Phase III Randomized Study of Intensity Modulated Radiation Therapy vs. Standard Wedging Adjuvant Breast Radiotherapy

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 7, 2006

Presenter: Jean-Philippe Pignol, M.D.
Presenter's Affiliation: Sunnybrook and Women's College Health Sciences Centre, Toronto , Ontario , Canada
Type of Session: Plenary

Background

The current standard adjuvant treatment of localized breast cancer is whole breast radiotherapy
Prior to using modern 3-D planning techniques, opposed tangent fields with compensating wedges have been used to deliver whole breast radiotherapy
Typical dose distributions using wedges are inhomogeneous, with hot-spots, especially near the infra-mammary fold. This region is where moist desquamation often occurs.
Intensity modulated radiotherapy (IMRT) plans are more homogeneous, but it is unknown whether IMRT can decrease acute skin toxicity, namely, moist desquamation

Materials and Methods

Phase III, two-center randomized to:
- Arm A: Standard planning with tangents and wedges (50 Gy)
- Arm B: IMRT planning (50 Gy)
  - A 16 Gy boost was used in both arms
  - Both the patient and the clinical research assistant were blinded
Patients were assessed for skin toxicity and quality of life both during and in the weeks following radiotherapy
Patients:
- 358 early stage breast cancer patients were accrued who were being treated with breast-only radiation
- Accrual occurred faster than expected over 20 months from 7/2003 to 3/2005
- 331 were included in the analysis (7 were excluded for dosimetry protocol violations)
Stratification:
- breast size and boost delivery
Endpoints:
- Primary: Rate of Grade 3-4 acute skin reaction and moist desquamation Grade 2-4 (NCI-CTG scale)
- Secondary: Time, onset, duration, and area of maximal skin toxicity. Quality of life.

Results

Dosimetry was improved in the IMRT arm:
- Hotspot: 110% (Wedges) vs. 105% (IMRT)
- Sagittal dose gradient: 8.7% (Wedges) vs. 0.9% (IMRT)
Acute skin toxicity was improved in the IMRT arm:
- Moist desquamation: 48% (Wedges) vs. 31% (IMRT), p<0.002
- Inferior mammary fold desquamation: 43% (Wedges) vs. 26% (IMRT), p<0.001
- Skin grade 3-4 (NCI-CTC): 36% (Wedges) vs. 27% (IMRT), p=0.062
Multivariate analysis showed that IMRT, breast volume, and treatment site were significantly correlated with less acute toxicity
IMRT was associated with less pain (p<0.001) and better quality of life

Author's Conclusions

The moist desquamation difference (17%) in this randomized trial between breast IMRT and wedges is consistent with results from Phase II trials of breast IMRT compared with matched controls
However, the overall rate of moist desquamation was much higher than has been reported in the literature, probably because skin toxicity was measured at points AFTER radiotherapy was completed, implying that moist desquamation is more common and delayed than was thought
The fast accrual of this study points to patients' interest in decreasing toxicity from radiation treatment

Clinical/Scientific Implications

Improving the homogeneity of dose distributions in breast radiotherapy by IMRT has been shown to decrease acute skin toxicity, especially moist desquamation in the infra-mammary fold
Improved homogeneity may be accomplished by techniques other than multiply segmented IMRT. In many patients, this can be accomplished by 3-D planning with lung corrections or forward-planned segmentation. This may be a much lower cost alternative to IMRT treatment of the breast. A formal cost analysis should be performed.
It is unclear whether it was the improved dosimetry or the slower dose-rate of IMRT that resulted in improved acute skin toxicity