Study Reveals Long-Term Benefits With Prone Hypofractionated Radiation Therapy and a Concurrent Boost in Early-Stage Breast Cancer
Prone accelerated intensity-modulated radiation therapy with a concomitant boost produced excellent local tumor control and cosmesis while sparing normal tissues in women with early-stage breast cancer, according to the 5-year study results reported by Osa et al in the International Journal of Radiation Oncology • Biology • Physics. An ongoing phase III randomized trial evaluating a dose and technique similar to those in this study may provide conclusive data about the future role of hypofractionation in women with breast cancer.
With a survival advantage linked to optimal local tumor control, adjuvant radiation therapy has assumed a prominent role after breast-conserving therapy for many women with early-stage breast cancer. However, this treatment remains underutilized. To improve compliance to such breast-conserving therapy, many investigators have shortened the overall treatment time by reducing the number of radiation visits.
Fewer Treatments Than Standard Therapy
Over the past 10 years, Osa and colleagues developed a technique that combined intensity-modulated radiation therapy with a concomitant daily boost to the tumor bed. In their prospective study evaluating this technique, 404 patients with early-stage breast cancer were enrolled into two consecutive protocols: 90 patients in the institutional trial 03-30 and 314 patients in the institutional trial 05-181.
The same therapeutic regimen was used in both trials: 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose, 48 Gy). With this approach, the investigators limited the overall treatment time to 3 weeks, compared with the standard 6-week approach with a sequential boost.
A total of 92% of patients received treatment in the prone position. The remaining 8% received treatment in the supine position because the lung and heart volumes were in the radiation field.
All of the women in both protocols had been treated previously with segmental mastectomy with negative margins. The mean age of all study patients was 56.6 years, and 83% had invasive ductal breast cancer. Nearly three-fourths of all patients had stage I disease, and 85% of them had no disease in the lymph nodes.
In both protocols, exclusion criteria included more than three cancerous axillary lymph nodes, previous radiation therapy to the ipsilateral breast, and prior or concurrent malignancy (except for skin cancer) unless disease-free for more than 5 years.
Benefits in Regional Tumor Recurrence and Cosmesis
The investigators reported a 5-year cumulative incidence rate of regional tumor recurrence of 0.53% (95% confidence interval [CI] = 0.41%?0.69%). In addition, the 5-year cumulative incidence rate of isolated ipsilateral breast tumor recurrence was 0.82% (95% CI = 0.65%?1.04%) and of contralateral breast cancer was 0.55% (95% CI = 0.42%?0.72%).
Furthermore, the 5-year cumulative survival rate was 98.7%, with a corresponding 5-year cumulative death rate of 1.28% (95% CI = 0.48%?3.38%). A total of 15 patients died: 5 of breast cancer and 10 of other causes.
The investigators noted that late treatment?related toxicities (6 or more months after therapy), such as pigmentation changes and breast fibrosis, were limited to grade 1 or 2 in most patients. The most common grade 3 side effect was telangiectasia, which occurred in 6 patients (1%).
A total of 377 study patients agreed to self-assess their cosmetic results. The final cosmetic results were considered to be excellent/good in 82% of patients (95% CI = 77%?85%).
Closing Thoughts
The investigators stated that their recurrence rates were comparable to those of several randomized trials that compared hypofractionated radiation therapy with standard-fractionated radiation therapy to the breast. They adopted the prone position from the start of all of their trials to address the concerns regarding the effect of this approach to radiation therapy on the heart and lungs. With this technique, they minimized the volumes of heart and lung in the treatment field.
“The prone setup was demonstrated to be an excellent strategy to protect [the] heart and lung in most women, independently from their body mass or breast size,” concluded the investigators.
The dose and fractionation approach used in this study are almost identical to those required for the hypofractionated arm of the ongoing Radiation Therapy Oncology Group 1005 study. The results of this phase III multi-institutional randomized trial may provide conclusive data on the future role of hypfractionated radiation therapy in treating early-stage breast cancer.
Silvia C. Formenti, MD, of the Department of Radiation Oncology, New York University School of Medicine, New York, is the corresponding author of the article in the International Journal of Radiation Oncology • Biology • Physics.
This study was supported by an IDEA grant by the Department of Defense. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
