Skip to main content
Download PDF
  • Systematic Review
  • Open access
  • Published:

Photobiomodulation therapy on chemo- and radiotherapy induced oral conditions: an umbrella review

BMC Oral Health volume 24, Article number: 1106 (2024) Cite this article

Abstract

Objectives

Photobiomodulation (PBM) is a laser-based therapy used to promote tissue repair, reduce inflammation and pain, and has been extensively studied in chemo- and radiotherapy-induced oral mucositis (OM). This review examines the level of evidence of systematic reviews (SRs) that have investigated PBM in such cases of OM.

Materials and methods

SRs evaluating PBM for both the treatment and prevention of OM in patients undergoing chemotherapy and/or radiotherapy and published before November 30, 2023, on PubMed, Cochrane, Embase, Web of Science, LILACS, TRIP and Open Grey databases were eligible for inclusion. We assessed the level of methodological and meta-analytic procedures.

Results

Of the 1201 SRs, 21 that met the inclusion criteria were included. The quality of evidence was assessed using the Assessing the Measurement Tool to Assess Systematic Reviews (AMSTAR2), and the majority was of critically low quality (n = 15, 71.4%) with only 28.5% of low quality. A total of 40 meta-analytic estimates were obtained and analyzed. Approximately 87.5% of the meta-analysis were significant (n = 33), but only one meta-analyses had a strength of “highly suggestive”, while the rest were classified as “weak”. When analyzing the overlap values, the covered area was 12.14% and the corrected covered area was 7.75%, indicating a moderate overlap. Only 4 SRs had a very high overlap and one had a high overlap.

Conclusion

The efficacy of PBM in the treatment of chemotherapy-induced OM is supported by low to critically low quality SRs and meta-analysis of low strength. This review highlights important areas that need to be addressed in future research on this topic.

Registration

CRD42023484013 (PROSPERO).

Peer Review reports

Introduction

Characterized as a debilitating condition of the oral epithelium, oral mucositis (OM) is one of the most common toxic side effects of chemo- and radiotherapy, affecting up to 90% of patients undergoing these treatments [1, 2]. OM results in extremely painful erythematous/ulcerative lesions on non-keratinised mucosa, such as the tongue, buccal mucosa, oropharynx, and lips, which can prevent oral intake. Not only does it have a negative impact on the patient’s quality of life, but in cases of severe OM there is an increased risk of local and systemic infection and, a reduction or delay in antineoplastic treatment, which may have a worrying impact on prognosis, and an increase in the cost of patient management. [3,4,5].

Furthermore, OM is associated with increased mortality in patients undergoing haematopoietic cell transplantation (HCT) (also known as haematopoietic stem cell transplantation). Despite its potentially devastating consequences, OM remains a significant challenge for patients undergoing cancer therapy, and therefore the management of OM is critical to the well-being of oncology patients. [4, 6].

Several interventions are currently available to prevent, relieve or alleviate the symptoms of OM, but their effectiveness remains uncertain. Basic oral care, anti-inflammatory agents, analgesics, photobiomodulation (PBM) and cryotherapy are the most common options [7]. PBM, also known as Low Level Laser Therapy (LLLT), is a non-invasive and non-thermal treatment that involves the application of low-level light sources of a specific wavelength to injured areas over a period of time to promote tissue repair and reduce inflammation and pain [8, 9]. The mechanism remains unclear, but evidence suggests that PBM acts on mitochondrial cytochrome C oxidase (CCO), which activates secondary signalling pathways leading to increased levels of ATP, cAMP and reactive oxygen species (ROS), promoting tissue regeneration [8, 9].

PBM has extensive applications in the prevention and treatment of OM in cancer patients undergoing various treatments. PBM is effective in preventing and treating OM in patients undergoing cancer treatment, such as high-dose chemotherapy for haematopoietic stem cell transplantation (HSCT) and radiotherapy for head and neck (H&N) cancer without concurrent chemotherapy (CT) [7]. In a recent guideline update, prevention of OM with intraoral PBM therapy was recommended in patients undergoing HSCT or in patients receiving H&N radiotherapy with or without CT [10].

Although many studies have evaluated the efficacy of PBM in the prevention and treatment of OM in cancer patients, the quality of these studies is variable and there is no consensus on laser parameters such as wavelength, power, amount and rate of energy delivered to the tissue, and time [7, 11]. Another explanation for ambiguous recommendations is the wide variety of protocols that can be applied, which exacerbates the lack of agreement on laser parameters and leads to different outcomes [12].

Therefore, we conducted an umbrella review to assess the level of evidence from systematic reviews (SRs) and meta-analysis that have examined PBMs the effect on the prevention and treatment of OM in patients undergoing CT and/or radiotherapy. Our objective was to offer an extensive overview of the current evidence and to pinpoint crucial elements that warrant enhancement in future investigations.

Materials and methods

We report this umbrella review upon the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline updated in 2020 [13]. The review protocol was approved a priori by all authors. The protocol was defined and discussed a priori with all authors and registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the following reference: CRD42023484013.

The review question was: “What is the level of evidence for the efficacy of PBM for chemo- and or/radiotherapy induced OM?”

The following PICO(S) statements were specified: Population (P) - cancer patients undergoing chemo- and/or radiotherapy with OM; Intervention (I) - PBM; Comparison (C) - placebo or related therapy; Outcome (O) - level of methodological and meta-analytic evidence of SRs; Setting (S) - SRs with or without meta-analysis.

2.1. Eligibility criteria

The following eligibility criteria were considered in the selection process: (1) the study must be a systematic review or a meta-analysis, (2) the data must be sourced from human studies, and (3) the study must examine the effectiveness of PBM in addressing chemo- and/or radiotherapy oral conditions. No restrictions on publication year or language were imposed.

2.2. Information sources search

Seven electronic databases were searched: Medline (via PubMed), Web of Science, EMBASE (The Excerpta Medica Database), LILACS (Latin-American scientific literature in health sciences), Cochrane Database of Systematic Reviews, CINAHL, and TRIP (Turning Research Into Practise). Grey literature was searched on https://opengrey.eu/. We merged keywords and subject headings in accordance with the thesaurus of each database and applied exploded subject headings, with the following syntax: (chemotherapy-induced OR chemotherapy) AND laser.

2.3. Study selection

IR and JB independently screened the titles and abstracts of the research papers. The level of agreement between the reviewers was assessed using kappa statistics. Any paper identified as potentially eligible by either reviewer was ordered for full-text review, which was also independently screened by the reviewers. Any disagreements that arose were resolved by discussion with a third reviewer, CZ.

2.4. Data extraction process and data items

Two researchers, IR and JB independently extracted authors and year of publication, objective/focal question, databases searched, number of studies included, type of studies included, main outcomes and main conclusions. Disagreements were resolved by discussion with a third reviewer, CZ.

2.5. Methodological quality appraisal

Two researchers (IR and JB) used the Assessing the Measurement Tool to Assess Systematic Reviews (AMSTAR 2) to evaluate the methodological quality of the reviews included in the present study. The AMSTAR 2 tool is a 16-item assessment that determines the overall confidence in the results of the review [14]. The quality of the SRs was rated based on the AMSTAR guidelines as follows: High quality meant “Zero or one non-critical weakness,” Moderate quality meant “More than one non-critical weakness,” Low quality meant “One critical flaw with or without non-critical weaknesses,” and Critically Low quality meant “More than one critical flaw with or without non-critical weaknesses.” The AMSTAR 2 online tool (https://amstar.ca/Amstar_Checklist.php, accessed in November 2023) was used to calculate the AMSTAR quality rate for each study.

2.6. Strength and validity of meta-analytic estimates

Data were processed and managed using Excel from MS Office 365. To assess the strength of meta-analytic estimates, according to Papadimitrou et al. [15], four levels of evidence have been defined: strong, very suggestive, suggestive and weak. [15, 16] (Table 1):

Table 1 Categorization of meta-analytical estimates
Full size table

The fail-safe number (FSN) for statistically significant meta-analysis was then determined using Rosenberg’s FSN method [20]. Subsequently, the median and range were calculated for each evidence grade (strong, highly suggestive, suggestive, and weak). If the FSN is small in comparison to the actual number of studies, it suggests that the results derived from the observed studies are not reliable due to publication bias, specifically the type of bias assumed by the method (i.e., a set of studies with null results is missing).

2.7. Overlap

Overlaps are identified as fundamental in well-done surveys, and this can be done comprehensively using the Corrected Covered Area (CCA) method. [21]. For this reason, we estimated CCA as percentages and categorised as per Pieper et al. [21]: 0–5 indicates low overlap, 6–10 moderate overlap, 11–15 high overlap, and > 15 very high overlap. A pairwise CCA grid was built in Microsoft Excel to identify which combinations of paired reviews had the highest overlap [21].

Results

3.1. Study selection

After a search of databases, a total of 1201 articles were retrieved for our search. Following removal of duplicates (n = 141), a total of 1060 records were screened for eligibility criteria using titles and abstracts, and 984 were excluded after title and/or abstract screening. Of the 76 articles assessed for eligibility for full paper review, 55 were excluded, with reasons for exclusion detailed in Supplementary Data 1. A final number of 21 SRs [12, 22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42] were therefore included in the qualitative synthesis. The PRISMA diagram is shown in Fig. 1.

Fig. 1
figure 1

PRISMA flowchart. Flow diagram visually summarising the screening and selection processes, and the numbers of articles recorded at each different stage

Full size image

3.2. Studies characteristics

Overall, these SRs were mainly produced in Brazil (n = 8) [12, 23, 25, 27, 31, 36, 42], China (n = 2) [26, 34] and the United Kingdom (n = 2) [33, 37], with contributions from groups in Canada [24], Iran [28], Israel [29], Indonesia [39], Malaysia [35], Norway [22], Singapore [40], Spain [38] and Syria [41] (Table 2). The populations included in the SRs were adults and children, with five reviews evaluating both. The type of cancer was heterogeneous, some studies didn’t specify the type of cancer, while others included more than one, such as head and neck and haematological cancers. The majority followed the PRISMA (n = 14) [24,25,26,27, 30, 31, 33, 35,36,37,38,39,40,41].

In terms of risk of bias (RoB), the Cochrane ROB tool (n = 9) [24, 26, 27, 30, 33, 37, 39, 40, 42], the Jadad scale (n = 4) [22, 23, 28, 34], the Cochrane ROB2 tool (n = 4) [31, 35, 36, 41], the PEDro scale (n = 1) [25] and the Critical Appraisal Skills Program Español (CASPe) checklist (n = 1) [38] were used, although one was not reported [12] and another was not assessed [29].

3.3. Methodological quality

When analysing the inter-rater reliability of the AMSTAR 2, good agreement was found (Cohen kappa score = 0.82; 95% confidence interval (CI): 0.78–0.86). None of the SRs were of high or moderate methodological quality. The majority were of critically low quality (n = 15, 71.4%) and only 28.5% were of low quality (Table 3). The included meta-analyses predominantly failed to report the sources of funding for the studies included in the review (n = 21, 95.5%), to explain the selection of study designs for inclusion in the review (n = 20, 90.9%), to provide a list of excluded studies and the reasons for the exclusions (n = 19, 86. 4%), to consider RoB in individual studies when interpreting and discussing the results of the review (n = 14, 63.6%), to use a comprehensive literature search strategy (n = 13, 59.1%), and to assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis (n = 13, 86.7%, considering that 7 SRs did not perform meta-analysis).

3.4 Meta-analytic estimates of strength, validity and overlap

Of the 21 SRs, 15 conducted meta-analysis (71.4.1%) [22,23,24,25,26,27,28, 30, 31, 34,35,36,37, 40, 42]. A total of 40 meta-analytic estimates were obtained and analysed. Overall, 27 meta-analyses used ratio measures (16 risk ratio and 11 odds ratio) and 13 difference measures (7 standardised mean difference [22, 26, 40] and 6 mean difference [22, 26,27,28, 36]). About 87.5% of the meta-analyses were significant (n = 33), but only one meta-analysis had a strength of “highly suggestive” [34], while the rest were classified as “weak”. The highly suggestive meta-analysis included 1190 participants, while the median number of participants in the meta-analysis classified as weak was 258 (ranging from 55 to 1035).

Analysing the overlap values, the covered area was 12.14% and the corrected covered area was 7.75%, indicating moderate overlap. We then examined the pairwise CCA grid to determine which combinations of paired reviews had the highest overlap (Fig. 2). Overall, the level of overlap between SRs was not significant, with only 4 having very high overlap and one having high overlap.

Fig. 2
figure 2

Overlap diagram in percentage (%) according to each included SR and year (Green cells indicate low overlap, yellow cells indicate moderate overlap, orange cells indicate high overlap and red cells indicate very high overlap)

Full size image

Among the meta-analyses with weak evidence, the FSN was higher than the number of studies included in 20.0% of the meta-analyses (n = 8), which means that the statistical significance of the summary estimates is very unlikely to change if more studies are added in the future.

Table 2 Characteristics of the included systematic reviews
Full size table
Table 3 Methodological quality assessment using AMSTAR2
Full size table

Discussion

Summary of main findings

This is the first umbrella review to comprehensively evaluate the level evidence of SRs of PBMs effect on the prevention and treatment of OM in patients undergoing CT and/or radiotherapy. We identify 21 SRs suggesting key factors that can inform and improve future research on the effect of PBM on patients with OM secondary to chemo- and radiotherapy. Although a significant number of SRs were included, both the methodological and meta-analytic domains show low consistency and validity, respectively.

AMSTAR 2, overlapping and meta-analytic appraisal

The AMSTAR tool has been designed to critically assess the quality of SRs, taking into account their critical and non-critical weaknesses [14]. Of the 16 domains evaluated in AMSTAR 2, domains 3 (Did the review authors explain their selection of study designs for inclusion in the review? ), 7 (Did the review authors provide a list of excluded studies and justify the exclusions? ) and 10 (Did the review authors report the sources of funding for the studies included in the review? ) were not addressed in more than 85% of the included SRs. Regarding domain 3, 90.5% of the SRs didn’t specify the followed search strategy, with the included studies and justifications [14]. Concerning domain 7, 85.7% of the SRs didn’t provide a list of excluded items with the corresponding reasons, thus increasing bias. [14]. in domain 10, 95.2% of the included trials did not report the source of funding, which is of great concern, as reporting the source of funding is important because commercially funded trials are known to be more likely to produce results in favour of the sponsoring product than independently funded trials [14]. Given the limitations and potential biases present in these studies, the validity and reliability of their findings may be called into question.

The overlap interpretation also showed worrying results due to low percentiles (Fig. 2). A large number of SRs are published each year and duplication of reviews on similar topics is common, and overlap may occur if they include one or more identical primary studies, such as RCTs [21]. Hence, it was expected that reviews published in the same year would have a high overlap, since they would have included the same studies, however, this isn’t in line with our findings. For example, two SRs, Zadik et al. (2019) and Cronshaw et al. (2020), had an overlap of 19.7%, which was the higher value obtained, while de Lima et al. (2020) and Heiskanen et al. (2020) had an overlap of 0.0%, as mentioned above. This leads us to believe that there might be a lack of consistency in the search strategy, which we also came across in the AMSTAR assessment.

The meta-analytic results go in line with the scarcity of quality evidence. Regarding the number of participants, only one study included more than 1000 participants, being the only “Highly suggestive” [34] whereas the remaining had a median number of 258 participants and were classified as “Weak”. This concern suggests that RCTs are failing in terms of numbers of participants and that their conclusions are not robust. Another important aspect to consider is the potential for bias in heterogeneity statistics, also due to small meta-analysis. It’s important to assess the homogeneity and heterogeneity of a trial because we can predict whether or not the effect of a particular treatment will be similar when applied to new people [44]. However heterogeneity is difficult to predict, especially in small meta-analyses [44] as presented in our results. Hence, larger studies of intervention, as RCTs, need to be conducted to have more predictable and reliable results.

Implications for practice and research

The findings of the analysis reveal considerable disparities in the quality of evidence, as the bulk of the studies incorporated were assessed as critically low and low. The results of this study align with those of a recent umbrella review [45], and raise doubts about the methodological proficiency of the groups responsible for the SRs and the quality of their review procedures.

Although the included studies have concluded that PBM is effective in reducing pain and severe OM, this can be questioned by the low quality of the included studies as we have identified. This is a major concern not only in clinical practice, where there’s a lack of robust evidence to support treatment outcomes, but also in research, where existing SRs are not rigorous, and the methodology is unreliable.

PBMs have been suggested by several authors to have a long-term carcinogenic effect, although long-term follow-up studies of patients treated with PBMs for OM prevention have not shown an increase in cancer recurrence. [10, 29, 46,47,48]. Hence, it’s crucial that the clinician informs the patient of the potential risks of PBM.

In addition, many of the included SRs mention the absence of guidelines and the need to define laser parameters [24, 29, 33, 34, 36, 37, 42]. RCTs are conducted according to their own protocol and do not have standardised parameters, which increases the variability of results. There is therefore an urgent need for more high-quality evidence that follows the latest guidelines and works to improve them so that patients receive the safest and most effective treatment.

Strengths and limitations

This umbrella review followed a strict protocol and the most recent tools available to evaluate the quality evidence of the included studies enhancing the trustworthiness of our findings.

There are limitations to this umbrella review that are worth mentioning. The fact that an overview synthesizes the results and conclusions of SRs, it does not provide an analysis of the primary studies included, preventing any conclusion regarding primary data. Yet, upon examining the meta-analytical strength, two significant constraints hinder the attainment of higher validity ranks: the low number of participants (< 1000 participants) and the bias potential of heterogeneity statistic due to small meta-analyses [44]. As such, the number of studies available contain still a very low number to provide more robust meta-analytical consistency and for this reason, this umbrella review support the need for larger studies of intervention, preferably randomized trials.

Conclusion

The level of evidence for the efficacy of PBM in chemo- and radiotherapy-induced oral conditions is constituted by SRs with inconsistent methodological quality, and the meta-analytical strength of which is low. This umbrella review underscores the salient aspects that warrant improvement in subsequent primary and secondary research pertaining to this subject matter.

Availability of data and materials

All data and materials are fully displayed in the manuscript or the studies included in this systematic review.

References

  1. Elad S, Yarom N, Zadik Y, Kuten-Shorrer M, Sonis ST. The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies. CA Cancer J Clin. 2022;72:57–77. https://doi.org/10.3322/caac.21704.

    Article  PubMed  Google Scholar 

  2. Brown TJ, Gupta A. Management of Cancer Therapy-Associated oral mucositis. JCO Oncol Pract. 2020;16:103–9. https://doi.org/10.1200/JOP.19.00652.

    Article  PubMed  Google Scholar 

  3. Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98:1531–9. https://doi.org/10.1002/cncr.11671.

    Article  PubMed  Google Scholar 

  4. Pulito C, Cristaudo A, Porta CL, Zapperi S, Blandino G, Morrone A, et al. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res. 2020;39:210. https://doi.org/10.1186/s13046-020-01715-7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Villa A, Sonis ST. Pharmacotherapy for the management of cancer regimen-related oral mucositis. Expert Opin Pharmacother. 2016;17:1801–7. https://doi.org/10.1080/14656566.2016.1217993.

    Article  CAS  PubMed  Google Scholar 

  6. Bruno JS, Al-Qadami GH, Laheij AMGA, Bossi P, Fregnani ER, Wardill HR. From pathogenesis to intervention: the importance of the Microbiome in oral Mucositis. Int J Mol Sci. 2023;24:8274. https://doi.org/10.3390/ijms24098274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120:1453–61. https://doi.org/10.1002/cncr.28592.

    Article  PubMed  Google Scholar 

  8. de Freitas LF, Hamblin MR. Proposed mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE J Sel Top Quantum Electron Publ IEEE Lasers Electro-Opt Soc. 2016;22:7000417. https://doi.org/10.1109/JSTQE.2016.2561201.

    Article  CAS  Google Scholar 

  9. Courtois E, Bouleftour W, Guy J-B, Louati S, Bensadoun R-J, Rodriguez-Lafrasse C, et al. Mechanisms of PhotoBioModulation (PBM) focused on oral mucositis prevention and treatment: a scoping review. BMC Oral Health. 2021;21:220. https://doi.org/10.1186/s12903-021-01574-4.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020;126:4423–31. https://doi.org/10.1002/cncr.33100.

    Article  PubMed  Google Scholar 

  11. Schubert MM, Eduardo FP, Guthrie KA, Franquin J-C, Bensadoun R-JJ, Migliorati CA, et al. A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Support Care Cancer. 2007;15:1145–54. https://doi.org/10.1007/s00520-007-0238-7.

    Article  PubMed  Google Scholar 

  12. Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL, For the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO), et al. Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:333–41. https://doi.org/10.1007/s00520-012-1605-6.

  13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10:89. https://doi.org/10.1186/s13643-021-01626-4.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;j4008. https://doi.org/10.1136/bmj.j4008.

  15. Papadimitriou N, Markozannes G, Kanellopoulou A, Critselis E, Alhardan S, Karafousia V, et al. An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites. Nat Commun. 2021;12:4579. https://doi.org/10.1038/s41467-021-24861-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bellou V, Belbasis L, Tzoulaki I, Evangelou E. Risk factors for type 2 diabetes mellitus: an exposure-wide umbrella review of meta-analyses. PLoS ONE. 2018;13:e0194127. https://doi.org/10.1371/journal.pone.0194127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ioannidis JPA, Tarone R, McLaughlin JK. The false-positive to false-negative ratio in epidemiologic studies. Epidemiology. 2011;22:450–6. https://doi.org/10.1097/EDE.0b013e31821b506e.

    Article  PubMed  Google Scholar 

  18. Johnson VE. Revised standards for statistical evidence. Proc Natl Acad Sci. 2013;110:19313–7. https://doi.org/10.1073/pnas.1313476110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sterne JAC. Sifting the evidence—what’s wrong with significance tests? Another comment on the role of statistical methods. BMJ. 2001;322:226–31. https://doi.org/10.1136/bmj.322.7280.226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rosenberg MS. The file-drawer problem revisited: a general weighted method for calculating fail-safe numbers in meta-analysis. Evol Int J Org Evol. 2005;59:464–8.

    Google Scholar 

  21. Lunny C, Pieper D, Thabet P, Kanji S. Managing overlap of primary study results across systematic reviews: practical considerations for authors of overviews of reviews. BMC Med Res Methodol. 2021;21:140. https://doi.org/10.1186/s12874-021-01269-y.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bjordal JM, Bensadoun R-J, Tunèr J, Frigo L, Gjerde K, Lopes-Martins RA. A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis. Support Care Cancer. 2011;19:1069–77. https://doi.org/10.1007/s00520-011-1202-0.

    Article  PubMed  Google Scholar 

  23. Figueiredo ALP, Lins L, Cattony AC, Falcão AFP. Laser terapia no controle da mucosite oral: um estudo de metanálise. Rev Assoc Médica Bras. 2013;59:467–74. https://doi.org/10.1016/j.ramb.2013.08.003.

    Article  Google Scholar 

  24. Oberoi S, Zamperlini–Netto G, Beyene J, Treister NS, Sung L. Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and Meta-analysis. PLoS ONE. 2014;9:e107418. https://doi.org/10.1371/journal.pone.0107418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Carneiro-Neto J, de-Menezes J, Moura L, Massucato E, de-Andrade C. Protocols for management of oral complications of chemotherapy and/or radiotherapy for oral cancer: systematic review and meta-analysis current. Med Oral Patol Oral Cir Bucal. 2016;0(0). https://doi.org/10.4317/medoral.21314.

  26. He M, Zhang B, Shen N, Wu N, Sun J. A systematic review and meta-analysis of the effect of low-level laser therapy (LLLT) on chemotherapy-induced oral mucositis in pediatric and young patients. Eur J Pediatr. 2018;177:7–17. https://doi.org/10.1007/s00431-017-3043-4.

    Article  PubMed  Google Scholar 

  27. Anschau F, Webster J, Capra MEZ, De Azeredo Da Silva ALF, Stein AT. Efficacy of low-level laser for treatment of cancer oral mucositis: a systematic review and meta-analysis. Lasers Med Sci. 2019;34:1053–62. https://doi.org/10.1007/s10103-019-02722-7.

    Article  PubMed  Google Scholar 

  28. Mazhari F, Shirazi AS, Shabzendehdar M. Management of oral mucositis in pediatric patients receiving cancer therapy: a systematic review and meta-analysis. Pediatr Blood Cancer. 2019;66:e27403. https://doi.org/10.1002/pbc.27403.

    Article  PubMed  Google Scholar 

  29. On behalf of The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO), Zadik Y, Arany PR, Fregnani ER, Bossi P, Antunes HS, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27:3969–83. https://doi.org/10.1007/s00520-019-04890-2.

    Article  Google Scholar 

  30. De Lima VHS, De Oliveira-Neto OB, Da Hora Sales PH, Da Silva Torres T, De Lima FJC. Effectiveness of low-level laser therapy for oral mucositis prevention in patients undergoing chemoradiotherapy for the treatment of head and neck cancer: a systematic review and meta-analysis. Oral Oncol. 2020;102:104524. https://doi.org/10.1016/j.oraloncology.2019.104524.

    Article  CAS  PubMed  Google Scholar 

  31. Campos TM, Do Prado Tavares Silva CA, Sobral APT, Sobral SS, Rodrigues MFSD, Bussadori SK, et al. Photobiomodulation in oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis followed by a cost-effectiveness analysis. Support Care Cancer. 2020;28:5649–59. https://doi.org/10.1007/s00520-020-05613-8.

    Article  PubMed  Google Scholar 

  32. Heiskanen V, Zadik Y, Elad S. Photobiomodulation Therapy for Cancer Treatment-related salivary gland dysfunction: a systematic review. Photobiomodulation Photomed Laser Surg. 2020;38:340–7. https://doi.org/10.1089/photob.2019.4767.

    Article  Google Scholar 

  33. Cronshaw M, Parker S, Anagnostaki E, Mylona V, Lynch E, Grootveld M. Photobiomodulation and oral mucositis: a systematic review. Dent J. 2020;8:87. https://doi.org/10.3390/dj8030087.

    Article  Google Scholar 

  34. Peng J, Shi Y, Wang J, Wang F, Dan H, Xu H, et al. Low-level laser therapy in the prevention and treatment of oral mucositis: a systematic review and meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020;130:387–e3979. https://doi.org/10.1016/j.oooo.2020.05.014.

    Article  PubMed  Google Scholar 

  35. Al-Rudayni AHM, Gopinath D, Maharajan MK, Veettil SK, Menon RK. Efficacy of Photobiomodulation in the treatment of Cancer Chemotherapy-Induced oral mucositis: a Meta-analysis with Trial Sequential Analysis. Int J Environ Res Public Health. 2021;18:7418. https://doi.org/10.3390/ijerph18147418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. De Oliveira AB, Ferrisse TM, Basso FG, Fontana CR, Giro EMA, Brighenti FL. A systematic review and meta-analysis of the effect of photodynamic therapy for the treatment of oral mucositis. Photodiagnosis Photodyn Ther. 2021;34:102316. https://doi.org/10.1016/j.pdpdt.2021.102316.

    Article  CAS  PubMed  Google Scholar 

  37. Redman MG, Harris K, Phillips BS. Low-level laser therapy for oral mucositis in children with cancer. Arch Dis Child. 2022;107:128–33. https://doi.org/10.1136/archdischild-2020-321216.

    Article  PubMed  Google Scholar 

  38. Sánchez-Martos R, Lamdaoui W, Arias-Herrera S. Therapeutic outcomes of Photobiomodulation in Cancer Treatment-induced oral mucositis: a systematic review. J Clin Exp Dent. 2023;e749–59. https://doi.org/10.4317/jced.60710.

  39. Danwiek J, Amtha R, Gunardi I. Management of oral mucositis: a systematic review. Minerva Dent Oral Sci. 2023;72. https://doi.org/10.23736/S2724-6329.23.04695-8.

  40. Chan X, Tay L, Yap SJ, Wu VX, Klainin-Yobas P. Effectiveness of photobiomodulation and oral cryotherapy on oral Mucositis among patients undergoing Chemotherapy Conditioning prior to hematological stem cell transplantation. Semin Oncol Nurs. 2023;39:151405. https://doi.org/10.1016/j.soncn.2023.151405.

    Article  PubMed  Google Scholar 

  41. Khalil M, Hamadah O, Saifo M. Preconditioning with Photobiomodulation as an effective method in preventing Chemotherapy-Induced oral mucositis: a systematic review. Photobiomodulation Photomed Laser Surg. 2023;41:597–607. https://doi.org/10.1089/photob.2023.0075.

    Article  CAS  Google Scholar 

  42. Cruz AR, Minicucci EM, Betini M, Almeida-Lopes L, Tieghi Neto V, Cataneo AJM. Efficacy of photobiomodulation in the treatment of oral mucositis in patients undergoing antineoplastic therapy: systematic review and meta-analysis. Support Care Cancer. 2023;31:645. https://doi.org/10.1007/s00520-023-08105-7.

    Article  PubMed  Google Scholar 

  43. Zadik Y, Arany PR, Fregnani ER, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27(10):3969–83. https://doi.org/10.1007/s00520-019-04890-2.

  44. Von Hippel PT. The heterogeneity statistic I2 can be biased in small meta-analyses. BMC Med Res Methodol. 2015;15:35. https://doi.org/10.1186/s12874-015-0024-z.

    Article  Google Scholar 

  45. Botelho J, Mascarenhas P, Viana J, Proença L, Orlandi M, Leira Y, et al. An umbrella review of the evidence linking oral health and systemic health: from the prevalence to clinical and circulating markers. Dentistry Oral Med. 2022. https://doi.org/10.1101/2022.04.11.22273715.

    Article  Google Scholar 

  46. On behalf of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO), Bowen JM, Gibson RJ, Coller JK, Blijlevens N, Bossi P, et al. Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines. Support Care Cancer. 2019;27:4011–22. https://doi.org/10.1007/s00520-019-04892-0.

    Article  Google Scholar 

  47. Antunes HS, Herchenhorn D, Small IA, Araújo CMM, Viégas CMP, De Assis Ramos G, et al. Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis. Oral Oncol. 2017;71:11–5. https://doi.org/10.1016/j.oraloncology.2017.05.018.

    Article  PubMed  Google Scholar 

  48. Brandão TB, Morais-Faria K, Ribeiro ACP, Rivera C, Salvajoli JV, Lopes MA, et al. Locally advanced oral squamous cell carcinoma patients treated with photobiomodulation for prevention of oral mucositis: retrospective outcomes and safety analyses. Support Care Cancer. 2018;26:2417–23. https://doi.org/10.1007/s00520-018-4046-z.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors declare that no financial support was received for the research, authorship, and/or publication of this article.

Clinical trial number

Not applicable.

Funding

This research received no external funding.

Author information

Authors and Affiliations

  1. Egas Moniz School of Health & Science, Egas Moniz Center for Interdisciplinary Research (CiiEM), Caparica, 2829-511, Portugal

    Inês Rodrigues, Vanessa Machado, Luísa Bandeira Lopes, Pedro Trancoso, António Mano Azul, José João Mendes, Carlos Zagalo & João Botelho

Authors
  1. Inês Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luísa Bandeira Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pedro Trancoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. António Mano Azul
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José João Mendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carlos Zagalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. João Botelho
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Inês Rodrigues: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing - original draft; Writing - review & editing. Vanessa Machado: Methodology; Resources; Software; Writing - original draft; Writing - review & editing. Luísa Bandeira Lopes: Writing - review & editing. Pedro Trancoso: Writing - review & editing. António Mano Azul: Writing - review & editing. José João Mendes: Supervision, Writing- Reviewing and Editing. Carlos Zagalo: Supervision, Writing- Reviewing and Editing. João Botelho: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Resources; Software; Supervision; Validation; Writing - original draft; Writing - review & editing.

Corresponding author

Correspondence to João Botelho.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rodrigues, I., Machado, V., Lopes, L.B. et al. Photobiomodulation therapy on chemo- and radiotherapy induced oral conditions: an umbrella review. BMC Oral Health 24, 1106 (2024). https://doi.org/10.1186/s12903-024-04793-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12903-024-04793-7

Keywords

BMC Oral Health

ISSN: 1472-6831

Contact us