{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:44:13Z","timestamp":1790181853198,"version":"4.1.0"},"reference-count":104,"publisher":"National Institute for Health and Care Research","issue":"46","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["15\/57\/160"],"award-info":[{"award-number":["15\/57\/160"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"published-print":{"date-parts":[[2022,12]]},"abstract":"\n Background<\/jats:title>\n Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n Nine NHS head and neck cancer sites in England and Wales.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n A total of 87 out of 380 participants were recruited who were aged \u2265\u200918 years and were undergoing head and neck cancer irradiation with \u2265\u200960\u2009Gy.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Random allocation (1\u2009:\u20091 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660\u2009nm, power output 75\u2009mW, beam area 1.5\u2009cm2<\/jats:sup>, irradiance 50\u2009mW\/cm2<\/jats:sup>, exposure time 60 seconds and fluence 3\u2009J\/cm2<\/jats:sup>. There were 20\u201330 spots per session. Sham low-level laser therapy was delivered in an identical manner.<\/jats:p>\n <\/jats:sec>\n \n Main outcome measure<\/jats:title>\n The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n<\/jats:italic>\u2009=\u200944; sham arm, n<\/jats:italic>\u2009=\u200943). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm.<\/jats:p>\n <\/jats:sec>\n \n Limitations<\/jats:title>\n The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient\u2019s mouth.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services.<\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n This trial is registered as ISRCTN14224600.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment<\/jats:italic>; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/uwnb3375","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T11:10:07Z","timestamp":1670584207000},"page":"1-172","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT"],"prefix":"10.3310","volume":"26","clinical-trial-number":[{"clinical-trial-number":"isrctn14224600","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2685-2426","authenticated-orcid":true,"given":"Michael","family":"Nugent","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, City Hospitals Sunderland NHS Foundation Trust, Sunderland, 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London: National Cancer Registration and Analysis Service; 2020."},{"key":"key20221209094551638_ref1-bib7","first-page":"850","article-title":"Analysis of oral mucositis risk factors during radiotherapy for nasopharyngeal carcinoma patients and establishment of a discriminant model","volume":"24","author":"Luo","year":"2005","journal-title":"Ai Zheng"},{"key":"key20221209094551638_ref1-bib8","doi-asserted-by":"publisher","first-page":"S71","DOI":"10.1017\/S0022215116000840","article-title":"Chemotherapy: United Kingdom national multidisciplinary guidelines","volume":"130","author":"Kelly","year":"2016","journal-title":"J Laryngol Otol"},{"key":"key20221209094551638_ref1-bib9","doi-asserted-by":"publisher","first-page":"E857","DOI":"10.3390\/cancers11060857","article-title":"Mucosal injury during anti-cancer treatment: from pathobiology to bedside","volume":"11","author":"Basile","year":"2019","journal-title":"Cancers"},{"key":"key20221209094551638_ref1-bib10","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1002\/cncr.28592","article-title":"MASCC\/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","volume":"120","author":"Lalla","year":"2014","journal-title":"Cancer"},{"key":"key20221209094551638_ref1-bib11","volume-title":"WHO\u2019s Cancer Pain Ladder for Adults","author":"World Health Organisation"},{"key":"key20221209094551638_ref1-bib12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.5978\/islsm.12-RE-01","article-title":"Low-level laser therapy: a standard of supportive care for cancer therapy-induced oral mucositis in head and neck cancer patients?","volume":"21","author":"Jadaud","year":"2012","journal-title":"Laser Ther"},{"key":"key20221209094551638_ref1-bib13","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1097\/CCO.0b013e328352eaa3","article-title":"Low-level laser therapy in the prevention and treatment of cancer therapy-induced mucositis: 2012 state of the art based on literature review and meta-analysis","volume":"24","author":"Bensadoun","year":"2012","journal-title":"Curr Opin Oncol"},{"key":"key20221209094551638_ref1-bib14","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000978.pub4","article-title":"Interventions for preventing oral mucositis for patients with cancer receiving treatment","volume":"12","author":"Worthington","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"key20221209094551638_ref1-bib15","doi-asserted-by":"publisher","first-page":"e107418","DOI":"10.1371\/journal.pone.0107418","article-title":"Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and meta-analysis","volume":"9","author":"Oberoi","year":"2014","journal-title":"PLOS ONE"},{"key":"key20221209094551638_ref1-bib16","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/S0140-6736(02)07948-5","article-title":"Use and abuses of screening tests","volume":"359","author":"Grimes","year":"2002","journal-title":"Lancet"},{"key":"key20221209094551638_ref1-bib17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1007\/s005200050256","article-title":"Low-energy He\/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer","volume":"7","author":"Bensadoun","year":"1999","journal-title":"Support Care Cancer"},{"key":"key20221209094551638_ref1-bib18","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.jclinepi.2013.05.016","article-title":"Single-center trials tend to provide larger treatment effects than multicenter trials: a systematic review","volume":"66","author":"Unverzagt","year":"2013","journal-title":"J Clin Epidemiol"},{"key":"key20221209094551638_ref1-bib19","doi-asserted-by":"publisher","first-page":"e813","DOI":"10.1136\/bmj.e813","article-title":"Impact of single centre status on estimates of intervention effects in trials with continuous outcomes: meta-epidemiological study","volume":"344","author":"Bafeta","year":"2012","journal-title":"BMJ"},{"key":"key20221209094551638_ref1-bib20","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.radonc.2013.10.010","article-title":"Delineation of the neck node levels for head and neck tumors: a 2013 update. 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