Oral Mucositis Assessment Scale Score Research Articles

MINIMAL IMPACT OF FOOD, DRINK, OR TEMPERATURE ON THE PHARMACOKINETICS OF A SUBLINGUAL FILM USING AA NOVEL PRODRUG OF EPINEPHRINE (DESF)

<h3>Introduction</h3> DESF is a novel alternative dosage form to Epinephrine injection. A pre-clinical study was conducted to test the effect of sublingual temperature (SL) and if exposure of the sublingual mucosa to food or drink prior to administration of DESF has an impact on the PK profile of epinephrine <i>in vivo</i>. <h3>Methods</h3> A total of 18 male Yucatan miniature swine, separated into three groups and dosed with DESF 12 mg, were used for this study. Group 1 did not receive a pre-treatment. Groups 2 and 3 were pretreated with either full-fat whole milk or extra virgin olive oil or with either warm or cool compresses at the dose site. Following dosage, the animals had Pharmacokinetics (PK) blood samples obtained at multiple timepoints, with Oral Mucositis Assessment Scale scores performed at pre-dose, 4-, and 24-hours post-dose. <h3>Results</h3> Similar PK profiles were observed for epinephrine regardless of pretreatment of food and drink. Groups pretreated with milk or oil displayed a mean Cmax and AUC similar to or higher than the control group. Tmax was similar for all treatment groups, between 25 to 30 minutes. As for the impact of temperature, pre-treatment with a warm or cool compress did not result in significantly different SL temperatures. Similar PK profiles were also observed for epinephrine regardless of pre-treatment. Simple linear regression analysis suggests that there was not a strong relationship between SL temperature and Cmax. <h3>Conclusion</h3> These results suggest that food, drink, and temperature each have minimal impact on the PK profiles of DESF.

A comparative study to assess the effectiveness of curcumin, mucosamin, and chlorhexidine in chemotherapy-induced oral mucositis

BackgroundOral mucositis is one of the most frequent and challenging side effects of chemotherapy. At present, none of the guidelines recommend the use of various mouthwashes available for the treatment of oral mucositis. MethodsThis study was designed to evaluate the efficacy of curcumin, mucosamin, and chlorhexidine in the treatment of chemotherapy-induced oral mucositis. In this randomized and double-blind study, 71 patients over 18 years, who received chemotherapy and suffered from chemotherapy-induced oral mucositis, were randomized into curcumin, mucosamin, and chlorhexidine groups. The World Health Organization (WHO) Oral Toxicity Scale, the Oral Mucositis Assessment Scale (OMAS), and the Numerical Rating Scale (NRS) were used to evaluate oral mucositis. The main endpoint included the onset of complete recovery after starting the treatment. FindingsBased on the WHO, OMAS for erythema, and NRS criteria, complete recovery was achieved from the third day in the curcumin group, which was significantly earlier compared to the other two groups (P < 0.05). The OMAS score for ulceration represented an improvement from day 5 in the curcumin group, which was significantly faster compared to the other two groups (P = 0.04). ConclusionsOur results indicated that all three approaches were effective in improving oral mucositis; however, curcumin could result in faster recovery in comparison with mucosamin and chlorhexidine. The use of curcumin in the treatment of oral mucositis appears to be a viable intervention for reducing potential compromise to treatment and improving the quality of life.

Behaviour and Prevention of 5'Fluorouracil and Doxorubicin-induced Oral Mucositis in Immunocompetent Patients with Solid Tumors: A Randomised Trial.

This study evaluated the efficacy of four methods to prevent chemotherapy-induced oral mucositis (OM) in patients with solid tumors (ST). In addition, the behaviour of OM was investigated in these oncological patients. Forty-eight patients, aged 27-84, were randomly allocated to different groups from the first day of chemotherapy (CT), in the following sequence: group 1: intensive oral care programme (IOCP); group 2: 0.12% chlorhexidine mouthrinse; group 3: 0.03% triclosan mouthrinse; group 4: low-level laser therapy (LLLT). Oral mucositis was evaluated on the 7th and 14th days by means of the Oral Mucositis Assessment Scale (OMAS). Thirty-one (64.5%) patients developed OM in the first cycle of CT and the pain was significantly associated with OM severity (p < 0.0001). The statistically significantly worst OMAS score was found for the lips and buccal mucosa (p < 0.0001). Despite a lack of statistical significance, IOCP and LLLT notably demonstrated potential effects to prevent OM in patients who presented with only oral erythema (75%) and lower peak of severity during the follow up, respectively. Improved oral care awareness is needed in patients undergoing 5'fluorouracil and doxorubicin, mainly to avoid pain caused by oral mucositis. Oral mucositis was more prevalent and aggressive in oral sites exposed to chronic trauma. The IOCP and LLLT approaches showed positive results to prevent oral mucositis and should be further investigated in similar and larger samples.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value <0.001). There was no difference in median pain score, (p value=0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value=0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer.

Oral mucositis (OM) is a common acute side effect during radiotherapy treatments for head and neck cancer (HNC), with a potential impact on patient's compliance to therapy, quality of life (QoL) and clinical outcomes. Its timely and appropriate management is of paramount importance. Several quantitative scoring scales are available to properly assess OM and its influence on patient-reported outcomes (PROs) and QoL. We prospectively assessed OM in a cohort of HNC patients submitted to radiation using the Oral Mucositis Assessment Scale (OMAS), while its impact on PROs and QoL was evaluated employing the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN) and the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-HN). Evaluation of OMAS scores highlighted a progressive increase in OM during treatment and a partial recovery after the end of radiation. These trends were correlated to PROs and QoL as evaluated with OMWQ-HN and FACT-HN questionnaires. In the present study, we provided a quantitative assessment of OM, PROs and QoL in HNC patient undergoing radiotherapy, potentially useful for future comparison.

Symptoms Reported by Head and Neck Cancer Patients during Radiotherapy and Association with Mucosal Ulceration Site and Size: An Observational Study.

BackgroundSelf-reported pain and impairment of oral functions varies markedly and often in spite of extensive oral mucositis (OM). The aim of the current study was to appraise how patient-reported debilitation caused by OM is influenced by the extent and possibly location of the OM lesions.MethodsPatients with head and neck cancer undergoing radiotherapy were examined before treatment, twice weekly during 6-7 weeks of therapy, and 3-4 weeks after therapy completion. OM signs of 33 participants were evaluated using the Oral Mucositis Assessment Scale (OMAS), while OM symptoms were recorded using Patient-Reported Oral Mucositis Symptom (PROMS)-questionnaires. Changes in OM experience as a function of OM signs was undertaken by comparing the aggregated and individual PROMS scale values at the point of transition of OMAS ulceration scores between 0 to 1, 1 to 2 and 2 to 3, respectively in the nine intra-oral locations designated in the OMAS. ANOVA with pairwise contrasts using the LSD procedure was applied for comparisons of mean changes of PROMS scale values for the participants who experienced an OMAS score of 2 or more during therapy (n=24).ResultsImpairment of eating hard foods was more when the OMAS score for ulceration anywhere in the mouth or in the soft palate changed from 1 to 2, compared to between score 0 and 1 (p=.002 and p=.05) or between score 2 and 3 (p=.001 and p=.02). Mouth pain increased more upon transition of OMAS score anywhere in the mouth from 1 to 2 compared to 0 to 1 (p=.05).ConclusionThe relationship between patient-reported impairment of oral function and pain caused by OM ulceration is not linear, but rather curvilinear. Our findings should prompt investigators of future interventional trials to consider using a less severe outcome than maximum OM scores as the primary study outcome.

Randomized double-blind placebo-controlled trial of celecoxib for oral mucositis in patients receiving radiation therapy for head and neck cancer

Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer (H&NC). OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Based on the role of inflammatory pathways in OM pathogenesis, we investigated effect of cyclooxygenase-2 (COX-2) inhibition on severity and morbidity of OM. In this double-blind placebo-controlled trial, 40 H&NC patients were randomized to daily use of 200 mg celecoxib or placebo, for the duration of RT. Clinical OM, normalcy of diet, pain scores, and analgesic use were assessed 2-3 times/week by blinded investigators during the 6-7 week RT period, using validated scales. Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over course of RT. Intention-to-treat analyses demonstrated no significant difference in mean Oral Mucositis Assessment Scale (OMAS) scores at 5000 cGy (primary endpoint). There was also no difference between the two arms in mean OMAS scores over the period of RT, mean worst pain scores, mean normalcy of diet scores, or mean daily opioid medication use in IV morphine equivalents. There were no adverse events attributed to celecoxib use. Daily use of a selective COX-2 inhibitor, during period of RT for H&NC, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. These findings also have implications for celecoxib use in H&NC treatment regimens (NCT00698204).

Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

AbstractGrades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P = .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P = .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P = .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P = .06; 53% vs 54%, P = .77; and 59% vs 63%, P = .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials.gov as #NCT00406393.

MuGard, an oral mucoadhesive hydrogel, reduces the signs and symptoms of oral mucositis in patients with lichen planus: a double-blind, randomized, placebo-controlled pilot study.

To determine if MuGard, a mouthwash shown to reduce the severity of oral mucositis when started before initiating antineoplastic therapy for head and neck cancers, is effective when painful, oral lesions are present in patients with biopsy-proven erosive oral lichen planus. This was a double-blind, randomized, placebo-controlled pilot study at a college of dental medicine. Twenty patients with oral lichen planus were randomly assigned to receive either MuGard (n= 10) or saline-bicarbonate control (n= 10). One teaspoonful of the assigned mouthwash was swished for 1 minute, 5 times a day, for 14 days. Outcome measures (Oral Mucositis Assessment Scale scores and visual analog scale pain scores) were obtained before the start of treatment and repeated on days 2, 7, and 14. Significant reductions in all outcome measures occurred in the MuGard-treated group. Number-needed-to-treat (NNT) to achieve a >50% reduction in averaged pain from baseline was 1.25, and to obtain complete relief, the NNT was 2.5. MuGard significantly reduces pain and ulceration associated with oral mucositis in patients with lichen planus.

Randomized double-blind placebo-controlled trial of celecoxib for radiation-induced oral mucositis.

9620 Background: Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck (H&amp;N) cancer. OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Due to the role of inflammatory pathways in the pathogenesis of OM, this study investigated the effect of inhibition of cyclooxygenase-2 (COX-2) on severity and morbidity of OM. Methods: In this randomized double-blind placebo-controlled trial,40 H&amp;N cancer patients were randomized to daily use of 200 mg celecoxib or matched placebo, for the duration of RT. Eligibility criteria included planned RT dose of ≥ 5000 cGy to 2+ areas of the mouth and no contraindication for celecoxib use. The planned sample size of 20 per arm provided 80% power to detect a 1 point difference in mean Oral Mucositis Assessment Scale (OMAS) score (range 0-5) at 5000 cGy RT (primary endpoint), applying a two-tailed, two-sample t-test at the 5% level of significance. Clinical OM, normalcy of diet, pain scores and analgesic use were assessed 2-3 times a week by blinded investigators during the 6-7 week period of RT, using validated scales. Results: Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over the course of RT. Intent-to-treat analyses demonstrated no significant difference in mean (SD) OMAS scores at 5000 cGy [celecoxib 1.32 (0.71), placebo 1.27 (0.86), p = 0.83, two sample t-test]. There was also no difference between the celecoxib and placebo arms respectively, in mean OMAS scores over the period of RT (SD) [0.98(0.77) &amp; 0.97 (0.86), p = 0.84], mean worst pain scores [3.38 (3.07) &amp; 3.31 (3.32), p = 0.83], mean normalcy of diet scores [5.43 (3.86) &amp; 5.11(3.94), p = 0.65], or mean daily opioid medication use in IV morphine equivalents [19.08 (16.57) &amp; 20.48 (19.07), p = 0.48], all by linear mixed model fixed effects regression analysis. There were no SAEs attributed to celecoxib use. Conclusions: Daily use of a selective COX-2 inhibitor, during the period of RT for H&amp;N cancer, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. Clinical trial information: NCT00698204.

Microbiology and epidemiology of oral yeast colonization in hemopoietic progenitor cell transplant recipients

We monitored the epidemiology and microbiology of oral yeast colonization in patients undergoing hemopoietic progenitor cell transplantation (HPCT) to examine associations between yeast colonization and oral mucositis. One hundred twenty-one consecutive HPCT patients were sampled for oral yeasts prior to fluconazole (FLC) prophylaxis, at transplantation, and weekly until discharge. Clinical oral mucositis screenings were performed triweekly. Yeast colonization was evident at 216 of 510 total visits. Candida albicans and Candida glabrata were the predominant organisms. Eight patients showed elevated minimal inhibitory concentrations to FLC. One patient developed fungal septicemia. Patients with oral mucositis assessment scale scores <20 had higher colonization rates than those with higher scores. FLC is effective in controlling a variety of oral yeasts in HPCT recipients. FLC-resistant yeasts do emerge and can be the source of fungal sepsis. A positive association was not shown between yeast colonization and the presence or severity of oral mucositis.

Effect of Pharmacokinetic Variability on the Toxicity and Efficacy of High-Dose Melphalan for Multiple Myeloma

AbstractAbstract 1349 Background:High dose melphalan is the most common conditioning regimen for patients undergoing autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM). However, toxicity and efficacy of this treatment are variable, with the sources of variability poorly understood. We hypothesized that variation in melphalan pharmacokinetics would explain differences in outcomes after transplant. Methods:We evaluated 41 patients with MM undergoing ASCT with high-dose melphalan conditioning. Patients received melphalan on day -2 at a dose of 200 mg/m2 (one patient with poor renal function received 180 mg/m2) and ASCT on day 0. Melphalan dose was calculated using ideal body weight (IBW), with adjusted IBW used for patients weighing >120% of IBW. We assessed toxicity on day +7 using the Oral Mucositis Assessment Scale (OMAS), a physician evaluated measurement of erythema and ulceration (on a scale of 0–5, with higher scores indicating more severe mucositis). Patients reported the severity of mouth soreness on a scale of 0–10 using the Mucositis Daily Questionnaire (MDQ) on days 0, +3, +7, +11, +19, and +28. Melphalan concentrations were measured using HPLC/tandem mass spectrometry in plasma samples obtained during infusion and 2, 4, 8, 15, and 30 minutes, and 1, 2, 3.5, 8, and 14 hours after its completion, as well as immediately prior to stem cell infusion. Melphalan area under the curve (AUC) was estimated by non-compartmental analysis. Results:Patients' median age was 57 years (range 39–72); 59% were male. We observed significant variation in melphalan exposure, with a range of 7.6–26.6 mg*h/L (median 13.5). Severity of oral mucositis was directly related to AUC (with an increase of 0.1 on the OMAS score for every 1 unit increase in AUC, p=0.003). The most severe mucositis was seen in the 4 patients with an AUC ≥17.5 (75% had OMAS scores >1), while severe mucositis was rarely seen in the 18 patients with AUC ≤12.5 (only 1 of 18 had an OMAS score >1). The association between AUC and maximum reported mouth soreness was not statistically significant (an increase of 0.2 on the MDQ scale for every 1 unit increase in AUC, p=0.17), but there was a trend toward higher maximum reported mouth soreness in the 4 patients with AUC≥17.5 (mean 7.5 vs. 4 for other patients, p=0.07). Eight patients had detectable melphalan concentrations at the time of stem cell infusion (mean 3.8 ng/mL, range 1.8–7.1), though time to neutrophil and platelet recovery did not differ for these patients compared with those with undetectable melphalan levels. Of 19 patients with measurable disease at the time of transplant, 8 had stable disease (SD), 9 partial response (PR), and 2 complete response (CR) at day +100. The 2 patients with CR had higher melphalan exposure than patients without a CR (mean AUC 19 vs 11.6, p= 0.002), but there was no discernable difference in melphalan levels between patients with a PR or SD. Conclusion:Using standard dosing calculations in a representative sample of patients with myeloma, melphalan drug exposure was highly varied. Drug exposure was correlated with severity of oral mucositis, and complete responses were seen only in patients with high drug exposure. Further analyses are planned into the effect of obesity and renal dysfunction on pharmacokinetics. Exploration of the appropriate target AUC and strategies for reducing variability in drug exposure have the potential to improve both efficacy and toxicity of this effective and commonly used therapy. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Effect of Obesity and Renal Insufficiency On Toxicity of High-Dose Melphalan for Multiple Myeloma.

Abstract 1177Poster Board I-199 BACKGROUND:High dose melphalan followed by an autologous peripheral blood stem cell transplant (ASCT) is standard initial therapy for multiple myeloma (MM). However, toxicity and efficacy of this treatment are variable, with the sources of variability being poorly understood. We hypothesized that obesity and renal insufficiency modulate the pharmacokinetics of melphalan and therefore impact treatment toxicity. METHODS:We evaluated 39 patients with MM undergoing high-dose melphalan followed by ASCT. Patients received melphalan on day -2 at a dose of 200 mg/m2 (one patient with poor renal function received 180 mg/m2) and ASCT on day 0. We assessed body composition using dual energy x-ray absorptiometry (DEXA) and renal function using 24 hour urine creatinine clearance. We assessed toxicity on day +7 using the Oral Mucositis Assessment Scale (OMAS), a physician evaluated measurement of erythema and ulceration (on a scale of 0-5, with higher scores indicating worse mucositis). We also assessed patient reported symptom scores for mouth and throat soreness using the Mucositis Daily Questionnaire (MDQ) periodically during the first month (on a scale of 0-10, with higher scores indicating worse soreness). RESULTS:The median age was 55 years (range 37-70). 59% were male. The median weight was 83 kg (48-128), with median percentage body fat as measured by DEXA of 31% (range 15–53), and the median glomerular filtration rate (GFR) was 105 ml/min (range 28-194). Results from univariate and multivariate analyses are shown in the table below. In univariate analyses, we observed a weak and statistically insignificant direct correlation between percent body fat and toxicity (as measured by OMAS score or peak soreness), and a weak and statistically significant indirect correlation between GFR and OMAS score. In a multi-variable linear regression model including percent body fat, weight, GFR, and actual melphalan dose, we observed a correlation between OMAS score and percent body fat, with an increase in body fat percentage of 0.10 associated with a 0.65 unit increase in OMAS score (p=0.01). In a similar multi-variable model, we observed a correlation between MDQ soreness score and percent body fat, with an increase in body fat percentage of 0.10 associated with a 2.07 increase in MDQ soreness score (p=0.05).Univariable modelMultivariable modelChange in OMAS scorepChange in OMAS scorep% body fat (per 10 percentage points)0.230.130.650.01GFR (per 10 ml/min)−0.080.02−0.060.09Weight (per 10 kg)−0.010.14−0.030.02Melphalan Actual Dose (per 10 mg)−0.060.100.010.08Change in peak soreness scorepChange in peak soreness scorep% body fat (per 10 percentage points)0.760.262.070.05GFR (per 10 ml/min)−0.030.860.030.89Weight (per 10 kg)−0.130.68−1.100.10Melphalan Actual Dose (per 10 mg)−0.050.750.380.19 CONCLUSION:More obese patients, as measured by percent body fat, have more severe oral mucositis after high dose melphalan, independent of melphalan dose, weight, and renal function. We are measuring melphalan pharmacokinetics in this group of patients, and further research should help guide rational chemotherapy dosing for this highly effective treatment. Disclosures:No relevant conflicts of interest to declare.

Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy

Knowledge of oral mucositis (OM) in patients with acute leukemia (AL) and chemotherapy (CT) has remained limited. Thus, a prospective, longitudinal study was undertaken to characterize clinical features, associated risk factors, and behavior of OM in a cohort of AL patients starting CT. Prospective and longitudinal study. A cohort of patients, older than 15 years of age with AL, scheduled to receive CT, was followed from March 2006 to October 2007. At baseline and three times per week, for 21 days, patients had an oral examination performed using the Oral Mucositis Assessment Scale (OMAS); also, oral pain and difficulty to swallow were recorded using a visual analog scale. Weekly, salivary flow measurements (Schirmer's test modified version) were done. A cohort of 29 AL patients was followed for a median time of 21 (range, 14-53) days; 12 (41.4%) developed OM, with a mean OMAS score of 0.181 (SD +/- 0.56) and a mean peak OMAS score of 1.8 (SD +/- 0.56). The OM onset mean time was 9.8 (range, 2-20, SD +/- 6.09) days, with a mean duration of 7 (range, 3-14, SD +/- 4.15) days. OM was significantly correlated with salivary flow [rs = 0.420 (P = 0.0051)], oral pain [rs = 0.47 (P < 0.0001)], ability to swallow [rs = 0.36 (P = 0.0001)], and type of food intake [rs = 0.38 (P < 0.0001)]. OM is a frequent and early side effect of CT closely correlated with oral pain, difficulty to swallow, and impairment in food intake.

Oral Mucositis Measured by the Oral Mucositis Assessment Scale (OMAS), but Not by the World Health Organization (WHO) Scoring System, Correlates with Nutritional Changes after Autologous Peripheral Blood Stem Cell Transplantation.

Objective: There is limited information regarding the relationship between oral mucositis (OM) and the nutritional status of autologous peripheral stem cell transplantation (APSCT) recipients. The objective of this study was to determine the relationship between OM, measured by two different instruments, and the nutritional status change of patients undergoing APSCT for lymphoid malignancies.Design: Eighty-two APSCT recipients were prospectively evaluated for OM by a physician or dentist not directly taking care of the patient. Oral examinations were performed 1–2 days before the administration of the conditioning regimen, the day of the transplant and 3 times weekly until resolution of mucositis. The presence of OM was assessed utilizing the objective portion of the OMAS which takes into account the degree of erythema and ulceration; and the WHO scoring system which combines both objective mucosal changes with functional outcomes such as the ability to eat. A registered dietician assessed the nutritional status (NS) of the patients before conditioning and at day 14 after transplantation, utilizing the Nutritional Status Classification Scheme (NSCS). The NSCS is a validated instrument developed by the Department of Veterans Affairs that stratifies patients in 4 categories or levels based on 7 indicators including nutrition history, unintentional weight loss, percent of ideal weight, diet, diagnosis, albumin, and total lymphocyte count. Defined levels range from patients with normal NS (level 1) to patients with severely compromised NS (level 4).Results: The mean age of study subjects was 56 (19–74) years, of these patients 76 (93%) were males. Of the 82 patients, 60 (73%) had multiple myeloma (MM), 17 (21%) had non-Hodgkin's lymphoma (NHL), and 5 (6%) had Hodgkin's lymphoma (HL). Conditioning regimens consisted of melphalan in 60 (73%), the combination of cyclophosphamide, etoposide and BCNU (CBV) in 19 (23%), and 3 (4%) received BCNU, etoposide, cytarabine, and melphalan (BEAM). Only 18% of the patients had a normal NS (level 1) before transplant. Most patients (73%) had mildly compromised NS (level 2) before transplant and the rest (9%) had moderately compromised NS (level 3). There was a statistically significant decrement in the NS 14 days after transplantation: 62% of the patients had moderate NS (level 3) and 5% has severely compromised NS (level 4) (p=0.002).Some degree of OM developed in 74 (90%) patients using the OMAS and 71 (87%) patients using the WHO scoring system. The NS change was associated with the OMAS (p=0.003) score but not with the WHO scoring system (p=0.094). There were no statistically significant correlation between change in NS and type of disease (0.496), conditioning regimen (0.496) and diarrhea (0.8849). There was a statistically significant correlation between change in NS and pain on swallowing (P=0.022), days with fever (P=0.036), neutrophil (P=0.01) and platelet (P=0.045) engraftment and length of hospital stay (P=0.004).Conclusions: Oral mucositis measured by the OMAS, but not by the WHO scoring system, correlates with nutritional changes after APSCT in patients with lymphoid malignancies. Decrement of the nutritional level in the NSCS correlated with adverse clinical outcome.

Analysis of Factors Influencing Skin Toxicity after Autologous Hematopoeitic Stem Cell Transplant.

Skin toxicity is a known but understudied complication of autologous stem cell transplantation (ASCT). Its assessment is complicated by the development of graft-vs-host disease following allogeneic transplantation. We chose therefore to study skin toxicity following autologous transplantation. We retrospectively reviewed the records of 392 patients undergoing ASCT to analyze risk factors for skin toxicity, its association with mucositis and its effect on survival. Skin toxicity was assessed three times a week during the transplant admission and was classified as none, mild, moderate, severe or life threatening. The most severe skin toxicity is used in this analysis. Mucositis was assessed using the modified oral mucositis assessment scale (OMAS). Median patient age was 53 years; 63% of patients had non-Hodgkin s lymphoma (NHL), 17.6% multiple myeloma, 13.5% Hodgkin disease (HD) and 5.9% acute leukemia. Peripheral blood progenitor cells were mobilized with G-CSF alone (36%) or the combination of etoposide plus G-CSF (64%). The preparative regimen was busulfan (Bu)/cyclophosphamide (Cy) /etoposide in 82% and Bu/Cy alone in 18%. Two hundred and sixty patients (67%) developed skin toxicity of which 143 patients (36.5%) had mild, 105 (26.8%) had moderate and 16 (3.9%) had severe skin toxicity. Factors associated with the development of any skin toxicity in univariable analysis were male gender (p=0.028), diagnosis of NHL (p<0.001) or HD (p=0.001), higher number of prior chemotherapy regimens (p<0.001), mobilization regimen containing etoposide (p< 0.001) and ASCT preparative regimen containing etoposide (p<0.001). Moderate skin toxicity correlated with the above as well. Only the inclusion of etoposide in the mobilization regimen was associated with an increased risk of severe skin toxicity (p=0.035). Etoposide in the preparative regimen remained the most significant risk factor for the development of skin toxicity in multivariable analysis. Higher OMAS score was associated with increased severity of skin toxicity (p<0.001) as shown in the boxplot below:Patients with severe skin toxicity appeared to have worse overall survival (p=0.054) and relapse-free survival (p=0.08), but these findings did not reach statistical significance.Conclusion: A substantial proportion of patients develop skin toxicity following autotransplantation. The inclusion of etoposide in the preparative regimen is associated with a significant increased frequency in multivariable analysis. The severity of skin toxicity correlates closely with the severity of mucositis. [Display omitted]

Orofacial pain: Stomatitis-related oral pain, salivary and plasma TNF-alpha levels in peripheral blood stem cell transplant oncology patients

Stomatitis-related oral pain is a negative sequela of conditioning regimens for peripheral blood stem cell transplant (PBSCT). Although the cytokine tumor necrosis factor-alpha (TNF-alpha)is associated with many chronic inflammatory conditions, its role in acute inflammation needs fuller elucidation. This pilot for a stomatitis intervention study is measuring multiple dimensions of stomatitis-related oral pain, and TNF-alpha concentrations in plasma and saliva in oncology patients pre and post PBSCT at baseline and at day 9 after chemotherapy. Research instruments include the Oral Mucositis Assessment Scale (OMAS) and the Painometer. TNF-alpha concentrations are measured by enzyme immunoassay (ELISA) (R & D Systems, Inc., Minneapolis, MN). Subjects (N = 20), average age 47 years with diverse late stage cancer diagnoses, reported previous stomatitis-related oral pain with chemotherapy (60%). Subjects received one of four PBSCT protocols; one subject received PBSC boost. Stomatitis was observed in 14 of 19 (73%) subjects, with half reporting oral pain. Stomatitis varied with treatment protocol. Stomatitis severity was significantly positively correlated with oral pain intensity (p < .001), worst oral pain in 24 hours (p < .001), and sensory and affective pain dimensions (p < .001), with more severe oral pain seen with swallowing when compared with oral pain at rest. Subjects with OMAS scores with greater than 4 reported significantly more oral pain (p < .01). Plasma TNF-alpha results varied within normal range. Salivary TNF-alpha levels were significantly different between baseline and post-chemotherapy (p = .017). In this pilot study, patient-reported pain was associated with stomatitis severity. Elevated salivary, but not plasma, TNF-alpha suggests a local mucosal inflammatory response that may be a target for future topical interventions.

The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy

Epidermal growth factor (EGF) is present in biologic fluids, including saliva, and plays a role in maintenance of the epithelial barrier and in healing of damaged mucosa. The purpose of this study was to assess the relation between salivary EGF and the severity of oral mucositis in patients with carcinoma of the head and neck during radiation therapy. Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected prior to radiation and each week during radiation treatment for 11 men and 7 women. Oral mucositis was evaluated using the National Cancer Institute (NCI) scale of 0-4 and the Oral Mucositis Assessment Scale (OMAS), which evaluates the extent of erythema (scale of 0-2) and ulcerations (scale of 0-3) in nine oral sites. The overall OMAS score of 0-45 reflected the mucosal condition. EGF was assayed in the saliva specimens. The total mean radiation dose delivered to the head and neck was 5667 centigrays (cGy) in a mean of 24 fractions. Ulcerative oral mucositis occurred in 94% of patients. The mean OMAS score ranged from 2.83 in the first week of treatment to 14.77 in the fifth week. The mean WRS and WSS volumes decreased significantly from pretreatment to the first week of radiation treatment and then remained stable. A similar pattern was seen for the mean total output of EGF. A significant and negative correlation was found between higher levels of EGF in stimulated saliva and low OMAS score, reflecting less severe erythema and ulceration. A general trend showing that less tissue damage was associated with a higher EGF level in resting saliva also was illustrated. EGF levels were correlated with the OMAS score; however, no correlation was found when assessing the NCI score, which combines tissue damage with function and symptoms in a single score. Radiation-induced mucositis appeared to be modified by saliva volume, total EGF, and concentration of EGF in the oral environment. Saliva volume and total EGF output decreased significantly in the first weeks of treatment and remained reduced throughout radiation therapy. The findings suggest that higher levels of EGF in saliva, particularly in stimulated saliva, prior to and during radiation treatment may be associated with less severe mucosal damage due to radiation therapy. It is also postulated that human EGF may affect the development and healing of radiation-damaged mucosa.