Description of the condition
Breast cancer is the most common cancer in women worldwide (Parkin 2005). In the United States of America it has been estimated that there will be 40,000 deaths annually from the disease and 210,000 new cases of invasive breast tumor diagnosed in 2010 (Jemal 2010). Developing countries present lower incidence rates when compared to developed countries (Parkin 2005). These differences might be related to societal features such as risk factors involved in cancerization (Berry 2005) and the availability of screening programmes (Parkin 2005; Ravdin 2007). Risk factors that have been associated with breast cancer include age and gender (Peto 2000), race and ethnicity (Jatoi 2007), benign breast disease (Degnim 2007), personal history of breast cancer (Kelsey 1981), lifestyle and dietary factors (Bernstein 2005; Lahmann 2004), reproductive and hormonal factors (Hsieh 1990), family history and genetic factors (Lichtenstein 2000), previous exposure to ionizing radiation (Henderson 2010), and environmental factors (Lipworth 2009).
For early-stage breast cancer, the standard treatment is breast-conserving surgery followed by radiation therapy. This approach is an effective alternative to mastectomy and leads to high local control rates with good cosmesis (i.e. breast appearance; Bartelink 2001; Fisher 2002). This conservative treatment of breast cancer is based on the surgical excision of the tumor, axillary management and conventional radiotherapy and once the pathological staging and biological markers are known, patients may undergo systemic (whole body) treatments as well (EBCTCG 2005a).
Radiation therapy has been used in patients with breast cancer who have undergone either radical mastectomy or breast-conserving treatments to assure better local control and survival (NCCN 2011; Recht 2001; Veronesi 2002). The effectiveness of conventional radiotherapy was demonstrated in randomized trials comparing radical mastectomy with breast-conserving surgery, showing equivalent overall survival and local control rates (Fisher 2002; Veronesi 2002). After conventional radiotherapy, about 30% of women develop high-grade acute skin toxicity (i.e. breast pain, erythema (redness), desquamation (peeling skin) and edema (swelling)) that is associated with a decrease in their quality of life (Al-Ghazal 1999). This toxicity may, therefore, influence both physician’s and patient’s decision regarding the use of conservative breast surgery and appropriate adjuvant (add on) therapy (Fernando 1996; Fisher 2002; NCCN 2011). The main risk factors of acute radiation-induced toxicity after conventional irradiation are large breast size and non-uniformities of dose (i.e. inhomogeneities) within tissues that receive up to 10% of the prescribed dose (Fernando 1996). Nevertheless, most historical publications use conventional radiation therapy without reference to any acceptable quality assurance standards. Since women with breast cancer usually have good prognoses and long life-expectancy, minimizing toxicities, even when mild, should be a goal of treatment.
Description of the intervention
The aim of radiation therapy is to treat the target volume (i.e. tissue that is to be irradiated to a specific dose) with a uniform (homogeneous) dose while minimizing radiation to surrounding normal tissues. In conventional radiotherapy, planning is based on two dimensions (using planar images such as X-ray) and the dose distribution calculation is made from a single plane (outline) of the patient. Using this technique, the dose range outside this boundary is not considered i.e. there is no exact dose/volume measurement for the entire breast, only information from a single axial plane. This means that other critical structures such as the lungs, heart, spinal cord and esophagus are often included in the treatment field, which may significantly contribute to the toxicity.
Since the 1980s, there have been considerable improvements in the hardware and treatment planning systems used in radiation therapy. These have included developments in three-dimensional conformal radiotherapy (3DCRT) which corrects non-conformities (i.e. the treated volume of tissue concurs with what was planned) and takes into account the patient's chest contour at different levels. With this method, however, the actual dose delivered is practically the same as in conventional radiotherapy, i.e. the non-uniformity in dose (inhomogeneity) remains the same. It is important to note that the dose prescriptions should meet some limits of acceptance such as those outlined by the International Commission on Radiation Units and Measurements (ICRU 62). In breast cancer, these recommendations are not always respected.
Intensity-modulated radiation therapy (IMRT) is a method that delivers highly conformal radiation with improved dose homogeneity and reduces the radiation dose to the normal, surrounding tissues. IMRT employs an inverse planning algorithm that produces dose distributions that are superior to conventional radiotherapy or 3DCRT. IMRT also allows higher doses to be delivered to the target volume (Webb 2003). In women with breast cancer, IMRT may reduce long-term complications by minimizing undesired radiation to organs-at-risk (such as the heart, lungs, spinal cord, ribs and skin). As a result, IMRT may improve quality of life and, perhaps, even overall survival.
How the intervention might work
The search for improvements in dose uniformity (i.e. homogeneity) is important in order to avoid over-treating areas inside the breast and surrounding tissues. The prescribed radiation dose to the target volume is at the level of 50 Gray (Gy) but there might be areas receiving 30% to 40% more radiation.
For breast cancer, IMRT provides optimal dose homogeneity. Its impact is in reducing both acute, and late, skin and connective tissue toxicities, and improving tolerance and quality of life (Barnett 2011; Donovan 2007; Pignol 2008). For those patients who present with a complex anatomy (i.e. pectus excavatum and flat chest) or need comprehensive nodal treatment, IMRT could represent a useful way to achieve safe delivery of radiation treatment by: (a) improving dose homogeneity, (b) sparing the contralateral breast and nearby organs at risk, such as the lung and heart (McCormick 2011), and (c) diminishing the likelihood of toxicities and secondary-malignancies over time. Reducing the dose of radiation to the heart is particularly desirable, as it would reduce subsequent ischemic heart disease (IHD) and treatment-related deaths from radiation therapy (IHD deaths dilute the survival benefit from post-operative radiation therapy; EBCTCG 2005b; Roychoudhuri 2007).
Some groups have been studying these new technologies in order to assess their potential benefits. Currently, there are three published randomized trials that we know of for women with breast cancer in which IMRT was compared with conventional techniques (Barnett 2011; Donovan 2007; Pignol 2008). In all of these trials, the focus was on the therapy of early-stage disease.The trials showed that IMRT increased radiation dose homogeneity, which was associated with a reduction in skin dermatitis and an improvement in breast cosmesis. These results highlight the potential advantages in minimizing toxicity outcomes, however, even with the reasonable availability of IMRT, the higher costs and complexity of this technology have meant that clinicians do not use it as part of routine clinical practice (Smith 2011).
Why it is important to do this review
To date there are no systematic reviews addressing the efficacy and safety of IMRT for breast cancer. Furthermore, there is still a lack of research on the toxicities related to radiation. Thus, the aim of this systematic review is to assess whether or not the safety and efficacy of IMRT are equivalent to conventional breast cancer radiotherapies.