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.

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.

Radiation dose and fractionation regimen for limited stage small cell lung cancer: a survey of current practice patterns of Chinese radiation oncologists / 中华放射肿瘤学杂志

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

The efficacy analysis of moderately hypofractionated IMRT combined with androgen deprivation therapy for locally advanced prostate cancer / 中华放射医学与防护杂志

Objective:To investigate the efficacy and adverse reactions of moderately hypofractionated intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) for locally advanced prostate cancer (LAPC).Methods:This study retrospectively analyzed the medical records of 40 LAPC patients who were admitted in The Second Hospital of Dalian Medical University during 2014-2020. The planning gross target volume (PGTV) dose for prostate gland and seminal vesicle gland was 64.8-70.0 Gy/25-28 f, 2.4-2.8 Gy/f and the dose of PGTVnd in 20 cases with positive pelvic lymph nodes was 60.0-64.4 Gy/25-28 f, 2.3-2.4 Gy/f. The dose of planning target volume (PTV) for the drainage area of pelvic lymph nodes was 45.0-50.4 Gy/25-28 f. The enrolled patients were treated with long-term ADT, including neoadjuvant, simultaneous, and adjuvant therapies. The efficacy and adverse reactions were evaluated. The prognostic factors affecting the biochemical failure-free survival (BFFS) were analyzed.Results:The median follow-up time was 31 months. The 2- and 3-year overall survival (OS) rates were 100% and 96.9%, respectively. The 1-, 2-, and 3-year BFFS rates were 90%, 76.8% and 72%, respectively. The 1-, 2-, and 3-year distant metastasis-free survival (DMFS) rates were 92.2%, 82.8% and 75.1%, respectively. Gleason (GS) score ( χ2=10.00, P < 0.05) and adjacent tissue invasion ( χ2=8.85, P<0.05) were prognostic factors related to BFFS for LAPC. Adjacent tissue invasion and GS 9-10 were independent poor prognostic factors. The incidence of acute urinary adverse reaction and rectal injury (grade≥2) was 7.5% and 20%, respectively. The incidence of late urinary adverse reaction and rectal injury (grade≥2) was 12.5% and 17.5%, respectively. Adverse reactions at grade 3-4 did not occur. Conclusions:The moderately hypofractionated IMRT combined with ADT is feasible for LAPC treatment, achieving satisfactory survival effects. 70 Gy/25-28 f, 2.5-2.8 Gy/f is a safe and effective moderate hypofraction scheme. Adjacent tissue invasion and GS score are prognostic factors related to BFFS for LAPC.

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.

Dosimetric evaluation, acute toxicity and short-term efficacy of postmastectomy hypofractionated internal mammary chain irradiation with electrons / 中华放射肿瘤学杂志

Objective:To investigate the dosimetric characteristics, acute toxicity and short-term efficacy of postmastectomy hypofractionated internal mammary (IM) chain irradiation with electrons in patients with high-risk breast cancer.Methods:A total of 155 patients with breast cancer who underwent modified mastectomy between November 2018 and January 2020 were selected. Among them, 137(88.4%) patients were classified as stage Ⅲ and 18(11.6%) as stage Ⅱ. All patients received standard chemotherapy, endocrine therapy and anti-Her2 targeted therapy. CTV im was divided into three subregions: CTV im1, CTV im2 and CTV im3, which represented the first, second and third intercostal IM, respectively. The planning target volume of subraclavicular region (PTV sc) was delineated. CTV cw and CTV im were irradiated with 6-15 MeV electron at 43.5 Gy in 15 fractions over 3 weeks. Moreover, PTV sc was irradiated with 6 MV X-ray at 43.5 Gy in 15 fractions over 3 weeks using two-dimensional radiotherapy (2DRT) or three-dimensional radiotherapy (3DRT). The dosimetric characteristics of CTV im, PTV sc, lung, heart, left anterior descending coronary artery (LAD) and right coronary artery (RA) were evaluated, and the acute toxicity and short-term efficacy were analyzed. Results:The mean dose (D mean) of CTV im was (43.3±2.6) Gy, D 95% was (30.5±8.3) Gy, V 90% was (85.0±10.5)% and V 80% was (91.0±7.4)%, respectively. The corresponding parameters of CTV im1 were significantly lower than those of CTV im2 and CTV im3(all P<0.001). Body mass index exerted no significant effect on IM dose ( P>0.05). Compared with 2DRT, 3DRT for SC significantly increased theD mean of CTV im[(43.4±2.6) Gy vs.(41.4±2.3) Gy, P=0.021], and the hot spot within PTV sc[V 110%: (26.7±17.5) cm 3vs.(12.5±8.4) cm 3, P=0.018; V 120%: (6.1±5.3) cm 3vs.(2.0±2.6) cm 3, P=0.023]. TheD mean of the ipsilateral lung was (9.8±1.9) Gy, and V 20Gy was (19.7±4.7)%. TheD mean of heart was (3.3±1.7) Gy in the whole group, (4.7±1.4) Gy for the left-sided breast cancer and (2.6±1.2) Gy for the right-sided breast cancer, respectively. TheD mean of LAD for the left-sided breast cancer was (13.9±4.9) Gy. TheD mean of RA for the right-sided breast cancer was (7.5±3.7) Gy. The incidence rates of ≥ grade 2 acute radiation dermatitis, esophagitis and pneumonitis were 19.3%, 4.5% and 2.6%, respectively. With a median follow-up time of 20.5 months (range: 9.9-41.8 months), 2 cases of chest wall recurrence, 2 regional lymph node recurrence, 6 distant metastases and 1 death were reported. Conclusions:When hypofractionated internal mammary chain is irradiated by electrons after mastectomy, the doses to the lung, heart and coronary artery are low, and the acute toxicities are mild. However, the dose to CTV im1 is inadequate. Although short-term efficacy is high, long-term follow-up is warranted.

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.

Implementation of Radiotherapy and Overcoming the Treatment Breaks in COVID-19 Crisis

Introduction: Tackling of; the patients who had defaultedfor radiation therapy due to implementation of lockdownfollowing COVID-19 outbreak, new patients presenting toout-patient department(OPD) and continuing Radiotherapytreatment without postponing during this health crisis ischallenging. Study objective was to evaluate the outcomesof hypofractionated radiation therapy in the COVID-19 eraand to provide guidance on measures for preparedness in theDepartment of Radiation Oncology to continue the treatmentand tackling treatment breaks.Material and Methods: Patients reporting to the OPD,patients who defaulted for treatment during lockdown phaseand newly diagnosed patients awaiting treatment wereincluded in the study. Hypofractionated schedules were usedfor treatment to reduce the overall treatment time and durationof hospital stayResults: Clinical response evaluation was done at the end of 1month by RECIST criteria. In Head and neck cancer patients60%, 26% and 13.3% of the patients showed CompleteResponse (CR), Partial response (PR) and Progressive diseaserespectively in primary disease and 46%, 40%, 13.3% of thepatients showed CR, PR and progressive disease respectivelyin nodal disease. Among Cervical cancer patients: 75% and25% of the patients showed CR and PR respectively. All Breastcancer patient were disease free at the time of assessment.Conclusion: Hypofractionated radiotherapy schedules to beused wherever feasible reducing the overall treatment timeand the exposure of Cancer patients to COVID-19 and viraltransmission can be mitigated with best clinical practice ofsanitization, wearing masks, Face shield, PPE and Socialdistancing.

Radiocirugía cerebral estereotáctica en el tratamiento de tumores de base de cráneo / Stereotactic brain radiosurgery in the treatment of skull base tumors

La radiocirugía estereotáctica ha demostrado efectividad en el tratamiento multimodal de los tumores de base de cráneo, de todas maneras se sugiere que en áreas radiobioló;gicamente sensibles (ej. nervios ó;pticos y tronco cerebral) la dosis radiante debería reducirse por los efectos radiotó;xicos. Para evitar la ineficacia terapó;©utica, una alternativa recientemente implementada es la radiocirugía multisesió;n (RCH). Se analizó; en forma retrospectiva una serie de tumores de base de cráneo, con el fin de evaluar el tratamiento con RCH a travó;©s del control tumoral en las imágenes post-tratamiento. Se evaluó; tambín edad, sexo, histología tumoral, volumen tumoral, protocolo radiante, Karnofsky performance status (KPS) pre-tratamiento y neurocirugía y tratamiento radiante previos. Fueron tratados 84 pacientes entre enero 2009 y enero 2017. La mediana de edad fue 51.5 aó;±os; sexo femenino: 53.6%. Hubo un 92.7% de no-progresió;n luego del tratamiento, con una mediana de tiempo de seguimiento de 36 meses. Los tumores tratados fueron principalmente adenomas hipofisarios, neurinomas del acó;ºstico, y meningiomas de base de cráneo. La mayoría de los pacientes recibió; un esquema de tratamiento fraccionado de 5 días, con una dosis total de 25 Gy. No se observó; radiotoxicidad tardía clínicamente manifiesta. En el análisis multivariado, un KPS alto pre-tratamiento fue significativamente asociado a la no-progresió;n tumoral. En esta serie, la alta incidencia de no-progresió;n tumoral indicaría que el tratamiento con RCH podría ser una opció;n terapó;©utica en algunos casos de tumores de base de cráneo, principalmente recurrencias o remanencias tumorales de adenomas hipofisarios, neurinomas y meningiomas.

Stereotactic radiosurgery has shown effectiveness in the multimodal treatment of skull base tumors, however it is suggested that in radiobiologically sensitive areas (eg. optic nerves and brainstem) the radiation dose should be reduced due to radiotoxic effects. To avoid the consequent therapeutic ineffectiveness, a recently implemented alternative is multisession radiosurgery (RCH). We retrospectively analyzed a series of patients with skull base tumors, in order to evaluate the treatment with RCH through tumor control in the post-treatment images. Age, sex, tumor histology, tumor volume, radiation protocol, pre-treatment Karnofsky performance status (KPS) previous neurosurgery and radiant treatment were also evaluated. Eighty-four patients were treated between January 2009 and January 2017. The median age was 51.5 years; females: 53.6%. There was a 92.7% non-progression after treatment, with a median follow-up time of 36 months. Treated tumors were mainly pituitary adenomas, acoustic schwannomas, and skull base meningiomas. Most of the patients received a 5-day fractionated treatment scheme, with a total dose of 25 Gy. No clinically manifest late radiotoxicity was observed. In the multivariate analysis, a high pre-treatment KPS was significantly associated with tumor non-progression. In our series, the high incidence of tumor non-progression would indicate that treatment with RCH could be a therapeutic option in some cases of skull-base tumors, mainly recurrences or tumor residuals of pituitary adenomas, neurinomas and meningiomas.

Dual partial arc volumetric-modulated arc therapy: The game changer for accelerated hypofractionated whole-breast radiotherapy with simultaneous integrated tumor cavity boost in early breast cancer - A comparative dosimetric study with single partial arc volumetric-modulated arc therapy

Introduction: In a previous study, we demonstrated clinical and dosimetric feasibility of single partial arc volumetric modulated arc therapy (VMAT) for accelerated hypofractionated whole breast radiotherapy with simultaneous integrated boost (SIB) to lumpectomy cavity for early breast cancer. In this dosimetric study, we compared dual partial arcs versus single arc. Patients and Methods: Fifteen consecutive patients for treatment with hypofractionated accelerated radiotherapy with SIB using VMAT were planned with single partial arc in an earlier study, initial result of which is published elsewhere. The comparative dosimetric plan was created using two partial arcs. Skewness and kurtosis test, Paired Student's t-test, and Wilcoxon signed-rank test were applied for statistical analysis. P < 0.05 was considered statistically significant. Results: Most planning targets are better achieved with dual arc technique. Coverage of planning target volume (PTV) whole breast (PTVWB) and PTV lumpectomy cavity (PTVBOOST) was significantly improved with dual partial arc without significant difference in conformity index and homogeneity index. Dual arc improved dosimetric parameter significantly. Mean dose (Dmean) and maximum dose (Dmax) of whole breast PTV as well as Dmax of PTVBOOST; ipsilateral and contralateral lung Dmean, Dmax, 5 Gy volume (V5); contralateral lung Dmean, Dmax, V5; Heart V25 and V18; Dmean of 5 mm thickness skin; Dmean and Dmax of ribs; and Dmean and Dmax of contralateral breast were improved with dual arc. Conclusion: This is first of its kind study establishing the advantage of dual partial arcs in the current context. Dual partial arcs improved dosimetry over single partial arc. Significant dose reduction can be achieved for multiple crucial organs at risk

Is moderate hypofractionation accepted as a new standard of care in north america for prostate cancer patients treated with external beam radiotherapy? Survey of genitourinary expert radiation oncologists

ABSTRACT Introduction: Several recent randomized clinical trials have evaluated hypofractionated regimens against conventionally fractionated EBRT and shown similar effectiveness with conflicting toxicity results. The current view regarding hypofractionation compared to conventional EBRT among North American genitourinary experts for management of prostate cancer has not been investigated. Materials and Methods: A survey was distributed to 88 practicing North American GU physicians serving on decision - making committees of cooperative group research organizations. Questions pertained to opinions regarding the default EBRT dose and fractionation for a hypothetical example of a favorable intermediate - risk prostate cancer (Gleason 3 + 4). Treatment recommendations were correlated with practice patterns using Fisher's exact test. Results: Forty - two respondents (48%) completed the survey. We excluded from analysis two respondents who selected radical hypofractionation with 5 - 12 fractions as a preferred treatment modality. Among the 40 analyzed respondents, 23 (57.5%) recommend conventional fractionation and 17 (42.5%) recommended moderate hypofractionation. No demographic factors were found to be associated with preference for a fractionation regimen. Support for brachytherapy as a first choice treatment modality for low - risk prostate cancer was borderline significantly associated with support for moderate hypofractionated EBRT treatment modality (p = 0.089). Conclusions: There is an almost equal split among North American GU expert radiation oncologists regarding the appropriateness to consider moderately hypofractionated EBRT as a new standard of care in management of patients with prostate cancer. Physicians who embrace brachytherapy may be more inclined to support moderate hypofractionated regimen for EBRT. It is unclear whether reports with longer follow-ups will impact this balance, or whether national care and reimbursement policies will drive the clinical decisions. In the day and age of patient - centered care delivery, patients should receive an objective recommendation based on available clinical evidence. The stark division among GU experts may influence the design of future clinical trials utilizing EBRT for patients with prostate cancer.

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.

Cosmesis in patients with breast neoplasia submitted to the hypofractionated radiotherapy with of intensity-modulated beam

SUMMARY OBJECTIVE: To assess the cosmetic satisfaction of patients diagnosed with breast cancer submitted to the hypofractionated radiotherapy with IMRT (hIMRT) technique and its correlation with dosimetric data of the radiotherapy planning. MATERIALS AND METHODS: The retrospective cohort study that assessed women with a diagnosis of malignant breast neoplasia submitted to the conservative treatment or radical mastectomy and treated with hIMRT. In the period between August 2007 to December 2014, in a philanthropic / private institution, 170 records were selected. The cosmetic assessment was carried out by means of the Harvard/RTOG/NSABP scale with one-year minimum range after treatment. The collected dosimetric data were: breast / chest wall volume, volume that received 95% (V95%) and 107% (V107%) of the prescribed dose. RESULTS: The volume of the treated breasts ranged from 169 to 2.103 ml (median = 702; IQR: 535 to 914 ml). Median V95% was 86.7% (54.6-96.6%; IQR: 80.0% to 90.6%); eight (5.7%) patients had V95% higher than 95%. Median V107% was 0% (0%-16.3%; IQR: 0.0% to 0.3% and 13); 9.3% patients had V107% higher than 2%. One hundred and thirty-three (78.2%) patients responded to the cosmetic assessment: 99 (74.4%) considered the cosmetic results excellent. Significant associations between cosmetic assessment and breast volume (p=0.875), V95% (p=0.294) e V107% (p=0.301) were not found. CONCLUSION: The cosmetic results showed favorable when using hIMRT, and the lack of correlation with usual the dosimetric data illustrates the capacity of hIMRT to minimize the heterogeneity of the dose in this endpoint, even in voluminous breasts.

RESUMO OBJETIVO: Avaliar a satisfação cosmética de pacientes diagnosticadas com câncer de mama submetidas à radioterapia hipofracionada com técnica IMRT (hIMRT) e sua correlação com dados dosimétricos do planejamento radioterápico. MATERIAIS E MÉTODOS: Estudo de coorte retrospectivo que avaliou mulheres com diagnóstico de neoplasia maligna de mama submetidas a tratamento conservador ou mastectomia radical e tratadas com hIMRT. No período de agosto de 2007 a dezembro de 2014, em uma instituição filantrópica/particular, foram selecionados 170 prontuários. A avaliação cosmética foi feita por meio da escala de Harvard/RTOG/NSABP com um intervalo mínimo de um ano após o tratamento. Dados dosimétricos coletados foram: volume da mama/plastrão, volume que recebeu 95% (V95%) e 107% (V107%) da dose prescrita. RESULTADOS: O volume das mamas tratadas variou de 169 a 2.103 ml (mediana = 702; IQR: 535 a 914 ml). O V95% mediano foi 86,7% (54,6-96,6%; IQR: 80,0% a 90,6%); oito (5,7%) pacientes tiveram o V95% superior a 95%. O V107% mediano foi 0% (0%-16,3%; IQR: 0,0% a 0,3% e 13); 9,3% pacientes tiveram o V107% superior a 2%. Cento e trinta e três (78,2%) pacientes responderam à avaliação cosmética: 99 (74,4%) consideraram o resultado cosmético excelente. Não foram encontradas associações significativas entre a avaliação cosmética e o volume da mama (p=0,875), V95% (p=0,294) e V107% (p=0,301). CONCLUSÕES: Os resultados cosméticos mostraram-se favoráveis com o uso de hIMRT, e a ausência de correlação com os dados dosimétricos usuais ilustra a capacidade do hIMRT em minimizar a heterogeneidade da dose neste desfecho, mesmo em mamas volumosas.

Fractionated Gamma Knife Radiosurgery as Initial Treatment for Large Skull Base Meningioma

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm³ who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm³ (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.

The application of high-dose grid radiotherapy technique / 中华放射肿瘤学杂志

High dose grid radiotherapy ( GRID ) refers to a single fraction of high-dose radiation ( 10-25 Gy) in which, beams are divided into multiple small beam lets through a grid collimator or MLC, resulting in non-uniform dose distribution of high and low dose area ("peak-to-valley" effect) in the target volume. Recently, as 3D radiotherapy ( 3DRT) technology emerged, the 2D GRID has been reconfigured into 3D dose LATTICE whereby high doses are concentrated at each lattice vertex within the radiation target volume with drastically lower dose between vertices through multiple focused non-coplanar beams with different radiation techniques. Compared with 2D GRID therapy, 3D LATTICE shows significant effect on"peak-to-valley" and minimizes radiation to surrounding tissues. Experimental and clinical data have shown that LATTICE therapies can reduce toxicity to normal tissue while stimulating bystander effects, endothelial cell death and immunogenic abscopal effects leading to enhanced killing of tumor cells and further improve the control of the local and distant disease. The clinic experience with LATTICE, although limited, has demonstrated favorable outcomes, especially for treating bulky tumors and palliative intend. The exact mechanism of the clinical advantages by LATTICE is not explicitly known and a more comprehensive biological study and clinical trials are called should be carried out.

Long-term cosmesis following a novel schedule of accelerated partial breast radiation in selected early stage breast cancer: result of a prospective clinical trial

PURPOSE: There is controversy regarding the cosmetic outcome after accelerated partial breast radiation (APBR). We report the cosmetic outcome from a single-arm prospective clinical trial of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged ≥65, with Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by physician/patient and objectively by using a computer program (BCCT.core) before APBR, during, and after completion of the treatment. RESULTS: The median age was 72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5 months. The 5-year locoregional control in this cohort was 97% and overall survival 87%. At the last follow-up, patients and physicians rated cosmesis as ‘excellent’ or ‘good’ in 100% and 91 %, respectively. The BCCT.core program scored the cosmesis as ‘excellent’ or ‘good’ in 87% of the patients at baseline and 81% at the last follow-up. The median V50 (20 Gy) of the whole breast volume (WBV) was 37.2%, with the median WBV V100 (40 Gy) of 10.9%. CONCLUSION: An excellent rate of tumor control was observed in this prospective trial. By using multiple assessment techniques, we are showing acceptable cosmesis, supporting the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

PURPOSE: Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. RESULTS: The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. CONCLUSION: In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.