Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with malignant oral tumors after definitive megavoltage irradiation, to analyze prognostic factors for PFS time and patterns of failure, and to analyze the influence of tumor recurrence and development of metastasis on survival. DESIGN: Prospective clinical trial. ANIMALS: 105 dogs with squamous cell carcinoma, fibrosarcoma, or malignant melanoma of the oral cavity without evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's regression model to determine significant prognostic factors and by use of a competing risk model to determine the differential effects of prognostic factors on type of, and time to, failure. In 8% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 7.6% of the dogs, chronic radiation reactions, including bone necrosis and fistula formation, developed. RESULTS: Prognostic factors that independently affected PFS time were histologic type and tumor T stage. Histologic type significantly influenced pattern of failure, but not time to failure, whereas clinical stage significantly influenced time to failure, but not type of failure. CLINICAL IMPLICATIONS: Irradiation was a safe and effective treatment of malignant oral tumors. Because the local efficacy of radiation was influenced only by tumor size, early treatment of oral tumors should improve the prognosis. In dogs without tumor recurrence, systemic metastases, rather than regional metastases, limited long-term survival after radiation therapy.     

Lymph node involvement and tumor depth in rectal cancers: an analysis of 805 patients

BACKGROUND: Superficial rectal tumors are said to involve regional lymph nodes rarely. This presumption must be proven beyond any doubt if less radical surgery is to be offered for such patients. PATIENTS AND METHODS: Eight hundred five cases (467 males; median age, 64 (range, 19-97) years) of rectal cancer were reviewed. RESULTS: Lymph node positivity, number of lymph nodes involved, lymphatic vessel, and venous and perineural invasion were significantly increased with increasing depth of invasion of tumor through the bowel wall in univariate analysis. The percentage of lymph node involvement at each tumor depth was as follows: T1, 5.7 percent; T2, 19.6 percent; T3, 65.7 percent; T4, 78.8 percent. Overall lymph node involvement was 59 percent. For patients younger than 45 years of age, the percentage of lymph node involvement was 33.3, 30, 69.3, and 83.3 percent compared with 3.1, 8.4, 64.2, and 78.8 percent for patients aged 45 years or above for T1, T2, T3, and T4, respectively. CONCLUSION: Increased depths of tumor penetration beyond T1 and age less than 45 years have an excessive incidence of lymph node positivity. The finding of lymphatic vessel invasion on biopsy is highly indicative of lymph node metastasis.     

Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue

Patients with chemotherapy-refractory gestational trophoblastic disease and brain metastasis are considered to have a very poor prognosis. We present the case of a patient who had failed several chemotherapeutic regimens. Despite transient responses to chemotherapy, she had not achieved a complete remission in 3 years, and had developed systemic disease and recurrent brain metastasis. She was treated with four cycles of high-dose ifosfamide, carboplatin, and etoposide with blood progenitor cell support. She tolerated this regimen well and has obtained a complete remission that is ongoing for 12 months.     

Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a cytokine of central importance for the angiogenesis associated with cancers and other pathologies. Because angiogenesis often involves endothelial cell (EC) migration and proliferation within a collagen-rich extracellular matrix, we investigated the possibility that VEGF promotes neovascularization through regulation of collagen receptor expression. VEGF induced a 5- to 7-fold increase in dermal microvascular EC surface protein expression of two collagen receptors-the alpha1beta1 and alpha2beta1 integrins-through induction of mRNAs encoding the alpha1 and alpha2 subunits. In contrast, VEGF did not induce increased expression of the alpha3beta1 integrin, which also has been implicated in collagen binding. Integrin alpha1-blocking and alpha2-blocking antibodies (Ab) each partially inhibited attachment of microvascular EC to collagen I, and alpha1-blocking Ab also inhibited attachment to collagen IV and laminin-1. Induction of alpha1beta1 and alpha2beta1 expression by VEGF promoted cell spreading on collagen I gels which was abolished by a combination of alpha1-blocking and alpha2-blocking Abs. In vivo, a combination of alpha1-blocking and alpha2-blocking Abs markedly inhibited VEGF-driven angiogenesis; average cross-sectional area of individual new blood vessels was reduced 90% and average total new vascular area was reduced 82% without detectable effects on the pre-existing vasculature. These data indicate that induction of alpha1beta1 and alpha2beta1 expression by EC is an important mechanism by which VEGF promotes angiogenesis and that alpha1beta1 and alpha2beta1 antagonists may prove effective in inhibiting VEGF-driven angiogenesis in cancers and other important pathologies.     

An analysis of test bias and differential item functioning due to race on the Mattis Dementia Rating Scale

The Mattis Dementia Rating Scale (MDRS) is a commonly used cognitive measure designed to assess the course of decline in progressive dementias. However, little information is available about possible systematic racial bias on the items presented in this test. We investigated race as a potential source of test bias and differential item functioning in 40 pairs of African American and Caucasian dementia patients (N = 80), matched on age, education, and gender. Principal component analysis revealed similar patterns and magnitudes across component loadings for each racial group, indicating no clear evidence of test bias on account of race. Results of an item analysis of the MDRS revealed differential item functioning across groups on only 4 of 36 items, which may potentially be dropped to produce a modified MDRS that may be less sensitive to cultural factors. Given the absence of test bias because of race, the observed racial differences on the total MDRS score are most likely associated with group differences in dementia severity. We conclude that the MDRS shows no appreciable evidence of test bias and minimal differential item functioning (item bias) because of race, suggesting that the MDRS may be used in both African American and Caucasian dementia patients to assess dementia severity.