Search

Background: Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC). Methods: Cohort A comprised 120 consecutive patients with mRCC receiving subcutaneous, low-dose interleukin-2 and interferon-α. Hyponatremia was assessed in univariate and multivariate analyses. An independent cohort of another 120 patients with mRCC was used for validation (cohort B). Results: In cohort A, estimated 5-year survival was 15% and median survival was 15.1 months. Serum sodium ranged between 126 and 144 mM. Twenty-four patients (20%) had serum sodium levels below normal range (1.5 upper normal level (P=0.002), and number of metastatic sites (+3) (P=0.003). In cohort B, serum sodium ranged between 128 and 146 mM. Seventeen patients (14%) had sodium levels below normal range. In multivariate analysis, serum sodium was validated as an independent prognostic factor (P=0.001). A significant association between lack of response and hyponatremia was observed in both cohorts (P=0.003 and P=0.02, respectively). Conclusion: Low serum sodium is a new, validated, independent prognostic, and predictive factor in patients with mRCC.

PurposeWe have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC).Patients and MethodsThe study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated.ResultsThe intratumoral neutrophils ranged from zero to 289 cells/mm2tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX ≤ 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added.ConclusionThe presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.

Purpose: The administration of interleukin-2 (IL-2) may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, thus potentially compromising this treatment option for patients with metastatic renal cell carcinoma. The impact of IL-2–based therapy on the accumulation of FOXP3-positive immune cells in the tumor microenvironment in metastatic renal cell carcinoma is unknown. Experimental Design: Baseline (n = 58) and on-treatment (n = 42) tumor core biopsies were prospectively obtained from patients with clear cell metastatic renal cell carcinoma before and during IL-2–based immunotherapy. Immunohistochemical expression of FOXP3 was estimated by stereological counting technique and correlated with other immune cell subsets and overall survival. Results: A significant increase in absolute intratumoral FOXP3-positive immune cells was observed comparing baseline (median 23 cells/mm2; range, 0-183) and on-treatment biopsies (median, 89 cells/mm2; range, 11-388; P < 0.001). The relative increase in individual patients was median 4.7-fold, range 0.3 to 230. FOXP3-positive cells were positively correlated with CD3-positive, CD4-positive, and CD8-positive tumor-infiltrating immune cells at baseline and during treatment (P < 0.05 in all comparisons). All patients achieving high numbers (>180 cells/mm2) of on-treatment FOXP3-positive intratumoral immune cells were dead within 22 months (n = 11), whereas patients with low numbers ( Conclusion: Intratumoral FOXP3-positive regulatory immune cells significantly increased during IL-2–based immunotherapy, and high numbers of on-treatment FOXP3-positive cells were correlated with poor prognosis in patients with metastatic renal cell carcinoma.

Udgivelsesdato: 2008-Jun

4591 Background: IL-2 is potentially curative in a subset of patients with mRCC. We assessed our 10 years experience of outpatient subcutaneous IL-2 based immunotherapy at a single institution. Met...

5102 Background: Recently, low serum sodium has been associated with poor disease-free and overall survival in localized renal cell carcinoma (RCC) (Vasudev, Clin Can Res. 2008). The present study investigated the prognostic impact of serum-sodium values below normal in patients with metastatic RCC (mRCC). Methods: A cohort of 120 consecutive patients with mRCC received subcutaneous, low-dose Interleukin-2 and Interferon-α at Dept. of Oncology, Aarhus University Hospital, from 2002 to 2004 (Cohort A). Baseline variables were collected retrospectively. Follow up was at least 4 years. Potential prognostic factors were analyzed by univariate and multivariate analyses. Endpoint was overall survival. An independent cohort of 120 consecutive patients with mRCC was used for validation. These patients were treated with interleukin-2 based regimens at the same institution from 1999 to 2002 (Cohort B). Data in this cohort were prospectively collected. Results: In cohort A, the estimated 5-year survival rate was 15% and the median survival was 15.1 months. Serum-sodium ranged between 126 and 144 mmol/l. Twenty-four patients (20%) had serum-sodium levels below normal range (7) (HR 1.75, CI 1.1–2.8, p = 0.018), lactate dehydrogenase >1.5 upper normal level (HR 2.09, CI 1.3–3.3, p = 0.002), and number of sites (+3) (HR 1.92; CI 1.3–2.9, p = 0.003). In cohort B, the observed 5-year survival rate was 15% and the median survival was 15 months. Serum-sodium ranged between 128 mmol/l and 146 mmol/l. Seventeen patients (14%) had sodium levels below normal range. In the multivariate analysis, serum-sodium was validated as an independent prognostic factor (HR 2.98, CI 1.54–5.77, p = 0.001). Conclusions: Low serum-sodium is a new, validated, independent prognostic factor in patients with metastatic RCC. No significant financial relationships to disclose.

5096 Background: Interleukin-2 (IL-2) based therapy is currently the only curative treatment for patients with metastatic renal cell carcinoma (mRCC). However, administration of IL-2 increases the ...