Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Activation of gelatinases in permanent human teeth after different experimental radiotherapy protocols

Abstract The objective of this study was to compare the activation of gelatinases in dentin-enamel junction (DEJ) and underlying dentin of permanent teeth after experimental radiotherapy in conventional and hypofractionated modalities. Newly extracted third molars (n = 15) were divided into three experimental radiotherapy groups: control, conventional (CR), and hypofractionated (HR) (n = 5 per group). After in vitro exposure to ionizing radiation, following standardized protocols for each modality, a gelatinous substrate was incubated on the tooth slices (n = 10 per group). Activation of gelatinases was measured by in situ zymography, expressed in arbitrary fluorescence units (mm2) from three tooth regions: cervical, cuspal, and pit. Fluorescence intensity was compared among radiotherapy protocols and tooth regions in each protocol, considering a significance level of 5%. Considering all tooth regions, the fluorescence intensity of the CR group was higher than the HR and control groups, both in DEJ and underlying dentin (p <0.001). In addition, the fluorescence intensity was higher in underlying dentin when compared to DEJ in all groups (p <0.001). Considering each tooth region, a statistically significant difference between CR and HR was only observed in the pit region of underlying dentin (p <0.001). Significant and positive correlations between fluorescence intensities in DEJ and underlying dentin were also observed (p <0.001). Experimental radiotherapy influenced the activation of gelatinases, as well as exposure to the conventional protocol can trigger a higher activation of gelatinases when compared to hypofractionated, both in DEJ and underlying dentin.

Resumo O objetivo deste estudo foi comparar a ativação de gelatinases na junção dentina-esmalte (DEJ) e na dentina subjacente de dentes permanentes após a radioterapia experimental nas modalidades convencional e hipofracionada. Os terceiros molares recém-extraídos (n = 15) foram divididos em três grupos de radioterapia experimental: controle, convencional (CR) e hipofracionada (HR) (n = 5 por grupo). Após a exposição in vitro à radiação ionizante, seguindo protocolos padronizados para cada modalidade, um substrato gelatinoso foi incubado nas fatias de dente (n = 10 por grupo). A ativação das gelatinases foi medida por zimografia in situ, expressa em unidades arbitrárias de fluorescência (mm2) de três regiões do dente: cervical, cúspide e fossa. A intensidade da fluorescência foi comparada entre os protocolos de radioterapia e as regiões do dente em cada protocolo, considerando um nível de significância de 5%. Considerando todas as regiões do dente, a intensidade de fluorescência do grupo CR foi maior do que a dos grupos HR e controle, tanto no DEJ quanto na dentina subjacente (p <0,001). Além disso, a intensidade da fluorescência foi maior na dentina subjacente quando comparada à DEJ em todos os grupos (p <0,001). Considerando cada região do dente, uma diferença estatisticamente significativa entre CR e HR foi observada apenas na região da fossa da dentina subjacente (p <0,001). Também foram observadas correlações significativas e positivas entre as intensidades de fluorescência no DEJ e na dentina subjacente (p <0,001). A radioterapia experimental influenciou a ativação das gelatinases, assim como a exposição ao protocolo convencional pode desencadear uma maior ativação das gelatinases quando comparada ao hipofracionamento, tanto no DEJ quanto na dentina subjacente.

Toxicities of hypofractionated radiotherapy after breast-conserving surgery: a literature review / 中华放射肿瘤学杂志

Hypofractionated radiotherapy, which provides equivalent efficacy and dose not increase toxicity compared with conventional fractionated radiotherapy following breast-conserving surgery, has become a preferred choice for whole breast irradiation. Given the low local recurrence risk and long survival time for early breast cancer survivors, radiation-associated toxicities are the focus of clinical practice. However, in the era of hypofractionated radiotherapy, the risk factors for radiation-associated toxicity remain undefined and further research is warranted. In this review, we aim to provide an overview of the toxicities of hypofractionated radiotherapy following breast-conserving surgery.

Incidence of radiodermatitis in breast cancer patients during hypofractionated radiotherapy / Incidencia de radiodermatitis en pacientes con cáncer de mama durante la radioterapia hipofraccionada / Incidência de radiodermatite em pacientes com câncer de mama durante a radioterapia hipofracionada

ABSTRACT Objective: To analyze the incidence, dose of occurrence, grade, severity, and associated risk factors for the development of radiodermatitis, by area of the irradiated breast, in women with breast cancer, during hypofractionated radiotherapy. Method: Observational, prospective, and longitudinal study, according to the guidelines of the Strengthening the Reporting of Observational studies in Epidemiology, carried out between May 2019 and May 2021. Results: A total of 104 women participated in the study, and 73.1% (95%CI: 64-82) developed signs of radiodermatitis during treatment. The majority (63.5%, 95%CI: 54-73) developed erythema in the axillary region with about 36.5 Grays. Women with large breasts and statin users are more likely to develop radiodermatitis. However, women with Phototype III skin color classification (light brown skin) are less likely to develop radiodermatitis, with skin color being a protective factor. Conclusion: The incidence of radiodermatitis in women with breast cancer during hypofractionated radiotherapy is significant. Therefore, the development of protocols for the management of this radiotoxicity is suggested, considering the cumulative dose and associated risk factors.

RESUMEN Objectivo: Analizar la incidencia, dosis de ocurrencia, grado, severidad y factores de riesgo asociados para el desarrollo de radiodermatitis, por área de la mama irradiada, en mujeres con cáncer de mama, durante radioterapia hipofraccionada. Método: Estudio observacional, prospectivo y longitudinal, según las directrices del Strengthening the Reporting of Observational studies in Epidemiology, realizado entre mayo de 2019 y mayo de 2021. Resultados: Participaron del estudio 104 mujeres, el 73,1% (IC 95%: 64-82) desarrollaron signos de radiodermatitis durante el tratamiento. La mayoría (63,5%, IC95%: 54-73) desarrolló eritema en la región axilar con alrededor de 36,5 Grays. Las mujeres con senos grandes y usuarias de estatinas tienen más probabilidades de desarrollar radiodermatitis. Sin embargo, las mujeres con color de piel clasificado como Fototipo III (piel morena clara) tienen menos probabilidades de desarrollar radiodermatitis, siendo el color de piel un factor protector. Conclusión: La incidencia de radiodermatitis en mujeres con cáncer de mama durante la radioterapia hipofraccionada es significativa. Por lo tanto, se sugiere el desarrollo de protocolos para el manejo de esta radiotoxicidad, considerando la dosis acumulada y los factores de riesgo asociados.

RESUMO Objetivo: Analisar a incidência, a dose de ocorrência, o grau, a severidade e os fatores de risco associados para o desenvolvimento de radiodermatite, por área da mama irradiada, em mulheres com câncer de mama, durante a radioterapia hipofracionada. Método: Estudo observacional, prospectivo e longitudinal, conforme diretrizes do Strengthening the Reporting of Observational studies in Epidemiology, realizado entre maio de 2019 e maio de 2021. Resultados: Participaram do estudo 104 mulheres, 73,1% (IC95%: 64-82) desenvolveram sinais de radiodermatite durante o tratamento. A maioria (63,5%, IC95%: 54-73) desenvolveu eritema na região axilar com cerca de 36,5 Grays. Mulheres com mamas volumosas e usuárias de estatinas possuem maior chance de desenvolver radiodermatite. Entretanto, mulheres com a cor da pele classificada como Fototipo III (pele morena clara) possuem menor chance de desenvolver radiodermatite, sendo a cor da pele um fator protetor. Conclusão A incidência de radiodermatite em mulheres com câncer de mama durante a radioterapia hipofracionada é expressiva. Sugere-se, portanto, o desenvolvimento de protocolos para o manejo desta radiotoxicidade, considerando a dose cumulativa e fatores de risco associados.

Incidence of acute radiodermatitis in women with breast cancer undergoing hypofractionated radiotherapy / Incidencia de radiodermatitis aguda en mujeres con cáncer de mama sometidas a la radioterapia hipofraccionada / Incidência de radiodermatite aguda em mulheres com câncer de mama submetidas à radioterapia hipofracionada

ABSTRACT Objective: To estimate the incidence and degree of acute radiodermatitis at the end and after the end of treatment in women with breast cancer undergoing hypofractionated radiotherapy. Methods: Observational, prospective, and longitudinal study, conducted between March 2019 and January 2020, in a radiotherapy outpatient clinic. Results: Thirty-two women participated in the study, among whom, in the last session of hypofractionated radiotherapy, 15 (46.9%) had radiodermatitis, erythema in 13 (40.6%), and wet peeling in 2 (6.3%). In the post-treatment evaluation, 27 (84.4%) had radiodermatitis, erythema in 17 (53.1%), dry peeling in 8 (25%), and wet peeling in 2 (6.3%). Conclusion: The general incidence of radiodermatitis after hypofractionated radiotherapy in women with breast cancer was 37.5%, erythema, 12.5%, and dry peeling, 25%. The development of care protocols for the management of radiodermatitis after treatment is of paramount importance.

RESUMEN Objetivo: Estimar la incidencia y el grado de radiodermatitis aguda al final y después el término del tratamiento en mujeres con cáncer de mama sometidas a la radioterapia hipofraccionada. Métodos: Estudio observacional, prospectivo y longitudinal, realizado entre marzo de 2019 y enero de 2020, en un ambulatorio de radioterapia. Resultados: Participaron del estudio 32 mujeres, de entre las cuales, en la última sesión de radioterapia hipofraccionada, 15 (46,9%) presentaban radiodermatitis, siendo eritema en 13 (40,6%) y descamación húmeda en 2 (6,3%). En la evaluación después del tratamiento, 27 (84,4%) presentaban radiodermatitis, siendo eritema en 17 (53,1%), descamación seca en 8 (25%) y descamación húmeda en 2 (6,3%). Conclusión: La incidencia general de radiodermatitis después radioterapia hipofraccionada en mujeres con cáncer de mama fue 37,5%: eritema, 12,5%; y descamación seca, 25%. Es de suma importancia el desarrollo de protocolos asistenciales para el manejo de radiodermatitis después del tratamiento.

RESUMO Objetivo: Estimar a incidência e o grau de radiodermatite aguda ao final e após o término do tratamento em mulheres com câncer de mama submetidas à radioterapia hipofracionada. Métodos: Estudo observacional, prospectivo e longitudinal, realizado entre março de 2019 e janeiro de 2020, em um ambulatório de radioterapia. Resultados: Participaram do estudo 32 mulheres, dentre as quais, na última sessão de radioterapia hipofracionada, 15 (46,9%) apresentavam radiodermatite, sendo eritema em 13 (40,6%) e descamação úmida em 2 (6,3%). Na avaliação após o tratamento, 27 (84,4%) apresentavam radiodermatite, sendo eritema em 17 (53,1%), descamação seca em 8 (25%) e descamação úmida em 2 (6,3%). Conclusão: A incidência geral de radiodermatite após radioterapia hipofracionada em mulheres com câncer de mama foi 37,5%: eritema, 12,5%; e descamação seca, 25%. É de suma importância o desenvolvimento de protocolos assistenciais para o manejo de radiodermatite após o tratamento.

Hypofractionated radiotherapy recommendations for localized prostate cancer in Brasil

SUMMARY OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.

Hypofractionated and hyper-hypofractionated radiation therapy in postoperative breast cancer treatment

SUMMARY INTRODUCTION: Radiation therapy is widely used as adjuvant treatment in breast cancer patients. In the last decades, several studies have been designed to evaluate the safety and efficacy of hypofractionated breast radiation therapy. More recently, even shorter regimens with doses above 4 Gy (hyper-hypofractionation) have also been proposed. This study aims to present a narrative review of the various hypofractionation protocols used to treat breast cancer patients with a focus on clinical application. RESULTS: Long-term results from several phase III randomized controlled trials demonstrated the safety and efficacy of hypofractionated breast radiation therapy using 15 or 16 fractions for early and locally advanced disease. The results of the initial clinical trials of hyper-hypofractionation are also encouraging and it is believed that these regimens may become routine in the indication of adjuvant radiation therapy treatment after the ongoing studies on this subject have matured. CONCLUSIONS: The idea that normal tissues could present high toxicity at doses above 2 Gy was opposed by clinical trials that demonstrated that moderate hypofractionation had similar results regarding oncological and cosmetic outcomes compared to conventional fractionation. Cosmetic and toxicity results from hyper-fractionation studies are in principle favorable. However, the long-term oncological results of studies that used hyper-hypofractionation for the treatment of breast cancer patients are still awaited.

RESUMO INTRODUÇÃO: A radioterapia é amplamente utilizada como tratamento adjuvante nas pacientes com câncer de mama. Nas últimas décadas, diversos estudos foram desenhados para avaliar a segurança e a eficácia da radioterapia hipofracionada moderada de mama. Mais recentemente, esquemas ainda mais curtos, com doses acima de 4 Gy (hiper-hipofracionamento), foram também propostos. Este estudo tem o objetivo de apresentar uma revisão narrativa dos diversos protocolos de hipofracionamento utilizados no tratamento do câncer de mama com o foco na aplicação clínica. RESULTADOS: Os resultados de longo prazo de diversos ensaios clínicos randomizados fase III demonstraram a segurança e a eficácia da radioterapia hipofracionada moderada utilizando 15 ou 16 frações para doença inicial e localmente avançada. Os resultados dos ensaios clínicos iniciais de hiper-hipofracionamento são também animadores e acredita-se que esses esquemas poderão se tornar rotina na indicação do tratamento adjuvante com radioterapia após a maturação dos estudos em andamento sobre esse tema. CONCLUSÕES: A ideia de que os tecidos normais poderiam apresentar toxicidade elevada com doses acima de 2 Gy foi pioneiramente contraposta por ensaios clínicos que comprovaram que o hipofracionado moderado apresentava resultados semelhantes em relação aos desfechos oncológicos e cosméticos quando comparados ao fracionamento convencional. Os resultados cosméticos e de toxicidade dos estudos de hiper-hipofracionamento são, em princípio, favoráveis. Todavia, ainda se aguardam os resultados oncológicos de longo prazo dos estudos que aplicaram o hiper-hipofracionamento para o tratamento das pacientes com câncer de mama.

Hypofractionated radiotherapy for early glottic cancer: a retrospective interim analysis of a single institution

PURPOSE: To evaluate the results of hypofractionated radiotherapy (HFX) for early glottic cancer. MATERIALS AND METHODS: Eighty-five patients with cT1-2N0M0 squamous cell carcinoma of the glottis who had undergone HFX, performed using intensity-modulated radiotherapy (IMRT, n = 66) and three-dimensional conformal radiotherapy (3D CRT, n = 19) were analyzed. For all patients, radiotherapy was administered at 60.75 Gy in 27 fractions. Forty-three patients received a simultaneous integrated boost (SIB) of 2.3–2.5 Gy per tumor fraction. RESULTS: The median follow-up duration was 29.9 months (range, 5.5 to 76.5 months). All patients achieved complete remission at a median of 50 days after the end of radiotherapy (range, 14 to 206 days). The 5-year rates for locoregional recurrence-free survival was 88.1%, and the 5-year overall survival rate was 86.2%. T2 stage was a prognostic factor for locoregional recurrence-free survival after radiotherapy (p = 0.002). SIB for the tumor did not affect disease control and survival (p = 0.191 and p = 0.387, respectively). No patients experienced acute or chronic toxicities of ≥grade 3. IMRT significantly decreased the dose administered to the carotid artery as opposed to 3D CRT (V₃₅, p < 0.001; V₅₀, p < 0.001). CONCLUSIONS: Patients treated with HFX achieved acceptable locoregional disease control rates and overall survival rates compared with previous HFX studies. A fraction size of 2.25 Gy provided good disease control regardless of SIB administration.