Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy treatment for head and neck squamous cell carcinoma.

OBJECTIVE: Opportunistic infections may affect the oral mucosa of patients undergoing radio/chemotherapy through exacerbation of oral mucositis. The aim of this study is to evaluate the oral shedding of all eight human herpesviruses and its possible association with oral mucositis. MATERIALS AND METHODS: In this prospective cohort study, we analyzed oral rinse samples, collected weekly, from 20 patients during radiotherapy treatment. Serologic status to HSV1 and HSV2, EBV, CMV, and VZV in three different periods was performed by ELISA assay. PCR and enzymatic digestion was performed to detect HSV1, HSV2, EBV, CMV, VZV, HHV6, HHV7, and HHV8. Oral mucositis was evaluated according to the WHO criteria. RESULTS: Oral shedding of EBV, HHV6, and HHV7 was observed in all weeks of radiotherapy. Considering the episodes of shedding, the highest frequency was found in patients with EBV excretion (55.0%). No virus reactivation was observed by serological analysis. EBV oral shedding frequency was significantly higher than that of other viruses and showing a positive correlation with oral mucositis grade ≥2. CONCLUSIONS: There was a positive correlation between EBV oral shedding and oral mucositis grade ≥2, particularly after 3 weeks of radiotherapy, a period in which the severity of mucositis was statistically higher. These findings allow us to infer that the local inflammatory environment in mucositis grade ≥2 is more favorable for EBV replication. CLINICAL RELEVANCE: Mucositis is a frequent and important side effect of radio/chemotherapy treatment. Understanding the possible participation of viruses in the mechanism of this condition is important to develop strategies for treatment and prevention.

Seroprevalence of herpes virus associated with the presence and severity of oral mucositis in children diagnosed with acute lymphoid leukemia.

INTRODUCTION: Acute lymphoid leukemia (ALL) is the hematologic neoplasia most commonly diagnosed in children. Among the secondary side effects of chemotherapy, mucositis is the most frequent complication. The aim of this study was to evaluate the seroprevalence of herpes viruses HSV-1, EBV, and CMV and the presence and severity of oral mucositis in children and adolescents diagnosed with ALL. METHODOLOGY: Ninety-two patients diagnosed with ALL were evaluated. Serum samples were collected before chemotherapy and tested by ELISA method. Presence of mucositis was observed on the first day before antineoplastic therapy (D0) and on 7th day post-therapy (D7). Classification of mucositis intensity was performed according to toxicity criteria established by the National Cancer Institute. RESULTS: 70.7% of the patients presented mucositis on the D7, and of these, 60% were classified as Grade I and 40% as Grade II; of the 92 individuals tested, 59 (64.1%) presented antibodies for HSV-1, 57 (62%) for EBV, 75 (81.5%) for CMV_IgG, and 21 (22.8%) for CMV_IgM. Using a logistic regression model, the presence of HSV-1 was observed to be 4.10 times greater in Grade II mucositis severity than in Grade I (P = 0.03). CONCLUSION: Based on the findings of this study, it was possible to conclude that infection by the herpes viruses HSV-1, EBV, and CMV is ubiquitous in the studied population and that HSV-1 may be a risk factor for aggravating the severity of mucositis.

A non-invasive oral rinse assay predicts bone marrow engraftment and 6 months prognosis following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: We have previously shown in a pediatric Hematopoietic stem cell transplant (HSCT) population that a non-invasive oral rinse can be used to monitor engraftment, neutrophil tissue delivery and susceptibility to infection post-HSCT. METHODS: Using the same oral rinse protocol, we studied neutrophil tissue delivery kinetics and its relationship to clinical parameters and outcomes following HSCT in 29 adult patients. Oral neutrophil counts were compared to circulating neutrophil levels, oral mucositis scores and patient health status at 6 months post-HSCT. RESULTS: Neutrophils were detected on average 8.4 ± 3.4 SD days earlier in the oral tissues than in the blood circulation, enabling us to confirm successful engraftment more than one week earlier than when using blood neutrophil counts alone. As well, in this population the time-span between oral engraftment (OE) and blood engraftment (BE) was a consistent predictor of treatment outcome at 6 months following HSCT where a BE-OE of <6 days resulted in 100% of patients having a negative outcome. CONCLUSION: We conclude that monitoring the timing of neutrophil delivery to the oral tissues with a non-invasive oral rinse has the potential to allow the physician to identify those patients who are at a high risk of HSCT failure within just a few weeks of the initiation of treatment.

Association between oral health and body cell mass in hospitalised elderly.

OBJECTIVE: To examine whether oral health in hospitalised elderly was associated with body cell mass (BCM) measured with Bioimpedance spectroscopy. BACKGROUND: Body cell mass is the tissue producing the metabolic work necessary for all body functions. BCM is mainly muscle tissue. Low BCM is associated with diseases, ageing and poor nutritional status. Reduced oral health is also associated with these parameters; thus, BCM and oral health may be related. METHODS: Body cell mass was measured using Bioimpedance spectroscopy in 138 acutely hospitalised elderly ≥70 years. The number of own teeth, posterior occluding tooth pairs and decayed teeth were registered. Oral hygiene was registered with Mucosal-Plaque Score, an index based on assessment of plaque accumulation and mucosal/gingival inflammation. Mini Nutritional Assessment-Short Form, body mass index and handgrip strength were used as nutritional indicators. Comorbidity was assessed with Cumulative Index Rating Scale. RESULTS: Mean age was 83.2 ± 5.9 years, ranging from 70 to 101 years. Dentition status was significantly and positively associated with BCM. Reduced oral hygiene was significantly associated with low BCM. These findings remained significant after adjusting for confounders. CONCLUSION: These results show that compromised oral health was significantly associated with reduced BCM in hospitalised elderly.

Outcome of surgical treatment of peri-implantitis: results from a 2-year prospective clinical study in humans.

AIM: The aim of the present study was to evaluate the outcome of a surgical procedure based on pocket elimination and bone re-contouring for the treatment of peri-implantitis. MATERIAL AND METHODS: The 31 subjects involved in this study presented clinical signs of peri-implantitis at one or more dental implants (i.e. ≥6 mm pockets, bleeding on probing and/or suppuration and radiographic evidence of ≥2 mm bone loss). The patients were treated with a surgical procedure based on pocket elimination and bone re-contouring and plaque control before and following the surgery. At the time of surgery, the amount of bone loss at implants was recorded. RESULTS: Two years following treatment, 15 (48%) subjects had no signs of peri-implant disease; 24 patients (77%) had no implants with a probing pocket depth of ≥6 mm associated with bleeding and/or suppuration following probing. A total of 36 implants (42%) out of the 86 with initial diagnosis of peri-implantitis presented peri-implant disease despite treatment. The proportion of implants that became healthy following treatment was higher for those with minor initial bone loss (2-4 mm bone loss as assessed during surgery) compared with the implants with a bone loss of ≥5 mm (74% vs. 40%). Among the 18 implants with bone loss of ≥7 mm, seven were extracted. Between the 6-month and the 2-year examination, healthy implants following treatment tended to remain stable, while deepening of pockets was observed for those implants with residual pockets. CONCLUSION: The results of this study indicated that a surgical procedure based on pocket elimination and bone re-contouring and plaque control before and following surgery was an effective therapy for treatment of peri-implantitis for the majority of subjects and implants. However, complete disease resolution at the site level seems to depend on the initial bone loss at implants. Implants with no signs of peri-implantitis following treatment tended to remain healthy during the 2-year period, while a tendency for disease progression was observed for the implants that still showed signs of peri-implant disease following treatment.

Identification of periodontal pathogens in healthy periimplant sites.

PURPOSE: : The aim of this study was to evaluate the presence of periodontopathogens in subgingival periimplant sites in partially edentulous patients using polymerase chain reaction procedures, with regard to areas with clinical and radiographic signs of health and areas presenting periimplant disease. MATERIALS AND METHODS: : Thirty nonsmoking, partially edentulous patients, aged 30 to 76 years, were included in this study and divided in 3 groups according their clinical and radiographic characteristics. Group A (n = 10) presented periimplant health, group B (n = 10) presented periimplant mucositis, and group C (n = 10) were patients with periimplantitis. Periimplant tissues were clinically examined as regards the color of mucosae, presence of bacterial plaque, depth and bleeding on probing, and local suppuration. History of periodontal disease was also considered. Radiographic analysis evaluated the presence of bone loss around the implant. Samples of periimplant crevicular fluid were collected to analyze the presence of periodontal pathogens, Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf), and Treponema denticola (Td). RESULTS: : The results showed that the history of periodontal disease is associated with periimplant disease. The bacteria Aa, Pg, Pi, Td, and Tf were present in periimplant sites clinically and radiographically characterized, as healthy periimplant tissues, mucositis, and periimplantitis. CONCLUSIONS: : We concluded that Aa, Pg, Pi, Td, and Tf are present in healthy and diseased conditions. Therefore, these periodontal pathogens are not strictly related to periimplant disease sites.

Laser phototherapy as topical prophylaxis against head and neck cancer radiotherapy-induced oral mucositis: comparison between low and high/low power lasers.

BACKGROUND AND OBJECTIVE: Oral mucositis is a dose-limiting and painful side effect of radiotherapy (RT) and/or chemotherapy in cancer patients. The purpose of the present study was to analyze the effect of different protocols of laser phototherapy (LPT) on the grade of mucositis and degree of pain in patients under RT. PATIENTS AND METHODS: Thirty-nine patients were divided into three groups: G1, where the irradiations were done three times a week using low power laser; G2, where combined high and low power lasers were used three time a week; and G3, where patients received low power laser irradiation once a week. The low power LPT was done using an InGaAlP laser (660 nm/40 mW/6 J cm(-2)/0.24 J per point). In the combined protocol, the high power LPT was done using a GaAlAs laser (808 nm, 1 W/cm(2)). Oral mucositis was assessed at each LPT session in accordance to the oral-mucositis scale of the National Institute of the Cancer-Common Toxicity criteria (NIC-CTC). The patient self-assessed pain was measured by means of the visual analogue scale. RESULTS: All protocols of LPT led to the maintenance of oral mucositis scores in the same levels until the last RT session. Moreover, LPT three times a week also maintained the pain levels. However, the patients submitted to the once a week LPT had significant pain increase; and the association of low/high LPT led to increased healing time. CONCLUSIONS: These findings are desired when dealing with oncologic patients under RT avoiding unplanned radiation treatment breaks and additional hospital costs.

A Meta-Analysis on the Efficacy of Zinc in Oral Mucositis during Cancer Chemo and/or Radiotherapy-An Evidence-Based Approach.

Zinc in various therapeutic doses was used on patients suffering from oral mucositis during cancer treatment. A meta-analysis was conducted to probe the role of oral zinc as a possible treatment option for oral mucositis. A literature search was done using PubMed, EBSCO, Cochrane, MedLine, ScienceDirect, ResearchGate and Google Scholar with key words. The analysis was directed to recognize and identify the use of zinc supplementations at a confidence interval (CI) 95% with p value significance taken as <0.05. A total number of 21,428 articles was retrieved. After thorough screening and assessment of the eligibility criteria, 10 articles were included in qualitative and quantitative analysis in the study. The 10 articles constituted a total sample size of 299 in the case group and 294 in the control group. Oral zinc doses used were 25 mg, 30 mg, 50 mg and 220 mg capsules and mouthwash of 0.2% zinc, as well as 0.5 g of granules dissolved in 5% sodium alginate solution. Two studies showed no significance, with the overall effect 1.61. Eight studies favored zinc over a placebo with an overall effect size of -0.89 at 95% CI of -1.08 and -0.70 which was statistically significant (Z=9.27, p<0.00001). This analysis suggests that zinc usage has shown significant reduction in the severity of oral mucositis but not prevention. The onset of the reaction was delayed and hastened healing. Pharyngeal mucositis, pain and quality of life of the individuals received no effect from zinc therapy.

Double-blind placebo-controlled multicenter phase II trial to evaluate D-methionine in preventing/reducing oral mucositis induced by radiation and chemotherapy for head and neck cancer.

BACKGROUND: The purpose of this study was to test if oral D-methionine (D-met) reduced mucositis during chemoradiotherapy. METHODS: We conducted a placebo-controlled double-blind randomized phase II trial of D-met (100 mg/kg p.o. b.i.d.) testing the rate of severe (grades 3-4) mucositis. RESULTS: Sixty patients were randomized. Grade 2 + oral pain was higher with placebo (79% vs 45%; P = .0165), whereas grade 2 + body odor was greater with D-met (3% vs 41%; P = .0015). Mucositis was decreased with D-met by the physician (World Health Organization [WHO], P = .007; Radiation Therapy Oncology Group [RTOG], P = .009) and patient functional scales (RTOG, P = .0023). The primary end point of grades 3 to 4 mucositis on the composite scale demonstrated a decrease with D-met (48% vs 24%; P = .058), which was borderline in significance. A planned secondary analysis of a semiquantitative scoring system noted decreased oral ulceration (2.2 vs 1.5; P = .023) and erythema (1.6 vs 1.1; P = .048) with D-met. CONCLUSION: Although not meeting the primary end point, results of multiple assessments suggest that D-met decreased mucositis.

Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients.

Mucositis Oral: actualización en el Diagnóstico, Prevención y Tratamiento / Oral mucositis: update in diagnosis, prevention and treatment

La mucositis oral (MO) es la reacción secundaria aguda más frecuente en la cavidad oral y tracto gastrointestinal en pacientes oncológicos sometidos a quimioterapia o radioterapia de cabeza y cuello que incide negativamente en la calidad de vida del paciente. Su tratamiento requiere de un manejo multidisciplinario con el objetivo de minimizar la incidencia y severidad de esta patología. El desconocimiento parcial respecto de su etiopatogenia imposibilita la realización de protocolos para el manejo de esta complicación. Si bien existe evidencia científica respecto a las alternativas de prevención y tratamiento, éstas dependen de la evaluación individual que haga el clínico con cada paciente. A continuación, se presenta una revisión bibliográfica actualizada de la literatura científica publicada y se discuten aquellos aspectos más relevantes en torno a la prevención y tratamiento de la mucositis oral.

Oral mucositis (OM) is the most common acute secondary reaction in the oral cavity and gastrointestinal tract in cancer patients undergoing chemotherapy or radiotherapy to the head and neck, which adversely affects the patient's quality of life even at the risk of death. This requires multidisciplinary knowledge and management in order to minimize the incidence and severity of this pathology. The partial lack of knowledge regarding its etiopathogenesis makes it impossible to establish standardized guidelines for the management of this complication. Although there is scientific evidence regarding prevention and treatment alternatives, these depend on the individual evaluation of each patient and the clinical scenario in which they are presented. An updated review of the published scientific literature is presented below and those aspects most relevant to the prevention and treatment of oral mucositis are discussed.

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.

[The immunomorphological characteristics of chronic recurrent ulcerative stomatitis].

The aim of the present study was to evaluate the immunomorphological characteristics of chronic recurrent ulcerative stomatitis. The patients were divided into 3 groups: 16 patients with mild, 15 patients with moderate, and 9 with severe stomatitis. The cytological smears were stained by Papanicolaou method. We have evaluated indexes of maturation (MI), keratinization (KI), destruction (DI), and inflammation-destruction (IDI). The immunocytochemistry was used to evaluate the local immune reactions. Anti-CD20 (pan-B marker), Anti-CD3 (pan-T marker), CD4 (marker of T helper), CD8 (marker of T cytotoxic lymphocytes) monoclonal antibodies were used (LSAB, DAB). The comparative analysis of cytological indexes in acute and remission phases of chronic recurrent ulcerative stomatitis showed that DI and IDI decreased in remission phase compared with acute phase, but did not return to norm. It seems that inflammation persists in remission phase despite the absence of symptomatic ulcerative lesion. In mild chronic recurrent ulcerative stomatitis the dynamic quantitative changes of immunocompetent cells in acute and remission phases show that the increased number of CD4+ T and CD20+ B lymphocytes has been found in remission phase indicating a persistent immune reaction and presence of non-eliminated pathogenic factors.

Immediate loading of mandibular overdentures supported by one-piece, direct metal laser sintering mini-implants: a short-term prospective clinical study.

BACKGROUND: Only a few studies have dealt with immediately loaded, unsplinted mini-implants supporting ball attachment-retained mandibular overdentures (ODs). The aim of this study is to evaluate treatment outcomes of ball attachment-retained mandibular ODs supported by one-piece, unsplinted, immediately loaded, direct metal laser sintering (DMLS) mini-implants. METHODS: Over a 4-year period (2009 to 2012), all patients referred to the Dental Clinic, University of Varese, and to a private practice for treatment with mandibular ODs were considered for inclusion in this study. Each patient received three or four DMLS mini-implants. Immediately after implant placement, a mandibular OD was connected to the implants. At each annual follow-up session, clinical and radiographic parameters were assessed, including the following outcome measures: 1) implant failures; 2) peri-implant marginal bone loss; and 3) complications. Statistical analysis was conducted using a life-table analysis. RESULTS: A total of 231 one-piece DMLS mini-implants were inserted in 62 patients. After 4 years of loading, six implants failed, giving an overall cumulative survival rate of 96.9%. The mean distance between the implant shoulder and the first visible bone-to-implant contact was 0.38 ± 0.25 and 0.62 ± 0.20 mm at the 1- and 4-year follow-up examinations, respectively. An incidence of 6.0% of biologic complications was reported; prosthetic complications were more frequent (12.9%). CONCLUSIONS: Within the limits of this study, it can be concluded that the immediate loading of one-piece, unsplinted, DMLS titanium mini-implants by means of ball attachment-supported mandibular ODs is a successful treatment procedure. Long-term follow-up studies are needed to confirm these results.

Angular stomatitis and riboflavin status among adolescent Bhutanese refugees living in southeastern Nepal.

BACKGROUND: Between 1990 and 1993, fear of ethnic persecution led 83,000 ethnic Nepalese to flee from Bhutan to refugee camps in Nepal, where they remained at the time of this study. Reported cases of angular stomatitis (AS), ie, thinning or fissuring at the mouth angles, increased 6-fold from December 1998 to March 1999, from 5.5 to 35.6 cases per 1000 per month. This increase came after the removal of a fortified cereal from rations. OBJECTIVES: The main objectives were to assess the prevalence of AS and of low concentrations of riboflavin, folate, vitamin B-12, and iron by using biochemical measures; to determine whether riboflavin status was associated with AS; and to assess the potential of AS as a screening measure for low riboflavin concentrations. DESIGN: In October 1999, we performed a survey among a random sample of 463 adolescent refugees in which we conducted interviews and physical examinations and obtained blood specimens for riboflavin assessment. Riboflavin status was assessed with the erythrocyte glutathione reductase (EC 1.6.4.2) activity coefficient. After we excluded those adolescents who had taken vitamins during the past month, 369 were eligible for analyses. RESULTS: AS was common (26.8%; 95% CI: 22.3, 31.3), the prevalence of low riboflavin concentrations was high (85.8%; 80.7, 90.9), and riboflavin status was associated with AS. Adolescents with AS had significantly lower riboflavin concentrations than did adolescents without AS (P = 0.02). The adjusted odds ratio for AS and low riboflavin concentrations was 5.1 (1.55, 16.5). CONCLUSION: Globally, riboflavin deficiency is rare. Its emergence in food-dependent populations can be a harbinger of other B-vitamin deficiencies.

Mucosal damage: a major risk factor for severe complications after cytotoxic therapy.

The oral and gastrointestinal mucosa is frequently damaged during chemotherapy and radiotherapy in patients with cancer, leading to a high incidence of mucositis (ie, oral, esophageal, lower gastrointestinal tract mucositis). Patients with mucositis often experience considerable pain and discomfort. Furthermore, neutropenic patients with mucositis have an increased risk of potentially life-threatening infections as well as prolonged hospital stays. Mucositis may also require that subsequent chemotherapy or radiotherapy doses be reduced, thereby potentially compromising the efficacy of cancer therapy. Standard care for oral mucositis is based on effective oral hygiene, appropriate analgesia, infection management, and parenteral nutrition when needed; few other approaches have been shown to be effective. The evaluation of new options to treat and prevent mucositis rather than control the symptoms is therefore an urgent priority. A comprehensive understanding of the complex pathobiology of mucositis will help to identify potential targets for new drugs. Promising investigational approaches have recently emerged. These include fibroblast growth factor-20, which is effective in animal models of chemotherapy/radiation-induced mucosal toxicity, and is being investigated in clinical studies. The candidate that is most advanced in terms of drug development is recombinant human keratinocyte growth factor (rHuKGF; palifermin), which in phase III clinical trials was shown to reduce the severity and duration of oral mucositis and improve clinical sequelae.

Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy.

In 1997, the National Cancer Institute (NCI) led an effort to revise and expand the Common Toxicity Criteria (CTC) with the goal of integrating systemic agent, radiation, and surgical criteria into a comprehensive and standardized system. Representatives from the Radiation Therapy Oncology Group (RTOG) participated in this process in an effort to improve acute radiation related criteria and to achieve better clarity and consistency among modalities. CTC v. 2.0 replaces the previous NCI CTC and the RTOG Acute Radiation Morbidity Scoring Criteria and includes more than 260 individual adverse events with more than 100 of these applicable to acute radiation effects. One of the advantages of the revised criteria for radiation oncology is the opportunity to grade acute radiation effects not adequately captured under the previous RTOG system. A pilot study conducted by the RTOG indicated the new criteria are indeed more comprehensive and were preferred by research associates. CTC v. 2.0 represents an improvement in the evaluation and grading of acute toxicity for all modalities.

Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review.

BACKGROUND AND PURPOSE: To determine the frequency of mucositis and associated outcomes in patients receiving radiotherapy (RT) for head and neck cancer through a systematic review of recently published literature. MATERIALS AND METHODS: According to the study protocol, databases were searched for randomized clinical trials (English only, 1996-1999) of patients with head and neck cancer receiving RT with or without chemotherapy that reported one or more outcomes of interest. RESULTS: Thirty-three studies (n=6181 patients) met inclusion criteria. Mucositis was defined using a variety of scoring systems. The mean incidence was 80%. Over one-half of patients (56%) who received altered fractionation RT (RT-AF) experienced severe mucositis (grades 3-4) compared to 34% of patients who received conventional RT. Rates of hospitalization due to mucositis, reported in three studies (n=700), were 16% overall and 32% for RT-AF patients. Eleven percent of patients had RT regimens interrupted or modified because of mucositis in five studies (n=1267) reporting this outcome. Data insufficiency or heterogeneity prohibited analysis of mucositis severity and other associated outcomes, such as oral pain, dysphagia and opioid use. CONCLUSIONS: Mucositis is a frequent, severe toxicity in patients treated with RT for head and neck cancer. While it appears that mucositis may lead to hospitalization and treatment interruptions, its overall impact on outcomes has not been adequately investigated.

A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients.

A system was developed for scoring oral mucositis in order to investigate its connection with fever and bacteraemia due to 'viridans' streptococci. A series of 42 allogeneic bone marrow transplant recipients given demethoxydaunorubicin and total body irradiation for conditioning therapy were monitored daily for the presence of lesions, erythema, oral oedema, pain and dysphagia, each of which was graded numerically at four levels. These values were added together to yield a daily mucositis score (DMS) with a scale of 0-15. Mucositis developed shortly after transplant and progressed within a few days to grade III (WHO grade 3-4) in the majority of patients. Bacteraemia due to 'viridans' streptococci was documented in 64% of cases and the organisms were first detected as fever developed and mucositis approached its peak. The WHO scheme defined mucositis as either absent or grade 3-4 corresponding to a DMS of 4 or 5, whereas a grading system based on the most pronounced sign or symptom resulted in three grades of severity which corresponded to a DMS of less than or equal to 4, 5-9 and greater than or equal to 10 respectively. However, only the DMS permitted monitoring of mucositis through all its stages of development. The scheme therefore offers the potential for exploring causal relationships between mucosal damage, granulocytopenia, fever and bacteraemia and can be included as an independent measure in studies of prevention and therapy of complications related to mucositis.

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.