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Use of 660-nm Diode Laser in the Prevention and Treatment of Human Oral Mucositis Induced by Radiotherapy and Chemotherapy

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The aim of this multidisciplinary study was to evaluate quantitatively and qualitatively the effect of a 660-nm diode laser in the prevention and treatment of human oral mucositis (OM) in patients suffering from head and neck cancer who had undergone radiotherapy and chemotherapy. OM is a severe oral lesion resulting from the toxic effects of treatment for cancer in the head and neck region. Low-level laser therapy is indicated to prevent and treat this oral complication and may be used alone or in association with conventional drug treatment, producing pain relief and wound repair. This study included 72 patients with head and neck cancer treated at the Cancer Hospital of Mato-Grosso, Brazil, and divided into a control group (C; n = 36) and a laser group (L; n = 36). Laser therapy was performed in combination with radiotherapy and chemotherapy twice a week using a diode laser (lambda = 660 nm, power = 30 mW, spot size = 2 mm, energy = 2 J per point). Statistically significant differences were observed between the two groups. Patients in group L usually did not present with OM or pain, but all patients in group C presented with OM ranging from Level I to III associated with pain. This difference was significant from week 1 on, increased until week 4 and remained stable up to week 7. Laser therapy was effective in preventing and treating oral effects induced by radiotherapy and chemotherapy, thus improving the patient's quality of life.
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Use of 660-nm Diode Laser in the Prevention
and Treatment of Human Oral Mucositis Induced
by Radiotherapy and Chemotherapy
Taı´s Zanin, D.D.S., M.S.,
1,2
Fatima Zanin, D.D.S., M.S., Ph.D.,
3
Artur Aburad Carvalhosa, D.D.S., Ph.D.,
2
Paulo Henrique de Souza Castro, D.D.S.,
2
Marcos Tadeu Pacheco, Ph.D.,
3
Iriana Carla Junqueira Zanin, D.D.S., M.S., Ph.D.,
4
and Aldo Brugnera Junior, D.D.S., M.S., Ph.D.
3
Abstract
Objective: The aim of this multidisciplinary study was to evaluate quantitatively and qualitatively the effect of a
660-nm diode laser in the prevention and treatment of human oral mucositis (OM) in patients suffering from
head and neck cancer who had undergone radiotherapy and chemotherapy. Background Data: OM is a severe
oral lesion resulting from the toxic effects of treatment for cancer in the head and neck region. Low-level laser
therapy is indicated to prevent and treat this oral complication and may be used alone or in association with
conventional drug treatment, producing pain relief and wound repair. Methods: This study included 72 patients
with head and neck cancer treated at the Cancer Hospital of Mato-Grosso, Brazil, and divided into a control
group (C; n ¼36) and a laser group (L; n ¼36). Laser therapy was performed in combination with radiotherapy
and chemotherapy twice a week using a diode laser (l¼660 nm, power ¼30 mW, spot size ¼2 mm, energy ¼2J
per point). Results: Statistically significant differences were observed between the two groups. Patients in group
L usually did not present with OM or pain, but all patients in group C presented with OM ranging from Level I
to III associated with pain. This difference was significant from week 1 on, increased until week 4 and remained
stable up to week 7. Conclusion: Laser therapy was effective in preventing and treating oral effects induced by
radiotherapy and chemotherapy, thus improving the patient’s quality of life.
Introduction
Oral mucositis (OM) is an inflammatory response of the
oral mucosa against the action of antineoplastic drugs
and ionizing radiation used in treating head and neck cancer.
1
It is characterized by hyperemia, edema, ulceration, pain,
sialorrhea, a burning feeling, and sometimes hemorrhage and
secondary infection, causing much suffering to the patient.
Conventional treatments are ineffective at controlling the
clinical problems caused by mucositis, which may include
deglutition, food ingestion, and speech, further decreasing the
patient’s quality of life.
1–3
OM results from radiation-induced mitotic death of the
mucosal epithelium basal cells, usually approximately 2 weeks
after the beginning of radiotherapy, when an irradiation dose
of approximately 2,000 cGy is used. OM is dose-limiting and
may lead to interruption or alteration of treatment, interfer-
ing with disease prognosis.
4–6
The use of both radiotherapy and chemotherapy highly
increases the incidence of OM, accounting for 80% to 100% of
cases. Forty percent of all patients undergoing chemotherapy
will develop some level of mucositis, the incidence being
even higher when associated with radiotherapy,
5
although
previous evaluation of buccal condition and follow-up by a
multidisciplinary team during cancer treatment may mini-
mize damage caused to buccal tissues.
7,8
The use of laser therapy has proved to decrease OM in-
tensity in patients undergoing radiotherapy and chemother-
apy, as an associated therapy or as an isolated therapy.
9,10
Additionally, preventive laser therapy is advisable because
it can trigger a sequence of tissue reactions linked to cellu-
lar homeostasis, resulting in cellular metabolic rate increase,
1
Photobiology and Lasertherapy Center, Vale do Paraı
´ba University, Sa
˜o Jose dos Campos, SP, Brazil.
2
Stomatology and Bucomaxillofacial Surgery Service, Cancer Hospital of Mato-Grosso, Cuiaba
´, MT, Brazil.
3
Biomedical Engineer Research Group, Camilo Castelo Branco University, Sa
˜o Jose dos Campos, SP, Brazil.
4
Microbiology and Immunology Laboratory, Federal University of Ceara
´, Sobral, CE, Brazil.
Photomedicine and Laser Surgery
Volume 28, Number 2, 2010
ªMary Ann Liebert, Inc.
Pp. 233–237
DOI: 10.1089=pho.2008.2242
233
higher collagen synthesis, DNA and RNA production and
beneficial effects on the immune system.
9
Also, laser therapy seems to increase the formation of
capillaries, the liberation of growth factors, and leukocyte
activity, which in turn inhibit or reduce the toxic effect of
radiotherapy and chemotherapy. The objective of this study
was to evaluate prospectively, quantitatively, and qualita-
tively the effect of diode laser (l¼660 nm, power ¼30 mW,
energy ¼2 J per point) in the prevention and treatment of
OM in patients suffering from head and neck cancer un-
dergoing radiotherapy and chemotherapy.
Materials and Methods
Ethical aspects
This research was performed in compliance with resolu-
tion 196=96 of the National Health Counsel of Brazil and was
submitted to the Ethics Committee of the Cancer Hospital of
Mato-Grosso and of the Vale do Paraiba University. In-
formed consent was obtained in accordance with the De-
claration of Helsinki.
Inclusion criteria
The criteria for inclusion in the study were aged 18 and
older, oral mucous intact on the first day of the experiment,
and capacity to cooperate with the treatment. Patients must
also have signed informed consent.
Exclusion criteria
Patients who did not meet the inclusion criteria, patients
who were receiving drugs for the treatment or prevention of
mucositis, and patients who the authors did not previously
evaluate and release were excluded from this study.
Characterization of sample
A multidisciplinary team of dentists, physicians, physical
therapists, dieticians, speech therapists, and psychologists
conducted this clinical study. Volunteer patients of both
sexes (60 men and 12 women), with no distinction of race or
social class and aged 34 to 80 were selected. All volunteers
had head and neck cancer and underwent radiotherapy and
chemotherapy. Seventy-two individuals fulfilled the study
requirements and were divided into two groups: one that
received laser treatment (L; 31 men, 5 women) and a control
group that did not receive laser treatment (C; 29 men, 7
women). Data about location, type, and clinical stage of
cancer were collected.
Data collection
The first contact with patients was an interview in which
they signed the ‘‘Term of Consent and Clarification,’’ which
guaranteed their anonymity. All volunteers were submitted
to adequacy of buccal cavity before receiving treatment.
Following the Cancer Hospital of Mato-Grosso protocol, all
adult patients with head and neck epidermoid cancer re-
ceived weekly sessions of chemotherapy (including cisplatin
70 mg=m
2
and a radioisotope) plus daily sessions of radia-
tion (medium daily dose of 1.8gy) except on weekends and
holidays. During radiotherapy sessions, teeth were protected
with a silicone tray containing neutral fluoride gel to protect
the enamel from radiation, avoiding demineralization once
xerostomy and inclination for infection were inevitable.
Data were collected through daily physical intraoral ex-
amination, and evaluation of OM was made according to the
association of three criteria: National Cancer Institute (NCI)
criteria, Brown scale to evaluate the incidence of OM, and the
Visual Analog Pain Scale (VAS).
Laser application
A trained technician, who performed the procedure
following standard techniques, performed laser irradiation.
For laser therapy, a diode laser (aluminium gallium in-
dium phosphide; Bio Wave-Kondortech, Sa
˜o Carlos, Brazil,
l¼660 nm, power ¼30 mW, spot size ¼2 mm, continuous
mode) was used. Energy used was at 2 J per point or scat-
tering on the affected area with 1 cm
2
per application point.
The affected area received irradiation in different points in
contact mode. Irradiated regions were as follows: three
points on jugal mucosa, three points on inferior lip internal
mucosa, three points on soft palate, two points on palatine
folds, two points on sublingual caruncles, and five points on
the tongue. Applications were done twice weekly, before or
after radiotherapy sessions.
Statistical analysis
Analysis of variance with a significance level of 0.05 was
performed considering the group effect (with and without
laser) and the moment effect (day 1 and weeks 1, 2, 3, 4, 5, 6,
and 7) for the three criteria used (NCI, Brown, and VAS). In
the case of significance of group or moment effect, multiple
comparisons of minimal squares were used to identify the
difference between the variables.
Results
Profile of patients
The location of cancer in the patients and its distribution
in the C and L groups are described in Table 1. Of the 72
Table 1. Overview of Cancer Location
in Experimental Groups
n (%)
Lesion
location Control group Laser group Total
Cervical lymph nodes 0 (0.0) 3 (8.3) 3 (8.3)
Gingiva 0 (0.0) 1 (2.7) 1 (2.7)
Jugal mucosa 2 (5.5) 0 (0.0) 2 (5.5)
Larynx 5 (13.9) 5 (13.9) 10 (27.8)
Lingual floor 1 (2.7) 1 (2.7) 2 (5.4)
Lips 2 (5.5) 1 (2.7) 3 (8.2)
Mandible 0 (0.0) 1 (2.7) 1 (2.7)
Maxilla 1 (2.7) 0 (0.0) 1 (2.7)
Nasopharynx 2 (5.5) 0 (0.0) 2 (5.5)
Nose 1 (2.7) 2 (5.5) 3 (8.2)
Oropharynx 5 (13.9) 3 (8.3) 8 (22.2)
Palate 3 (8.3) 4 (11.1) 7 (19.4)
Salivary glands 2 (5.5) 2 (5.5) 4 (11.0)
Tongue 7 (19.4) 11 (30.5) 18 (49.9)
Tonsils 3 (8.3) 2 (5.5) 5 (13.8)
Vocal cords 2 (5.5) 0 (0.0) 2 (5.5)
234 ZANIN ET AL.
patients analyzed in this study, 61.2% had clinical Stage IV,
17.2% had clinical Stage III, 20.4% had clinical Stage II, and
1.2% had clinical Stage I of the disease; 86.6% of the patients
underwnet surgery for tumor removal during or after this
study.
OM evaluation according to the NCI scale
The results of evaluation according to the NCI scale can be
found in Figure 1. Comparing the two groups, statistically
significant differences were observed from the first week on
(p <0.001). Patients in group L did not present differences in
the oral aspect during the experiment (p ¼0.41) with an in-
crease in the NCI scale results being observed during week 4
(p ¼0.01) and returning to normal the following week. All
patients in group C had OM levels varying from I to III on
the NCI scale. This difference was significant from week 1 on
(p <0.001), increased until week 4 and then remained stable
up to week 7 of the cancer treatment (p ¼0.68).
OM measurement according to the Brown scale
Differences in OM results between the two groups was
also significant when the Brown scale was used (p <0.001).
The absence of significant differences with the Brown scale
results found in group L during the experimental period
(p ¼0.42) suggests that laser therapy was successful in pre-
venting and controlling OM lesions. In the control group,
OM incidence increased from week 1 until week 4 (p
0.001), remaining stable up to week 7 (p ¼0.17), with mod-
erate to severe OM lesions being observed (Fig. 2).
Pain evaluation according to the VAS
The VAS results can be found in Figure 3. As previously
described, comparing the groups, statistically significant
differences were observed from the first week on (p ¼0.02).
Also, according to the VAS, patients in group C presented
increasing indexes of pain from weeks 1 to 4 (p ¼0.008),
remaining constant to week 7 (p ¼0.44), whereas patients in
group L reported absence of pain during the entire cancer
treatment (p ¼0.05).
Comparative analysis of NCI and Brown scales
Figure 4 illustrates the comparative analysis between the
NCI and Brown scales, in which the agreement between the
OM evaluation and measurement results found in this study
can be observed (p <0.001).
Discussion
The quality of life of patients with cancer has long been
discussed. Moreover, the treatment of head and neck cancer
is mutilating, and the effects of radiotherapy and chemo-
therapy are unpleasant. Tadiobiological or toxic products
cause radiotherapy-induced mucosal lesions associated with
cancer treatments. Thus, the diverse microbiota living in the
mouth can lead to development of infection caused by bac-
teria, fungi, and viruses from indigenous microbiota.
11
Laser therapy is based on nonthermal mechanisms (18C)
of light on biological tissues, and its use in the preven-
tion and treatment of mucositis induced by antineoplastic
FIG. 1. Oral mucositis evaluation accord-
ing to the National Cancer Institute (NCI)
scale during the experimental period.
FIG. 2. Oral mucositis evaluation mea-
surement according to the Brown scale
during the experimental period.
USE OF DIODE LASER IN ORAL MUCOSITIS 235
treatment has presented promising results, especially in
clinical studies.
12–15
First, we determined irradiation parameters and energy of
2 J per point. Bensadoun
16
analyzed the use of helium-neon
(He-Ne) laser in the prevention of radiotherapy-induced OM
in 30 patients in a prospective randomized manner. Our
study had a larger number of patients (n ¼84), and qualita-
tive and prospective analyses with detailed procedures were
performed. Also, calculation of energy per point in the area
of irradiated tissue is more appropriate for laser therapy
calculations when there is scattering of light in the tissue.
17
Because of decreasing immunity and increasing OM as a
result of cancer treatment, some patients in group C under-
going radiotherapy associated with chemotherapy had the
antineoplastic treatment temporarily suspended. This did
not occur in group L. Although Lopes
8
provided daily laser
applications during radiotherapy, the authors suggested
that, in the future, three weekly sessions should be provided.
In this study, two weekly applications were performed
because of the difficulties of volunteers in returning more
frequently for laser treatment.
While studying the beneficial effects of laser therapy as a
prophylactic treatment method, many authors have per-
formed studies with patients likely to develop OM, such as
those undergoing conditioning for bone marrow transplant
and radiotherapy and chemotherapy for head and neck
tumors.
1,3,9,18,19
Similarly, statistical data in our studys
showed that patients receving laser treatment in association
with radiotherapy and chemotherapy had a lower incidence
of OM and pain.
Bensadoun
14
and Lopes
8
evaluated the prophylactic ap-
plication of laser and observed that a decrease in OM was
significant. In this study, laser was also applied preventively,
because laser irradiation started at the beginning of radio-
therapy and chemotherapy. Results obtained were positively
significant (p <0.05), corroborating the above-mentioned
findings.
Thus, Lopes
8
observed that, in the group treated with ra-
diotherapy and laser, all patients completed the planned ra-
diotherapy treatment, whereas in the untreated group, 13.8%
of patients had to interrupt their treatments because of de-
creased immunity provoked by secondary asthenia and de-
glutition difficulties. This observation is in agreement with
Balakirev et al.,
3
who concluded that interruption time to treat
complications resulting from radiotherapy and chemother-
apy in pediatric patients was reduced up to two times in the
group receiving laser therapy. Our results are in agreement
with Lopes
8
and Balakirev et al.,
3
because in group C, 15
patients needed to interrupt radiotherapy treatment, whereas
in group L, no patients interrupted radiotherapy or chemo-
therapy sessions.
The results obtained in this study and in literature reviews
showed the improvement in the quality of life of patients
with cancer receiving laser therapy in association with ra-
diotherapy and chemotherapy. OM, pain, dysphonia, and
dysphagia were minimized with laser therapy. Thus, benefits
and improvement in quality of life observed in patients re-
ceiving laser therapy justify the adoption of this therapy
associated with conventional cancer treatment.
Conclusion
A 660-nm diode laser, within the parameters used in this
study, was effective in the prevention and treatment of OM in
FIG. 3. Pain evaluation according to the
Visual Analog Pain Scale during the exper-
imental period.
FIG. 4. Comparative analysis of oral mu-
cositis evaluation (NCI scale) and measure-
ment of lesion (Brown Scale) observed in
this study (p 0.001).
236 ZANIN ET AL.
patients undergiong radiotherapy and chemotherapy treat-
ment, providing them more comfort and a better quality of
life.
Author Disclosure Statement
No competing financial interests exist.
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Address correspondence to:
Aldo Brugnera Junior, D.D.S., M.S., Ph.D.
Rua Groenla
ˆndia, 183
Jardim Paulista
01434–000 Sa
˜o Paulo, SP
Brazil
E-mail: brugnera@globo.com
USE OF DIODE LASER IN ORAL MUCOSITIS 237
... The PBM is recommended for the prevention and treatment of OM in patients receiving cancer treatments. Several studies have demonstrated the effectiveness of anti-inflammatory effects in supporting tissue repair [13,33,[37][38][39][40][41][42][43][44][45]. Nevertheless, clinical evidence still shows that some patients present recurring episodes of OM during their cancer therapy despite being treated with LLLT [37]. ...
Article
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Oral mucositis (OM) is a painful condition caused by chemotherapeutic or radiotherapeutic cancer treatments, occurring in patients with different tumour characteristics and locations. OM greatly impacts a patient’s quality of life and cancer recovery. Current OM management strategies are not providing sufficient prevention and treatment; new approaches to injury management are needed. Studies on the benefit of omega-3 free fatty acids (FFA) in human health have increased significantly in recent years. FFA properties have been studied extensively, including their potential therapeutic use in inflammatory conditions. However, omega-3 FFA’s use as a supplementary treatment for OM has not been clinically tested. Preliminary evidence suggests that utilising FFA to manage OM could be a useful strategy for lesion management, assisting with healthy oral mucosa recovery. This review will describe the incidence, risk factors, biology of OM and the current treatment strategies, leading to a discussion of the utility of omega-3 FFA as a novel therapeutic agent for OM.
... LLLT was first used particularly in the care of cancer patients who developed radio-and/or chemotherapy-induced oral mucositis during their treatment. This treatment promoted pain relief in these patients, which significantly decreased the use of opioid analgesics and accelerated the wound healing process, reducing hospitalizations and the interruption of antineoplastic treatment (2)(3)(4)(5)(6)(7)(8). ...
... Photobiomodulation with LEDs has been proposed as a safe and low-cost alternative tool for the prevention of OM with features similar to those of low-level laser therapy (LLLT) [11,12](artigo SCC). The present study evaluated the e cacy of LEDs for the prevention and treatment of oral mucositis in pediatric patients receiving high doses of MTX, and identi ed laboratory parameters that act as risk factors for the development of OM. ...
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Purpose The present, retrospective cohort study evaluated the efficacy of photobiomodulation (PBM) with LEDs to prevent and treat oral mucositis (OM) in pediatric patients receiving high doses of MTX, and the relationship of the occurrence of OM with laboratory parameters as possible risk factors for the development of OM. Methods The medical records of children who received high doses of MTX (> 2g/m²) and photobiomodulation with LEDs were reviewed. Development of OM, hepatic and renal function, hemogram, delayed MTX excretion, febrile neutropenia were analyzed. Results Only 28 cases of OM were observed in the 358 cycles of high-dose MTX analyzed. Oral mucositis was associated with low levels of hemoglobin (p < 0.0001), hematocrits (p < 0.0001), ALT (p < 0.0001), and AST (p = 0.002). The risk of developing OM was associated with AST (OR 7.24; 95%CI 2.56–20.45), urea (OR 6.95; 95%CI 1.49–32.42), hemoglobin (OR 6.04; 95%CI 2.33–15.64), and febrile neutropenia (OR 4.41; 95%CI 2.89–15.73). This risk increases when these parameters are associated. Conclusion The low incidence of mucositis, compared with the literature, indicates that PBM can prevent and reduce the severity of OM, as well as hospitalization time. The risk of OM development is associated with febrile neutropenia, hematological, and kidney and liver toxicity, with the risk increasing when these factors are associated.
... The frequency and different properties of the laser are resolved principally by the organization of a functioning medium, which can be a gas, a gem, or a strong state semiconductor. [29] investigated that Laser therapy was performed in combination with radiotherapy and chemotherapy twice a week using a diode laser (660 nm, power 30 mW., spot size 2 mm, energy 2 J per point) on 36 patient of laser group with head and neck cancer concluded that laser therapy is effective in mucositis of patient under the treatment of cancer. Shoheir Shehata et. ...
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The efficacy of low-energy helium-neon and copper vapor lasers for prevention and treatment of postoperative and irradiation complications was assessed in 195 patients with locally advanced tumors of the head and neck. The control group included 118 patients. Intravenous laser irradiation of the blood was associated with a higher percentage of wound healing by first intention and better course of the postoperative period. Laser treatment of skin irradiation fields was shown to improve skin tolerance to the neutron beam. The study failed to establish tumor growth stimulation by the laser irradiation in terms of recurrence and metastasis development. The data obtained showed low-energy laser irradiation to offer promise for prevention and treatment of postoperative and irradiation complications.
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Oral mucositis is a common complication of bone marrow transplantation (BMT) conditioning therapy. Sequelae consist of increased risk for infection, moderate to severe pain, compromised oral function, and bleeding. This study investigated helium-neon laser treatment for prevention of conditioning-induced oral mucositis in BMT patients. Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed. Twenty patients received laser radiation to their oral mucosa, either left or right of midline. The contralateral side was sham-treated and served as a control. Mucositis severity was scored independently by two modified versions of the Oral Mucositis Index Scale (OMI-A and OMI-B) and the Eastern Cooperative Oncology Group (ECOG) Oral Toxicity Scale; pain severity was scored by subjects on a visual analogue scale (VAS). Cumulative scores were analyzed for differences between the laser-treated and sham-treated sides. Oral mucositis and pain scores were significantly lower for the treated versus the untreated side by OMI-A and B (P < 0.005) and VAS (P = 0.027) criteria, respectively. Ulcerative lesions occurred in all patients bilaterally; severity increased until Day +6, and lesions resolved by Day +21. Mucositis was more severe for patients conditioned with busulfan/carboplatin/thiotepa than for patients conditioned with busulfan/cyclophosphamide/etoposide. Helium-neon laser treatment was well-tolerated and reduced the severity of conditioning-induced oral mucositis in BMT patients.
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