Oral health-related quality of life after radiation therapy for head and neck cancer: the OraRad study.

PURPOSE: Head and neck cancer (HNC) treatment results in morbidity impacting quality of life (QOL) in survivorship. This analysis evaluated changes in oral health-related QOL (OH-QOL) up to 2 years after curative intent radiation therapy (RT) for HNC patients and factors associated with these changes. METHODS: 572 HNC patients participated in a multicenter, prospective observational study (OraRad). Data collected included sociodemographic, tumor, and treatment variables. Ten single-item questions and 2 composite scales of swallowing problems and senses problems (taste and smell) from a standard QOL instrument were assessed before RT and at 6-month intervals after RT. RESULTS: The most persistently impacted OH-QOL variables at 24 months included: dry mouth; sticky saliva, and senses problems. These measures were most elevated at the 6-month visit. Aspects of swallowing were most impacted by oropharyngeal tumor site, chemotherapy, and non-Hispanic ethnicity. Problems with senses and dry mouth were worse with older age. Dry mouth and sticky saliva increased more among men and those with oropharyngeal cancer, nodal involvement, and use of chemotherapy. Problems with mouth opening were increased by chemotherapy and were more common among non-White and Hispanic individuals. A 1000 cGy increase in RT dose was associated with a clinically meaningful change in difficulty swallowing solid food, dry mouth, sticky saliva, sense of taste, and senses problems. CONCLUSIONS: Demographic, tumor, and treatment variables impacted OH-QOL for HNC patients up to 2 years after RT. Dry mouth is the most intense and sustained toxicity of RT that negatively impacts OH-QOL of HNC survivors. GOV IDENTIFIER: NCT02057510; first posted February 7, 2014.

Exposed bone in patients with head and neck cancer treated with radiation therapy: An analysis of the Observational Study of Dental Outcomes in Head and Neck Cancer Patients (OraRad).

BACKGROUND: Patients with head and neck cancer (HNC) treated with radiation therapy (RT) are at risk for jaw osteoradionecrosis (ORN), which is largely characterized by the presence of exposed necrotic bone. This report describes the incidence and clinical course of and risk factors for exposed intraoral bone in the multicenter Observational Study of Dental Outcomes in Head and Neck Cancer Patients (OraRad) cohort. METHODS: Participants were evaluated before RT and at 6, 12, 18, and 24 months after RT. Exposed bone was characterized by location, sequestrum formation, and other associated features. The radiation dose to the affected area was determined, and the history of treatment for exposed bone was recorded. RESULTS: The study enrolled 572 participants; 35 (6.1%) were diagnosed with incident exposed bone at 6 (47% of reports), 12 (24%), 18 (20%), and 24 months (8%), with 60% being sequestrum and with 7 cases (20%) persisting for >6 months. The average maximum RT dose to the affected area of exposed bone was 5456 cGy (SD, 1768 cGy); the most frequent associated primary RT sites were the oropharynx (42.9%) and oral cavity (31.4%), and 76% of episodes occurred in the mandible. The diagnosis of ORN was confirmed in 18 participants for an incidence rate of 3.1% (18 of 572). Risk factors included pre-RT extractions (P = .008), a higher RT dose (P = .039), and tobacco use (P = .048). CONCLUSIONS: The 2-year incidence of exposed bone in the OraRad cohort was 6.1%; the incidence of confirmed ORN was 3.1%. Exposed bone after RT for HNC is relatively uncommon and, in most cases, is a short-term complication, not a recurring or persistent one.

Now we are 30: 10 more years of MASCC.

This paper chronicles the third decade of MASCC from 2010. There was a generational change in this decade, building on the solid foundation of the founders. It included the first female President, and a new Executive Director with a background in strategy and business development and operations as applied to healthcare. The headquarters moved from Copenhagen to Toronto. The first meeting to be held outside of Europe or North America was held in Adelaide, Australia, and the membership in the Asia Pacific region expanded. A program of international affiliates saw national supportive care organisations formally link with MASCC. In cancer supportive care, there was a raft of new toxicities to manage as immunotherapies were added to conventional cytotoxic treatment. There was also a greater emphasis on the psychosocial needs of patients and families. New MASCC groups were formed to respond to this evolution in cancer management. The MASCC journal, Supportive Care in Cancer, continued to grow in impact, and MASCC published two editions of a textbook of supportive care and survivorship. The decade ended with the challenge of the COVID-19 pandemic, but that served to highlight the importance of good supportive care to patients with cancer.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis. METHODS: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.

Efficacy and safety of Dentoxol® in the prevention of radiation-induced oral mucositis in head and neck cancer patients (ESDOM): a randomized, multicenter, double-blind, placebo-controlled, phase II trial.

PURPOSE: The aim of this study was to assess the efficacy and safety of Dentoxol mouthrinse in reducing the severity of oral mucositis (OM) secondary to radiation therapy (RT) for head and neck cancer. METHODS: A randomized, double-blind, placebo-controlled, multicenter phase II clinical trial was conducted. Subjects were asked to use Dentoxol (n = 55) or control (n = 53) mouthrinse 5 times/day during RT. Twice a week, OM was assessed clinically using the WHO scale and the Oral Mucositis Daily Questionnaire (OMDQ) was completed. RESULTS: The incidence of severe OM was 40.7% in the Dentoxol group and 51% in the control group (p = 0.265). Comparing all recorded clinical assessments, severe OM was seen in 13.3% of all assessments in the Dentoxol group vs. 21.8% in the control group (p = 0.000). There was a statistically significant lower proportion of assessments showing severe OM in the Dentoxol group at weeks 4, 5, and 6 of RT. The mean duration of severe OM was 11.95 days in the Dentoxol group vs. 14.59 days in the control group (p = 0.502). There was no difference between groups in mouth pain and its impact on function. The use of Dentoxol was safe and was not linked to any serious adverse events. CONCLUSION: The use of Dentoxol 5 times/day is safe and resulted in significantly fewer time-points with severe OM and a delay in the onset of severe OM, compared with a control rinse. A phase III clinical trial is warranted to confirm efficacy and address the limitations of this study.

Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the clinical practice guidelines for the use of growth factors and cytokines for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: recommendation, suggestion, and no guideline possible. RESULTS: A total of 15 new papers were identified within the scope of this section and were merged with 51 papers that were reviewed in the previous guidelines update. Of these, 14, 5, 13, 2, and 1 were randomized controlled trials about KGF-1, G-CSF, GM-CSF, EGF, and erythropoietin, respectively. For the remaining agents there were no new RCTs. The previous recommendation for intravenous KGF-1 in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) conditioned with high-dose chemotherapy and TBI-based regimens is confirmed. The previous suggestion against the use of topical GM-CSF for the prevention of OM in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation remains unchanged. CONCLUSIONS: Of the growth factors and cytokines studied for the management of OM, the evidence supports a recommendation in favor of KGF-1 and a suggestion against GM-CSF in certain clinical settings.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible. CONCLUSIONS: Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain.

Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the 2013 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines on oral cryotherapy for the management of oral mucositis (OM) caused by cancer therapies. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The evidence for each intervention for specific cancer treatment modalities was assigned a level of evidence (LoE). The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the LoE, the guidelines were set as: recommendation, suggestion, or no guideline possible. RESULTS: A total of 114 papers were identified: 44 from PubMed and 70 from Web of Science. After abstract triage and merging with the 2013 database, 36 papers were reviewed. The LoE for prevention of OM with oral cryotherapy in patients undergoing autologous hematopoietic stem cell transplant using high-dose melphalan conditioning protocols was upgraded, and the guideline changed to recommendation. Additionally, the recommendation for prevention of OM with oral cryotherapy in patients receiving bolus 5-fluorouracil for the treatment of solid tumors was confirmed. No guidelines were possible for other clinical settings. CONCLUSIONS: The evidence supports recommendations for the use of oral cryotherapy for the prevention of OM for either (i) patients undergoing autologous hematopoietic stem cell transplant with high-dose melphalan conditioning protocols or (ii) patients receiving bolus 5-fluorouracil chemotherapy.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.

Recurrent oral ulceration: Etiology, classification, management, and diagnostic algorithm.

Recurrent oral ulcerations are manifestations of a heterogeneous set of both general and more-or-less specific oral diseases due to numerous potential etiologies, including, but not limited to, infections, medications, autoimmune disease, and other systemic disease. This review discusses the pathogenesis, clinical presentation, diagnosis, and management of the common causes of recurrent oral ulceration. The following types/etiologies of recurrent oral ulceration are covered: traumatic ulceration, chemical ulceration, recurrent aphthous stomatitis, medication-related ulceration, infectious ulceration, mucocutaneous disease, and autoimmune/systemic disease. A diagnostic algorithm for recurrent oral ulceration is also presented.

Development of the MASCC/ISOO clinical practice guidelines for mucositis: an overview of the methods.

New studies and literature continue to emerge on the management of mucositis secondary to cancer therapy. The evidence-based clinical practice guidelines for mucositis were first published in 2004 and updated in 2007 and 2014 by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The existing 2014 guidelines for mucositis are being updated in line with new literature to inform clinical practice. This paper describes the materials and methods employed for the comprehensive updates to the guidelines for managing mucositis.

Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review.

INTRODUCTION: The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. OBJECTIVE: To review characteristics of ONJ in cancer patients receiving non-antiresorptives. METHODS: A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. RESULTS: Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications. CONCLUSIONS: Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.

Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible. RESULTS: Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1-2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration. CONCLUSIONS: The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.

Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: The aim of this systematic review was to update the clinical practice guidelines for the use of anti-inflammatory agents in the prevention and/or treatment of oral mucositis. METHODS: A systematic review was conducted by the Multinational Association of Supportive Care in Cancer/ International Society of Oral Oncology (MASCC/ISOO) subcommittee on mucositis guideline update. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the clinical practice guidelines published in 2014. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guidelines. RESULTS: A total of 11 new papers across five interventions were examined. The recommendation for the use of benzydamine mouthwash for the prevention of radiotherapy-induced mucositis remained unchanged. New suggestion for the use of the same for prevention of mucositis associated with chemoradiotherapy was made. No guideline was possible for any other anti-inflammatory agents due to inadequate and/or conflicting evidence. CONCLUSIONS: Of the anti-inflammatory agents studied for oral mucositis, the evidence supports the use of benzydamine mouthwash in the specific populations listed above. Additional well-designed research is needed on other (class of agents) interventions and in other cancer treatment settings.

Systematic review of basic oral care for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: The aim of this study was to update the clinical practice guidelines for the use of basic oral care (BOC) interventions for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention in each cancer treatment setting was assigned an evidence level. The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. RESULTS: A total of 17 new papers across six interventions were examined and merged with a previous database. Based on the literature, the following guidelines were possible. The panel suggests that the implementation of multi-agent combination oral care protocols is beneficial for the prevention of OM during chemotherapy, head and neck (H&N) radiation therapy (RT), and hematopoietic stem cell transplantation (Level of Evidence III). The panel suggests that chlorhexidine not be used to prevent OM in patients undergoing H&N RT (Level of Evidence III). No guideline was possible for professional oral care, patient education, saline, and sodium bicarbonate, and expert opinion complemented these guidelines. CONCLUSIONS: The evidence supports the use of multi-agent combination oral care protocols in the specific populations listed above. Additional well-designed research is needed on the other BOC interventions prior to guideline formulation.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines.

PURPOSE: The aim of this study was to update the clinical practice guidelines for the use of agents for the prevention and/or treatment of gastrointestinal mucositis (GIM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers across 13 interventions were examined of which 25 were included in the final review. No new guidelines were possible for any agent due to inadequate and/or conflicting evidence. Existing guidelines for probiotics and hyperbaric oxygen were unchanged. CONCLUSIONS: Of the agents studied for the prevention and treatment of GIM, the evidence continues to support use of probiotics containing Lactobacillus spp. for prevention of chemoradiotherapy and radiotherapy-induced diarrhea in patients with pelvic malignancy, and hyperbaric oxygen therapy to treat radiation-induced proctitis. Additional well-designed research is encouraged to enable a decision regarding palifermin, glutamine, sodium butyrate, and dietary interventions, for the prevention or treatment of GIM.

Clinical registry of dental outcomes in head and neck cancer patients (OraRad): rationale, methods, and recruitment considerations.

BACKGROUND: Most head and neck (H&N) cancer patients receive high-dose external beam radiation therapy (RT), often in combination with surgery and/or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on the oral and maxillofacial tissues, some of which persist for the life of the patient. However, dental management of these patients is based largely on individual and expert opinion, as few studies have followed patients prospectively to determine factors that predict adverse oral sequelae. In addition, many previous studies were conducted before wide-spread adoption of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. The objective of this multi-center study is to systematically evaluate the oral health of subjects for 2 years after commencement of RT, with the goal of identifying risk factors that predict adverse oral outcomes post-RT. METHODS: This is a prospective multi-center longitudinal cohort study of H&N cancer patients who receive high-dose RT with curative intent. Planned enrollment is 756 subjects at 6 primary clinical sites (and their affiliated sites) in the USA. A baseline visit is conducted prior to the beginning of RT. Follow-up visits are conducted at 6, 12, 18 and 24 months from the start of RT. The primary outcome measure is the 2-year rate of tooth loss in patients who have received at least one session of external beam RT for H&N cancer. Secondary outcome measures include the incidence of exposed intraoral bone; incidence of post-extraction complications; change in Decayed Missing and Filled Surfaces (DMFS); change in periodontal measures; change in stimulated whole salivary flow rates; change in mouth opening; topical fluoride utilization; chronic oral mucositis incidence; changes in RT-specific quality of life measures; and change in oral pain scores. DISCUSSION: This study will contribute to a better understanding of the dental complications experienced by these patients. It will also enable identification of risk factors associated with adverse outcomes such as tooth loss and osteoradionecrosis. These findings will support the development of evidence-based guidelines and inform the planning of future interventional studies, with the goal of advancing improvements in patient care and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02057510 , registered 5 February 2014.

Ultrasensitive microfluidic array for serum pro-inflammatory cytokines and C-reactive protein to assess oral mucositis risk in cancer patients.

In addition to disease diagnostics, there is a need for biomarkers to predict severity of cancer therapy side effects such as oral mucositis. Oral mucositis is an inflammatory lesion of oral mucosa caused by high-dose chemotherapy and/or radiation that is especially prevalent during oral cancer treatment. We describe here a semi-automated, modular microfluidic immunoarray optimized for ultrasensitive detection of pro-inflammatory cytokines involved in pathobiology of oral mucositis. Our goal is to methodologically identify risk of mucositis early in oral cancer treatment, before the onset of lesions. Biomarkers include tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and C-reactive protein (CRP). Protein analytes were captured from serum in a capture chamber by 1-µm magnetic beads coated with antibodies and enzyme labels. Beads are then transported downstream to a detection chamber containing an eight-sensor array coated with glutathione-coated gold nanoparticles (GSH-AuNP) and a second set of antibodies to capture the beads with analyte proteins. In this first application of the immunoarray to four-protein multiplexed measurements, ultralow detection limits of 10-40 fg mL(-1) in 5 µL serum were achieved for simultaneous detection in 30 min. Mass detection limits were 2.5-10 zmol, as few as 1500 molecules. Accuracy and diagnostic utility of the arrays were demonstrated by correlation of levels of the four biomarker proteins in serum from head and neck cancer patients with results from standard ELISA. This approach may lead to rapid, low-cost estimates of projected risk for severity of oral mucositis in cancer patients to enable improved therapeutic management.