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Moderately hypofractionated post-operative radiation therapy for breast cancer: Preferences amongst radiation oncologists from countries in Latin America and the Caribbean

Gustavo Nader Marta12, Fabio Y. Moraes3, Rejane Carolina de Oliveira Franco4, Heloisa A. Carvalho56, Andre Guimaraes Gouveia7, Gustavo Cartaxo de Lima Gössling2, Rafaela Gomes de Jesus2, Gustavo Ferraris8, Pablo Munoz Schuffenegger9, Gustavo Sarria10, Adela Poitevin Chacon11, Raúl Murillo12, Luis Ernesto Moreno Sánchez13, Elizabeth Gamarra-Cabezas14, Arthur Accioly Rosa152, Mauricio Silva162, Marcos Duarte de Mattos17, Diego Chaves Rezende Morais15, Douglas Guedes de Castro18, Alan Dal Pra19, Beatriz E Amendola20, José Máximo Barros21, Tomas Merino Lara22, Nicolas Isa23, Dolores de la Mata24, Iván Hidalgo12, Diego Giménez-Velilla25, Lijia Aviles26, Francisco Gomez Montenegro27, Nestor O. Sanchez Chacin28, Gustavo Werutsky2, Gustavo Viani29
Rep Pract Oncol Radiother 2023;28(3):340-351.

Abstract

Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer.

Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions.

Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules.

Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.

research paper

Reports of Practical Oncology and Radiotherapy

2023, Volume 28, Number 3, pages: 340–351

DOI: 10.5603/RPOR.a2023.0046

Submitted: 20.03.2023

Accepted: 27.06.2023

© 2023 Greater Poland Cancer Centre.

Published by Via Medica.

All rights reserved.

e-ISSN 2083–4640

ISSN 1507–1367

Moderately hypofractionated post-operative radiation therapy for breast cancer: preferences amongst radiation oncologists from countries in Latin America and the Caribbean

Gustavo Nader Marta12Fabio Y. Moraes23Rejane Carolina de Oliveira Franco4Heloísa de Andrade Carvalho25André Guimaraes Gouveia26Gustavo Cartaxo de Lima Gössling2Rafaela Gomes de Jesus2Gustavo Ferraris7Pablo Munoz Schuffenegger28Gustavo Sarria Bardales9María Adela Poitevin Chacón10Raúl Murillo1112Luis Ernesto Moreno Sánchez13Elizabeth Gamarra-Cabezas1415Arthur Accioly Rosa216Maurício Fraga da Silva21718Marcos Duarte de Mattos19Diego Chaves Rezende Morais220Douglas Guedes de Castro221Alan Dal Pra222Beatriz E. Amêndola23José Máximo Barros21425Tomas Merino Lara26Nicolás Isa27Dolores de la Mata Moya228Iván Hidalgo29Diego Gimenez Velilla3031Lijia Elizabeth Avilés Loayza3233Francisco Gomez Montenegro34Nestor O. Sanchez Chacin35Gustavo Werutsky2Gustavo Arruda Viani236
1Department of Radiation Oncology, Hospital Sírio-Libanês, Sao Paulo, Brazil
2Latin American Cooperative Oncology Group (LACOG), Brazil
3Department of Oncology, Division of Radiation Oncology, Queen’s University — Kingston Health Science Centre, Kingston, ON, Canada
4Gerald Bronfman Department of Oncology — Radiation Oncology Department — McGill University, Canada
5Department of Radiology and Oncology — Radiotherapy Division — Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
6Juravinski Cancer Centre, Department of Oncology, Division of Radiation Oncology, Hamilton, ON, Canada
7Centro Radioterapia Dean Funes, Córodoba, Argentina
8Radiation Oncology Unit, Department of Hematology — Oncology, Pontificia Universidad Catolica de Chile, Chile
9Instituto Nacional Enfermedades Neoplásicas, Peru
10Medica Sur, Radiation Oncology Department, Mexico
11Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogota, Colombia
12Facultad de Medicina, Pontificia Universidad Javeriana, Bogota, Colombia
13Instituto Nacional del Cáncer Rosa De Tavares (INCART), Savia Care Centro Avanzado de Radioterapia, Centro Gamma Knife Dominicano, Dominican Republic
14Departamento de Radio-Oncología, Instituto Oncológico Nacional “Dr. Juan Tanca Marengo”
15Sociedad de Lucha Contra el Cáncer (SOLCA), Guayaquil, Ecuador
16Oncoclinicas Salvador — Hospital Santa Izabel
17Santa Maria Federal University, Santa Maria, RS, Brazil
18Clínica de Radioterapia de Santa Maria, RS, Brazil
19Barretos Cancer Hospital
20Oncoclinicas Recife and Hospital Santa Águeda, Brazil
21Department of Radiation Oncology, A.C. Camargo Cancer Center, Brazil
22Department of Radiation Oncology, University of Miami Miller School of Medicine, United States
23Innovative Cancer Institute, South Miami, United States
24VIDT Oncologia Radiante, Argentina
25Centro de Radioterapia del Hospital Universitario Austral, Argentina
26Department of Hematology Oncology, school of Medicine, Pontificia Universidad Catolica de Chile, Chile
27Clinica IRAM, Santiago de Chile, Chile
28Cancer Center — ABC Medical Center, Mexico.
29Centro Javeriano de Oncología — Hospital Universitario San Ignacio, Colombia
30Instituto Nacional del Cáncer INCAN Paraguay
31Centro Oncológico Revita
32Oncoservice, Bolivia
33Sociedad Boliviana de Cancerologia Filial La Paz, Bolivia
34Radiation Oncology Department- Instituto Oncológico Nacional de Panamá, Panama
35Radiation therapy Service, Instituto Medico San Nicolas, Aruba
36Ribeirão Preto Medical School, Department of Medical Imagings, Hematology and Oncology of University of São Paulo (FMRP-USP), Brazil

Address for correspondence: Gustavo Nader Marta, Department of Radiation Oncology, Hospital Sírio-Libanês, Sao Paulo, Brazil, Rua Dona Adma Jafet 91, Bela Vista – Sao Paulo, Brazil, tel: 01308050; e-mail: gustavonmarta@gmail.com

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially

Abstract
Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer.
Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions.
Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules.
Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.
Key words: breast cancer; radiation therapy; moderately hypofractionated
Rep Pract Oncol Radiother 2023;28(3):340–351

Introduction

Breast cancer is the most common malignant tumour in women in Latin America and the Caribbean (LAC) with an estimated 210,100 new cases in 2020 [1]. In general, a multidisciplinary therapeutic approach, which has been correlated to improvement of overall survival rates, comprising surgical oncology, medical oncology and radiation oncology is needed for the optimal management of breast cancer patients [2].

Post-operative radiation therapy (RT) reduces the risk of cancer mortality and loco-regional recurrence rates in most patients who received breast-conserving surgery and mastectomy [3, 4]. Historically, conventional radiation doses with 50 Gy to 50.4 Gy in 25–28 fractions over the course of 5 to 6 weeks were used as a standard scheme. This originates from the traditional radiobiology concept about the doses needed to treat subclinical disease in combination with the historical assumption that breast cancer is less sensitive to changes in the dose per fraction than dose-limiting healthy tissues [5, 6].

The all-purpose engagement of hypofractionation is to decrease the treatment period by shrinking the total number of fractions and offering a therapeutic schedule that is more convenient and optimized for patients. Considering LAC geography and access to cancer care, the benefits of hypofractionation can also be related to increasing patients` access to medical care in case of insufficient capacity, reducing indirect costs related to interruption from work and travelling to the radiation oncology department, and reducing healthcare treatment costs [7–9].

The safety and efficacy of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by at least eight randomised controlled trials that mostly included early-stage patients [10–21]. Several guidelines recommended moderately hypofractionated post-operative whole breast irradiation as the new standard, and its recommendation has become increasingly broad, including not only selected patients with early disease. Currently, although some institutions still have concerns about its generalised application [22], moderately hypofractionated radiation therapy to the breast, chest wall (with/without breast reconstruction), and regional lymph nodes is considered as safe and effective as conventionally fractionated schedules and has been adopted as a treatment option for the vast majority of patients in many centers [8].

In view of the evidence on the benefits of moderately hypofractionated post-operative radiation therapy and presuming there may be differences concerning its application in clinical practice. It is known that many of the problems and difficulties found in LAC countries are common. Drawing a general picture of how moderately hypofractionated post-operative radiation therapy for breast cancer has been performed is important for a global understanding of the subject. Thus, we developed a survey to evaluate the current patterns of practice and to assess possible aspects that affect the decision-making process regarding the use of fractionation in patients with breast cancer in LAC countries. We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer.

Materials and methods

Radiation oncologists who are members of local radiation therapy societies from Argentina, Aruba, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Mexico, Panama, Paraguay, Peru and Uruguay were invited to participate in this study. Between February and March 2022, an invitation email was sent to 1004 radiation oncologists.

We applied the same questionnaires containing 38 questions as used in the European survey study [23]. Questions were organised on a multi-choice setting, allowing multiple answers and also free-text responses. It was not necessary to translate and validate the questionnaire in Portuguese and Spanish as the instrument was applied in its original format in English.

We created an online survey (via REDCAP). The participation in the survey was voluntary and respondents did not receive any fee. In the current study, we presented the diverse features of fractionation use in post-operative radiation therapy for breast cancer.

The statistical analyses

The dichotomic and continuous variables were treated as proportions (percentage) and median with standard deviation, respectively. The influence of the following medical aspects in the radiation oncologists’ choices to recommend moderately hypofractionated post-operative radiation therapy schedules was investigated: number of breast cancer cases per month, age group, practice setting, years of practice, time dedicated to breast cancer, and academic institution. The treatment (dose to organs at risk, dose inhomogeneity, use of high tangents, regional nodal irradiation, internal mammary node irradiation, flap-based breast reconstruction, and implant-based breast reconstruction) and tumour aspects (breast cancer stage, breast size, tumour side, breast cancer molecular subtype, tumour grade, surgical margins) were tested for association with the decision or contraindication to recommend moderately hypofractionated post-operative. A chi-square test was used in all the analyses. For each subgroup analysis, the odds ratio and 95% confidence interval (CI) were calculated. Statistical significance was defined as a p-value of 0.05. The statistical analysis was performed with the software SPSS version 25.0 and SAS® version 9.4.

Results

A total of 173 radiation oncologists (17.2% of the total number of invitations) answered the questionnaire. Most respondents practiced in Brazil n = 90 (52.0%), Argentina n = 23 (13.2%) and Mexico n = 12 (6.9%) as described in Figure 1.

155227.png
Figure 1. Number of radiation oncologists and countries that were included

Only 25 of participants had an academic affiliation (14.4%), and 146 (84.4%) had practiced for at least 5 years since completing residency; 68.8% of the respondents affirmed that they dedicated at least 25% of their clinical time to breast cancer patients, with 54.3% treating 11 or more cases of breast cancer per month.

Discussing the decision to treat breast cancer patients with post-operative radiation therapy in a multidisciplinary tumour board is mostly done only for non-standard cases by 38.1% of the respondents (Supplementary File Tab. S1).

The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. For whole breast plus regional node irradiation, post-mastectomy (chest wall and regional node irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2%, 71.1% and 53.7% of respondents, respectively (Fig. 2). When boost dose to the primary tumour bed is indicated, majority of respondents would offer a hypofractionated schedule (i.e., 3–4 daily fractions of 2.5–3.0 Gy). Simultaneous integrated boost delivery with the photon beam technique was preferred by most radiation oncologists (Supplementary File Table S2).

155236.png
Figure 2. Radiation oncologists and their fractionation preference. WBI whole breast irradiation; RNI regional nodal irradiation
Table 1. Participants’ characteristics

Characteristics

N

%

Age group (years)

< 35

25

14.4

3545

84

48.5

4660

38

22

6170

22

12.7

> 70

4

2.3

Years in practice

< 5 years

27

15.6

510 years

36

20.8

1120 years

63

36.4

>20 years

46

26.6

Number of breast cancer patients treated per month

< 5

6

3.4

510

72

41.8

1120

55

31.9

> 20

39

22.6

Number of radiation oncologists treating breast cancer patients in participant’s place of work

1

13

7.5

2

29

16.7

3

43

24.8

4

21

12.1

> 5

66

38.1

Other

1

0.5

Percentage of clinical time dedicated to breast cancer patients

< 25%

54

31.2

2550%

85

49.1

5175%

25

14.5

> 75%

9

5.2

Table 2 demonstrates the medical aspects influencing radiation oncologists’ choices to recommend moderately hypofractionated post-operative radiation therapy schedules. The main factor influencing the moderate hypofractionated choice was < 50% of time dedicated to breast cancer, odds ratio (OR) 6.98 [95% confidence interval (CI), p = 0.031].

Table 2. Medical aspects influencing the decision of radiation oncologists to recommend moderately hypofractionated post-operative radiation therapy schedules

Characteristics

Hypofractionation (n = 146)

Other (n = 27)

OR (95% CI)

p-value

N

%

N

%

Patients number at clinic

≥ 10 patients

< 10 patients

81

65

44.5

55.5

12

13

52

48

1.35 (0.573.16)

0.488

% Time dedicated to breast cancer

≤ 50%

> 50%

114

32

78

22

25

1

96

4

6.98 (1.1053.70)

0.031

Age group

≤ 45 years

> 45 years

95

51

65

35

13

13

50

50

1.86 (0.814.32)

0.143

Setting practice

Public

Private

89

57

61

39

16

10

61.5

38.5

0.97 (0.412.30)

0.955

Academic hospital

No

Yes

123

23

84

16

24

2

92.3

7.7

0.44 (0.082.00)

0.283

Timing working as radiation oncologist

< 10years

≥ 10years

54

92

37

63

9

17

38.4

61.6

1.11 (0.462.66)

0.817

Number of radiation oncologists at the service

1

> 1

9

132

6.3

93.7

4

27

13

87

0.36 (0.101.20)

0.110

Academic institution

Yes

No

23

123

15.7

84.3

2

24

7.7

92.3

0.44 (0.092.90)

0.283

Clinical-pathological and financial aspects influencing the decision of radiation oncologists to recommend moderately hypofractionated post-operative radiation therapy schedules is presented in the Table 3. Of all evaluated features, patients age (p = 0.009), regional nodal irradiation (p = 0.002) and implant-based breast reconstruction (p = 0.031) were the characteristics that significantly impacted on the decision to adopt moderately hypofractionated post-operative radiation therapy.

Table 3. Clinical-pathological and financial aspects influencing the decision of radiation oncologists to recommend moderately hypofractionated post-operative radiation therapy schedules

Characteristics

Hypofractionation

Other

OR (95% CI)

p-value

N

%

N

%

Age

114

78.0

12

54

3.01 (1.27.2)

0.009

Breast cancer stage

111

76.0

19

73

1.10 (0.43.3)

0.747

Breast size

111

76.0

18

69

1.41 (0.563.21)

0.461

Tumour side (right or left)

135

92.5

23

88

1.60 (0.416.19)

0.491

Breast cancer molecular subtype

131

89.7

22

85

1.59 (0.415.23)

0.444

Tumor grade

126

86.3

22

84

1.15 (0.353.5)

0.819

Surgical margins

123

84.2

22

84

0.97 (0.313.01)

0.962

Dose to organs at risk

104

71.2

20

77

0.74 (0.271.98)

0.551

Dose inhomogeneity

115

78.8

19

73

1.37 (0.523.51)

0.519

Use of high tangents

140

95.9

25

96

0.93 (0.108.00)

0.950

Regional nodal irradiation

105

71.9

13

50

2.56 (1.16.00)

0.002

Internal mammary node irradiation

105

71.9

19

73

0.94 (0.362.40)

0.903

Flap-based breast reconstruction

126

86.3

23

88

0.82 (0.223.00)

0.766

Implant-based breast reconstruction

136

93.1

21

65

3.24 (1.110)

0.031

Financial issues/reimbursement

100

68.5

20

77

0.65 (0.241.73)

0.389

Table 4 shows the absolute contraindications for the use of moderately hypofractionated post-operative radiation therapy schedules as reported by radiation oncologists. The two most important factors for not indicating hypofractionation were breast cancer stage (p = 0.036), and flap-based breast reconstruction (p = 0.04).

Table 4. Absolute contraindications for the use of moderately hypofractionated post-operative radiation therapy schedules as reported by radiation oncologists

Characteristics

HYPO

Other

OR (95% CI)

p-value

N

%

N

%

Age

139

95.2

20

76.9

2.62 (0.6210.7)

0.176

Breast cancer stage

142

97.3

23

88.5

4.63 (1.0722)

0.036

Breast size

139

95.2

25

96.1

0.79 (0.086.74)

0.832

Breast side (right or left)

145

99.3

26

100

1.83 (0.0746)

0.672

Breast cancer molecular subtype

144

98.6

25

96.1

2.88 (0.2533)

0.374

Tumor grade

4

2.7

20

76.9

6.00 (0.9044.6)

0.05

Surgical margins

141

96.6

23

88.5

3.68 (0.8216.8)

0.07

Dose to organs at risk

117

80.1

19

73.1

1.49 (0.513.87)

0.415

Dose inhomogeneity

121

82.9

22

84.6

0.88(0.272.79)

0.827

Use of high tangents

144

98.6

26

100

1.09 (0.0523.4)

0.548

Regional nodal irradiation

136

93.1

22

84.6

2.47 (0.718.58)

0.143

Internal mammary node irradiation

124

84.9

22

84.6

1.02 (0.323.26)

0.967

Flap-based breast reconstruction

139

95.2

21

80.7

3.14 (1.0711.3)

0.04

Implant-based breast reconstruction

124

84.9

23

88

0.73 (0.202.66)

0.638

Financial issues/reimbursement

143

97.9

25

96.1

1.91 (0.1919)

0.577

Discussion

To the best of our knowledge, this is the first study to assess the LAC radiation oncologists’ preferences related to the use of moderately hypofractionated post-operative radiation therapy in breast cancer patients. A total of 173 radiation oncologists corresponding to 13 countries responded to the survey which made it possible to understand the treatment profile that has been carried out in these countries. The results of our study showed that moderately hypofractionated post-operative radiation therapy had been used not only for selected early-stage breast cancer patients, but also in cases after mastectomy and when regional nodal irradiation is needed. In other words, despite the greater tendency to use moderately hypofractionated post-operative radiation therapy for patients that do not need regional nodal irradiation, it is observed that the hypofractionation has been gaining ground in clinical practice, even when regional nodal irradiation is needed or after mastectomy with or without reconstruction.

In our study, the factors that most affected the decision to utilize moderately hypofractionated post-operative radiation therapy in clinical practice were percentage of time dedicated to breast cancer, regional nodal irradiation, implant-based breast reconstruction, and patient’s age. Moreover, breast cancer stage, and flap-based breast reconstruction were factors more commonly associated with absolute contraindications for the use of hypofractionated schedules. These findings are similar to the European study which, by evaluating the responses of 412 radiation oncologists from 44 countries, demonstrated that many factors can affect the decision to use hypofractionation in clinical practice [23]. It is important to recognise that the clinical application of the moderately hypofractionated post-operative radiation therapy differs across the globe, with rates ranging from 34.5% to 95% [24–29]. Previous authors reported breast laterality and volume, younger age, breast cancer stage, triple-negative tumour, and radiation plan inhomogeneity as factors related to lower hypofractionation utilization [26–28, 30].

Numerous prospective randomised trials have studied several features of hypofractionated irradiation in breast cancer patients. Primarily, these studies with almost 8000 patients have demonstrated that hypofractionation is as safe and effective as conventional fractionation. Nevertheless, most of these studies involved mostly patients with early-stage disease who received breast-conserving therapy. Most patients underwent whole breast radiation therapy without regional nodal irradiation [12, 15–18, 20]. Therefore, the utilization of moderately hypofractionated post-operative radiation therapy is not globally adopted in patients who received mastectomy or need regional nodal irradiation due to overconcern about toxicity related to the treatment [8].

Some experts advocate that the use of moderate hypofractionation for regional nodal irradiation must be evaluated with attention until outcomes of other clinical trials are available due to the long-term side effects of this treatment, especially regarding heart and lung functions [31]. Furthermore, there could be unease related to the fact that chemotherapy was used in 14%, 11%, 35%, 22% of patients in the OCOG trial [14, 15], START A [17, 18] and START B [16, 17], respectively, and most patients received a non-standard chemotherapy regimen. Nonetheless, standard chemotherapy (anthracycline and taxane-based) schedules were used in the Chinese trial [19] and the Shaitelman et al. [32] study with suitable side effects outcomes. Although these trials [19, 32] had a shorter follow-up, current evidence of using conventional dose radiation therapy after breast-conserving surgery and mastectomy (with or without regional nodal irradiation) comes from randomized trials that mostly used a non-standard chemotherapy regime as well [3, 4]. Moreover, the START trials’ data demonstrated that the rates of ischemic heart disease and lung fibrosis were remarkably low (less than 2%) [33]. Even though these values can be higher than those noticed by other authors using modern diagnostic instruments, patients rarely developed symptoms consistent with pulmonary and cardiac side effects that required medical intervention [34-37].

The treatment-related side effects are possibly more associated with the radiation therapy technique than the dose scheme used. The estimated absolute risks for second cancer or heart disease (with cardiac mortality) from modern radiation therapy were very low compared to older therapies [38]. Thus, the hypothesis of contemporary homogeneously delivered volume-based radiation therapy techniques can be applied to understanding that treatment effects should be undistinguishable regardless of the target volumes. Data from prospective and retrospective studies also showed that hypofractionated post-mastectomy radiation therapy with or without regional nodal irradiation is safe, with low rates of side effects and suitable local control results [22, 37, 39–48].

Many patients undergo implant and autologous breast reconstruction before and after RT [49]. Several studies demonstrated that radiation therapy might lead to post-operative increase of capsular contracture rates and infection. In some situations, this could result in the removal of the implant [50–53]. Interestingly, besides the fact that implant-based reconstruction significantly affected the decision for choosing the fractionation scheme, flap-based reconstruction was a categorical contraindication for the higher dose per fraction schedule in most responses. In our opinion, this finding reflects a higher fear of complications with irradiation of reconstructed breasts with higher doses per fraction, mainly with autologous tissue that, however, should be demystified. And, if there are any concerns, they should be mostly related to implant-based reconstruction. It is important to highlight that none of the published randomized phase III trials that formally compared the results of moderate hypofractionation to conventionally fractionated irradiation [13, 15–19] included patients with implant and autologous breast reconstruction. On the other hand, all of these trials showed that most breast side effects that could be strongly associated with radiation-related toxicities in implant and autologous breast reconstruction (skin retraction, fibrosis and breast shrinkage) were lower or, at least, equal in patients who underwent hypofractionation. A retrospective experience from a Korean group [2] demonstrated that there were no differences in late effects regarding the timing and type of breast reconstruction related to both radiation therapy fractionation schemes. Additionally, there is no randomized phase III trial that validated the use of a conventional radiation dose after breast reconstruction. Historically, the conventional dose has been empirically used when breast reconstruction techniques were described [54, 55]. Over the past decades, in clinical practice, once the treatment was performed with conventional doses, there was a simple incorporation of reconstructive surgeries in this scenario. Thus, the available medical evidence of using hypofractionation or conventional fractionated irradiation can be considered equivalent in patients with breast reconstruction.

Even though there is high level evidence to support the use of hypofractionation-based radiation therapy for breast cancer and its use may have significant financial benefits, it fails to be widely adopted in many countries [56]. This might be explained by the fact that the adoption of shorter treatment regimens may have significant implications on health economics, resulting in a financial loss depending on the reimbursement arrangement [57]. While in countries like the Netherlands and the United Kingdom (where reimbursement is independent from the number of fractions) hypofractionated breast irradiation is used by most centres for nearly all patients (except in the case of re-irradiation and concomitant chemoradiation); in more reimbursement-driven models with payment per fraction, including Germany, France, the United States, there is a lot of reluctance towards applying hypofractionation in daily practice [57]. Despite the reimbursement issue being an important factor for the adoption of hypofractionation in clinical practice in many countries, our study showed that this factor is considered in a limited number of respondents.

Our study has some limitations, most notably limited sampling and respondent availability. Even though the survey participants offer some perception about moderately hypofractionated post-operative radiation therapy clinical practice for breast cancer patients in LAC, the responders are self-selected. So, the results would not be robustly representative, illustrating a lack of radiation oncology community representation. However, most responders (54.5%) declared that they treated at least 11 breast cancer patients per month, and the great majority (96.6%), at least five patients per month (Tab. 1). So, the sample seems to represent a community with experience in breast cancer treatment. In addition, the ones that dedicate less time of their clinical practice to breast cancer are those that would choose other fractionation scheme rather than the hypofractionated one (Tab. 2). Therefore, our study can positively stimulate radiation oncologists in their reflections and decision-making on whether or not to accept hypofractionated breast radiation therapy in their daily clinical practice, in order to take the road towards higher convenience for the patients and less societal costs. The adoption of hypofractionation in emerging countries is not just a subject of cost-effectiveness but one of entrance to improved medical health assistance and patient survivorship [58, 59].

Conclusion

In conclusion, even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to many patients. Its unrestricted and wide application in clinical practice across LAC still faces some reluctance, especially when regional nodal irradiation is needed or after mastectomy with or without reconstruction.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by G.N.M., G.A.V. and R.G.deJ. The first draft of the manuscript was written by Gustavo Nader Marta and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Taiane Francieli Rebelatto and Álvaro Notejane for providing technical support.

Ethical approval

The study was approved by the Brazilian Ethical Review Authority (CAAE: 52076121.7.0000.5336; number: 5.081.397).

Conflict of interest

None declared.

Funding

None declared.

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