Novel: Light Therapy for Oral Mucositis in Cancer Patients

Alexander M. Castellino, PhD

July 23, 2019

Various forms of light therapy, known collectively as photobiomodulation (PBM), can be used for oral mucositis occurring as a side effect of cancer treatment.

However, PBM is not on the radar of most oncologists in the United States, who tend to use mouthwashes for this adverse event.

But that may change now that PBM is recommended in new guidelines for oral mucositis resulting from cancer treatment. The new guidelines were drawn up by the Multinational Association of Supportive Care in Cancer (MASCC) and International Society of Oral Oncology (ISOO).

They were published online July 8 in the journal Supportive Care in Cancer.

Based on a systematic review of 33 clinical trials, the new guidelines recommend intra-oral PBM therapy for the prevention of oral mucositis in patients with head and neck cancer who are undergoing treatment with radiotherapy alone, or radiotherapy with chemotherapy; it's also recommended also for patients who are undergoing  hematopoietic stem cell transplant (HSCT). No side effects of PBM therapy were reported.

Coauthor Praveen R. Arany, PhD, MDS, MMSc, assistant professor in the department of oral biology and biomedical engineering at the University at Buffalo in New York, said that PBM is often delivered via intra-oral devices that deliver laser or LED light directly into the oral cavity, but there are also extra-oral delivery devices that are placed on the cheeks, lips, and throat of the individual.

PBM therapy, Arany explained, generally delivers low-level laser therapy, low-level light therapy, light-emitting diodes, and broadband visible light in the near-visible and near-infrared spectrum at very low, non-thermal doses.

"At a high power, light is often used to destroy tissue. But at a low power, it has the ability to relieve pain or inflammation and promote healing," Arany told Medscape Medical News.

"There is a sense of disbelief that light therapy can work," Arany acknowledged, but emphasized that such PBM therapy can enhance patient care.

"With PBM therapy, the right amount of light in the right place can bring therapeutic benefit," Arany said. "The therapy could potentially serve as an alternative to opioids, which are often prescribed to alleviate the symptoms of oral mucositis."

Coauthor Sharon Elad, DMD, professor and chair of the division of oral medicine at the University of Rochester Medical Center's Eastman Institute for Oral Health in New York, agreed.

"These updated guidelines will provide healthcare professionals with better tools to deliver care for cancer patients," she said in a statement.

Many oncologists and related healthcare professionals use mouthwashes in cancer patients who have developed oral mucositis.

However, in 2015, the American Academy of Nursing recommended against the use of mixed medication mouthwashes — commonly referred to as "magic mouthwash" — to prevent or manage oral mucositis.

These mouthwashes are compounded by a pharmacy and typically have a mixture of compounds including analgesics and opioids, Arany explained.

In addition, they provide only symptomatic relief, may have a potential for abuse, and do not really address the issue, he said.

Light therapy actually reverses the damage caused by mucositis and is associated with healing, Arany said. It promotes the activation of a growth factor such as transforming growth factor-beta (TGF-ß) that has a central role in wound healing

There have been no studies comparing oral mouthwashes with PBM therapy. Although the clinical trials that were reviewed in drawing up the new guidelines did have a control group, "the control was a placebo, an active-treatment or no intervention. The specifics of the study design and the control used varied," Elad commented.

Elad told Medscape Medical News that the use of PBM therapy is supported by high-level evidence that was published in the literature.

"This refers to randomized clinical trials, with no flaws in the study design, in which the reported physical settings were reproducible. This led to the recommendation of its use as part of the MASCC/ISOO clinical practice guidelines," she said.

There is great variability in the device and protocols used to deliver the PBM therapy, the panel notes. "Each guideline is specific for a certain patient population, and for a certain clinical and device-related setting," Elad said.

In most cases, PBM is used the day before or the day of therapy and its frequency would vary and depend on the protocol for each treatment, Arany said.

However, it can also be used once oral mucositis has developed, as in the following patient case reports.

Patients Testimonies: "It's a No Brainer"

Medscape Medical News spoke to two cancer patients, Max and Brandon, both of whom received PBM therapy for oral mucositis via different routes.

PBM was delivered by Annette Quinn, RN, MSN, program manager of radiation oncology at the University of Pittsburgh Medical Center in Pennsylvania, who has been using PBM on patients with cancer for both the treatment or prevention of oral mucositis.

Max F., 27 years of age and a real estate agent, was diagnosed with Hodgkin's and non-Hodgkin's lymphoma in June 2018 and was prescribed several rounds of chemotherapy. After only two days on chemotherapy, Max developed between 5 and 10 open and painful sores in his mouth.

"The pain was between 9 and 10 on a scale of 0 to 10 and was the worst of any of the side effects I experienced," Max told Medscape Medical News.

He was prescribed an oral mouthwash that numbed the pain. "But the pain came right back 10 minutes later," he said.

The mouth sores were preventing me from eating and drinking. Max, age 27

Max knew that to keep his chemotherapy schedule he had to maintain his weight and strength. "The mouth sores were preventing me from eating and drinking," he said. "More than any other side effect, the mouth sores made minute-by-minute life very difficult."

Max was referred for PBM therapy for the oral mucositis, although he had received only chemotherapy (and not radiation); as such, he is not in the patient populations that are specified in the new guidelines.   

Brandon, a 32-year-old who works with an emergency medical technician (EMT) unit, was diagnosed with acute lymphocytic leukemia in February 2018.

After undergoing extensive chemotherapy, he was scheduled to receive a stem cell transplant from an unmatched donor in August 2018. Six days prior to receiving the transplant, Brandon was scheduled for 4 days of radiation therapy and 2 days of chemotherapy.

PBM was part of the protocol and was provided to Brandon prior to and during radiotherapy, and following stem cell transplantation, for the prevention of oral mucositis.

Max and Brandon both told Medscape Medical News that the PBM therapy procedure was simple and took only 5 to 10 minutes. After wearing protective goggles, light was shone in the oral cavity (and directly at the mouth sores in Max's case) and also externally on the cheeks.

"It [the procedure] was simple, painless and did not have any side effects," they said.

"It seems like a small thing, but it was a big deal for my situation. It allowed me to maintain my [treatment] schedule," Max commented.

"This was a no brainer. It is a harmless procedure that can help you," Brandon said.

Arany is president of the World Association for photobiomoduLation Therapy (WALT) and immediate past-president of the North American Association for photobiomoduLation therapy (NAALT).

PBM has existed for decades and is used across several clinical conditions, including Alzheimer's disease, Parkinson's wounds, chronic wounds, and mucositis, he said. Recent improvements in the technology have made the treatment more affordable for wider use.

Arany noted that PBM use is rising across Europe, Brazil, India, Canada, and several other nations, but it is not used much in the United States, he acknowledged.

Elad noted that the excellent randomized controlled trials reviewed to formulate the guidelines were not conducted in the United States, and the devices used for these trials are not necessarily available in the US. "The devices that are available in the US may or may not have the exact same setting options. Therefore, the challenge to implement the knowledge universally is a major factor in the slow application of PBM therapy for oral mucositis," she said.

The fact that PBM is now listed in the new guidelines for oral mucositis "is a major milestone for the field," Arany commented.  

"We are confident it will set a clear path for several exciting clinical applications for photobiomodulation therapy, from concussions and wound healing to exciting new work with regenerative medicine and stem cells," he said in a statement.

Elad noted that, following the full publication of the guidelines, a short summary, which will be translated into multiple languages, will be posted on the MSG [MASCC/ISOO mucositis study group] webpage.

"Additionally, we plan to develop information sheets on the MSG webpage that will present the highlights of the guidelines in a practical, concise way," she said.

The previous mucositis guidelines from MASCC/ISOO, published in 2013, were adapted by the National Comprehensive Cancer Network as well as by other societies. "Since this latest guideline update was published only a few days ago it may take a while for other societies to formulate a formal statement," Elad said.

However, there are still gaps in the guidelines: for example, they do not mention patients who are treated with chemotherapy alone, such as Max in the patient case above.  

"Even with the best evidence-based interventions, we don't yet have an ultimate guideline for mucositis in all clinical settings. We look forward to future research to help shape a more universal implementation of PBM therapy as well as identify additional effective and validated protocols," Elad noted.

Arany has received grants and consulting fees from Lumitex/MuReva, NIDCR/NIH , NeomedLight, NST Consulting, Phillips Research Labs, CuraLase, American Society of Lasers in Surgery and Medicine, and the American Dental Education Association. He has received non-financial travel support from Thor Photomedicine and Weber Medical. In addition, Arany has a patent issued for Laser systems for dental therapy. Elad has disclosed no relevant financial relationships.

Supportive Care in Cancer. Published online July 8, 2019. Abstract

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