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Chinese Medical Journal ; (24): 954-962, 2021.
Article in English | WPRIM | ID: wpr-878130


BACKGROUND@#Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.@*METHODS@#A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS).@*RESULTS@#We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05).@*CONCLUSION@#Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Chemoradiotherapy , Disease-Free Survival , Female , Humans , Neoplasm Staging , Prospective Studies , Retrospective Studies , Th17 Cells , Treatment Outcome , Uterine Cervical Neoplasms/therapy
São Paulo; s.n; 2021. 70 p.
Thesis in Portuguese | LILACS, Inca | ID: biblio-1348850


INTRODUÇÃO: A quimiorradioterapia neoadjuvante (QRTN) consolidou-se como a principal estratégia para o tratamento do câncer de reto localmente avançado (CRLA). No entanto, respostas heterogêneas são observadas com o tratamento neoadjuvante, com apenas 15-20% dos pacientes com resposta patológica completa (RPC). Diante da necessidade de estratificar os pacientes em respondedores e não respondedores à QRTN antes do seu início, com o objetivo de aprimorar a seleção daqueles com maior probabilidade de obter uma RPC, vários estudos avaliam a identificação de possíveis biomarcadores. O objetivo primário deste estudo prospectivo foi analisar se a ausência da expressão do homólogo B de RAD23 (RAD23B) e da timidilato sintase (TYMS) nas células tumorais circulantes (CTCs) se correlacionaria com a RPC para os pacientes submetidos à QRTN e, assim, identificar possíveis respondedores ao tratamento. Os desfechos secundários foram avaliar a cinética das CTCs antes (C1) e após QRTN (C2), além da correlação da expressão de marcadores de resposta imune, como o Tumor Growth Factor ß Receptor I (TGF-ßRI) e Programmed Death ligand-1 (PD-L1) com a sobrevida livre de doença (SLD) e sobrevida global (SG). MÉTODOS: Entre 2016 e 2020, 63 pacientes com CRLA (cT3/T4 e/ou N+) submetidos a QRTN foram incluídos no estudo. As CTCs foram isoladas por ISET e avaliadas por imunocitoquímica. A expressão de RAD23B, TYMS, PD-L1 e TGF-ßRI foi avaliada nesta ordem de prioridade de acordo com o objetivo primário do estudo em cada momento de coleta e a disponibilidade de células (contagem de CTCs > 0) na amostra. RESULTADOS: Em C1, RAD23B foi detectado em 54,1% dos pacientes sem RPC e sua ausência em 91,7% dos pacientes com RPC (p = 0,014); Na segunda coleta, dos 13 pacientes com RPC, 10 não apresentaram expressão de RAD23B nas CTCs. Para os pacientes que não obtiveram RPC com QRTN, 51,7% apresentavam a expressão de RAD23B em CTC em C2 (p = 0,06). Na análise univariada (OR =0,077;IC 95%, 0,009-0,661; p = 0,019) e multivariada (OR= 0,064;CI 95%, 0,006-0,75; p = 0,029) para RPC, observamos que a expressão de RAD23B foi associado com menor chance de resposta em comparação com os pacientes com a ausência da expressão do RAD23B na C1. A ausência da expressão da TYMS foi observado em 90% dos pacientes com RPC e sua expressão em 51,7% sem RPC (p = 0,057). Na avaliação da cinética da CTCs pacientes com CTC2> CTC1 (cinética desfavorável) tiveram pior SLD (p = 0,00025) e SG (p = 0,0036) em comparação com aqueles com CTC2 ≤CTC1 (cinética favorável). A expressão de TGF-ßRI em qualquer momento das coletas correlacionou-se com pior SLD (p = 0,059). CONCLUSÃO: Demonstramos uma possível correlação entre a ausência de expressão de RAD23B e TYMS nas CTCs com a RPC, sendo um resultado importante para identificar os respondedores ao tratamento neoadjuvante, ajudando individualizar a abordagem terapêutica. Além disso, a cinética desfavorável e a expressão de TGF-ßRI nas CTCs se correlacionaram com pior sobrevida

INTRODUCTION: Neoadjuvant chemoradiotherapy (NCRT) has established itself as the main strategy for the treatment of locally advanced rectal cancer (LARC). However, heterogeneous responses are observed with neoadjuvant treatment, with only 15-20% of patients with complete pathological response (pCR). Given the need to stratify patients into responders and non-responders to NCRT prior to its initiation, in order to improve the selection of those most likely to obtain a pCR, several studies have assessed the identification of potential biomarkers capable of stratifying and monitoring the patient's response. The primary objective of this prospective study was to analyze whether the absence of RAD23 homolog B expression (RAD23B) and thymidylate synthase (TYMS) in circulating tumor cells (CTCs) would correlate with pCR for patients undergoing NCRT and thus identify possible responders to treatment. The secondary outcomes were to evaluate the kinetics of CTCs before (C1) and after NCRT (C2), in addition to the correlation of the expression of immune response markers, such as Tumor Growth Factor ß Receptor I (TGF-ßRI) and Programmed Death ligand- 1 (PD-L1) with clinical outcomes such as disease-free survival (DFS) and overall survival (OS). METHODS: Between 2016 and 2020, 63 patients (pts) with LARC (cT3 / T4 or N +) submitted to NCRT were included in the study. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). The expression of RAD23B, TYMS, PD-L1 and TGF-ßRI was evaluated in this order of priority according to the primary objective of the study at each time of collection (C1, C2 and C3) and the availability of cells (CTC count> 0) in the sample. RESULTS: In C1, RAD23B was detected in 54.1% of patients without pCR and its absence in 91.7% of patients with pCR (p = 0.014). In the second collection, of the 13 patients with pCR, 10 did not show RAD23B expression in the CTCs. For patients who did not obtain pCR with NCRT, 51.7% had RAD23B expression in CTC in C2 (p = 0.06). In the univariate (OR = 0.077; 95% CI, 0.009-0.661; p = 0.019) and multivariate (OR = 0.064; 95% CI, 0.006-0.75; p = 0.029) logistic regression models for pCR, we observed that the expression of RAD23B was associated with a lower chance of response compared to patients with the absence of RAD23B expression in C1. The absence of TYMS expression was observed in 90% of patients with pCR and its expression in 51.7% without pCR (p = 0.057). In the evaluation of CTCs kinetics patients with CTC2> CTC1 (unfavorable kinetics) had worse DFS (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤CTC1 (favorable kinetics). TGF-ßRI expression at any time of the collections was correlated with worse DFS (p = 0.059). CONCLUSION: We demonstrated a possible correlation between the absence of RAD23B and TYMS expression in CTCs with pCR, being an important result to identify respondents to neoadjuvant treatment, helping to individualize the therapeutic approach. In addition, the unfavorable kinetics and expression of TGF-ßRI in CTCs correlated with worse survival.

Rectal Neoplasms , Neoadjuvant Therapy , Neoplastic Cells, Circulating , Immunohistochemistry , Chemoradiotherapy
Clinics ; 76: e2226, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249587


OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. Intensity-modulated radiation therapy and volume-modulated arc therapy have become the main treatments for esophageal carcinoma; however, side effects caused by radiotherapy greatly impact the quality of life in these patients. This study aimed to explore the impact of serum superoxide dismutase (SOD) levels on the prognosis of patients with ESCC undergoing radiotherapy. METHODS: Patients aged between 18 and 80 years with lower-middle ESCC who underwent radiotherapy were eligible for this assessment. Adverse events, responses, treatment outcomes, and overall survival (OS) were assessed. Between 2012 and 2014, 195 patients were enrolled, of which 65 were assigned to the low- and high-SOD groups based on their serum SOD values. RESULTS: The baseline characteristics were similar between the two groups, except for the T staging. Adverse events in the low-SOD group were significantly higher than those in the high-SOD group (radiation esophagitis, p=0.007; radiation pneumonitis, p=0.032; leukopenia, p=0.023; thrombocytopenia, p=0.037; anemia, p=0.041). There were no significant differences in response, treatment outcomes, or OS. CONCLUSION: In conclusion, high serum SOD activity improved post-radiotherapy quality of life but did not impact the prognosis of patients with ESCC. To the best of our knowledge, this study is the first to report that serum SOD activity is associated with radiation-induced toxicity and moderately increased radiotherapeutic response in patients with ESCC undergoing radiotherapy.

Humans , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Esophageal Neoplasms/radiotherapy , Esophageal Squamous Cell Carcinoma/radiotherapy , Prognosis , Quality of Life , Superoxide Dismutase , China , Chemoradiotherapy
Braz. j. otorhinolaryngol. (Impr.) ; 86(6): 676-686, Nov.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1142591


Abstract Introduction: Three-weekly cisplatin dose is accepted for standard treatment for concurrent chemo-radiotherapy in nasopharyngeal carcinoma. However, different chemotherapy schedules are presented in the literature. Objective: We intend to compare toxicity and outcomes of high dose 3-weekly cisplatin versus low dose weekly-cisplatin and cumulative dose of cisplatin in the patients with nasopharyngeal carcinoma. Methods: 98 patients were included in the study, between 2010 and 2018. Cumulative doses of cisplatin (≥200 mg/m2 and <200 mg/m2) and different chemotherapy schedules (weekly and 3-weekly) were compared in terms of toxicity and survival. Besides prognostic factors including age, gender, T category, N category and radiotherapy technique were evaluated in uni-multivariate analysis. Results: Median follow-up time 41.5 months (range: 2-93 months). Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 68.9% vs. 90.3% (p = 0.11); 66.2% vs. 81.6% (p = 0.15); 87.3% vs. 95.7% (p = 0.18); 80.1% vs. 76.1% (p = 0.74) for the group treated weekly and 3 weekly, respectively. There was no statistically significant difference between groups. Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 78.2% vs. 49.2% (p = 0.003); 75.8% vs. 47.9% (p = 0.055); 91% vs. 87.1% (p = 0.46); 80% vs. 72.2% (p = 0.46) for the group treated ≥200 mg/m2 and <200 mg/m2 cumulative dose cisplatin. There was statistically significant difference between groups for overall survival and there was close to being statistically significant difference between groups for local relapse-free survival. Age, gender, T category, N category, chemotherapy schedules were not associated with prognosis in the uni-variety analysis. Radiotherapy technique and cumulative dose of cisplatin was associated with prognosis in uni-variate analysis (HR = 0.21; 95% CI: 0.071-0.628; p = 0.005 and HR = 0.29; 95% CI: 0.125-0.686; p = 0.003, respectively). Only cumulative dose of cisplatin was found as an independent prognostic factor in multivariate analysis (HR = 0.36; 95% CI: 0.146-0.912; p = 0.03). When toxicities were evaluated, such as hematological toxicity, dermatitis, mucositis, nausea and vomiting, there were no statistically significant differences between cumulative dose of cisplatin groups (<200 mg/m2 and ≥200 mg/m2) and chemotherapy schedules (3-weekly and weekly). But malnutrition was statistically significant higher in patients treated with 3-weekly cisplatin compared with patients treated with weekly cisplatin (p = 0.001). Conclusion: A cisplatin dose with ≥200 mg/m2 is an independent prognostic factor for overall survival. Chemotherapy schedules weekly and 3-weekly have similar outcomes and adverse effects. If patients achieve ≥200 mg/m2 dose of cumulative cisplatin, weekly chemotherapy schedules may be used safely and effectively in nasopharyngeal carcinoma patients.

Resumo Introdução: Três doses semanais de cisplatina com quimiorradioterapia concomitante são aceitas como o tratamento-padrão para carcinoma nasofaríngeo. No entanto, diferentes esquemas quimioterápicos são recomendados na literatura científica. Objetivo: Comparar a toxicidade e os resultados de 3 doses altas semanais de cisplatina versus dose baixa semanal de cisplatina em pacientes com carcinoma nasofaríngeo e verificar a dose cumulativa de cisplatina. Método: Foram incluídos 98 pacientes, entre 2010 e 2018. As doses cumulativas de cisplatina (≥ 200 mg/m2 e < 200 mg/m2) e diferentes esquemas de quimioterapia (semanal e a cada 3 semanas) foram comparadas em termos de toxicidade e sobrevida. Além disso, fatores prognósticos, inclusive idade, sexo, categoria T, categoria N e técnica de radioterapia, foram avaliados na análise uni-multivariada. Resultados: O tempo médio de seguimento foi de 41,5 meses (intervalo: 2-93 meses). Sobrevida global de cinco anos, sobrevida livre de recidiva local, sobrevida livre de recidiva regional e sobrevida livre de metástases a distância foram: 68,9% vs. 90,3% (p = 0,11); 66,2% vs. 81,6% (p = 0,15); 87,3% vs. 95,7% (p = 0,18); e 80,1% vs. 76,1% (p = 0,74) para os grupos tratados semanalmente e 3 x/semana, respectivamente. Não houve diferença estatisticamente significante entre os grupos. Taxas de sobrevida global, sobrevida livre de recidiva local, sobrevida livre de recidiva regional e sobrevida livre de metástases a distância em cinco anos foram; 78,2% vs. 49,2% (p = 0,003); 75,8% vs. 47,9% (p = 0,055); 91% vs. 87,1% (p = 0,46); 80% vs. 72,2% (p = 0,46) para o grupo tratado com ≥ 200 mg/m2 e < 200 mg/m2 de dose cumulativa de cisplatina. Houve diferença estatisticamente significante entre os grupos para sobrevida global e houve uma diferença quase estatisticamente significante entre os grupos para sobrevida livre de recidiva local. Idade, sexo, categoria T, categoria N e esquemas de quimioterapia não foram associados ao prognóstico na análise univariada. A técnica de radioterapia e dose cumulativa de cisplatina foram associadas ao prognóstico na análise univariada (HR = 0,21; IC 95%: 0,071 ± 0,628; p = 0,005 e HR = 0,29; IC 95%: 0,125 ± 0,686; p = 0,003, respectivamente). Apenas a dose cumulativa de cisplatina foi considerada um fator prognóstico independente na análise multivariada (HR = 0,36; IC 95%: 0,146 ± 0,912; p = 0,03). Quando as toxicidades foram avaliadas, como toxicidade hematológica, dermatite, mucosite, náusea e vômito, não houve diferença estatisticamente significante entre a dose cumulativa dos grupos cisplatina (< 200 mg/m2 e ≥ 200 mg/m2) e esquemas de quimioterapia (semanal e a cada 3 semanas). Entretanto, a desnutrição foi estatisticamente maior em pacientes tratados com cisplatina a cada 3 semanas em comparação com pacientes tratados com cisplatina semanalmente (p = 0,001). Conclusão: Uma dose de cisplatina ≥ 200 mg/m2 é fator prognóstico independente para sobrevida global. Os esquemas de quimioterapia semanais e a cada 3 semanas têm resultados e efeitos adversos semelhantes. Se os pacientes atingirem uma dose cumulativa ≥ 200 mg/m2 de cisplatina, os esquemas semanais de quimioterapia podem ser usados com segurança e eficácia em pacientes com carcinoma nasofaríngeo.

Humans , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Carcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Treatment Outcome , Disease-Free Survival , Chemoradiotherapy , Neoplasm Recurrence, Local , Neoplasm Staging
J. coloproctol. (Rio J., Impr.) ; 40(3): 202-208, July-Sept. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134988


Abstract Background: Anorectal carcinoma includes the anal margin, the anal canal, and the lower rectum. The incidences of anal tumors represent 1.4 % of all gastrointestinal tumors. Patients and methods: Our study is retrospective and was conducted at Baghdad Medical City. Patient's data were collected from the medical records through a predesigned sheet that included the following information: demographic data, medical history, past-history, presenting symptoms, pathological data, and treatment details. Results: The median age was 49 years. As regard tumor extension, 85.71 % of patients had anal disease, while anorectal cancer was encountered in 14.28 % of cases only. Male to female ratio was 1:3. Most of cases were SCC 78.57 %. Only 11 patients (39.28 %) were diagnosed as Stage I, whereas 12 patients (42.85 %) had Stage II-III disease. Moderate differentiated tumors are the most common. The tumor mass located between 5-10 cm das a distance from anal verge in 12 (42.85 %) of patients. We found 6 (21.42 %) patients with positive virology tests with no specificity detected. APR was the mainstay for treatment of stage I disease. Neoadjuvant treatment followed by TME resection was the treatment found in locally advanced tumors. The mean Overall Survival (OS) for patients received neoadjuvant CRT in the study was 43.5 months, while, the mean OS was 45.73 months in the adjuvant setting. Univariate analysis for OS according to prognostic factors revealed that sites of cancer, grades and histopathology were significant independent prognostic factors for OS in this study. The anal canal tumor was associated with shorter OS (33.25) months in comparison to the anorectal cancer (OS = 47.22 months). Based on tumor grade, well and moderate differentiation have better OS (60.21 months) while, poorly grade was associated with shorter OS (43.07 months). On the concern of SCC, it was associated with shorter OS (37 months) in comparison to higher survival in patients with adenocarcinoma (46.13 months). Conclusion: Anal canal cancer has poorer prognosis than anorectal. The early-stage has a better OS that needs more effort for early diagnosis and treatment.

Resumo Antecedentes: O carcinoma anorretal inclui a margem anal, o canal anal e o reto inferior. A incidência de tumores anais representa 1.4 % de todos os tumores gastrointestinais. Pacientes e métodos: Nosso estudo é retrospectivo e foi realizado no Baghdad Medical City. Os dados do paciente foram coletados dos registros médicos por meio de uma folha pré-projetada que incluía as seguintes informações: dados demográficos, histórico médico, histórico anterior, sintomas de apresentação, dados patológicos e detalhes do tratamento. Resultados: A idade média foi de 49 anos. Quanto à extensão do tumor; 85,71 % dos pacientes apresentavam doença anal, enquanto o câncer anorretal foi encontrado em 14,28 % dos casos. A proporção homem/mulher foi de 1:3. A maioria dos casos foi de CEC 78,57 %. Apenas 11 pacientes (39,28 %) foram diagnosticados como Estágio I, enquanto 12 pacientes (42,85 %) apresentavam doença em Estágio II?III. Tumores diferenciados moderados são os mais comuns. A massa tumoral localizada entre 5-10 cm das distâncias da margem anal em 12 (42,85 %) dos pacientes. Foram encontrados 6 (21,42 % pacientes com testes virológicos positivos sem especificidade detectada. A TAEG foi a base para o tratamento da doença em Estágio I. O tratamento neoadjuvante seguido pela ressecção do TME foi o tratamento encontrado em tumores localmente avançados. A sobrevida global média OS dos pacientes que receberam TRC neoadjuvante no estudo foi de 43,5 meses, enquanto a OS média foi de 45,73 meses no cenário adjuvante. A análise univariada para OS de acordo com fatores prognósticos revelou que locais de câncer, notas e histopatologia foram fatores prognósticos independentes significativos para OS neste estudo. O tumor do canal anal foi associado a SG mais curtos 33,25 meses em comparação ao câncer anorretal OS = 47,22 meses. Com base no grau do tumor, a diferenciação boa e moderada apresenta melhor OS 60,21 meses, enquanto o grau ruim foi associado a um OS mais curto 43,07 meses. No que diz respeito ao CEC, este foi associado a uma OS mais curta 37 meses em comparação à maior sobrevida em pacientes com adenocarcinoma 46,13 meses. Conclusão: O câncer de canal anal tem pior prognóstico que o anorretal. O estágio inicial tem um sistema operacional melhor que precisa de mais esforço para diagnóstico e tratamento precoces.

Humans , Male , Female , Anus Neoplasms/epidemiology , Rectal Neoplasms/epidemiology , Adenocarcinoma , Anal Canal , Prognosis , Chemoradiotherapy
Rev. argent. coloproctología ; 31(1): 21-27, mar. 2020. tab
Article in Spanish | LILACS | ID: biblio-1102171


Introducción: El tratamiento del carcinoma anal escamoso (CAE) en los pacientes HIV positivos resulta controvertido. Si bien las guías actuales recomiendan realizar en los pacientes con buen estado inmunológico la quimiorradioterapia (QRT) concurrente estándar, algunos autores consideran que estos pacientes presentan mayor toxicidad y peores resultados a largo plazo, por lo que requerirían un abordaje diferente. El objetivo de este trabajo es comparar los resultados del tratamiento del CAE en los pacientes VIH positivos y negativos. Diseño: Estudio retrospectivo comparativo. Pacientes y métodos: Se revisaron retrospectivamente las historias clínicas de los pacientes tratados en el Sector Coloproctología, Hospital Fernández, entre 01/2007 y 10/2018. Los del conducto anal se dividieron en: Grupo I: VIH negativos y Grupo II: VIH positivos. Se compararon variables demográficas, factores de riesgo específicos, estadificación, QRT (drogas, toxicidad y respuesta), tratamiento quirúrgico curativo/paliativo, persistencia/recurrencia y supervivencia específica y global. Resultados: Se incluyeron 28 pacientes (18 mujeres); margen: 2, conducto: 26 (Grupo I: 15. Grupo II: 11). Los VIH positivos eran en su mayoría hombres que tienen sexo con hombres vs. 100% de mujeres VIH negativas (p<0,01), más jóvenes (45,2±0,9 vs. 63,6±8; p<0,01) y tabaquistas (82% vs. 27%; p=0,005). No hubo diferencia significativa en la estadificación, aunque el Grupo II tuvo tumores con complicaciones más severas. Pudieron completar el tratamiento: Grupo I: 93%, Grupo II: 64% (p<0,05). Tuvieron respuesta completa a la QRT 13/14 (93%) pacientes del Grupo I y 3/7 (43%) del Grupo II (p<0,01). Hubo 3 recurrencias, 2 locorregionales y 1 a distancia (p=NS). Los VIH positivos requirieron más cirugías (82% vs. 27%; p<0,01). A 5 pacientes (4 del Grupo II) se les realizó una resección abdominoperineal (RAP). Tuvieron colostomía definitiva, con o sin RAP, el 46% de los pacientes, la mayoría VIH positivos (82% vs. 27%; p=0,002). En los VIH positivos el RR de mortalidad por cáncer fue 4 (IC95%: 1,01-16,5; p=0,02) y el RR de mortalidad global fue 5,45 (IC95%: 1,42-20,8; p=0,002). Tuvieron menor supervivencia, tanto global (p=0,001) como libre de enfermedad (p=0,01). Mediana de seguimiento: 27 meses (4-216).Conclusiones: Los pacientes VIH positivos con CAE se diferenciaron de los VIH negativos en una menor tasa de respuesta completa a la QRT y una mayor necesidad de tratamiento quirúrgico. Además, tuvieron una supervivencia global y libre de enfermedad significativamente menor que los VIH negativos. (AU)

INTRODUCTION: The treatment of anal squamous cell carcinoma (SCC) in HIV-positive patients is controversial. Although current guidelines recommend performing standard concurrent chemoradiotherapy (CRT) in patients with good immune status, some authors believe that these patients have greater toxicity and worse long-term results, so they would require a different approach. The purpose of this study was to compare the results of SCC treatment in HIV-positive and HIV-negative patients.DESIGN: Comparative retrospective study.PATIENTS AND METHODS: The records of patients treated in the Coloproctology Section, Hospital Fernández, between 01/2007 and 10/2018 were retrospectively reviewed. Those of the anal canal were divided into: Group I: HIV-negative and Group II: HIV-positive. Demographic variables, specific risk factors, staging, CRT (drugs, toxicity, and response), curative/palliative surgical treatment, persistence/recurrence, and cancer-specific and global survival were compared.RESULTS: 28 patients (18 women), margin: 2, conduit: 26 (Group I: 15. Group II: 11). The HIV-positive were mostly men who have sex with men (vs. 100% HIV-negative women; p<0.01), younger (45.2 ± 0.9 vs. 63.6 ± 8; p<0.01) and smokers (82% vs. 27%; p=0.005). There was no significant difference in staging, although Group II had tumors with more severe complications. Completed the treatment: Group I: 93%, Group II: 64% of patients (p<0,05). Thirteen out of 14 (93%) patients in Group I, and 3/7 (43%) patients in Group II had a complete response to CRT (p<0.01). There were 3 recurrences, 2 loco-regional and 1 distance (p=NS). HIV-positive required more surgery (82% vs. 27%; p<0.01). 5 patients (4 of Group II) underwent an abdominal-perineal resection (APR). Forty six percent of patients had permanent colostomy, with or without APR, most of them were HIV-positive (82% vs. 27%; p=0.002). In HIV-positive patients, the RR of cancer mortality was 4 (95% CI: 1.01-16.5; p=0.02) and the RR of overall mortality was 5.45 (95% CI: 1.42-20, 8; p=0.002). They also had lower overall (p=0.001) and disease-free survival (p=0.01). Median follow-up: 27 months (4 - 216).CONCLUSION: HIV-positive patients with anal SCC were different from HIV-negative patients in that they had a lower complete response rate to CRT, and a greater need for surgical treatment. They had a significantly lower overall and disease-free survival than HIV-negative patients. (AU)

Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , HIV Infections/complications , Chemoradiotherapy , Anus Neoplasms/surgery , Anus Neoplasms/complications , Anus Neoplasms/mortality , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/mortality , Survival Analysis , Retrospective Studies , Treatment Outcome , Proctectomy , Neoplasm Recurrence, Local , Neoplasm Staging
Clinics ; 75: e1553, 2020. tab, graf
Article in English | LILACS | ID: biblio-1133414


OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Humans , Male , Female , Brain Neoplasms/therapy , Glioblastoma/therapy , Antineoplastic Agents, Alkylating/therapeutic use , Chemoradiotherapy/methods , Temozolomide/therapeutic use , Neoplasm Recurrence, Local/epidemiology , Survival , Brain Neoplasms/pathology , Brazil/epidemiology , Retrospective Studies , Treatment Outcome , Chemotherapy, Adjuvant , Glioblastoma/mortality , Glioblastoma/pathology
Rev. pediatr. electrón ; 17(2): 4-6, 2020.
Article in Spanish | LILACS | ID: biblio-1129817


La mucositis es una respuesta inflamatoria del epitelio de la mucosa a los efectos citotóxicos de la quimioterapia y la radioterapia, que causan dolor y ulceración oral severa. En los estudios de los últimos años se ha propuesto el uso de la miel en el manejo de la mucositis oral inducida por quimioterapia y radioterapia en pacientes pediátricos. La miel reduce la severidad y duración de la mucositis, reduce el dolor y es un producto agradable a los niños. Por tanto, podría ser un producto eficaz tanto en la profilaxis como en el tratamiento de la mucositis oral. Sin embargo, la pequeña cantidad de investigaciones realizadas en humanos no es suficiente para establecer recomendaciones generalizadas. Por ello, se debe aumentar las investigaciones en este campo. Con ello se podrá examinar la eficacia y posibles complicaciones a corto y largo plazo, explorar su posible efecto sinérgico con otras terapias, analizar su rentabilidad económica y el tipo de miel más adecuado. De esta forma, los profesionales sanitarios podrán ofrecer a los pacientes pediátricos los mejores cuidados basados en las últimas evidencias científicas demostradas.

Mucositis is an inflammatory response of the mucosal epithelium to the cytotoxic effects of chemotherapy and radiation therapy, causing pain and severe oral ulceration. In the studies of recent years, the use of honey has been proposed in the management of oral mucositis induced by chemotherapy and radiotherapy in pediatric patients. Honey reduces the severity and duration of mucositis, reduces pain and is a child-friendly product. Therefore, it could be an effective product both in the prophylaxis and in the treatment of oral mucositis. However, the small amount of human research is not enough to establish widespread recommendations. Therefore, research in this field should be increased. With this, it will be possible to examine the efficacy and possible complications in the short and long term, explore its possible synergistic effect with other therapies, analyze its economic profitability and the most appropriate type of honey. In this way, healthcare professionals will be able to offer pediatric patients the best care based on the latest scientific evidence.

Humans , Child , Mucositis/therapy , Honey , Chemoradiotherapy/adverse effects , Head and Neck Neoplasms/therapy
Article in English | WPRIM | ID: wpr-811216


OBJECTIVE: To compare patient survival outcomes between completion hysterectomy and conventional surveillance in locally advanced adenocarcinoma of the cervix after concurrent chemoradiotherapy (CCRT).METHODS: Patients with adenocarcinoma of the cervix after CCRT were identified in a tertiary academic center database from 2004 to 2018. Patients received completion hysterectomy or surveillance after CCRT. We compared the progression-free survival (PFS) and overall survival (OS) between the patients with or without adjuvant hysterectomy. Surgery features, operative complications, and pathologic characteristics were documented. Patient outcomes were also analyzed according to clinicopathologic factors.RESULTS: A total of 78 patients were assigned to completion surgery and 97 to surveillance after CCRT. The PFS was better in the surgery group compared to the CCRT only group, at 3 years the PFS rates were 68.1% and 45.2%, respectively (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.282–0.749; p=0.002). Adjuvant surgery was also associated with a higher rate of OS (HR=0.361; 95% CI=0.189–0.689; p=0.002), at 3 years, 87.9% and 67%, respectively. Tumor stage, size, lymph-vascular space invasion (LVSI), lymphadenopathy were associated with PFS but not with OS. Hysterectomy specimens revealed 64.1% (50/78) of the patients had pathologic residual tumor. Patients age less than 60, tumor size over 4 cm, stage IIB and persistent residual disease after CCRT were most likely to benefit from hysterectomy. Hysterectomy was associated with a lower rate of locoregional recurrence but did not reach statistical significance (5.13% vs. 13.5%, p=0.067).CONCLUSION: Completion hysterectomy after CCRT was associated with better survival outcome compared with the current standard of care.

Adenocarcinoma , Cervix Uteri , Chemoradiotherapy , Disease-Free Survival , Female , Humans , Hysterectomy , Lymphatic Diseases , Neoplasm, Residual , Recurrence , Standard of Care , Uterine Cervical Neoplasms
J. coloproctol. (Rio J., Impr.) ; 39(4): 309-318, Oct.-Dec. 2019. tab, ilus
Article in English | LILACS | ID: biblio-1056647


Abstract Background: Rectal cancer is one of the most common malignant tumors of gastrointestinal tract. Combining chemotherapy with radiotherapy has a sound effect on its management. Objectives: Assessment the patterns of characterizations of rectal cancer. Evaluation of the efficacy, and long-term survival of pre-/ postoperative chemoradiation. Collecting all eligible evidence articles and summarize the results. Methods: By this systematic review and meta-analysis study, we include data of chemoradiation of rectal cancer articles from 2015 until 2019. The research was carried out at Baghdad Medical City oncology centers. Accordance with the PRISMA guidelines, and the Newcastle-Ottawa Scale used. Results: Starting with gender distribution as M:F ratio of 0.94:1.06. Regarding the age, recorded mean ± SD of 48.7 ± 14.2 years. Rectosigmoid represented the most common site as 50(49.5%), and adenocarcinoma was common histopathology as 76(75.2%) of patients, with localized stage in 50(49.5%). The moderate differentiation was most grade as 65(64.4%). The distant from anal verge mostly seen was 5-10 cm in 59(58.4%). The pulmonary was commonest site of metastasis in 11(10.9%). Most patients undergo APR operation, which has done in 41(40.6%). Adjuvant chemoradiation received by 40(39.6%) patients, whereas neoadjuvant chemoradiation gave to 25 patients. A total of 2609 articles from 12 databases met our search strategies. The highest Newcastle-Ottawa score (8) demonstrated in three studies, and median score (7) calculated in five studies. Conclusions: The incidence belonged to 5th and 6th decade of life. Rectosigmoid represented the most common site. Mostly, the 5-10 cm distant of tumor from anal verge was common finding. The pulmonary was most site of metastasis. We concluded the formulation of a novel point that survival benefit found in many pre or postoperative chemoradiation trials in rectal cancer.

Resumo Introdução: O câncer retal é um dos tumores malignos mais comuns do trato gastrointestinal. A combinação de quimioterapia e radioterapia em seu tratamento é eficaz. Objetivos: Avaliar os padrões de caracterização do câncer retal. Avaliar a eficácia e sobrevida a longo prazo em pacientes submetidos a quimiorradioterapia pré- ou pós-operatória. Coletar todos os artigos de evidências qualificados e resumir os resultados. Métodos: Esta revisão sistemática e metanálise incluiu dados de ensaios clínicos randomizados por cluster de 2015 até 2019. A pesquisa foi realizada nos centros de oncologia do Baghdad Medical City. As diretrizes PRISMA e a escala de Newcastle-Ottawa foram utilizadas para avaliar os estudos. Resultados: Quanto à distribuição por sexo, observou-se uma relação homem:mulher de 0,94:1,06. Em relação à idade, a média ± DP foi de 48,7 ± 14,2 anos. O retossigmoide fpo o local mais comum em 50 pacientes (49,5%); a histopatologia mais comum foi adenocarcinoma, observada em 76 pacientes (75,2%), com estágio localizado em 50 (49,5%). Diferenciação moderada foi observada em 65 pacientes (64,4%). A distância da borda anal variou entre 5 e 10 cm em 59 pacientes (58,4%). O pulmão foi o local mais comum de metástase, sendo observado em 11 pacientes (10,9%). A maioria dos pacientes (41 [40,6%]) foi submetida à ressecção abdominoperineal. Um total de 40 pacientes (39,6%) foram submetidos a quimiorradioterapia adjuvante e 25, a quimiorradioterapia neoadjuvante. Na revisão da literatura, foram encontrados 2.609 artigos que atendiam aos critérios de pesquisa utilizados em 12 bancos de dados. Três estudos atingiram o escore máximo na escala de Newcastle-Ottawa (8); cinco estudos atingiram o escore mediano (7). Conclusões: No presente estudo, a maior incidência de câncer retal foi observada entre a quinta e sexta décadas de vida. O retossigmoide foi o sítio tumoral mais comum. A maioria dos tumores estava localizado entre 5 a 10 cm de distância da margem anal. O pulmão foi o local mais importante de metástase. No presente estudo, quimiorradioterapia pré- ou pós-operatória estava relacionada a uma maior sobrevida em casos de câncer retal.

Humans , Male , Female , Rectal Neoplasms , Rectal Neoplasms/drug therapy , Chemoradiotherapy, Adjuvant , Radiotherapy , Drug Therapy , Chemoradiotherapy
Rev. chil. pediatr ; 90(6): 598-605, dic. 2019. tab
Article in Spanish | LILACS | ID: biblio-1058190


INTRODUCCIÓN: La radioterapia, quimioterapia y la cirugía empleada en el tratamiento de los tumores cerebrales tienen efectos en el eje hipotálamo-hipofisario y pueden resultar en disfunción endocrina hasta en el 96% de los casos. PACIENTES Y MÉTODO: Estudio retrospectivo y descriptivo en pacientes diagnos ticados de meduloblastoma sometidos a tratamiento con quimio y radioterapia en los últimos 20 años en un hospital terciario. Se analizan variables edad, sexo, peso, talla, índice de masa corporal (IMC) al final del seguimiento, estadio de maduración sexual, niveles séricos de TSH y T4 libre, ACTH/cortisol e IGF-1, FSH, LH, estradiol, testosterona, perfil lipídico (colesterol total) y prueba de función dinámica de hormona de crecimiento. RESULTADOS: Muestra total de 23 pacientes. El déficit de hormona de crecimiento es la secuela más frecuente (82 %) seguido de disfunción ti roidea (44,8%) y disfunción puberal (24,1%). Solo se diagnosticó un caso de diabetes insípida y 2 casos de déficit de corticotrofina. CONCLUSIONES: El seguimiento a largo plazo de los supervivientes de meduloblastoma tratados con quimio y radioterapia revela una prevalencia muy alta de disfun ción endocrina, particularmente de deficiencia de hormona del crecimiento y de hipotiroidismo. Creemos oportuna la monitorización y el seguimiento a largo plazo de estos pacientes con el fin de garantizar un manejo terapéutico adecuado de aquellas disfunciones tratables.

INTRODUCTION: Radiation therapy, chemotherapy, and surgery used to treat brain tumors have effects on the hy pothalamic-pituitary-adrenal axis and can result in endocrine dysfunction in up to 96% of cases. PATIENTS Y METHOD: Retrospective and descriptive study in patients diagnosed with medulloblasto ma who underwent treatment with chemo and radiotherapy in the last 20 years in a tertiary hospital. The variables analyzed were age, sex, weight, height, body mass index (BMI) at the end of follow-up, sexual maturity stage, serum levels of TSH and free T4, ACTH/cortisol and IGF-1, FSH, LH, estradiol, testosterone, lipid profile (total cholesterol), and growth hormone dynamic function test. RESULTS: Total sample of 23 patients. Growth hormone deficiency is the most frequent sequelae (82%) fo llowed by thyroid dysfunction (44.8%), and disorders of puberty (24.1%). Only one case of diabetes insipidus and two cases of corticotropin deficiency were diagnosed. CONCLUSIONS: Long-term follow- up of medulloblastoma survivors treated with chemo and radiotherapy reveals a very high prevalence of endocrine dysfunction, especially growth hormone deficiency and hypothyroidism. We believe that monitoring and long-term follow-up of these patients is necessary in order to ensure adequate therapeutic management of those treatable dysfunctions.

Humans , Male , Female , Child, Preschool , Child , Cerebellar Neoplasms/therapy , Chemoradiotherapy/adverse effects , Medulloblastoma/therapy , Puberty, Precocious/etiology , Thyroid Diseases/etiology , Cerebellar Neoplasms/blood , Retrospective Studies , Adrenocorticotropic Hormone/deficiency , Human Growth Hormone/deficiency , Diabetes Insipidus/etiology , Endocrine System Diseases/etiology , Overweight/etiology , Cancer Survivors , Hypogonadism/etiology , Medulloblastoma/blood
Rev. colomb. gastroenterol ; 34(4): 438-444, oct.-dic. 2019. graf
Article in Spanish | LILACS | ID: biblio-1092974


Resumen El carcinoma del canal anal es responsable de hasta el 4% de los casos de cáncer de colon, recto y ano; el tipo histológico más común es el carcinoma escamocelular. Una proporción no despreciable de pacientes se presenta con enfermedad metastásica al momento del diagnóstico. En estos estadios, el pronóstico es pobre y su tratamiento usualmente se basa en quimioterapia paliativa con cisplatino y 5-fluorouracilo, con tasas de supervivencia que no superan el 30% a 5 años. Algunos estudios recientes han sugerido que el tratamiento multidisciplinario con quimiorradiación, que se brinda en estadios más tempranos de la enfermedad, podría mejorar la supervivencia en un grupo seleccionado de pacientes. A continuación, presentamos el caso de un paciente masculino de 54 años con carcinoma escamocelular del canal anal con compromiso metastásico extenso y con VIH atendido en una institución especializada en el manejo de cáncer, en el cual se logró remisión completa de la enfermedad luego del manejo con quimiorradioterapia concomitante con mitomicina C y 5-fluorouracilo y se mantiene en remisión después de cerca de 4 años de haberse suspendido el tratamiento. Se discute el caso y se revisa la literatura al respecto.

Abstract Anal canal carcinoma is responsible for up to 4% of all cases of colon, rectum and anus cancer. The most common histological type is squamous cell carcinoma. A non-negligible proportion of patients have metastasized by the time of diagnosis. In these stages the prognosis is poor, and treatment is usually based on palliative chemotherapy with cisplatin and 5-fluorouracil. Five year survival rates do not exceed 30%. Some recent studies have suggested that multidisciplinary chemoradiotherapy (chemotherapy combined with radiation therapy) in earlier stages of the disease could improve survival for a select group of patients. We present the case of a 54-year-old male patient with squamous cell carcinoma of the anal canal with extensive metastasis who also had HIV. He was treated at an institution specializing in cancer treatment where complete remission of the disease was achieved after treatment with chemoradiotherapy with Mitomycin C and 5-fluorouracil. He remains in remission four years after discontinuation of treatment. We discuss the case and review the literature.

Humans , Male , Middle Aged , Anal Canal , HIV , Chemoradiotherapy , Neoplasm Metastasis , Anus Neoplasms , Carcinoma, Squamous Cell , Literature
Rev. Assoc. Med. Bras. (1992) ; 65(10): 1295-1299, Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1041027


SUMMARY AIM To examine the relationship between treatment response and hypoxia-inducible factor-1 alpha (HIF-1α) levels in patients with locally advanced non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT). METHODS Eighty patients with NSCLC were included in the study and treated at Acibadem Mehmet Ali Aydınlar University Medical Faculty. HIF-1 α levels were measured before and after CRT by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS Patients' stages were as follows; stage IIIA (65%) and stage IIIB (35%). Squamous histology was 45%, adenocarcinoma was 44%, and others were 11%. Chemotherapy and radiotherapy were given concurrently to 80 patients. Forty-five (56%) patients received cisplatin-based chemotherapy, and 35 (44%) received carboplatin-based chemotherapy. Serum HIF-1α levels (42.90 ± 10.55 pg/mL) after CRT were significantly lower than the pretreatment levels (63.10 ± 10.22 pg/mL, p<0.001) in patients with locally advanced NSCLC. CONCLUSION The results of this study revealed that serum HIF-1α levels decreased after CRT. Decrease of HIF-1α levels after the initiation of CRT may be useful for predicting the efficacy of CRT.

RESUMO OBJETIVO Examinar a relação entre a resposta ao tratamento e os níveis de fator 1 induzida por hipóxia (HIF-1α) em pacientes com câncer de pulmão de células não pequenas localmente avançado (NSCLC) que receberam quimiorradioterapia (CRT). MÉTODO Oitenta pacientes com NSCLC foram incluídos no estudo e foram tratados na Faculdade de Medicina da Acibadem Mehmet Ali Aydınlar University. O nível de HIF-1α foi medido antes e depois da TRC pelo método de ensaio imunoenzimático (ELISA). RESULTADOS Os estágios dos pacientes foram os seguintes; estágio IIIA (65%) e estágio IIIB (35%). A histologia escamosa foi de 45%, o adenocarcinoma de 44% e o outro de 11%. Quimioterapia e radioterapia foram dadas simultaneamente a 80 pacientes. Quarenta e cinco (56%) pacientes receberam quimioterapia à base de cisplatina e 35 (44%) receberam quimioterapia à base de carboplatina. Os níveis séricos de HIF-1α (42,90 ± 10,55 pg / mL) após a TRC foram significativamente menores do que os níveis pré-tratamento (63,10 ± 10,22 pg / mL, p <0,001) em pacientes com NSCLC localmente avançado. CONCLUSÃO Os resultados deste estudo revelaram que os níveis séricos de HIF-1α diminuíram após a TRC. A diminuição dos níveis de HIF-1α após o início da TRC pode ser útil para prever a eficácia da TRC.

Humans , Male , Female , Aged , Adenocarcinoma/blood , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Hypoxia-Inducible Factor 1, alpha Subunit/blood , Lung Neoplasms/blood , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Middle Aged
Rev. otorrinolaringol. cir. cabeza cuello ; 79(2): 229-239, jun. 2019.
Article in Spanish | LILACS | ID: biblio-1014442


RESUMEN Los análogos del platino, como el cisplatino, y la radioterapia son usados de forma individual y en conjunto para el tratamiento de diversas neoplasias en población adulta y pediátrica. Sin embargo, el uso de estos tratamientos puede generar ototoxicidad, especialmente cuando son usados de forma combinada para neoplasias que comprometen cabeza y cuello, manifestándose principalmente como una hipoacusia progresiva e irreversible que compromete la calidad de vida. Diversos mecanismos han sido propuestos para explicar el daño en las estructuras auditivas generado por estos tratamientos, incluyendo la producción de especies reactivas del oxígeno y la inflamación, desencadenando muerte celular. Si bien distintas estrategias otoprotectoras han sido probadas en humanos, es aún incierta su efectividad y seguridad en combinación con los tratamientos oncológicos. El objetivo de la siguiente revisión es proporcionar una visión general y actualizada de la ototoxicidad inducida por quimio-radioterapia basada en platinos, discutiendo sus bases, características clínicas, potenciales tratamientos y estrategias preventivas que se han desarrollado en los últimos años.

ABSTRACT Platinum analogues, such as cisplatin, and radiotherapy are used separately or in combination to treat several neoplasms in pediatric and adult populations. Nonetheless, the use of these treatments may lead to ototoxicity, especially when these treatments are concomitantly used to treat head and neck cancers, which can manifest as progressive and irreversible hearing loss that decreases quality of life. Several mechanisms have been proposed in order to explain the damage to the auditory structures induced by these treatment modalities, including: reactive oxygen species production and inflammation, leading to cell death. Although several otoprotective strategies have been attempted in humans, their effectiveness and security are unclear. The objective of this review is to provide an updated and general overview on platinum-based chemoradio-therapy induced ototoxicity, discussing its basis, clinical features, potential treatments and preventive strategies developed in recent years.

Humans , Cisplatin/adverse effects , Chemoradiotherapy/adverse effects , Ototoxicity/etiology , Ototoxicity/prevention & control , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Hearing Loss, Sensorineural/etiology
Article in Korean | WPRIM | ID: wpr-785902


PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.

Chemoradiotherapy , Colorectal Neoplasms , Dysbiosis , Fusobacterium , Gastrointestinal Microbiome , Genes, vif , Genome , Humans , Microbiota , Neoadjuvant Therapy , Prevotella , Radiotherapy , Rectal Neoplasms , Sequence Analysis, RNA , Transcriptome
Article in English | WPRIM | ID: wpr-785880


PURPOSE: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx).MATERIALS AND METHODS: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method.RESULTS: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014).CONCLUSION: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.

Biomarkers , Carcinoma, Hepatocellular , Chemoradiotherapy , Humans , Magnetic Resonance Imaging , Methods , Perfusion Imaging , Response Evaluation Criteria in Solid Tumors , ROC Curve , Sensitivity and Specificity , Ultrasonography
Article in English | WPRIM | ID: wpr-739672


BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.

Brain , Central Nervous System , Chemoradiotherapy , Diagnosis , Drug Therapy , Glioblastoma , Humans , Korea , Radiotherapy
Article in English | WPRIM | ID: wpr-739574


PURPOSE: To assess the feasibility of transanal total mesorectal excision in difficult cases including obese patients or patients with bulky tumors or threatened mesorectal fascias. METHODS: We performed laparoscopy-assisted transanal total mesorectal excision in patients with biopsy-proven rectal adenocarcinoma located 3–12 cm from the anal verge as part of a prospective, single arm, pilot trial. The primary endpoint was resection quality and circumferential resection margin involvement. Secondary endpoints included the number of harvested lymph nodes and 30-day postoperative complications. RESULTS: A total of 12 patients (9 men and 3 women) were enrolled: one obese patient, 7 with large tumors and 8 with threatened mesorectal fascias (4 patients had multiple indications). Tumors were located a median of 5.5 cm from the anal verge, and all patients received preoperative chemoradiotherapy. Median operating time was 191 minutes, and there were no intraoperative complications. One patient needed conversion to open surgery for ureterocystostomy after en bloc resection. Complete or near-complete excision and negative circumferential resection margins were achieved in all cases. The median number of harvested lymph nodes was 15.5. There was no postoperative mortality and 3 cases of postoperative morbidity (1 postoperative ileus, 1 wound problem near the stoma site, and 1 anastomotic dehiscence). CONCLUSION: This pilot study showed that transanal total mesorectal excision is also feasible in difficult laparoscopic cases such as in obese patients or those with bulky tumors or tumors threatening the mesorectal fascia. Additional larger studies are needed.

Adenocarcinoma , Arm , Chemoradiotherapy , Conversion to Open Surgery , Fascia , Humans , Ileus , Intraoperative Complications , Laparoscopy , Lymph Nodes , Male , Mortality , Pilot Projects , Postoperative Complications , Prospective Studies , Rectal Neoplasms , Transanal Endoscopic Surgery , Wounds and Injuries