Faculty Bibliography

OBJECTIVE: To compare the clinical behavior and outcome of uterine carcinosarcomas and grade 3 endometrioid carcinomas. METHODS: Data on patients with grade 3 endometrioid adenocarcinomas and uterine carcinosarcomas, from 1988 to 2004, was obtained from the Surveillance, Epidemiology, and End Results database. Mortality was analyzed using Cox proportional hazards models. Survival analysis was performed with the Kaplan-Meier method and log rank test. RESULTS: The cohort included 8,986 women with 5,024 (56%) grade 3 endometrioid carcinomas and 3,962 (44%) uterine carcinosarcomas. Women with uterine carcinosarcomas were older (aged 70 years compared with 66 years; P<.001) and more often nonwhite (23% compared with 15%; P<.001). These women presented with more advanced disease (stage III/IV 41% compared with 31%; P<.001). Multivariable analysis demonstrated that uterine carcinosarcoma histology, advanced age, nonwhite race, and advanced stage were independent predictors of poor survival. Cancer-specific mortality was 45% lower in women with grade 3 endometrioid carcinomas (hazard ratio 0.55; 95% confidence interval [CI] 0.5-0.6). The 5-year cancer-specific survival was lower for women with uterine carcinosarcoma for each disease stage. Survival for stage IC was 38% (95% CI 33-45%) for uterine carcinosarcoma compared with 68% (95% CI 63-73%) for grade 3 endometrioid carcinoma. For stage III, survival was 22% (95% CI 19-26%) for uterine carcinosarcoma compared with 45% (95% CI 41-49%) for grade 3 endometrioid carcinoma. CONCLUSION: Carcinosarcomas present at more advanced stage and have worse survival than grade 3 endometrioid carcinomas. Carcinosarcomas may represent a distinct biologic entity. LEVEL OF EVIDENCE: II

Skin injury is a common side effect of breast-cancer radiation therapy. Although physicians often observe skin toxicity, quantifying its severity remains a challenge. We present a novel quantitative ultrasonic technique to evaluate skin changes associated with radiotherapy. An in vivo study with twelve breast-cancer patients was conducted. All patients received a standard course of post-surgery radiation therapy. Each patient received ultrasound scans to the irradiated breast and the untreated (contra-lateral) breast. Radio-frequency (RF) backscatter signals and B-mode images were acquired simultaneously. To quantify the severity of skin injury, two metrics were calculated from the RF signals: skin thickness and Pearson correlation coefficient of the subcutaneous layer. Comparing to the non-irradiated skin, the average thickness of the irradiated skin increased by 40% (p=0.005) and the average correlation coefficient of the irradiated hypodermis decreased by 35% (p=0.02). This study demonstrates the feasibility of using a non-invasive ultrasonic technique to detect and quantify radiation-induced skin changes

Purpose: Several studies have reported computerized tomography (CT) overestimates prostate volume by 30 to 50% in comparison to ultrasound in prostate radiation therapy. To further elucidate this phenomenon, we compared the differences in prostate volume assessed by ultrasound and CT, specifically with in vivo and ex vivo ultrasound, and ex vivo CT. Method and Materials: Seven patients with localized prostate cancer treated with radical prostatectomy were enrolled. Each patient was scanned with transrectal ultrasound (TRUS) prior to surgery. Prostate specimens were immediately scanned post‐surgery with both ultrasound and CT. 3‐D imaging scans were acquired from the base to the apex of the prostate in the axial plane in 2 mm and 1.25 mm slices for ultrasound and CT imaging, respectively. The prostate gland was contoured on each 3‐D ultrasound and CT image set by one radiation oncologist and then volume calculations were made based on voxel size. Results: The in vivo prostate volume acquired with ultrasound was on average 33.2 cc (range 25.7 – 41.3 cc). The ex vivo CT and ultrasound volumes of the prostate specimens were 32.8 cc (range 24.7 – 41.1) and 32.7 cc (range 24.9 – 40.3), respectively. The ex vivo and ex vivo ultrasound prostate volume measurements were within 5% of each other. Overall, there was a 1 to 2% reduction between the imaged pre and post‐surgery prostate volumes. For each individual specimen the concordance between the CT and ultrasound volumes was within 5%. Conclusion: While several studies have consistently reported larger prostate volumes when using CT as compared to transrectal ultrasound, our study shows no intrinsic difference between ultrasound and CT imaging in terms of prostate volume measurements. Therefore, we propose the difficulty with precise prostate contour delineation encountered with CT imaging results in the frequent overestimation of the prostate gland size seen in prostate radiation therapy

OBJECTIVES: To retrospectively compare the biochemical disease-free survival (BDFS) of patients treated with standard dose external beam radiotherapy (SD-EBRT), SD-EBRT plus androgen deprivation (AD), and brachytherapy-based treatment (brachytherapy with or without EBRT with or without AD). METHODS: All 297 patients with intermediate-risk prostate cancer treated with these radiation-based treatments at our institution from August 1989 to June 2001 were included. Biochemical relapse was defined according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, a prostate-specific antigen level of 1.5 ng/mL or greater and rising on two consecutive occasions (the 'Bolla' definition), and the current prostate-specific antigen nadir plus 2 ng/mL with failure dated 'at call' (the 'Houston/Phoenix' definition). The number of patients treated with SD-EBRT, SD-EBRT plus AD, and brachytherapy-based treatment was 141, 84, and 72, respectively. The year of treatment was analyzed as a prognostic factor. The median follow-up was 32.3, 34.7, and 41.5 months for the ASTRO, Bolla, and Houston/Phoenix definitions, respectively. RESULTS: The brachytherapy-based treatment resulted in improved BDFS compared with SD-EBRT (ASTRO definition, 5-year BDFS rate 88% +/- 5% versus 49% +/- 5%, P <0.01; Bolla definition, 88% +/- 8% versus 49% +/- 5%, P <0.01; Houston/Phoenix definition, 81% +/- 10% versus 64% +/- 5%, P = 0.01). SD-EBRT plus AD was superior to SD-EBRT alone using the Bolla definition (5-year BDFS 76% +/- 7% versus 49% +/- 5%, P <0.01) and the Houston/Phoenix definition (85% +/- 6% versus 64% +/- 5%, P = 0.01), but not using the ASTRO definition (P = 0.17). Multivariate analysis, including prostate-specific antigen, clinical stage, Gleason score, and year of treatment, demonstrated improved biochemical outcomes for brachytherapy-based treatment versus SD-EBRT (ASTRO, P <0.01; Bolla, P <0.01; and a trend toward significance with Houston/Phoenix, P = 0.07) and for the addition of AD to SD-EBRT (Bolla, P <0.01 and Houston/Phoenix, P = 0.03). The year of treatment trended toward significance (P = 0.077) on multivariate analysis using the ASTRO definition. CONCLUSIONS: For patients with intermediate-risk prostate cancer, brachytherapy-based treatment and the addition of AD to SD-EBRT resulted in improved biochemical outcomes compared with the outcomes with SD-EBRT alone; however, these findings were dependent on the definition of biochemical failure used. The year of treatment may be an important prognostic factor in intermediate-risk prostate cancer

PURPOSE: To investigate how the performance characteristics of ultrasound tissue typing (UTT) affect the design of a population-based prostate dose-painting protocol. METHODS AND MATERIALS: The performance of UTT is evaluated using the receiver operating characteristic curve. As the imager's sensitivity increases, more tumors are detected, but the specificity worsens, causing more false-positive results. The UTT tumor map, obtained with a specific sensitivity and specificity setup, was used with the patient's CT image to guide intensity-modulated radiotherapy (IMRT) planning. The optimal escalation dose to the UTT positive region, as well as the safe dose to the negative background, was obtained by maximizing the uncomplicated control (i.e., a combination of tumor control probability and weighted normal tissue complication probability). For high- and low-risk tumors, IMRT plans guided by conventional ultrasound or UTT with a one-dimensional or two-dimensional spectrum analysis technique were compared with an IMRT plan in which the whole prostate was dose escalated. RESULTS: For all imaging modalities, the specificity of 0.9 was chosen to reduce complications resulting from high false-positive results. If the primary tumors were low risk, the IMRT plans guided by all imaging modalities achieved high tumor control probability and reduced the normal tissue complication probability significantly compared with the plan with whole gland dose escalation. However, if the primary tumors were high risk, the accuracy of the imaging modality was critical to maintain the tumor control probability and normal tissue complication probability at acceptable levels. CONCLUSION: The performance characteristics of an imager have important implications in dose painting and should be considered in the design of dose-painting protocols