Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: a randomized clinical trial.

BACKGROUND: We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer. METHODS: open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18-75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression. RESULTS: the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37). CONCLUSIONS: there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-23w5fv . Registered 10 January 2017 - Retrospectively registered.

Use of interstitial brachytherapy in pelvic recurrence of cervical carcinoma: Clinical response, survival, and toxicity.

PURPOSE: The purpose of this study was to evaluate clinical response, postrecurrence survival, disease-free survival (DFS), and toxicity related to reirradiation in pelvic recurrence of cervical carcinoma. METHODS AND MATERIALS: A retrospective cohort study of 45 women undergoing high-dose-rate interstitial brachytherapy (HDR-IB) was conducted from 1998 to 2014. Clinical information, as well as data on the malignancy, primary treatment, HDR-IB technique, and toxicity, was collected. Statistical analysis used chi-square or Fisher's exact test, Kaplan-Meier survival curves and log-rank test, and Cox regression, with p < 0.05 for significance. RESULTS: There were 30 cases (67%) of complete clinical response, with a followup period of 9-129 months (20 alive, 10 died). The 5-year postrecurrence survival rate was 52%. Among 15 women without complete clinical response, the survival rate was low (<8 months). In the 30 women with complete clinical response, the 5-year DFS was 42%. All analyzed variables were not associated with survival. Ultrasonography-based needle placement was not associated with disease control or toxicity. Toxicity was reported in 23 women (51%) with 14 fistulas, unrelated to clinical response. However, there was a higher occurrence of fistula when chemotherapy was used. CONCLUSIONS: Reirradiation using HDR-IB for pelvic recurrence of cervical carcinoma yielded a good complete clinical response rate. Postrecurrence survival and DFS rates were higher than expected, equivalent to salvage surgery, but with significant toxicity. Despite toxicity, this technique can be an alternative for selected cases.

Factors associated with changes in vaginal length and diameter during pelvic radiotherapy for cervical cancer.

OBJECTIVES: This study reports the incidence and factors associated with vaginal stenosis and changes in vaginal dimensions after pelvic radiotherapy for cervical cancer. METHODS: A descriptive longitudinal study with 139 women with cervical cancer was conducted from January 2013 to November 2015. The outcome variables were vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE v3.0) and changes in vaginal diameter and length after the end of radiotherapy. Independent variables were the characteristics of the neoplasm, clinical and sociodemographic data. Bivariate analysis was carried out using χ 2, Kruskal-Wallis and Mann-Whitney's test. Multiple analysis was carried out using Poisson regression and a generalized linear model. RESULTS: Most women (50.4%) had stage IIIB tumors. According to CTCAE v3.0 scale, 30.2% had no stenosis, 69.1% had grade 1 and 0.7% had grade 2 stenosis after radiotherapy. Regarding changes in vaginal measures, the mean variation in diameter was - 0.6 (± 1.7) mm and the mean variation in length was - 0.6 (± 1.3) cm. In the final statistical model, having tumoral invasion of the vaginal walls (coefficient + 0.73, p < 0.01) and diabetes (coefficient + 1.16; p < 0.01) were associated with lower vaginal stenosis and lower reduction of vaginal dimensions. Advanced clinical stage (coefficient + 1.44; p = 0.02) and receiving brachytherapy/teletherapy (coefficient - 1.17, p < 0.01) were associated with higher reduction of vaginal dimensions. CONCLUSIONS: Most women had mild vaginal stenosis with slight reductions in both diameter and length of the vaginal canal. Women with tumoral invasion of the vagina have an increase in vaginal length soon after radiotherapy due to a reduction in tumoral volume.

Fatores associados à variação no comprimento e diâmetro vaginal após radioterapia pélvica para câncer do colo uterino / Factors associated with changes in vaginal length and diameter after pelvic radiotherapy for cervical cancer

Introdução: o câncer do colo uterino é o quarto tipo de câncer mais comum entre as mulheres. O tratamento pode incluir a radioterapia e um dos eventos adversos é a estenose vaginal. Objetivos: avaliar a incidência de estenose vaginal através de medidas objetivas e uma escala subjetiva, e identificar os fatores associados à ocorrência desse evento adverso após a radioterapia pélvica. Métodos: estudo longitudinal descritivo realizado de janeiro/2013 a novembro/2015 com 139 mulheres portadoras de neoplasia maligna do colo uterino, estádio I-IIIB, com idades entre 18-75 anos que haviam sido convidadas a participar de um ensaio clínico randomizado para avaliar diversos tratamentos para estenose vaginal após radioterapia. O desfecho foi a estenose vaginal, avaliada através da escala de estenose vaginal Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) e da diferença entre as medidas do comprimento e do diâmetro da vagina logo após o término da radioterapia. As variáveis independentes foram as características da neoplasia, dados clínicos e sociodemográficos. A análise bivariada foi realizada usando os testes do qui-quadrado, Kruskal-Wallis e Mann-Whitney. A análise multivariada foi realizada através da regressão de Poisson e do modelo linear generalizado. Resultados: a média de idade foi de 47,2 (± 13,4) anos e 40,3% das mulheres estavam na pós-menopausa. Metade delas apresentava câncer do colo do útero estadio IIIB (50,4%). Pela escala CTCAEv3.0, 42 mulheres (30,2%) não apresentaram estenose, 96 mulheres (69,1%) apresentaram estenose grau 1 e uma mulher (0,7%) apresentou estenose grau 2 logo após a radioterapia. Com relação às alterações das medidas vaginais, a variação média de diâmetro foi -0,6 (± 1,7) mm e a variação média do comprimento foi -0,6 (± 1,3) cm. Quinze mulheres apresentaram redução do diâmetro vaginal, sendo que em 93,5% delas a redução foi de 0,5 cm e em 1 mulher a redução foi de 1 cm. Com relação ao comprimento vaginal, 65,7% apresentaram diminuição da medida, sendo que dessas, 62% tiveram diminuição de 0,5-1 cm; 32% tiveram diminuição de 1,5-2,5 cm e 6% tiveram diminuição de 3-4 cm. Por outro lado, 11 mulheres (8%) tiveram aumento do comprimento vaginal, sendo que dessas, 36,3% tiveram aumento de 0,5-1 cm; 36,3% tiveram aumento de 1,5-2,5 cm; 18,3% tiveram aumento de 3-4 cm e 9,1% tiveram aumento de 5 cm. Na análise multivariada, mulheres com invasão vaginal apresentaram menos estenose vaginal pela escala CTCAEv3.0 (coeficiente:-0,51;p<0,01). Quanto à variação do diâmetro, mulheres com estadiamento clínico IIIA/IIIB apresentaram redução da medida mais frequentemente (coeficiente:+1,44;p=0,02). Quanto à variação do comprimento, mulheres que realizaram teleterapia/braquiterapia apresentaram maior redução da medida (coeficiente:-1,17;p<0,01) e mulheres portadoras de diabetes (coeficiente:+1,16; p<0,01) e com invasão vaginal pelo tumor (coeficiente:+0,73;p<0,01) apresentaram aumento da medida. Conclusões: a maioria das mulheres apresentou estenose leve, com redução discreta do comprimento do canal vaginal. Estadiamento clínico avançado e realizar uma associação de braquiterapia e teleterapia se associaram a uma maior frequência de estenose. Mulheres com neoplasias do colo que invadem a vagina apresentam aumento das medidas do comprimento vaginal logo após a radioterapia devido à redução do volume tumoral. (AU)

Introduction: cervical cancer is the fourth most common cancer among women. Treatment may include radiation therapy and one of the adverse events is vaginal stenosis. Objectives: to evaluate the incidence of vaginal stenosis using objective measures and a subjective scale, and to identify factors associated with the occurrence of this adverse event after pelvic radiotherapy for cancer of the cervix. Methods: a longitudinal descriptive study conducted from Jan/2013 to Nov/2015 with 139 women suffering from malignant cervical cancer, stage I-IIIB, aged 18-75 years who had been invited to participate in a randomized clinical trial to evaluate various treatments for vaginal stenosis after radiotherapy. The main outcome was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAEv3.0) and through changes in vaginal diameter and length after the end of radiotherapy. Independent variables were the characteristics of the neoplasm, clinical and sociodemographic data. Bivariate analysis was carried out using chi-squared test, Kruskal-Wallis and Mann-Whitney's test. Multiple analysis was carried out using Poisson regression and a generalized linear model. Results: The mean age was 47.2 (± 13.4) years and 40.3% of women were postmenopausal. Half of them had cervical cancer stage IIIB (50.4%). By CTCAEv3.0 scale, 42 women (30.2%) showed no stenosis, 96 women (69.1%) had grade 1 stenosis and one woman (0.7%) had grade 2 stenosis after radiotherapy. Regarding changes in vaginal measures the average change in diameter was 0.6 (± 1.7) mm and the average length variation was -0.6 (± 1.3) cm. Fifteen women had reduced vaginal diameter, and in 93.5% of them the reduction was 0.5 cm and in one woman the reduction was 1 cm. Regarding vaginal length, 65.7% showed a decrease in extent, and of these, 62% had decreased 0.5-1 cm; 32% had decreased 1.5-2.5 cm and 6% had a reduction of 3-4 cm. On the other hand, 11 women (8%) had an increase in vaginal length, and of these, 36.3% had an increase of 0.5-1 cm; 36.3% had an increase of 1.5-2.5 cm; 18.3% had an increase of 3-4 cm and 9.1% had an increase of 5 cm. In multivariate analysis, women with tumoral invasion of the vaginal walls had fewer vaginal stenosis by CTCAEv3.0 scale (coefficient: -0.51, p <0.01). As to changes in diameter, women with clinical stage IIIA/IIIB had reductions in this measure more frequently (coefficient: +1.44; p=0.02). As to changes in vaginal length, women who underwent teletherapy/brachytherapy showed greater reduction in this measure (coefficient: -1.17; p <0.01) and women with diabetes (coefficient: +1.16; p <0.01) and tumoral invasion of the vaginal walls (coefficient: +0.73; p <0.01) had increases in this measure more frequently. Conclusion: most women had mild stenosis, with a slight reduction of the length of the vagina. Advanced clinical stage and performing a combination of brachytherapy and teletherapy were associated with a higher frequency of stenosis. Women with cervical cancer which invades the vaginal walls have increases in vaginal length after radiotherapy due to reduction in tumoral volume.(AU)