|Ahead of print publication
Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience
Salvatore Cozzi1, Maria Paola Ruggieri1, Lilia Bardoscia1, Masoumeh Najafi2, Gladys Blandino1, Lucia Giaccherini1, Moana Manicone1, Dafne Ramundo1, Ala Rosca1, Dario Salvatore Solla1, Andrea Botti3, Daniele Lambertini3, Patrizia Ciammella1, Cinzia Iotti1
1 Radiation Therapy Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Italy
2 Department of Radiation Oncology Shohadaye Haft-e-Tir Hospital, Iran University of Medical Science, Teheran, Iran
3 Medical Physics Unit, Department of Oncology and Advanced technology, AUSL-IRCCS di Reggio Emilia, Italy
|Date of Submission||31-Mar-2021|
|Date of Decision||21-Jun-2021|
|Date of Acceptance||02-Jul-2021|
|Date of Web Publication||11-Nov-2022|
Radiation Therapy Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia
Source of Support: None, Conflict of Interest: None
BACKGROUND: After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases.
MATERIALS AND METHODS: The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed.
RESULTS: Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018–49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection.
CONCLUSIONS: The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.
Keywords: Coronavirus outbreak, COVID-19 pandemic, hypofractionated radiotherapy, patients safety, radiotherapy, radiotherapy work-flow
|How to cite this URL:|
Cozzi S, Ruggieri MP, Bardoscia L, Najafi M, Blandino G, Giaccherini L, Manicone M, Ramundo D, Rosca A, Solla DS, Botti A, Lambertini D, Ciammella P, Iotti C. Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=361023
| > Introduction|| |
The severe acute respiratory syndrome coronavirus (SARS-CoV)-2-related disease (COVID-19) pandemic emerged in 2019 as a public health emergency worldwide. Since February 2020, Italy has been experiencing one of the deadliest COVID-19 outbreaks in the world. In such dramatic public health emergency, cancer patients have an increased risk of developing serious complications from COVID-19 infection because of their compromised immune system due to systemic or radiation treatments.
Radiation therapy (RT) facilities have been overwhelmed by the COVID-19 emergency. Radiation oncology departments were forced to quickly adapt their health-care system and establish new possible solutions and priorities to ensure treatment delivery to cancer patients, and maintain the safety of health professionals, patients, and caregivers. In fact, since conventional radiation treatments usually are delivered in daily, consecutive fractions over several days, radiotherapy units might represent a possible site of SARS-CoV2 exposure.
Several experiences of radiation oncology departments to be re-organized to protect patients, families, and health professionals from COVID-19 have been reported in the literature. There may be a tradeoff between the risk of cancer progression in case of RT interruption and the likelihood of COVID 19 infection in case of RT initiation or continuation.,
According to the most remarkable Italian cancer societies, life-saving treatments for oncological patients should have been guaranteed to every cancer patient during COVID-19 outbreak.
The Italian Association of Radiotherapy and Clinical Oncology, in line with the European Societies for Medical Oncology and Therapeutic Radiology and Oncology and the American homologues American Society of Clinical Oncology (ASCO) and American Society for Radiation Oncology (ASTRO), has been continually producing recommendations and guidelines with detailed instructions for radiation oncologists on how to rapidly and safely cope with the ongoing pandemic, considering the local and national health authorities' indications., Among the main inputs suggested by the guidelines, the implementation of hypo-fractionated or moderately hypo-fractionated treatments schedules was unanimously approved as the main measure to be adopted in clinical practice to minimize overcrowding in hospital facilities, hence mitigate the SARS-CoV2 infection risk among frail and vulnerable patients, as well as within the staff. A lot of specific protocols and protective measures to optimize RT delivery and prevent the COVID-19 spread have been developed recently. The purpose of this work is to report our experience in dealing with COVID-19 emergency at our Institution, the way we have re-organized our clinical activity, changed our priorities and stressed the use of hypofractionation in the radiation treatment of cancer patients and to evaluate how these measures has decreased the risk of the disease.
| > Materials and Methods|| |
RT Unit of Reggio Emilia (Italy) quickly adapted to the COVID-19 outbreak and immediately established practical definition of priorities. Reorganization of patient's circuit from the first medical examination to follow-up visits was carried out. Telemedicine consultations were encouraged. Numerous, internal recommendations were developed to allow an optimal RT planning and delivery to all cancer patients for whom RT was indicated, as well as institutional policies and procedures for the entire healthcare service. Our department has decided not to block the service, but to guarantee access to care for all patients. The strategy adopted by radiotherapy department was to treat all patients, unless they showed severe symptom of COVID-19 infections that make unable to access the facility. Daily triage for patients and staff, use of personal protective equipment (PPE), hand washing, environment sanitization, social distancing and limitations for the patients' caregivers access to clinics, unless absolutely essential for nonself-sufficient patients, were adopted. In order to identified asymptomatic patients, body temperature was measured for each patients and a careful analysis of family members who were positive for COVID-19 was collected. Reverse Transcription-Polymerase Chain Reaction tests were performed on patients with hyperpyrexia or who had virus infection-related symptoms in the previous 2 weeks, or with sick relatives. Patients with suspected or confirmed COVID-19 infection were treated at the end of the day, using an alternative access path to avoid contact with the remaining patients.
We decided not to postpone any treatment unless there was a serious clinical impairment affecting the safety and efficacy of treatments and access. We also opted to implement hypofractionation, since we have been using moderate hypofractionated RT schedules in different clinical settings for years in clinical practice.
We reviewed our clinical activity from February 15 to April 30, 2020, and made a comparison with the outcomes from the same period in 2018. A direct comparison with 2019 was not possible, since one of the 3 Linear accelerators (LinAc) at our Institution was not working temporarily. We investigated the total number of RT courses performed, patients' admissions and sessions. Then, we focused on the fractionation schedules for breast cancer, prostate cancer, and bone metastases. Among prostate cancer patients, we also analyzed the number of stereotactic treatments (stereotactic body RT [SBRT]) applied for low-to favorable intermediate-risk patients, according to D'Amico Risk Classification,, compared to the routine use of moderate hypofractionation schedule in RTOG 0415 (70 Gy in 28 daily fractions) in this setting.
| > Results|| |
From February 15th to April 30th, 2020, the major part of orthovoltage RT for skin cancer in elderly patients were suspended, as well as nonurgent follow-up visits (replaced, when possible by telemedicine consultations). No reduction in the number of new diagnoses, no RT delivery beyond the recommended waiting time, and no declined or postponed treatments were recorded.
Two hundred and ninety-nine patients underwent radiation treatments at our Radiation Oncology Unit, compared to 284 patients in the same observation period in 2018 (that is 5.3% increase in number of treatments). We observed the total number of treatment courses increased by 11% (310 and 344 in 2018 and 2020, respectively). We also recorded a 43% decrease in the total number of sessions, from 3566 to 2036 in 2018 and 2020, respectively (1530 fewer sessions). [Table 1] summarizes the described findings. No selection of entry to treatment was made on the basis of age, and there was no decrease in treatment for elderly.
|Table 1: Clinical practice at our radiation oncology unit in 2018 and 2020 observation period|
Click here to view
Between February 15, 2018 and April 30, 2018, 90 (31.7%) women in total were treated for breast cancer with adjuvant whole breast irradiation (WBI). Fractionation RT schedules were applied as follows: 67 (74.4%) patients received 40.5 Gy in 15 daily fractions, 18 (20%) patients 45 Gy in 18 daily fractions, and finally, 5 (5.6%) conventional fractionated RT with total target dose of 50 Gy in 25 daily fractions. In the homologue observation period in 2020, 80 (26.7%) breast cancer patients were treated instead. The 18-fractions RT schedules were abandoned and the 3 Gy per 13 daily fractions (totally 39 Gy) was introduced in 27 (33.7%) women. We also observed a global 27% reduction in the use of 40.5 Gy in 15 fractions, (49 adjuvant WBI, 61.2%). [Figure 1] reports details on fractionation RT schedules and the number of treated patients. All treatment were performed using 3DCRT, DIBH treatment were not routinely used.
|Figure 1: Fractionation schedules and number of patients treated for breast cancer|
Click here to view
Regarding prostate cancer, a total of 30 (10.6%) patients underwent exclusive RT in 2018, 4 (13%) of which were treated using SBRT 35 Gy in 5 every-other-day fractions, the remaining 26 (86.7%) with moderate RTOG 0415 hypofractionation. In 2020, the number of SBRT increased by 5% (18.2% patients treated with the same ultra-hypofractionation schedule over 22 prostate cancer).
When we focused on palliative treatments for bone metastases, we recorded several hypofractionation schedules. The most frequent schedules were 20 Gy in 4 or 5 daily fractions (17 (6%) in 2018 and 14 (4.7%) in 2020, respectively, and the single shot with target dose ranging from 8 Gy to 15 Gy (66 (23.2%) and 74 (24.7%) in 2018 and 2020, respectively). Overall, there was a 17.5% decrease in the use of multi-fraction palliative RT, in favor of a 12% increase in the use of single-fraction schedules.
Among the 299 treated patients in 2020, only 3 patients (1%) tested positive for SARS-Cov2 swabs: One tested positive during treatment, the others, 2 and 9 days after the end of radiotherapy, respectively. On the other side, only one of forty-two (2.3%) Radiation Oncology care-providers developed asymptomatic COVID-19 infection (revealed by subsequent, positive serological test with negative swab).
| > Discussion|| |
Emilia Romagna was one of the most affected COVID-19 pandemic regions in Italy. Reggio Emilia, SARS-Cov2 epidemic reached its peak in the second half of March.
Along this period, it was necessary to clearly define organizational priorities in the Radiation Oncology departments. A meeting was quickly arranged to discuss how to proceed during the COVID-19 emergency while keeping both cancer patients and hospital staff safe.
Guided by the first national and international recommendations that had been emerging in the early days, we decided to adopt the following preventive measures: (1) Do not restrict or postpone the access for patients newly diagnosed with cancer; (2) Do not change the internal organization of the department, e.g., by implementing the rotation of the healthcare staff working in our Radiotherapy facility (medical doctors, nurses, therapists, physicists, administrative personnel), as reported in the literature;, (3) Reserve only telemedicine services for follow-up visits; (4) Stress on the correct hygienic-sanitary practices necessary for contagion reduction: Daily patients and staff triage, use of PPE, hands washing, environment sanitization social distancing and limitations for the patients' caregivers' access to the department, unless absolutely essential; (5) Treat patients with suspected or confirmed COVID-19 infection at the end of the day, using specially dedicated paths; (6) Suspend orthovoltage RT for skin cancer in elderly patients; (7) Apply a more extensive use of hypo-fractionated schedules, that had already been the standard of care for various cancer diseases at our department for some years.
Unlike many Radiotherapy Centers, in the period of maximum pandemic spread, we recorded over 5% increase of the treated patients at our Institution. This means that all cancer patients have been guaranteed to continue the therapeutic procedure in the best way, without any impact on the outcome of disease. Such great result was obtained by reducing the total number of sessions per patient, decreasing the total entry time for individual patients, hence lowering the risk of SARS-CoV2 infection. Our center has been heavily focusing on the use of hypofractionation schedules for some years,, so we decided to accentuate its implementation in such a critical time, in accordance with international guidelines and biological dose equivalences.,, Hence, the enhancement of the use of hypofractionation has allowed the reduction of the “treatment waiting list” and this explains the increase in the number of patients treated in the period compared.
In particular, a real revolution was made in the treatment of breast cancer. Conventional fractionation was reserved only for young patients submitted to postmastectomy RT following immediate breast reconstruction. We also omitted the postlumpectomy boost in patients with favorable prognostic factors (e.g., age ≥50 years, absence or minimal ductal carcinoma in situ (DCIS), low-grade invasive/Luminal A cancer), in line with the available literature reporting the boost to the tumor bed to be optional, due to the minimal impact on local recurrence and no impact on survival. In contrast, a 9-to-12-Gy boost (3–4 fractions) was regularly administered according to the scheme proposed by Coles, or with simultaneous integrated boost technique, in patients ageing <50 years, in those with positive surgical margins, high-grade invasive cancer, or presence of extensive DCIS. The 18-fractions schedule, initially used for low-risk breast cancers patients aged ≤60 years, was abandoned in favor of the START A Trial 13-fractions schedule, with no increase in acute cutaneous and subcutaneous toxicity. Breast cancer treatment were performed with 3DCRT technique through the use of 2 or 4 tangential fields.
Regarding prostate cancer, since 2008, for the first time in Italy, our Radiation Oncology Unit has adopted a moderate hypo-fractionated scheme for the treatment of low-to very high-risk prostate cancer with a radical intent. To date, moderate hypofractionation is considered as the standard therapeutic approach in this setting, and it is routinely performed on the basis on a wide spread of advanced RT technologies and a large amount of scientific evidence.,,, Moreover, in recent years, many studies have investigated the use of SBRT in patients with low-to intermediate-risk and selected high-risk prostate cancer., The HYPO-RT-PC Trial not only demonstrated the non-inferiority of SBRT compared to conventionally fractionated RT, but recorded rectal toxicity rates comparable to conventional treatments, with a slight increase in acute genitourinary toxicity (6%), and no differences in late quality of life (QoL) outcomes.,, Based on these data, in line with the ASTRO-ASCO-AUA evidence-based guidelines, we applied ultra-hypofractionation in selected low-to favorable intermediate-risk prostate cancer with good baseline urinary function assessed by IPSS score. Thirteen percent of patients underwent prostate SBRT in 2020, with great advantages in terms of QoL and reduction of the risk of COVID-19 infections.
On the other side, patients with symptomatic bone metastases are known to be the most critical ones. They require immediate treatment, often direct contact with healthcare professionals for patient positioning and careful clinical assistance. They usually show an extreme fragility in both the planning CT scan acquisition and RT delivery on the LinAc, thus present one of the highest risks for COVID-19 infection transmission. None of these patients were delayed on treatment at our Institution. Extreme attention was paid to them. Outcomes from two recent literature reviews,, showing 8-Gy single-fraction RT to be as safe and effective as multifraction irradiation for relief of painful symptoms, have prompted us to use single dose in this setting of patients, more frequently. We recorded a significant 12% increase in single-session treatments during COVID-19 outbreak. Such approach has been proved to be a crucial point in the management of fragile patients, potentially more susceptible to SARS-CoV2 infection.
It is well known that hypofractionated or stereotaxic schedules require dedicated quality assurance programs and a very precise check of the set-up, which are resource intensive as well as time consuming. The use of imaging to maximize precision and accuracy throughout the entire process of RT it has now become the standard in almost every radiotherapy center. Modern Image Guided RT (IGRT) techniques, improving soft tissue localization, coupled with frequent imaging/repositioning cycles (ideally, before each treatment session), reduce uncertainties, therefore, allowing margins reduction and possibly less toxic treatments. For the most part, images are acquired just after the patient has been positioned for treatment, and then special matching software is used to compare the images to reference images from the treatment plan. The system then calculates a “shift” and sends instructions to the treatment couch, which moves to bring the targeted tumor into precise alignment for treatment.
For clinicians in radiation departments that are deploying these technologies for the first time, the prospect of setting up an IGRT program can seem daunting. It requires establishment of protocols that specify which tools to use, and when. And everyone – from the doctors and physicists to the dosimetrists and therapists – must acquire new skills and work together in unfamiliar ways.
In our center we have been using daily IGRT for all radical Intensity Modulated RT or Stereotactic Radiation Therapy treatments for many years; historically, the portal films or, later on, electronic megavoltage images (obtained with electronic portal imaging devices, EPID) were used as IGRT; since 2008, first with the tomotherapy then with the trubeam SX, the 3D IGRT has been induced, using KV or MV computed tomography (CT). We have created specific protocols for each anatomical district and pathology (timing, image acquisition methods, tolerance limits of movements, etc.) we have organized multiple training sessions for all staff (doctors, physicists, dosimetrists and therapists), and after a learning curve of a few months, the whole procedure of image acquisition and verification was not time consuming. The acquisition of strong confidence with modern IGRT has improved the quality of our treatments and has allowed us, at a critical moment like that of the COVID-19 pandemic, to perform stereotactic and hypofractionated treatments for the majority of patients.
Finally, among the 299 treated patients during the observation period amid COVID-19 pandemic, only 3 patients tested positive for the SARS-CoV2 swab (one tested positive during treatment, the others, 2 and 9 days after the end of radiotherapy, respectively), and only one physician among the 42 staff members in our department tested positive for COVID-19 antibodies, revealing a previous, asymptomatic contagion, so that a 3-days quarantine was prescribed until the negative result of COVID-19 molecular swab was available. None of the other care-providers in our department developed any COVID-19 signs or symptoms. Epidemiological study of the positive doctor showed how the infection occurred within the family, and thanks to the measures adopted, he did not transmit the infection to other care-providers.
| > Conclusions|| |
The global challenges for the health-care system due to COVID-19 pandemic had no comparable situation in recent times worldwide. Unprecedented measures were required to face such critical situation to minimize the risks of infections for patients and health-care professionals. In particular, this was true for cancer patients whose life-saving treatments needed to be guaranteed in safety. We reorganized our priorities to ensure continuity of cancer care. Our experience showed that the adoption of a modified workflow, including a more extensive use of hypofractionation and an appropriate clinical practice allowed the maintenance of an effective RT service. Despite the increased number of treated patients in 2020, the careful application of patients and staff triage, and the strict adoption of protective measures allowed us to safely submit oncological patients to RT, potentially at increased risk of SARS-Cov2 infection. The procedures applied, ensured both a very low risk of contagion at our department and a very low number of patients developing COVID-19 infection during or soon after RT.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Viscariello N, Evans S, Parker S, Schofield D, Miller B, Gardner S, et al
. A multi-institutional assessment of COVID-19-related risk in radiation oncology. Radiother Oncol 2020;153:296-302.
Di Franco R, Borzillo V, D'Ippolito E, Scipilliti E, Petito A, Facchini G, et al.
COVID-19 and radiotherapy: Potential new strategies for patients management with hypofractionation and telemedicine. Eur Rev Med Pharmacol Sci 2020;24:12480-9.
Jereczek-Fossa BA, Pepa M, Marvaso G, Bruni A, Buglione di Monale E Bastia M, Catalano G, et al.
COVID-19 outbreak and cancer radiotherapy disruption in Italy: Survey endorsed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Radiother Oncol 2020;149:89-93.
Alterio D, Volpe S, Bacigalupo A, Bonomo P, De Felice F, Dionisi F, et al.
Head and neck radiotherapy amid the COVID-19 pandemic: Practice recommendations of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Med Oncol 2020;37:85.
D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al.
Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969-74.
D'Amico AV, Whittington R, Malkowicz SB, Cote K, Loffredo M, Schultz D, et al.
Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 2002;95:281-6.
Lee WR, Dignam JJ, Amin MB, Bruner DW, Low D, Swanson GP, et al.
Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol 2016;34:2325-32.
Belkacemi Y, Loaganadane G, Grellier N, Fonteneau G, Zaoui G, Coraggio G, et al.
Radiation therapy department reorganization during the coronavirus disease 2019 (COVID-19) outbreak: Keys to securing staff and patients during the first weeks of the crisis and impact on radiation therapy practice from a single institution experience. Adv Radiat Oncol 2020;5:644-50.
Filippi AR, Russi E, Magrini S, Corvò R. Letter from Italy: First practical indications for radiation therapy departments during COVID-19 outbreak. Int J Radiat Oncol Biol Phys 2020;107:597-9.
Ciammella P, Podgornii A, Galeandro M, Micera R, Ramundo D, Palmieri T, et al
. Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: Predictive clinical and dosimetric factors Radiat Oncol 2014;9:97.
Deantonio L, Cozzi S, Tunesi S, Brambilla M, Masini L, Pisani C, et al.
Hypofractionated radiation therapy for breast cancer: Long-term results in a series of 85 patients. Tumori 2016;102:398-403.
Zaorsky NG, Yu JB, McBride SM, Dess RT, Jackson WC, Mahal BA, et al.
Prostate cancer radiotherapy recommendations in response to COVID-19. Adv Radiat Oncol 2020;5:659-65.
Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al.
Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010;362:513-20.
Grellier N, Hadhri A, Bendavid J, Adou M, Demory A, Bouchereau S, et al.
Regional lymph node irradiation in breast cancer may worsen lung damage in coronavirus disease 2019 positive patients. Adv Radiat Oncol 2020;5:721-5.
De Rose F, Fogliata A, Franceschini D, Cozzi S, Iftode C, Stravato A, et al
. Postmastectomy radiation therapy using VMAT technique for breast cancer patients with expander reconstruction. Med Oncol 2019;36:48.
Coles CE, Aristei C, Bliss J, Boersma L, Brunt AM, Chatterjee S, et al.
International guidelines on radiation therapy for breast cancer during the COVID-19 pandemic. Clin Oncol (R Coll Radiol) 2020;32:279-81.
Vrieling C, van Werkhoven E, Maingon P, Poortmans P, Weltens C, Fourquet A, et al.
Prognostic factors for local control in breast cancer after long-term follow-up in the EORTC boost vs no boost trial: A randomized clinical trial. JAMA Oncol 2017;3:42-8.
START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, et al.
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.
Pollack A, Walker G, Horwitz EM, Price R, Feigenberg S, Konski AA, et al.
Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. J Clin Oncol 2013;31:3860-8.
Incrocci L, Wortel RC, Alemayehu WG, Aluwini S, Schimmel E, Krol S, et al.
Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): Final efficacy results from a randomised, multicenter, openlabel, phase 3 trial. Lancet Oncol 2016;17:1061-9.
Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, et al.
Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2016;17:1047-60.
Cushman TR, Verma V, Khairnar R, Levy J, Simone CB 2nd
, Mishra MV. Stereotactic body radiation therapy for prostate cancer: Systematic review and meta-analysis of prospective trials. Oncotarget 2019;10:5660-8.
Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, et al.
Stereotactic body radiation therapy for localized prostate cancer: A systematic review and meta-analysis of over 6,000 patients treated on prospective studies. Int J Radiat Oncol Biol Phys 2019;104:778-89.
Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M, et al.
Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 2019;394:385-95.
Fransson P, Nilsson P, Gunnlaugsson A, Beckman L, Tavelin B, Norman D, et al.
Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): Patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. Lancet Oncol 2021;22:235-45.
Morgan SC, Hoffman K, Loblaw DA, Buyyounouski MK, Patton C, Barocas D, et al.
Hypofractionated radiation therapy for localized prostate cancer: An ASTRO, ASCO, and AUA evidence-based guideline. J Clin Oncol 2018;36:JCO1801097.
Gutman S, Merrick GS, Butler WM, Wallner KE, Allen Z, Galbreath RW, et al.
Severity categories of the international prostate symptom score before, and urinary morbidity after, permanent prostate brachytherapy. BJU Int 2006;97:62-8.
Chow R, Hoskin P, Hollenberg D, Lam M, Dennis K, Lutz S, et al.
Efficacy of single fraction conventional radiation therapy for painful uncomplicated bone metastases: A systematic review and meta-analysis. Ann Palliat Med 2017;6:125-42.
Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy – A systematic review of the randomised trials. Cochrane Database Syst Rev 2004;2004:CD004721.