Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator.

Purpose: To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. Methods and Materials: The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). Results: A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n = 131); luminal B, 19.1% (n = 40); HER2 enriched 13.4% (n = 28); and triple negative, 4.8% (n = 10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Conclusions: Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Meta-analysis of long-term efficacy and safety of hypofractionated radiotherapy in the treatment of early breast cancer.

PURPOSE: To evaluate the efficacy and safety of hypofractionated radiotherapy in women with early stage breast cancer after breast conservative surgery. METHODS: We performed a search for randomized controlled trials (RCTs) that compare conventional fractioning and hypofractioned radiotherapy. The studied outcomes were local and loco-regional recurrence, disease-free survival, mortality, cardiac ischemia, rib fracture and pulmonary fibrosis up to 5 years and 5 years after treatment. Shrinkage of the breast, breast tightening, telangiectasia, breast edema, shoulder stiffness and arm edema were evaluated within 10 years. Cosmesis and acute skin radiation toxicity were evaluated. RESULTS: Ten publications of six RCTs were included. No statistical difference in local and loco-regional recurrence, disease-free survival, mortality, cardiac ischemia, ribs fracture and pulmonary fibrosis, shrinkage of the breast, breast tightening, shoulder stiffness, arm edema and cosmesis was found. However, there was a significant difference in favor of hypofractionated for breast edema (RR 0.68, 95% CI 0.53 to 0.88, p = 0.003, 4675 patients), telangiectasia (RR 0.41, 95% CI 0.19 a 0.87, p = 0.02, 5167 patients), and acute skin radiation toxicity (RR 0.34, 95% CI 0.19 to 0.61, p = 0.0003, 347 patients). CONCLUSION: There is no difference between conventional fractionation and hypofractionated in terms of efficacy when we evaluate local recurrence, loco-regional recurrence, distance recurrence, disease-free survival and mortality. There is also no difference concerning safety when we assess the occurrence of fibrosis, ischemia and ribs fractures. Hypofractionated showed better results in relation to breast edema, telangiectasia, and acute skin radiation toxicity.

Intraoperative radiation therapy in early breast cancer using a linear accelerator outside of the operative suite: an "image-guided" approach.

PURPOSE: To present local control, complications, and cosmetic outcomes of intraoperative radiation therapy (IORT) for early breast cancer, as well as technical aspects related to the use of a nondedicated linear accelerator. METHODS AND MATERIALS: This prospective trial began in May of 2004. Eligibility criteria were biopsy-proven breast-infiltrating ductal carcinoma, age >40 years, tumor <3 cm, and cN0. Exclusion criteria were in situ or lobular types, multicentricity, skin invasion, any contraindication for surgery and/or radiation therapy, sentinel lymph node involvement, metastasis, or another malignancy. Patients underwent classic quadrantectomy with intraoperative sentinel lymph node and margins evaluation. If both free, the patient was transferred from operative suite to linear accelerator room, and IORT was delivered (21 Gy). Primary endpoint: local recurrence (LR); secondary endpoints: toxicities and aesthetics. Quality assurance involved using a customized shield for chest wall protection, applying procedures to minimize infection caused by patient transportation, and using portal films to check collimator-shield alignment. RESULTS: A total of 152 patients were included, with at least 1 year follow-up. Median age (range) was 58.3 (40-85.4) years, and median follow-up time was 50.7 (12-110.5) months. The likelihood of 5-year local recurrence was 3.7%. There were 3 deaths, 2 of which were cancer related. The Kaplan-Meier 5-year actuarial estimates of overall, disease-free, and local recurrence-free survivals were 97.8%, 92.5%, and 96.3%, respectively. The overall incidences of acute and late toxicities were 12.5% and 29.6%, respectively. Excellent, good, fair, and bad cosmetic results were observed in 76.9%, 15.8%, 4.3%, and 2.8% of patients, respectively. Most treatments were performed with a 5-cm collimator, and in 39.8% of the patients the electron-beam energy used was ≥12 MeV. All patients underwent portal film evaluation, and the shielding was repositioned in 39.9% of cases. No infection or anesthesia complications were observed. CONCLUSIONS: Local control with IORT was adequate, with low complication rates and good cosmetic outcomes. More than one-third of patients benefited from the "image-guidance" approach, and almost 40% benefited from the option of higher electron beam energies.

Intraoperative full-dose of partial breast irradiation with electrons delivered by standard linear accelerators for early breast cancer.

Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with invasive ductal carcinoma (T ≤ 3.0 cm) at low risk for local relapses were treated. All had unicentric lesions by imaging methods and negative sentinel node. After a wide local excision, 21 Gy were delivered on the parenchyma target volume with electron beams. Local recurrences (LR), survival, toxicity, and cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40-85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The cumulative incidence rates of LR, distant metastases, and BC death were 3.2%, 1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results were excellent or good in most of the patients. Conclusions. IORT with electrons delivered by standard Linacs is feasible, efficient, and well tolerated and seems to be beneficial for selected patients with early infiltrating BC.

Early stage breast cancer and radiotherapy: update.

Breast cancer (BC) is the most common malignancy among women. Therapeutic options are based on disease staging, histopathological characteristics, age, and others. The objective of the present study is to carry out an update of the concepts and definitions of radiotherapy (RT) in conservative treatment of early-stage breast cancer, with emphasis on indications, contraindications, RT dose fractionation schedules (classic, hypofractionated and partial breast irradiation), adjuvant RT in ductal carcinoma in situ (DCIS) and molecular predictors of recurrence. MEDLINE, SciELO and Cochrane databases were used for article selection. Adjuvant RT is indicated for patients with BC who underwent conservative breast surgery. In selected patients, hypofractionated or partial breast irradiation can be used. Adjuvant RT should be provided for all patients with DCIS. The correlation of RT and molecular predictors of local and systemic recurrence are not yet well-known.

Câncer de mama estádio inicial e radioterapia: atualização / Early stage breast cancer and radiotherapy: update

O câncer de mama é a neoplasia maligna mais frequente entre as mulheres. A escolha terapêutica depende do estádio clínico da doença, das características anatomopatológicas, idade, entre outros. O objetivo do presente estudo é apresentar uma atualização dos conceitos e definições da radioterapia (RT) no tratamento conservador do câncer de mama estádio inicial, enfatizando as indicações, contraindicações, dose e fracionamento da RT (esquema clássico, hipofracionado e irradiação parcial da mama), RT adjuvante no carcinoma ductal in situ (CDIS), irradiação das cadeias linfonodais e relação da RT com preditores moleculares de recorrência. Foram utilizadas as bases de dados MEDLINE, SciELO e Cochrane para a seleção dos principais artigos disponíveis sobre a temática proposta. A RT adjuvante tem um papel definido na abordagem das pacientes com câncer da mama submetidas à terapia cirúrgica conservadora. Em pacientes selecionadas, podem-se empregar esquemas de RT hipofracionada ou irradiação parcial das mamas. Todas as pacientes com CDIS devem receber RT adjuvante. Não se sabe a correlação do papel da RT com preditores moleculares de recorrência local e sistêmica.

Breast cancer (BC) is the most common malignancy among women. Therapeutic options are based on disease staging, histopathological characteristics, age, and others. The objective of the present study is to carry out an update of the concepts and definitions of radiotherapy (RT) in conservative treatment of early-stage breast cancer, with emphasis on indications, contraindications, RT dose fractionation schedules (classic, hypofractionated and partial breast irradiation), adjuvant RT in ductal carcinoma in situ (DCIS) and molecular predictors of recurrence. MEDLINE, SciELO and Cochrane databases were used for article selection. Adjuvant RT is indicated for patients with BC who underwent conservative breast surgery. In selected patients, hypofractionated or partial breast irradiation can be used. Adjuvant RT should be provided for all patients with DCIS. The correlation of RT and molecular predictors of local and systemic recurrence are not yet well-known.

Bilateral reduction mammaplasty for immediate breast conservation surgery reconstruction and intraoperative radiotherapy: a preliminary report.

BACKGROUND: Breast conservation surgery and postoperative radiotherapy are widely accepted as the treatment of choice for patients with early breast cancer. Despite its oncologic benefits, the radiotherapy may cause unpredictable outcomes in soft tissues, especially in patients undergoing breast reconstruction. Described recently, intraoperative irradiation (IORT) has been indicated for selected patients as an alternative to radiotherapy with fewer adverse local effects. Clinical use of reduction mammaplasty (RM) techniques in oncologic breast surgery has been described previously. However, no previous studies have mentioned its application after breast conservation surgery and IORT. METHODS: The authors used RM to reconstruct a partial breast tissue defect secondary to breast conservation surgery followed by IORT treatment in a 46-year-old patient with an 11-mm invasive ductal carcinoma between the superior internal quadrants of the right breast. RESULTS: Satisfactory breast volume and shape were achieved, and no immediate or late complications were observed. After 2 postoperative years, no evidence of fat necrosis, tumor recurrence, or tissue volume loss was observed. CONCLUSION: The initial data indicate that RM in the setting of breast conservation surgery reconstruction and IORT is feasible. With appropriate patient selection, respecting indications and limitations, RM has its place among the various reconstructive techniques. Additional studies with larger clinical series and longer follow-up periods are necessary to analyze the precise IORT effects in patients submitted to immediate breast conservation surgery reconstruction.

DNA measurements after radiation - induced tissue structure of thyroid gland of rats

INTRODUÇAO: A exposição da tireóide à irradiação está associada à alteração do componente cromossômico nessa glândula. OBJETIVO: Avaliar o conteúdo de DNA (ploidia) em glândula tireóide submetida à radiação. MATERIAL E MÉTODOS: Foram irradiadas tireóides de 75 ratos; 25 foram usados como grupo controle e não sofreram irradiação. A exposição à irradiação foi realizada com o uso de Cobalt-60 na região cervical anterior direita com espaço de 3-30cm, com anel traqueal de 2º e 6º e dose de 600 centigrays (cGY). O conteúdo de DNA (ploidia) foi obtido com o método de Feulgen-Thionin e quantificado com o aparelho CAS 200 de citometria estática. RESULTADO: Dos 92 casos, 88 (95,7 por cento) foram diplóides, independente do tempo de exposição; aneuploidia foi observada em quatro casos (4,3 por cento), somente no grupo sacrificado aos 33 dias. Oito casos foram excluídos por problemas técnicos. CONCLUSAO: A irradiação afeta muito precocemente o conteúdo de DNA nuclear levando a aneuploidia.