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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 2  |  Page : 262-267

Adjuvant hypofractionated radiation in carcinoma breast – Photon versus Electron: Comparison of treatment outcome


1 Department of Radiation Oncology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita University, Kochi, Kerala, India
2 Department of Radiation Oncology, HCG Institute of Oncology, Bengaluru, Karnataka, India
3 Department of Medical Physics, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita University, Kochi, Kerala, India

Date of Web Publication23-Jun-2017

Correspondence Address:
G Prameela Chelakkot
Department of Radiation Oncology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita University, Kochi - 682 041, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.192851

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 > Abstract 

Background: Breast cancer tissue is sensitive to hypofractionation. This is an analysis of patients treated with hypofractionated protocols since 2009, at our tertiary cancer center.
Methods: Details of breast cancer patients treated with adjuvant hypofractionated external beam radiation therapy (EBRT) from January 2009 to December 2014 were retrieved and analyzed.
Results: One thousand seven hundred and eighty patients received adjuvant EBRT during this period. Three hundred and eight were offered hypofractionated schedule. One hundred and eighty-eight had modified radical mastectomy (MRM) and 120 had breast conservation surgery (BCS). Dose was 40 Gy in 15 fractions to chest wall/breast, and tumor bed boost of 10 Gy in 5 fractions, where indicated, using three-dimensional conformal radiotherapy (3DCRT). Electrons were used in 159 and photons in 149. Single en face electron field was used for chest wall in MRM patients, and tangential photon beams for the whole breast. Patients on follow-up were assessed for locoregional recurrence, chest wall, breast or ipsilateral upper limb edema, brachial neuralgia, local skeletal events, pulmonary and cardiac symptoms, and cosmetic results. Two developed chest wall recurrence, one each in electron and photon arms. No skeletal, cardiac, or pulmonary adverse events were recorded. About 13.6% had arm edema, which was staged according to the International Society of Lymphology lymphedema staging, as Stage I-7.8%, Stage II-3.9%, and Stage III-1.9%. Twenty-six treated with electrons had arm edema. Increased incidence of arm edema in MRM patients could be attributed to combined surgical and radiation morbidity. Five-year overall survival was 81.9%.
Conclusion: Hypofractionation is an accepted cost-effective standard of care in adjuvant breast radiation. Single en face electron field is well tolerated, and 3DCRT planning ensures homogeneous chest wall coverage, respecting dose constraints to organs at risk.

Keywords: Adjuvant breast radiation, chest wall radiation, hypofractionated radiation, single en face electron field


How to cite this article:
Chelakkot G P, Ravind R, Sruthi K, Chigurupati N, Kotne S, Holla R, Madhavan R, Dinesh M. Adjuvant hypofractionated radiation in carcinoma breast – Photon versus Electron: Comparison of treatment outcome. J Can Res Ther 2017;13:262-7

How to cite this URL:
Chelakkot G P, Ravind R, Sruthi K, Chigurupati N, Kotne S, Holla R, Madhavan R, Dinesh M. Adjuvant hypofractionated radiation in carcinoma breast – Photon versus Electron: Comparison of treatment outcome. J Can Res Ther [serial online] 2017 [cited 2022 Dec 2];13:262-7. Available from: https://www.cancerjournal.net/text.asp?2017/13/2/262/192851


 > Introduction Top


Breast cancer tissue is sensitive to treatment using high-dose fractionations, as has been proved and results of the UK Standardization of Breast Radiotherapy (START) Randomized Trials and Ontario Trials showed benefits of hypofractionated radiation.[1] START trials used photon energy for treating chest wall and breast, and electron boost for tumor bed. We, at our tertiary cancer care center, have been using hypofractionated protocols with both photons and electrons from 2009. This is an analysis of our patients treated with hypofractionated regimen, and a comparison of treatment outcomes using photons and electrons.


 > Methods Top


Details of breast cancer patients, who received adjuvant external beam radiation using hypofractionated regimen from January 2009 to December 2014, were retrieved from electronic medical records, radiotherapy treatment charts, and digital imaging details, and other communications in medical records. The data were compiled and analyzed for recurrence and toxicity profile. All data were analyzed using the latest version of SPSS 17.0 version for windows (Statistical Package for the Social Sciences [SPSS], IBM Corporation), and survival analysis done using Kaplan–Meier method.


 > Results Top


During this 5-year period, 1780 patients received adjuvant external beam radiation to chest wall/breast. Of these, 308 patients were offered hypofractionated schedule; the rest having had treatment using standard schedule of 50 Gy in 25 fractions with conventional fractionation. Decision to use hypofractionated protocol was at the discretion of treating physician, and there was no institutional randomization. Two were male patients. Right- and left-sided lesions were equal (50%). Surgery offered was either, a breast conservation surgery (BCS), which was done for 120 patients, or a modified radical mastectomy (MRM), which was done for 188 patients. Options for subsequent adjuvant treatment in the form of chemotherapy and/or hormones were decided based on histopathology findings.

Sequencing of radiation depended on whether chemotherapy was being offered, in which case it was usually after completion of same. All patients received a dose of 4000 cGy in 15 fractions, at 266.66 cGy per fraction, 5 fractions a week, to chest wall or whole breast, and a tumor bed boost of 1000 cGy in 5 fractions, at 200 cGy per fraction, 5 fractions a week, where indicated, using three-dimensional conformal radiotherapy (3DCRT). Patients who had undergone MRM did not receive a boost either to the chest wall or the scar. On the other hand, a dose of up to 50 Gy to the tumor bed is preferred for BCS patients. Except for five patients in the BCS group, all patients had received tumor bed boost of 10 Gy in 5 fractions. Boost was not offered in these five, as adequate dose was achieved to the tumor bed with the tangents.

Patients were positioned supine, on breast-board (angled-board), face turned to opposite side, and hand abducted and fixed on arm rests in the board. Custom-made breast masks were used for immobilization in case of large pendulous breasts, both in BCS patients and reconstructed breasts. Laser alignment with scale on breast-board and fiducials fixed on patient ensured reproducibility. Computerized axial tomogram with 3–5 mm thick slices was taken from chin to the level of L2 vertebra. Images thus acquired are sent to contouring and planning systems (FOCAL ® by IMPAC ® Medical Systems, Inc., Elekta ® Inc.). RTOG guidelines are used for contouring and 3DCRT planning carried out. The clinical target volume included the whole breast in BCS or reconstructed breasts and chest wall with mastectomy scar in MRM patients. Supraclavicular field (SCF) was treated when indicated. Medial and lateral tangential photon pairs were used for whole breast radiation. Boundaries of chest wall en face electron field were medially midline, laterally midaxillary line, superiorly lower border of SCF or below the head of clavicle, and inferiorly 2 cm below opposite infra-mammary fold. A separate internal mammary portal was not routinely used. For an inner quadrant lesion with node positivity, coverage of internal mammary nodal stations was ensured. Care was taken to avoid radiation to opposite breast, and where required, it was strapped away from field.

Decision on photon or electron was made based on chest wall thickness and optimum coverage. Chest wall thickness of up to approximately 3 cm, as observed from the simulation scan, was considered for en face electrons since beyond 3 cm the coverage is bound to be inadequate. Electron energies of 6–10 MeV are usually preferred, and only very rarely is a 12 MeV beam used. Uniformity of the chest wall is one other factor which is considered while opting for an electron beam because with a nonuniform chest wall, the coverage would also be heterogeneous. Care is also taken to see whether the scar will be encompassed within the field. Another factor that would compromise dose distribution in an electron field is the field size, as a very small field would lead to irregular dose coverage to the edges of the field and the deeper tissue, due to peaking of the beam but is not a concern in en face electron, where the field is always large. The size of the electron applicators usually used is 20 cm × 20 cm or 25 cm × 25 cm.

Electron energy was chosen so that with rescaling, the 40 Gy isodose line covers chest wall adequately including costal wall depth. Electrons were used in 159 (51.6%) patients and photons in 149 (48.4%) patients. In photon group, the energy commonly used was 6 MV, and dose was prescribed to 100% isodose line. For MRM patients, where electrons were used, unique single en face electron portals were designed for chest wall. The energy of electron beam ranged from 6 to 12 MeV (6 MeV - 38.9%, 8 MeV - 44.0%, 10 MeV - 14.4%, and 12 MeV - 2.5%). Isodose distributions were critically evaluated to ensure adequate chest wall coverage and were rescaled where required. A dose variation of 95–105% was observed. In most patients, treatment volume encompassed <2 cm of lung. Once planning is done, electron field is drawn over patient's chest wall for making Cerrobend cutout [Figure 1]. Daily field matching with supraclavicular photon field if present, avoids junctional hot spots. After completion of initial whole breast radiation, a tumor bed boost followed where indicated. Photons or electrons were used for boost fields. Electrons were used for boost in 36.5% (42/115) and photons in 63.5% (73/115). Care was taken to ensure that mean cardiac dose for left-sided lesions was within acceptable limits, and institution adhered to the QUANTEC constraints. Dose distributions were reviewed in weekly institutional chart rounds and modified when indicated. Patient characteristics are given in [Table 1].
Figure 1: En face electron cutout and treatment setup

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Table 1: Patient characteristics

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Twenty-three (7.5%) patients had Grade 1–2 skin reactions over the irradiated area, on completing treatment, which was managed symptomatically. Median follow-up was 41.6 months (range: 1.17–92.7 months). Patients on follow-up were assessed for locoregional recurrence, chest wall, breast or ipsilateral upper limb edema, brachial neuralgia, pulmonary and cardiac symptoms, skeletal complications, second primary in contralateral breast, and cosmetic results. Routine chest imaging at regular intervals was done only for 131 of the 308 patients, of whom, 105 were normal studies. Nine patients showed pulmonary metastases (0.029%). Fibrotic changes were noticed in nine patients, of whom eight were in the electron group (0.05%) and 1 (0.006%) in the photon group. No patient had presented with symptomatic pneumonitis. Two (0.65%) patients had developed chest wall recurrence; one in each arm. Median time to chest wall recurrence was 16.35 months. One patient in photon arm had developed opposite breast malignancy. No cardiac or skeletal adverse events were recorded. Forty-two patients (13.6%) had ipsilateral arm edema, which was staged according to the International Society of Lymphology (ISL) lymphedema staging, as ISL Stage I (24/308-7.8%), Stage II (12/308-3.9%), and Stage III (6/308-1.9%) [Appendix 1 [Additional file 1]]. Twenty-six patients treated with electrons (26/159-16.4%), and 16 treated with photons (16/149-10.7%), had arm edema. The 5-year overall survival was 81.9%. Electron group had a 5-year OS of 80.6% and photon group had 83.3%, but there was no significant advantage (P = 0.716 - log-rank [Mantel-Cox]) for one over the other [Figure 2] and [Figure 3].
Figure 2: Kaplan–Meier graph showing projected OS

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Figure 3: Kaplan–Meier graph showing projected OS Electron versus Photon

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 > Discussion Top


Chest wall recurrence after mastectomy was a challenge faced from Halsted's times. The need to address postmastectomy chest wall arose as an option for reducing this, and the earliest publication on chest wall radiation was by Paterson and Russel in 1959.[2] Cohen in 1952 had observed that α/β value for locally advanced and recurrent chest wall tumors could be in the range of 4–5 Gy, which was later substantiated by Douglas.[3] Yarnold et al. in 2005, further emphasized that α/β value for adenocarcinoma for locoregional tumor control was 4.6 Gy and for late changes was 3.4 Gy. They also suggested that fewer larger fractions were safe and effective in these tumors,[4] and trials of hypofractionation in breast took off from here.

Electrons have been in use for postmastectomy chest wall radiation in various institutes around the globe. Kirova from Curie Institute, Paris, showed improved and homogeneous coverage of chest wall with electron beam.[5] The use of electrons as an alternative to photon-based tangential fields for chest wall started empirically, with intent to reduce the load on physicist and dosimetrist, without compromising treatment outcomes. Although used in conventional fractionation treatment, there is a dearth of publications on the use of electron fields in hypofractionated schedules, probably because most centers deal with early breast cancer patients, who have had conservative surgery, and hence treat the whole breast using tangential photon pairs.

Diverse group of patients attend our tertiary care center, which include patients treated in-house with either BCS or MRM based on stage, patients who have had BCS or MRM at peripheral centers and are referred for further care, patients with early stage of disease, who have opted for mastectomy, and locally advanced breast cancer patients who even after neoadjuvant chemotherapy have had mastectomy. Hence, we have a higher proportion of postmastectomy patients compared to literature. There is no randomization to conventional fractionation or hypofractionated schedules, and the choice is usually physicians. Patients' financial, logistic, and social issues are confounding factors influencing the decision. Health providers in a highly populated treatment center like ours also welcome fewer treatment fields and reduced treatment times. Single en face electron field, hence, is much preferred in this context since less number of treatment fields reduce the treatment time considerably, and the total expenses incurred by the patients are reduced to a great extent.

Our experience with hypofractionated regimen dates from 2009 and the schedule followed is 40 Gy in 15 fractions at 266.66 cGy fractions, 5 fractions a week. Usually, tangential photon beams are used for whole breast and a single en face electron field for chest wall. Patients were planned using the CMS XiO (CMS - XiO Planning System - XiO Release V5.00.01 (Linux) Elekta - IMPAC Medical Systems, Inc.; Stockholm, Sweden) software and the electron beam algorithm was done, in the initial years using pencil beam algorithms and later using Monte Carlo algorithms, which also has the advantage that heterogeneity correction is inbuilt. For electron beam, rescaling either down or up, and use of bolus, modulated and optimized the chest wall coverage. Benefit of an internal mammary field treatment, still remaining a gray zone,[6] is not routinely included in treatment, as an institutional policy.

Dosimetric evaluation of dose to chest wall was not routinely carried out. However, our local recurrence rates of 1.08% in the entire group, with 1.06% in electron group and 1.09% in photon group, is ample evidence to show that there was no underdosing of chest wall. Local recurrence after chest wall radiation has been very minimal, and literature review shows there is no difference in incidence in short and long course treatments,[7] proving the equivalence of both. Our observation further substantiates that in hypofractionated treatment, use of electrons is noninferior to photons, with respect to local control. Radiation to chest wall or whole breast has not increased the incidence of second malignancy of contralateral breast, either. In our group, only one patient (0.3%), who belonged to the photon arm, had a second malignancy in the contralateral breast.

Worrying complications of postmastectomy radiation are lymphedema, skeletal complications, pulmonary fibrosis and pneumonitis, and cardiac complications. Pierce in his review on postmastectomy chest wall radiation has suggested that the factors consistently affecting lymphedema are the extent of axillary surgery and effect of axillary radiation.[8] Pierce quoted a combined risk of up to 40%. Our combined incidence was 13.6%, which is much lower (Donker et al. - 59.3% and 58.3% at 1 and 5 years) to that quoted by various trials.[9] Lymphedema was 14.9% in our MRM group and 11.7% in BCS group. Incidence of lymphedema was more in patients treated with electrons, among MRM patients (16.4%-26/159). Among photon group, 10.7% had lymphedema which included two MRM patients. Donker et al., in 2013, concluded that incidence of lymphedema was significantly higher after axillary dissection than after axillary radiation, but combination treatment resulted in an incidence of 59.3% at 1st year and 58.3% at 5 years. Probably, because of our institutional policy, where both surgeons and radiation oncologists address all three levels of axillary nodes, MRM patients had 16.4% incidence of lymphedema, which is still much less than that quoted by Donker et al. in AMAROS trial. The increased incidence could also be attributed to advanced disease in MRM group. Norman et al. in 2010 observed that incidence of lymphedema was more after anthracycline-based chemotherapy, and that there was no increase in the risk of lymphedema with adjuvant radiation.[10]

Although overt cardiac toxicities were not recorded in our series, it needs to be emphasized that cardiac changes take a longer time to manifest, and data are still immature to definitely rule out same, as was also opined by Jagsi, in their review article.[11] Appelt et al. had shown that EQD2 for 40 Gy favored hypofractionation [12] such as 40 Gy/15, 39 Gy/13, and 42.5 Gy/16 fractions. Cardiac dose can be modulated by selecting appropriate electron energy and if needed by photon-electron combinations. Symptomatic radiation pneumonitis was also not observed in our group, probably due to judicious selection of electron energy, rescaling, and assigning a bolus when required. Postradiation chest wall fibrosis also was minimal, and radiation-induced skeletal complications were not documented in our group.


 > Conclusion Top


Hypofractionation is accepted as standard of care in adjuvant breast radiation and is cost-effective. Electrons can be considered as an alternative to photons in busy centers, as single en face electron field is well tolerated, and 3DCRT planning ensures homogeneous chest wall coverage, respecting dose constraints to organs at risk. Daily treatment being less time-consuming, en face electron field can be considered in centres with heavy patient loads. Our analysis would conclude that single en face electron in postmastectomy chest wall is equivalent and noninferior to tangential photon pair.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK standardisation of breast radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 2013;14:1086-94.  Back to cited text no. 1
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2.
Paterson R, Russel M. Breast cancer; evaluation of postoperative radiotherapy. J Fac Radiol 1959;10:174-80.  Back to cited text no. 2
    
3.
Douglas BG. Superfractionation: Its rationale and anticipated benefits. Int J Radiat Oncol Biol Phys 1982;8:1143-53.  Back to cited text no. 3
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4.
Yarnold J, Ashton A, Bliss J, Homewood J, Harper C, Hanson J, et al. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: Long-term results of a randomised trial. Radiother Oncol 2005;75:9-17.  Back to cited text no. 4
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5.
Kirova YM, Campana F, Fournier-Bidoz N, Stilhart A, Dendale R, Bollet MA, et al. Postmastectomy electron beam chest wall irradiation in women with breast cancer: A clinical step toward conformal electron therapy. Int J Radiat Oncol Biol Phys 2007;69:1139-44.  Back to cited text no. 5
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Obedian E, Haffty BG. Internal mammary nodal irradiation in conservatively-managed breast cancer patients: Is there a benefit? Int J Radiat Oncol Biol Phys 1999;44:997-1003.  Back to cited text no. 6
    
7.
Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 2002;94:1143-50.  Back to cited text no. 7
    
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Pierce LJ. The use of radiotherapy after mastectomy: A review of the literature. J Clin Oncol 2005;23:1706-17.  Back to cited text no. 8
    
9.
Donker M, Rutgers E, Velde CV, Mansel R, Westenberg A, Orzalesi L, et al. Axillary lymph node dissection vs axillary radiotherapy: A detailed analysis of morbidity. Ann Surg Oncol 2014;21:2-3.  Back to cited text no. 9
    
10.
Norman SA, Localio AR, Kallan MJ, Weber AL, Torpey HA, Potashnik SL, et al. Risk factors for lymphedema after breast cancer treatment. Cancer Epidemiol Biomarkers Prev 2010;19:2734-46.  Back to cited text no. 10
    
11.
Jagsi R. Progress and controversies: Radiation therapy for invasive breast cancer. CA Cancer J Clin 2014;64:135-52.  Back to cited text no. 11
    
12.
Appelt AL, Vogelius IR, Bentzen SM. Modern hypofractionation schedules for tangential whole breast irradiation decrease the fraction size-corrected dose to the heart. Clin Oncol (R Coll Radiol) 2013;25:147-52.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]


This article has been cited by
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