Chromogranin A staining as a prognostic variable in newly diagnosed Gleason score 7-10 prostate cancer treated with definitive radiotherapy.

PURPOSE: To demonstrate the association of neuroendocrine differentiation, as identified by chromogranin A (CgA) staining, with clinical outcomes in newly diagnosed prostatic adenocarcinoma treated with definitive radiotherapy (RT). MATERIALS/METHODS: Patients with Gleason score ≥7 adenocarcinoma were identified from our outcomes database. RT consisted of external beam, brachytherapy, or external beam with brachytherapy boost. Biopsy specimens were stained for neuroendocrine differentiation with CgA. Results were interpreted by a single pathologist. CgA staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Clinical outcomes were blinded at the time of pathologic evaluation. RESULTS: CgA staining was performed on 289 patients. 149 patients had Gleason score 7, and 140 were Gleason score 8-10. Median follow-up was 6.5 years. For patients with <1% versus >1% CgA staining, pretreatment characteristics were well-balanced. CgA staining was detected in 90 cases (31%). 58 patients had focal positive (<1%) CgA staining, and 32 cases had >1% of tumor cells CgA positive. Patients with >1% CgA staining had inferior biochemical control, clinical failure, distant metastases (DM), and cause-specific survival (CSS) rates. Ten-year rates of DM were 8% versus 48% for patients with <1% versus >1% CgA positive cells, respectively (P < 0.001). CSS at 10 years was 95% versus 76%, respectively (P < 0.001). Local control was equivalent in the two patient cohorts. Patients with <1% CgA staining had similar outcomes to those patients with 0% staining. CONCLUSIONS: Neuroendocrine differentiation involving >1% of tumor cells on prostate cancer biopsies is a predictor of DM and CSS in patients treated with primary RT.

Testicular cancer with extensive gonadal and renal vein tumor thrombus.

Tumor thrombus has been demonstrated to occur with hepatocellular and renal cell carcinoma, however, rarely occurs in testicular germ cell malignancies. Tumor thrombus results from the intravascular invasion of malignant cells, different from the hypercoagulable state induced by malignancy, and has significant implications with regards to prognosis and therapeutic options. We describe a case of an otherwise healthy 30-year-old patient with extensive gonadal and renal vein tumor thrombus from testicular germ cell cancer, as well as discuss the diagnosis and treatment options for this type of metastatic disease.

Impact of a prostate multidisciplinary clinic program on patient treatment decisions and on adherence to NCCN guidelines: the William Beaumont Hospital experience.

OBJECTIVES: In order to demonstrate the impact of multidisciplinary care in the community oncology setting, we evaluated treatment decisions after the initiation of a dedicated prostate and genitourinary (GU) multidisciplinary clinic (MDC). METHODS: In March 2010, a GU MDC was created at William Beaumont Hospital with the goal of providing patients with a comprehensive multidisciplinary evaluation and consensus treatment recommendations in a single visit. Urologists, radiation, and medical oncologists along with ancillary support staff participated in this comprehensive initial evaluation. The impact of this experience on patient treatment decisions was analyzed. RESULTS: During the first year, a total of 182 patients were seen. Compared with previous years, low-risk MDC patients more frequently chose external beam radiation therapy (41.1% vs. 26.6%, P=0.02), and active surveillance (14.3% vs. 6.1%, P=0.02) and less frequently prostatectomy (30.4% vs. 44.0%, P=0.03). Similar increases in external beam were seen in intermediate and high-risk patients. Increased use of hormonal therapy was found in high-risk patients compared with the years before the initiation of the MDC (76.2% vs. 51.1%, P=0.03). Increased adherence to National Comprehensive Cancer Network (NCCN) guidelines was seen with intermediate-risk patients (89.8% vs. 75.9%, P=0.01), whereas nonsignificant increases were seen in low-risk (100% vs. 98.9%, P=0.43) and high-risk patients (100% vs. 94.2%, P=0.26). CONCLUSIONS: The establishment of a GU MDC improved the quality of care for cancer patients as demonstrated by improved adherence to National Comprehensive Cancer Network guidelines, and a broadening of treatment choices made available.

Phase I study of conformal radiotherapy and concurrent full-dose gemcitabine with erlotinib for unresected pancreatic cancer.

PURPOSE: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. METHODS AND MATERIALS: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m(2)) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. RESULTS: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. CONCLUSION: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Prognostic significance of neuroendocrine differentiation in patients with Gleason score 8-10 prostate cancer treated with primary radiotherapy.

PURPOSE: To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT). METHODS AND MATERIALS: Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints. RESULTS: Median follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (<1% n = 21, 1-10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED. CONCLUSIONS: For Gleason score 8-10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.

Vascular endothelial growth factor in the management of hepatocellular carcinoma: a review of literature.

The importance of tumor angiogenesis in tumor biology is now widely accepted. Hepatocellular carcinoma (HCC) is a highly vascular tumor, and angiogenesis is believed to play a considerable role in its development and progression. The authors reviewed the role of circulating vascular endothelial growth factor (VEGF) in screening for HCC and in risk stratification and treatment monitoring. They searched the world medical literature by accessing MEDLINE and PubMed for articles on: 1) the utility of circulating VEGF for HCC screening in patients with cirrhosis; 2) the role of circulating VEGF as a predictor of the invasive potential of HCC; and 3) monitoring anti-HCC treatment effects by serial measurements of circulating VEGF. They found evidence to support a potential role for VEGF in screening and surveillance of HCC. They also found support for developing the use of VEGF in the monitoring of treatment outcomes. Several studies suggested that the circulating VEGF level may be an independent prognostic marker in HCC. Further studies are needed to determine the utility of circulating VEGF in screening of patients with cirrhosis and to determine its potential role as a prognostic and predictive biomarker in patients with HCC. Cancer 2009. (c) 2009 American Cancer Society.