|Year : 2021 | Volume
| Issue : 1 | Page : 16-20
Postmastectomy chest wall irradiation with electron beam technique – 10-year single-center retrospective analysis
Beena Kunheri1, JS Lakshmi2, KU Pushpaja3, Nisha Annie George4, Keechilat Pavithran5
1 NCCCR - National Centre for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar; Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita Viswavidyapeetham, Kochi, Kerala, India
2 Department of Radiation Oncology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India
3 Department of Radiation Oncology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Viswavidyapeetham, Kochi, Kerala, India
4 University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, Leicestershire, LE1 5WW, UK
5 Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
|Date of Submission||24-Mar-2021|
|Date of Decision||25-Mar-2021|
|Date of Acceptance||25-Mar-2021|
|Date of Web Publication||23-Jul-2021|
Dr. Beena Kunheri
Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita Viswavidyapeetham, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
BACKGROUND: Postmastectomy radiation therapy (PMRT) is delivered routinely with photon techniques, chest wall radiation with electron techniques have the advantage of reduced deeper tissue doses and can be tried in suitably selected cases. This study is to retrospectively evaluate the locoregional control, toxicity, disease-free survival (DFS), and overall survival of patients treated with postmastectomy chest wall electron radiation at a single center.
MATERIALS AND METHODS: The data of 450 patients who received PMRT with electron therapy from 2004 to 2014 were analyzed. Patients were treated with three-dimensional (3D) conformal radiation therapy with 6–8 MeV electrons to chest wall and 6 MV photons to supraclavicular fossa and medial axilla. Data collection was done from hospital medical records and analyzed with IBM SPSS 20.0. The results are given in mean ± standard deviation for continuous variables or as percentage for categorical variables. Kaplan–Meier survival analysis and log-rank tests were used. P < 0.05 was considered as statistically significant.
RESULTS: Patients' median age was 64 years (range: 24–74 years). Early stage accounted for 108 (24%) patients, 306 (68%) were advanced stage, and for 36 (8%) patients, stage was unknown. Of these, 174 (38.7%) patients were offered hypofractionated schedule and 276 (61.3%) with conventional fractionation. No Grade 3–4 skin reactions were reported over the irradiated area on treatment completion. Twenty-three (5.1%) patients had chest wall recurrence and 33 (7.3%) patients developed locoregional recurrence. Overall recurrence including systemic metastasis was 127 (28.2%). Long-term data did not show any cardiac or pulmonary mortality documented as radiation related. The median follow-up of our group was 67 months (6–173 months). DFS at 5 and 10 years was 81.4% and 79.5%, respectively. OS at 5 and 10 years was 85.2% and 79.7%, respectively.
CONCLUSION: PMRT with chest wall enface electron is feasible, and the advantage of electron field is better sparing of deeper structures, especially cardia in left-sided postmastectomy irradiation, thus more complex techniques such as Intensity Modulated Radiation Treatment (IMRT) and respiratory gating can be reserved for patients with more complicated anatomy where routine 3DCRT technique is unacceptable in terms target coverage and critical normal tissue sparing.
Keywords: Chest wall, electron technique, postmastectomy radiation therapy
|How to cite this article:|
Kunheri B, Lakshmi J S, Pushpaja K U, George NA, Pavithran K. Postmastectomy chest wall irradiation with electron beam technique – 10-year single-center retrospective analysis. Ann Oncol Res Ther 2021;1:16-20
|How to cite this URL:|
Kunheri B, Lakshmi J S, Pushpaja K U, George NA, Pavithran K. Postmastectomy chest wall irradiation with electron beam technique – 10-year single-center retrospective analysis. Ann Oncol Res Ther [serial online] 2021 [cited 2021 Oct 16];1:16-20. Available from: http://www.aort.com/text.asp?2021/1/1/16/322149
| Introduction|| |
Breast cancer is the most common malignancy in females across the world, with an annual incidence of 2,088,849 (11.6%) and with a mortality of 626,679 (6.6%). Multidisciplinary management with surgery, chemotherapy, radiation, hormonal therapy, and anti-Her treatment depending on various risk factors plays a major role in local control and survival of these patients. Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) as evidenced from various randomized and retrospective series., The recent Early Breast Cancer Trialists' Collaborative Group meta-analysis had proven the local control and survival benefit with PMRT. Historically even though PMRT was associated with locoregional control (LRC), overall survival (OS) was compromised because of late RT-induced morbidity. Now with modern techniques, morbidities with PMRT have significantly reduced. Post Mastectomy chest wall irradiation using electron beam has been criticized for increased pulmonary and cardiac toxicity. Pulmonary toxicity was encountered mainly because of higher electron energy >8 Mev used in earlier studies causing more penetration into the underlying pulmonary tissue. With appropriate use of electron energy, preferably ≤8 Mev can achieve adequate coverage in carefully selected cases. Planning computed tomography (CT) scan allows the evaluation of electron distribution slice by slice and would be preferable for selecting optimum electron energy and beam angle. Because of the rapid dose fall-off, deeper doses are much less and would be ideal in case of left-sided postmastectomy RT with thin, more, or less uniform chest wall thickness.
In our center, postmastectomy chest wall is treated with enface electron in suitable cases, and the goal is to treat dermal lymphatics and subcutaneous tissue using 6–8 Mev electrons with reduction in pulmonary and cardiac doses. This is a retrospective review of outcome of our patients treated with postmastectomy chest wall RT.
This is a retrospective study conducted in a tertiary care hospital at the Department of Radiation Oncology. All patients who received postmastectomy chest wall irradiation using electrons were included in this analysis. Patients who underwent breast conservation surgery and patients who received postmastectomy chest wall irradiation using photons were excluded. Data were collected using predefined pro forma from our hospital medical records and radiation treatment plans. Clinical data of 450 patients treated between 2004 and 2014 were collected and analyzed.
The primary objective was to assess the LRC. The secondary objectives were to assess the toxicity, disease-free survival (DFS), and OS.
| Materials and Methods|| |
Data of breast cancer patients who received adjuvant postmastectomy chest wall irradiation using electron beams were collected. Four-fifty patients received PMRT with chest wall electron during the period 2004–2014.
Radiation dose was 5000 cGy/25 fractions initially, and after the publication of long-term results of START B trial, department protocol changed to hypofractionated schedule of 4000 cGy/15 fractions. All the patients underwent radiation treatment planning using planning CT scan. Thin uniform-shaped chest wall was treated using low-energy electron 6–8 MeV, and supraclavicular fossa (SCF)/medial axilla was treated using 6 MV photons. CT based planning was done to decide on optimum electron energy and field angle. Fields were drawn over the skin after the computerized planning, and electron field is matched with supraclavicular photon field. Patients' characteristics are shown in [Table 1]. [Figure 1] is a sample of a typical electron field plan used in our patients.
Posttreatment patients were reviewed weekly during treatment, and posttreatment patients were followed up every 3–4 months for the first 2 years and then 6 monthly for the next 3 years and thereafter annually. Toxicity, if present, was recorded using Radiation Therapy Oncology Group criteria for acute and late grading.
LRR refers to the recurrence of cancer cells (of the same histology) at the same side chest wall or the regional lymph nodes, i.e., axilla, SCF, and internal mammary nodes.
LRR-free survival refers to the duration of time from the date of diagnosis till first local or/and regional disease event.
DFS refers to the duration of time from the date of diagnosis till first disease event/death.
OS refers to the duration of time from the date of diagnosis till the date of death.
Patients were censored on the date of last follow-up. Data set was locked on March 15, 2020.
Data were analyzed with IBM SPSS 20.0 (SPSS Inc., Chicago, IL, USA). The results were given in mean ± standard deviation for continuous variables or as percentage for categorical variables. To obtain the association of categorical variables, Chi-square statistics with continuity correction test (wherever applicable) were used. To find the survival probability of breast cancer patients receiving postmastectomy chest wall irradiation with electron beam therapy, Kaplan–Meier analysis was used, and log-rank test was used for comparing the survival probability of different subgroups. P < 0.05 was considered as statistically significant.
| Results|| |
A total of 450 patients who received PMRT with electron beam therapy from 2004 to 2014 were analyzed. Patients' median age was 64 years (range: 24–74 years). The Karnofsky Performance Scale of all the patients was above 80. The stage of disease was categorized using the American Joint Committee on Cancer 7th edition TNM staging system. Regarding the molecular status, 257 (59.4%) patients were luminal type, 114 (26.3%) patients were triple negative, and 62 (14.3%) patients were human epidermal growth factor receptor 2 (Her2/neu) enriched. Stage distribution was Stage II -108 (24%), Stage III - 302 (67.1%) and Stage IV- 4 (0.9%). The stage was unknown for 36 (8%) patients. Of these, 174 (38.7%) patients were offered hypofractionated radiation schedule and 276 (61.3%) were treated with conventional fractionation. Three hundred and ninety-nine patients received chemotherapy, of which 280 (62.2%) were adjuvant chemotherapy, 32 (7.1%) received neoadjuvant, and 87 (19.3%) received 3–4 cycles as neoadjuvant and remaining cycles as adjuvant.
The median follow-up was 67 months (range: 6–173 months). Majority had Grade 1 acute skin toxicity and 5% had Grade 2 reactions. No Grade 3 or 4 acute toxicities were documented during treatment. We could not find any documented cardiac and pulmonary toxicities attributed to radiation in the patient records. We had retrieved 30 patients' dosimetric data to see the cardiac and lung doses. Since it is a retrospective review, retrieval of old plans was difficult. The mean cardiac dose was 180.2 cGy (range: 20–336 cGy) for left-sided breast cancer, whereas for right-sided breast cancer, the mean cardiac dose was 71.2 cGy (range: 14–103 cGy). The mean V20 of the ipsilateral lung was 19.85% (range: 4.19%–39.06%). The evaluation of recurrence pattern showed that 23 (5.1%) had local alone recurrence, 33 (7.3%) had loco regional recurrence and 107 (23.8%) had systemic recurrence. The pattern of recurrence is presented in [Table 2]. LRR-free survival in PMRT patients receiving electron therapy at 2, 5, and 10 years was 91.1%, 83.7%, and 79.5%, respectively. DFS in PMRT patients receiving electron therapy at 2, 5, and 10 years was 88.1%, 81.4%, and 79.5%, respectively. DFS is shown in [Figure 2]. On subgroup analysis it was found that LRR-free survival at 2 years, 5 years and 10 years for Stage II was 91.9%, 86.5% and 86.5% respectively; Stage III was 92.9%, 83.6% and 79.4% respectively and for Stage IV was 75% at 2 years. Similarly, the 2-, 5-, and 10-year DFS for Stage II was 89.2%, 86.6%, and 86.6% and Stage III was 88.8%, 80.2%, and 79.4%, respectively. For Stage IV, DFS was 33% at 15 months. OS in PMRT patients receiving electron therapy at 2, 5, and 10 years was 92.5%, 85.2%, and 79.7%, respectively.
|Figure 2: Disease free survival (DFS) in PMRT patients receiving electron therapy|
Click here to view
| Discussion|| |
Breast cancer is the second most common cause of cancer-related death in women all over the world. Postmastectomy radiation to chest wall, dermal lymphatics, and subcutaneous tissue improves local recurrence and OS by 8% to 10% when given along with systemic chemotherapy or hormonal therapy.,, In the literature, majority of the locally advanced breast cancers underwent mastectomy followed by chest wall irradiation.
The stage-wise distribution of the patients administered post mastectomy radiation included Stage II 108 patients (24%). 306 (68%), Stage III 302 patients (67.1%) and Stage IV 4patients (0.9%). In our center, oligometastatic patients were treated with radical intent and that may be the reason for inclusion of Stage IV for postmastectomy radiation. Stage II patients were given postmastectomy radiation if there are other risk factors such as high proliferation index, margin positivity, triple negative, Her2 positive, and young patients.
Postmastectomy chest wall electron therapy was not widely used because of cardiac and pulmonary toxicities that were reported in the past. However, all those reported studies have used >8 Mev electron energy causing more penetration into the underlying pulmonary tissues. In our center, chest wall is routinely treated with enface electron using 6–8 Mev and rescaled to 80%–85% isodose lines for improved chest wall coverage.
Wang et al., in 2017, evaluated the toxicity pattern of 200 patients receiving PMRT using intensity-modulated radiation therapy (IMRT) reported, ipsilateral lung V20 as 32.24% ± 2.95% and mean cardiac dose as 6.99 ± 3.01 Gy (left sided: 9.30 ± 1.21 Gy). In our study, the mean cardiac dose for left-sided breast cancer was 1.8 Gy (range: 0.2–3.36 Gy), whereas for right-sided breast cancer, it was 0.71 Gy (range: 0.14–1.03 Gy). The V20 of the ipsilateral lung was 19.85% (range: 4.19%–39.06%). In comparison with Wang's data, our data show that both cardiac and lung doses were lower. The lower electron energies between 6-8 MeV resulted in less deeper penetration and lesser cardiac and lung doses. This can translate into lower pulmonary and cardiac toxicities, especially in left-sided tumors. In our cohort, no cardiac or pulmonary toxicities were reported attributable to radiation.
A study from Manchester reported chest wall recurrence to be 17% in their patients treated with 8 Mev electron beam. Danish PMRT studies with electron beam therapy to the chestwall reported 9% LRR rate., Most recently, Amin-Zimmerman et al. reported 7.3% of LRR rate. On analyzing the local recurrence in our patients, 5.1% had local recurrence and 7.3% had LRRs, which is in par with other studies.
In our study population, DFS at 5 and 10 years was 81.4% and 79.5% and OS at 5 and 10 years was 85.2% and 79.7%, respectively. Few studies of postmastectomy chest wall irradiation using photons and few studies using electrons reported survival at 10 years between 65% and 75%.,,
Since this is a retrospective study design, this study is subject to the inherent flaws of that study design. A prospective evaluation of the dosimetric parameters with correlation of outcome and toxicity will throw more light on the use of electron beams for PMRT and its long-term outcome.
| Conclusion|| |
Postmastectomy radiation using enface chest wall electron field with three-dimensional conformal radiation therapy planning offers a suitable alternative for photon field in carefully selected cases. The advantage of electron field is the better sparing of deeper structures, especially cardia in left-sided postmastectomy irradiation with equivalent local control and survival. When compared to intensity-modulated radiation therapy (IMRT) and other respiratory gating techniques, it is simple and is less labor intensive to implement in an existing linear accelerator facility.
We would like to thank Ms. Greeshma, Department of Medical Statistics, Amrita Institute of Medical Sciences, Amrita School of Medicine.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
Borm KJ, Oechsner M, Combs SE, Duma MN. Deep-inspiration breath-hold radiation therapy in breast cancer: A word of caution on the dose to the axillary lymph node levels. Int J Radiat Oncol Biol Phys 2018;100:263-9.
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al.
Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233-41.
EBCTCG (Early Breast Cancer Trialists' Collaborative Group); McGale P, Taylor C, Correa C, Cutter D, Duane F, et al.
Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014;383:2127-35.
Hehr T, Budach W, Paulsen F, Gromoll C, Christ G, Bamberg M. Evaluation of predictive factors for local tumour control after electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer. Radiother Oncol 1999;50:283-9.
Kuhnt T, Richter C, Enke H, Dunst J. Acute radiation reaction and local control in breast cancer patients treated with postmastectomy radiotherapy. Strahlenther Onkol 1998;174:257-61.
START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, et al.
The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet 2008;371:1098-107.
Edge SB, Compton CC. The American Joint Committee on Cancer: The 7th
edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-4.
DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin 2017;67:439-48.
Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, et al.
Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997;337:949-55.
Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al.
Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353:1641-8.
Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, et al.
Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956-62.
Wang Q, Jie W, Liang Z, Wu H, Cheng J. Postmastectomy intensity modulation radiated therapy of chest wall and regional nodes: Retrospective analysis of the performance and complications up for 5 years. Medicine (Baltimore) 2017;96:e7956.
Magee B, Ribeiro GG, Williams P, Swindell R. Use of an electron beam for post-mastectomy radiotherapy: 5-year follow-up of 500 cases. Clin Oncol (R Coll Radiol) 1991;3:310-4.
Amin-Zimmerman F, Paris K, Minor GI, Spanos W. Postmastectomy chest wall radiation with electron-beam therapy: Outcomes and complications at the University of Louisville. Cancer J 2005;11:204-8.
Gaffney DK, Leavitt DD, Tsodikov A, Smith L, Watson G, Patton G, et al.
Electron arc irradiation of the postmastectomy chest wall with CT treatment planning: 20-year experience. Int J Radiat Oncol Biol Phys 2001;51:994-1001.
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.
[Figure 1], [Figure 2]
[Table 1], [Table 2]