key: cord-0950854-1nj4mqkl
authors: Portaluri, M.; Barba, M.C.; Musio, D.; Tramacere, F.; Pati, F.; Bambace, S.
title: Hypofractionation in COVID-19 Radiotherapy: A Mix of Evidence Based Medicine and of Opportunities
date: 2020-07-02
journal: Radiother Oncol
DOI: 10.1016/j.radonc.2020.06.036
sha: ae6a39e4f01895047472c4e9d9f05e2d74e830e5
doc_id: 950854
cord_uid: 1nj4mqkl

nan

Since January 2020, the spread of the COVID-19 pandemic in China and, in the next weeks, in Italy and then in the rest of Europe and the world, has had an enormous impact on the organization, safety procedures and prescription behavior of the physicians in radiation oncology. The main concerns expressed in the numerous comments, letters and papers published in the last three months are a) how to assure the normal supply of the radiotherapy treatments; b) how to keep constant the number of Healthcare Workers (HCW); c) how to identify radiotherapy (RT) patients SARS-CoV-2 positive; d) how to protect HCW from the viral infection; e) how to protect the patients from the infections; f) how to reduce the postponing and the delay of RT start.

In previous communications, the initial modifications of the clinical activity in a radiotherapy department in Southern Italy -an area with a relative of low incidence of infections -were described soon after the declaration of the pandemic (1) and some criticism were addressed towards the safety recommendations of the national governmental and the scientific institutions, as they were contradictory and arguably inadequate to ensure patients' and HCWs' safety (2). Many papers have been published with the aim to resume the Hypofractionated (HF) schedules which are considered more suitable for avoiding many visits to the hospital centre, for respecting the time between surgery and RT and thus reducing the risk of infection. Last 29 April, a search on Pubmed (www.pubmed.gov) based on the query radiotherapy+covid-19 gave 53 papers. Among these, we selected those regarding fractionation scenario. In table 1, the HF schedules proposed in this pandemic period, from different countries, are summarized (3-14). They are well known schedules, already used with different motivations: a) short life expectancy or poor general conditions; b) advanced age and logistic problems in reaching the RT hospital; c) radiobiological evidence in tumors with higher sensitivity than conventional fraction dose (breast, prostate); d) the need to reduce inpatient stay for palliative treatments; e) the increasing demand of >RT, in countries with universal access to health services, produced a relative shortage of machines and an increasing of waiting times.

Evidence-based decisions are a cornerstone also in medical sciences, at least at theoretical; its matching in the practices is however, sometimes, difficult to detect. For instance, point e) of the motivations for prescribing HF schedules, in Italy it is difficult to find it in a private setting (also when the private structure supplies radiotherapy on behalf of Health Public Service(HPS)) because reimbursement is on daily session basis. Recently, in the era of dynamic conformational techniques, the use of HF schedule has become more diffuse, also in the private structures, because they obtain in some region -the HPS is regional in Italy -a better reimbursement. During a pandemic, it may happen the occurrence of fault lines in medicine. One of these is the "willingness on the part of clinicians to abandon the prime dictum of medicine, to do no harm, and rush into treatments that not only may be useless but may well be dangerous. (15) The fact is, most physician are not trained to recognize good science from bad. Nor do they have the time to analyze every study, and too many are willing to ignore the need for reliable evidence when fear sets in" (16). Are we going to his pitfall? Some fractionations in Head & Neck tumors, in a scenario where the RT resources are severely reduced, are quite anecdotic and based only on the consensus and preference of the physician (3). While for breast (5), in stage I NSLC (4), rectum (8,9), prostate (11), the schedules are supported by clinical trials, for some other schedules, such as some palliative one in glioblastoma (10) or whole breast over 70-year (12), their efficacy is still to be proved.

At the onset of the pandemic, many treatments were postponed by the patients themselves or by the RT departments to minimize the number of the visits in the RT centers to the urgent and binding cases (1). So this decision could have theoretically impacted on the outcomes of some treatments. HF RT should be delivered only where solid scientific evidence is available, while some shortest courses in palliative setting likely are unuseful and therefore it would be better to deny them. In a palliative setting, the pandemic will allow us, perhaps, to avoid inappropriate therapy to some patients.

Another aspect regards the patient's consciousness. About ten years ago, when we started HF schedule of 15 fractions, after a breast conservative surgery with the publication of START trials (17,18), a strong argue with a patient occurred because she was concerned that our proposal to shorten the treatment time was due to the willingness to reduce the waiting times, rather than to work more and harder to treat all patients with the best schedules. It is now more frequent to meet patients who ask us to be treated in 5 fractions (9).

"Therefore, efforts should focus on making healthcare professionals, more sensitive to the limitations of the evidence, training them to do critical appraisal, and enhancing their communication skills so that they can effectively summarize and discuss medical evidence with patients to improve decision-making". (15) We hope that the pandemic will not lead us to join to HF schedules uncritically, driven only by the urgency of the moment and let us time to discriminate what is solid and what is weak. The need of respecting the timing (19) cannot be harmful for our patients and the lack of administrative support by means of delivery of adequate protections and timely staff recruitment cannot be changed by bad RT treatments. 

chemosensitive: 25 Gy/5 f or Aggressive NHL,chemorefractory: 30 Gy/6 f Localized aggressive NHL, exclusive RT: 36-39 Indolent lymphoma

Gy/2-3 f Solitary bone plasmocitoma or solitary extram spine/H&N site) and 36 Gy/12 f (spine/H&N Palliation: symptomatic aggressive: 25 Gy/5 f Zaorsky (11) USA-UK Prostate IR/HR localized: 5 to 7 f (SBRT) (v. 2020 NCCN post-prostatectomy: 52.5 Gy/20 f oligometastatic: 1 or 3 fractions (SBRT) low volume

15 f (omit RT in case o Invasive: 40.05 Gy/15 f or 26 Gy/5f (o N+: 40.05 Gy/15 f Postmastectomy (Hypofractionation i Gy/15 f PBI: 38.5 Gy/10 f (BID) or 30 Gy/5 f or (daily) PBI (IORT): 20 Gy/1 f Lung NSCLC stage I: 45 Gy/3 f or 60 Gy/8 f o NSCLC stage III: 66 Gy/24 f SCLC limited stage

USA Palliation Brain metastases: WBRT: 20 Gy/5 f Cord compression: 8 Gy/1 f Tumor bleeding: 14.8 Gy x 4 f (BID) or 20 Gy x 5 f SVC syndrome/Airway Obstruction 17 Gy/2 f (weekly) or 20