March 3, 2020
by Annette Quinn, RN, MSN; David Clump, MD; Karen Holeva, MS; Dwight Heron, MD, FACRO
Oral mucositis (OM) is an acute complication resulting from chemoradiotherapy in the management of head and neck malignancies causing pain, decreased oral intake, risk of infection, and modifications to a patient’s treatment regimen. Over the last decade, the prevalence of oral mucositis has increased due to new chemotherapy, introduction of targeted agents such as Cetuximab, and the ability to delivery higher doses of radiation therapy. Nearly all patients with head and neck tumors treated with chemoradiotherapy experience some degree of mucositis and generally 50% develop grade III or grade IV oral mucositis.1 In addition, 20% of oncological treatment interruptions are due to this complication and/or related pain.2 As a result, treatment can be prolonged and clinical outcomes subsequently compromised. In addition to its impact on a patient’s quality of life, course of treatment and morbidity and mortality, mucositis can also have a significant economic cost. An estimated 15% of patients treated with radical radiotherapy to the oral cavity and oral pharynx required hospitalization for treatment-related complications.3 Photo-bio-modulation (PBM), formally known as low level laser therapy, has shown significant benefit in helping to decrease the incidence of OM in this challenging patient population.
Treatment for oral mucositis is still essentially palliative utilizing pain medications to mask the effects of concurrent chemoradiotherapy. As a result, there are essentially no effective treatments that focus on radiation-induced OM. A recent Cochrane review, analyzed the prospective data assessing the management of OM. Here, thirty-two prospective trials including 1505 patients were analyzed. Three comparisons for mucositis treatment including two or more trials were assessed: benzydamine HCl versus placebo, sucralfate versus placebo and PBM versus sham procedure. Interestingly, only PBM showed a reduction in severe mucositis when compared with the sham procedure, RR 5.28 (95% confidence interval (CI) 2.30 to 12.13).4
Low Level Laser Therapy
The mechanism of action of PBM has been described as an activation of energy production by the cytochromes in the mitochondria of oral mucosa cells, by the transmission of electrons. The laser promotes rapid regeneration of the myofibroblasts originating in the fibroblasts and the growth factors of these fibroblasts maintain repair and cytotoxic protection. This affords an ideal opportunity to implement PBM in the management of radiation-induced mucositis.
To date, there are several studies about laser therapy in the prevention/treatment of mucositis caused by radiotherapy. Despite the different protocols used, these studies have shown that PBM can produce some benefit to reduce the severity of oral mucositis and pain. This is supported by the findings of the Cochrane review and more recent prospective studies.
One prospective study reported by Carvalho et al., determined the effect of the PBM in the prevention and treatment of mucositis in head and neck cancer patients. Here, 70 patients with malignant neoplasms in the oral cavity or oropharynx were evaluated and subsequently randomized into two low-level laser therapy groups: Group 1 (660 nm/15 mW/3.8 J/cm2/spot size 4 mm2) or Group 2 (660 nm/5 mW/ 1.3 J/cm2/spot size 4 mm2) starting on the first day of radiotherapy. OM was assessed daily and weekly using the NCI and WHO scales. Oral pain was scored daily with a visual analogue scale before laser application. The patients in Group 1 had a mean time of 13.5 days (range 6–26 days) to present mucositis grade II, while the patients in Group 2 had a mean time of 9.8 days (range 4–14 days) (both WHO and NCI p = 0.005). In addition, Group 2 also presented a higher mucositis grade than Group 1 with significant differences found in weeks 2 (p = 0.019), 3 (p = 0.005) and 4 (p = 0.003) for WHO scale and weeks 2 (p = 0.009) and 4 (p = 0.013) for NCI scale. The patients in Group 1 reported lower pain levels (p = 0.004). The authors concluded that PBM during radiotherapy was found to be effective in controlling the intensity of mucositis and pain.5 This study is currently the best evidence supporting PBM in the management of head and neck cancer patients receiving definitive treatment with chemoradiotherapy.5
University of Pittsburgh Experience
With mounting positive clinical evidence and practice guideline recommendations from both Cochrane and MASCC in favor of the use of PBM, the University of Pittsburgh Medical Center’s Department of Radiation Oncology, in December 2014, has initiated a PBM program to help improve the quality of life in patient’s undergoing head and neck cancer treatment.
Staff physicians at UPMC Shadyside participate in a Head and Neck Cancer multidisciplinary conference in collaboration with the Department of Otolaryngology, Medical Oncology and Dentistry. Here patients are discussed from not only a disease management standpoint including potential enrollment in clinical protocols, but also in terms of the individual patient’s feasibility in completing therapy based upon their disease state and social circumstances. This is a necessary component of the multidisciplinary management team since prolonging the treatment, whether it’s from pain control, weight loss, or other factors, leads to inferior outcomes. As a result, PBM was a welcomed addition to the tiresome management of oral mucositis resulting from chemoradiotherapy.
Patients receiving definitive treatment for malignant neoplasms in the oral cavity and/or oropharynx with a technique known as intensity modulated radiation therapy (IMRT) and doses in facial fields equal to or higher than 70.0 Gy, either exclusively or associated with chemotherapy are seen on the first day of consultation by the oncology nurse. Before commencing of treatment, patients undergo oral care protocol including oral examination, preventive dental treatment, instructions for oral care during radiation therapy and prescription mouthwashes and fluoride.
At the commencement of radiation therapy, patients are treated with the Thor PBM system. The LX2 control unit equipped with the 1390 mW, 69 diode LED cluster probe is used to treat patients based on the following protocol as recommended by the manufacturer (See Appendix A). Briefly, patients are treated Day 1 of therapy and then every Monday, Wednesday and Friday for the duration of their radiation therapy.
Appendix A & B
A complete oral assessment is performed 3x/week as well as mucositis grading using the CTCA. Patients who begin to develop ulcerative lesions then have those specific lesions targeted using the intraoral probe.
To date, over 700 patients receiving radiation therapy for head and neck carcinoma have been treated with PBM. None of the patients experienced a treatment break related to OM nor a dose reduction in their chemotherapy or targeted agent. Pain medication use has been decreased in this population, as well as the use of feeding tubes. Patients experienced zero side effects from PBM and to date no patient has discontinued the use of the laser due to lack of benefit in relieving or preventing their OM (Figs. 1 & 2).
OM before PBM.
Resolution of OM after PBM.
The PBM program has been so successful in the radiation oncology facility at UPMC that currently we have extended use to the inpatient stem cell transplant population for prevention of oral mucositis in this extremely high-risk subset of patients.
A 79-year-old, nonsmoking male who initially presented with a sore throat to his primary care physician in December of 2013. Through a series of workups, the patient was eventually diagnosed with an HPV positive, stage III squamous cell carcinoma of the right tonsil and a synchronous stage I squamous cell carcinoma of the right aryepiglottic fold. He underwent transoral laser excision of both primary sites and a right selective nodal dissection including 1 of 35 lymph nodes involved with disease. His case was discussed at a multidisciplinary tumor board with concern for high risk of local regional relapse given pre-operative imaging showing questionable prevertebral skeletal muscle involvement. Thus, he was treated with adjuvant radiotherapy with concurrent Cisplatin chemotherapy. On treatment number 13 patient developed a Grade 3 OM most notable on his left tongue. He was started on oral pain medications and PBM was initiated.
After three treatments of PBM patient had significant improvement of OM and then stabilization at grade 1 mucositis by completion. Pain medications were tapered and patient experienced no treatment-related breaks in the radiation or chemotherapy (Figs. 3 & 4).
OM seen on treatment number 13 in a head and neck cancer patient receiving concurrent chemoradiotherapy (before).
Resolution of OM after three treatments of LLLT.
Oral Health welcomes this original article.
About the Author
Annette Quinn has been a nurse in the Oncology department since 2002, in 2016 she has received an Excellence in Radiation Oncology award from the Oncology Nursing Society. She has published a number of articles, articles and book chapters on the side-effects of radiation oncology and treatment of oral mucositis. Annette lectures all over the USA on the topics of Radiation oncology and treatment of oral mucositis using low level laser therapy.
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