Clinical investigation: Cervix
Long-term results of adjuvant hypofractionated radiotherapy for breast cancer in elderly patients

Presented in part at the 45th Annual Meeting of the ASTRO, Salt Lake City, UT, October 2003.
https://doi.org/10.1016/j.ijrobp.2004.04.059Get rights and content

Abstract

Purpose

To evaluate early and late reactions, local control, disease-free survival, cause-specific survival, and overall survival of elderly breast cancer patients treated with adjuvant once-weekly hypofractionated radiotherapy (RT).

Methods and materials

Between 1987 and 1999, 150 patients (median age, 78 years) who presented with 151 nonmetastatic breast tumors were treated with surgery and then adjuvant hypofractionated RT. The clinical stage distribution was as follows: T1 in 47.7%, T2 in 43.2%, T3 in 6.1%, and T4 in 3.0%. Axillary lymph nodes were positive in 33.8% of cases. Estrogen receptors were present in 89.9%, and progesterone receptors in 77.3%. Conservative breast surgery was performed in 71.5% and total mastectomy in 28.5%. RT was delivered once weekly in five fractions of 6.5 Gy to a total dose of 32.5 Gy. A boost was delivered to the tumor bed in 33.1%. Adjuvant hormonal therapy was given in 76.2% of patients. The median follow-up was 65 months.

Results

The Kaplan-Meier rate of all grades of early skin reactions was 26.5%, and the rate of all late reactions was 45.5%, mainly Grades 1 and 2. Early and late reactions were greater in those who underwent boost RT. The long-term local recurrence rate was 2.3%. The 5-year and 10-year disease-free survival rate was 80% and 71.5%, respectively. The corresponding rates for cause-specific survival were 89.1% and 77.6%. The 5-year and 10-year overall survival rate was 71.6% and 46.5%, respectively. These endpoints were influenced by tumor size, lymph node status, and hormone receptor status to varying degrees; however, tumor size appeared to be a major determinant on multivariate analysis.

Conclusions

This hypofractionated RT scheme resulted in mild early reactions and acceptable late toxicity, in addition to providing excellent long-term local control. It can be proposed to patients who would have difficulties sustaining daily treatment because of old age or disabling associated disease.

Introduction

Elderly breast cancer management will be a major public health concern in the next few years. Old age is one of the greatest risk factors for breast cancer (1) and the incidence of breast cancer in elderly women is constantly increasing. Few data are available on treatment of these patients, because they have been poorly represented in prospective clinical trials (2). Although breast carcinoma in the elderly generally presents with more biologically favorable prognostic factors than in the younger patient (3), the disease is often diagnosed at a more advanced stage owing to negligence or the absence of a screening program at this age. In addition, these patients sometimes present with several comorbidities that often lead to undertreatment. Epidemiologic reviews have shown that elderly women are less likely to receive the standard locoregional treatment, especially radiotherapy (RT) 4, 5, 6, 7, 8. The treatment of these patients should consider not only the breast cancer prognosis, but also life expectancy, quality of life, and the patient's wishes. Less cumbersome therapeutic alternatives that could secure good tumor control without altering the quality of life are highly needed. We have developed a hypofractionated once-weekly RT regimen to treat these patients as adjuvant therapy. The preliminary data have been previously presented (9) and have been updated in this study with an adequate number of patients and sufficient follow-up. Emphasis was on early and late sequelae and patient outcome.

Section snippets

Patients

Between 1987 and 1999, 150 patients presenting with 151 primary breast tumors (Stage I–III) underwent a schedule of adjuvant, postoperative, once-weekly, hypofractionated RT. The mean age of the population was 76.6 ± 0.7 years (median, 78 years). Of the 150 patients, 17 were <70 years old and were treated with this scheme because of associated disease and/or a long distance between their home and the RT facility. Forty-three patients (28.5%) underwent mastectomy, generally because of tumor

Early and late effects

Early reactions, mainly erythema, were observed in 42 patients, with a Kaplan-Meier estimate and standard error of 26.5% ± 4%. They were classified as Grade 1 in 28 cases and Grade 2 in 14 cases. The corresponding Kaplan-Meier estimates were 18.6% ± 3% and 9.4% ± 3% (Fig. 1). . No Grade 3 effects occurred. Patients who had received a boost to the tumor bed had a 37% ± 7% probability of early effects of either grade vs. 22% ± 4% in those having received only the five weekly fractions (p = 0.01;

Discussion

In the 1960s, different hypofractionation schedules were evaluated as palliative treatment of breast cancer 14, 15, 16. Because of the poor radiation quality and technique, the severity of late effects led to abandonment of those protocols. More recently, adjuvant hypofractionated and accelerated RT schedules have been evaluated in Phase III randomized trials. These trials compared 23 Gy in 4 fractions within 17 days (17) or 42.5 Gy in 16 fractions within 22 days vs. standard RT (18).

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