Multi-institutional validation of a new renal cancer-specific survival nomogram

PURPOSE: We tested the hypothesis that the prediction of renal cancer-specific survival can be improved if traditional predictor variables are used within a prognostic nomogram. PATIENTS AND METHODS: Two cohorts of patients treated with either radical or partial nephrectomy for renal cortical tumors were used: one (n = 2,530) for nomogram development and for internal validation (200 bootstrap resamples), and a second (n = 1,422) for external validation. Cox proportional hazards regression analyses modeled the 2002 TNM stages, tumor size, Fuhrman grade, histologic subtype, local symptoms, age, and sex. The accuracy of the nomogram was compared with an established staging scheme. RESULTS: Cancer-specific mortality was observed in 598 (23.6%) patients, whereas 200 (7.9%) died as a result of other causes. Follow-up ranged from 0.1 to 286 months (median, 38.8 months). External validation of the nomogram at 1, 2, 5, and 10 years after nephrectomy revealed predictive accuracy of 87.8%, 89.2%, 86.7%, and 88.8%, respectively. Conversely, the alternative staging scheme predicting at 2 and 5 years was less accurate, as evidenced by 86.1% (P = .006) and 83.9% (P = .02) estimates. CONCLUSION: The new nomogram is more contemporary, provides predictions that reach further in time and, compared with its alternative, which predicts at 2 and 5 years, generates 3.1% and 2.8% more accurate predictions, respectively.     

Anti-vascular endothelial growth factor receptor-1 antagonist antibody as a therapeutic agent for cancer.

PURPOSE: Vascular endothelial growth factor receptor-1 (VEGFR-1) plays important roles in promotion of tumor growth by mediating cellular functions in tumor vascular endothelium and cancer cells. Blockade of VEGFR-1 activation has been shown to inhibit pathologic angiogenesis and tumor growth, implicating VEGFR-1 as a potential therapeutic target for the treatment of cancer. We have thus developed a VEGFR-1 antagonist human monoclonal antibody designated as IMC-18F1 and evaluated its antitumor activity in preclinical experimental models to show the therapeutic potential of the antibody for cancer treatment in clinic. EXPERIMENTAL DESIGN: Human IgG transgenic mice were used for generation of anti-VEGFR-1 antibodies. Anti-VEGFR-1-specific blocking antibodies were identified using solid-phase binding and blocking assays. Inhibitory antitumor cell activity of IMC-18F1 was assessed in cell-based kinase and growth assays. Pharmacokinetic/pharmacodynamic studies were done to determine the association of antibody blood level with antitumor efficacy of the antibody in vivo. Antitumor efficacy of the anti-VEGFR-1 antibodies as monotherapy and in combination with cytotoxic agents was evaluated in human breast cancer xenograft models. RESULTS: A fully human neutralizing antibody, IMC-18F1, was shown to be a high-affinity (KD=54 pmol) inhibitor of VEGFR-1 ligand binding (VEGF-A, VEGF-B, and placental growth factor). IMC-18F1 inhibited ligand-induced intracellular activation of VEGFR-1 and mitogen-activated protein kinase signaling and prevented ligand-stimulated in vitro growth of breast cancer cells. In vivo, IMC-18F1 suppressed the growth of human breast tumor xenografts in association with reduced mitogen-activated protein kinase and Akt activation, reduced tumor cell proliferation, and increased tumor cell apoptosis. Pharmacokinetic/pharmacodynamic studies established a plasma elimination half-life of 5 days for IMC-18F1 and a steady-state trough plasma therapeutic threshold of 88 microg/mL. Importantly, inhibition of mouse and human VEGFR-1 with MF1 and IMC-18F1, respectively, enhanced the antitumor efficacy of cytotoxic agents commonly used to treat breast cancer. CONCLUSIONS: Based on preclinical validation studies, IMC-18F1 anti-VEGFR-1 has potential to provide clinical benefit to cancer patients.     

Early spontaneous regression of a hypothalamic/chiasmatic mass in neurofibromatosis type 1: MR findings

A patient with neurofibromatosis type 1 was found to have an enhancing mass in the hypothalamus and in the anterior optic pathway. A 3-month MR study showed a reduction in the size and enhancement of the mass. At a 9-month MR follow-up the mass disappeared and ceased to enhance. This report shows the unusual behaviour of a hypothalamic/chiasmatic mass confirming that in such asymptomatic cases the conservative management can be considered the treatment of choice. Received: 27 July 1999; Revised: 20 October 1999; Accepted: 19 November 1999     

Clinical evolution of chronic pancreatitis and quality of life

Nowadays the availability of reliable, efficacious methods of assessing the outcome of chronic pancreatitis is mandatory, especially in view of the several new procedures developed to relieve the symptoms of the disease. Together with the traditional evaluation of postoperative morbidity and mortality and the assessment of exo/endocrine function in patient follow-up, we currently consider the patient's perception of his or her health status as a priority. This information is obtained by administering quality of life questionnaires along with reliable physical and psychometric evaluation.     

Basal and forskolin-stimulated cyclic adenosine monophosphate in intact human platelets during the menstrual cycle

In previous studies we observed modifications of cyclic adenosine monophosphate and adenylate cyclase activity in human endometrium during the menstrual cycle. In the present study our intension was to verify whether these modifications occur in isolated intact platelets. The results demonstrate that in nine normal women platelet cyclic adenosine monophosphate content varies during the menstrual cycle both in basal and in stimulated conditions (in vitro addition of forskolin). In fact, significantly higher levels of cyclic adenosine monophosphate were consistently observed during the proliferative phase. These findings provide evidence that platelet cyclic adenosine monophosphate metabolism normally varies during the menstrual cycle, which suggests a possible involvement of this system in some important clinical events.     

Prognostic factors in renal cell carcinoma

In order to evaluate the prognostic factors of renal cell carcinoma (RCC), a retrospective study was carried out on 215 patients (150 men, 65 women) who had undergone surgical treatment from March 1979 to December 1986. The average age of the patients was 58 years (ranging from 15 to 85 years). The ratios of survival to tumor stage and grade, as well as to nodal and venous involvement, distant metastases at the time of diagnosis (as TNM classification) were evaluated by means of the actuarial method (life table). Corrected 5-year survival rates for stage T1-T4 were 100, 81, 68.9 and 0%, respectively. Grade 1 and grade 2 tumors had a 5-year survival rate of 66.5 and 52.8%, respectively; grade 3 had a 3-year survival rate of 46.5%. Nodal involvement at the time of diagnosis had a prediction value for the 3- and 5-year survival rate of 39.8 and 34.5%, respectively. Metastases at time of diagnosis had a 14.1% prediction value for a 3-year survival rate. Tumor extension to the vena cava (21 patients) affected survival in a significant way (55.8% at 3 years). A definite tendency towards lower stage and grade was observed in incidentally diagnosed RCC (11%). In conclusion, stage, grade, nodal and venous involvement as well as metastases at the time of diagnosis have a significant prognostic value in RCC. These data and the lack of early diagnostic methods for RCC suggest the routine use of renal ultrasonography in clinically asymptomatic patients during examination for suspected abdominal diseases and in high-risk patients (Von Hippel-Lindau disease smokers).