Hypofractionated whole breast irradiation in association with hypofractionated or normofractionated boost to the tumor bed in early breast cancer: tolerance and efficacy analysis

Background The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. Materials and methods A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. Results The median follow-up was 49.5 months (26–67). Median age was 57 years (36–82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. Conclusions Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control (AU)

Intraoperative irradiation in breast cancer: preliminary results in 80 patients as partial breast irradiation or anticipated boost prior to hypo-fractionated whole breast irradiation

PurposeTo present the first results of intraoperative irradiation (IORT) in breast cancer with a low-energy photon system used as partial breast irradiation (PBI) or as an anticipated boost before whole breast hypo-fractionated irradiation (IORT + WBI), concerning tolerance, side effects, quality of life, and patient-reported outcomes.Materials and methodsEighty patients treated with an Intrabeam® system of 50 kV X-rays received a 20 Gy dose intraoperatively were included. Moderate daily hypofractionation of 2.7 Gy in 15 fractions up to 40.5 Gy was administered if high-risk factors were present. Acute post-operative toxicity, surgery complications, chronic toxicity, patient-reported cosmesis and Breast-Q questionnaire were performed at follow-up visits.ResultsThirty-one patients were treated as PBI and the remaining 49 as IORT + WBI. Only the IORT + WBI group presented acute toxicity, mainly mild acute dermatitis (11 patients) and one subacute mastitis. A total of 20 patients presented fibrosis (18 patients grade I, 2 patients grade II), 15 (30.5%) patients in the IORT + WBI group and 3 (9.6%) patients in the group of PBI. The cosmesis evaluation in 73 patients resulted poor, fair, good or excellent in 2, 7, 38 and 26 patients, respectively. In PBI group Breast-Q scored higher, especially in terms of their psychosocial well-being (78 vs 65) and satisfaction with radiation-induced toxicity (77 vs 72, respectively) compared to IORT + WBI group.ConclusionIORT is a well-tolerated procedure with low toxicity, good cosmesis and favorable patient-reported outcomes mainly when administered as PBI.

Implicaciones de la pandemia en la radioterapia para el cáncer de mama. Radioterapia hipofraccionada / Implications of the pandemic in radiotherapy for breast cancer. Hypofractionated radiation therapy

La pandemia por el nuevo coronavirus (SARS-CoV-2) ha puesto a prueba los sistemas de salud de todo el mundo, de una forma tan apremiante que no se veía hace muchos años. Las implicaciones en la atención en salud no afectan únicamente a los pacientes con la COVID-19, sino que son transversales a todas las enfermedades. Específicamente en cáncer de mama, los esquemas de radioterapia hipofraccionada constituyen una alternativa válida y segura que ayuda a disminuir la exposición de las pacientes al nuevo virus, la congestión de las instituciones de salud y los costos propios de los tratamientos oncológicos especializados. En este artículo, se realizó una revisión de la literatura más relevante sobre los regímenes acortados de radioterapia en cáncer de mama: hipofraccionamiento e hipofraccionamiento extremo, y sobre su equivalencia con el fraccionamiento estándar. Al final, se destacan las recomendaciones de diferentes sociedades científicas y expertos internacionales, para considerar esquemas de radioterapia hipofraccionados, a propósito de la contingencia de salud mundial. (AU)

The current pandemic due to the new coronavirus (SARS-CoV-2) has put health systems around the world to the test, in a way so urgent that had not been seen in several years. The implications in health care not only affect patients with COVID-19, but they are transversal to all pathologies. Specifically in breast cancer, hypofractionated radiotherapy schemes constitute a valid and safe alternative that helps reduce the exposure of patients to the new virus, the congestion of health institutions and the costs of specialized cancer treatments. In this article, we conducted a review of the most relevant literature on shortened radiotherapy regimens in breast cancer: hypofractionation and extreme hypofractionation, and their equivalence with fractionation. In the end, the recommendations of different scientific societies and international experts are highlighted, to consider hypofractionated radiotherapy schemes, regarding the global health contingency. (AU)

Dosimetric impact of rectum and bladder anatomy and intrafractional prostate motion on hypofractionated prostate radiation therapy

Objective The objective of this study was to evaluate the dosimetric impact on hypofractionated prostate radiation therapy of two geometric uncertainty sources: rectum and bladder filling and intrafractional prostate motion.Materials and methodsThis prospective study included 544 images (375 pre-treatment cone-beam CT [CBCT] and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients. We recalculated the dose on each pre-treatment CBCT once the positioning errors were corrected. We also recalculated two dose distributions on each post-treatment CBCT, either using or not intrafractional motion correction. A correlation analysis was performed between CBCT-based dose and rectum and bladder filling as well as intrafraction prostate displacements.ResultsNo significant differences were found between administered and planned rectal doses. However, we observed an increase in bladder dose due to a lower bladder filling in 66% of treatment fractions. These differences were reduced at the end of the fraction since the lower bladder volume was compensated by the filling during the treatment session. A statistically significant reduction in target volume coverage was observed in 27% of treatment sessions and was correlated with intrafractional prostate motion in sagittal plane > 4 mm.ConclusionsA better control of bladder filling is recommended to minimize the number of fractions in which the bladder volume is lower than planned. Fiducial mark tracking with a displacement threshold of 5 mm in any direction is recommended to ensure that the prescribed dose criteria are met. (AU)

Synchronous bilateral breast cancer treated with a 3-week hypofractionated radiotherapy schedule: clinical and dosimetric outcomes

Background and purpose Synchronous bilateral breast cancer (SBBC) accounts for 1–3.5% of breast cancer patients. The aim of this study was to evaluate dosimetric issues, clinical outcomes, and acute toxicities for SBBC patients receiving synchronous bilateral hypofractionated radiotherapy (SBHRT) and to compare them with patients treated with synchronous bilateral normofractionated RT schedule (SBNRT). Materials and methods From April 2016 to March 2020, 39 SBBC patients were referred to our institution. Patients were divided according to their prescription dose: Group A: 50 Gy/25fx (fractions), B: 60–64 Gy/25fx, C: 40.05 Gy/15fx; D: 48 Gy/15fx. Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE)v.5.0. Results 34 patients were finally evaluated. Median follow-up was 24 months for NF schedule and 9 months for HF schedule. In the HF schedule, no acute side-effects > G2 were observed and no dermatitis was reported in 6th month´s assessments. 95% of patients have no evidence of disease and only 1 patient presented local relapse in the first mammography after RT. No distant failures or deaths were observed. Regarding dosimetric issues, the inter-patient average Dmean for the heart was: Group A: 5.0 Gy (4.6–5.5), Group B: 4.4 Gy (4.1–5.4), Group C: 4.8 Gy (4.5–5.1) and Group D: 5.3 Gy (4.4–5.6). For the lungs, the inter-patient average Dmean was: Group A: 10.8 Gy (9.8–12.2), Group B: 11.5 Gy (11.3–12), Group C: 9.8 Gy (9.3–10.5) and Group D: 10.5 Gy (10–11.3). Conclusions This is the first study reporting the safety, feasibility, and tolerability of 40.05 Gy/15fx over 3 weeks for the treatment of SBBC patients. Further study with larger accrual is mandatory (AU)

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients

Aims To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients (AU)

Moderate hypofractionated post-prostatectomy radiation therapy is feasible and well tolerated: experience from a single tertiary cancer centre

Purpose Conventional post-prostatectomy radiation therapy comprises 6.5–8 weeks of treatment, therefore, hypofractionated and shortened schemes arouse increasing interest. We describe our experience regarding feasibility and clinical outcome of a post-prostatectomy moderate hypofractionated image-guided radiotherapy schedule Materials and methods From Oct 2015–Mar 2020, 113 patients, median age of 62 years-old (range 45–76) and prostate adenocarcinoma of low risk (30%), intermediate risk (49%) and high risk (21%) were included for adjuvant (34%) or salvage radiation therapy (66%) after radical prostatectomy (RP). All patients underwent radiotherapy with image-guided IMRT/VMAT to a total dose of 62.5 Gy in 2.5 Gy/fraction in 25 fractions. Sixteen patients (14%) received concomitant androgen deprivation therapy. Results With a median follow-up of 29 months (range 3–60 months) all patients but three are alive. Eleven patients (10%) developed exclusive biochemical relapse while 19 patients (17%) presented macroscopically visible relapse: prostatectomy bed in two patients (2%), pelvic lymph nodes in 13 patients (11.5%) and distant metastases in four patients (4%). The 3 years actuarial rates for OS, bFRS, and DMFS were 99.1, 91.1 and 91.2%, respectively. Acute and late tolerance was satisfactory. Maximal acute genitourinary (AGU) toxicity was G2 in 8% of patients; maximal acute gastrointestinal (AGI) toxicity was G2 in 3.5% of patients; maximal late genitourinary (LGU) toxicity was G3 in 1% of patients and maximal late gastrointestinal (LGI) toxicity was G2 in 2% of patients. There were no cases of severe acute or late toxicity. No relationship was found between acute or late GI/GU adverse effects and dosimetric parameters, age, presence of comorbidities or concomitant treatments (AU)

Weekly radiotherapy in elderly breast cancer patients: a comparison between two hypofractionation schedules

Purpose Weekly irradiation in breast cancer in elderly patients is a treatment option, whose tolerance may be influenced by the fractionation used. The objective of this study is to compare the tolerance and long-term side effects of two different fractionations. Materials and methods 47 elderly patients were recruited after conservative or radical treatment that also received irradiation with a dose per fraction of 6.25 Gy or 5 Gy for one session per week, 6 sessions in total. The long-term tolerance results are compared by assessing toxicity using CTCAE version 5.0 scales for dermatitis, telangectasia, fibrosis and pain of the irradiated breast. In addition, objective parameters of skin status (erythema, hyperpigmentation, elasticity and hydration) by a multi-probe MultiSkin Test-Center system were obtained and compared between groups. Results After an average follow-up of 5 years, all patients were free of disease and with complete local control. A total of 20 patients with 6.25 Gy fractionation and 27 patients with 5 Gy fractionation have been included. Patients treated with lower fractionation had a lower incidence of dermatitis, telangectasia, fibrosis, or local pain. The decrease in elasticity measured by the multi-probe system was smaller with the fractionation of 5 Gy. No differences were observed in the other objective parameters. Conclusion Weekly irradiation with 5 Gy fractionation is better tolerated than with higher fractionation (AU)

How to integrate stereotactic body radiation therapy and hypofractionation in the management of stage III lung cancer in the age of immunotherapy / Cómo integrar la radioterapia estereotáxica fraccionada y el hipofraccionamiento en el manejo del cáncer de pulmón localmente avanzado en la era de la inmunoterapia

The constant advances in the field of lung cancer immunotherapy have recently reached the treatment of locally advanced disease with the approval of durvalumab after concurrent chemoradiation. However, radiation therapy continues to be key for controlling the disease at this stage. Over the years, different strategies have been employed to try to optimize outcomes using radiotherapy, with cardiac and pulmonary toxicity as the main limitation on its success. The interest in the use of hypofractionation and stereotactic body radiation therapy for stage III non-small cell lung cancer has increased as knowledge regarding these kinds of treatments has been enhanced. Hypofractionation is a relatively frequent treatment, although the level of evidence that supports it is limited. For its part, stereotactic body radiation therapy has been particularly studied as a boost after chemoradiation, with encouraging results. In both cases, study of how to integrate these tools with chemotherapy and particularly with immunotherapy is essential, as they may have an immunomodulatory role

The constant advances in the field of lung cancer immunotherapy have recently reached the treatment of locally advanced disease with the approval of durvalumab after concurrent chemoradiation. However, radiation therapy continues to be key for controlling the disease at this stage. Over the years, different strategies have been employed to try to optimize outcomes using radiotherapy, with cardiac and pulmonary toxicity as the main limitation on its success. The interest in the use of hypofractionation and stereotactic body radiation therapy for stage III non-small cell lung cancer has increased as knowledge regarding these kinds of treatments has been enhanced. Hypofractionation is a relatively frequent treatment, although the level of evidence that supports it is limited. For its part, stereotactic body radiation therapy has been particularly studied as a boost after chemoradiation, with encouraging results. In both cases, study of how to integrate these tools with chemotherapy and particularly with immunotherapy is essential, as they may have an immunomodulatory role

El fenómeno de "pain flare": un efecto secundario no tan inusual en Radioterapia (RT) paliativa y anti-álgica / The "pain flare" phenomenon: a not-so-unusual side effect on palliative and anti-algica radiotherapy (RT)

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Radiocirugía para el control sintomático en pacientes con cáncer en estadios avanzados / Radiosurgery for symptomatic control in patients with advanced stage cancer

La radioterapia es una modalidad terapéutica cada vez más usada en el campo de los cuidados paliativos. Los avances técnicos en Oncología Radioterápica permiten que la radiocirugía estereotáxica y la radioterapia estereotáxica corporal puedan administrar altas dosis de radiación de manera precisa y conformada a la lesión que queremos tratar usando esquemas de tratamientos cortos en el tiempo, sin afectar al tejido sano periférico. Esto es lo que recibe el nombre de hipofraccionamiento, y es el fundamento de esta técnica. El esquema de dosis usado con estas técnicas permite lograr un mayor efecto biológico y, por lo tanto, mayor efectividad sobre el tejido irradiado. La radiocirugía proporciona un control sintomático rápido, eficaz y duradero con una toxicidad mínima y, como consecuencia, da lugar a una potencial mejora en la calidad de vida de estos pacientes. Estas características hacen que esta técnica emergente sea una de las mejores opciones de tratamiento disponibles para los pacientes con enfermedad avanzada

External beam radiation therapy is increasingly being used in the field of palliative care. Technical advances in Radiation Oncology enable high doses of radiation to be precisely and accurately delivered to the target lesion using stereotactic radiosurgery and stereotactic body radiotherapy, with short treatment regimens and without affecting the peripheral healthy tissue. This is called hypofractionation, and is the foundation on which the technique rests. Radiosurgery provides a rapid, effective and durable symptomatic control with minimal toxicity and consequently a potential improvement in the quality of life of these patients. These features make this emerging technique one of the best treatment options currently available for patients with advanced disease