A significant decrease in rectal volume and diameter during prostate IMRT.

PURPOSE: To record changes in rectal volume (RV) and diameter (RD) of patients with prostate adenocarcinoma prior to and at an interim period during radiotherapy, which could potentially affect treatment toxicity and tumor control. METHODS: Three hundred and fifteen patients treated with intensity modulated radiotherapy (IMRT) underwent planning CT scans before radiation and after 45 Gy. For each scan, RV and RD were recorded and compared using a two-tailed paired t-test. Robust linear regression analysis assessed correlation between initial RV and percent RV change. RESULTS: The mean change in RV was -8.62 cm(3) and in RD was -0.19 cm(3), (p<0.05). A decrease ≥10% in RV and RD was seen in 159 patients (50.5%) and 117 patients (37.1%), respectively. Patients with ≥10% volume change had larger initial RVs than those with <10% decrease, (78.1 vs. 50.8 cm(3), p<0.0001). CONCLUSIONS: A significant decrease in RV and RD occurs during prostate IMRT delivery. More than half of patients had decreased RV and over a third had decreased RD. This observation is pertinent to prostate localization, planning margins, and implies that dose-volume histogram (DVH) analysis of rectal irradiation based on pre-treatment CT scanning may inaccurately estimate the risk of rectal toxicity when the initial RV is larger than 70 cm(3).

The impact of pretreatment prostate volume on severe acute genitourinary toxicity in prostate cancer patients treated with intensity-modulated radiation therapy.

PURPOSE: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm(3), respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. RESULTS: Patients with large prostates (>50 cm(3)) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm(3) increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. CONCLUSIONS: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

Bcl-2 expression is altered with ovarian tumor progression: an immunohistochemical evaluation.

BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy. The ovarian tumor microenvironment is comprised of tumor cells, surrounding stroma, and circulating lymphocytes, an important component of the immune response, in tumors. Previous reports have shown that the anti-apoptotic protein Bcl-2 is overexpressed in many solid neoplasms, including ovarian cancers, and contributes to neoplastic transformation and drug-resistant disease, resulting in poor clinical outcome. Likewise, studies indicate improved clinical outcome with increased presence of lymphocytes. Therefore, we sought to examine Bcl-2 expression in normal, benign, and cancerous ovarian tissues to determine the potential relationship between epithelial and stromal Bcl-2 expression in conjunction with the presence of lymphocytes for epithelial ovarian tumor progression. METHODS: Ovarian tissue sections were classified as normal (n = 2), benign (n = 17) or cancerous (n = 28) and immunohistochemically stained for Bcl-2. Bcl-2 expression was assessed according to cellular localization, extent, and intensity of staining. The number of lymphocyte nests as well as the number of lymphocytes within these nests was counted. RESULTS: While Bcl-2 staining remained cytoplasmic, both percent and intensity of epithelial and stromal Bcl-2 staining decreased with tumor progression. Further, the number of lymphocyte nests dramatically increased with tumor progression. CONCLUSION: The data suggest alterations in Bcl-2 expression and lymphocyte infiltration correlate with epithelial ovarian cancer progression. Consequently, Bcl-2 expression and lymphocyte status may be important for prognostic outcome or useful targets for therapeutic intervention.

Urinary levels of Bcl-2 are elevated in ovarian cancer patients.

OBJECTIVE(S): The poor prognosis associated with ovarian cancer is due to the lack of overt early symptoms and the absence of reliable diagnostic screening methods. Since many tumors overexpress anti-apoptotic proteins, the purpose of this study was to determine whether elevated levels of the anti-apoptotic protein Bcl-2 were present in urine from patients with ovarian cancer. METHODS: Bcl-2 was assayed by ELISA in urine samples from two cohorts consisting of a total of 77 healthy women, 161 women with benign gynecologic disease and 150 women with ovarian cancer, 13 with early and 137 with late stage disease, respectively. Wherever possible, parallel serum samples were measured for CA125 levels by ELISA. RESULTS: Urinary levels of Bcl-2 from healthy individuals or women with benign disease averaged 0.59 ng/ml+/-0.61 and 1.12 ng/ml+/-0.79, respectively. In contrast, urinary levels of Bcl-2 averaged 2.60 ng/ml+/-2.23 and 3.58 ng/ml+/-1.55 from women with early (N=13) and late (N=137) stage ovarian cancer. Further, urinary levels of Bcl-2 were elevated in ovarian cancer patients regardless of tumor grade, stage, size, histologic subtype, creatinine levels or patient age, but appeared to complement CA125 measurements. CONCLUSION(S): Levels of Bcl-2 are elevated in the urine of patients with ovarian cancer and may be of diagnostic and/or prognostic clinical importance. Further studies of urinary Bcl-2 as a biomarker for ovarian cancer alone or in combination with other markers are warranted.