RESUMO
BACKGROUND: Mucositis and dysphagia are common adverse effects of radiotherapy (RT) treatment of locally advanced squamous cell cancer of the head and neck (LA-SCCHN). Chemotherapy added to RT increases survival rates but causes worse mucositis and dysphagia. The aim of this analysis was to assess the impact of p16 status on mucositis, dysphagia, and feeding tube use in LA-SCCHN among patients treated with RT±cetuximab in the phase 3 IMCL-9815 trial. METHODS: Patients received RT plus weekly cetuximab or RT alone. Subgroup analyses were conducted on patients with p16-positive (n=75) or p16-negative (n=106) oropharyngeal cancer (OPC), as determined by immunohistochemical analysis. The onset and duration of mucositis and dysphagia by treatment arm and p16 status were displayed using Kaplan-Meier curves and the log-rank test. P values for the incidence of mucositis and dysphagia were calculated using the Fisher exact test. Feeding tube use was assessed as the percent of patients reporting use. RESULTS: The baseline characteristics of patients treated with RT±cetuximab were similar in both the p16-positive and p16-negative OPC subgroups. Patients within the p16-positive OPC subgroup had higher Karnofsky scores and were more likely to have stage T1-T3 cancer and be from the United States. Regardless of p16 status, there was no difference in the onset or duration of grade 3/4 mucositis or dysphagia in patients receiving RT plus cetuximab compared with those receiving RT alone. In the overall population, and the p16-positive and p16-negative OPC subpopulations, feeding tube use was not different for patients receiving RT plus cetuximab compared with RT alone. CONCLUSION: Regardless of p16 status, the addition of cetuximab to RT did not alter the incidence, time to onset, severity, or duration of mucositis and dysphagia and did not impact the frequency of feeding tube use.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Cetuximab/uso terapêutico , Quimiorradioterapia/efeitos adversos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Mucosite/etiologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Quimiorradioterapia/métodos , Transtornos de Deglutição/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosite/patologia , Papillomaviridae/isolamento & purificação , Estomatite/etiologia , Estomatite/patologiaRESUMO
Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.
Assuntos
Antineoplásicos/efeitos adversos , Candidíase/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estomatite/etiologia , Adulto , Idoso , Candidíase/patologia , Feminino , Hospitalização , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Estomatite/patologia , Adulto JovemRESUMO
PURPOSE: Oral mucositis induced by radiotherapy impacts quality of life. Previous studies have reported on the use of the hamster as a model for radiation-induced oral mucositis; however, details regarding factors such as radiation dose response, effects on myeloperoxidase (MPO) activity and related histopathological changes remain unclear. In the present study using the hamster, we evaluated the dose dependency of radiation-induced oral mucositis and the effects of keratinocyte growth factor (palifermin). METHODS: Oral mucositis was induced in the cheek pouch by X-irradiation using single doses in the range 20-50 Gy. To evaluate the protective effect of palifermin, administration was carried out (5 mg/kg) on days 1, 2 and 3 or on days 9, 10 and 11 after single irradiation at a dose of 40 Gy. RESULTS: The oral mucositis score, MPO activity and histopathological findings of inflammation increased in a dose dependent manner. Palifermin treatment stimulated the proliferation of mucosal epithelial cells. Additionally, palifermin when administered on days 1, 2 and 3 after irradiation (40 Gy) reduced the severity of oral mucositis. CONCLUSIONS: The hamster was found to be a suitable model for radiation-induced oral mucositis, with excellent results regarding the evaluation of radiation dose response and drug reactivity.
Assuntos
Bochecha/patologia , Modelos Animais de Doenças , Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Lesões por Radiação/patologia , Lesões por Radiação/prevenção & controle , Estomatite/patologia , Estomatite/prevenção & controle , Animais , Bochecha/efeitos da radiação , Cricetinae , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Humanos , Mesocricetus , Doses de Radiação , Tolerância a Radiação/efeitos dos fármacos , Protetores contra Radiação/administração & dosagem , Resultado do TratamentoRESUMO
The aim of present study was to assess the radioprotective effects of the local application of amifostine to treat acute buccal mucositis in guinea pigs. A total of 32 guinea pigs were randomized into four groups: (Group A) topically administered 50 mg of amifostine plus radiotherapy (RT); (Group B) 100 mg amifostine plus RT; (Group C) normal saline plus RT; and (Group D) normal saline plus sham RT. The opportunity for administration was 15 min before irradiation. When administered, the cotton pieces that had been soaked with 0.5 ml amifostine solution or saline were applied gently on the buccal mucosa of each guinea pig for 30 min. The animals in Groups A, B and C were irradiated individually with a single dose of 30 Gy to the bilateral buccal mucosa. Eight days after irradiation, the animals were scored macroscopically; they were then euthanized, and the buccal mucosal tissues were processed for hematoxylin-eosin staining and ICAM-1 immunohistochemical analysis. In Groups A and B, the mean macroscopic scores were 2.9 ± 0.6 and 2.4 ± 1.1, respectively. There was no significant difference between the two groups (P > 0.05). However, when they were separately compared with Group C (4.4 ± 0.7), a noticeable difference was obtained (P < 0.05). No mucositis was observed in Group D. Comparisons of the expression of ICAM-1 were in agreement with the macroscopic data. Histologically, superficial erosion, exudate and ulcer formation were all observed in the RT groups; only the severity and extent were different. The microscopic observations in the amifostine-treated groups were better than in Group C. The results demonstrated that topical administration of amifostine to the oral mucosa is effective treatment of acute radiation-induced mucositis.
Assuntos
Amifostina/administração & dosagem , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/patologia , Estomatite/tratamento farmacológico , Estomatite/patologia , Doença Aguda , Administração Tópica , Animais , Cobaias , Molécula 1 de Adesão Intercelular/imunologia , Doses de Radiação , Lesões por Radiação/imunologia , Protetores contra Radiação/administração & dosagem , Estomatite/imunologiaRESUMO
Oral mucositis remains one of the most common and troubling side effects of standard chemoradiation regimens used for the treatment of head and neck cancer. Virtually all patients who receive cumulative radiation doses of more than 30 Gy that includes oral mucosal fields will develop the condition. Not only does mucositis cause extreme discomfort, often necessitating opioid analgesia, but it is also associated with increased use of health resources and cost of treatment. The incremental cost of mucositis in patients with head and neck cancer is more than $17 000 (US). Much has been learned about the pathobiology that underlies the condition. The departure from the historical paradigm of direct cell death as being the primary cause for mucosal injury in favor of a more comprehensive view of the impact of chemoradiation on all the cells of the mucosa, has resulted in a picture of mucositis pathogenesis, which is biologically broad based. Although there are currently few treatment options for oral mucositis at the moment, the recognition that its underlying biology is complex has provided a range of treatment options that are currently being developed.
Assuntos
Antineoplásicos/efeitos adversos , Lesões por Radiação/patologia , Estomatite/etiologia , Animais , Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Custos de Cuidados de Saúde , Humanos , Doses de Radiação , Lesões por Radiação/economia , Lesões por Radiação/terapia , Estomatite/economia , Estomatite/patologia , Estomatite/terapiaRESUMO
Oral mucositis is a debilitating complication of anticancer treatment, characterised by erythematous, atrophic, erosive or ulcerative lesions. Oral mucositis is almost always painful, affects eating, sleeping, and speech and affects the physiological and social well-being of the patient. The pathophysiology of the condition is not well understood. Guidelines to the treatment of oral mucositis are often contradictory so that there is no evidence based standard treatment protocol. Therefore the treatment is empiric. This paper offers a brief review of current knowledge of the pathophysiology and treatment of oral mucositis.
Assuntos
Antineoplásicos/efeitos adversos , Irradiação Craniana/efeitos adversos , Mucosite/etiologia , Estomatite/etiologia , Fatores Etários , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Mucosa Bucal/patologia , Mucosite/patologia , Mucosite/terapia , Neutropenia/etiologia , Cuidados Paliativos , Fatores de Risco , Fatores Sexuais , Estomatite/patologia , Estomatite/terapiaRESUMO
BACKGROUND: An impediment to mucositis research has been the lack of an accepted, validated scoring system. The objective of this study was to design, test, and validate a new scoring system for mucositis that can be used easily, is reproducible, and provides an accurate system for research applications. METHODS: A panel of experts, convened to design an objective, simple, and reproducible assessment tool to evaluate mucositis with specific application to multicenter clinical trials, developed a scale that measured objective and subjective indicators of mucositis. Nine centers participated in the study's validation. Paired investigators at each center evaluated patients receiving chemotherapy or head and neck radiation. Objective measures of mucositis evaluated ulceration/pseudomembrane formation and erythema. Subjective outcomes of mouth pain, ability to swallow, and function were measured. Analgesia use for mouth sensitivity was recorded. RESULTS: One hundred eight chemotherapy and 56 radiation therapy patients were evaluated. Seventy-eight percent of chemotherapy patients and 64% of radiation therapy patients had clinically significant mucositis. Cumulative daily mucositis scores demonstrated a high correlation among observers. Using area under the curve analysis, it was found that for chemotherapy patients, the highest correlations (correlation coefficient > 0.92) occurred for the scores that selected the three highest daily values over the course of mucositis assessment. High interobserver correlations were noted for patients receiving radiation therapy. Objective mucositis scores demonstrated strong correlation with symptoms. CONCLUSIONS: The scoring system evaluated was easily used, showed high interobserver reproducibility, was responsive over time, and measured those elements deemed to be associated with mucositis. The use of concomitant symptomatic measurements appeared to be unnecessary.
Assuntos
Antineoplásicos/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/efeitos da radiação , Lesões por Radiação/classificação , Radioterapia/efeitos adversos , Estomatite/classificação , Adulto , Ensaios Clínicos como Assunto , Documentação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valores de Referência , Reprodutibilidade dos Testes , Estomatite/patologiaRESUMO
PURPOSE: The purposes of this descriptive, longitudinal study were to evaluate the MacDibbs Mouth Assessment instrument for the assessment of mucositis in the radiation therapy patient being treated for head and neck cancer and to describe the course of radiation-induced mucositis in these patients. DESCRIPTION OF STUDY: This pilot study used self-report and provider assessment, as well as medical record review, to obtain data about ambulatory radiation therapy outpatients (n = 10). The participants were primarily male, white, middle-aged, married or partnered, unemployed, edentulous, currently smoking, and using alcohol. RESULTS: One or more mucositis ulcers were observed in all patients and occurred at an average of 2858.2 cGy. The corresponding Mouth Symptom Score was 5.9 (instrument range 0-21). Interrater reliability for 13 of the 14 items was 100%. The one difficulty encountered with the MacDibbs was in the measurement of ulcers longer than the periodontal probe used to measure them. CLINICAL IMPLICATIONS: The MacDibbs should prove useful for clinicians and researchers because it is efficient, easy to use, emphasizes accurate diagnosis of oral changes, has an easily discernible endpoint, and assesses signs and symptoms.
Assuntos
Avaliação em Enfermagem/métodos , Radioterapia/efeitos adversos , Estomatite/enfermagem , Estomatite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mucosa Bucal , Saúde Bucal , Projetos Piloto , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Estomatite/etiologiaRESUMO
We have analysed both the nuclear-cytoplasmic (N/C) ratio and nuclear volume densities (VVN) in defined strata from human hard palate lesions with and without malignant potential to determine the prognostic reliability and/or validity of this parameter. Measurements of cellular and nuclear areas of basal and spinous cells from normal (N) and pathological palatal epithelium were made on histological sections using an image analyser. The lesions comprised fibrous hyperplasia (FH), traumatic inflammation (INF), benign hyperkeratosis (HK), squamous cell papilloma (PP), dysplastic epithelium adjacent to invasive carcinoma (CE) and islands of invasive squamous cell carcinoma (CI). In basal cells, no significant differences were detected in comparisons of N/C and VVN between all pathological groups and the N control group. The mean value for CE was lower than that obtained for N. In spinous cells, the only statistically significant comparison was between IF and FH for both N/C and VVN. Both parameters were lower in CE than in N. Of all groups analysed except CI, the CE group is the only one likely to possess an increased malignant potential. The N/C ratio therefore seems to be of no value as a predictor of malignancy in palatal epithelial lesions.
Assuntos
Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Mucosa Bucal/patologia , Palato/patologia , Carcinoma/patologia , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/patologia , Epitélio/ultraestrutura , Humanos , Hiperplasia , Processamento de Imagem Assistida por Computador , Leucoplasia Oral/patologia , Doenças da Boca/patologia , Neoplasias Bucais/patologia , Invasividade Neoplásica , Neoplasias Palatinas/patologia , Papiloma/patologia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estomatite/patologiaRESUMO
Oral complications can be serious and disabling problems for patients undergoing cancer therapy. Therefore, the authors wanted to develop a sensitive and specific instrument to measure oral mucosal changes during therapy. The Oral Mucosa Rating Scale (OMRS) has an examination rating scale to quantify the type and severity of clinically evident oral mucosal changes (atrophy, erythema, ulceration, and pseudomembranous, hyperkeratotic, lichenoid, and edematous changes), with a scale ranging from 0 to 3 (normal to severe). Separate visual analogue scales are obtained for oral pain and dryness. One hundred eighty-eight bone marrow transplant recipients were studied from before transplant through day 42 after transplant. The OMRS then was used to develop a specific index for assessing acute oral mucositis after bone marrow transplant--the Oral Mucositis Index (OMI). The OMI internal consistency measures (Chronbach alpha and Guttman split-half coefficients) were strong (range, 0.84 to 0.93). Support for the validity of the OMI is presented. These scales should help improve the study of oral complications of cancer therapy.