Evaluation of Dose Integrated Accelerated Irradiation in Older Women (≥ 70 Year) With Early and Loco-regionally Advanced Stages of Breast Cancer
Evaluation of Dose Integrated Accelerated Irradiation in Older Women (≥ 70 Year) With Early and Loco-regionally Advanced Stages of Breast Cancer
Adjuvant radiotherapy in breast cancer improves local control, also in the elderly. Hormonal therapy in hormone sensitive tumors improves results but can not substitute radiotherapy. Improved local control leads to less breast cancer related morbidity and mortality, also in an older population (Schonberg, JCO, 2011).
Unfortunately, in older patients with lower life expectancy, adjuvant radiotherapy is often omitted. Following reasons are invoked:
Hypofractionation is feasible without increased toxicity, and combines better local control with patient comfort and lower costs. Further lowering the number of fractions (from 15-21 to 5) will further improve patient comfort, but is challenging when different doses are needed in the same target volume. This problem is addressed using advanced techniques permitting dose-integration.
In the elder with cancer, several unrecognized geriatric problems, including depression and cognitive impairment, can be detected by CGA . Some problems do interact with cancer treatment. In this study screening and assessment is provided to support patients and to develop an inventory of radiotherapy obstacles.
Our study includes breast cancer patients, ≥70 years old, referred for adjuvant radiotherapy after surgical treatment. A schedule of 5 fractions is offered, encompassing different targets of treatment.
Adjuvant radiotherapy in breast cancer improves local control and overall survival, also in the elderly. Hormonal therapy in hormone sensitive tumors improves results but can not substitute radiotherapy (EBCTCG, Lancet, 2011). Improved local control, leads to less breast cancer related morbidity and mortality, also in an older population (Schonberg, JCO, 2011).
Unfortunately, in older patients with lower life expectancy, adjuvant radiotherapy is often perceived as too cumbersome. As a consequence, patients who could have benefit from breast conserving therapy are referred for mastectomy. Even when breast-conserving surgery is chosen, adjuvant radiotherapy is sometimes omitted in frail patients over 70 years fearing the burden of daily transportation to the radiation department. However, omitting radiotherapy results in a higher risk of loco-regional recurrence. It has been shown that older patients have a worse prognosis due to suboptimal treatment, especially in locally advanced breast cancer (Schonberg, JCO, 2011).
Following reasons are invoked by the patients or the care-givers:
Hypofractionation and acceleration are proven to be feasible in recent trials (cf. Start Trial, Fast Trial).
Based on these data and in order to overcome above mentioned obstacles for radiotherapy in breast cancer, we start a study with accelerated radiotherapy in women above 70 years old.
As we are experienced in advanced techniques as IMRT, VMAT, simultaneous dose-integration and IGRT, we will use simultaneous dose integrated protocols to permit inclusion of early as well as locally advanced breast cancer.
Integration of doses within one global volume encompasses several advantages:
In order to evaluate the impact of accelerated radiotherapy on the well being of the patient and on the treatment cost, quality of life (QoL) will be measured and a cost-analysis will be performed.
Methodology of research At the radiotherapy intake consultation, patients with age ≥70 years are extensively informed on the advantages and the possible risks of accelerated irradiation. A written documentation of the study is provided to permit consultation of family and general practitioner before consent for participation. Until 1 week before the start of radiotherapy, patients can decide wether or not to participate in this study without impact on the starting day. Inclusion is performed after signing the informed consent.
The aim is to include 70 patients aged ≥ 70 years, who, after signing the informed consent, will be treated with the accelerated schemes over 10 days (5 sessions, every other day). Following doses are prescribed
Positioning of the patient depends on technical possibilities and patient rigidity:
End points of our study are acute and chronic toxicity, loco-regional control and QoL.
The study is divided in two different strata (first group without lymph node irradiation, second group with lymph node irradiation) for following reasons:
Groups
An application for funding to perform geriatric assessment is introduced. In the elder with cancer, several unrecognized geriatric problems, including depression and cognitive impairment, can be detected bij CGA . Some of these problems even interact with cancer treatment. In this study screening and assessment is provided to develop an inventory of obstacles for undergoing radiotherapy.
When screening scores positive (G8 score ≤ 14/17) geriatric assessment will be performed to evaluate the problems and needs of the patient. Patients will be referred for appropriate treatment and support. As described by Schönberg, treatment in early stage breast cancer might even lead to improved morbidity and mortality when compared to a non-cancer population, due to the 'healthy user' effect, detecting otherwise unrevealed problems. In the scope of this study, this effect can not be evaluated.
Power analysis To estimate the number of patients needed, we applied the Wilson score confidence interval test for binomial proportion, which is a 2-sided exact method for power analysis, using "SAS Power and Sample Size".
Group 1:
To achieve a conditional probability of 87% with an alpha-error of 0,1, a number of 35 patients would be needed. To compensate for drop-outs, we include 40 patients in this study-arm.
Group 2 To achieve a conditional probability of >95% with an alpha-error of 0,1, a number of 25 patients would be needed. To compensate for drop-outs, we include 30 patients in this study-arm.
Inclusion Criteria:
Exclusion Criteria: