Research Article
Intraoperative Radiotherapy with the Use of Low Energy X-Rays for the Treatment of Early Breast Cancer
Antonio Maffuz-Aziz1*, Judith Huerta-Bahena2, Carlos Alberto Domínguez-Reyes1, Juan Alberto Tenorio-Torres1, Santiago Sherwell-Cabello1, Silvia López-Hernández1 and Sergio Rodríguez-Cuevas1
1Department of Surgery, Instituto de Enfermedades de la Mama FUCAM, México
2Department of Radiation Oncology, Instituto de Enfermedades de la Mama FUCAM, México
*Corresponding author: Antonio Maffuz-Aziz, Instituto de Enfermedades de la Mama FUCAM, Av. Bordo 100, Colonia Ejido de Santa Ursula Coapa, Mexico City, Mexico
Published: 11 May, 2018
Cite this article as: Maffuz-Aziz A, Huerta-Bahena J,
Domínguez-Reyes CA, Tenorio-Torres
JA, Sherwell-Cabello S, López-
Hernández S, et al. Intraoperative
Radiotherapy with the Use of Low
Energy X-Rays for the Treatment of
Early Breast Cancer. Clin Oncol. 2018;
3: 1465.
Abstract
The present study shows the experience, with the use of partial accelerated Intraoperative Radiation Therapy (IORT) to the breast, by the use of 50kV X-ray system (Karl Zeiss Intrabeam), after conservative surgery, for patients with early breast cancer, describing the short-term results in relation to the tolerance and complications of treatment, and in the medium and long term in relation to tumor relapse and overall survival. 230 patients were included in a period of more than 6 years, median age was 57 years (range 40-86 years), and the median tumor size was 1.4cm (range 0.4 cm – 3.2 cm), criteria of ASTRO and ESTRO were applied for the selection of cases. The median followup was 48 months (range 12-89 months), 31 patients (13.5%) required complementary external radiotherapy, for adverse prognostic factors, acute complications presented in 23% of the cases, the vast majority (94%), were minor complications resolved spontaneously or by a simple procedure in the office (seroma, small dehiscence, edema, mild radioepithelitis). Local recurrence occurred in 4 patients (1.7%), 3 in the surgical bed or scar, and one axillary, in three of four relapses, breast conservation was possible, since they were resolved with local resection and external radiotherapy. Two patients had distant relapse, one bone and one pulmonary, the latter died 10 months after the relapse was documented, and is the only death in the current series. IORT can be considered as an alternative to external total radiotherapy for well-selected patients, who meet criteria of partial radiation therapy to the breast.
Introduction
Conservative surgery followed by total radiotherapy to the breast, is the treatment of choice in patients with early breast cancer, and it provides a locoregional control, similar to that of total mastectomy, but with the aesthetic and psychological benefit of the breast conservation. Patients receiving postoperative radiation therapy, require treatment 5 days a week for 3 to 6 weeks [1- 3]. Up to a third of the patients treated with conservative surgery in North America, do not receive postoperative radiotherapy, because of the distance they must travel from their homes to the radiation center, and cannot go daily. This fact affects women with breast cancer throughout the world, mainly elderly women [4-5]. In some countries, doctors and patients occasionally reject conservative surgery and choose a total mastectomy in order to avoid radiotherapy [6-8]. Related to this, Intraoperative Radiotherapy (IORT), and some other shorter and localized forms of radiotherapy have been evaluated.It has been shown, that local relapse after conservative surgery, occurs in the majority of cases (around 90%) near the surgical site, and tumors that appear in a different quadrant, are often classified as a second primary, and these events, apparently occur with the same frequency after the removal of the primary tumor regardless of whether or not, the patient received total radiation therapy to the breast [9-11]. Therefore, it has been established, that some patients can be safely treated with partial radiation therapy to the breast, in which only the surgical site after the removal of the primary tumor is irradiated. Such management can be done through different systems,that include brachytherapy techniques with interstitial implants or balloon catheters, IORT with electrons or with 50 kV X-rays or three-dimensional conformal external radiotherapy [12]. The aim of the present study is to show the experience, with the use of partial accelerated IORT to the breast, by the use of 50 kV X-ray system (Karl Zeiss Intrabeam), after conservative surgery, describing the short-term results in relation to the tolerance and complications of treatment, and in the medium and long term in relation to tumor relapse and overall survival.
Table 1,2
Table 1,2
Describe the general characteristics of the population, and related
variables to the primary tumor and prognostic factors involved in recurrence.
Table 2
Material and Method
This is a retrospective study, which included patients diagnosed
with early breast cancer (AJCC clinical stages I and IIA), treated
primarily with breast-conserving surgery and lymphatic mapping
with sentinel lymph node biopsy (+/- radical axillary dissection, in the
case of positive sentinel lymph node in intraoperative examination)
which received post tumorectomy, IORT with the 50 kV X-ray system
(Karl Zeiss Intrabeam) a dose between 20 and 22 Gy, from February
2010 to July 2016. All the patients underwent imaging studies to
rule out multifocality. They were initially evaluated with digital
mammography and ultrasound, and in some of them, with magnetic
resonance, tomosynthesis (three-dimensional mammography) and/
or high-resolution ultrasound scan, and only those patients, in whom
the absence of multifocality was demonstrated, were eligible for
RTIO.
The procedure is carried out in the following way:
a) Breast tumor is removed, with intraoperative radiological and
histopathological evaluation of the specimen, to guarantee negative
surgical margins. Lymphatic mapping with sentinel lymph node
biopsy for axillary staging is also performed.
b) Once negative surgical margins are obtained, the tumor bed
is prepared, to allow the entire spherical device of the equipment to
adapt breast tissue of the surgical bed; suture is made in the surgical
bed and upper margin to completely enclose the spherical device.
c) The dose to be administered is calculated and the spherical
device is installed in the energy source, to subsequently apply it in the
lumpectomy site, the sutures are "closed" and sonographic control is
carried out, verifying that the surgical bed is completely in contact
with the spherical device and the planned dose is applied.
d) The equipment is removed, and the primary repair or
oncoplastic procedure of the surgical bed is performed.
Patients with adverse pathological prognostic factors received
complementary external radiotherapy, taking the dose received
intraoperatively as the boost in the tumor bed.
Patients with ductal carcinoma in situ, or infiltrating lobular
carcinoma were excluded from the present study, since there is
no clear evidence of its benefit of partial breast irradiation, in
these histological varieties. The clinical and histopathological
characteristics of each patient were evaluated, including age, body
mass index, tumor size, surgical margins of resection, histological
grade, lymphovascular invasion, intraductal component, lymph node
involvement, hormonal receptors, Her-2 neu and Ki 67, as well as the
adjuvant treatment received after surgery (chemotherapy, antiHer-2
treatment, complementary external radiotherapy, hormone therapy).
Table 3
Table 4
Results
A total of 230 patients with breast cancer, with 234 tumors (4 patients with bilateral cancer) were included between February 2010 and July 2016. (Table 1, 2), describe the general characteristics of the population, and related variables to the primary tumor and prognostic factors involved in recurrence. Conservative surgery with IORT, was performed bilaterally in the same surgery in 4 cases, and in combination with oncoplastic procedures in 34 cases. All patients received adjuvant treatment according to stage, and biological subtype. (Table 3) describes the adjuvant treatment that patients received, 31 (13.5%) of them were eligible for complementary external radiotherapy, for adverse prognostic factors detected in the final surgical piece, taking the dose received intraoperatively, as boost. Ten patients required another surgery for positive margins (4.3%), 7 of them underwent total mastectomy, and 3 re-excision and complementary external radiotherapy. There was an incidence of acute complications in 23% of the cases, of them, the vast majority (94%), were minor complications resolved spontaneously or by a simple procedure in the office (seroma, small dehiscence, edema, mild radioepithelitis) and without sequelae for the patients, only 3 patients (6%) presented severe complications, two of them attended with infection manifested with fever, skin edema and extensive erythema, requiring in-hospital management with antimicrobials, and one patient presented breast tissue radionecrosis, being necessary surgical remove and repaired by vertical mammoplasty with contralateral symmetry. Regarding the late sequelae of the treatment, 15 patients (6.5%) presented fibrosis with breast retraction and apparent aesthetic defect, only one of them required an aesthetic procedure with placement of prosthesis for breast remodeling. The median follow-up was 48 months (range 12-89 months), there were 4 locoregional relapses, (Table 4) three in the surgical bed or scar, and one axillary, in three of four relapses, breast conservation was possible, since they were resolved with local resection and external radiotherapy. The median time from initial treatment to relapse was 45 months (range of 32 to 55 months). Two patients had distant relapse, one bone and the other pulmonary, the latter died 10 months after the relapse was documented and is the only death in the current series of patients. Thus, the overall survival, with a median follow-up of 48 months, was 99.5% and the local recurrence was 1.7%.
Discussion
The American Society for Radiation Oncology (ASTRO), and
the European Society for Therapeutic Radiology and Oncology
(ESTRO), have issued recommendations for the selection patients
who can be treated with partial breast irradiation (intraoperative or
postoperative) after conservative surgery, there are selection criteria
known as appropriate or for patients with low risk, cautionary
or intermediate risk, and high risk of recurrence. In general, it is
recommended for women older than 50 years (although it is feasible
at 40 years, as a cautionary criteria), with tumors of 3 cm or less,
unifocal, infiltrating ductal histology and other varieties of good
prognosis (mucinous, tubular, medullary or colloid), luminal subtype,
absence of lymph node metastases, and negative surgical margins
[13,14]. The justification for the use of partial breast irradiation, is
based on the fact that most relapses after breast-conserving surgery
occur at the lumpectomy site. In the present study, we used the 50 kV
X-ray system (Intrabeam of Karl Zeiss) for IORT, the pivotal study
with the use of this therapeutic modality is the TARGIT A, published
by Vaidya and cols, in which randomized 3,451 patients to receive
standard treatment with total external radiotherapy to the breast, or
IORT, including patients ≥ 45 years, with tumors of ≤ 3.5 cm, N0-1,
M0 and unifocal infiltrating ductal carcinoma, demonstrating only
a slight increase in risk of local relapse at 5 years (1.3 vs. 3.3%) for
the group treated with IORT, without a significant impact on overall
survival [15]. Factors related to local relapse after partial breast
irradiation have been described, in a study published by Shah [16]
in which 1,961 patients were included; the absence of expression of
estrogen receptors was found as the only factor associated with local
recurrence, a major tendency (but not significant) in women under
50 years of age. The risk of local recurrence in early breast cancer
is higher in the first 5 years after treatment, regardless of baseline
prognostic factors, 30% of local recurrences occurs within 36 months
after initial treatment. Different series have reported that patients
whose develop local recurrence within the first two years, have a
significantly worse prognosis than those who recur after 5 years. The
longer interval between initial treatment and the occurrence of local
relapse, the better the prognosis [17-19]. In the present study, 1.7%
of locoregional relapses occur, with median of 48 months of primary
treatment at the time of relapse, the patients included in the present
study, most of them meet "appropriate" selection criteria for partial
radiotherapy, and only some with "cautionary" criteria, of the latter,
most of them, received external radiotherapy additional to the IORT
(13%).
Zhang et al. [20] in a meta-analysis of 5415 patients, which
included, in addition to others, TARGIT A [15] and ELIOT [21]
trials, and in which the comparison was made between IORT and
external total radiotherapy in early breast cancer, finding a significant
difference in the relative risk of ipsilateral tumor recurrence in patients
treated with IORT (RR=2.83, 95% CI: 1.23-6.51), it should be noted
that patient selection, was not homogeneous and therefore these
results should be interpreted with caution. There was no significant
difference between the two groups in relation to overall mortality,
mortality from breast cancer and distant metastases. Several reports,
documented that in some patients, it is decided to perform a total
mastectomy, even being candidates for breast conservation, due to
the time it takes to travel to distant sites, where they may receive
adjuvant radiotherapy, total radiotherapy, involves 3 to 6 weeks to
complete an adequate dose. Additionally, in the developing countries
there is not a sufficient number of radiotherapy equipment’s to cover
their healthcare needs [22-24]. In a study published by Bargallo-
Rocha [25], clearly describes the beneficial impact of the use of
IORT in the saving of transfer time and the number of visits to the
radiotherapy center, leading to a cost reduction of 12% per patient.
IORT offers as an additional benefit that in most cases is offered as a
single treatment, in a single dose shortening time and guaranteeing
a complete locoregional treatment. It can also be accompanied by
oncoplastic procedures with adequate oncological control and a
good cosmetic result, offering then in a single operative time, the
extirpation of the primary tumor, the radiation to the surgical bed
and the remodeling of the breast shape, even with contralateral breast
symmetry. On the other hand, adequate tolerance to IORT has been
demonstrated, with no increase in postoperative local complications
(infection, dehiscence or necrosis). Other additional advantage of
IORT is the direct application on the tumor bed, without the risk of
having a topographical mistake; the irradiation of the skin is avoided,
minimizing radiation skin damage. The field to be irradiated is
smaller and the dose is very homogeneous, the late effect is minimal
in terms of fibrosis, and the cosmetic result is usually very good [26].
Conclusion
In conclusion, IORT can be considered as an alternative to external total radiotherapy for well-selected patients, who meet criteria of partial radiation therapy to the breast.
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