Prophylactic breast irradiation reduces background parenchymal enhancement (BPE) on MRI: A secondary analysis.

PURPOSE: We recently showed that prophylactic breast irradiation (PBI) reduces the risk of contralateral breast cancer in BRCA mutation carriers undergoing treatment for early breast cancer. It has been suggested that Background Parenchymal Enhancement (BPE) may be a biomarker for increased risk of breast cancer. METHODS: For participants in the trial we reviewed the MRI prior to enrollment and following radiation treatment and scored the contralateral breast for BPE and density. RESULTS: Significant reduction of BPE was more commonly noted following PBI (p = 0.011) compared to the control group. CONCLUSION: Reduction of BPE by PBI may contribute to its prophylactic effect.

Changes of lung parenchyma density following high dose radiation therapy for thoracic carcinomas - an automated analysis of follow up CT scans.

BACKGROUND: An objective way to qualify the effect of radiotherapy (RT) on lung tissue is the analysis of CT scans after RT. In this analysis we focused on the changes in Hounsfield units (ΔHU) and the correlation with the corresponding radiation dose after RT. METHODS: Pre- and post-RT CT scans were matched and ΔHU was calculated using customized research software. ΔHU was calculated in 5-Gy-intervals and the correlation between ΔHU and the corresponding dose was calculated as well as the regression coefficients. Additionally the mean ΔHU and ΔHU in 5-Gy-intervals were calculated for each tumor entity. RESULTS: The mean density changes at 12 weeks and 6 months post RT were 28,16 HU and 32,83 HU. The correlation coefficient between radiation dose and ΔHU at 12 weeks and 6 months were 0,166 (p = 0,000) and 0,158 (p = 0,000). The resulting regression coefficient were 1439 HU/Gy (p = 0,000) and 1612 HU/Gy (p = 0,000). The individual regression coefficients for each patient range from - 2,23 HU/Gy to 7,46 HU/Gy at 12 weeks and - 0,45 HU/Gy to 10,51 HU/Gy at 6 months. When looking at the three tumor entities individually the highest ΔHU at 12 weeks was seen in patients with SCLC (38,13 HU) and at 6 month in those with esophageal carcinomas (40,98 HU). CONCLUSION: For most dose intervals there was an increase of ΔHU with an increased radiation dose. This is reflected by a statistically significant, although low correlation coefficient. The regression coefficients of all patients show large interindividual differences.

Intervening Nidal Brain Parenchyma and Risk of Radiation-Induced Changes After Radiosurgery for Brain Arteriovenous Malformation: A Study Using an Unsupervised Machine Learning Algorithm.

OBJECTIVE: To assess the sensitivity and specificity of arteriovenous malformation (AVM) nidal component identification and quantification using an unsupervised machine learning algorithm and to evaluate the association between intervening nidal brain parenchyma and radiation-induced changes (RICs) after stereotactic radiosurgery. METHODS: Fully automated segmentation via unsupervised classification with fuzzy c-means clustering was used to analyze the AVM nidus on T2-weighted magnetic resonance imaging studies. The proportions of vasculature, brain parenchyma, and cerebrospinal fluid were quantified. These were compared with the results from manual segmentation. The association between the brain parenchyma component and RIC development was assessed. RESULTS: The proposed algorithm was applied to 39 unruptured AVMs in 39 patients (17 female and 22 male patients), with a median age of 27 years. The median proportion of the constituents was as follows: vasculature, 31.3%; brain parenchyma, 48.4%; and cerebrospinal fluid, 16.8%. RICs were identified in 17 of the 39 patients (43.6%). Compared with manual segmentation, the automated algorithm was able to achieve a Dice similarity index of 79.5% (sensitivity, 73.5%; specificity, 85.5%). RICs were associated with a greater proportion of intervening nidal brain parenchyma (52.0% vs. 45.3%; P = 0.015). Obliteration was not associated with greater proportions of nidal vasculature (36.0% vs. 31.2%; P = 0.152). CONCLUSIONS: The automated segmentation algorithm was able to achieve classification of the AVM nidus components with relative accuracy. Greater proportions of intervening nidal brain parenchyma were associated with RICs.

Pretreatment 18F-fluorodeoxyglucose Uptake in the Lung Parenchyma Predicts Poor Survival After Stereotactic Body Radiation Therapy in Patients With Stage I Non-Small Cell Lung Cancer.

PURPOSE: In this study, we aimed to evaluate the prognostic value of fluorodeoxyglucose uptake in the lung parenchyma and the presence of subclinical interstitial lung disease on computed tomography as predictive factors for survival following stereotactic body radiation therapy in patients with stage I non-small cell lung cancer. METHODS: We retrospectively evaluated 125 patients with stage I non-small cell lung cancer who underwent stereotactic body radiation therapy at our institute between December 2005 and March 2013 for various demographic and clinical parameters. The fluorodeoxyglucose uptake in the lung parenchyma corrected with computed tomography value (tissue fraction-corrected standardized uptake value) was quantified using fluorodeoxyglucose-positron emission tomography/computed tomography before the therapy. Additionally, the radiological findings of interstitial lung disease on computed tomography were evaluated. The prognostic analyses were performed using the Kaplan-Meier analysis and Cox proportional hazards regression model for univariate and multivariate analyses. RESULTS: The median follow-up period was 39 months. The 3-year overall survival rate was 67.9%, and the 3-year progression-free survival rate was 52.0%. The multivariate analysis indicated that the tissue fraction-corrected standardized uptake value was correlated with the patients' overall survival ( P = .027, hazard ratio: 2.694, 95% confidence interval: 1.109-8.057). The presence of subclinical interstitial lung disease showed no correlation with the overall survival ( P = .535, hazard ratio: 1.256, 95% confidence interval: 0.592-2.473). CONCLUSION: The results indicated that fluorodeoxyglucose uptake in the lung parenchyma, expressed as the tissue fraction-corrected standardized uptake value, was an independent prognostic factor in patients with stage I non-small cell lung cancer who have received stereotactic body radiation therapy.

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

BACKGROUND: The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. MATERIAL AND METHODS: Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. RESULTS: Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. CONCLUSIONS: SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability.

BACKGROUND/AIMS: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. METHODS: Primary bmMSCs were obtained from the marrow of six-week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O2) or hypoxic conditions (2.5% O2). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included H&E staining, Masson staining and α-SMA staining; meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. RESULTS: Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. CONCLUSION: Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α.

Breast Background Parenchymal Enhancement on Screening Magnetic Resonance Imaging in Women Who Received Chest Radiotherapy for Childhood Hodgkin's Lymphoma.

RATIONALE AND OBJECTIVES: Breast magnetic resonance imaging (MRI) is recommended for the screening of women with a history of chest radiotherapy and consequent increased breast cancer risk. The purpose of this study was to evaluate the impact of prior chest radiotherapy on breast tissue background parenchymal enhancement (BPE) at screening breast MRI. MATERIALS AND METHODS: A departmental database was reviewed to identify asymptomatic women with either a history of chest radiotherapy for Hodgkin's lymphoma or age-matched controls who underwent screening breast MRI between 2009 and 2013. MRI studies were analyzed on an automated breast MRI viewing platform to calculate breast BPE and breast density. RESULTS: A total of 61 cases (mean age 41.6 ± 6.75 years) and 61 controls (mean age 40.8 ± 6.99 years) were included. The age of patients at the time of chest radiotherapy was 22.6 ± 8.17 years. Screening MRI was performed 19.0 ± 7.43 years after chest radiotherapy. BPE was significantly higher in patients who received chest radiotherapy (50% vs. 37%, P <0.01). A weak to moderate positive correlation (r > 0.3; P < 0.03) was found between BPE and number of years post radiotherapy. There was a trend toward significant difference between the two groups in the correlation of BPE and age (P = 0.05). Breast density was not significantly different between the two groups. CONCLUSIONS: BPE is significantly greater in women who receive chest radiotherapy for childhood Hodgkin's lymphoma, and unexpectedly, it positively correlates with the number of years passed after radiation therapy. Long-term biological effects of radiation therapy on breast parenchyma need further research.