A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

Purpose: This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Results: Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. Conclusion: HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT40155531.

Glioblastoma - treatment and obstacles.

Background: Glioblastoma is the most common and aggressive primary tumor in adults. A narrative review of all the relevant papers known was conducted. Materials and methods: Reviews, clinical trials, and randomized controlled trials published from 1981 through September 2021 and written, or at least abstracted, in English were analyzed. Results: The standard of care for glioblastoma is the maximum safe resection possible, followed by radiation therapy and concurrent temozolomide (TMZ) and daily TMZ and tumor treatment fields (TTFields) after irradiation. There is no evidence to date of the benefit of brachytherapy, radiosurgery (SRS), fractional stereotactic radiotherapy (FSRT), and hyperfractionated radiotherapy over conventional external beam radiation therapy (EBRT) for the primary tumor. The assessment of age and performance status before treatment in the elderly enables hypofractionated radiotherapy. The research of tumor molecular signatures contributes to the choice of the best-targeted drug therapy. In recurrent glioblastoma, it is necessary to balance the risks and benefits of re-radiation and association with bevacizumab. Solid data confirming the role of immunotherapy in the treatment of malignant glioma are still lacking. Conclusions: Although the treatment of glioblastoma has evolved in terms of local control, mortality remains close to 12 months after diagnosis. To obtain better results and reduce recurrence, future research needs to investigate the frontiers of knowledge, such as the elucidation of the molecular mechanisms related to the tumor, the optimization of drugs to overcome the blood-brain barrier effectively, and the discovery of new therapies aimed at the heterogeneous profile of this neoplasm.

Practical Prediction Model for Ovarian Insufficiency after Radiation / Modelo prático de predição para insuficiência ovariana após radiação

Abstract Objective The present study aimed to develop a useful mathematical model that predicts the age at which premature ovarian insufficiency might occur after teletherapy radiation. A diagnosis of premature or early menopause has physical and psychological consequences, so women may need support and long-term medical follow-up. Methods To correlate ovarian radiation dose with ovarian function, we used the formula described by Wallace et al.: √g(z) = 10(2-0,15z), where "g(z)" and "z" represent oocyte survival rate and the radiation dose (in Gray), respectively. By simulating different ages and doses, we observed a pattern that could be used to simplify the relationship between radiation dose and remaining time of ovarian function. Results We obtained a linear function between ovarian radiation dose and loss of ovarian function (LOF) that is the percentage of decrease in the time to the ovarian failure compared with the time expected for a woman at the same age without irradiation exposition. For patients <40 years old and with ovarian radiation doses < 5 Gy, the equation LOF = 2.70 + (11.08 × Dose) can be applied to estimate the decrease in time to premature ovarian insufficiency. Conclusion The present study reports a practicable theoretical method to estimate the loss of ovarian function. These findings can potentially improve the management and counseling of young women patients submitted to radiotherapy during their reproductive years.

Resumo Objetivo O presente estudo teve como objetivo desenvolver um modelo matemático útil que prediz a idade na qual a insuficiência ovariana prematura pode ocorrer após a radioterapia externa (teleterapia). O diagnóstico de menopausa prematura ou precoce tem consequências físicas e psicológicas; portanto, as mulheres podem precisar de apoio e acompanhamento médico de longo prazo. Métodos Para correlacionar a dose de radiação ovariana com a função ovariana, foi usada a fórmula descrita por Wallace et al.: √g(z) = 10(2-0,15z), na qual "g(z)" e "z" representam a taxa de sobrevivência do oócito e a dose de radiação (em Gray), respectivamente. Ao simular diferentes idades e doses, observamos um padrão que poderia ser usado para simplificar a relação entre a dose de radiação e o tempo restante da função ovariana. Resultados Obtivemos uma função linear entre a dose de radiação ovariana e a perda da função ovariana (LOF, na sigla em inglês) que é a porcentagem de diminuição no tempo até a falência ovariana em relação ao tempo esperado para uma mulher da mesma idade sem exposição à radiação. Para pacientes<40 anos de idade e com doses de radiação ovariana < 5 Gy, a equação LOF = 2,70 + (11,08 × Dose) pode ser aplicada para estimar a redução no tempo até a insuficiência ovariana. Conclusão O presente estudo relata um método teórico viável para estimar a perda da função ovariana. Estes achados podem melhorar potencialmente o manejo e o aconselhamento de pacientes jovens submetidas à radioterapia durante seus anos reprodutivos.

Practical Prediction Model for Ovarian Insufficiency after Radiation.

OBJECTIVE: The present study aimed to develop a useful mathematical model that predicts the age at which premature ovarian insufficiency might occur after teletherapy radiation. A diagnosis of premature or early menopause has physical and psychological consequences, so women may need support and long-term medical follow-up. METHODS: To correlate ovarian radiation dose with ovarian function, we used the formula described by Wallace et al.: √g(z) = 10(2-0,15z), where "g(z)" and "z" represent oocyte survival rate and the radiation dose (in Gray), respectively. By simulating different ages and doses, we observed a pattern that could be used to simplify the relationship between radiation dose and remaining time of ovarian function. RESULTS: We obtained a linear function between ovarian radiation dose and loss of ovarian function (LOF) that is the percentage of decrease in the time to the ovarian failure compared with the time expected for a woman at the same age without irradiation exposition. For patients < 40 years old and with ovarian radiation doses < 5 Gy, the equation LOF = 2.70 + (11.08 x Dose) can be applied to estimate the decrease in time to premature ovarian insufficiency. CONCLUSION: The present study reports a practicable theoretical method to estimate the loss of ovarian function. These findings can potentially improve the management and counseling of young women patients submitted to radiotherapy during their reproductive years.

OBJETIVO: O presente estudo teve como objetivo desenvolver um modelo matemático útil que prediz a idade na qual a insuficiência ovariana prematura pode ocorrer após a radioterapia externa (teleterapia). O diagnóstico de menopausa prematura ou precoce tem consequências físicas e psicológicas; portanto, as mulheres podem precisar de apoio e acompanhamento médico de longo prazo. MéTODOS: Para correlacionar a dose de radiação ovariana com a função ovariana, foi usada a fórmula descrita por Wallace et al.: √g(z) = 10(2-0,15z), na qual "g(z)" e "z" representam a taxa de sobrevivência do oócito e a dose de radiação (em Gray), respectivamente. Ao simular diferentes idades e doses, observamos um padrão que poderia ser usado para simplificar a relação entre a dose de radiação e o tempo restante da função ovariana. RESULTADOS: Obtivemos uma função linear entre a dose de radiação ovariana e a perda da função ovariana (LOF, na sigla em inglês) que é a porcentagem de diminuição no tempo até a falência ovariana em relação ao tempo esperado para uma mulher da mesma idade sem exposição à radiação. Para pacientes < 40 anos de idade e com doses de radiação ovariana < 5 Gy, a equação LOF = 2,70 + (11,08 x Dose) pode ser aplicada para estimar a redução no tempo até a insuficiência ovariana. CONCLUSãO: O presente estudo relata um método teórico viável para estimar a perda da função ovariana. Estes achados podem melhorar potencialmente o manejo e o aconselhamento de pacientes jovens submetidas à radioterapia durante seus anos reprodutivos.

Impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional hand hygiene approach in 3 cities in Brazil.

BACKGROUND: Hand hygiene (HH) is the main tool for cross-infection prevention, but adherence to guidelines is low in limited-resource countries, and there are not available published data from Brazil. METHODS: This is an observational, prospective, interventional, before-and-after study conducted in 4 intensive care units in 4 hospitals, which are members of the International Nosocomial Infection Control Consortium (INICC), from June 2006-April 2008. The study was divided into a 3-month baseline period and a follow-up period. A multidimensional HH approach was introduced, which included administrative support, supplies availability, education and training, reminders in the workplace, process surveillance, and performance feedback. Health care workers were observed for HH practices in each intensive care unit during randomly selected 30-minute periods. RESULTS: We recorded 4,837 opportunities for HH, with an overall HH compliance that increased from 27%-58% (P < .01). Multivariate analysis showed that some variables were associated with poor HH compliance: men versus women (49% vs 38%, P < .001), nurses versus doctors (55% vs 48%, P < .02), among others. CONCLUSIONS: With the implementation of the INICC approach, adherence to HH was significantly increased. Programs should be aimed at improving HH in variables found to be predictors of poor HH compliance.