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Purpose To discuss the role of benzydamine in the prevention and treatment of radiation-induced oral mucositis (OM) in head and neck (H&N) cancer patients. This document represents an expert opinion paper on indications and key-role aspects in OM pathogenesis, prevention and treatment. Oral mucositis OM represents a common side effect of chemotherapy (CHT) and radiotherapy (RT). It consists in a painful erythema involving the oral cavity mucosa, which may progress to ulceration. Five biologically dynamic phases are considered crucial in mucositis: “initiation, signalling, amplification, ulceration and healing”. Oral environment and microbiota are fundamental in mucositis development being involved in susceptibility to infections and in ulceration consequences. Different agents against mucositis have been studied and the use of benzydamine is strongly supported in literature. The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines recommend its use for the prevention of OM in H&N patients undergoing RT and RT/CHT. Benzydamine Benzydamine is a local anti-inflammatory drug with analgesic properties. It can decrease TNF-α, IL-1β and prostaglandin synthesis, also inhibiting leukocyte-endothelial interactions, neutrophil degranulation, vasodilation and vascular permeability. Literature agrees on the beneficial effects of benzydamine in preventing and reducing oral mucositis severity in H&N cancer patients undergoing RT/CHT. Conclusions Mucositis represents a major concern in H&N cancer patients and a clinical and economical issue. A multimodal and multidisciplinary approach is needed for its management. International guidelines recommend benzydamine for OM prevention and treatment in H&N cancer patients, but further “real world” trials should be designed.

Medical doctors’ (MDs), but not patients’, perception of supportive care in cancer (SCC) in France has been previously assessed in a national survey. This study evaluated MDs and patients’ perceptions of the SCC organization and implementation in France. The French SCC Association conducted two observational studies: study 1 (S1), containing a 30-point questionnaire sent to 2263 MDs, and study 2 (S2), containing a 40-point questionnaire sent to 2000 patients. Overall, 711 MDs completed S1 and 1562 patients completed S2. In S1, 81% of MDs reported relying on a SCC organization and 76% attended SCC multidisciplinary discussions. MDs considered palliative (98%), psychological (98%), and social care (98%) as the top 3 SCC areas of importance for patients. In contrast, patients’ priorities were psychology (61%), nutrition (55%) and organization of intake consultations (55%). The concept of SCC was familiar to 34% of patients; according to MDs, this concept was introduced mainly by MDs (78%) and admission nurses (41%). Outpatients identified as professional resources for SCC information general practitioners (84%), nurses (58%), and pharmacists (52%). Patients reported supportive treatment being prescribed in 63% of cases, with 64% receiving information on the negative side-effects. Among MDs, 87% reported proposing palliative and 41% adjuvant SCC treatment. Furthermore, 72% of MDs recommended SCC treatment at the metastatic stage, and 36% immediately following diagnosis. Oncologists play a vital role in enhancing SCC efficacy. This can be increased by implementing a multidisciplinary integrated approach or by assuring the availability of patient information.

Necrosis of the oral mucosa following head and neck cancer radiation therapy presents considerable clinical management challenges. We report three cases of symptomatic persisting oral ulcerations where the addition of photobiomodulation therapy resulted in a rapid resolution of the oral lesions and in patient symptoms. These cases suggest that photobiomodulation may represent an adjunct to care of these difficult to manage complications in oncology.

This commentary attempts to clarify the setting of photobiomodulation (BPM) therapy in the management of oral mucositis. The suggested dose range balances efficacy data with our current understanding about PBM safety. The literature about the molecular basis of photobiomodulation and its controversial relationship to malignant transformation is briefly presented.

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/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (

PurposeThere 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.MethodsThis study is a narrative non-systematic review.ResultsWe 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.ConclusionBased 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.

PurposeDermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL.MethodsA comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments.ResultsThirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14)).ConclusionsWhile there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

PurposeDysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalence, complications, and impact on quality of life in patients with a variety of different cancers, particularly in those treated with curative chemoradiation for head and neck cancer.MethodsThe literature search was limited to the English language and included both MEDLINE/PubMed and EMBASE. The search focused on papers reporting dysphagia as a side effect of cancer and cancer therapy. We identified relevant literature through the primary literature search and by articles identified in references.ResultsA wide range of assessment tools for dysphagia was identified. Dysphagia is related to a number of factors such as direct impact of the tumor, cancer resection, chemotherapy, and radiotherapy and to newer therapies such as epidermal growth factor receptor inhibitors. Concomitant oral complications such as xerostomia may exacerbate subjective dysphagia. Most literature focuses on head and neck cancer, but dysphagia is also common in other types of cancer.ConclusionsSwallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed.

Cutaneous adverse events induced by epidermal growth factor receptor (EGFR) inhibitors can hamper the patients' quality of life. The aim of our work was to draft an algorithm for the optimised management of this skin toxicity.This algorithm was built in three steps under the responsibility of a steering committee. Step I: a systematic literature analysis (SLA) has been performed. Step II: the collection of information about practices was performed through a questionnaire.These questions were asked during regional meetings to which oncologists, gastro-enterologists, radiotherapists, and dermatologists were invited. Step III: a final meeting was organised involving the bibliography group and the steering committee and regional scientific committees for proposing a final algorithm.Step I: 14 publications were selected to evaluate the use of cyclines as curative or prophylactic treatment of the folliculitis induced by EGFR inhibitors. Nineteen publications were retained for the topical treatment of the folliculitis. Forty-six articles were selected for the management of the cutaneous lesions in link with appendages and 12 for xerosis and pruritus. Step II: 96 delegates attended the seven regional meetings and 67 questionnaires were analysed. Step III: a final algorithm was proposed on the basis of the conclusions of the first two steps and expert opinions present at this final meeting. The different propositions were unanimously approved by the 14 experts who voted.This multidisciplinary study summarising published data and current practices produced a therapeutic algorithm, which should facilitate the standardised, optimised management of skin toxicity associated with EGFR inhibitors in France.

Advances in the understanding of the mechanisms involved in oncogenesis have led to the development of so-called targeted therapies such as epidermal growth factor receptor (EGFR) inhibitors, which take on an increasingly important role in the management of cancer. These treatments have the advantage not to trigger the adverse effects traditionally encountered with chemotherapy, such as nausea, vomiting or haematological toxicity. However, they do cause new forms of toxicity: the most common one is skin toxicity. It is important to be aware of it because it can be debilitating, adversely impacting patients’ quality of life and altering treatment compliance, although it appears to be correlated with treatment response in certain series. Non-specialists can have difficulty in recognising this unusual skin toxicity. The dermatologic side effects most frequently triggered by EGFR inhibitors are discussed in this article. They are divided into three categories depending on their target: inflammation of the pilo-sebaceous follicle, represented by EGFR inhibitor-associated folliculitis, which occurs at an early stage and is frequent; alteration in the skin barrier, primarily responsible for xerosis, fissures and pruritus, which are frequent and delayed; and lesions of the skin appendages (paronychia, pyogenic granuloma, hair changes), which are delayed and less frequent. It is essential for all practitioners concerned to know about these dermatologic side effects in order to ensure better global management of patients, particularly in terms of quality of life.

This phase III trial was designed to test trolamine emulsion compared with the usual supportive care for patients with head and neck cancer undergoing radiation therapy with concurrent chemotherapy.Patients with biopsy-proven head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy and weekly concurrent cisplatin 40 mg/m(2) at the South Egypt Cancer Institute (Assiut) were randomly assigned to one of the following groups: treatment group (prophylactic trolamine emulsion every 8 h, 4 h apart from the radiotherapy session) or control group (usual supportive care). The primary outcome was the reduction of grade III or higher skin toxicity, as per RTOG Acute Radiation Toxicity Criteria.From March 2008 to June 2009, 30 patients were entered onto the trial. The average age was 54.5 years. Patients were predominately male (83%) and most continued to use tobacco products (70%). The rate of skin-reaction was 100% in both groups. A mild radiation reaction (grades I and II) occurred as follows: 80% (12/15 cases) in the treatment group and 46.6% (7/15 cases) in the control group. A grade III skin reaction developed in 20% (3/15 cases) in the treatment group and 53.3% (8/15 cases) in the controls. There was a significant difference (P0.01) between the two groups.Our results confirm that trolamine emulsion significantly reduces the intensity of acute dermatitis following 3D-CRT with weekly cisplatin in HNSCC.

This systematic review represents a thorough evaluation of the literature to clarify the impact of cancer therapies on the prevalence, quality of life and economic impact, and management strategies for cancer-therapy-induced trismus. A systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of trismus. The level of evidence, recommendation grade, and guideline (if possible) were given for published preventive and management strategies for trismus. We reviewed a total of 22 published studies between 1990 and 2008. Most of them assessed the prevalence of this complication, and few focused on management. The weighted prevalence for trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies. No clear guideline recommendations could be made for the prevention or management of trismus. Newer radiation modalities may decrease the prevalence of trismus compared to conventional radiotherapy. Few studies have addressed the quality of life impact of trismus, and no studies were identified to assess the economic impact of trismus. The few preventive and management trials identified in the literature showed some promise, although larger, well-designed studies are required to appropriately assess these therapies before recommendations can be provided.

Oral mucositis (OM) is a significant early complication of hematopoietic cell transplantation (HCT). This phase III randomized double-blind placebo-controlled study was designed to compare the ability of 2 different low level GaAlAs diode lasers (650 nm and 780 nm) to prevent oral mucositis in HCT patients conditioned with chemotherapy or chemoradiotherapy. Seventy patients were enrolled and randomized into 1 of 3 treatment groups: 650 nm laser, 780 nm laser or placebo. All active laser treatment patients received daily direct laser treatment to the lower labial mucosa, right and left buccal mucosa, lateral and ventral surfaces of the tongue, and floor of mouth with energy densities of 2 J/cm2. Study treatment began on the first day of conditioning and continued through day +2 post HCT. Mucositis and oral pain was measured on days 0, 4, 7, 11, 14, 18, and 21 post HCT. The 650 nm wavelength reduced the severity of oral mucositis and pain scores. Low level laser therapy was well-tolerated and no adverse events were noted. While these results are encouraging, further study is needed to truly establish the efficacy of this mucositis prevention strategy. Future research needs to determine the effects of modification of laser parameters (e.g., wavelength, fluence, repetition rate of energy delivery, etc.) on the effectiveness of LLE laser to prevent OM.

Mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review of the literature on mucositis. The goal of this literature review is to update previously published guidelines for the management of mucositis. This article reports the findings of the subgroup charged with reviewing the literature related to amifostine.

Alimentary mucositis is a significant complication of cancer therapy, with important clinical and economic implications.In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology conducted an evidence-based review of the literature on alimentary mucositis. The goal of this literature review was to update previously published guidelines for the management of mucositis.This article reports the findings of the subgroup charged with reviewing the literature related to anti-inflammatory interventions. Considerable preclinical and clinical evidence suggests that the use of anti-inflammatory agents may be a promising approach to reduce the severity of mucositis. However, there was not enough evidence to support any new guidelines advocating the use of any specific anti-inflammatory intervention.Thus, there is a need for well-designed clinical trials evaluating the use of anti-inflammatory agents in the management of mucositis.