Eric Jadaud. ICO Paul papin, Service de radiothérapie. 2 rue moll. 49933 Angers Cedex 9. France
Low-level laser therapy: a standard of supportive care for cancer therapy-induced oral mucositis in head and neck cancer patients?
E Jadaud 1, RJ Bensadoun 2 1: Institut de Cancérologie de l’Ouest, Paul Papin, Service d’Oncologie Radiothérapie, 49933 Angers Cedex 9, France 2: Service d’Oncologie radiothérapique, CHU de Poitiers, BP 577, 86021 Poitiers Cedex, France
Background and aims: Oral mucositis (OM) is still a common and severe acute side-effect of many oncologic treatments, especially in patients treated for head and neck cancer. It may affect quality of life, require supportive care and impact treatment planning and its efficacy. Low-level laser therapy (LLLT) seems to promote pain relief and reduces OM incidence and its severity. It has been recommended for these patients as a treatment option but without any consensus in the LLLT procedure. New recommendations and perspectives for clinical trials will be discussed.
Materials (Subjects) and Methods: Step by step, the efficacy of soft laser in the management of iatrogenic oral mucositis has been evaluated during the last two decades. Its effectiveness and level of recommendation got stronger with time. We will report and discuss some major results and the latest recommendations published on this topic.
Results: The major clinical results have been reported and analysed last year in a first meta-analysis 1). 11 randomized placebo-controlled trials were selected with a total of 415 patients treated with chemotherapy and/or radiotherapy for head and neck cancer. The relative risk for developing OM was significantly reduced after LLLT but only for a dose between 1 to 6 Joules per point. Pain, severity and duration of OM grade ≥ 2 were also reduced without difference with placebo for possible side-effects. Nine years after the positive results published for patients treated by radiotherapy alone 2), a new French randomized, multicentric, phase III trial for patients treated with new standard treatment, using LLLT in accordance to recent recommendations is ongoing. Seven centers are specifically established for this trial which should include a hundred patients.
Conclusions: The very encouraging results of LLLT in the prevention and treatment of OM in patients treated by chemotherapy or radiotherapy for advanced head and neck cancer could soon be proposed as a new standard of care, according to the multinational Association of Supportive care in Cancer (MASCC) criteria. Modern lasers are less time consuming and extraoral applicators for a possible use by trained paramedical staff could be helpful to complete clinician practice. A preventive dose of 2 J/cm2 and a curative dose of 4 J/cm2 if using a red wavelength lasers are now recommended. Key words: low-level laser therapy, oral mucositis, radiation therapy, chemotherapy
Supportive Care in Cancer https://doi.org/10.1007/s00520-019-04890-2
Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines
Yehuda Zadik1,2 & Praveen R. Arany3 & Eduardo Rodrigues Fregnani4 & Paolo Bossi5 & Héliton Spindola Antunes 6 & René-Jean Bensadoun7 & Luiz Alcino Gueiros8 & Alessandra Majorana9 & Raj G. Nair10 & Vinisha Ranna11 & Wim J. E. Tissing12 & Anusha Vaddi13 & Rachel Lubart 14 & Cesar Augusto Migliorati15 & Rajesh V. Lalla16 & Karis Kin Fong Cheng17 & Sharon Elad13 & On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)
Received: 31 January 2019 /Accepted: 22 May 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract
Purpose To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM). Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible. Results Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1–2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration.
Conclusions The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is
Photomedicine and Laser Surgery Volume 33, Number 11, 2015 ª Mary Ann Liebert, Inc. Pp. 540–546 DOI: 10.1089/pho.2015.3954
Pilot Study on the Efficacy of Combined Intraoral and Extraoral Low-Level Laser Therapy for Prevention of Oral Mucositis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation
Marcos Soto, DDS, MSc,1 Rajesh V. Lalla, DDS, PhD,2 Roseane Vasconcelos Gouveia, MD,1 Victor Gattardello Zecchin, MD,1 Adriana Seber, MD, MSc,1 and Nilza Nelly Fontana Lopes, DDS, MSc, PhD3
Abstract
Objective and background data: Studies suggest that intraoral low-level laser therapy (LLLT) can ameliorate oral mucositis in adult patients receiving high-dose chemotherapy. The objective of this study was to evaluate the use of a combined protocol of intraoral and extraoral LLLT in children undergoing hematopoietic stem cell transplantation (HSCT).
Methods: Twelve children undergoing HSCT were treated four times a week with a combined protocol of intraoral and extraoral LLLT, for a mean duration of 22 days. Clinical and functional mucositis scores were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). These scores were compared with a matched retrospective control group of 12 children who did not receive LLLT during HSCT. Results: Clinical mucositis scores were significantly lower in the LLLT group than in the control group ( p = 0.004). Incidence of ulcerative oral mucositis was also significantly lower in the LLLT group ( p = 0.027). Functional limitation associated with diet/swallowing was less severe in the LLLT group; however, this was not statistically significant.
Conclusions: This study indicates that a combined protocol of intraoral and extraoral application of LLLT can reduce the severity of oral mucositis in pediatric patients undergoing HSCT. Randomized double-blind clinical trials with a larger number of subjects are needed to further test such combined protocols.
Photomedicine and Laser Surgery, Volume 31, Number 12, 2013
Low-Level Laser in Prevention and Treatment of Oral Mucositis in Pediatric Patients with Acute Lymphoblastic LeukemiaJurema Freire Lisboa de Castro, DDS, MSc, PhD,* Elizabeth Galamba Fernandes Abreu, DDS, MSc,1Andreza Veruska Lira Correia, DDS, MSc,* Catarina da Mota Vasconcelos Brasil, DDS, MSc,* Danyel Elias da Cruz Perez, DDS, MSc, PhD,* and Francisco de Paula Ramos Pedrosa, MD#
*Postgraduate Program in Dentistry, Oral Pathology Unit, Federal University of Pernambuco, Recife, Pernambuco,Brazil.
#Pediatric Oncology Department, Professor Fernando Figueira Integrated Medical Institute, Recife, Pernambuco,Brazil.
Address correspondence to: Andreza Veruska Lira Correia, Postgraduate Program in Dentistry, Oral Pathology Unit
ederal University of Pernambuco
Recife, Pernambuco
Brazil E-mail:
Objective: The aim of this study was to evaluate the influence of low-level laser therapy (LLLT) on the prevention and treatment of oral mucositis (OM) in pediatric cancer patients taking methotrexate.
Background data: OM is a very common, potentially severe side effect, caused by treatment with radiotherapy and chemotherapy for cancer.
Methods: Forty patients with acute lymphoblastic leukemia, who received high doses of methotrexate, were distributed into two groups. Group A (Preventive Group) was composed of patients who received preventive laser (red-subgroup A1 or infrared-subgroup A2) for 5 days, beginning on the 1st day of infusion. Group B (Treatment Group) was composed of patients who received laser treatment only if they developed post-chemotherapy mucositis (red-subgroup B1 or infrared-subgroup B2). Laser was used at wavelengths of 660�nm or 830�nm with output 100�mW, power density 3.57�W/cm2, spot size 0.028�cm2, energy of 1�J, resulting in an energy density of 35�J/cm2 for 10�sec in the prophylactic group, and energy of 2�J, resulting in energy density of 70�J/cm2 for 20�sec in the therapeutic group.
Results: The percentage of patients who did not develop OM was higher in Group A (60% vs. 25%). In Group B, 3/20 patients developed grade IV OM (15%), and a significant difference was found between the two subgroups at the end of treatment (p=0.019).
Conclusion: Prophylactic laser produced a better outcome than when patients did not receive any preventive intervention, and red laser (660 nm) was better than infrared (830�nm) in the prevention and treatment of OM.
Geisa Badauy Lauria Silva, D.D.S., M.Sc.,1 Elismauro Francisco Mendonc¸a, D.D.S., M.Sc., Ph.D.,2, Cesar Bariani, M.D.,1 Heliton Spindola Antunes, D.D.S., M.Sc.,3 and Maria Alves Garcia Silva, D.D.S., M.Sc., Ph.D.2
Abstract
Background data and Objective: Patients who have received high doses of chemotherapy, either alone or in combination with total body irradiation often cite oral mucositis (OM) as the most debilitating side effect. The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) on the prevention of conditioning-induced OM in hematopoietic stem cell transplantation (HSCT).
Methods: We randomized 42 patients who underwent autologous or allogeneic HSCT. A low-level InGaAlP diode laser was used, emitting light at 660 nm, 40mW, and 4 J/cm2. An evaluation of OM was carried out using the World Health Organization scale. Results and Conclusion: In the LLLT group, 57.1% of patients had an OM grade 0, 9.6% had grade 1, and 33.3% had grade 2, whereas in the control group, only 4.8% of patients were free of OM (grade 0).
Results: Our results indicate that the preventive use of LLLT in patients who have undergone HSCT is a powerful instrument in reducing OM incidence.
Fernanda de Paula Eduardo, D.D.S., M.S.D., Ph.D.,1 Leticia Bezinelli, D.D.S.,1, Ana Claudia Luiz, D.D.S., M.S.D.,1 Luciana Correa, D.D.S., M.S.D., Ph.D.,2, Cristina Vogel, R.N.,1 and Carlos de Paula Eduardo, D.D.S., M.S.D., Ph.D.3
Abstract
Background data and Objective: Oral mucositis (OM) is one of the worst cytotoxic effects of chemotherapy and radiotherapy in patients undergoing hematopoietic cell transplantation (HCT), and it causes severe morbidity.
Laser phototherapy has been considered as an alternative therapy for prevention and treatment of OM. The aim of this study was to describe the incidence and severity of OM in HCT patients subjected to laser phototherapy, and to discuss its effect on the oral mucosa.
Methods: Information concerning patient age and gender, type of basic disease, conditioning regimen, type of transplant, absence or presence of pain related to the oral cavity, OM grade, and adverse reactions or unusual events were collected from 30 patients undergoing HCT (allogeneic or autologous). These patients were given oral laser phototherapy with a InGaAIP laser (660 nm and 40 mW) daily. The data were tabulated and their frequency expressed as percentages.
Results: In the analysis of those with OM, it was observed that 33.4% exhibited grade I, 40% grade II, 23.3% grade III, and 3.3% grade IV disease. On the most critical post-HCT days (D_5 and D_8), it was observed that 63.3% of patients had grade I and 33.3% had grade II disease; no patients had grade III or IV disease in this period. This severity of OM was similar to that seen in other studies of laser phototherapy and OM.
Conclusion: The low grades of OM observed in this survey show the beneficial effects of laser phototherapy, but randomized clinical trials are necessary to confirm these findings.
Photomedicine and Laser Surgery, Volume 27, Number 1, 2009
Gholamreza Esmaeeli Djavid1, Amirhossein Emami2, Leila Ataie-Fashtami3, Seyed reza Safaeinodehi2, Farzad Merikh-Baiat4, Mohsen Fateh1, Nasrin Zand3, 1Photobiostimulation Research Group, Iranian Center for Medical Laser, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran
2Assistant Professor of Hematology and Oncology, Valiasr Hospital, Tehran University of Medical Sciences, Tehran, Iran, 3Assistant Professor of Dermatology, Iranian Center for Medical Laser, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran, 4Researcher, Tehran University of Medical Sciences, Tehran, Iran
Objective: Chemotherapy-induced oral mucositis (COM) is a common, debilitating complication of cancer therapy. The aims of this study were to evaluate the effect of low level laser therapy (LLLT) on prevention of COM in patients with hematologic malignancies.
Background data: OM is a very common, potentially severe side effect, caused by treatment with radiotherapy and chemotherapy for cancer.
Methods: Fifty-five patients hospitalized to undergo chemotherapy in Imam Hospital were included into the study. These patients were divided into two groups. The oral cavity of the patients were illuminated by continues laser beam using a GaAlAs laser device with wavelength of 630 nm, power output 30 mW, and dose of 5 J/cm2 for six days (LLLT group). The patients in the second group underwent placebo irradiation (power output equal to zero) with the similar protocol. The severity of the COM was clinically evaluated based on WHO grading scale. The patientys� quality of life was assessed before and after the intervention according to EORTC QLQ-C30 questionnaire.
Results: The incidence of COM in LLLT group (31%) was less than the placebo group (41%). Mean duration of COM healing was 4.8 and 12 days in LLLT and placebo groups, respectively (p=0.03). Xereostomia was significantly less severe in LLLT group in comparison with the placebo group (p=0.007).
Conclusion: Our findings showed that LLLT significantly reduced the incidence of oral mucositis of WHO grade 3 and 4 as the most debilitating form of oral mucositis, in which oral alimentation is impossible. Also, LLLT could reduce duration of oral mucositis, decreased the risk of secondary infection, and accelerated return to normal nutrition.
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, Triana Carla Junqueira Zanin, D.D.S., M.S., Ph.D.,4 and Aldo Brugnera Junior, D.D.S., M.S., Ph.D.3
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; n¼36) and a laser group (L; n¼36). Laser therapy was performed in combination with radiotherapy and chemotherapy twice a week using a diode laser (l¼660 nm, power¼30mW, spot size¼2 mm, energy¼2 J 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.
Photomedicine and Laser Surgery, Volume 28, Number 2, 2010
Geisa Badauy Lauria Silva, D.D.S., M.Sc.,1 Elismauro Francisco Mendonc¸a, D.D.S., M.Sc., Ph.D.,2, Cesar Bariani, M.D.,1 Heliton Spindola Antunes, D.D.S., M.Sc.,3 and Maria Alves Garcia Silva, D.D.S., M.Sc., Ph.D.2
Background data and Objective: Patients who have received high doses of chemotherapy, either alone or in combination with total body irradiation often cite oral mucositis (OM) as the most debilitating side effect. The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) on the prevention of conditioning-induced OM in hematopoietic stem cell transplantation (HSCT).
Methods: We randomized 42 patients who underwent autologous or allogeneic HSCT. A low-level InGaAlP diode laser was used, emitting light at 660 nm, 40mW, and 4 J/cm2. An evaluation of OM was carried out using the World Health Organization scale.
Results: Our results indicate that the preventive use of LLLT in patients who have undergone HSCT is a powerful instrument in reducing OM incidence.
Conclusion: In the LLLT group, 57.1% of patients had an OM grade 0, 9.6% had grade 1, and 33.3% had grade 2, whereas in the control group, only 4.8% of patients were free of OM (grade 0).
Photomedicine and Laser Surgery, +Volume 29, Number 1, 2011
René-Jean Bensadoun, M.D. , Professor and Chairman, Radiation Oncology Department, CHU de Poitiers, Address: BP 577, 86021 - Poitiers Cedex, France , E-mail:
Abstract: We discuss the promising state of the art of Photomedicine for preventative and therapeutic usage in Oral Mucositis (OM) due to cancer therapy.
Recent findings: Photomedicine using LLLT or LED is very effective with intra-oral and extra-oral devices in the management of OM, based on several reports including randomised control studies. A systematic review identified 33 relevant articles which were subjected to meta-analysis based on which laser parameters in routine practice are being defined. Meta-analysis showed that LLLT reduced risk of OM with relative risk (RR) 2.45 (CI 1.85-3.18), reduced duration, severity of OM and reduced number of days with OM (4.38 days, p=0.0009). Relative risk was similar between the red (630-670 nm) and infrared (780-830 nm) LLLT. Pain-relieving effect based on the Cohen scale was at 1.22 (CI 0.19-2,25).
Conclusion: There is moderate to strong evidence in favour of Photomedicine at optimal doses as a safe, relatively inexpensive intervention for cancer therapy-induced OM. It is envisaged that Photomedicine will soon become part of routine oral supportive care in cancer.
Laser in medicine, vol I, issue 1, October 2012
Objective: The aim of this study was to evaluate the usefulness of low-level laser therapy (LLLT) for the control of painful stomatitis in patients with hand-foot-and-mouth disease (HFMD).
Background data: LLLT has been successfully applied to various painful oral mucosal diseases, although there have been few reports on LLLT for HFMD patients.
Methods: Through a randomized double-blind placebo controlled trial, the painful period of HFMD stomatitis was compared between the LLLT group (n=11) and the placebo LLLT one (n=9), which had similar clinical backgrounds. The LLLT parameters supplied were as follows: wavelength of 830 nm, power of 30 mW, frequency of 30 Hz, and energy output of 1.1 J/cm2. Acceptability and safety of the treatment were also evaluated.
Results: The painful period was shorter in the LLLT group (4.0 +/- 1.3 days) than in the placebo LLLT one (6.7 +/- 1.6 days) with a statistically significant difference (p<0.005). The treatment was judged acceptable for 90.0% (18 of 20) of patients. No adverse events were observed in any cases.
Conclusion: LLLT is a useful method to control HFMD stomatitis by shortening the painful period, with its high acceptability and lack of adverse events.
Alyne Simo�es, D.D.S., Ph.D.,1 Luana de Campos, D.D.S.,1 Douglas Nesadal de Souza,1
Jonas Alencar de Matos, D.D.S.,1 Patricia Moreira Freitas, D.D.S., M.S., Ph.D.,2 and Jose Nicolau, D.D.S., Ph.D.1
Abstract: The common consequences of radiotherapy (RT) to the head and neck are oral mucositis, xerostomia, and severe pain. The aim of this study was to verify how laser phototherapy (LPT) used for oral mucositis could influence xerostomia symptoms and hyposalivation of patients undergiong RT. Patients were divided into two groups:
12 individuals receiving three laser irradiations per week (G1) and 10 patients receiving one laser irradiation per week (G2). A diode laser (660 nm, 6 J=cm2, 0.24 J, 40mW) was used until completely healing of the lesions or the end of the RT. At the first and last laser sessions, whole resting and stimulated saliva were collected, and questionnaires were administered. According to Wilcoxon and Student statistical test, xerostomia for G1 was lower than for G2 ( p<0.05), and salivary flow rate was no different before and after RT, except for stimulated collection of G2, which was lower (p<0.05).
Our results suggest that LPT can be beneficial as an auxiliary therapy for hypofunction of salivary glands.
Photomedicine and Laser Surgery, Volume 28, Number 3, 2010
