27 research outputs found
Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805
Purpose—Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo. We aimed to determine the prognostic and predictive role of MVD in RCC.
Experimental Design—We obtained pretreatment primary RCC nephrectomy tissues from 822 patients on E2805 and constructed tissue microarrays. Using quantitative immunofluorescence, we measured tumor MVD as the area of CD34-expressing cells. We determined the association with disease-free survival (DFS), overall survival (OS), treatment arm, and clinicopathologic variables.
Results—High MVD (above the median) was associated with prolonged OS for the entire cohort (p = 0.021) and for patients treated with placebo (p = 0.028). The association between high MVD and OS was weaker in patients treated with sunitinib or sorafenib (p = 0.060). MVD was not associated with DFS (p = 1.00). On multivariable analysis, MVD remained independently associated with improved OS (p = 0.013). High MVD correlated with Fuhrman grade 1–2 (p \u3c 0.001), clear cell histology (p \u3c 0.001), and absence of necrosis (p \u3c 0.001) but not with gender, age, sarcomatoid features, lymphovascular invasion, or tumor size.
Conclusions—High MVD in resected high-risk RCC patients is an independent prognostic, rather than predictive, biomarker of improved OS. Further studies should assess whether incorporating MVD into clinical models will enhance our ability to predict outcome and if low MVD can be used for selection of high-risk patients for adjuvant therapy trials
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Assessing a Prostate Cancer Brachytherapy Technique Using Early Patient-Reported Symptoms: A Potential Early Indicator for Technology Assessment?
Brachytherapy for early prostate cancer can cause long-term urinary, bowel, and sexual dysfunction. Modifying technique may mitigate complications, but definitive outcome assessment requires long-term follow-up. Although radiation dose plausibly mediates all treatment-related toxicity, short-term symptoms may indicate long-term outcomes. We sought an early indication of whether a modified brachytherapy technique successfully decreased toxicity in the anticipated direction by assessing changes in symptoms and symptom distress 3 months after treatment. In a prospective study of clinically localized prostate cancer using a validated, patient-reported questionnaire, we assessed 85 men, whose primary treatment was brachytherapy alone, prior to treatment and 3 months after the procedure. Twenty-two men received standard ultrasound-guided brachytherapy (SB), and 63 men received magnetic resonance imaging–guided brachytherapy (MB), a technique intended to decrease urinary toxicity by reducing urethral irradiation. Patient age and other sociodemographic variables were similar in the 2 groups. The MB group experienced a greater increase in urinary obstruction/irritation symptoms (P = 0.02) and sexual function distress, but not sexual dysfunction (P = 0.22), whereas the SB group reported a smaller increase in bowel symptoms (P = 0.04) and bowel distress (P = 0.02). We found reduced short-term urinary obstruction/irritation and increased bowel problems after MB consistent with the hypothesized effects of the modified technique, although no obvious mechanism explains the decreased sexual function distress in MB patients. Whether these short-term changes predict long-term outcome differences will require much longer follow-up. However, these results suggest that measuring early symptoms may indicate whether an altered brachytherapy treatment technique has intended favorable consequences, potentially accelerating technology assessment