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Purpose There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength , typically between 633 and 685 nm or 780–830 nm; energy density , laser or light-emitting diode (LED) output between 10 and 150 mW; dose , 2–3 J (J/cm 2 ), and no more than 6 J/cm 2 on the tissue surface treated; treatment schedule , two to three times a week up to daily; emission type , pulsed (<100 Hz); and route of delivery , intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.

Background: The oral cavity is a potential source of infectious complications in patients treated with myelosuppressive chemotherapy (CT). Pre-chemotherapy oral examination to identify foci of infection is recommended, but it is unclear whether this should include panoramic radiography. The present study aimed to evaluate the additional diagnostic merit of panoramic radiography as part of pre-CT oral screening. Methods: Patients with solid tumors scheduled to receive a myelosuppressive CT were eligible. The foci definition followed the guidelines of the Dutch Association of Maxillofacial Surgery. Oral foci assessed by clinical evaluation and panoramic radiography were compared. Results: In 33 out of 93 patients (35.5%), one or more foci were identified by clinical examination, whereas in 49.5% of patients, panoramic radiography showed pathology. In 19 patients, an oral focus was missed by clinical examination only, whereas in 11 patients, panoramic radiography indicated periodontal bone loss, but advanced periodontitis was not substantiated by clinical examination. Conclusions: Panoramic radiographs complement clinical examinations and have additional diagnostic value. Nevertheless, the additional merit seems small, and the clinical relevance may vary depending on the anticipated risk of developing oral complications and the need for detailed diagnosis and rigorous elimination of oral foci prior to the start of cancer therapy.

Febrile neutropenia (FN) is an inflammatory response causing fever that may develop during cancer therapy-induced neutropenia. FN may herald life-threatening infectious complications and should therefore be considered a medical emergency. Patients presenting with FN are routinely subjected to careful history taking and physical examination including X-rays and microbiological evaluations. Nevertheless, an infection is documented clinically in only 20–30% of cases, whereas a causative microbial pathogen is not identified in over 70% of FN cases. The oral cavity is generally only visually inspected. Although it is recognized that ulcerative oral mucositis may be involved in the development of FN, the contribution of infections of the periodontium, the dentition, and salivary glands may be underestimated. These infections can be easily overlooked, as symptoms and signs of inflammation may be limited or absent during neutropenia. This narrative review is aimed to inform the clinician on the potential role of the oral cavity as a potential source in the development of FN. Areas for future research directed to advancing optimal management strategies are discussed.

Purpose There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods This study is a narrative non-systematic review. Results We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.

Aim Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) may experience oral complications associated with chronic graft-versus-host disease (cGVHD). These complications may significantly affect quality of life, even many years post-HSCT. Current treatment options for oral cGVHD are limited and often include steroid or other immunomodulatory medications, which may not adequately control the oral condition. A non-immunosuppressive intervention for symptomatic relief in oral cGVHD would thus be a welcome addition to the treatment paradigm. Materials and methods We report seven cases of oral cGVHD that were treated with photobiomodulation therapy (PBM), previously known as low-level laser therapy (LLLT). Patients underwent at least two PBM treatments per week in addition to local treatment with steroids, and if on systemic therapies, these were either unchanged or dosage was reduced during the period of PBM therapy. Follow-up data is presented for 4 weeks of treatment. Results Oral pain, sensitivity, and dry mouth improved in most patients. These findings suggest PBM therapy may represent an additional approach for management of oral cGVHD, and suggest that controlled studies should be conducted to confirm the efficacy and safety of PBM therapy in oral cGVHD and to determine optimal PBM therapy protocols.

Oral mucositis induced by conventional cytotoxic cancer therapies is a common and significant clinical problem in oncology. Mucositis symptoms, which include severe pain, may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy, and often affect patients' quality of life. In addition, ulcerative mucositis represents a risk factor for local or systemic infectious complications that may be life-threatening in immunosuppressed patients. The development of biologically based targeted cancer therapies, which aim to block the growth, spread, and survival of tumors by interfering with specific molecular targets, may have reduced mucosal injury, but did not eliminate it. This article will review the epidemiology, pathobiology, and management of oral mucositis associated with conventional cytotoxic therapies for malignant diseases and will briefly summarize emerging information on oral mucosal injury associated with targeted therapies. Considerations for future research aimed at the development of more efficient and effective supportive care approaches will be presented, with emphasis on the contribution of dental researchers and clinicians in these efforts.

To evaluate the possible changes of the oral microbiome during myelosuppressive chemotherapy (CT) and to investigate the potential relationship between the oral microbiome, the presence of oral mucositis (OM) and febrile neutropenia (FN). A prospective, longitudinal, observational study was conducted in patients receiving myelosuppressive CT for a solid tumor or lymphoma. Oral rinsing samples were retrieved before, during and after the start of CT, but also when OM or FN was present. The samples were analyzed using 16S rRNA gene amplicon sequencing and statistical analysis was performed using alpha (Shannon) and beta (PERMANOVA) diversity analyses. Furthermore, differential abundances were analyzed using ALDEx2v1.32.0. Differences between groups were calculated using the Mann Whitney -test, Kruskal-Wallis test and Wilcoxon Signed Rank using R. Forty-six patients, with a mean follow up of 114 days, were included for analysis and a total of 138 oral rinsing samples were available in the CLR-transformed data for PERMANOVA and 137 samples-for alpha diversity calculation. Significant changes in alpha diversity were seen when OM or FN was present. Moreover, significant changes were seen in beta diversity during the course of the CT treatment and when OM was present. Genera showing substantial changes in relative abundance were during the course of CT treatment and and when OM was present. Changes in the oral microbiome were observed during the CT-regimen and when OM was present. Furthermore, changes of the oral microbiota during FN episodes were observed; however, larger studies should be performed to substantiate our results.

Introduction: Febrile neutropenia (FN) is a potential life-threatening complication of myelosuppressive chemotherapy, particularly when induced by infection. There is evidence that FN can originate from the oral cavity, but its contribution to FN is largely understudied in patients treated for solid tumors. The aim of this study was to assess the prevalence of FN in these patients and to evaluate its relation with dental foci and oral mucositis.Material and Methods: A prospective longitudinal observational study was conducted. Patients diagnosed with solid tumors and lymphoma scheduled to be treated with myelosuppressive chemotherapy with an intermediate risk of developing FN were included. A pre-chemotherapy dental examination was performed and patients were followed during and after chemotherapy regimen. During subsequent hospital visits for chemotherapy administration, the oral cavity was inspected and oral mucositis (OM) was scored using the CTC-AE version 3.0. When patients presented with fever, a comprehensive full body examination including laboratory/microbiological/imaging investigation was performed.Results: Eighty-eight patients were included. Pre-chemotherapy, 39 patients (44.3%) were diagnosed with a dental focus. During chemotherapy, 46 patients developed OM (53.4%), of which 15 patients had a maximum score of grade II (ulcerative mucositis). Ten patients developed FN during the follow-up period. Patients with FN more often suffered from ulcerative OM compared to patients without FN; both FN and mucositis risk was associated with the myelotoxicity of chemotherapy. However, no relation could be established between the presence of dental foci prior to chemotherapy and the development of FN (p > 0.05).Conclusion: A significant relation was identified between ulcerative OM and FN, but no robust conclusions could be drawn with respect to a relationship between the presence of dental foci and FN.