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rather than secondary to evidence suggesting lack of benet. What is known is that breast cancer in the elderly
postmenopausal patient tends to be prole favorable and
more likely indolent and, thus, this may be the subgroup
to benet most from every other year imaging.42 Further, if a woman’s overall health is poor, such that her
life expectancy is less than 5 years, it is very reasonable
to forgo all breast imaging, as death from breast cancer
is not a signicant concern. However, in an otherwise
healthy 70-year-old woman, actuary studies would suggest another 16.5 years of life, making every other year
mammography very reasonable and a worthwhile intervention.43 Twenty-six percent of breast cancer deaths are
in women over the age of 75, and yet 50% of women
over age 80 are expected to live another 10 years. For this
reason, every other year screening mammograms should
be performed in average-risk women over the age of 70
in reasonably good health.
High-Risk Screening
is could easily be a chapter unto itself, but briey a woman
qualies for high-risk screening when her lifetime risk of breast
cancer exceeds 20–30%. High-risk screening is usually dened
as staggered annual 3D mammogram and magnetic resonance
imaging (MRI) or whole breast ultrasound. ere are several
factors that increase a woman’s risk for breast cancer. Genetic
predisposition is responsible for 10–15% of breast cancers,
and penetrance varies widely by the both the gene and heterogeneity.44 is would include the well-recognized BRCA1
and 2 mutations,45 with lifetime risk of 50–85% and 45%,
respectively.
and CHEK2 (Li-Fraumeni syndrome), PTEN (Cowden and
Bannayan-Riley-Ruvalcaba syndromes), CDH1 (hereditary
diuse gastric cancer), STK11 (Peutz-Jeghers syndrome),
PALB2 (interacts with BRCA2), and ATM (ataxia-telangiectasia) genes.
ere are also those women with very strong family histories of breast cancer without a recognizable mutation,
sometimes called gene X.48 Here, familiarity may be the
key rather than genetics, and a nding of two or more rstdegree relatives with breast cancer, especially those diagnosed
at a young age, remains signicant. Exposure to mantle or
chest radiation at a young age also signicantly increases the
risk of breast cancer, starting approximately 8 years postXR T.
A personal history of breast cancer is a risk factor for
breast cancer, but clearly every woman with a history of
breast cancer does not need high-risk screening. A metaanalysis of 10,801 women treated with lumpectomy/BCT
found a 10-year recurrence rate of 19.3% and a 15-year cancer death rate of 21.4%.51 Overall, radiotherapy reduced the
10-year risk of any (i.e., locoregional or distant) rst recurrence from 35% to 19.3% (absolute reduction, 15.7%) and
reduced the 15-year risk of breast cancer death from 25.2%
to 21.4% (absolute reduction, 3.8%); radiotherapy reduced
the absolute recurrence risk at 10 years from 31.0% to
49,50
46,47
Other less common mutations include TP53
15.6% and absolute mortality rate from 20.5% to 17.2%.
In women with node-negative (pN0) disease, the absolute
recurrence reduction varied according to age, grade, ER status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate
(10–19%), or lower (<10%) absolute reductions in the
10-year recurrence risk.
Based on a paper published in 2018 in the Journal of
the American College of Radiology by Debra Monticciolo
and Michael Hassett out of Dana-Farber Cancer Institute
and Brigham & Women’s Hospital, the take-home keys for
high-risk screening are52:
1. For women with genetics-based increased risk (and their
untested rst-degree relatives) or those with a calculated
lifetime risk of 20% or more, high-risk imaging should
be performed annually beginning at age 30.
2. For women with histories of chest radiation therapy
before the age of 30, high-risk imaging should be performed annually beginning at age 25 or 8 years after
radiation therapy, whichever is later.
3. For women with genetics-based increased risk (and their
untested rst-degree relatives), histories of chest radiation (cumulative dose of ≥10 Gy before age 30), or a calculated lifetime risk of 20% or more, breast MRI should
be performed annually beginning at age 25–30.
4. For women with personal histories of breast cancer and
dense breast tissue, or those diagnosed before age 45,
high-risk imaging is recommended.
5. For women with personal histories not included in the
previous items, or with ADH, atypical lobular hyperplasia, or LCIS, high-risk imaging should be considered,
especially if other risk factors are present.
Conclusions and Current Imaging
Guidelines Per Society
Due to the continued controversy on when screening
should begin, the ACS and the USPSTF formed panels to
revisit the question and their recommendations. e latest update from the USPSTF 2015,53 although relaxing
on their overall stance, continues to recommend biannual
screening mammography starting at age 50. Further, the
ACS guidelines are somewhat confusing recommending
annual screening starting at age 40 as a “qualied recommendation,” described as “e majority of individuals in
this situation would want the suggested course of action,
but many would not.”
e main reason for recommending screening starting
at age 50 rather than 40 was to reduce the number of “false
positives” dened as imaging recalls and “unnecessary” or
benign biopsies. However, they failed to dene what is
acceptable in the context of lives lost (i.e., how many recalls
avoided is equivalent to one death). As stated earlier, the
National Cancer Institute’s CISNET, which was used by
both panels, shows that, if women in their 40s wait until age
50 to start screening mammograms and then are screened
54
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every other year, as many as 100,000 lives will be lost that
could have been saved by annual screening starting at age
40.53 Waiting until age 45 to begin annual screening and
then shifting to biennial screening at age 55 would result in
more than 38,000 women currently in their 40s unnecessarily dying from breast cancer.
35
Approximately 10% of women undergoing screening
mammography will require “something” more. Half will
be told everything is good after additional imaging (mammogram and/or ultrasound). Approximately 25% (2.5% of
those screened) are asked to return in 6 months for a short
interval follow-up, and approximately 20% (2% of women
screened) will be advised to undergo minimally invasive,
imaging-guided needle biopsy.54 Among these women,
20–40% will be found to have cancer.
55
Much of this controversy is supported by the idea of
“overdiagnosis,” the nding and treating of malignancies
that were never destined to cause death. is is seen with
some favorable, low-grade DCIS. However, invasive breast
cancer left alone will grow into a palpable cancer, with lethal
capability.
33,56
In Harvard’s two largest teaching hospitals,
more than 70% of women dying of breast cancer did not
perform regular screening mammograms, including women
in their 40s.
57
e death rate from breast cancer remained unchanged
from the 1940s to the 1980s when screening mammography was rst introduced. By the 1990s, we began to see the
death rate drop, and today 36% fewer women die each year
from breast cancer.58 Male breast cancer remains relatively
stable, with higher overall mortality secondary to more
advance stage at diagnosis, as tumors are not identied until
palpable and often symptomatic.
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20
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Radiation Therapy Considerations and
Oncoplastic Breast Surgery
KENNETH L. FAN AND MAURICE Y. NAHABEDIAN
Introduction
e surgical treatment of breast cancer has undergone a
paradigm shift and evolved from the Halsted radical mastectomy to the simple mastectomy and now includes breast
conservation therapy (BCT). BCT is dened as local excision of the primary tumor (i.e., lumpectomy, quadrantectomy) or breast-conserving surgery (BCS) followed by
radiation therapy (RT). BCT was ushered into standard
of care by six large randomized prospective trials demonstrating equivalent survival rates with BCT compared with
mastectomy in early disease.
a critical component of the treatment regimen by reducing the recurrence rate by 50% and reducing breast cancer
deaths by 16% after BCS.
are tumor eradication, prolonging survival, and maximizing
quality of life with oncoplastic strategies.9
1-6
RT has been shown to be
7,8
e goals of therapy with BCT
Biological Basis of Radiation in Treatment
of Breast Cancer
RT is dened as the delivery of ionizing energy to control
malignancy while limiting damage to surrounding normal
tissues. Two major methods of radiation delivery are available: (1) External Beam Radiation erapy (EBRT) and (2)
Brachytherapy. EBRT delivers high-energy photon or electron x-ray beams to tissue from outside the body. Brachytherapy delivers lower energy radiation within the patient’s
body to treat the volume of tissue in the immediate vicinity.
Ionizing radiation as a therapeutic modality underwent
rapid growth in the early part of the 20th century when
Regaud demonstrated that certain internal reproductive cells
may be targeted without causing major burns to the skin.10
e overarching goal is to optimize the “therapeutic ratio,” a
risk benet analysis of healthy versus cancerous tissue, when
planning a radiotherapy regimen. e eect of radiation is
known as the continuum, which describes the sequence of
events that occur when ionizing energy is directed at a cell.11
Strong circumstantial evidence suggests cellular damage is
a result of direct action of charged particles or free radical
formation leading to DNA damage.12 At the later end of
the continuum, reproductive integrity is lost when DNA
is unrepairable or mis-rejoined, leading to cell death over
hours to years. Tumor control is achieved when clonogenic
cells are destroyed or otherwise unable to maintain growth.
Based on the theoretical radiobiological modeling of the
dose response of normal tissue compared with cancer cells,
conventional fractionation divides the total radiation into
several smaller doses over a period of several days to impart
less toxic side eects on late responding healthy cells.13 Cellular damage is regulated by the 4Rs of radiotherapy: repair
of sublethal damage between dose fractions, reassortment
of cells into more sensitive stages of the cell cycle, reoxygen-
ation of tumor cells for increased sensitivity, and repopula-
tion of the surviving fraction due to cell division.
Radiation in Breast Conservation Therapy
and Invasive Ductal Carcinoma
BCT has become an alternative to mastectomy for most
patients with early stage invasive ductal carcinoma. is
is possible with modern multimodal patient selection and
treatment. Indications for BCT are as follows (Table 20.1)9:
Early Stage Tumor/Tumor Size
e majority of trials demonstrating equivalent outcomes to
mastectomy had upper size limit of 2–4 cm,
ers permitted an upper limit of 5 cm.
stage III, neoadjuvant chemotherapy should be considered
before BCS.
signicantly higher than those initially candidates for BCT
(14.5% vs 6.9%).15 With improved patient selection and
coordination among specialties, the locoregional control has
been shown to be equal in those who do and do not receive
neoadjuvant chemotherapy.
14,15
Older trials indicate local failure rate was
16,17
1,2
3,6
whereas oth-
In tumors >5 cm or
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TABLE
Indications and Contraindications for Breast
20.1
Conserving Therapy
Indications Contraindications
<5 cm tumor Inability to achieve negative
margins*
Unifocal disease Prior chest irradiation*
Patient preference and
compliance
Patients with comorbidities Inflammatory breast cancer*
*Absolute contraindications
Poor aesthetic outcome*
Pregnancy
Collagen vascular disease
Prior breast augmentation
Unifocal Disease
Historically, multifocal (two or more tumors in the
same quadrant) and multicentric (two or more tumors
in the separate quadrant or 4–5 cm apart) disease has
been considered a contraindication to BCT, with historical ipsilateral breast tumor recurrence (IBTR) rates
of 20–40%.18 However, studies with carefully selected
patients demonstrate IBTR rates at 10 years are comparable to mastectomy.19 These tumors tended to be
multifocal, smaller (≤1 cm), without extensive ductal
carcinoma in-situ (DCIS), and in older women. Clear
margins are paramount, as positive margins and lowgrade tumors were the strongest predictors of IBTR (see
“Inability to Achieve Clear Margins”).
Patient Preference/Compliance
Patients presenting for BCT must be motivated to preserve the breast and be willing to adhere to the radiotherapy regimen to follow. Historically, no difference
was seen in psychological adjustment between BCT
and mastectomy, but improved body image and sexual
function were seen in BCT cohorts.
with the BreastQ questionnaire found breast conservation without reconstruction to be associated with lower
physical well-being in the chest area, sexual well-being,
and overall satisfaction compared with mastectomy
and reconstruction, possibly due to resulting asymmetry and radiation effect (Fig. 20.1).22 The addition of
oncoplastic breast reconstruction results in high level of
long-term satisfaction, improved quality of life, and selfesteem.
23-25
Patients should be offered reconstruction
when available and necessary (see “Inadequate Aesthetic
Outcome”).
Certain situations make BCT untenable due to the consequences associated with radiation.9 e conditions are as
follows (Table 1):
20,21
A recent study
• Fig. . Breast conservation therapy without plastic reconstruction
demonstrating a contour abnormality on the left following radiation
therapy. Breast excision involving greater than 10% of the breast volume without reconstruction results in significant patient distress and
lower satisfaction.
34
Inability to Achieve Clear Margins
Margins, based on the recommendations of consensus
statements, are dened as invasive cancer on inked margins, the presence of which results in a twofold to threefold increase in IBTR (Table 20.2).
26,27
is increase is
not nullied by a boost of radiation, systemic therapy,
or favorable biology.27 So long as negative margins are
achieved, consensus statements agree that routinely
obtaining wider margins does not necessarily result in
decreased risk of IBTR.27 However, when close margins
present in younger patients with extensive intraductal
component (EIC), re-excision may be benecial.27
Tumor distribution, shape, or proximity to the chest wall
may preclude the ability to achieve negative margins. e
likelihood of this occurrence is increased with multicentric disease. Persistent positive margin after reasonable
surgical attempts may be an indication to convert to a
mastectomy.
Further dierentiation can be made between extensively positive and focally positive margins, which is
dened as tumor involvement in three or fewer low-power
microscopic elds. e risk of 8-year IBTR among excised
tumors with focally positive margins was only marginally
increased and further mitigated by systemic therapy.28
ese patients may still be candidates for BCT. Clinical
consideration of re-excision and additional adjuvant systematic therapy is warranted if focal margin involvement
is present.29
Pregnancy
WBI should be avoided in pregnant women due to the risk
of mutagenesis to the developing embryo. Application of
accelerated partial breast irradiation (APBI) is still controversial and not routinely performed. Oftentimes, the
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TABLE
Consensus Guidelines on the Use of Re-excision for Non-negative Margins after BCS after WBI for Early
20.2
Invasive Breast Cancer
Society Position
American College of Radiology (2015) • When margins are microscopically involved, re-excision should be pursued
• Wider margins may be more important in young patients, estrogen receptor negative,
or EIC
American Society of Breast Surgeons
(2013)
Society of Surgical Oncology/American
Society for Radiation Oncology
27
(2014)
National Comprehensive Cancer
Network (2015)
American Society of Clinical Oncology
(2014)
Adapted from Freedman G. Breast conserving therapy for invasive breast cancers. In: Bland K, Copeland E, Klimberg VS, Gradishar W, eds. The breast: compre-
hensive management of benign and malignant diseases. New York, NY: Elsevier; 2018:693–705.
• Re-excision is not recommended for <2 mm margin after lumpectomy for invasive
cancer, with or without DCIS. Re-excision is decided on by case, depending on
number of close margins, location of margin, and radiation therapy
• When there is no ink on the tumor, wider margins do not lower risk of IBTR
• No evidence of increased margin exists for patients ≤40 years old
• Recurrence after positive margin is not mitigated by radiation boost, favorable
biology, or systemic therapy
• Negative margin is defined as no ink on tumor, as defined in the SSO/ASTRO
guideline
• It may be reasonable to treat select cases of focally positive margins with a radiation
boost
• Endorses SSO/ASTRO guidelines
• Emphasis on postlumpectomy mammography in cases with microcalcifications
pregnancy delays diagnosis of breast cancer, and patients
present with larger tumors necessitating mastectomy. However, should the tumor characters allow BCT and the pregnancy allows for excision, radiation may be delayed until
after delivery (see “Timing”).30
Prior Chest Irradiation
Patients with a prior history of irradiation (breast cancer,
Hodgkin’s lymphoma) are generally ineligible for BCT as
total tolerable dose of the previously irradiated tissue will
likely be exceeded. In such scenarios, the standard of care is
mastectomy; however, case reports have been described with
APBI in patients refusing mastectomy.31
Collagen Vascular Disease
Many radiation oncologists will not treat patients with collagen vascular disease.32 ere is an increased incidence in
severe acute toxicity with RT delivered to the breast, presenting as severe desquamation. Coordination of radiation
oncology and rheumatology is necessary should BCT be
pursued.
Inadequate Aesthetic Outcome
Patients with micromastia and a large tumor present a
unique surgical challenge for BCT. Lack of reconstruction after BCT results in distortion, asymmetry, and lower
physical and sexual well-being.22 Unfortunately, women
with micromastia may be automatically triaged to mastectomy without full understanding of the options.33
• Fig. . The biplanar technique is illustrated on the right breast that
included placement of a 100-mL implant (volume replacement) and
parenchymal redistribution (volume displacement).
Oncoplastic techniques have been described that combine
volume displacement and replacement in a single procedure. Plastic surgery consultation should be considered
when >10% breast volume loss is anticipated.34 Techniques
for volume replacement include glandular tissue rearrangements, biplanar implant placement, and local and free aps
(Fig. 20.2).
33,35,36
ese reconstructions mitigate volume
loss and have been shown to result in high levels of patient
satisfaction and improved quality of life.
23-25,33
Consultation with plastic surgery should also be pursued with a subareolar position of the tumor or when the resulting scar is
in a poor orientation.
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• Fig. . Results following breast conservation in the setting of pre-
vious breast augmentation are demonstrated depicting contracture,
distortion, and asymmetry.
Prior Breast Augmentation
Prior breast augmentation has typically precluded BCT due
to poor cosmetic outcome. Nahabedian etal in a retrospective
review of 48 cases found patients with prior augmentation are
more likely to undergo mastectomy (72.9%) compared with
BCT (57%) with signicantly lower rates of BCT (25.5% vs
43%), despite comparable disease stage.37 Tumors in augmented
patients were more likely detected when smaller in diameter but
less likely to be detected on screening mammography. Studies
have demonstrated increased complications following BCT
in the setting of prior breast augmentation, including erosion, pain, and capsular contracture that range from 30–65%,
despite optimized radiation dosimetry (Fig. 20.3).
38-40
half of the patients required implant removal demonstrating
that, even with modern radiotherapeutic techniques, the incidence of capsular contracture and poor cosmesis remains high.
e following conditions require special consideration:
Age
Although age is not a contraindication in and of itself, a
meta-analysis of trials indicates that, of women who underwent BCT, those who were <40 years old had a 5.9% per
year chance of IBTR, a 2.7% per year for 40–49 years, a
1.9% per year for 50–59 years, a 1.6% for 60–69 years,
and 1.0% for ≥70 years. Locoregional recurrence and mortality are similarly high in mastectomy among younger
women.
41,42
is may be in part due to the higher incidence
of adverse tumor biology.43 However, large cohort studies
indicate improved survival may be seen in women >50 years
and those with comorbidity not treated with chemotherapy
when comparing BCT to mastectomy.44
Nodes
Patients with positive axillary nodes do not have an
increased incidence of IBTR compared with patients with
Up to
• Fig. . The results following oncoplastic reconstruction and radia-
tion of the right breast with a symmetry reduction mammaplasty on
the left.
positive nodes.45 In fact, a large cohort study found benet
of BCT for T2N1 versus T2N0, perhaps due to the use of
systemic therapy for node-positive patients.44 Patients with
extracapsular node involvement do not have an increased
risk of IBTR.46
Extensive Intraductal Component
Patients with EIC warrant careful consideration. EIC is
dened as intraductal carcinoma (DCIS) prominently present within the borders of the primary tumor (when DCIS
comprises 25% or more of the tumor or present within all
visualized ducts) and when intraductal carcinoma is present in adjacent tissue, either as an extension beyond the
inltrating margin or as separate foci in grossly normal
adjacent tissue.47 Negative margins are dicult to achieve
with diuse microcalcications, despite en bloc incisions.48
So long as positive margins are achieved, IBTR are mitigated in tumors with EIC.49 Postoperative mammography can be helpful in identifying residual calcications for
re-excision.27
Large Breasts
BCT in large breasts has been demonstrated to have significantly inferior cosmetic result compared with small
breasts due to the larger skin folds resulting in dose inhomogeneity and increased skin toxicity.
women were found to have late radiation changes in
39% of cases, compared with 6% in women with small
breasts. However, this does not preclude large-breasted
women from receiving BCT. An oncoplastic therapeutic mammaplasty may be performed in conjunction with
adjuvant radiation to improve cosmetic outcome (Fig.
20.4).53
50-52
Large-breasted
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Whole Breast Irradiation
External Beam Radiation Therapy (Whole
Breast Irradiation)
e diversity of clinical indications for breast radiotherapy
contributes to the diversity in the characteristics of EBRT.
Electron EBRT travels a nite depth within the soft tissue, and
surface dose increases with increasing electron energy. As such,
electron EBRT is useful for supercial treatment of chest wall
and internal mammary nodes or when a limited area surrounding a defect requires a boost dose after WBI. Photon beams
penetrate greater depths, with theoretical less total radiation
dose to the skin. e majority of patients receiving EBRT are
treated with tangential photon elds. Cobalt machines delivering photons were historically the main modality in which
many of the initial trials were based on. Disadvantages include
less precisely dened beam edge irradiating surrounding tissue
(penumbra), poor delivery to deeper tissues, and sta exposure. Over the past 25 years, linear accelerators (LINACS) have
replaced cobalt machines due to the rates of secondary malignancies and heart disease.54 LINACS, with modern modications, are designed to deliver precise doses of radiation in a
wide range of beam energies with limited personnel exposure.
TABLE
Standard Plans for Whole Breast Radiation
20.3
Whole Breast
Irradiation
Boost
Hypofractionation
3D Conformal
IMRT
IMRT, Intensity modulated radiation therapy.
1,2,7,61
68
72-73
90
45–50 Gy over 5 weeks (5 per
week, 1.8–2.0 Gy each session)
60–65 Gy over 7 weeks (5 per
week, 1.8–2.0 Gy each session)
63-64
40–42 Gy over 3 weeks (5 per
week, 2.6–2.8 Gy each session)
35–38.5 Gy over 10 fractions,
twice daily
40 Gy over 15 fractions
fewer, larger fractions, also known as hypofractionated-WBI
(hWBI), is as eective in tumor control with similar normal
tissue damage and cosmetic outcome (see Table 20.3). e
updated American Society for Radiation Oncology (ASTRO)
2018 guidelines now specify hWBI to be appropriate in any
age, stage, and with chemotherapy.67
Timing after Surgery
e optimal timing of RT after surgery is unknown,
although 6–8 weeks is the generally agreed upon upper
55-57
limit.
Huang etal in a systematic review found 1.62
higher odds of IBTR when radiotherapy was administered
>8 weeks after surgery.57 e absolute increase in the risk of
IBTR is 1.0% per month delay in starting radiotherapy.58
Delays >3 months are associated with increased mortality.59
When chemotherapy is required, no dierence in IBTR or
survival has been found if WBI occurs before or after treatment, so long as RT is begun within 7 months from sur-
57,60
gery.
Staggering treatment is preferred over concurrent
therapies to reduce toxic eect.
Radiation Dosage: Standard Fractionation
versus Hypofractionation
e schedule for standard fractionated WBI, daily doses of
2 Gy in 5 weeks for a total dose of 45–50 Gy, have been
established by previous trials (Table 20.3).
assists in locoregional control of the disease, eliminating
potential microdisease, reducing the IBTR rates such that it
is equivalent to mastectomy.62 e rationale for delivery of
such dosages is based on dogma that has suggested normal
tissue was more sensitive to larger fraction size. erefore,
smaller daily fractions induce irreparable damage to malignant tumor DNA (which typically lack repair mechanisms)
with less collateral injury to surrounding tissues.
Studies with >10 year follow-up have suggested that breast
cancer cells have similar dose response curve rates to radiation when compared with native tissue.
1,2,7,61
61,63-66
Radiation
61
Delivery of
Radiation Boost
Additional radiation treatment or a “boost” delivered to
the lumpectomy excision site after WBI has been shown in
EORTC randomized control trials to decrease the risk of
IBTR, but not mortality, through 20 year follow-up compared with WBI alone.68 ese eects were most pronounced
in women ≤40 years, who are at greater risk for IBTR. Boost
did not modify mortality risk in these patients. However, radiation boost increased the incidence of severe breast brosis by
vefold compared with patients who did not receive a boost.68
is trial did not assess margin status. Although patients with
close margins may benet from increased doses, the literature
and consensus statements are mixed in this regard.29
Partial Breast Irradiation
Broadly speaking, partial breast irradiation may be delivered
as APBI or intraoperative radiation therapy (IORT).
Accelerated Partial Breast Irradiation
APBI focuses radiation to 1–2 cm of tissue surrounding
tumor beds considered to be high risk and is directed to
where IBTR usually occurs (Fig. 20.5).61 APBI may be
delivered with brachytherapy or external beam radiation.69
Brachytherapy requires specic equipment and infrastructure. Interstitial therapy is a complex technique where
multiple rows of catheters are left protruding out of the
skin for 1 week. Delivery of radiation doses requires dedicated suites to protect personnel. Applicator-based brachytherapy relies in commercially available device to deliver
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• Fig. . Partial breast radiation following oncoplastic reduction
mammaplasty of the left breast.
radiation. is device may be placed intraoperatively or as
a second procedure. Multilane applicators have permitted
varying doses to reduce radiation exposure to normal tissue. Studies, although promising, are limited in size and
design.
3D Conformal Therapy
3D conformal radiation therapy (3D-CRT) represents the
rst of conforming techniques, referring to radiotherapy
that is able to “conform” to the target shapes and potentially delivering complex dosages within targets while minimizing inadvertent damage to normal tissue (Table 20.4).70
In this forward-planning technique, treatment parameters
(number of beams, intensity, shape, angle) are decided, and
the resulting dose distribution is calculated and evaluated.
is technique allows for improved spatial distribution of
dose, but normal tissues may not be completely excluded.71
Treatment dose is delivered over the course of 5–7 days in
10 fractions that are delivered twice a day with at least 6
hours between each course for a total dosage of 35–38.5
72,73
Gy.
results,
with ≤3 cm breast cancer or DCIS to 3D-CRT or WBI,
demonstrated poor aesthetic outcome at 3 years based on
interim examination of results.78 e delayed development
of brosis, fat necrosis, and poor aesthetic outcome were
corroborated by smaller studies.
the subtle variations in planning techniques and dose constraints result in substantial dierences in outcome.82
Although smaller studies have shown positive
74-77
the RAPID trial, randomizing 2135 women
79-81
is likely indicates
TABLE
Components of Conformal Therapy
20.4
Treatment Plans
Target volumes defined in three-dimensional
1)
contours from CT (or other) imaging
2) Multiple beam directions to cross fire targets
3) Individually shaped or intensity modulated beams
that conform to the target volume shape and
desired dosages
4) Use of image guidance, patient setup and immobilization, and management of motion so deviations
from treatment plan are limited
CT, Computed tomography.
Intensity Modulated Radiation Therapy
Intensity modulated radiation therapy (IMRT) represents the next evolution of conforming techniques. Two
key additional features are seen that include nonuniform
intensity of radiation beams as well as computerized inverse
planning.71 e complex intensity distribution of the individual beams diers from 3D-CRT, where beams are uniform. Inverse planning involves rst selecting the desired
distribution of dosages. e radiation oncologist denes
critical organs and tumors on imaging, slice by slice, and
the planner determines the target doses for each. An optimization program is run to nd suitable treatment parameters best matching all criteria. is aords highly complex
target conformity, such as that required for radiation treatment of tumors wrapped in the central nervous system.
With this technique, normal tissue is spared, and missing
tissue, such as lumpectomy defects, may be compensated
for. However, there is an increase in clinician time for target and treatment planning, and an increase in total body
irradiation dose.
Data for IMRT is still pending. Some trials indicate
low toxicity, IBTR, and satisfactory breast aesthetics,
yet others found suboptimal, declining cosmesis.
88,89
83-87
e
IMPORT LOW trial, a 5.8-year follow-up with 2018
randomized women, demonstrated non-inferiority when
comparing IBTR and cosmetic outcome compared with
standard WBI or WBI with a simultaneously integrated
boost.90
ASTRO Recommendations
Based on preliminary studies, ASTRO recently broadened
their criteria for APBI outside of clinical trials. eir recommendations are cited in Table 20.5.82
Intraoperative Radiation
IORT partial breast irradiation represents an alternative to
APBI, where a single large dose of radiation via an x-ray
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TABLE
2017 ASTRO Recommendations for APBI
20.5
Patient
Group Recommendations
Suitability Age: ≥50 years
Margins: Negative by at least 2 mm
T stage: T1
DCIS:
• Screen detected
• Low to intermediate grade
• Size ≤ 2.5 cm
• Resected with margins negative at ≥ 3 mm
Cautionary Age:
• 40–49 y if other suitable criteria are met
• ≥50 y if patient has at least one of the
pathological factors below and does not
have any “unsuitable” factors
Margins:
• Close margins (<2 mm)
DCIS:
• Pure DCIS ≤ 3 cm if criteria for “suitability”
are not fully met
Pathological factors:
• Size of invasive component: 2.1–3.0 cm
• T2
• Limited/focal lymphovascular space invasion
• ER(-)
• Clinically unifocal with total size 2.1–3.0 cm*
• Invasive lobular histology
• Extensive intraductal component ≤ 3 cm
Unsuitable Age:
• <40 y
• 40–49 y and do not meet the criteria for
cautionary
Margins: Positive
DCIS: >3 cm
*Microscopic multifocality allowed, provided the lesion is clinically unifocal (a single discrete lesion by physical exam and ultrasound/mammography) and the total lesion size (including foci and multifocality and
intervening normal breast parenchyma) falls between 2.1 and 3.0 cm.
From Correa C, Harris EE, Leonardi MC, et al. Accelerated partial breast
irradiation: Executive summary for the update of an ASTRO EvidenceBased Consensus Statement. Pract Radiat Oncol. 2017;7(2):73–79.
source or electrons may be delivered at the time of surgery,
or as a second procedure. Advantages include minimization
of dose to normal tissue and patient convenience. However,
remedial WBI may be needed in a cohort of patients, as the
nal pathology status is unknown at the time of surgery.
ere is also an inability to verify dose and volumes of tissue
treated. Two large trials have compared IORT delivery systems to WBI: the ELIOT trial examined electron beams91 or
TARGIT with low-energy x-rays.92 Both trials have found
an increased rate of IBTR compared with WBI. However,
women who met the “suitability” criteria had a low rate of
IBTR of 1.5% in the ELIOT trial (see Table 20.5). Contro-
versy has been raised of the TARGIT trial design and their
denition of noninferiority.93 ere were increased rates of
fat necrosis but lower rates of skin brosis.82 Lung brosis
was lower in the ELIOT trial and deaths from cardiovascular causes in the TARGIT trial in the IORT cohorts, indicating improved critical organ sparing.
ASTRO recommendation, as a result of the ELIOT trial,
is that electron IORT should be limited to women with
invasive cancer of the suitable category (see Table 20.5).82
Use of low-energy x-ray, based on the TARGIT trials and
its ensuing controversy, should be restricted to clinical trials;
only women with invasive cancer in the suitable category
should be enrolled. Furthermore, patients should be counseled that IBTR is higher in both IORT methods based on
the results from the trials’ data.
Management of Side Effects
Based on the radiobiological continuum, complications as a
result of RT can occur from hours to days to years. e consequences of radiation exposure to normal tissue includes,
but is not limited to, fatigue, myelosuppression, radiation
dermatitis, poor cosmesis of breast tissue, long-term chest
wall or soft tissue complications (i.e., pain, decreased range
of motion, rib fractures, brachial plexopathy), pulmonary
eects, cardiac complications, and radiation-related second
malignancies (listed from most to least common).94 Longitudinal outcomes have demonstrated increased mortality
from heart disease in left sided breast cancer and ipsilateral
secondary lung cancer, particularly in RT performed in the
70s, 10–20 years later.
Fatigue is common in patients following RT and plateaus at weeks 4–5, but returns to baseline within a few
months.
94,96,97
combination of radiotherapy and chemotherapy than
when treated with radiation alone.96 Persistent lethargy
is another common problem among breast cancer survivors, with reports of fatigue 20–40 years after diagnosis.98 Although exercise, such as yoga, may improve
symptoms,96 systemic disorders such as anemia, should
be ruled out. Although rarely of signicance, myelosuppression is common after radiation with subsequent
suppression of leukocytes, lymphocytes, and platelets.97
Routine blood counts are not recommended; however,
special attention should be made for patients receiving
both chemotherapy and radiation for signs of infection
or leukopenia.
Nearly all women experience radiation dermatitis as a
result of BCT.99 ese changes are dose respondent (Table
20.6). Transient erythema initially presents with initiation
of therapy. More prolonged skin changes begin 2 weeks after
therapy resembling a skin burn (Fig. 20.6). ese changes
are rated by the National Cancer Institute’s Common Terminology for Adverse Events (CTCAE) (Table 20.7).
Ninety-ve percent of women present with stage 1 or 2
acute dermatitis.
ment, the majority of symptoms resolve within a month of
cessation of treatment. However, late eects such as hyperpigmentation, telangiectasias, and brosis can arise over the
ensuing months to years. Reducing sun exposure, minimizing skin trauma during washing, and topical steroids have
95
Women experience more fatigue with a
100
101
Following completion of radiation treat-
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