Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.

BACKGROUND: Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity. METHODS AND RESULTS: We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity. CONCLUSIONS: Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.

Prevention of Atrial Fibrillation in High-risk Patients Undergoing Lung Cancer Surgery: The PRESAGE Trial.

OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24 hours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation.

Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial.

Patients with newly resected stage II melanoma (n = 104) were randomized to receive adjuvant vitamin D3 (100,000 IU every 50 days) or placebo for 3 years to investigate vitamin D3 protective effects on developing a recurrent disease. Median age at diagnosis was 50 years, and 43% of the patients were female. Median serum 25-hydroxy vitamin D (25OHD) level at baseline was 18 ng/mL, interquartile range (IQ) was 13-24 ng/mL, and 80% of the patients had insufficient vitamin D levels. We observed pronounced increases in 25OHD levels after 4 months in the active arm (median 32.9 ng/mL; IQ range 25.9-38.4) against placebo (median 19.05 ng/mL; IQ range 13.0-25.9), constantly rising during treatment. Remarkably, patients with low Breslow score (<3 mm) had a double increase in 25OHD levels from baseline, whereas patients with Breslow score ≥3 mm had a significantly lower increase over time. After 12 months, subjects with low 25OHD levels and Breslow score ≥3 mm had shorter disease-free survival (p = 0.02) compared to those with Breslow score <3 mm and/or high levels of 25OHD. Adjusting for age and treatment arm, the hazard ratio for relapse was 4.81 (95% CI: 1.44-16.09, p = 0.011). Despite the evidence of a role of 25OHD in melanoma prognosis, larger trials with vitamin D supplementation involving subjects with melanoma are needed.

Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach.

Electroporation uses pulsed, high-intensity electric fields to temporarily increase cell membrane permeability by creation of pores, through which small molecules, such as chemotherapeutic agents, can diffuse inside cells before they reseal. The combination of electroporation with the administration of otherwise low-permeant cytotoxic drugs is known as electrochemotherapy (ECT). The two most commonly used drugs are bleomycin and cisplatin. ECT has already been proven to be effective in diverse tumor histotypes, including melanoma and basal and squamous cell carcinoma, Kaposi sarcoma, and breast cancer, also in those cases nonresponding to classical chemotherapies or other loco-regional treatment modalities, with a good safety profile. ECT can be proposed as loco-regional therapy for disseminated cutaneous and subcutaneous tumor lesions as alternative treatment modality to conventional therapies or as palliative care, in order to improve patients' quality of life.

Pulsed dose-rate perioperative interstitial brachytherapy for soft tissue sarcomas of the extremities and skeletal muscles of the trunk.

BACKGROUND: This study evaluated the role of pulsed dose-rate (PDR) brachytherapy (BRT), delivered alone or as a boost to external beam radiotherapy, as adjuvant therapy for the local control of soft tissue sarcomas of the extremities and skeletal muscles of the trunk that have undergone surgical treatment. METHODS: Between July 1998 and January 2002, 42 patients were treated with a combination of surgery and BRT alone (18 patients) or BRT/external beam radiotherapy (24 patients) for the treatment of primary (n = 32) and recurrent (n = 10) soft tissue sarcomas located in the proximal extremity (n = 17), distal extremity (n = 17), and trunk (n = 8). Tumor size was <5 cm in 20 cases and >5 cm in 22 cases, with histological grading of 1 (n = 7), 2 (n = 18), or 3 (n = 17). The median BRT dose delivered was 15 Gy, and the median external beam irradiation dose was 50 Gy. RESULTS: With a median follow-up of 34 months, the 36-month survival was 83.9% (SE, 6.1%), and the local control was 89%. CONCLUSIONS: PDR interstitial BRT for soft tissue sarcoma is an effective, well-tolerated adjuvant radiation treatment that offers several practical advantages, among which are low acute and late toxicity with maximum normal tissue and critical structure sparing and overall shorter radiotherapy and hospital stay.