|Year : 2022 | Volume
| Issue : 1 | Page : 8-12
FAST-Forward trial in breast cancer: A prospective pilot study addressing dosimetric and practice feasibility in Indian scenario
A Mohanapriya1, Kanhu Charan Patro1, Sanjukta Padhi2, Chittaranjan Kundu1, Partha Sarathi Bhattacharyya1, Venkata Krishna Reddy Pilaka1, M Mrityunjaya Rao1, AC Prabu3, Ayyalasomayajula Anil Kumar3, Srinu Aketi3, P Prasad3, Venkata Naga Priyasha Damodara1, V S Premchand Kumar Avidi1, K Keerthiga1, Arya Pradhan2, Ajitesh Avinash2
1 Department of Radiation Oncology, Mahatma Gandhi Cancer Hospital and Research Institute, Visakhapatnam, Andhra Pradesh, India
2 Department of Radiation Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, Odisha, India
3 Department of Medical Physics, Mahatma Gandhi Cancer Hospital and Research Institute, Visakhapatnam, Andhra Pradesh, India
|Date of Submission||11-Nov-2021|
|Date of Decision||01-Dec-2021|
|Date of Acceptance||14-Jan-2022|
|Date of Web Publication||02-Sep-2022|
Dr. Kanhu Charan Patro
Department of Radiation Oncology, Mahatma Gandhi Cancer Hospital and Research Institute, Visakhapatnam, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Aims: To evaluate the dosimetry and practice feasibility in patients of breast carcinoma undergoing postoperative radiotherapy (RT) to the whole breast (WB) as per the FAST-Forward trial protocol. Materials and Methods: A total of 10 patients aged more than 18 years with histopathology proved early stage invasive carcinoma of breast after breast conservation surgery (BCS) were considered for receiving adjuvant RT to the WB with a total dose of 26 Gy in five fractions at a rate of 5.2 Gy per fraction delivered over 5 days. Boost to the tumor bed with a dose of 10 Gy in four fractions was delivered to the BCS cavity with adequate margin as per protocol. Targets were contoured according to the ESTRO guidelines. Heart and ipsilateral lung were considered as organs at risk. Target coverage and dose to the heart and ipsilateral lung were evaluated by dose–volume histograms. All patients were evaluated clinically for acute toxicity such as skin reaction and breast pain weekly once during RT, at the completion of RT, and at 3 months of follow-up. Results: Out of 10 patients, eight patients had right-sided breast carcinoma. As per protocol, we were able to achieve a dose constraint to ipsilateral lung in only three patients (V30%(7.8Gy) ≤ 17%). The range of excess dose variations in remaining seven patients was between 0.4% and 4.5%. Dose constraint to the heart has been achieved in all right-sided breast cancer patients (V25%(6.5Gy) ≤ 5). In left-sided breast cancer patients, an excess range of dose variation was between 0.8% and 2%. Only one patient developed grade III skin reaction at the end of RT (Common Toxicology Criteria for Acute Effects Grade 1). Conclusion: The FAST-Forward trial protocol (26 Gy in five fractions) can be effectively delivered in patients with postoperative invasive early stage breast cancer. The hurdle we faced was lung dose constraint, which was difficult to achieve in certain patients.
Keywords: Breast cancer, dosimetric evaluation, FAST-Forward, India
|How to cite this article:|
Mohanapriya A, Patro KC, Padhi S, Kundu C, Bhattacharyya PS, Pilaka VK, Rao M M, Prabu A C, Kumar AA, Aketi S, Prasad P, Damodara VN, Kumar Avidi VP, Keerthiga K, Pradhan A, Avinash A. FAST-Forward trial in breast cancer: A prospective pilot study addressing dosimetric and practice feasibility in Indian scenario. J Curr Oncol 2022;5:8-12
|How to cite this URL:|
Mohanapriya A, Patro KC, Padhi S, Kundu C, Bhattacharyya PS, Pilaka VK, Rao M M, Prabu A C, Kumar AA, Aketi S, Prasad P, Damodara VN, Kumar Avidi VP, Keerthiga K, Pradhan A, Avinash A. FAST-Forward trial in breast cancer: A prospective pilot study addressing dosimetric and practice feasibility in Indian scenario. J Curr Oncol [serial online] 2022 [cited 2023 May 27];5:8-12. Available from: http://www.https://journalofcurrentoncology.org//text.asp?2022/5/1/8/355586
| Introduction|| |
Breast carcinoma is the most common cancer in Indian women with an annual incidence of 2,261,419 in 2020. The management for breast cancer requires multimodality therapy, i.e., surgery followed by adjuvant chemotherapy and/or radiotherapy (RT). All women with early stage breast cancer who undergo breast conservation surgery (BCS) should receive adjuvant RT. Earlier, adjuvant RT after BCS was delivered with a total dose of 50 Gy in 25 fractions over 5 weeks., The current radiation schedule is 40 Gy in 15 fractions over 3 weeks, which is based on START A and START B trials (UK)., This schedule showed similar outcome as conventional regimen in terms of locoregional relapse rate and late adverse effects. The current study was based on recent hypofractionation trial called as FAST-Forward trial. As per this schedule, radiation was delivered with a total dose of 26 Gy in five fractions at a rate of 5.2 Gy per fraction over 5 days followed by a boost of 10 Gy in four fractions to the BCS patients., This study was conducted to evaluate the clinical and dosimetric feasibility of the FAST-Forward trial in early stage breast cancer patients post BCS.
| Materials and Methods|| |
A total of 10 patients of histopathology-proved invasive breast cancer were included for the study with age ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, post BCS, and pT1-3pN0-1M0.
Patients with age ≥ 65 years, ECOG ≥ 3, and contralateral/previous breast cancer and those requiring regional lymph nodal region radiation were excluded from the study.
All the eligible patients received adjuvant radiation to the whole breast (WB) and boost to the tumor bed. The total radiation dose was 26 Gy, which was delivered at 5.2 Gy per fraction in 1 week, followed by boost of 10 Gy at 2.5 Gy per fraction to the tumor bed delivered over 4 days.
Computed tomography simulation and immobilization
After informed consent, all eligible patients underwent computed tomography (CT) simulation in the supine position using a breast board angled 7.5° with arms abducted above the head and the head turned to the contralateral side. Immobilization was done using a customized thermoplastic breast mask.
The position of the patient was assessed by the CT laser alignment. Three fiducials were placed on the body surface of the patient or the customized thermoplastic breast mask for reference. BCS scar was marked with copper wire. Clinical assessment was done at the time of simulation to delineate the clinical border of breast (the superior, inferior, medial, and lateral borders were marked with fiducials). The patient was given intravenous non-iodinated contrast at a dose of 1–1.5 mg/kg body weight with an injecter (MEDRAD®Salient, Rege Imaging & Cine Films Private Limited, New Delhi, India) and simulation scan was taken with 5 mm slice thickness from the neck to the mid abdomen.
Delineation of target volume and organ at risk
On the planning CT, the target volumes were contoured as per ESTRO breast contouring guidelines and as per the FAST-Forward planning pack whereas the organs at risk (OARs) were contoured as per Radiation Therapy Oncology Group guidelines.
Clinical target volume (CTV) of the WB included WB from 5 mm below the skin surface down to the deep fascia excluding the muscle and underlying ribs cage or 5 mm anterior to the lung/ chest wall interface. The contouring was done cranially from the inferior edge of the sternoclavicular joint. The caudal border was the most caudal slice of the visible breast. The medial border was lateral to medial perforating vessels, maximally to the edge of the sternum, whereas the lateral border was anterior to the lateral thoracic artery. The CTV of the WB should not extend beyond the edges of the palpable or visible breast in medial and lateral directions.
Planning target volume (PTV) of the WB was obtained by adding 10 mm margin to the CTV of the WB.
Dose–volume histogram (DVH) for the PTV was obtained by limiting 5 mm from the skin surface and 5 mm from the lung/chest wall interface that was used for dosimetric evaluation.
CTV of the tumor bed was obtained by contouring the surgical clips and adding a 10 mm margin. In the absence of clips, CTV of the tumor bed was outlined by including seroma cavity or any changes in the surrounding tissue architecture.
PTV of the tumor bed was obtained by adding 10 mm margin to the CTV of the tumor bed.
Ipsilateral lung was auto-contoured excluding the airways and vessels.
Heart was contoured from the slice where the pulmonary trunk and the pulmonary artery were seen as separate structures till its inferior extent as it appeared well defined compared to the surrounding tissues in the abdomen. Heart was outlined to the extent of the pericardial sac excluding the pericardial fat.
Skin was not contoured as an OAR and not given a constraint. The dose to the skin was not evaluated as FAST-Forward planning protocol was not mentioned about the same.
The RT planning was done using the Monaco Treatment Planning System version 5.5 with collapsed cone algorithm. All patients were planned with 3-dimensional conformal technique (and included field-in-field technique) with daily cone beam CT (CBCT). The plan consisted of two standard tangential fields (i.e., medial and lateral tangential fields) with non-divergent posterior field edges. The isocenter was placed at the center of PTV of the WB. The field sizes were selected in order to cover the PTV of the WB with about 1.5 cm anterior flash. Ipsilateral lung and heart were shielded by multileaf collimator wherever possible without compromising PTV coverage. A 6 MV beam energy was used for treatment. The boost phase was planned by photon beam. Electron beam had been used for certain patients in whom dose constraints to OAR exceeded with photon beam.
Radiotherapy plan analysis
RT treatment plans were analyzed using DVH for PTV coverage and doses to ipsilateral lung and heart. An optimal PTV coverage should be between 95% and 107% of the prescribed dose. PTV coverage of the tumor bed was evaluated simultaneously while evaluating PTV of the WB. An optimal coverage of PTV of the tumor bed should be 95% of the prescribed dose. Dose constraints for ipsilateral lung i.e., V30%(7.8Gy) ≤ 17% was considered mandatory but V30%(7.8Gy) ≤ 15% was considered optimal and those for heart was V25%(6.8Gy) ≤ 5% and V5%(1.3Gy) ≤ 25%, respectively. Volume of lung receiving 30% of the prescribed dose and volume of heart receiving 25% of the prescribed dose were analyzed.
| Results|| |
Out of 10 BCS patients taken up in this study, eight patients had right-sided breast cancer as shown in [Table 1]. PTV dose coverage of V95%(24.70Gy) ≥ 90% (i.e., volume receiving 95% of dose [24.70 Gy] more than 90%) was achieved in eight patients with minimal variation around 0.3%–0.8% in two patients. Volume of ipsilateral lung receiving 30% of dose (7.8 Gy) should receive less than or equal to 17%. Mandatory lung dose could be achieved in three patients with minimal variation ranging from 0.4% to 4.5% in rest of the patients. Mandatory heart dose were within normal limit in right-sided breast patients. For the left-sided breast cancer, volume receiving 25% of the dose (6.8 Gy) ranged from 0.8% to 2% from the mandatory dose. All patients tolerated well and completed the treatment without interruption.
|Table 1: Showing PTV coverage and the OARs dose constraints of 10 patients|
Click here to view
All patients were evaluated for skin reaction and other side effects such as breast pain and breast edema by photographs as a baseline before, during, at completion, and 3 months after completing radiation treatment [Table 2] and [Figure 1][Figure 2][Figure 3]. All patients had grade 1 dermatitis and mild-to-moderate breast pain at completion of radiation. No skin reaction and breast pain were noted at 3 months after treatment completion. PTV volume was not correlated with skin toxicity as the same was not evaluated by the FAST-Forward trial.
| Discussion|| |
Adjuvant RT is an indication for BCS patient. The target volume to be treated was the entire breast and boost to the tumor bed with total dose between 45 Gy and 50 Gy at a daily dose of 1.8–2 Gy as a standard fractionation. There are ample studies on hypofractionated regimen comparing the standard conventional fractionation. In the UK START A trial, the standard regimen of 50 Gy in 25 fractions over 5 weeks was compared with 41.6 Gy or 39 Gy in 13 fractions over 5 weeks, and in the UK START B trial, the standard regimen was compared with 40 Gy in 15 fractions over 3 weeks. After 10 years of follow-up, it has been confirmed that hypofractionated radiation is safe and effective as standard regimen for patients with early breast cancer. Subsequently, the FAST-Forward trial compared the UK trial 3-week regimen with 1-week regimen with a dose 26 Gy in five fractions, 5.2 Gy per fraction over 1 week, and 10 Gy in four fractions as a boost to the tumor bed.
In this study, adjuvant radiation was delivered in 10 post BCS patients as per the FAST-Forward planning protocol with an intention to identify the feasibility of FAST-Forward trial in India. WB was irradiated with 26 Gy in five fractions followed by boost 10 Gy in four fractions to the tumor bed. All patients were assessed for signs and symptoms of acute toxicities, mainly skin reaction, during radiation, at the end of radiation, and 3 months after treatment completion [Table 2]. Acute reaction of the skin was graded using Common Toxicology Criteria for Acute Effects (CTCAE) [Table 3]. Weekly assessments were continued until the reaction resolved to CTCAE grade 1 or less from higher reaction grades. None of the patients had Grade 2 or more toxicities such as skin reactions, breast pain, and edema during post RT.
Lung dose was difficult to achieve in most (seven patients) of the patients.
This could be achieved by deep Inspiration Breath Hold (DIBH) technique. Advantages and difficulties of FAST Forward trial are depicted in [Table 4].
This study was conducted with a few patients and late toxicity was not documented.
| Conclusion|| |
A total dose of 26 Gy in five fractions can be effectively delivered in patients with postoperative invasive early breast cancer. The lung dose constraint was the main hurdle to achieve. Further studies using more patients need to be conducted to validate this study in Indian scenario. As breast cancer is ranked first in India among females, hypofractionation would reduce the total treatment duration and be patient convenient and cost-effective.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Veronesi U, Luini A, Del Vecchio M, Greco M, Galimberti V, Merson M, et al
. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 1993;328:1587-91.
Fisher B, Costantino J, Redmond C, Fisher E, Margolese R, Dimitrov N, et al
. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993;328:1581-6.
Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, et al
; START Trialists’ Group. The UK standardisation of breast radiotherapy (START) trial A of radiotherapy hypofractionation for treatment of early breast cancer: A randomised trial. Lancet Oncol 2008;9:331-41.
Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, et al
; START Trialists’ Group. 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.
Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, et al
; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet 2020;395:1613-26.
Brunt AM, Wheatley D, Yarnold J, Somaiah N, Kelly S, Harnett A, et al
; FAST-Forward Trial Management Group. Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward trial. Radiother Oncol 2016;120:114-8.
Offersen BV, Boersma LJ, Kirkove C, Hol S, Aznar MC, Biete Sola A, et al
. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol 2015;114:3-10.
Planning Pack for the FAST-Forward Trial. Available at: https://d1ijoxngr27nfi.cloudfront.net/docs/default-source/default-document-library/fast-forward-planning-pack.pdf
. [Last accessed on May 2013].
Duane F, Aznar MC, Bartlett F, Cutter DJ, Darby SC, Jagsi R, et al
. A cardiac contouring atlas for radiotherapy. Radiother Oncol 2017;122:416-22.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]