Taking into account the potential biases of retrospective studies in evaluating the prognostic relevance of a new marker, the value of determination of intratumoral microvessel density seems to be different among the diverse tumor types. An attempt at classification is proposed, as follows:
Furthermore, the two studies on vascularity and prognosis conducted in children with brain tumors (141) or adults (142) found a significant correlation between microvessel count and clinical outcome. S imilarly, the few studies performed until now on angiogen-esis in bone marrow or lymph nodes of patients with hematologic malignancies were positive.
Prior to suggesting prospective clinical trials, more information from well-designed and large retrospective studies are needed to better identify the tumor types and subgroups of patients in whom the prognostic value of angiogenesis is more promising.
The data summarized in Table 3 suggest that the patients with high-risk, operable breast cancer, with highly vascularized tumors, do not benefit from conventional adjuvant hormone or chemotherapeutic treatments. However, a proper evaluation of the predictive capability of a marker needs a prospective controlled, randomized comparative study of therapy vs no therapy. Such a study design may also identify the subgroup of patients who do not benefit from conventional anticancer therapy, for whom novel therapeutic approaches, such as inhibition of angiogenesis, may be useful.
The studies by Hollingsworth et al. (123) and Gasparini et al. (124), on vascularization of patients with advanced stages of ovarian cancer suggest that highly vascularized ovarian cancers are poorly responsive to platinum-based combined chemotherapy. Similar findings were reported also for patients with highly vascularized squamous cell carcinomas of the head and neck treated with concurrent chemoradiation therapy (120). In addition, Vacca et al. found that the patients with active or recurrent or progressive multiple myeloma treated with chemotherapy had a significantly higher degree of angiogenesis in the bone marrow, compared to those with nonactive or responsive disease.
Once antiangiogenic compounds become suitable for phase II-III clinical trials, the search for surrogate markers of responsiveness to the pharmacological modulation of angiogenesis will then be another area of translational research of clinical importance, allowing for a more rationale therapeutic approach.
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