Red Light Therapy for Oral Mucositis: Scientific Evidence

60 patients receiving radiotherapy for head and neck cancer took part in a 2013 randomized controlled trial in Brazil of low-level laser therapy for the mouth complications of that treatment. 30 patients were treated with a diode laser at 685 nm and 35 mW for 25 seconds per application, and 30 received a sham laser, with mouth sores, pain, and saliva flow assessed 1 week into radiotherapy and at the 15th and 30th sessions. Every patient in both groups developed some degree of oral mucositis. Researchers found that the laser group had milder mucositis, less pain, and more saliva than the sham group at the later assessments.

2013 brought a meta-analysis from Brazil of laser therapy for preventing oral mucositis in patients receiving cancer treatment. 12 studies were included in the systematic review and 7 in the pooled analysis, with the studies using lasers at 632 to 1064 nm and 40 to 60 mW, and the cutoff for the calculation set at mucositis above grade 3. About 9 times greater protection against mucositis above grade 3 was seen in patients given laser therapy than in those without it. The authors called for larger studies to evaluate this preventive effect more fully.

When preventive low-level laser therapy was compared with a placebo laser in 94 head and neck cancer patients receiving radiotherapy together with the chemotherapy drug cisplatin, a 2013 randomized controlled trial found a 6-fold difference in severe oral mucositis. The patients, enrolled between June 2007 and December 2010, received either a 660 nm diode laser at 100 mW delivering 1 J and 4 J/cm² or the placebo. The laser was applied in contact with the lips, the inside of the cheeks, the sides and underside of the tongue, and the floor of the mouth in 12-minute sessions over 39 days, and mucositis was graded on 2 systems, with quality of life measured by questionnaire. 6.4% of laser patients developed grade 3 or 4 mucositis against 40.5% of placebo patients. Quality-of-life scores after treatment also favored the laser group for physical and emotional functioning, fatigue, pain, swallowing, and eating in company.

Researchers in Iran evaluated low-power laser for preventing oral mucositis, dry mouth, and pain caused by chemotherapy in a 2013 randomized controlled trial of 24 adults treated between 2009 and 2010. The laser group received 630 nm light at 30 mW and 5 J/cm² to the lining of the mouth. The trial found that mucositis, dry mouth, and pain were all less severe in the laser group, across a range of cancers, with a statistically significant difference. The authors concluded that low-power laser might lessen the intensity of mucositis.

Whether the evidence for laser and other light therapies was strong enough to support clinical practice guidelines for oral mucositis was the question a 2013 review from the United States set out to answer. An international mucositis study group graded the evidence for each intervention in each cancer-treatment setting and issued a recommendation, a suggestion, or no guideline for each. The authors concluded with a new recommendation for low-level laser at 650 nm and 40 mW delivering 2 J/cm² in 2 seconds per point to prevent mucositis in adults receiving a stem cell transplant after high-dose chemotherapy, with or without whole-body radiation, and a new suggestion for low-level laser at around 632.8 nm to prevent mucositis in head and neck cancer patients receiving radiotherapy without chemotherapy. For other patient groups and other light sources, the evidence was too thin for any guideline, though it was described as generally encouraging.

In 2012, a randomized controlled trial in India tested preventive low-level laser therapy against a sham treatment for oral mucositis in 221 head and neck cancer patients receiving radiotherapy together with the chemotherapy drug cisplatin. 111 patients received helium-neon laser light at 632.8 nm and 24 mW, delivering 3 J per point and 36 to 40 J per session without touching the tissue, to the inside of the cheeks, the sides and underside of the tongue, the inside of the lips, the floor of the mouth, and the roof of the mouth, avoiding the cancer site, in 15- to 20-minute sessions 5 days a week for 45 days, and 110 received sham treatment daily before radiotherapy. Researchers found significantly fewer cases of severe mucositis in the laser group, along with less pain, less swallowing difficulty, and lower use of opioid painkillers. Neither patients, staff, nor assessors knew who received the active laser.

This 2012 review covered low-level energy laser and the other options for managing mucositis of the mouth and throat caused by radiotherapy, with or without chemotherapy, for head and neck cancer, alongside how the condition develops, who is most at risk, and how common it is. Management was described as still mostly supportive, resting on pain medication and nutritional support, and the laser studies covered wavelengths of 632.8 to 904 nm, 5 to 200 mW, and 1 to 100 mW/cm² in sessions of 10 to 100 seconds, 1 to 3 times a week. According to the review, several recent studies have shown low-level energy laser to be particularly useful in preventing and treating mucositis caused by chemotherapy and radiotherapy.

18 patients with oral mucositis from the chemotherapy drug 5-fluorouracil who received red laser, red plus infrared laser, or no laser showed the clearest gains with the combined lasers in a 2012 clinical trial in Brazil. The patients, 12 of them men, were split into 3 groups of 6 with median ages of 47.5, 62.5, and 53 years, and the laser groups received 660 nm red light, alone or followed by 780 nm infrared light, at 15 to 30 mW and 3.8 to 7.5 J/cm² in 10-second contact applications to the lining of the mouth once a day for 5 days while chemotherapy was running. 5 of 6 patients in the combined group had been limited to liquid or soft foods before treatment, and 5 of 6 were eating solid food afterward, a statistically significant change, whereas eating did not change in the no-laser group and the improvement with red light alone fell short of significance. Mucositis grades also appeared to fall with the combined lasers, and all laser-treated patients reported being satisfied with their mouths by the fourth and fifth days.

Researchers in 2012 tested a low-level helium-neon (He-Ne) laser against a sham treatment for preventing and treating oral mucositis in a randomized controlled trial of 121 mouth cancer patients in India receiving radiotherapy together with chemotherapy. 60 patients received He-Ne laser light at 632.8 nm, 24 mW, and 3.5 J/cm² to the lining of the mouth just before each of their 33 radiotherapy sessions over 6.5 weeks, alongside the chemotherapy drug cisplatin every 3 weeks, and 61 received sham treatment, with a blinded assessor grading mucositis, pain, and the need for feeding through a drip each week. 29% of laser patients developed severe mucositis against 89% of sham patients, severe pain affected 18% against 71%, opioid painkiller use 7% against 21%, and drip feeding 30% compared with 39%, each a statistically significant difference. The trial also found that severe mucositis and pain lasted less time in the laser group, and that only sham patients (9%) needed a break in their cancer treatment.

Red and infrared low-level laser therapy (LLLT) appeared equally able to lower the risk of oral mucositis, according to a 2012 meta-analysis of laser for mucositis caused by cancer therapy. The analysis drew on 33 articles identified in a systematic review, covering both inside-the-mouth and outside-the-mouth devices at 630 to 950 nm and 5 to 200 mW, usually applied at least 3 times a week. Risk of mucositis was lower with LLLT than without, its duration and severity were reduced, patients spent 4.38 fewer days with mucositis, and pain relief was measurable, with red light at 630 to 670 nm and infrared at 780 to 830 nm giving similar results. The authors concluded that there was moderate to strong evidence for LLLT as a well-tolerated and relatively cheap option, and recommended 10 to 100 mW diodes at 2 to 3 J/cm² for prevention and up to 4 J/cm² for treatment, applied to single spots daily, every other day, or at least 3 times a week until the sores resolve. No adverse side effects were reported.

Grade 2 mucositis took 13.5 days to appear with the higher of 2 laser doses against 9.8 days with the lower dose in a 2011 randomized controlled trial in Brazil of low-level laser therapy (LLLT) for preventing and treating radiation-induced mucositis. 70 patients with cancer of the mouth or throat were randomized to 660 nm light at either 15 mW and 3.8 J/cm² or 5 mW and 1.3 J/cm², applied to the lining of the mouth in 10-second applications, 5 days a week from the first day of radiotherapy over 7 weeks, with mucositis graded daily and weekly and pain self-rated daily before each application. Researchers found that the lower-dose group also had higher mucositis grades in weeks 2, 3, and 4 and reported more pain, with each of these differences statistically significant. LLLT during radiotherapy was concluded to be effective in controlling both mucositis and pain, with the higher dose doing better.

According to its authors, a 2011 review set out to summarize the evidence and clinical guidelines for preventing and treating oral mucositis caused by intensive anticancer treatment. The review covered low-energy laser phototherapy at 632.8 nm and 0.12 to 0.24 J/cm² given daily, alongside cold therapy with ice chips, an allopurinol mouthwash, a growth-factor drug, supplementary glutamine, radiation techniques that spare the mouth lining, pain control with morphine applied to the mouth, and general hygiene. Cold therapy with ice chips and low-energy laser phototherapy appeared useful as preventive measures, and the allopurinol mouthwash and laser phototherapy as treatment. Supplementary glutamine, the review said, should stay within research protocols.

Across 415 patients in 11 placebo-controlled trials, a 2011 meta-analysis from Norway pooled the effects of low-level laser therapy (LLLT) on preventing and treating oral mucositis caused by chemotherapy or radiotherapy in head and neck cancer patients. The trials used red and infrared lasers at 630 to 1064 nm and 10 to 100 mW, typically 3 times a week, and their quality was rated acceptable. According to the analysis, the risk of developing mucositis was significantly lower after LLLT than after placebo laser, the preventive effect grew stronger when only trials delivering more than 1 J were counted, patients with existing sores spent 4.38 fewer days at grade 2 or worse, and severity was lower as well. Every trial recorded possible side effects, and these did not differ from placebo.

Treating sores on the roof of the mouth and at the corners of the mouth with red light and a sore inside the nose with infrared light, a 2011 observational study in Brazil used laser phototherapy (LPT) for oral mucositis in 1 patient receiving radiotherapy after surgery to remove a mouth cancer that had grown into the upper jaw bone. The mouth sores were treated in contact with a 660 nm diode laser at 40 mW, giving 2.4 J/cm² per point and 14.4 J/cm² per session, the nose sore through the skin with a 780 nm laser at 70 mW giving 2.1 J/cm² per point and 6.3 J/cm² per session, and each nostril was treated with a single 2.4 J/cm² dose of the red laser, 3 times a week for 4 weeks. Radiotherapy went ahead without interruption, and the report found LPT effective against the mucositis. Long-term controlled trials would still be needed to set preventive and curative protocols.

Published in 2011, this observational study from Brazil reported on a child with oral mucositis caused by chemotherapy for acute lymphoblastic leukemia. The sores on the back of the roof of the mouth and the lining of the mouth were treated once a day with LED light at 630 nm, 100 mW, and 6 J/cm², held close to the tissue, for 10 days. The sores had cleared after 10 days of treatment. The authors concluded that LED therapy was effective in this case because it eased pain and sped up tissue repair.

Among 16 children with a mean age of 9.4 years who had developed chemotherapy-induced oral mucositis, a 2011 observational study tested low-level laser therapy for pain relief and wound healing. Every child was treated with a diode laser at 830 nm and 150 mW, with the energy adjusted to the severity of each sore across a range of 2 to 16 J/cm², repeated every 2 days until the sore healed, while pain was rated before and immediately after each treatment and any difficulty using the mouth was recorded. Researchers found that pain eased as soon as the light was applied, and that on average 2.5 treatments within a week were enough to heal a sore, with less energy needed for milder grades. Immediate pain relief and faster healing resolved those difficulties in every case.

57.1% of patients given low-level laser therapy (LLLT) developed no oral mucositis at all in a 2011 randomized controlled trial in Brazil of laser for preventing mucositis caused by the high-dose chemotherapy given before a stem cell transplant. 42 patients receiving either their own or donor cells were randomized to LLLT or a control group, with the laser group treated with a diode laser at 660 nm, 40 mW, and 4 J/cm² in 4-second contact applications to the lips, the inside of the cheeks, the sides and underside of the tongue, and the floor of the mouth, over 9 days. Only 4.8% of the control group stayed free of mucositis, while in the laser group 9.6% reached grade 1 and 33.3% grade 2. The trial found preventive LLLT to be a strong tool for lowering the rate of mucositis in transplant patients.

Comparing low-level laser therapy (LLLT) with the antacid aluminum hydroxide taken by mouth, a 2010 clinical trial in Brazil examined the prevention of oral mucositis in 25 patients receiving radiotherapy, with or without chemotherapy, for head and neck cancer. 12 patients received LLLT at 830 nm, 15 mW, and 12 J/cm² to the inside of the lower lip, the back of the roof of the mouth, the inside of the cheeks, the sides of the tongue, and the floor of the mouth before each radiotherapy session, 5 days a week for 35 days, and 13 patients took aluminum hydroxide 4 times a day throughout radiotherapy, including weekends. By the 13th radiotherapy session, self-rated pain was significantly lower in the laser group, and mucositis and pain scores stayed lower in that group across the course. Neither group needed a break in radiotherapy, and while both approaches appeared to reduce severe mucositis, LLLT seemed better at delaying its appearance.

72 patients with head and neck cancer took part in a 2010 clinical trial in Brazil of a 660 nm diode laser for preventing and treating oral mucositis caused by radiotherapy and chemotherapy. Half were assigned to a laser group and half to a control group, and the laser group received low-level laser therapy at 30 mW and 2 J per point in contact with the inside of the cheeks, the inside of the lower lip, the back of the roof of the mouth, under the tongue, and the tongue itself, twice a week for 7 weeks alongside their cancer treatment. Patients in the laser group mostly appeared to escape both mucositis and pain, while every patient in the control group developed mucositis of grade 1 to 3 with pain. The gap between the groups was statistically significant from week 1, widened until week 4, and held steady to week 7.

A 2009 randomized controlled trial in Brazil compared therapeutic laser plus a standard mouthwash against the mouthwash alone for preventing and treating oral mucositis in patients receiving a donor stem cell transplant after high-dose chemotherapy. 22 patients were split into 2 groups, with 12 receiving 2 diode lasers at 660 and 780 nm, 25 mW, and 6.3 J/cm² in 10-second applications over 15 days followed by the mouthwash, and 10 receiving the mouthwash only. Mucositis was less frequent in the laser group, and its average severity scores were lower on both of the grading systems used, with each of these differences reaching statistical significance. The authors concluded that laser reduced both the frequency and the severity of mucositis and could serve as a new form of prevention and treatment.

3 laser schedules were tested against each other in a 2009 randomized controlled trial of laser phototherapy (LPT) for oral mucositis in 39 patients receiving radiotherapy for head and neck cancer. 1 group received low-power laser 3 times a week, a second received a combined high-power and low-power laser 3 times a week, and a third received low-power laser once a week. The low-power light was a diode laser at 660 nm, 40 mW, 6 J/cm², and 0.24 J per point, and the high-power light was a diode laser at 808 nm and 1 W/cm², applied in contact with or close to the mouth lining over 7 to 14 days. According to the trial, every schedule held mucositis grades at the same level through to the last radiotherapy session, but only the 2 schedules given 3 times a week also kept pain levels steady. Patients treated once a week reported a significant rise in pain, and the combined high-power and low-power protocol lengthened healing time.

1 of 9 children treated with low-level laser therapy (LLLT) still had mouth sores 7 days after diagnosis, compared with 9 of 12 given a sham treatment, in a 2009 randomized controlled trial of chemotherapy-induced oral mucositis. The 21 children and adolescents, with a mean age of 8.2 years and 86% of them being treated for leukemia or lymphoma, were receiving chemotherapy or a stem cell transplant and entered the trial as soon as mucositis appeared, with the laser group receiving infrared light from a diode laser at 830 nm, 100 mW, and 4 J/cm² once a day for 5 days on top of routine mouth care. Mucositis lasted 5.8 days on average in the laser group and 8.9 days in the sham group, a statistically significant difference. The trial found that adding LLLT to mouth care could shorten chemotherapy-induced mucositis in children, and the authors suggested it as a first-line option.

Published in 2009, this observational study from Brazil described a 15-year-old girl whose severe oral mucositis from head and neck radiotherapy was treated with laser phototherapy (LPT). After surgery to remove a cancer of the upper jaw and roof of the mouth, she received 35 radiotherapy sessions and developed severe (grade 3) sores across the inside of the cheeks, the gums, the lips, the roof of the mouth, and the tongue, leaving her unable to move her tongue freely or eat solid food. Throughout radiotherapy, she received mouth-care guidance and LPT from a 660 nm diode laser at 40 mW, 6 J/cm², and 0.24 J per point in contact with the whole mouth, with a 1 W laser held away from the tissue over ulcerated areas only. Researchers found that pain and dry mouth eased after the first session, that she was pain-free after 5 sessions even though the sores were still grade 2, and that all sores had cleared after 17 sessions, restoring normal mouth function and her quality of life.

2009 brought an observational study from Brazil in which all 30 stem cell transplant patients were given daily laser phototherapy to the lining of the mouth, with the aim of describing how often and how badly oral mucositis developed. The patients, receiving either donor or their own cells, were treated once a day with a diode laser at 660 nm and 40 mW, delivering 4 or 6 J/cm², and their mucositis grade, mouth pain, and any adverse reactions were recorded. On the most critical days after transplant, days 5 and 8, 63.3% of patients had grade 1 mucositis and 33.3% grade 2, with no grade 3 or 4 cases in that window, while across the whole study 23.3% reached grade 3 and 3.3% grade 4. According to the study, these low grades pointed to a benefit of laser phototherapy, although randomized trials would be needed to confirm it.

0 episodes of oral mucositis across 5 chemotherapy cycles was the result recorded for 1 patient in a 2008 observational study of LED phototherapy for preventing chemotherapy-induced mouth sores. The patient, a 34-year-old man with Hodgkin's disease receiving a 4-drug chemotherapy regimen on days 1 and 15 of each cycle, was given infrared LED light inside the mouth at 880 nm, 74 mW, and 3.6 J/cm² in 60-second applications for 5 consecutive days from day 1 of each cycle, with mucositis graded and pain rated on days 1, 3, 7, 10, and 13 after chemotherapy. Mucositis never developed, and he reported no pain at any point. The authors concluded that LED therapy was safe and effective in this case, while noting that randomized studies with more patients would be needed to confirm the method.

Most chemotherapy cycles covered by preventive laser produced no mouth sores at all, according to a 2008 randomized controlled trial of low-level laser therapy for chemotherapy-induced oral mucositis in young patients in Brazil. 13 patients were involved across 32 chemotherapy cycles, with 22 cycles in patients free of mucositis randomized to preventive laser or placebo light, and 10 cycles in patients who already had mucositis treated with the laser, using 685 nm light at 35 mW delivering 72 J/cm² and 1 to 3 J per point, in 54-second sessions 3 times a week for 5 days, held in near contact with the cheeks, lips, floor of the mouth, tongue, roof of the mouth, and corners of the mouth. Only 27% of placebo cycles ended without mucositis, compared with 73% of preventive laser cycles, with another 18% at grade 1, a statistically significant difference. Patients treated for existing sores appeared to get marked pain relief and less severe mucositis even when their white blood cell counts were very low, and the authors concluded the therapy is feasible for young patients given its ease of use and high acceptance.

Comparing active low-energy laser (LEL) with sham illumination in patients who already had mild mouth sores, and testing it alone as prevention in patients with a history of severe sores, a 2008 randomized controlled trial from Belgium reported results from 2 studies of LEL for oral mucositis caused by chemotherapy or radiotherapy. The first study enrolled 26 patients with solid tumors who had all developed severe mucositis during an earlier identical course of chemotherapy, and the second randomized 36 patients with blood cancers on intensive chemotherapy to LEL or sham, using light at 630 to 670 nm, 2 J/cm², and 50 to 500 mW in 5-minute sessions over 3 days. The preventive treatment succeeded in 81% of patients, and treatment of existing sores succeeded in 83%, compared with 11% with sham, whose sores also reached grade 3 sooner. LEL was described as an effective and safe approach to preventing or treating mucositis from cancer chemotherapy.

A 2008 clinical trial evaluated a helium-neon (He-Ne) laser for preventing and treating radiation-induced oral mucositis in 24 hospitalized mouth cancer patients in India. The patients were assigned to a laser group or a control group, with the laser group receiving 632.8 nm light at 10 mW, 1.8 J/cm², and a pulse frequency of 10 Hz, first from a scanning device for 8 days and then from a handheld probe held in near contact with 6 sites in the mouth for 5 minutes each, over a 25-day course. Pain, difficulty with everyday mouth functions, and mucositis were rated on every treatment day and followed to the end of cancer treatment. The trial found that laser given during radiotherapy reduced the severity of mucositis, pain, and difficulty with everyday mouth functions.

Wavelengths of 650 and 780 nm were tested against a placebo in a 2007 randomized controlled trial of low-level laser therapy for preventing oral mucositis in patients having a stem cell transplant. 70 patients in the United States, given high-dose chemotherapy with or without radiation to prepare for the transplant, were assigned to a 650 nm laser group, a 780 nm laser group, or a placebo group, with the active groups receiving 2 J/cm² at 40 or 60 mW each day to the inside of the lower lip, both cheeks, the sides and underside of the tongue, and the floor of the mouth, from the first day of that preparation through 2 days after the transplant. Only the 650 nm wavelength appeared to reduce the severity of mucositis and pain, which were measured up to 21 days after transplant. The treatment was well tolerated, and no adverse events were noted, though the authors said further study was needed to establish the approach.

38 patients who received low-power laser therapy or no laser before a stem cell transplant showed sharply different rates of severe mucositis in a 2007 randomized controlled trial. The patients, receiving either their own or donor cells, were treated with a diode laser at 660 nm, 50 mW, and 4 J/cm² in contact with the inside of the cheeks, the whole surface of the tongue, the floor of the mouth, the roof of the mouth, and the lips, in sessions of about 4 minutes over 6 days. Researchers found that 94.7% of the laser group had mucositis no worse than grade 2, including 63.2% with grade 0 or 1, compared with 31.5% of the control group. Large ulcers of 9.1 to 18 cm² appeared in 5.3% of the laser group against 73.6% of controls, and the authors reported that upfront LPLT had become standard at their center.

50 patients with mouth cancer took part in a 2006 randomized controlled trial in India of low-level helium-neon (He-Ne) laser therapy for preventing and treating radiation-induced oral mucositis. All were receiving a curative radiotherapy dose of 66 Gy in 33 sessions over 6 weeks, and were split into a laser group of 25, treated with 632.8 nm light at 10 mW and 1.8 J/cm² to the lining of the mouth, and a control group of 25 given painkillers, numbing gels, and saline and antiseptic mouth rinses. According to the trial, pain scores and mucositis grades at the end of radiotherapy were both lower in the laser group, with a statistically significant difference. All patients tolerated the laser without any adverse effect or reaction.

Researchers in 2006 in a clinical trial tested light-emitting diode (LED) phototherapy for chemotherapy-induced oral mucositis in patients whose cancer had spread. 12 patients aged 34 to 82 at a center in Italy received non-laser LED light at 630 to 660 nm, 7.8 mW, 0.99 J/cm², and 2.34 J inside the mouth for 5 minutes, 3 times a day for 7 days, and were compared with a control group of 12 patients with similar sores who were not randomized. The healing rate, measured from a daily mucositis score, rose from 117% to 164%, and 7 of the LED-treated patients healed faster than the control group, the study reported. The authors described the treatment as safe and said the result needed confirming in a larger trial.

Across 2649 participants pooled from the studies it covered, a 2005 review from the United States weighed the strategies used to prevent and treat oral mucositis caused by chemotherapy and radiotherapy. Low-level laser therapy (LLLT) at 632.8 nm, in 30-minute sessions over 6 days, was among the approaches reviewed, alongside cold therapy for patients receiving the drug 5-fluorouracil and a long list of drugs and mouthwashes. Most of the drug options had produced conflicting, inconclusive, or limited results, and no single strategy was universally accepted. Laser therapy appeared useful for preventing mouth sores in patients having a stem cell transplant, as did cold therapy for patients given 5-fluorouracil. For sores that had already formed, care still focused mainly on easing symptoms.

According to a review published in 2005 in Belgium, researchers examined the evidence for low-level laser therapy (LLLT) in preventing and treating oral mucositis caused by chemotherapy or radiotherapy, a condition with no standard prevention or treatment. The review noted that an expert panel had found too little evidence to recommend most of the usual approaches, and that laser results were hard to compare because different operators used it differently and trials in the field are hard to run. The authors concluded that the evidence for LLLT reducing the severity of chemotherapy- or radiotherapy-associated mucositis was nonetheless substantial, even though controlled prevention studies remained few.

Measuring pain before and after every laser application, a 2005 clinical trial in Norway tested low-level laser therapy for pain relief in 13 adults who had developed moderate chemotherapy-induced oral mucositis. Each patient was treated over 5 days with a diode laser at 830 nm and 250 mW, delivering 35 J/cm² to the lining of the mouth. According to the trial, the daily average pain felt before and after each treatment fell by 67%, a statistically significant change. No control group could be formed because few patients had mucositis at the hospital, so the authors cautioned that a placebo effect could not be ruled out.

11 of 15 patients developed no mouth sores at all in a 2002 clinical trial in the United States of laser therapy for chemotherapy-induced oral mucositis. Every patient had previously had a severe (grade 3 or 4) episode of mucositis during 5-fluorouracil given by continuous drip, and all received standard mouth-care instructions. Laser therapy at 830 nm, 45 to 70 mW, and 0.7 to 0.8 J/cm² was applied 24 hours before chemotherapy and then weekly through the cycle, in sessions of 15 to 30 minutes, while a light-based probe measured blood flow in the lining of the mouth. Mucositis appeared to be both rarer and milder than before, with 3 patients reaching grade 1 or 2 and 1 patient grade 3 or 4, and blood flow in the lining of the mouth did not change. Patients tolerated the laser well and reported no added discomfort.

This 2001 review examined mucositis caused by chemotherapy and radiotherapy in head and neck cancer patients and the place of low-level laser therapy (LLLT) in preventing and treating it. The review, from France, covered treatment with 632.8 nm laser light at 20 to 100 mW and doses of 2 to 4 J/cm² applied to the lining of the mouth, against a background in which newer radiation schedules and combined chemotherapy were raising rates of mucositis. Few of the local or body-wide treatments available showed a real preventive effect, and LLLT stood out as the approach with the most promise for managing this side effect.

In 1999, a randomized controlled trial tested a low-energy helium-neon laser (LEL) against placebo light for preventing radiation-induced oral mucositis in 30 patients with cancer of the mouth or throat. The patients, treated in France, were receiving radiotherapy alone at 65 Gy over 7 weeks, and the LEL group received 632.8 nm light at 60 mW and 2 J/cm² to 9 points on the inside of the cheeks, the back of the roof of the mouth, and the back of the throat before each radiotherapy session. Researchers found that severe (grade 3) mucositis occurred at a rate of 7.6% with LEL against 35.2% without, and severe pain at 1.9% against 23.8%. Pain stayed lower in the laser group from week 2 to week 7 of treatment.

Researchers in France tested helium-neon laser therapy for preventing oral mucositis in a 1997 randomized controlled trial of 30 patients about to receive their own stem cells or bone marrow after high-dose chemotherapy and whole-body radiation. The laser group received 632.8 nm light at 60 mW and 1.5 J/cm² in contact with 5 sites on the lining of the mouth, in 10-second applications once a day for the 5 days before the transplant, and examiners checked their mouths daily for 20 days afterward. Cumulative mucositis scores were lower in the laser group, severe (grade 3) sores were fewer and shorter-lived, and patients reported less mouth pain, needed less morphine, and had less dry mouth and easier swallowing, though the need for feeding through a drip did not fall. Treatment was well tolerated and reduced mucositis, the authors concluded, though the best treatment schedule still had to be worked out.

A design that treated 1 side of the mouth with laser and sham-treated the other let each patient act as their own control in a 1995 randomized controlled trial of helium-neon laser for oral mucositis after bone marrow transplant. 20 patients in the United States received 632.8 nm light at 25 mW and 1 J/cm² in near contact with the inside of the cheeks and lips, the sides and underside of the tongue, the back of the roof of the mouth, and the floor of the mouth, in 40-second sessions, 5 times a week for 5 days. According to the trial, both mucositis severity and self-rated pain were lower on the treated side than on the sham side, with a statistically significant difference on both measures. Sores appeared on both sides in every patient, peaked around day 6, and cleared by day 21. Patients tolerated the treatment well.

43% of 53 chemotherapy cycles in a comparison group produced mouth sores in a 1992 observational study from France of helium-neon (He-Ne) laser therapy for mucositis caused by chemotherapy. Patients receiving combination chemotherapy that included the drug 5-fluorouracil were given He-Ne laser light at 632.8 nm, either to heal sores already present or to prevent them. The study found that preventive laser cut the rate of mouth complications to 6% across 101 chemotherapy cycles, and that curative laser shortened healing time and reduced how often the chemotherapy had to be changed. Every patient who received preventive laser completed cancer treatment on schedule, although the study noted that controlled trials would be needed to confirm the effect.

A 4-group design split 80 adult and child stem cell transplant patients first by regular or low risk and then by active or placebo light in a 2012 randomized controlled trial in the United States of near-infrared LED phototherapy applied from outside the mouth for the pain of oral mucositis. The active groups received 670 nm LED light at about 50 mW/cm² and 4 J/cm² to both cheeks and the front of the throat from 0.79 inches away for 80 seconds once a day from the day of transplant through day 14, while the placebo groups received the same procedure from an identical device giving under 5 mW/cm², and blinded assessors graded the mouth and recorded self-rated pain 3 times a week. Only the regular-risk patients given active light appeared to gain a statistically significant reduction in pain, seen at day 14 on 1 of the 3 grading systems used, against their placebo counterparts. Both active groups improved in almost every other measure, but those differences did not reach significance.

No clear reduction in severe oral mucositis followed preventive low-level laser (LLL) therapy in a 2012 randomized controlled trial in Brazil of 75 head and neck cancer patients receiving radiotherapy together with the chemotherapy drug cisplatin. 37 patients received LLL therapy from a diode laser at 660 nm, 10 mW, 2.5 J/cm², and 0.1 J in 10-second applications before each radiotherapy session, over a 60 to 70 Gy course, and the rest received a placebo laser, with the aim of reducing the rate of grade 3 or 4 mucositis from 80% to 50%. Severe mucositis affected 4 laser patients versus 5 placebo patients at week 2, 4 versus 12 at week 4, and 8 versus 9 at week 6, none of which reached statistical significance, and severe pain did not differ between the groups. According to the trial, LLL therapy did not reduce severe mucositis, although a small benefit could not be ruled out, and it did prevent breaks in radiotherapy, which 6 placebo patients needed and no laser patients did.

When researchers compared 24 stem cell transplant patients given preventive laser therapy with 25 earlier patients who had not received it, a 2007 observational study in Brazil found a later start and shorter course of oral mucositis. The laser group received 660 nm light at 10 mW and 2.5 J/cm² to the inside of the cheeks and lips, the tongue, and the floor of the mouth, in 10-second applications from the start of high-dose chemotherapy until 2 days after the transplant, and all 49 patients were examined daily for 30 days. Mucositis began on average 6.12 days after transplant with laser versus 4.36 days without, though every patient developed some degree of it, and mouth pain lasted 2.45 days instead of 5.64, while morphine use tended to fall. The difference in time to full healing, day 14 against day 25, was not statistically significant. The authors concluded that laser therapy could be useful for these patients but that randomized trials were needed to confirm its real effect.

Among 32 children receiving high-dose chemotherapy before a bone marrow transplant, a 2002 clinical trial in the United States tested near-infrared light from LEDs for preventing oral mucositis. Starting on the day of transplant, each child received 670 nm LED light at 56 mW/cm² held against the outside of the left cheek for 71 seconds once a day for 14 days, with a sham treatment on the right, while dentists graded the inside of the cheeks and the sides of the tongue and the children rated their mouth and throat pain. 53% of the children developed ulcerative mucositis, against an expected 70% to 90%, and pain in the left and right cheeks was 48% and 39% lower than throat pain around day 7. The trial found no difference between the treated and untreated sides in mucositis grade or pain, and more studies were called for.

No change in cancer survival or recurrence was observed after preventive photobiomodulation (PBM) for oral mucositis in a 2018 observational study of 152 patients with advanced mouth cancer in Brazil. The patients had received PBM at 660 nm, 40 mW, 1000 mW/cm², and 10 J/cm² in 10-second sessions, 5 per week over 5 days, to protect the lining of the mouth during radiotherapy, and were followed for an average of 40.84 months. Survival was 46.7%, and survival without the cancer returning was 51.8%, while 29.6% of patients saw the cancer come back near the original site, 6.57% saw it spread elsewhere, and 12.5% developed a new cancer. These figures appeared similar to published results for patients treated without PBM, so preventive PBM did not seem to change the course of the cancer.

Whether a low-energy laser could prevent oral mucositis in children with cancer was the question a 2007 randomized controlled trial in Brazil set out to answer. 60 patients aged 3 to 18 (mean 8.7), 65% of them boys, who were receiving chemotherapy or a stem cell transplant were split into a laser group of 29 and a control group of 31, with the laser group receiving 780 nm light at 60 mW and 4 J/cm² to the inside of the cheeks and lips, the edge of the tongue, the back of the roof of the mouth, and under the tongue for 5 days after chemotherapy began, while an examiner unaware of the allocation graded mucositis on days 1, 8, and 15. Both groups developed sores at similar rates, with 13 laser patients and 7 controls affected on day 8 and 13 against 11 on day 15, and the grades did not differ between groups on either day. The trial found no evidence that preventive laser helped when good dental and mouth care was already provided.