Abbreviated course of radiotherapy (RT) for breast cancer.
The use of RT as a component of breast-conserving therapy or after mastectomy has been proven to reduce the risk of local-regional recurrence (LRR) and to improve long-term breast cancer-specific and overall survival. As has been the common practice in the United States and Continental Europe, the majority of studies that demonstrated these benefits utilized daily radiation doses ranging from 1.8-2 Gray (Gy). However, due to geographic limitations, patient preferences and financial considerations, there have been continued attempts to evaluate the efficacy and toxicity of abbreviated courses of breast RT. Two key factors in these attempts have been: (1) advances in radiobiology allowing for a more precise estimation of equivalent dosing; and (2) advances in the delivery of RT that have resulted in substantially improved dose homogeneity in the target volume. As an alternative to approximately five weeks of daily treatment at 1.8-2 Gy, delivering radiobiologically-equivalent total doses in hypofractionated, abbreviated schedules has been evaluated in five randomized controlled trials, as well as many prospective and retrospective experiences. These studies have generally demonstrated equivalent rates of LRR, disease-free survival and overall survival with the use of hypofractionated regimens. Despite theoretical and historic concerns that hypofractionated regimens could increase damage to normal tissue, the rates of acute and long-term toxicities have generally not been increased in most recent series. Some toxicities, however, may take years to decades to manifest. Questions still remain regarding which patients are appropriate for abbreviated treatment. The majority of patients included in the studies supporting hypofractionated treatment were of older age with early-stage invasive ER+ disease of predominantly lower histological grade. This favorable subset of patients is also the most eligible for other alternative treatment approaches, such as partial-breast irradiation or hormonal therapy alone. Additionally, few to none of the patients included in most studies were treated with mastectomy, lymph node irradiation, a lumpectomy cavity radiation boost, or adjuvant chemotherapy. The existing evidence prompted the American Society for Radiation Oncology (ASTRO) to convene a task force to issue an evidence-based guideline in 2010 delineating the patients for whom an abbreviated radiation course is most supported by the current evidence [Smith et al. 2010, Int J Radiat Oncol Biol Phys]. Ongoing and future studies will further clarify the suitability of a hypofractionated treatment approach for the patient subgroups underrepresented in available trials. Additionally, alternative abbreviated treatment regimens, including those in which treatment is given once weekly and treatments that include an integrated lumpectomy cavity boost, are actively being investigated. Finally, innovative radiation techniques, such as the use of higher energies, prone treatment, and breathing-adapted therapy have further increased the homogeneity of breast irradiation and minimized dose delivered to nearby critical normal structures. Consequently, increasing experience with these techniques may expand the population of patients amenable to hypofractionated therapy.
Harvard Radiation Oncology Program, Dana-Farher Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Jonathan D
JD
Schoenfeld
Jay R
JR
Harris
D000328:Adult; D000368:Aged; D001071:Appointments and Schedules; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015331:Cohort Studies; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015412:Mastectomy, Segmental / Q000379:methods / Q000401:mortality; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D057240:Patient Preference; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States