Chemotherapy increases the prevalence of radiotherapy-related trismus in head and neck cancer patients: A systematic review and meta-analysis.

Background: To evaluate the influence of chemotherapy on the prevalence of trismus in irradiated head and neck cancer patients. Material and Methods: This systematic review guided by PRISMA-2020 and registered in PROSPERO (CRD42021255377) screened 963 articles in 7 scientific-databases (PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO) and 3 grey-literature databases (Open Grey, Google Scholar, ProQuest) and eight articles were included for qualitative synthesis, meta-analysis (combined odds ratio, inverse variance method plus random effects), heterogeneity analysis (I² and Tau²), one-of-out evaluation and publication bias analysis (Eggs' and Begg's tests) (RevMan®, p<0.05). The Newcastle-Ottawa Quality Assessment Scale Cohort Studies was used to assess the risk of bias (RoB). The classification assessment, development, and recommendations (GRADE) approach was used to assess the certainty of evidence. Results: The eight articles evaluated 1474 patients treated with chemoradiotherapy and 858 patients treated with radiotherapy. Five articles had low RoB, and three had high RoB. Chemoradiotherapy significantly (p=0.0003) increased the prevalence of trismus (OR=2.55, 95% CI = 1.53-4.23) compared to radiotherapy, with significant (p=0.010) but low heterogeneity (I²=59%;Tau²=0.29). There was no significant risk of publication bias, one-out analysis showed no significant difference between studies, and GRADE showed a moderate level of evidence. Trismus was directly associated to worse quality of life. Conclusions: The incidence of trismus increases when chemotherapy is combined with radiotherapy for head and neck cancer, which negatively impacts the quality of life. Key words:Radiotherapy, Chemoradiotherapy, Head and Neck Neoplasms, Trismus, Quality of Life.

Photobiomodulation therapy in the treatment of radiotherapy-related trismus of the head and neck.

This study evaluated photobiomodulation therapy (PBMT) for treatment of trismus in patients undergoing radiotherapy for head and neck cancer (HNC). Sixteen patients, 10 men and 6 women, who had a mouth opening < 35 mm and underwent RT were included. The patients were evaluated daily before and after the PBMT application, measuring mouth opening and performing pain scores for the masticatory muscles using the visual analog scale (VAS). We used the infrared laser (~ 808 nm) extraorally, 0.1 W power, 3 J energy, 30 s (107 J/cm2) per point, applied to temporalis anterior, masseter muscles, and temporomandibular joints (TMJ). An intraoral point was made in the trigonoretromolar region towards the medial pterygoid muscle. The mean mouth opening of the patients increased by more than 7 mm throughout the treatment. The pain scores on the initial days showed an immediate reduction after PBMT on the ipsilateral side in the muscles and TMJ. Throughout PBMT applications, there was a significant reduction in pain scores in all muscles and the TMJ. The radiation dose of all patients was above 40 Gy, which is the threshold dose for the risk of developing trismus. SPSS software was used and adopted a confidence of 95%. The Kolmogorov-Smirnov normality test, Wilcoxon test, and Spearman correlation were performed. PBMT controls muscular pain and reduced mouth opening limitation in HNC during radiotherapy. Further studies are needed to evaluate the preventive capacity of PBMT protocols for RT trismus-related HNC.

Oral hygiene protocols reduce the severity and incidence of oral mucositis during antineoplastic treatment: a systematic review and meta-analysis of randomized and non-randomized clinical trials.

OBJECTIVE: The objective of this systematic review was to determine whether oral and dental hygiene protocols (DHPs) reduce the incidence and severity of oral mucositis (OM) during antineoplastic treatment. MATERIALS AND METHODS: This PROSPERO-registered systematic review (CRD42021295322) was based on searches of publicly accessible databases, including PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and gray literature (Google Scholar, ProQuest, and Energy) until December 2021. Twenty-five articles from these searches and 14 articles retrieved from the references therein were evaluated in this systematic review and meta-analysis. The risk of bias (RoB) was assessed using RoB-2 and ROBINS-I for randomized (RCT) and non-randomized (n-RCT) clinical trials, respectively. A meta-analysis was performed on RCTs and n-RCTs in two subgroups to evaluate oral mouth rinses or DHP. GRADE-pro was used to assess the degree of certainty of the evidence. RESULTS: Of the 3367 articles retrieved, 25 RCTs and 14 n-RCTs involving 2109 and 754 patients, respectively, were included in the analyses. RoB was low for RCTs and moderate-to-very severe for n-RCTs. High heterogeneity and publication RoB were identified. In RCTs, mouth rinses (p = 0.830) and DHP (p = 0.100) did not reduce the incidence of OM. However, mouth rinses strongly reduced the severity of OM (p < 0.001; Cohen's d = - 1.87, 95% confidence interval [CI] = - 2.49 to - 1.24). In non-RCTs, mouth rinses (p < 0.001) and DHP (p < 0.001) reduced the relative risk of OM 0.38 (95% CI = 0.24 to 0.59) and 0.64 (95% CI = 0.53 to 0.70) times, respectively. In addition, DHP strongly reduced OM severity (Cohen's d = - 0.81, 95% CI = - 1.03 to - 0.59). GRADE-pro showed high certainty of OM severity and incidence in RCTs and non-RCTs, respectively, and low (OM incidence in RCTs) to very low (OM severity in non-RCTs) certainty in other outcomes. CONCLUSION: DHPs strongly reduce the severity and moderately reduce the incidence of OM. However, further studies with low heterogeneity are needed to validate these findings.

Photobiomodulation therapy prevents dysgeusia chemotherapy induced in breast cancer women treated with doxorubicin plus cyclophosphamide: a triple-blinded, randomized, placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness of photobiomodulation (PBMT) in preventing dysgeusia in breast cancer patients treated with doxorubicin-cyclophosphamide (AC). METHODS: This is a phase II, randomized, triple-blind, placebo-controlled clinical trial involving 112 breast cancer patients treated with AC. The patients were divided equally into two groups: a test group treated with 2 J red laser and 3 J infrared laser on 21 points that were symmetrically distributed on the tongue on day 0 of four cycles of AC, and an equal placebo group treated with simulated PBMT to blind the patient, evaluator, and statistician. The clinicopathological and sociodemographic data, results of taste test, and subjective taste analysis, and the QoL, ECOG performance status, body mass index, and other side effects were recorded. The data were analyzed using ANOVA-RM/Bonferroni, Friedman/Dunn, and chi-square/Fisher's exact tests. RESULTS: PBMT patients showed less objective and subjective taste loss (p<0.05). On the other hand, the placebo group showed a higher ECOG status (p=0.037) and more significant weight loss (p<0.001) after four cycles of AC. The QoL was significantly higher in the PBMT group (p<0.05) at all assessment periods, and PBMT treatment also reduced the incidence of cachexia (p=0.020), anorexia (p<0.001), diarrhea (p=0.040), oral mucositis (p=0.020), and vomiting (p=0.008). CONCLUSION: PBMT reduced the taste loss and improved the overall health status and QoL of patients with breast cancer treated with AC. TRIAL REGISTRATION: Brazilian Clinical Trials Registry ( www.ensaiosclinicos.gov.br ) approval number RBR-9qnm34y, registered on 01/05/2021.

Treatment of Severe Refractory Hematuria due to Radiation-Induced Hemorrhagic Cystitis with Dexamethasone.

Treatment of pelvic neoplasms with radiotherapy may develop sequelae, especially RHC. An 85-year-old male patient was admitted to a hospital emergency with gross hematuria leading to urinary retention and was diagnosed with RHC. The urinary bladder was probed, unobstructed, and maintained in continuous three-way saline irrigation. During 45 days of hospitalization, the patient underwent two cystoscopic procedures for urinary bladder flocculation, whole blood transfusions, and one platelet apheresis. None of these interventions led to clinical resolution. As the patient hematological condition was deteriorating, dexamethasone (4 mg i.v., bolus of 6/6, 12/12, and 24 h during five days) and epoetin alpha (1000 IU, 1 ml, s.c., for four weeks) were administered which led to the remission of the urinary bleeding. Dexamethasone therapy may be considered for RHC, when conventional treatments are not effective or are not possible, avoiding more aggressive interventions such as cystectomy.

Assessment of the quality of life of elderly with diagnosis of oral squamous cell carcinoma submitted to combined modality therapy / Avaliação da qualidade de vida de idosos com diagnóstico de carcinoma oral de células escamosas, submetidos à terapia combinada

Introduction: Evaluating the quality of life allows a more accurate clinical control as well as the provision of prognostic information for specific groups. This study was designed to evaluate the quality of life of elderly diagnosed with oral squamous cell carcinoma submitted to combined modality therapy. Methods: This is a retrospective and observational study, with cross-sectional quantitative character. A total of 206 records of patients with head and neck cancer treated between April 2013 and October 2014 were analyzed. Eleven patients over six months of treatment completion were included in the study. The questionnaire of quality of life of the University of Washington (UW-QOL) was applied. The data were collected regarding the social-demographic, clinical-pathological and therapeutic profiles, and the non-stimulated salivary flow was measured. Statistical analysis of quantitative data was performed by the Spearman nonlinear correlation, considering a confidence of 95%. Results: Chewing, saliva and speech showed the lowest scores (31.8; 42.3; 60.6, respectively). Statistically significant correlation was found between: shoulder and mood (r=0.787); swallowing and chewing (r=0.761); completion time of radiotherapy and recreation (r=0.659); activity and recreation (r=0.653); pain and swallowing (r=0.626); chewing and speech (r=0.607); age and speech (r=-0.617). Conclusions: Elderly with oral squamous cell carcinoma diagnosis sunmitted to combined modality therapy presented the areas related to chewing, saliva and speech as the most committed ones. Older individuals have greater impairment of speech, as well as those with longer completion of radiotherapy have better results related to the recreation area. (AU)

Introdução: A avaliação da qualidade de vida permite controle clínico confiável e provisão prognóstica para grupos específicos. Este estudo foi desenhado para avaliar a qualidade de vida de idosos com diagnóstico de carcinoma oral de células escamosas submetidos à terapia combinada. Método: Trata-se de estudo observacional e retrospectivo, de caráter quantitativo com corte transversal. Foi analisado um total de 206 prontuários de pacientes com câncer de cabeça e pescoço tratados entre abril de 2013 e outubro de 2014. Onze pacientes com mais de seis meses de conclusão do tratamento foram incluídos no estudo. O questionário de qualidade de vida da Universidade de Washington (UW-QOL) foi aplicado. Foram coletados dados relacionados ao perfil sociodemográfico, clínicopatológico e terapêutico, e foi mensurado fluxo salivar não estimulado. A análise estatística dos dados quantitativos foi realizada por meio da correlação não linear de Spearman, considerando uma confiança de 95%. Resultados: Mastigação, saliva e fala apresentaram os menores escores (31,8; 42,3; 60,6, respectivamente). A correlação estatisticamente significante foi observada entre: ombro e humor (r=0,778); deglutição e mastigação (r=0,761); tempo de conclusão da radioterapia e recreação (r=0,659); atividade e recreação (r=0,653); dor e deglutição (r=0,626); mastigação e fala (r=0,607); idade e fala (r=-0,617). Conclusões: Idosos com carcinoma oral de células escamosas, submetidos à terapia combinada, apresentaram áreas relacionadas à mastigação, à saliva e à fala como as mais acometidas. Indivíduos mais velhos apresentaram maior comprometimento da fala, assim como os que apresentavam maior tempo de conclusão da radioterapia apresentaram melhores resultados relacionados à recreação. (AU)

A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide.

PURPOSE: To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development. MATERIALS AND METHODS: Hamsters' cheeks were treated with Co-60 radiation (10, 20, 30 or 35 Gy). Three days later, oral mucosa scarification was performed with a needle. The animals were euthanized at day 13 (D + 13) after irradiation. Gross and microscopic alterations were evaluated by a new score system that we developed. Also, neutrophil infiltration, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-10, inducible nitric oxide synthase (iNOS), nitric oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish the roles of TNF-α and IL-1ß and iNOS in our model using pharmacological approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively. RESULTS: We found that a single administration of 35 Gy of Co-60, followed by mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals with mucositis lost weight and had a survival median of 13 days, the time at which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF-α and IL-1ß and a reduced concentration of IL-10. PTX partially prevented the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60-induced oral mucositis through reducing NO production. CONCLUSION: We described a novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF-α, IL-1ß and NO seem to play a role in the pathophysiology of this model.

Emprego do samário 153-EDTMP no tratamento do adenocarcinoma de próstata avançado. Resultados preliminares / The use of samarium 153-EDTMP for treatment of advanced prostatic adenocarcinoma

Introduçäo: Os autores analisam os efeitos do emprego endovenoso do Samário 153-EDTMP no tratamento de 35 pacientes portadores de adenocarcinoma de próstata refratário à hormonioterapia com metástases ósseas dolorosas. Material e métodos: Entre novembro de 1995 e março de 1998, 35 pacientes com metástase óssea de adenocarcinoma de próstata näo responsivo ao tratamento hormonal foram submetidos à aplicaçäo endovenosa do Samário 153-EDTMP (1,0 a 1,5 mCi/Kg de peso), com finalidade antiálgica. Sessenta porcento dos pacientes tinham pelo menos 20 metástases ósseas, 30 porcento usaram morfina e 68,5 porcento já haviam sido irradiados. Foram avaliadas a resposta à dor, a mielotoxicidade e os níveis de PSA após a aplicaçäo. Resultados: Verificou-se resposta completa à dor em 8 (24,2 porcento) e resposta parcial em 14 pacientes (42,4 porcento) dentre 33 pacientes avaliáveis, totalizando-se 66,6 porcento de resposta global à dor. O tempo de duraçäo de resposta variou de 30 a 60 dias nos casos de resposta completa e entre 20 a 90 dias nos casos de resposta parcial. A ocorrência de toxicidade medular ocorreu em 17 de 23 casos avaliáveis sendo predominantemente através de leucopenia e plaquetopenia sempre de regressäo espontânea, sendo que em nenhum caso a toxicidade foi letal. A queda parcial de PSA após a aplicaçäo ocorreu em 3 e a progressäo em 19 de 22 casos avaliáveis. O seguimento dos pacientes variou entre 7 e 903 dias (média 190 dias), com sobrevida global de 51,1 porcento aos 6 meses e de 20,9 porcento ao final de um ano. A sobrevida mediana foi de 6,2 meses. Conclusöes: Os resultados sugerem que o Samário é uma alternativa segura no tratamento paliativo do câncer de próstata hormônio refratário

Retinoblastoma associado a estenose pulmonar congênita / Retinoblastoma associated with congenital pulmonary stenosis

Retinoblastoma é o tumor intra-ocular mais comum na infância, representando 1 porcento de todos os tumores pediátricos. Em muitos casos a predisposiçÝo genética é observada. Anomalias congênitas têm sido descritas. Nós reportamos dois casos de retinoblastoma associado com estenose pulmonar. IdentificaçÝo precoce e tratamento deste defeito cardíaco associado a terapia efetiva para retinoblastoma têm resultado em longa sobrevida livre de doença para estes dois pacientes sem seqüela cardíaca. Uma avaliaçÝo de todos os pacientes com retinoblastoma é justificada para excluir outras anomalias que poderiam comprometer o excelente resultado destes pacientes.