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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 6  |  Page : 1309-1313

Synchronous bilateral breast cancer patients treated with hypofractionated bilateral breast irradiation: A dosimetric and clinical study


1 Department of Radiation Oncology, Government General Hospital, Guntur, Andhra Pradesh, India
2 Department of Radiation Oncology, Nizamís Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Submission28-Feb-2020
Date of Decision24-Jul-2020
Date of Acceptance04-Sep-2020
Date of Web Publication18-Dec-2020

Correspondence Address:
Monica Malik
Department of Radiation Oncology, Nizamís Institute of Medical Sciences, Hyderabad, Telangana,
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_241_20

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 > Abstract 


Background: Bilateral breast irradiation is technically challenging and there is limited information regarding optimal technique and outcomes. Hypofractionated Radiotherapy (HFRT) has emerged as the new standard of care in early breast cancer. However, there are concerns in using hypofractionation for bilateral breast irradiation due to larger volumes and potential toxicity. Our aim was to analyze the dosimetric data and clinical outcomes in these patients.
Materials and Methods: Patients with synchronous bilateral breast cancer (SBBC) treated with bilateral breast irradiation were analyzed. All patients received simultaneous bilateral breast with or without regional nodal irradiation using a hypofractionated schedule of 40 Gy in 15 fractions over 3 weeks with single isocenter bi-tangential field-in-field intensity-modulated radiation therapy (FIF-IMRT) technique.
Results: Seven patients of SBBC were treated at our institute from 2015 to 2017. All patients were postmenopausal females. Five patients underwent bilateral modified radical mastectomy; two patients underwent bilateral breast conservative surgery. All patients received systemic anthracycline-based chemotherapy. The mean cardiac dose was 3.73 ± Gy and V 25 was 3.26% ± 1.96%. V 20 of lung ranged from 23.48% ± 4.47% and the mean esophageal dose was 3.6 ± 2.00 Gy. No patient had acute toxicity higher than Grade 2. At a median follow-up of 48 months, one patient died due to systemic progression. No patient reported any late toxicity.
Conclusion: Bilateral breast irradiation using a hypofractionated schedule with single isocenter FIF-IMRT technique is technically feasible with minimal acute toxicity and no significant late effects on early follow-up.

Keywords: Field-in-field intensity-modulated radiation therapy, hypofractionated radiotherapy, synchronous bilateral breast cancer


How to cite this article:
Narasimhulu B C, Valiyaveettil D, Joseph D, Ahmed SF, Vijayakrishna E, Malik M. Synchronous bilateral breast cancer patients treated with hypofractionated bilateral breast irradiation: A dosimetric and clinical study. J Can Res Ther 2020;16:1309-13

How to cite this URL:
Narasimhulu B C, Valiyaveettil D, Joseph D, Ahmed SF, Vijayakrishna E, Malik M. Synchronous bilateral breast cancer patients treated with hypofractionated bilateral breast irradiation: A dosimetric and clinical study. J Can Res Ther [serial online] 2020 [cited 2021 Nov 27];16:1309-13. Available from: https://www.cancerjournal.net/text.asp?2020/16/6/1309/303893




 > Introduction Top


Synchronous bilateral breast cancer (SBBC) presents significantly worse outcomes than that of unilateral breast cancer.[1],[2] There is no standard treatment guideline for SBBC. Radiotherapy (RT) treatment planning for SBBC cases is challenging due to irregular geometry, problems of junction overlap, and dose constraints of organs at risk (OAR).[3] Majority of the studies on bilateral breast RT have focused on techniques and dosimetric data with sparse information on clinical toxicity and outcomes. We conducted an analysis of the dosimetric and clinical data for patients of SBBC treated with hypofractionation using the conformal field-in-field technique.


 > Materials and Methods Top


Patient selection

Medical records of patients with histopathological diagnosis of SBBC who received bilateral RT at our institute from 2015 to 2017 were reviewed. After approval of the ethics committee, demographic and clinical data such as age, comorbidities, menstrual history, and obstetric history were collected. Tumor and treatment-related variables such as type of surgery, tumor size, number of nodes involved, stage, chemotherapy, estrogen receptor, progesterone receptor, HER2/neu receptor status, hormonal therapy, and RT details were recorded. All dosimetric data were collected from the treatment planning system.

Contouring and planning

Targets and OARs (heart, lungs, esophagus, and spinal cord) were contoured according to the Radiation Therapy Oncology Group (RTOG) guidelines. Planning target volume (PTV) total structure was generated using Boolean operation, i.e., PTV (combined) = PTV (right breast/chest wall) + PTV (left breast/chest wall) ± supraclavicular fossa to calculate the homogeneity and conformity index (CI).

Dose conformity characterizes the degree to which the high-dose region conforms to the target volume. Dose homogeneity characterizes the uniformity of the absorbed dose within the target.

Homogeneity index

Homogeneity index (HI) is calculated as:



Where, D2%, D98%, and D50% represent the doses received by 2%, 98%, and 50% volumes of the PTV.

Conformity index

RTOG recommended CI as a ratio of the reference isodose volume to the target volume.



VRI is a reference isodose volume, and TV is the target volume.

All plans were made using 3 mm axial free-breathing computed tomography slices on the treatment planning system (Eclipse™ v. 8.6.0; Varian® Medical Systems, Palo Alto, CA) for treatment on a Varian Clinac iX with a 120-leaf multileaf collimator (MLC; Varian Medical Systems). Radiation fields were planned using a single isocenter with bitangential beam arrangement for each breast/chest wall with field-in-field forward planning intensity-modulated radiation therapy (FIF-IMRT) technique using 6 MV beams with 0.7–1 cm gap between medial tangential portals of each side [Figure 1]. A single anteroposterior field was used for regional nodal irradiation (RNI) when indicated. Bolus was not used for any chest wall planning. All patients received HFRT, 2.667 Gy/fraction for 15 fractions, 5 fractions a week to the chest wall/breast ± RNI to a dose of 40.05 Gy with a surgical bed boost of 10 Gy (2 Gy/fraction) to breast-conserving surgery patients.
Figure 1: Beam arrangements and dose distributions

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The mean lung dose was restricted to 15 Gy with V20 Gy <30% (no more than 30% of the OAR volume receiving 20 Gy) for the lungs and V25 Gy <20% for the heart. The heart was spared using the MLC whenever possible without compromising target volume coverage.

A composite plan was produced by summing the regional irradiation plan and the whole breast/chest plan of both sides.

The assessment of acute toxicity was done periodically during treatment and was managed accordingly.

Follow-up

On follow-up, lung, heart, and esophageal toxicity was assessed clinically, and patients were evaluated with further investigations if clinically indicated.

Statistics

Descriptive statistics such as the mean and standard deviation were performed for the most relevant dosimetric parameters. Statistics were done using Microsoft Excel and SPSS v 20 (IBM Corp. Armonk, NY, USA).


 > Results Top


Seven patients of SBBC (14 tumors) were treated at our institute from 2015 to 2017 with bilateral breast irradiation following surgery and adjuvant chemotherapy. The mean age was 59 years (range 45–65 years). All patients were female and postmenopausal. Five patients had preexisting comorbidities which comprised of hypertension or diabetes or both. No patient had preexisting heart disease or coronary artery disease. No patient had a family history of malignancy.

The most common site of the lump was the upper outer quadrant (5/14), followed by the central quadrant (4/14), lower outer quadrant (3/14), lower inner (1/14), and upper inner quadrant (1/14). Thirteen tumors were infiltrating duct cell carcinoma NOS and one tumor was infiltrating tubulolobular carcinoma. Other tumor-related factors are documented in [Table 1]. All patients received anthracycline-based chemotherapy. No patient received trastuzumab. Treatment-related details are documented in [Table 2]. All relevant dosimetric data from the treatment planning system are documented in [Table 3] and [Table 4].
Table 1: Tumor characteristics

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Table 2: Treatment details

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Table 3: Dosimetric data: Targets

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Table 4: Dosimetric data: organs at risks

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All patients completed the planned RT course without any interruptions. No acute toxicities higher than Grade 2 were reported.

Follow-up

At a median follow-up of 48 months, no significant late toxicities including skin fibrosis, limitation of shoulder mobility, arm edema, clinical radiation pneumonitis, or cardiac effects have been reported. Five patients are currently on adjuvant endocrine therapy. One patient progressed systemically and developed liver and bone metastases and died.


 > Discussion Top


The incidence of bilateral breast cancer (BBC) is increasing as a result of routine use of contralateral breast mammography in newly diagnosed breast cancers and improved life expectancy after breast cancer treatment.[4] The overall incidence of BBC has been shown to range from 1.4% to 12%.[5],[6],[7],[8] The incidence of SBBC is uncommon, ranging from 0.7% to 3.0%. Unlike the treatment of unilateral breast cancer, RT planning and treatment of SBBC is challenging because it can be potentially associated with more toxicity due to a larger area of treatment. For complex treatment volumes such as SBBC, various techniques have been described in literature such as three-dimensional conformal RT (3DCRT), IMRT, and volumetric-modulated arc therapy (VMAT). The 3DCRT technique is affected by increased dose heterogeneity over the treatment volume due to the variability in breast/chest contours. There is also a risk of underdosing or overdosing at the field junctions.[9] This may be overcome using field-in-field forward planning IMRT.

Highly conformal techniques such as VMAT improve the target dose coverage and cosmetic outcomes.[10],[11],[12],[13],[14],[15] However, when using arc in multiple directions, larger volumes of lungs are exposed to irradiation. There is a greater degree of conformality with standard IMRT, helical tomotherapy, and VMAT plans at the cost of low-dose regions encompassing larger volumes of heart and lungs[14] compared with the 3DCRT technique. There have been studies comparing the 3DCRT and IMRT techniques with Rapid Arc.[16],[17] Newer studies comparing different planning techniques[18],[19] showed highly conformal planning techniques such as VMAT, IMRT, or hybrid plans show dosimetric advantage.

However, when patients require complex treatment, which includes bilateral breasts or chest wall along with RNI (coverage of supraclavicular and axillary levels I–III), there is no consensus of the optimal radiation treatment technique. 3D-CRT with tangential fields is recommended by the American Society of Radiation Oncology. This recommendation is due to the lack of clinical advantages of highly conformal IMRT techniques comparing to 3D-CRT, in terms of advantages in survival or reduction in the risk of recurrence.[20]

In developing countries and resource-restricted settings, availability, affordability, and accessibility for more conformal RT techniques such as IMRT, VMAT, and tomotherapy are limited for most patients. Our method using a single isocenter bi-tangential fields using FIF-IMRT is a simple technique avoiding overlap regions with good reproducibility, less treatment time, and no complex setup or QA requirements.

Most of the published studies have used conventional fractionation for bilateral breast irradiation which is 45–50 Gy in 1.8–2 Gy/fraction over 5 weeks with or without a boost to the surgical bed of 10–16 Gy.[21],[22],[23],[24] In recent times, hypofractionated radiotherapy (HFRT) has emerged as the new standard of care for early breast cancer as evidence from large randomized trials shows comparable or even better disease-free survival and toxicity profile.[25],[26] These HFRT trials have a small proportion of patients who received postmastectomy irradiation, RNI, or chemotherapy and with no reported detrimental effects.

A systematic review and meta-analysis comparing hypofractionated with conventional fraction RT in treatment of early breast cancer concluded that based on available evidence, HFRT with 2.5–3.0 Gy/fraction should be the better choice for treatment of early breast cancer patients.[25] However, the hypofractionated dose schedule has not been studied in bilateral breast irradiation, and there are potential concerns about the large volumes irradiated and toxicities. We have used HFRT for all our patients and have observed similar outcomes.

Cardiac toxicity is a major concern for breast cancer irradiation causing ischemia.[27] The radiobiology of radiation-induced cardiac damage has not been established well. It can be a complex interplay of multiple factors such as comorbidities, chemotherapy (anthracyclines) and targeted therapy (anti-HER2 agents like trastuzumab), and radiation (mean heart dose or dose to LAD).[28],[29] According to the OARs sparing, Dmean of 3–4 Gy and V 25 Gy <10% to the heart are considered acceptable values for unilateral breast irradiation with respect to the risk of long-term cardiac mortality by 3D-CRT.[30] Our study using bi-tangential FIF-IMRT could achieve D mean of 3.73 Gy and V 25 Gy of 3.26% in these patients.

For the lungs, V 20 Gy <30% and a D mean <13 Gy were recommended to limit the risk of symptomatic radiation pneumonitis. This is a rare side effect in unilateral breast irradiation due to present radiation techniques. A higher irradiation volume in bilateral cases increases the risk.[31],[32],[33],[34] The mean V20 for the total lung was 23.48% and the mean lung dose of both the lungs of all the patients was 10.78 Gy. None of our patients developed radiation pneumonitis.

Our analysis suggests that the treatment of SBBC with hypofractionated radiation using bi-tangential FIF-IMRT is feasible with minimal acute toxicity. Limitations of this study include a small patient number and short follow-up duration.



Hypofractionation is a potentially viable strategy in bilateral breast irradiation and can improve treatment compliance, patient satisfaction, and reduce costs. A longer follow-up is warranted to assess late effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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