TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Effect of obesity on prostate-specific antigen recurrence after radiation therapy for localized prostate cancer as measured by the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiation and Oncology (RTOG-ASTRO) Phoenix consensus definition.

BACKGROUND: Given the limited data regarding the impact of obesity on treatment outcomes after external beam radiation therapy (EBRT) for the definitive treatment of prostate cancer, the authors sought to evaluate the effect of obesity as measured by body mass index (BMI) on biochemical disease recurrence (BCR) using the most current 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiation and Oncology (RTOG-ASTRO) Phoenix consensus definition (prostate-specific antigen [PSA] nadir + 2 ng/mL). METHODS: A retrospective cohort study identified men who underwent primary EBRT for localized prostate cancer between 1989 and 2003 using the Center for Prostate Disease Research (CPDR) Multi-center National Database. BMI was calculated (in kg/m(2)) and the data were analyzed. Univariate and multivariate Cox proportional hazards regression analyses were used to determine whether BMI significantly predicted BCR. RESULTS: Of the 1868 eligible patients, 399 (21%) were obese. The median age of the patients and pretreatment PSA level were 70.2 years and 8.2 ng/mL, respectively. Of 1320 patients for whom data were available with which to calculate PSA recurrence (PSA nadir + 2 ng/mL), a total of 554 men (42.0%) experienced BCR. On univariate analysis, BMI was found to be an independent predictor of PSA recurrence (P = .02), as was race, pretreatment PSA level, EBRT dose, clinical T classification, Gleason score, PSA nadir, and the use of androgen-deprivation therapy (ADT). On multivariate analysis, BMI remained a significant predictor of BCR (P = .008). CONCLUSIONS: To the authors' knowledge, this is the first study to report the association between obesity and BCR after EBRT for localized prostate cancer as measured by the updated 2006 RTOG-ASTRO definition. A higher BMI is associated with greater odds of BCR after undergoing definitive EBRT.

Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury.

PURPOSE: The purpose of this study was to determine if radiation-induced lung injury is associated with prolonged oxidative stress, and whether chronic overexpression of extracellular superoxide dismutase (EC-SOD) in the lung of transgenic mice protects against radiation-induced lung injury. METHODS AND MATERIALS: Whole-lung radiation was delivered to EC-SOD overexpressing B6C3 transgenic (XRT-TG) mice and wild-type littermates (XRT-WT). Pulmonary function was assessed by breathing frequency. Right lung wet weight was used as a gross indicator of lung damage. Histopathology was used to assess collagen deposition and tissue fibrosis according to an established grading system. Immunohistochemistry was used to stain and quantify the number of macrophages. ELISA was used to measure activated TGF-beta1. Oxidative stress was assessed by measuring lipid oxidation products (malondialic acid) by HPLC. RESULTS: Four of six XRT-WT mice required euthanasia at 15-19 weeks postradiation because of respiratory distress, whereas no XRT-TG mouse developed distress. All assessments of lung damage at 15-20 weeks postradiation were higher for XRT-WT mice compared with the XRT-TG mice, including breathing frequency (380 vs. 286 bpm, p

Low-dose radiation for posttransplant lymphoproliferative disorder.

Initial treatment for posttransplant lymphoproliferative disorder (PTLD) usually involves discontinuation of immunosuppressants. Anti-CD20 monoclonal antibody and/or antivirals are typically employed for persistent disease. Chemotherapy is generally reserved as a final option. The role of radiation therapy, and doses required, have not been well established. Low-dose involved field radiation therapy was used in three pediatric bone marrow transplant (BMT) patients with biopsy-proven PTLD. One patient received a matched T-cell-depleted BMT for dyskeratosis congenita. Two patients with acute myelogenous leukemia received an unrelated umbilical cord blood transplant, and a matched-related allogeneic BMT. All patients required intubation for respiratory distress due to PTLD. Initial treatment was discontinuation or decrease in FK-506. Anti-CD20 antibody was started in all patients, and foscarnet in one patient. All patients were treated with three 150-cGy fractions, for a total dose of 450 cGy. Time from BMT to development of PTLD was 4, 2, and 32 months, respectively. Duration of observation on initial medical therapy prior to irradiation was 11 days, 12 days, and 1 day, respectively. The radiation was well tolerated with no acute complications. Two patients were extubated at 8 and 4 days postradiation, respectively. The first patient had complete radiographic resolution of the mass and adenopathy at 4 months after radiation. The second died of pulmonary hemorrhage and disseminated aspergillosis infection, but had significant regression of disease in the irradiated area 15 days after radiation. The third had pronounced shrinkage of his mediastinal mass. A biopsy was taken of a persistent mass 4 months after radiation, with no evidence of lymphoproliferative disease. These cases demonstrate that low-dose radiation for PTLD is effective for palliation and produces a durable response with no acute toxicity.

A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury.

Radiation therapy (RT) is an important therapeutic modality in the treatment of thoracic tumors. The maximum doses to these tumors are often limited by the radiation tolerance of lung tissues. Lung injury from ionizing radiation is believed to be a consequence of oxidative stress and a cascade of cytokine activity. Superoxide dismutase (SOD) is a key enzyme in cellular defenses against oxidative damage. The objective of this study was to determine whether the SOD mimetic AEOL 10113 [manganese (III) mesotetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+))] increases the tolerance of lung to ionizing radiation. AEOL 10113 was able to significantly reduce the severity of RT-induced lung injury. This was strongly supported with histopathology results and measurements of collagen deposition (hydroxyproline content). There was a significant reduction in the plasma level of the profibrogenic cytokine transforming growth factor-beta (TGF-beta) in the group of rats receiving RT + AEOL 10113. In conclusion, the novel SOD mimetic, AEOL 10113, demonstrates a significant protective effect from radiation-induced lung injury.

Gastrointestinal toxicity of transperineal interstitial prostate brachytherapy.

PURPOSE: To characterize the severity and time course of rectal toxicity following transperineal prostate brachytherapy using prospectively recorded data, and to determine factors associated with toxicity. METHODS AND MATERIALS: One hundred thirty-four patients with prostate cancer treated with transperineal brachytherapy from 1997 to 1999 had rectal toxicity data available for analysis. Patients with Gleason score (GS) > 6, prostate-specific antigen (PSA) > 6, or stage > T2a were treated initially with external beam radiation therapy followed by brachytherapy boost; patients with none of these features were treated with brachytherapy alone. Both iodine-125 and palladium-103 sources were used, and loaded according to a modified Quimby distribution. At each follow-up, toxicity was recorded according to a modified RTOG gastrointestinal scale. RESULTS: Thirty-nine percent of patients experienced gastrointestinal toxicity, mostly Grade 1. Median duration of symptoms was 6 months. Two patients experienced Grade 3 toxicity, both of whom had minimal symptoms until their 12-month follow-up. There was no Grade 4 or 5 toxicity. The addition of external beam radiation therapy (p = 0.003), higher clinical stage (p = 0.006), and Caucasian race (p = 0.01) were associated with increased incidence of toxicity. CONCLUSION: Most patients with rectal toxicity have very mild symptoms. There is a small risk of severe late toxicity. External beam radiation, higher stage, and race are associated with toxicity.