Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long-term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long-term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time.

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols.

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.

A Systematic Review of Laser Photobiomodulation Dosimetry and Treatment Protocols in the Management of Medications-Related Osteonecrosis of the Jaws: A Rationalised Consensus for Future Randomised Controlled Clinical Trials.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management.

Dosimetric parameters and radiotherapy simulation methods used in preclinical studies of radiation damage to the dentition: a systematic review.

OBJECTIVE: This systematic review investigated the dosimetric parameters used in preclinical studies. STUDY DESIGN: Searches were performed in 3 databases (PubMed, Scopus, and Embase) and gray literature to identify studies for review. In vitro and ex vivo studies that examined the effect of radiation on human permanent teeth were included. The modified Consolidated Standards Of Reporting Trials checklist of items for reporting preclinical in vitro studies was used to assess the risk of bias. RESULTS: In total, 32 studies met the inclusion criteria. The average radiation dose of in vitro studies was 53 (±22) Gy and in ex vivo studies was 69 (±1) Gy. Twenty-two studies used 5 different fractionation schemes. Twenty-two of the included studies did not report the radiotherapy modality of those reporting. Twenty studies used linear accelerators, and 7 used Cobalt-60 with the source-surface-distance of radiation ranging from 1.5 to 100 cm. Distilled water was the storage solution for the dental structure used most commonly. Biases were observed, including small sample sizes, lack of randomization, and blinding processes. CONCLUSION: The dosimetric parameters used in the preclinical studies, including radiation dose, radiotherapy modality, fractionation regime, and the storage solutions used did not support the hypothesis of direct effects of radiation on the dental structure.

A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus was first recognized in late 2019 and remains a significant threat. We therefore assessed the use of local methylene blue photodynamic viral inactivation (MB-PDI) in the oral and nasal cavities, in combination with the systemic anti-viral, anti-inflammatory and antioxidant actions of orally ingested methylene blue (MB) and photobiomodulation (PBM) for COVID-19 disease. The proposed protocol leverages the separate and combined effects of MB and 660nm red light emitted diode (LED) to comprehensively address the pathophysiological sequelae of COVID-19. A total of eight pilot subjects with COVID-19 disease were treated in the Bahamas over the period June 2021-August 2021, using a remote care program that was developed for this purpose. Although not a pre-requisite for inclusion, none of the subjects had received any COVID-19 vaccination prior to commencing the study. Clinical outcome assessment tools included serial cycle threshold measurements as a surrogate estimate of viral load; serial online questionnaires to document symptom response and adverse effects; and a one-year follow-up survey to assess long-term outcomes. All subjects received MB-PDI to target the main sites of viral entry in the nose and mouth. This was the central component of the treatment protocol with the addition of orally ingested MB and/or PBM based on clinical requirements. The mucosal surfaces were irradiated with 660 nm LED in a continuous emission mode at energy density of 49 J/cm2 for PDI and 4.9 J/cm2 for PBM. Although our pilot subjects had significant co-morbidities, extremely high viral loads and moderately severe symptoms during the Delta phase of the pandemic, the response to treatment was highly encouraging. Rapid reductions in viral loads were observed and negative PCR tests were documented within a median of 4 days. These laboratory findings occurred in parallel with significant clinical improvement, mostly within 12-24 h of commencing the treatment protocol. There were no significant adverse effects and none of the subjects who completed the protocol required in-patient hospitalization. The outcomes were similarly encouraging at one-year follow-up with virtual absence of "long COVID" symptoms or of COVID-19 re-infection. Our results indicate that the protocols may be a safe and promising approach to challenging COVID-19 disease. Moreover, due its broad spectrum of activity, this approach has the potential to address the prevailing and future COVID-19 variants and other infections transmitted via the upper respiratory tract. Extensive studies with a large cohort are warranted to validate our results.

Outpatient Oral Neuropathic Pain Management with Photobiomodulation Therapy: A Prospective Analgesic Pharmacotherapy-Paralleled Feasibility Trial.

Neuropathic pain (NP) can be challenging to treat effectively as analgesic pharmacotherapy (MED) can reduce pain, but the majority of patients do not experience complete pain relief. Our pilot approach is to assess the feasibility and efficacy of an evidence-based photobiomodulation (PBM) intervention protocol. This would be as an alternative to paralleled standard analgesic MED for modulating NP intensity-related physical function and quality of life (QoL) prospectively in a mixed neurological primary burning mouth syndrome and oral iatrogenic neuropathy study population (n = 28). The study group assignments and outcome evaluation strategy/location depended on the individual patient preferences and convenience rather than on randomisation. Our prospective parallel study aimed to evaluate the possible pre/post-benefit of PBM and to allow for a first qualitative comparison with MED, various patient-reported outcome measures (PROMs) based on Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT-II) were used for up to a nine-month follow-up period in both intervention groups (PBM and MED). The PBM protocol applied to the PBM group was as follows: λ810 nm, 200 mW, 0.088 cm2, 30 s/point, 9 trigger and affected points, twice a week for five consecutive weeks, whereas the MED protocol followed the National Institute of Clinical Excellence (NICE) guidelines. Our results showed that despite the severe and persistent nature of the symptoms of 57.50 ± 47.93 months at baseline in the PBM group, a notably rapid reduction in PISmax on VAS from 7.6 at baseline (T0) to 3.9 at one-month post-treatment (T3) could be achieved. On the other hand, mean PISmax was only reduced from 8.2 at baseline to 6.8 at T3 in the MED group. Our positive PBM findings furthermore support more patients' benefits in improving QoL and functional activities, which were considerably impaired by NP such as: eating, drinking and tasting, whereas the analgesic medication regimens did not. No adverse events were observed in both groups. To the best knowledge of the authors, our study is the first to investigate PBM efficacy as a monotherapy compared to the gold standard analgesic pharmacotherapy. Our positive data proves statistically significant improvements in patient self-reported NP, functionality, psychological profile and QoL at mid- and end-treatment, as well as throughout the follow-up time points (one, three, six and nine months) and sustained up to nine months in the PBM group, compared to the MED group. Our study, for the first time, proves the efficacy and safety of PBM as a potent analgesic in oral NP and as a valid alternative to the gold standard pharmacotherapy approach. Furthermore, we observed long-term pain relief and functional benefits that indicate that PBM modulates NP pathology in a pro-regenerative manner, presumably via antioxidant mechanisms.

Oropharyngeal candidiasis in head and neck cancer patients treated with radiation: update 2011.

BACKGROUND: Oropharyngeal candidiasis (OPC) is a major cause of morbidity in patients with malignancies. It is a common complication of head and neck radiation therapy and can result in pain, dysgeusia (taste changes), anorexia, malnutrition, and esophageal or systemic dissemination. Clinicians should be aware of current epidemiology, elements of diagnosis, and therapeutic trials guiding the recent recommendations for prophylaxis and management of OPC, a disease often incorrectly perceived as benign. METHODS: This review discusses OPC with focus in head and neck cancer patients receiving radiotherapy. RESULTS: Local treatments are recommended as first-line therapy in milder forms of OPC. In the setting of local therapy, products that provide prolonged contact time and are not sucrose sweetened may result in successful prevention and management with low risk of oral/dental complications. CONCLUSION: Diagnosis and management of OPC is required in head and neck cancer patients treated with radiation. Local therapy is suggested as first-line treatment for OPC, unless severe clinical infection or high risk immune suppression necessitate systemic therapy. The availability of effective locally delivered (topical) medications may provide potential for prophylaxis for carriers of Candida species in head and cancer patients during radiation therapy.

Role of Photobiomodulation Therapy in Modulating Oxidative Stress in Temporomandibular Disorders. A Systematic Review and Meta-Analysis of Human Randomised Controlled Trials.

This systematic review and meta-analysis (PROSPERO registration; ref CRD 42020198921) aimed to govern photobiomodulation therapy (PBMT) efficacy in temporomandibular disorder (TMD). PRISMA guidelines and Cochrane Collaboration recommendations were followed. Differences in pain reduction assessment by qualitative measurement with visual analogue scale pain (VAS), pressure threshold (PPT) and maximum mouth opening (MMO) were calculated with 95% confidence intervals and pooled in a random effects model with a subgroup analysis, evaluating the role of follow-up duration. Heterogeneity was analysed using Q and I2 tests. Publication bias was assessed by visual examination of funnel plot symmetry. Qualitative analysis revealed 46% of the 44 included studies showed a high risk of bias. Meta-analysis on 32 out of 44 studies revealed statistically significant intergroup differences (SSID) for VAS (SMD = -0.55; 95% CI = -0.82 to -0.27; Z = 3.90 (p < 0.001)), PPT (SMD = -0.45; 95% CI = -0.89 to 0.00; Z = 1.97 (p = 0.05)) and MMO (SMD = -0.45; 95% CI = -0.89 to 0.00; Z = 1.97 (p = 0.05)), favouring PBMT compared to control treatment strategies. Sensitivity analysis revealed SSID (SMD = -0.53; 95% CI = -0.73 to -0.32; Z = 5.02 (p < 0.0001)) with low heterogeneity (Τ2 = 0.02; χ2 = 16.03 (p = 0.31); I2 = 13%). Hence, this review, for first time, proposed suggested recommendations for PBMT protocols and methodology for future extensive TMD research.

Role of Photobiomodulation Therapy in Neurological Primary Burning Mouth Syndrome. A Systematic Review and Meta-Analysis of Human Randomised Controlled Clinical Trials.

Mitochondrial homeostasis is crucial for energy production and neuronal survival in neurological primary burning mouth syndrome (npBMS). Photobiomodulation therapy (PBMT) has been utilised in npBMS management, however, its role of intervention remains controversial. The aim of this systematic review and meta-analysis of CRD 42020198921 PROSPERO registration reference was to oversee and determine the efficacy of PBMT in patients with npBMS, identifying the gaps and bridge them by proposing recommendations for future studies purposes. PRISMA guidelines and Cochrane Collaboration recommendations followed. Various search engines employed to analyse a total of 351 studies of which 12 were included. A wide range of utilised PBM wavelengths was between 635-980 nm and the power output ranged between 30 mW and 4000 mW. A high risk of bias (RoB) was noted in 7 out of 12 included studies (58.3%), as results of qualitative analysis. Meta-analysis findings of 4 out of 12 studies showed statistically significant intergroup differences (SSID) for visual analogue scale (VAS) values (MD = -1.47; 95% CI = -2.40 to -0.53; Z = 3.07 (p = 0.002) whereas meta-analysis on 5 out of 12 studies revealed SSID for anxiety/depression and quality of life (MD = -1.47; 95% CI = -2.40 to -0.53; Z = 3.07 (p = 0.002), favouring PBMT group to the control treatment strategies. Despite the inconsistency and diversity in PBM parameters (wavelength, power, light source, spot size, emission mode, energy per point, total energy) and treatment protocols (exposure time, number of sessions, time interval between sessions, treatment duration)-majority of the included studies showed positive PBM results. The high RoB and meta-analytical heterogeneity in the eligible studies warrant the necessity to perform well-designed and robust RCTs after acknowledging the drawbacks of the available scientific literature and addressing our suggested recommendations highlighted in our review.

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. METHODS AND MATERIALS: Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 µg (n = 56), 100 µg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). RESULTS: SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. CONCLUSIONS: Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.

Free-flap head and neck reconstruction and quality of life: a 2-year prospective study.

OBJECTIVES: This prospective study was designed to evaluate quality of life (QOL) after free-flap head and neck reconstruction. STUDY DESIGN: Prospective study. METHODS: : Between January 2004 and December 2005, a total of 95 patients underwent microvascular reconstruction of the head and neck at our Institution (Centre Antoine-Lacassagne, Nice, France) and were initially included in this study. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Head and Neck Cancer Quality of Life Questionnaire were completed before surgery, and at 6 and 12 months thereafter. Sixty-five patients completed the questionnaires on at least two of the assessment dates. Predictive factors of Quality of Life (QOL) scores at 6 months were researched among the following: age, sex, comorbidity, radiotherapy, tumor recurrence, tumor stage, and type of surgery. RESULTS: Global QOL remained stable over time. Physical, social, and role functioning deteriorated significantly after treatment. Pain decreased markedly. Social eating, senses, and speech difficulties increased significantly at 6 months, but stabilized between 6 and 12 months. Problems concerning mouth opening and social contact augmented progressively until the 12th postoperative month. Sex, type of surgery, and radiotherapy were the main factors influencing QOL 6 months after treatment. CONCLUSIONS: Despite some functional impairments, global QOL was preserved after major head and neck ablative surgery and microvascular free-flap reconstruction.

Impact of intensity-modulated radiotherapy on health-related quality of life for head and neck cancer patients: matched-pair comparison with conventional radiotherapy.

PURPOSE: To assess the benefit of intensity-modulated radiotherapy (IMRT) compared with conventional RT for the quality of life (QOL) of head and neck cancer survivors. METHODS AND MATERIALS: Cross-sectional QOL measures (European Organization for Research and Treatment of Cancer QOL questionnaire C30 and head and neck cancer module) were used with a French multicenter cohort of patients cured of head and neck cancer (follow-up > or = 1 year) who had received bilateral neck RT (> or = 45 Gy) as a part of their initial treatment. We compared the QOL mean scores regarding RT modality (conventional RT vs. IMRT). The patients of the two groups were matched (one to one) according to the delay between the end of RT and the timing of the QOL evaluation and the T stage. Each QOL item was divided into two relevant levels of severity: "not severe" (responses, "not at all" and "a little") vs. "severe" (responses "quite a bit" and "very much"). The association between the type of RT and the prevalence of severe symptoms was approximated, through multivariate analysis using the prevalence odds ratio. RESULTS: Two comparable groups (67 pairs) were available. Better scores were observed on the head and neck cancer module QOL questionnaire for the IMRT group, especially for dry mouth and sticky saliva (p < 0.0001). Severe symptoms were more frequent with conventional RT concerning saliva modifications and oral discomfort. The adjusted prevalence odds ratios were 3.17 (p = 0.04) for dry mouth, 3.16 (p = 0.02) for sticky saliva, 3.58 (p = 0.02) for pain in the mouth, 3.35 (p = 0.04) for pain in the jaw, 2.60 (p = 0.02) for difficulties opening the mouth, 2.76 (p = 0.02) for difficulties with swallowing, and 2.68 (p = 0.03) for trouble with eating. CONCLUSION: The QOL assessment of head and neck cancer survivors demonstrated the benefit of IMRT, particularly in the areas of salivary dysfunction and oral discomfort.

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis.

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team.

In vivo measurements with MOSFET detectors in oropharynx and nasopharynx intensity-modulated radiation therapy.

PURPOSE: To evaluate the feasibility of in vivo measurements with metal oxide semiconductor field effect transistor (MOSFET) dosimeters for oropharynx and nasopharynx intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: During a 1-year period, in vivo measurements of the dose delivered to one or two points of the oral cavity by IMRT were obtained with MOSFET dosimeters. Measurements were obtained during each session of 48 treatment plans for 21 patients, all of whom were fitted with a custom-made mouth plate. Calculated and measured values were compared. RESULTS: A total of 344 and 452 measurements were performed for the right and left sides, respectively, of the oral cavity. Seventy percent of the discrepancies between calculated and measured values were within +/-5%. Uncertainties were due to interfraction patient positions, intrafraction patient movements, and interfraction MOSFET positions. Nevertheless, the discrepancies between the measured and calculated means were within +/-5% for 92% and 95% of the right and left sides, respectively. Comparison of these discrepancies and the discrepancies between calculated values and measurements made on a phantom revealed that all differences were within +/-5%. CONCLUSION: Our experience demonstrates the feasibility of in vivo measurements with MOSFET dosimeters for oropharynx and nasopharynx IMRT.

[2003 Update of Standards, Options and Recommendations for management of patients with salivary gland malignant tumors (excluding lymphoma, sarcoma and melanoma) (summary report)]. / Standards, Options et Recommations 2003 pour la prise en charge des patients atteints de tumeurs malignes des glandes salivaires (lymphomes, sarcomes et mélanomes exclus), mise à jour (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPG s according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concern the place of fine needle aspiration biopsy in preoperative diagnosis, the place of cervical lymph node area surgical treatment, the place of postoperative irradiation and neutron therapy in the treatment of unresectable tumors and also the place of medical imaging, especially RMI, for the diagnosis of these tumors.

Radical ablative surgery and radial forearm free flap (RFFF) reconstruction for patients with oral or oropharyngeal cancer: postoperative outcomes and oncologic and functional results.

CONCLUSIONS: Radical ablative surgery and radial forearm free flap (RFFF) reconstruction provide promising oncologic and functional results in patients with oral or oropharyngeal cancer. OBJECTIVES: To assess the postoperative outcomes and the oncologic and functional results, with their main predictive factors, after radical ablative surgery and RFFF reconstruction for patients with oral or oropharyngeal cancer. PATIENTS AND METHODS: Between 2000 and 2006, we prospectively analyzed the postoperative, oncologic and functional outcomes of all previously untreated patients who underwent this type of surgery. RESULTS: A total of 132 patients were enrolled in this study. There were three RFFF failures. The rate of surgical complications was 20%. The 5-year locoregional control and overall survival rates were 68% and 52%, respectively. Advanced age, high comorbidity index, elevated overall stage and tumoral involvement of the inner part of the cheek were correlated with a lower overall survival rate. A good functional result was obtained for oral diet, speech, mouth opening and aesthetic outcome in 87%, 80%, 86% and 88% of the patients, respectively. High comorbidity index, large flap surface, radiotherapy and tumoral involvement of the mobile tongue were significant predictors of poorer functional or aesthetic outcomes.

[Osteonecrosis of the jaw and bisphophonates in oncology]. / Ostéonécrose des maxillaires et bisphosphonates en cancérologie.

Bisphosphonates are potent osteoclastic inhibitors that are indicated in the prevention of bone complications. They could also be of interest in the prevention of bone metastases. Several recent international publications have highlighted the onset of osteonecrosis of the jaw (ONJ) in patients treated with bisphosphonates. These osteonecroses manifest in the form of bone exposure, recent tooth mobility, swelling and inflammation and, occasionally, localised pain but they can remain asymptomatic for weeks or even months. The prevalence of these osteonecroses in cancer patients treated with bisphosphonates could range from 1 to 10%. In most cases (60 to 80%), ONJ develops after alveolo-dental surgery (e.g. tooth extraction). Length of exposure to bisphosphonate probably increases the risk. Our recommendations regarding the diagnosis, classification, prevention and treatment of cases of ONJ observed during bisphosphonate administration are based on published studies and our experience. It is obvious that the use of bisphosphonates is undoubtedly beneficial in the treatment of bone complications but the incidence of ONJ during long-term treatments and at high doses warrants preventive measures. These measures are straightforward : bucco-dental repair prior to treatment, good hygiene and regular monitoring during treatment. Current, non-invasive procedures are still permitted. In other cases, the suspension of treatment is indicated until healing is complete. The increase in the incidence of ONJs, serious adverse events, raises the issue regarding duration and administration of bisphosphonate treatment in the management of bone metastases. Studies are currently underway in an attempt to answer this issue.

Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis: a prospective, randomized, single-blind, multicenter, comparative, phase III trial in patients treated with radiotherapy for head and neck cancer.

BACKGROUND: Topical antifungal treatments are recommended but rarely used as first-line therapy for oropharyngeal candidiasis (OPC) in patients with cancer. Miconazole Lauriad 50-mg mucoadhesive buccal tablet (MBT) Loramyc reportedly delivered rapid and prolonged, effective concentrations of miconazole in the mouth. The objective of the current study was to compare MBT with miconazole 500-mg oral gel (MOG) in patients with head and neck cancer. METHODS: Two hundred eighty-two patients with head and neck cancer received a 14-day treatment of either single-dose MBT or MOG administered in 4 divided doses. The primary endpoint was clinical success at Day 14, and secondary endpoints included clinical success at Day 7, clinical cure, improvement in clinical symptoms, mycologic cure, recurrence rate, and safety. RESULTS: The success rate was statistically not inferior (P < .0001) in the MBT population to the rate observed in the MOG group (56% vs 49%, respectively; P < .0001). After adjustment for the extent of lesions and salivary secretions, a trend toward superiority was observed in favor of MBT (P = .13), particularly among patients with multiple lesions (P = .013). Results for secondary endpoints were comparable to those observed for the primary endpoint. Compliance with MBT was excellent, and >80% of patients completed treatment. Both treatments were safe. CONCLUSIONS: The success rate of MBT Loramyc was significantly not inferior to that of MOG in the treatment of cancer patients with OPC; and, after adjusting for prognostic variables, it was more effective than MOG. MBT was well tolerated and, thus, may be recommended as first-line treatment in cancer patients who have OPC as an alternative to systemic antifungal agents. Society.

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.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.