Cryoablation of renal tumors: long-term follow-up from a multicenter experience.

PURPOSE: To retrospectively investigate long-term outcomes of renal cryoablation from a multicenter database. METHODS: 338 patients with 363 renal tumors underwent cryoablation in 4 centers in North-Eastern Italy. 340/363 tumors (93.7%) were percutaneously treated with CT guidance. 234 (68.8%) were treated after conscious sedation, 76 (22.3%) under local lidocaine anesthesia only and 30 (8.8%) under general anesthesia. Treatment efficacy and complication rate considered all procedures. Oncologic outcomes considered a subset of 159 patients with 159 biopsy proven renal cell carcinoma. RESULTS: Mean tumor size was 2.53 cm. Technical success was achieved in 355/363 (97.8%) treatments. Treatment efficacy after the first treatment was achieved in 348/363 (95.9%) tumors. Statistical analysis revealed a significant lower treatment efficacy for ASA score >3, Padua score >8, tumor size >2.5 cm, use of >2 cryoprobes, presence of one single kidney. In the subset of 159 patients, recurrence-free survival rates were 90.5% (95% CI 83.0%, 94.9%) at 3 years and 82.4% (95% CI 72.0%, 89.4%) at 5 years; overall survival rates were 96.0% (95% CI 90.6%, 98.3%) at 3 years and 91.0% (95% CI 81.7%, 95.7%) at 5 years; no patient in this subset developed metastatic disease. Clavien-Dindo >1 complications were recorded in 14/369 procedures (3.8%) and were related to age >70 years, tumor size >4 cm and use of >2 cryoprobes. CONCLUSION: Cryoablation performed across four different centers in a large cohort of predominantly small renal tumors showed that this technique provides good recurrence-free survival rates and overall survival rates at three- and five-year with very low major complications rate.

Interleukin-2 chronotherapy for metastatic renal cell carcinoma: Results of a phase I-II study.

BACKGROUND: Interleukin-2 (IL-2) was the cornerstone treatment for metastatic renal cell carcinoma (RCC) until the advent of tyrosine kinase inhibitors, but it still has therapeutic value. As a single bolus of IL-2 causes toxicity, there is interest in administration regimens with better tolerability and efficacy. Chronotherapy is the administration of therapy according to the circadian rhythm's influence on the immune and hormonal systems. This phase I-II trial evaluated the safety of IL-2 chronotherapy in metastatic RCC patients and determined the maximum tolerated dose. The secondary objective was to identify prognostic factors for survival. METHODS: Three chronomodulation schedules (5:00-13:00, 13:00-21:00, and 21:00-5:00) were tested. Each schedule was an 8-h IL-2 infusion, with a Gaussian distribution of drug concentration peaking at 4 h. To identify the maximum tolerated dose, the dose for different patients was escalated from 2 MIU/m2 (level I) to 18.6 MIU/m2 (level VI). RESULTS: Thirty patients were enrolled and completed treatment. Two patients were treated at 5:00-13:00, 15 at 13:00-21:00, and 13 at 21:00-5:00. Nine cases of grade 3 toxicity occurred in 7 patients at the highest dose (18.6 MIU/m2); no grade 4 toxicity occurred. The maximum tolerated dose was 14.0 MUI/m2. Patients were followed for a median of 16 months (range, 2-107). One patient was lost to follow-up, 3 patients were alive at last contact, and 26 patients died. Six patients achieved long-term survival (≥48 months). There was one complete response, four partial responses, 11 cases of stable disease and 14 of progressive disease. The response rate was 16% (5/30) and disease-control rate was 53% (16/30). Median progression-free survival was 4.5 months, and median overall survival was 14.5 months. Kaplan-Meier analyses revealed significant associations between overall survival and ECOG performance score (0 vs. 1-2), MSKCC score (0-2 vs. ≥ 3), IMDC risk score (0-2 vs. ≥ 3), IL-2 dose level (IV-VI vs. I-III), and prolactin (increase vs. no increase), and but not for chronotherapy schedule. CONCLUSION: IL-2 chronotherapy appears to be safe, moderately toxic and active in metastatic RCC. It may represent a new modality of IL-2 administration for these patients.

Dietary vitamins E and C and prostate cancer risk.

BACKGROUND: The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer. MATERIAL AND METHODS: Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors. RESULTS: Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer. DISCUSSION: The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.