As discussed above, in the early post-mastectomy radiotherapy
trials, older techniques of radiotherapy delivery and altered
fractionation schemes resulted in severe chronic morbidity, most
notably, cardiac toxicity. In the recent update of the meta-analysis
of post-mastectomy trials, which provided cause-specific mortality,
standardized mortality ratios demonstrated that patients who receive
post-mastectomy radiotherapy have a significant increase in cardiac
mortality that exceeds 1.5 times the risk of controls . Despite
this increase, survival was improved in the more recent trials
due to the reduction in breast cancer deaths. Therefore, reduction
of radiotherapy-associated toxicity would result in a further
increase in overall survival.
Current radiotherapy techniques differ significantly from those
used in the early trials. In general, both the volume of heart
irradiated and the dose delivered to the heart are significantly
less than in the trials reviewed in the meta-analysis. The major
variable determining the amount of heart and lung that will be
included in the treatment field is the decision to treat the internal
mammary nodes. The factors involved in deciding whether to irradiate
the internal mammary nodes have been discussed elsewhere .
As shown in Figure 1, the proximity of the internal mammary region
to the heart adds a level of complexity to the treatment planning
process; the primary challenge is how to deliver a full dose to
the internal mammary nodes while minimizing exposure to the heart.
Computed tomographic studies in patients in whom the internal
mammary nodes were not intentionally treated have demonstrated
that on average, 0% of the heart is in the radiation field for
a right-sided cancer vs approximately 12% for a left-sided lesion
. Outcome studies in which the internal mammary nodes were
excluded from the radiation field have not shown an increase in
cardiac morbidity compared to outcomes in women who did not receive
radiotherapy [15,53,54]. For patients in whom the internal mammary
nodes were intentionally treated, the percentage of heart included
in the treatment field varies depending on the field arrangement.
A detailed discussion of various techniques to be considered when
incorporating the internal mammary nodes into the treatment field
is presented elsewhere . Three basic techniques are compared
here for the purposes of discussion.
Techniques for Including Internal Mammary Nodes--In Figure
2, the internal mammary nodes are treated in concert with the
chest wall in "deep" tangential photon fields. This
approach provides uniform coverage of both regions and ease of
technical set-up. However, the obvious disadvantage of this technique
is incorporation of increased cardiac (for a left-sided lesion)
and lung volume into the high-dose region, as well as inclusion
of the medial aspect of the contralateral intact breast in the
Figures 3 and 4 show alternative plans for treatment of the same
desired target volumes. In Figure 3, a combination of photons
and electrons is used to treat the chest wall and internal mammary
nodes. The chest wall is encompassed largely within the tangential
fields, while the remaining medial chest wall and internal mammary
nodes are treated by an electron field. Since electron radiotherapy
delivers the dose only to a specified depth and then decreases
rapidly to negligible levels, cardiac volume in the full-dose
region is minimal. Figure 4 demonstrates the use of electron beams
to encompass the entire target volume, which, depending on patient
anatomy, could reduce the volume of both lung and heart in the
Although the treatment plans shown in Figures 3 and 4 deliver
minimal dose to the heart and lung, they are less favorable dosimetrically
than the deep tangents shown in Figure 2 due to inhomogeneity
at the junction of the fields at surface and at depth. Far more
sophisticated techniques are available that attempt to even out
the areas of dose inhomogeneity while minimizing dose to critical
structures. These include conformal moving-beam electron therapy
(electron arc radiotherapy) and three-dimensional treatment planning
techniques. Suffice it to say that no one plan is optimal for
every patient. Treatment planning must be individualized on a
case-by-case basis with the aid of CT-based planning systems such
that beam arrangements can be optimized with respect to the target
volumes and patient anatomy. In this way, maximal dose homogeneity
can be delivered to the appropriate structures while minimizing
radiation exposure to pulmonary and cardiac tissue. This is especially
critical, as many women are receiving potentially cardiotoxic
doxorubicin-based chemotherapy regimens that could further compromise
Clearly, a great deal of controversy still surrounds the use of
post-mastectomy chest wall irradiation. Proponents of post-mastectomy
radiotherapy point to a lowering of chest wall failure rates,
improvements in disease-free survival, reductions in the distant
metastasis rate and the number of deaths from breast cancer, and
the overall survival advantage demonstrated in the recent Danish
study [48,49]. Detractors point to a failure to show a consistent
survival advantage attributable to chest wall irradiation even
in a large meta-analysis . They also note that the "Halstedian"
concept, which holds that variations in local therapy would have
a measurable impact on overall outcome, has been discarded. However,
it may be true that local therapy influences survival in some
patients. Thus, the Halstedian and alternative hypotheses to explain
breast cancer spread may not be an either/or proposition; rather,
a combination of these mechanisms may be responsible for the spread
of this cancer [16,55]. Certainly, there may be a group of patients
who have been rendered free of systemic disease by adjuvant chemotherapy
only to have minimal locoregional disease still present. Such
is the case in the setting of high-dose chemotherapy with stem-cell
support [32,33], which is why most current high-dose therapy protocols
include chest wall irradiation.
Resolution of questions about the usefulness of chest wall irradiation
will come about only through continued clinical research. It is
time to initiate a new post-mastectomy chest wall trial in North
America. Such a study should incorporate high-quality systemic
adjuvant chemotherapy and sophisticated radiotherapy designed
to treat all tissues at risk with a minimum amount of radiation
delivered to the heart. This trial should include women with four
or more positive nodes, who have a higher risk of local chest
wall failure than those with one to three positive nodes. Approximately
20,000 women diagnosed with breast cancer annually in the United
States have four or more positive nodes, so that accruing patients
to such a trial should not be a problem. The trial should be large
enough to detect a 6% to 7% improvement in survival, similar to
that seen in the Danish study.
Without sufficient clinical trial data from the modern era, such
as would be obtained from such a study, we will endlessly debate
the role of chest wall irradiation following mastectomy. Discussions
are underway with the major cooperative trials groups regarding
their willingness to undertake such a study.
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