Impact of severe oral mucositis in pediatric cancer patients on resource utilization and cancer treatment plans.

BACKGROUND: Oral mucositis is a common chemotherapy-related adverse event that may result in serious complications. Few studies have evaluated mucositis in pediatric patients. OBJECTIVE: To evaluate the impact of severe mucositis on resource utilization and on treatment plans of pediatric cancer patients. SETTING: Comprehensive cancer center in Amman, Jordan. METHOD: Retrospective study on pediatric patients undergoing active cancer treatment with a hospital admission diagnosis of severe oral mucositis (January 2015-December 2019). Patients undergoing bone marrow transplant were excluded. Severe oral mucositis was defined as interfering with oral intake and requiring intravenous opioids. MAIN OUTCOME MEASURE: We reviewed the electronic billing system and patient medical charts to determine the resources utilized during hospitalization, cost, and the impact on subsequent treatment protocols. RESULTS: During the study period, 200 patients were eligible; the average age was 8.6±5.6 years (SD) and 45% had acute lymphoblastic leukemia. The median hospital stay was 6 days (range 2-21) with a total median cost of US$ 2,176 (range 635-13,976) per admission. The median medication cost was US$ 1,075 (range 135-9010), and 85% of the patients received antibiotics during hospitalization, at a median cost of US$ 487 (range 23-2,193). Modification of the chemotherapy treatment protocol was required in 110 patients, which included dose reduction (60%), delay (38%), and discontinuation (2%). CONCLUSION: Severe oral mucositis is associated with significant resource utilization and modification of the treatment protocols. Further studies are needed to identify strategies to reduce the impact of mucositis in this patient population.

Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database.

BACKGROUND: Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. METHODS: The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). RESULTS: Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. CONCLUSIONS: Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.

Efficacy of Aloe-Vera Use for Prevention of Chemotherapy-Induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial.

Oral mucositis can be caused by chemotherapy and can affect a patient's quality of life. Nowadays, to prevent chemotherapy-induced oral mucositis (CIOM) is a crucial point in palliative care centers. This trial aimed to assess the effectiveness of aloe-vera in that concept. The trial was accomplished at Hematology Department of Hospital of Children of Damascus University, Syria. Acute lymphoblastic leukemia (ALL) children were the population from which 26 children were enrolled in the study. They were aged between 3 and 6 years old and were randomly referred according to the intervention into two groups, Aloe-vera (AV) and sodium bicarbonate 5% (13 each). Spongeous sticks were used to help in applying the material on tongue, labial and buccal mucosa, lips, floor of the mouth, and hard palate. Two blinded external examiners evaluated oral mucosa weekly for up to 2 months using the World Health Organization grading scale. Mann-Whitney U test was used to analyze data. According to the observed findings, CIOM degrees were less severe in the aloe-vera group than in the sodium bicarbonate group. Statistically significant difference of occurrence of different CIOM degrees between groups was recorded in the 2nd, 3rd, 4th, and 7th weeks of follow-up period. Moreover, Mann-Whitney U test indicated that patients in the sodium bicarbonate group began CIOM sooner than those in the aloe-vera group with a statistically significant difference (p = .001). These findings show that topical application of aloe-vera solution is effective in the prevention of CIOM in ALL children.

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.

A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.

PURPOSE: Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL. METHODS: We assessed 25-hydroxyvitamin D (25(OH)D3) and 24,25-dihydroxyvitamin D (24,25(OH)2D3) levels in 99 children with ALL before the start of 4 × 5 g/m2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D3 levels < 30 and < 50 nmol/L. Oral mucositis was defined as grade ≥ 3 according to the National Cancer Institute Criteria. RESULTS: Vitamin D deficiency occurred in respectively 8% (< 30 nmol/L) and 33% (< 50 nmol/L) of the patients at T0, and more frequently in children > 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D3 and 24,25(OH)2D3 levels at T0 and the change in 24,25(OH)2D3 levels during therapy were not associated with the development of severe oral mucositis. CONCLUSIONS: This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.

Prevention of oral mucositis secondary to antineoplastic treatments in head and neck cancer by supplementation with oral glutamine.

OBJECTIVES: to evaluate the efficacy of glutamine in the prevention of the incidence of oral mucositis secondary to cancer therapies in patients with head and neck cancer (HNC). Secondary objectives were to know the incidence of odynophagia, interruptions of treatment and the requirements of analgesia and nasogastric tube. MATERIAL AND METHODS: prospective cohort study of patients with squamous cell carcinoma of HNC treated with radiotherapy ± concomitant chemotherapy. We compared 131 patients receiving glutamine orally at a dose of 10 g/8 hours with 131 patients who did not receive it. RESULTS: patients not taking glutamine had a hazard ratio 1.78 times higher of mucositis (95% CI [1.01-3.16], p = 0.047). Regarding odynophagia, patients not taking glutamine had a hazard ratio 2.87 times higher (95% CI [1.62-5.18], p = 0.0003). The 19.8% of patients who did not take glutamine discontinued treatment versus6.9% of patients who took (p = 0.002). Regarding support requirements, 87.8% of patients without glutamine required analgesia versus 77.9% of patients with glutamine (p = 0.03) and nasogastric tube was indicated in 9.9% and 3.1% respectively (p = 0.02). CONCLUSION: oral glutamine in patients receiving cancer treatments for HNC prevents the incidence of oral mucositis and odynophagia, and decreases treatment interruptions and the use of analgesia and nasogastric tube.

Propolis in the prevention of oral mucositis in breast cancer patients receiving adjuvant chemotherapy: A pilot randomised controlled trial.

Chemo-induced oral mucositis (OM) is associated with significant symptoms, treatment delays and increased costs. This pilot randomised controlled trial aimed at evaluating the safety, tolerability and compliance with propolis in breast cancer patients receiving doxorubicin and cyclophosphamide, testing preliminary clinical efficacy of propolis in the prevention of OM, and prospectively evaluating the incidence of OM. Sixty patients were randomised to receive either a dry extract of propolis with 8%-12% of galangin plus mouth rinsing with sodium bicarbonate (experimental arm), or mouth rinsing with sodium bicarbonate (control arm). OM was evaluated with the NCI-CTCAE v4.0 after 5, 10, 15 and 21 days of treatment. Compliance with, tolerability of propolis and adverse events were recorded. The incidence of OM was also prospectively evaluated for 6 months. Two patients (6.7%) manifested a suspected skin reaction to propolis. No patient in the experimental arm developed OM > G1, while in the control arm OM > G1 was 16.7% (p = .02). The incidence of OM ≥ G1 at the end of cycles 2-8 was higher at the second (25%) and fifth cycles (45.8%). Propolis plus bicarbonate was safe, well tolerated and promisingly effective in the prevention of OM in patients with breast cancer.

Effectiveness of Black Mulberry Molasses in Prevention of Radiotherapy-Induced Oral Mucositis: A Randomized Controlled Study in Head and Neck Cancer Patients.

OBJECTIVES: Radiation-induced oral mucositis is one of the problems experienced by 70%-80% of patients receiving radiation therapy (RT). This randomized controlled trial assessed the effectiveness of black mulberry molasses in the prevention of oral mucositis in head and neck cancer patients receiving RT. INTERVENTIONS AND OUTCOME MEASURES: Eighty head and neck cancer patients scheduled to undergo RT to the oropharyngeal mucosa were randomly assigned to receive RT (42) or RT plus mulberry molasses (38). The research data were collected with a Patient Description Form, Common Terminology Criteria for Adverse Events, version 4.0, an Oral Assessment Guide, and the University of Washington Quality of Life Assessment Questionnaire. RESULTS: The incidence and severity of oral mucositis were lower in the black mulberry molasses group. However, black mulberry molasses usage was an only independent and significant factor in prevention of mucositis [HR 0.63 (%95 GI 0.40-0.98)]. There were no differences between the quality of life scores of experimental and control groups. CONCLUSIONS: This randomized controlled study showed that black mulberry molasses usage is an effective intervention in the prevention of the radiation-induced mucositis of head and neck cancer patients. However, to confirm these results, further studies are needed.

Influences of FLU/BU and FLU/MEL on incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients.

In the present study, we compared the incidence and severity of oral mucositis among patients undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with busulfan 12.8 mg/kg (FB12.8), with busulfan less than or equal to 9.6 mg/kg (FB9.6), and with melphalan 140 mg/m2 (FM). The incidence of oral mucositis after FB12.8 was the highest among these 3 groups. After FM, all of the patients had developed oral mucositis by day 7. The mean disease duration of oral mucositis after FB12.8 was 13.5 days, whereas the mean disease duration after FM was 24.9 days, and was significantly prolonged as compared to that after FB12.8 (p=0.0009). The incidence of severe oral mucositis (grade 3) after FM was significantly higher than that after FB12.8 (p=0.03). As stated above, although the incidence of oral mucositis after FB12.8 was higher than that after FM, oral mucositis after FB12.8 showed improvement relatively quickly without deterioration. In contrast, the higher incidence of severe oral mucositis and the delay in resolution of mucositis after FM were remarkable.

Randomized study of the clinical effects of ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

OBJECTIVES: Omega-3 (ω-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. METHODS: Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received ω-3-rich enteral nutrition (EN; n = 31) or ω-3-poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of ω-3 fatty acids was 900 mg in the ω-3-rich group and 250 mg in the ω-3-poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers. RESULTS: The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the ω-3-rich group, than in the ω-3-poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the ω-3-rich group than in the ω-3-poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the ω-3-rich group than in the ω-3-poor group (P = 0.012 and P = 0.015, respectively). CONCLUSIONS: ω-3-rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the ω-3-poor EN support.

Nutritional, microbiological, and therapeutic factors related to mucositis in head and neck cancer patients: a cohort study / Factores nutricionales, microbiológicos y terapéuticos relacionados con el desarrollo de mucositis en pacientes con cáncer de cabeza y cuello: un estudio de cohorte

Purpose: the objective was to demonstrate if treatment modality, nutritional status and oropharyngeal flora contribute to the development of mucositis in radiotherapy-treated head and neck cancer. Methods: single-cohort study of patients with head and neck cancer (H&N) in which radiotherapy was indicated. Nutritional status was evaluated using SGA, BMI, and FFMI. A buccal smear was performed before radiotherapy for cultivation of bacteria and yeasts. Mucositis was evaluated using the WHO grades. Relative risk (RR) and its 95% CI were calculated. Results: the study included 35 patients, 74.3% males, 63.8 (9.9) years of age, and 34.3% malnourished. The diagnoses included larynx (40.0%), oral (25.7%), and pharynx cancer (11.4%). Treatment comprised 66.0 Gy of radiation, chemotherapy (60.0%), and surgery (57.1%). Bacteria were found in 28.6%, including Staphylococcus aureus (8.6%) and Escherichia coli (8.6%). Yeasts (Candida spp.) were found in 35.3%. Mucositis was more frequent in patients with definitive radiotherapy [100% vs. 65%, p = 0.01; RR = 1.54 (CI95% 1.12 to 2.12)]. Neither SGA nor BMI or FFMI were related to the development or severity of mucositis. Positive cultures for bacteria before radiotherapy were related to severe mucositis [44.4% vs. 12%, p = 0.039; RR = 4.17 (CI95% 1.22 to 14.24)], but there was no relationship with the presence of yeasts. Previous surgery was not associated with the appearance of the studied strains of bacteria. Conclusion: bacterial colonization of the oropharynx prior to radiotherapy may be a factor for severe mucositis in H&N patients (AU)

Objetivo: el objetivo fue demostrar si la modalidad de tratamiento, el estado nutricional y la flora orofaríngea contribuyen al desarrollo de mucositis en pacientes con cáncer de cabeza y cuello tratados con radioterapia. Métodos: estudio de cohorte de pacientes con cáncer de cabeza y cuello (CyC) tratados con radioterapia. El estado nutricional se evaluó utilizando VGS, IMC e IMM. Se realizó un frotis bucal antes de la radioterapia para el cultivo de bacterias y levaduras. Se evaluó la mucositis usando los criterios de la OMS. Se calcularon el riesgo relativo (RR) y su IC del 95%. Resultados: el estudio incluyó a 35 pacientes, 74,3% hombres, 63,8 (9,9) años de edad, y 34,3% desnutridos. Los tumores estaban localizados en laringe (40,0%), boca (25,7%) y faringe (11,4%). El tratamiento consistió en 66,0 Gy de radiación, quimioterapia (60,0%) y cirugía (57,1%). Se encontraron bacterias en 28,6%, incluyendo Staphylococcus aureus (8,6%) y Escherichia coli (8,6%). Se encontró Candida spp. en el 35,3%. La mucositis fue más frecuente en los pacientes con radioterapia radical [100% vs. 65%, p = 0,01; RR = 1,54 (IC95% 1,12 a 2,12)]. Ni VGS, IMC ni IMM se relacionaron con el desarrollo o la gravedad de la mucositis. Los cultivos positivos para bacterias antes de la radioterapia se relacionaron con mucositis severa [44,4% vs. 12%, p = 0,039; RR = 4,17 (IC95% 1,22 a 14,24)], pero no hubo ninguna relación con la presencia de levaduras. La cirugía no se asoció con la aparición de las cepas estudiadas de bacterias. Conclusión: la colonización bacteriana de la orofaringe antes de la radioterapia puede ser un factor para la mucositis graves en pacientes con cáncer CyC (AU)

Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis.

The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product.

[Low level laser therapy in inflammatory and infectious oral diseases]. / Photothérapie par diode électroluminescente des pathologies inflammatoires et infectieuses de la cavité orale.

PURPOSE: Low Level Laser Therapy (LLLT) is an increasingly studied technique. The authors of a meta-analysis published in 2012 had already confirmed the effectiveness of LLLT for radio-induced mucitis. Our purpose was to check its indication for similar pathologies. MATERIAL AND METHODS: The articles were selected with the PubMed engine. The selected terms were "Low Level Laser Therapy", "oral surgery", "oral infection", "oral inflammation", "oral mucosal lesions", "oral mucosal disease", "stomatitis", "aphtous", "Herpes", "oral lichen planus", and "oral ulceration". The analysis was made on the following criteria: assessment criteria, methodological quality, and bias. We estimated the level of proof according to Sackett's modified score. RESULTS: Six articles were selected. Two focused on the effectiveness of LLLT for Herpes simplex virus 1 oral symptoms. Two focused on the effectiveness of LLLT for oral lichen planus. One focused on the effectiveness of LLLT for recurrent aphthous stomatitis. The last one focused on the usefulness of LLLT to control stomatitis pain in the hand-foot-and-mouth disease. CONCLUSION: All the selected studies were assessed with a Sackett's score of IV. No study presented the required quality standards to recommend the treatment of LLLT for the selected indications.

The Indian Spice Turmeric Delays and Mitigates Radiation-Induced Oral Mucositis in Patients Undergoing Treatment for Head and Neck Cancer: An Investigational Study.

PURPOSE: Radiation-induced oral mucositis is an acute morbidity seen in patients undergoing treatment for head and neck cancers. In this study, we evaluated the efficacy of turmeric in preventing radiation-induced mucositis. METHODS: This was a single-blinded, randomized, controlled clinical trial and was conducted with head and neck cancer patients requiring 70 Gy of radiation or chemoradiotherapy (daily radiotherapy plus carboplatin once a week). Eligible patients (n = 80) were randomly assigned to receive either turmeric gargle (n = 40) or povidone-iodine ([n = 40] active comparator condition) during chemo/radiotherapy during the period of treatment. Oral mucositis was assessed using the RTOG (Radiation Therapy Oncology Group) grading system before the start, during, and at the end of the treatment by an investigator unaware of the treatment. The primary endpoint of this study was the incidence of mucositis every week during the 7-week period. The secondary endpoint was the effect of turmeric gargle on the incidence of treatment breaks, loss of scheduled treatment days, and decrease in body weight at the end of the treatment. RESULTS: This study clearly suggests that when compared with the cohorts using povidone-iodine gargle, the group using turmeric as a mouthwash had delayed and reduced the levels of radiation-induced oral mucositis and was statistically significant at all time points (P< 0.001 toP< 0.0001). Additionally, the cohorts using turmeric had decreased intolerable mucositis (P< 0.001) and lesser incidence of treatment breaks in the first half of the treatment schedule before 4 weeks (P< 0.01) and reduced change in body weight (P< 0.001). CONCLUSIONS: Gargling with turmeric by head and neck cancer patients undergoing radiation therapy provided significant benefit by delaying and reducing the severity of mucositis. Turmeric is readily available, relatively inexpensive, and highly accepted making it useful in cancer treatment.

The impact of individual in vivo repair of DNA double-strand breaks on oral mucositis in adjuvant radiotherapy of head-and-neck cancer.

PURPOSE: To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). PATIENTS AND METHODS: Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60-66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. RESULTS: Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade≥3 mucositis (n=18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade≤2 mucositis (n=13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. CONCLUSIONS: Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.

[Early-onset radiation complications and tissue damage in the treatment of head and neck tumors].

The report discusses the results of an evaluation of the effectiveness of combined radiotherapy in 1,192 cases of head and neck tumors divided into 4 groups: distant radiotherapy in standard fractions of 1.8-2.3 Gy, 5 times a week, TTD of 60 Gy (group 1 - 486 40.8%); radiotherapy + local UHF hyperthermia + regional intraarterial chemotherapy + hyper glycemia + administrations of regional intraarterial chemotherapy + hyperglycemia + local UHF hyperthermia (group 2 - 244 20.5%); accelerated superfractition radiotherapy with variable STD of 1 and 1.5/2 Gy, TTD of 60 Gy, plus neoadjuvant polychemotherapy with cisplatin 100 mg/lm2 + 5-fluorouracil, continuous intravenous infusion of 3,000 mg for 72 h (group 3 - 204 17%1); combined photon-neutron therapy (group 4 - 258 21.6%): neutron beam therapy - 36 (3%); interstitial neutron brachytherapy with 252 Cf sources in combination with external beam gamma-therapy and chemotherapy. Overall radiation injury incidence was 1,087 (91.2%); oral mucositis grade I (WHO) - 110 (9.2%), grade II - 166(13.9%), grade III - 811 (68%), radiation dermatitis - 279 (23.4%), grade I/II - 196 (16.4%), grade III/IV - 83 (7%). Grade III/IV side effects developed in 26.7% after gamma therapy and in 72.2% - in the photon-neutron group (p < or = 0.0001). Skin damage was rare, as expected, in the photon-brachytherapy group (1.8%) (p < or = 0.0001). Hence, Cf252 neutron brachytherapy and radiotherapy with concomitant chemotherapy appeared to produce the most sparing effects.

Avaliação do uso do laser de baixa intensidade e do Light-Emitting Diode (LED) no comportamento de fibroblastos e na redução da incidência da mucosite bucal em crianças sob tratamento quimioterápico / Evaluation of the use of low-intensity laser and Light-Emitting Diode (LED) on the behavior of fibroblasts and in reducing the incidence of oral mucositis in children under chemotherapy

Avaliou-se o uso do laser de baixa intensidade e do Light-Emitting Diode (LED) no comportamento de fibroblastos e na redução da incidência da mucosite bucal em crianças sob tratamento quimioterápico. Para tanto, o estudo foi executado em dois períodos experimentais distintos. No primeiro período, foi realizada a análise da viabilidade de fibroblastos Balb/c 3T3 cultivados sob déficit nutricional irradiados com laser vermelho (660nm, 40mW), laser infravermelho (780nm, 50mW) e LED vermelho (637 ± 15nm, 40mW) por 4 e 8 segundos através dos ensaios de redução do MTT e captação do vermelho neutro. No segundo período experimental realizou-se ensaio clínico randomizado duplo-cego para avaliar a eficácia do laser vermelho (660nm, 40mW) e do LED vermelho (637 ± 15nm, 40mW) na redução da incidência e da severidade da mucosite bucal e da dor relacionada em crianças portadoras de câncer submetidas a quimioterapia utilizando-se o sistema de graduação da mucosite bucal da Organização Mundial de Saúde e a Escala de Dor de Faces Revisada associada à escala analógica visual. A análise estatística foi realizada utilizando-se o teste não paramétrico de Kruskal-Wallis e analise de variância do modelo linear geral com nível de significância de 5% (p = 0,05). Observou-se com a redução do MTT uma tendência de aumento da proliferação celular relacionado diretamente com o tempo de irradiação, no entanto, não significante estatisticamente. Após 72 horas, os grupos que apresentaram maior proliferação celular foram: grupo irradiado com laser infravermelho, grupo irradiado com LED, grupo irradiado com laser vermelho, grupo controle positivo e grupo controle negativo. Já através da captação do vermelho neutro, após 72 horas o grupo que apresentou maior proliferação celular foi o grupo controle positivo (cultivado sob condições nutricionais ideais) seguido pelo grupo irradiado com laser infravermelho, grupo controle negativo e grupos irradiados com LED e laser vermelho.

The use of low-intensity laser and Light-Emitting Diode (LED) on the behavior of fibroblasts and in reducing the incidence of oral mucositis in children under chemotherapy were evaluated. The study was performed in two separate experiments. In the first moment, the viability of fibroblasts Balb/c 3T3 cultured under nutritional stress irradiated with red laser (660nm, 40mW), infrared laser (780nm, 50mW) and red LED (637 ± 15nm, 40mW) for 4 and 8 seconds was analyzed through the MTT and neutral red assays. The second experiment carried out was a double-blind randomized clinical trial aiming to assess the effectiveness of red laser (660nm, 40mW) and red LED (637 ± 15nm, 40mW) in reducing the incidence and severity of oral mucositis and related pain in children with cancer undergoing chemotherapy using the World Health Organization oral mucositis grading system and the Faces Pain Scale - Revised associated with a visual analogue scale. Statistical analysis was performed using the Kruskal-Wallis nonparametric test and ANOVA with a significance level of 5% (p = 0.05). It was observed with the MTT assay a trend of cell proliferation increase directly related to the irradiation time, however, not statistically significant. After 72 hours, the groups that showed higher cell proliferation were: infrared laser irradiated group, LED irradiated group, red laser irradiated group, positive control group and negative control group. By the neutral red assay, though, after 72 hours the group that showed higher cell proliferation was the positive control (grown under ideal nutritional conditions) followed by the group irradiated with infrared laser, the negative control group and groups irradiated with red laser and LED. By analyzing the results and considering the used parameters and phototherapy protocol, it is plausible to conclude that phototherapy with lowintensity laser and light emitting diode (LED) showed no toxicity at...

O uso da terapia com laser de baixa potência como método de prevenção de mucosite oral nos pacientes submetidos ao transplante de medula óssea

O tratamento com quimioterapia de altas doses no condicionamento do transplante de medula ósea, produz efeitos indesejáveis na cavidade oral e o de maior magnitude c a mucosite oral (MO). Através do uso do laser de baixa potencia como terapia aplicada a mucosa oral, o autor avaliou a possibilidade da redução da incidência e/ou do grau de severidade da MO em pacientes submetidos ao transplante de medula óssea auto logo ou alogênico. Durante o período de janeiro de 2004 a maio de 2005, trinta e oito pacientes portadores de doenças hematol6gicas foram randomizados em um grupo composto de 19 pacientes que receberam radiação laser e outro grupo composto de 19 pacientes que não receberam a radiação laser. O laser utilizado foi um diodo de InGaAIP, com compril11ento de onda de 660 nm e 50 mW de potencia. A técnica utilizada foi pontual, tocando a mucosa, dosimetria de 4 J/cm2, ca1culado sobre a área do feixe de 0,196 cm2. A análise dos resultados mostrou que 0 grupo que recebeu a aplicação do laser teve uma menor incidência de mucosite oral e os pacientes que apresentaram mucosite neste grupo a apresentaram em menor proporção. Baseado nestes dados pode-se afirmar que o laser de baixa potencia e um instrumento capaz de reduzir a incidência de MO.

High-dose chemotherapy followed by bone marrow transplant produces undesirable effects in the oral cavity leading to oral mucositis (OM). Mucositis may be a painfull and debilitating side-effect. Through the use of the low power laser as therapy applied to the oral mucosa membrane, the author evaluated the potencial for a reduction in the incidence and/or severity of oral mucositis in patients submitted to autologus or alogenic bone marrow transplant. From January 2004 to May 2005, thirty eight patients bearers of hcmatological diseases were randomized into a group composed of 19 patients that received laser radiation and a group composed of 19 patients that did not receive the laser radiation. For the irradiation was used an diode InGaAIP, emiting light at 660 nm wavelenght with output power of 50 mW, giving an energy density of 4 J/cm2 measured at the end of fiberoptic with 0, 196cm2 of section area during the experiment. The tip of the laser device touched the oral mucosa.The results showed that the group which received the application of the laser had a smaller incidence of OM and even in the patients that presented mucositis in this group, it occurred in lower incidence. Based on these results we can affirm that the low level laser therapy is an instrument capable of reducing the incidence of OM.

Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children.

AIM: To test the efficacy of a multiple micronutrient fortified salt in improving the micronutrient status and health of school children and its effect on cognition. METHODS: A salt fortified with multiple micronutrients was developed containing chelated ferrous sulphate, microencapsulated vitamin A, B1, B2, B6, B12, folic acid, niacin, calcium pantothenate and iodine. The efficacy of the fortified salt was assessed in 7-11 year old school children in Chennai, India. In the experimental group (N=63), the food in the school kitchen was cooked with the fortified salt for a period of one year. The control group (N=66) consisted of day scholars who did not eat at the school. Hemoglobin, red blood cell count, hematocrit, serum vitamin A, urinary iodine and prevalence of angular stomatitis were measured at baseline and at the end of the study after one year. A battery of 7 memory tests (The personal information test, the Mann-Suiter Visual memory screen for objects, The digit span forward test, The digit span backward test, The delayed response test, The Benton Visual Retention Test and The Cattells retentivity test), one test for attention and concentration (Letter cancellation test) and one test for intelligence (Raven's coloured progressive matrices) were administered to all the children at baseline and endline. RESULTS: There was a significant (p<0.05) improvement in the experimental group in hemoglobin, red cell count, urinary iodine and serum vitamin A whereas in the control group there was a statistically significant decline (p<0.05) in hemoglobin, hematocrit, red cell count and urinary iodine. Angular stomatitis was eliminated from baseline 30.4% in the experimental group whereas it increased from 3.25% to 25.5% in the control group. In 4 tests out of the 7 memory tests and in the letter cancellation test for attention, the mean increment in scores in the experimental group is significantly more (p<0.05) than the control group. There was no significant improvement in overall intelligence as seen in the Ravens progressive matrices between the experimental and control groups. CONCLUSION: The study shows that the multiple micronutrient fortified salt is effective in improving multiple micronutrient status and cognition in children.