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      Adapting Radiation Therapy Treatments for Patients with Breast Cancer During the COVID-19 Pandemic: Hypo-Fractionation and Accelerated Partial Breast Irradiation to Address World Health Organization Recommendations

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          Abstract

          To the Editor: On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a global pandemic. Public health officials have urged communities to minimize transmission by changing their habits, including posttravel self-isolation, increased hygiene vigilance, remote working, and social distancing. 1 To accommodate these measures, radiation therapy departments are adapting by limiting on-site staff, patient visits, and patient-to-staff interactions, reconciling the goals of minimizing exposure for both patients and health care providers while maintaining quality cancer care. During this pandemic, opportunities exist to reduce patient visits and thus potential exposure to COVID-19 and to judiciously allocate radiation therapy operation resources by implementing alternative hypofractionated regimens for select, safe treatment sites. Radiation therapy for patients with breast cancer represents a significant proportion of treatment delivery workload in any radiation therapy department. Some centers may consider omission or deferral of radiation therapy in those patients perceived to have a lower risk of adverse outcomes, such as patients with ductal carcinoma in situ or early stage disease with low-risk features. However, with an unknown and potentially lengthy timeline for the pandemic, many patients and clinicians are not comfortable with these options. Modeling studies predict that this pandemic may take months to peak, and these heightened public health measures may remain in place for many months. 1 Therefore, strategies to adapt to this “new normal” are crucial to maintaining access to radiation therapy for patients with cancer. Our strategy is based on the appropriate use of hypofractionation and accelerated partial breast irradiation (APBI). The focus on breast radiation therapy is crucial because of its significant impact on radiation therapy resources. The adoption of hypofractionation for patients, including those requiring locoregional irradiation, and the option of APBI for suitable patients based on international consensus guidelines can serve to significantly reduce the number of radiation therapy fractions and, as a result, minimize patient exposure during treatment and counteract increased pressure on the health care system. Hypofractionation regimens, such as 42.5 Gy in 16 fractions or 40 Gy in 15 fractions, have demonstrated equivalent local control and cosmetic outcomes in most patients after breast conserving therapy. 2 Although less commonly used in postmastectomy with regional nodal irradiation, hypofractionation is comparable to standard fractionation with favorable long-term efficacy results and low overall toxicity. 3 More recently, 1-week 5-fraction regimens have been compared with the 40 Gy in 15 fractions whole breast radiation in the UK FAST FORWARD trial for treatment of early stage disease, with favorable acute toxicity. 4 We are now awaiting the local control and survival data outcomes from this trial. Compared with the conventional 5-week fractionation of 50 Gy in 25 fractions, these shortened courses save patients between 9 and 20 visits to the cancer center. The evidence supporting APBI for early stage breast cancer is also maturing. In 2019, 2 separate phase 3 randomized control trials—RAPID and NSABP B39/Radiation Therapy Oncology Group (RTOG) 0413—reported on the efficacy of APBI fractionation regimens compared with whole breast irradiation. 5 , 6 The results are favorable, showing no statistical difference in overall survival and comparable local control for patients treated in the APBI arm. The evidence supporting APBI agrees with the American Society of Radiation Oncology 7 patient selection guidelines. Many centers have adopted the use of APBI in a limited capacity, primarily for patients on clinical trials. Publications describing APBI techniques that meet major trial constraints with simple 3-dimensional conformal techniques, and more recently advanced techniques for improved dosimetry, are available to support radiation planning. 8 Implementing an APBI fractionation of 27 Gy in 5 fractions can save a further 10, 11, or 20 treatment visits for select patients. In our tertiary care facility, the majority of patients with breast cancer (all stages; intact breast and postmastectomy locoregional) receive the standard 3-week regimen of 42.5 Gy in 16 fractions. In consideration of COVID-19 and after a multidisciplinary review, our center is now offering a 5-fraction APBI option for eligible patients. 9 A review of the last 3 months of patient treatment data was performed at our institution to determine the impact of this change on radiation therapy resources. Across all tumor sites, 770 total patients were treated; of these, patients with breast cancer represented 30% of all delivered fractions. For our patient population, approximately 40% of patients with breast cancer are suitable candidates for APBI. Over a 3-month span, a 5-fraction regimen of APBI for these eligible patients with breast cancer could reduce the number of daily treatment visits by approximately 500 and 900 for 16- and 25-fraction regimens, respectively. Across all radiation therapy resources, this overall reduction is approximately 5% to 10% of total daily fractions. Flattening the COVID-19 curve may necessitate careful adoption of measures that decrease interaction within radiation therapy departments and minimize treatment interruptions, without compromising cancer outcomes. At a time when health care systems aim to minimize stress on the system’s resources, radiation therapy can do its part to adapt. As noted by Achard et al, 10 the use of practical measures to ensure the treatment of patients undergoing radiation therapy must balance pragmatism and safety. The use of hypofractionated regimens and APBI may be the treatment option that best fits the balance of patient and staff safety while maintaining access to quality cancer care during the pandemic.

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          Most cited references 5

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          Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial

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            External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial

            Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation.
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              Five-field IMRT class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation.

              A comprehensive set of planning guidelines was developed to aid in achieving reproducible dosimetric results for external beam accelerated partial breast irradiation (APBI). The methodology for the development of class solutions for dosimetric planning of the APBI technique, including dose constraint recommendations, is presented for target coverage and conformity as well as normal tissues.
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                Author and article information

                Contributors
                Journal
                Adv Radiat Oncol
                Adv Radiat Oncol
                Advances in Radiation Oncology
                The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.
                2452-1094
                2 April 2020
                2 April 2020
                Affiliations
                [a ]Department of Oncology, University of Calgary, Calgary, Alberta, Canada
                [b ]Tom Baker Cancer Centre, Calgary, Alberta, Canada
                [c ]Department of Physics and Astronomy, University of Calgary, Calgary, Alberta, Canada
                [d ]Grand Prairie Cancer Centre, Grand Prairie, Alberta, Canada
                Author notes
                []Corresponding author: Lisa Barbera, MD, MPA Lisa.barbera@ 123456albertahealthservices.ca
                Article
                S2452-1094(20)30062-2
                10.1016/j.adro.2020.03.011
                7194663
                © 2020 The Author(s)

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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