De-escalated Approaches to Radiotherapy Can Benefit Patients
Hypofractionation and tailored radiotherapy can help avoid radiation-associated toxicities in women with early breast cancer.
SAN ANTONIO—Hypofractionation, tailored radiotherapy, selective use of booster radiation doses, and even foregoing radiotherapy entirely, in some cases, can help avoid radiation-associated toxicities in women with early breast cancer, reported Timothy J. Whelan, MD, of the Juravinski Cancer Centre in Canada.1
Dr Whelan's talk was part of an educational session on minimizing interventions in breast cancer held at the 2015 San Antonio Breast Cancer Symposium.
“Advances in molecular biology and radiation technology are likely to lead to improvements in personalized approaches to radiotherapy for early breast cancer,” he said.
Whole-breast irradiation (WBI) was long the standard approach for adjuvant radiotherapy after breast conserving surgery (BCS). “Numerous trials of WBI show a reduced 10-year local recurrence,” said Dr Whelan. “The standard approach was 50 Gy in 25 fractions plus a boost of 10 Gy-16 Gy in 5 to 8 fractions.”
But that approach has “significant limitations,” Dr. Whelan noted, including inconvenient treatment durations of up to 6.5 weeks, significant acute and late morbidity, and costliness. Side effects included skin erythema, desquamation, fatigue, breast edema, pain, pneumonitis, skin telangiectasia, breast fibrosis, adverse cosmesis (post-treatment breast appearance), and a “very low risk” of cardiac disease and second cancers, he said.
Recent decades have seen an increasingly recognized drop in local recurrence rates, attributable to the use of breast cancer screening, advances in surgery and adjuvant systemic therapy, and also improvements in radiotherapy technology and the understanding of radiobiology, Dr Whelan said.
That's leading to “major changes in the application of radiotherapy following BCS,” he noted, with an eye toward better “tailoring therapy to maintain local control, improve quality of life, and reduce health care costs.” Examples include hypofractionation, selective use of boost irradiation, partial breast irradiation, avoidance of breast irradiation altogether, and more selective use of lymph node irradiation, he said.
“Hypofractionation involves giving fewer fractions of larger doses of radiation per fraction, over a shorter period of time,” he explained. “Based on the hypothesis that breast cancer cells are equally sensitive to large doses per fraction as normal tissue, hypofractionation was developed to improve convenience and reduce costs for women receiving WBI.”
New evidence indicates that acute toxicity is lower and quality of life is better with hypofractionated schedules. The 2011 ASTRO guideline recommends hypofractionation for women older than 50 with node-negative, T1-2 breast cancer—but offers no consensus recommendation for women younger than 50, he noted. New ASTRO guidelines for WBI are expected next year, and may address these issues in more detail.
Accelerated partial breast irradiation (APBI) is another strategy for tailoring radiotherapy. It involves “delivery of larger dose per fraction to the surgical cavity, plus a 1 cm to 2 cm margin, after BCS in patients with early-stage breast cancer,” he said.
Several methods are available for delivering APBI, he noted: interstitial brachytherapy, intraoperative radiotherapy, 3-dimensional conformal radiotherapy (3DCRT), TARGIT, and MammoSite.
Intraoperative APBI has yielded promising improvements in 5-year local recurrence rates, he noted. The evidence is still coming in for 3DCRT, with 2 trials underway (NSABP B39/RTOG 0413 and OCOG-RPAID), Dr Whelan reported.
It also makes sense to limit boost irradiation to patients with high-risk disease, such as women who are younger than 50, with grade 3 histology or triple-negative breast cancer, Dr. Whelan said.
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“The genomic era provides a unique opportunity to understand the molecular biology of breast cancer,” Dr. Whelan said. “Most molecular biomarkers have been applied to identifying risk of distant recurrence and the need for chemotherapy. Recently, biomarkers have been applied to predicting the risk of local recurrence following BCS.”
Biomarkers might similarly help identify patients who are most likely to benefit from regional nodal irradiation, which appears to improve disease-free survival.
- Whelan TJ. Tailoring or omitting radiotherapy in early breast cancer. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 8, 2015; San Antonio, TX.