key: cord-0810508-5rxfgvec
authors: Chargari, Cyrus; Chopra, Supriya; Viswanathan, Akila N.; Deutsch, Eric
title: BRACHYTHERAPY ISSUES AND PRIORITIES IN THE CONTEXT OF COVID-19 OUTBREAK
date: 2020-06-02
journal: Adv Radiat Oncol
DOI: 10.1016/j.adro.2020.04.034
sha: f91e0b9ec08173217285226b4bcb54eb5eeaf065
doc_id: 810508
cord_uid: 5rxfgvec

Brachytherapy has a major role in patient’s cure and cannot be substituted or excessively delayed in rapidly growing tumors (e.g.; cervical cancer). However, COVID-19 pandemic infection requires workflow adaptation in order to ensure treatment continuity for patients while ensuring safety of health care professionals. Because of a drastic reduction of all operating room capacity with exception of critical emergencies, it is mandatory to have COVID-19 recommendations applicable to the field of brachytherapy, taking into account specific constraints. Strategies for infection prevention and rationalization of health care resources are discussed. Herein we place brachytherapy in the context of reduced access to radiotherapy facilities and underscore strategies to be implemented in order to protect patients and health workers while ensuring that patients will still receive the most appropriate curative treatment.

Brachytherapy has a major role in patient's cure and cannot be substituted or excessively delayed in rapidly growing tumors (e.g.; cervical cancer). However, COVID-19 pandemic infection requires workflow adaptation in order to ensure treatment continuity for patients while ensuring safety of health care professionals. Because of a drastic reduction of all operating room capacity with exception of critical emergencies, it is mandatory to have COVID-19 recommendations applicable to the field of brachytherapy, taking into account specific constraints. Strategies for infection prevention and rationalization of health care resources are discussed. Herein we place brachytherapy in the context of reduced access to radiotherapy facilities and underscore strategies to be implemented in order to protect patients and health workers while ensuring that patients will still receive the most appropriate curative treatment.

In the context of the international public health emergency related to the COVID-19 outbreak, radiotherapy facilities have to adapt in order to ensure safety of caregivers and ensure treatment continuity for patients. 1 As recently highlighted, radiotherapy departments have adapted their practice. 2;3;4 Staff reorganizations and reduction of patients' access to radiotherapy facilities have been created, in order to minimize the risk of infection transmission and spare health care providers, a population identified at high risk. 5 The management of COVID-19 suspect or positive patients has been addressed for external beam radiotherapy (EBRT), but practical aspects of brachytherapy have not been fully addressed. 6 Guidelines overall tend to prioritize locally advanced, curable disease for EBRT and to suggest limitation of treatments wherever there is no strong clinical benefit for immediate EBRT. Strategies for infection prevention, rationalization of clinical workload and working practice in the presence of COVID-19 infected patients have been published. 7, 8 It seems crucial to extend COVID-19 recommendations to the field of brachytherapy, which has specific constraints related to professional exposure and is an essential component of treatment to achieve patients' cure in numerous clinical situations, especially in cervical cancer. Furthermore, the COVID-19 pandemic infection has led to a drastic reduction of all operating room capacity with exception of critical emergencies.

In addition to recently published EBRT guidelines, we highlight strategies that may be implemented in brachytherapy facilities in this emergency context in order to protect patients and health workers.

Compared to EBRT, the higher risk of perioperative contamination and the difficulty to have a dedicated operative workflow for infected patients in most brachytherapy centers imply that a careful triage evaluation is done prior to patient hospitalization, in order to preclude access of COVID-19 infected patients to the operating room. Indeed, preparation of a dedicated operating room with dedicated ventilators for COVID+ patients is usually not possible. Therefore, systematic patient screening for infection by careful questioning and clinical examination, followed by PCR (polymerase chain reaction) testing +/-systematic chest computed tomography (to screen for false PCR-negative patients) has practical implications to avoid contamination of other patients and ensure safety of health care providers. PCR testing of all patients before a brachytherapy procedure should be strongly considered to preclude that an infected patient will enter brachytherapy operating room. In some countries, such systematic approach may however not be possible due to test unavailability and only cases meeting screening criteria due to suspicious symptoms are tested. Patients with symptomatic or even asymptomatic COVID-19 suspected or proven infection should have their treatment postponed and the patient should follow the CDC testbased or non-test-based strategies until COVID negative, and be cleared by the infectious disease team before re-scheduling the brachytherapy procedure, as for non-urgent procedures per surgical guidelines. 9

For COVID-19 negative patients, treatment should be scheduled according to the cancer-related clinical condition (TABLE 1). The dual objective to limit professionals/patients exposure and to optimize operating room activities requires prioritizing radical treatments for patients with non-operated tumors. Given the major contribution of brachytherapy in patients cure probability, clear priority should be given to brachytherapy for locally advanced cervical cancers. It has been clearly shown that brachytherapy use was associated with a survival benefit in these patients, with overall survival probability significantly lower among women who do not receive brachytherapy after controlling for other prognostic factors. 10, 11 Therefore, LACC patients should be treated with upfront chemoradiation plus brachytherapy and neither EBRT boosts (including stereotactic boosts) nor neoadjuvant approaches should be used, given the deleterious impact of these approaches on patient outcome. 12, 13 Overall treatment time is another major benchmark for treatment quality and an independent prognostic factor for local control, along with concurrent chemotherapy use. 14 It is therefore appropriate not to postpone brachytherapy in COVID-19 negative patients, given the detrimental effect of treatment interruptions and of increasing overall treatment time. Other major indication for brachytherapy includes head and neck tumors treated with brachytherapy alone (e.g. squamous cell carcinoma of the lip, oral mucosa, or nasal region) and penile glans cancers. In these curative situations for which brachytherapy provides both dosimetric and functional superiority over any other EBRT modality, it seems unsuitable to postpone treatment or to replace brachytherapy with external irradiation. 15 Furthermore, brachytherapy use will decrease constraints for EBRT facilities and societies by considerably decreasing the total number of patients travelling.

Brachytherapy can therefore be seen as a tool for advanced hypofractionation and therefore for reduction of patients' access to EBRT facilities (e.g. brachytherapy boost in prostate cancer patients, or interstitial brachytherapy for accelerated partial breast irradiation). 16, 17 In the setting of the COVID-19 pandemic, hypofractionation is an attractive therapeutic option in the context of reduced radiotherapy resources and a potential approach minimize virus spread by limiting patients travelling. 18 Brachytherapy boost has shown benefit in progression-free survival when applied to high and intermediate-risk prostate cancer. However, in this specific case, the benefit of brachytherapy boost should be weighed against the difficulties to access operating room in the pandemic context and the fact that a benefit in overall survival has not been demonstrated. For the same reasons, non-urgent treatments may be postponed (e.g. 125iodine seeds implantation for low-risk prostate cancer, treatment of basal cell carcinoma, and others). If the pandemic situation should be long-lasting, brachytherapy may be seen as an attractive approach to minimize patients' exposure related to daily standard fractionation EBRT lasting seven to eight weeks. In few highly specialized centers, brachytherapy is indicated in pediatric rhabdomyosarcoma. 19 In this situation, children usually receive chemotherapy first with the timing of local treatment decided according to a personalized approach, taking into account tumor response and a multidisciplinary analysis of the theoretical risk of tumor progression on chemotherapy.

High-risk brachytherapy procedures requiring upper endoscopic procedures for applicator placement (oesophagus, pulmonary cancers) should be postponed after careful analysis of the benefit/risk ratio, given the possibility to use alternative non-invasive approaches and the fact that those procedures, at high risk for COVID-19 transmission, are in most cases palliative in intent. 15 In 

In the COVID-19 context, it is necessary to protect health care workers and minimize the risk of COVID-19 transmission by avoiding any non-essential exposure of professionals.

It is therefore recommended to deny access to the operating room to non-essential person.

Each time it is technically feasible, it is necessary to have maximum one operating radiation oncologist, one nurse and one physicist (for real time treatment planning) in the same operating room. In some indications (e.g. head and neck or pediatric applications), the treatmentmay however require the presence of additional operators. Guidelines for surgical procedures have been provided elsewhere. 8 Safety issues in the COVID-19 context also apply for brachytherapy. We therefore recommend favoring interventions under local / locoregional anesthesia to minimize health care workers exposure by avoiding the risks linked to 6 endotracheal intubations a procedure being at risk for COVID19 diffusion. In the pandemic context, the lack of anesthetists and ventilator equipment should also be taken into account.

For endocavitary gynecological applications, there is increasing evidence that proper application can be achieved under local anesthesia. For interstitial brachytherapy procedures, scarce data are available for local anesthesia but spinal anesthesia is being routinely used in numerous centers, providing good comfort for patients in most cases of pelvic (gynecological, lower gastrointestinal tract, urogenital) malignancies. 21 

Brachytherapy has a major role in patients' cure and cannot be substituted or excessively delayed in rapidly growing tumors. This situation of unprecedented challenges, however, requires workflow adaptation, protection measures for patients and health care workers, and rationalization. 7 If the COVID-19 pandemic should persist, then we do believe it is of utmost priority to provide an appropriate definition of clinical priorities including brachytherapy. It is necessary to ensure that in the emergency context treatment remain guided by clinical evidence, and that patients who are in line for curative therapy will not be undertreated. 24 This is especially true for LACC patients, for whom utilization of alternative modalities for primary tumor boosting may lead to a poor outcome. 25 

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