Breast cancer after thoracic radiotherapy in young patients: what does the radiologist need to know?

Radiation-induced secondary tumors constitute a rare complication of radiation therapy and typically occur in or near the irradiated area. Women who undergo thoracic radiotherapy before 30 years of age have a significantly greater lifetime risk of developing breast cancer than do those in the general population. It is recommended that a patient who has previously received thoracic radiotherapy with a radiation dose ≥ 10 Gy subsequently undergo annual screening with mammography and magnetic resonance imaging, beginning eight years after the initial treatment or when the patient has reached 25 years of age (whichever comes later). The treatment of secondary breast cancer in this population should be individualized and should be discussed with a multidisciplinary team to avoid toxicity related to the treatment of the primary cancer.

Os cânceres secundários induzidos por radiação são complicações raras da radioterapia e geralmente ocorrem na área tratada ou próximo a ela. Mulheres com menos de 30 anos de idade tratadas com radioterapia torácica têm risco significativamente aumentado de desenvolver câncer de mama ao longo da vida, em comparação com a população em geral. Para as pacientes tratadas com irradiação torácica com dose igual ou superior a 10 Gy é recomendado rastreamento anual com mamografia e ressonância magnética iniciando oito anos após o tratamento, desde que este início seja após 25 anos de idade. O tratamento do câncer de mama secundário nessa população deve ser individualizado e discutido com equipe multidisciplinar, para evitar toxicidade relacionada ao tratamento do câncer primário.

Breast cancer after thoracic radiotherapy in young patients: what does the radiologist need to know? / Câncer de mama após radioterapia torácica em pacientes jovens: o que o radiologista precisa saber?

Abstract Radiation-induced secondary tumors constitute a rare complication of radiation therapy and typically occur in or near the irradiated area. Women who undergo thoracic radiotherapy before 30 years of age have a significantly greater lifetime risk of developing breast cancer than do those in the general population. It is recommended that a patient who has previously received thoracic radiotherapy with a radiation dose ≥ 10 Gy subsequently undergo annual screening with mammography and magnetic resonance imaging, beginning eight years after the initial treatment or when the patient has reached 25 years of age (whichever comes later). The treatment of secondary breast cancer in this population should be individualized and should be discussed with a multidisciplinary team to avoid toxicity related to the treatment of the primary cancer.

Resumo Os cânceres secundários induzidos por radiação são complicações raras da radioterapia e geralmente ocorrem na área tratada ou próximo a ela. Mulheres com menos de 30 anos de idade tratadas com radioterapia torácica têm risco significativamente aumentado de desenvolver câncer de mama ao longo da vida, em comparação com a população em geral. Para as pacientes tratadas com irradiação torácica com dose igual ou superior a 10 Gy é recomendado rastreamento anual com mamografia e ressonância magnética iniciando oito anos após o tratamento, desde que este início seja após 25 anos de idade. O tratamento do câncer de mama secundário nessa população deve ser individualizado e discutido com equipe multidisciplinar, para evitar toxicidade relacionada ao tratamento do câncer primário.

Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Postmastectomy Radiation Therapy Bolus Associated Complications in Patients Who Underwent 2-stage Breast Reconstruction.

Purpose: This study aimed to evaluate the association of bolus and 2-stage breast reconstruction complications, and whether the dosimetric advantage translates into improvements in local control. Methods and Materials: We retrospectively analyzed data from 2008 to 2019 of women who underwent a mastectomy and a planned 2-stage breast reconstruction, followed by adjuvant radiation therapy. We reviewed all data from medical records and radiation plans regarding patient characteristics, diagnoses, surgeries, complications, pathology, staging, systemic therapy, radiation therapy, and outcomes, and compared complication rates according to bolus usage. Results: A total of 288 women, age 25 to 71 years, were included in the study. Of these women, 6 were treated with daily bolus and 19 with alternate days bolus, totaling 25 of 288 patients (8.7%) in the bolus group. A total of 226 patients (78.5%) had the second stage performed. The median follow-up time was 61 months. The rates for 5-year overall survival and locoregional control were both 97%, and the metastasis-free rate was 83%. In the first stage, 6.25% of patients in the entire cohort had an infection and 4.2% had implant loss. Daily bolus significantly increased the risk of expander infection (hazard ratio [HR]: 10.3; 95% confidence interval [CI], 1.7-61.8) and loss (HR: 13.89; 95% CI, 2.24-85.98), but alternate-day bolus showed a nonsignificant increase for expander infection (HR: 1.14; 95% CI, 0.14-9.295) and loss (HR: 1.5; 95% CI, 0.19-12.87). Bolus was not associated with second-stage complications or local-regional failure. Local infection and implant loss were more frequent in the second than in the first stage (5.2% vs 10.2% and 4.2% vs 12.8%, respectively). Conclusions: Skin bolus significantly increased first-stage breast reconstruction complications (infection and reconstruction failure). Despite the small sample size and the need for future studies, these findings need to be taken into consideration when planning treatment and reconstruction, and recommendations should be individualized.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Impact of cranial stereotactic radiotherapy associated with immunotherapy with nivolumab and ipilimumab on overall survival in patients with melanoma brain metastases: a real-world evidence.

PURPOSE: To evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting. METHODS/PATIENTS: The study was performed by using TriNetX, a global health network dataset of electronic medical records from patients in 49 healthcare organizations. We queried for patients with specific terms between January 2016 and December 2020 and run a propensity score matching (PSM) analysis. OS was estimated by Kaplan-Meier and log-rank test was applied. RESULTS: After initial query and PSM, 114 patients were selected in each cohort. Median OS was 327 days in CNI and not reached in the CNI + SRT cohort, with OS probability of 54.4 and 40.9%, respectively (log-rank P = .0057). CNI + SRT was associated with significantly decreased mortality (HR, 0.57; 95% CI 0.377-0.853; proportionality P = .0034). CONCLUSIONS: This real-world analysis showed that CNI + SRT led to an improvement in OS compared to CNI.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms.

OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Radiation therapy with elective lymph node irradiation for breast cancer: dosimetric study and impact on cardiovascular risk and second neoplasms

SUMMARY OBJECTIVE: The aim of this study was to perform dosimetric analysis of radiotherapy (RT) plans with or without elective nodal irradiation (ENI) and estimate whether the increase in mean doses (MDs) in the heart and lungs with ENI may lead to late side effects that may surpass the benefits of treatment. METHODS: The dosimetric analysis of 30 treatment plans was done with or without ENI. The planning and dose-volume histograms were analyzed, and the impact on the mortality of cardiovascular and lung cancer was estimated based on the correlation of the dosimetric data with data from population studies. RESULTS: RT with ENI increased the doses in the lungs and heterogeneity in the plans compared to breast-exclusive RT. When the increase in MDs is correlated with the increase of late side-effect risks, the most important effect of ENI is the increased risk of lung cancer, especially in patients who smoke (average increase in absolute risk=1.38%). The increase in the absolute risk of cardiovascular diseases was below 0.1% in the all the situations analyzed. CONCLUSIONS: ENI increases the heterogeneity and the doses at the lungs. When recommending ENI, the risks and benefits must be taken into account, considering the oncology factors and the plan of each patient. Special attention must be given to patients who smoke as ENI may lead to a significant increase in MD in the lung and the increased risk of radiation-induced lung cancer may surpass the benefits from this treatment.

Partial breast irradiation: when less could be more.

Breast cancer is the most commonly diagnosed cancer in Brazilian women and the leading causing of cancer death among them. Breast-conserving surgery (BCS) followed by whole breast radiotherapy has become the standard care for early breast cancer. Although the omission of adjuvant breast radiotherapy has been associated with worse oncological outcomes, distance from treatment centers directly affects the employment of adjuvant breast irradiation. In addition to distance, patients from low- and middle-incoming countries suffers from a paucity of radiotherapy centres. It was estimated that 46.6% of the oncological patients requiring radiation therapy for a new primary cancer in 2016 did not received this treatment in the Brazilian public health system. Accelerated partial breast irradiation significantly reduces the treatment time and have the potential to overcome the logistics and social barriers related to adjuvant breast irradiation. During the lasts 30 years, 8 randomized phase III clinical trials showed that partial breast irradiation is a safe, effective, and convenient treatment for selected early breast cancer patients. At AC Camargo Cancer Center experience, for selected patients, partial breast irradiation achieved a 10 years local control of 95.6%. At Angelina Caron Hospital, a regional reference for cancer treatment in the state of Paraná, the median traveled distance from patients home to the radiotherapy department is 24 Km (11-287 Km). The implementation of partial breast irradiation, specially the intraoperative technique, could save patients a median of 1,440 traveled distance.

Intraoperative breast radiotherapy: survival, local control and risk factors for recurrence.

BACKGROUND: Whole breast irradiation reduces loco-regional recurrence and risk of death in patients submitted to breast-conserving treatment. Data show that radiation to the index quadrant alone may be enough in selected patients. AIM: To report the experience with intra-operative radiotherapy (IORT) with Electron-beam Cone in Linear Accelerator (ELIOT) and the results in overall survival, local control and late toxicity of patients submitted to this treatment. MATERIALS AND METHODS: 147 patients treated with a median follow up of 6.9 years (0.1â¿¿11.5 years). The actuarial local control and overall survival probabilities were estimated using the Kaplan Meier method. All tests were two-sided and p â¿¤ 0.05 was considered statistically significant. RESULTS: Overall survival of the cohort in 5 years, in the median follow up and in 10 years was of 98.3%, 95.1% and 95.1%, respectively, whereas local control in 5 years, in the median follow up and in 10 years was of 96%, 94.9% and 89.5%, respectively. Two risk groups were identified for local recurrence depending on the estrogen or progesterone receptors, axillary or margin status and lymphovascular invasion (LVI) (p = 0.016). CONCLUSIONS: IORT is a safe and effective treatment. Rigorous selection is important to achieve excellent local control results.

BREAST CANCER SURVIVAL IN A BRAZILIAN CANCER CENTER: A COHORT STUDY OF 5, 095 PATIENTS / Sobrevida do câncer de mama em um centro de câncer brasileiro: um estudo de coorte de 5. 095 pacientes

Objectives: To describe the age group, clinical stage at diagnosis, treatment, and survival rates of breast cancer patients treated in a Brazilian specialized Cancer Center. Method: A hospital-based retrospective cohort study is presented herein, on women with breast cancer diagnosed between January 1, 2000 and December 31, 2012. Data were extracted from the Hospital Cancer Registry of the A.C.Camargo Cancer Center. Data on age group, histology of the tumor, TNM classification, clinical stage and treatments were described in absolute and relative frequencies for three periods. Survival curves were estimated with the Kaplan-Meier estimator. Hazard ratio (HR) and 95% confidence interval (95%CI) were calculated for all variables. Results: A total of 5,095 female breast cancer patients were identified, with most stages classified as I and II (60%). The overall survival was 82.7% for the period of 2000­2004, and 89.9% for 2010­2012 (p<0.001). Patients with invasive ductal carcinoma, who were treated with surgery and hormonal therapy, showed a reduction in the risk of death in the most recent period HRadj=0.42 (95%CI 0.34­0.53) (2010­2012). Conclusions: Early stage diagnosis and combined treatment (including HT) are predictive prognostic factors for high survival rates in patients with invasive breast cancer. Specialized cancer centers can provide valuable indications regarding cancer control policies, evaluating overall survival for breast cancer and its associated prognosis.

Objetivos: Descrever as faixas etárias, estadiamento clínico ao diagnóstico, tratamento e sobrevida global das pacientes com câncer de mama tratadas em um centro de câncer brasileiro. Método: Estudo de uma coorte retrospectiva de base hospitalar, com mulheres diagnosticadas de câncer de mama entre 1º de janeiro de 2000 e 31 de dezembro de 2012. Os dados foram extraídos do Registro Hospitalar de Câncer do A. C. Camargo Cancer Center. Faixa etária, tipo histológico, classificação TNM, estadiamento clínico e tratamento foram descritos em frequência absoluta e relativa estratificados em três períodos. As curvas de sobrevida global foram estimadas pelo método de Kaplan-Meier. A Hazard ratio (HR) com intervalo de confiança de 95% foram calculados para todas as variáveis. Resultados: O total de 5.095 pacientes mulheres com câncer de mama foi identificado, a maioria era estágio inicial 60% (I e II). A sobrevida global foi de 82,7% para o período de 2000­2004 e 89,9% para 2010­2012 (p<0,001). Pacientes com carcinoma ductal invasivo que foram tratadas com cirurgia e hormonioterapia, mostraram redução do risco de morte no período mais recente HRaj=0,42 (0,34­0,53 em 2010­2012). Conclusões: Diagnóstico precoce e tratamento combinado (incluindo hormonioterapia) são fatores prognósticos preditivos para altas taxas de sobrevida em pacientes com câncer de mama invasivo. Centros especializados em câncer podem prover informações valiosas sobre as políticas de controle do câncer, avaliando a sobrevida global do câncer de mama e fatores associados ao prognóstico.

Intraoperative radiation therapy for the treatment of recurrent retroperitoneal and pelvic tumors: a single-institution analysis.

BACKGROUND: Patients with recurrent retroperitoneal and pelvic region tumors often require multimodal therapies. Intraoperative radiation therapy (IORT) can deliver high-dose radiation to tumor beds, even if first-line external beam radiation therapy (EBRT) was administered. We evaluated local control (LC) and survival in patients receiving IORT for recurrent tumors. METHODS: We retrospectively analyzed 41 patients with isolated pelvic or retroperitoneal recurrences of colorectal, gynecological, or retroperitoneal primary tumors. Following salvage surgery, all patients underwent tumor bed IORT via electron beam or high dose rate brachytherapy. Isolated IORT (median dose: 15 Gy) was administered to patients who had received first-line EBRT; other patients received IORT (median dose 12 Gy) plus EBRT. Local (LF), regional (RF), and distant failures (DF) were evaluated, and the Kaplan-Meier method and log-rank test were used to evaluate and compare overall survival (OS) from the date of IORT. RESULTS: Forty-one patients underwent 44 treatments, including 27 (61.3%) isolated IORT and 17 (38.7%) IORT and EBRT combination regimens. The median follow-up was 8.1 years (range: 4.4-11.7 years), and the 2, 5, and 8 year overall LC rates were 87.9, 64.0, and 49.8%, respectively. Regarding resection status, the respective 2, 5, and 8 year LC rates were 90, 76, and 76% for R0 resection and 75, 25, and 0% for R1 resection (p < 0.001). The 2, 5, and 8 year OS rates were 68, 43, and 26%, respectively. OS was better among patients with LC (p < 0.001). Twenty-four patients (58.5%) experienced a DF, and the 5 year OS rates for the patients with and without DF were 36 and 52%, respectively (p = 0.04). In a multivariate analysis, LF (p = 0,012) and recurrent retroperitoneal sarcoma (p = 0,014) were identified as significant predictors of worse OS. Thirteen patients (31%) developed clinically treatable complications related to IORT. CONCLUSIONS: Many patients achieve long-term OS and LC without significant morbidity after salvage surgery and IORT, especially in case of clear margins.

Recommendations for hypofractionated whole-breast irradiation

SUMMARY This recommendation consensus for hypofractionated whole-breast radiotherapy (RT) was organized by the Brazilian Society of Radiotherapy (SBRT) considering the optimal scenario for indication and safety in the technology applied. All controversies and contraindication matters (hypofractionated RT in patients who underwent chemotherapy [CT], hypofractionated RT in lymphatic drainage, hypofractionated RT after mastectomy with or without immediate reconstruction, boost during surgery, hypofractionated RT in patients under 50 years old, hypofractionated RT in large breasts, hypofractionated RT in histology of carcinoma in situ [DCIS]) was discussed during a meeting in person, and a consensus was reached when there was an agreement of at least 75% among panel members. The grade for recommendation was also suggested according to the level of scientific evidence available, qualified as weak, medium, or strong. Thus, this consensus will aid Brazilian radiotherapy experts regarding indications and particularities of this technique as a viable and safe alternative for the national reality.

RESUMO Este consenso de recomendações para a radioterapia (RT) hipofracionada de toda a mama foi organizado pela Sociedade Brasileira de Radioterapia (SBRT) considerando o cenário ideal para indicação e segurança na tecnologia aplicada. Questões de controvérsias e contraindicações (RT hipofracionada em pacientes submetidas à quimioterapia [QT], RT hipofracionada nas drenagens linfáticas, RT hipofracionada após mastectomia com ou sem reconstrução imediata, a realização de reforço de dose em leito cirúrgico [ou boost], RT hipofracionada em pacientes com idade menor que 50 anos, RT hipofracionada em mamas volumosas, RT hipofracionada em histologia de carcinoma in situ [CDIS]) foram discutidas em encontro presencial, sendo o consenso atingido quando existisse concordância de pelo menos 75% dos panelistas. O grau de recomendação foi também sugerido de acordo com o nível de evidência científico disponível, qualificado entre fraco, médio ou forte. Assim, este consenso deverá servir para auxiliar os especialistas da radioterapia brasileira em relação às indicações e particularidades dessa técnica, como uma alternativa segura e viável para a realidade nacional.

Recommendations for hypofractionated whole-breast irradiation.

This recommendation consensus for hypofractionated whole-breast radiotherapy (RT) was organized by the Brazilian Society of Radiotherapy (SBRT) considering the optimal scenario for indication and safety in the technology applied. All controversies and contraindication matters (hypofractionated RT in patients who underwent chemotherapy [CT], hypofractionated RT in lymphatic drainage, hypofractionated RT after mastectomy with or without immediate reconstruction, boost during surgery, hypofractionated RT in patients under 50 years old, hypofractionated RT in large breasts, hypofractionated RT in histology of carcinoma in situ [DCIS]) was discussed during a meeting in person, and a consensus was reached when there was an agreement of at least 75% among panel members. The grade for recommendation was also suggested according to the level of scientific evidence available, qualified as weak, medium, or strong. Thus, this consensus will aid Brazilian radiotherapy experts regarding indications and particularities of this technique as a viable and safe alternative for the national reality.