with the planar separation of the implant needles.
The data from this study offer more specific dosimetric parameters that may be used to minimize the risk of normal tissue injury after APBI brachytherapy.
Regarding the use of adjuvant chemotherapy, one should "proceed with caution".

Clinical/Scientific Implications

The use of brachytherapy in post-lumpectomy breast cancer is an attempt to deliver high doses of radiation to tumor cells while sparing the surrounding normal tissues.
With proper case selection and delivery technique, HDR brachytherapy has great promise, in that it eliminates radiation exposure, allows for shorter treatment times, and can be performed on an outpatient basis.
It is expected that the use of HDR brachytherapy will greatly expand over the next decade, and that refinements will occur primarily with the integration of imaging (computed tomography, magnetic resonance imaging, intraoperative ultrasonography) and optimization of dose distribution.
It is anticipated that better tumor localization and normal tissue definition will both help to optimize dose distribution to the tumor and to reduce normal tissue exposure.
We need well-controlled randomized trials addressing issues of efficacy, toxicity, quality of life, and cost- versus- benefit ratios of HDR brachytherapy as compared to standard external beam irradiation in the treatment of early breast cancer patients.