Homing in on vascular cell adhesion molecule-1 (VCAM-1) expression in metastatic ovarian cancer with SPECT could gauge response to therapy and potentially improve survival, according to a study published Sept. 12 in the Journal of Nuclear Medicine.
Survival rates of ovarian cancer, currently the deadliest gynecologic cancer, are a dismal 30 to 40 percent at the five-year mark. However, this is mostly due to the advanced stage of the cancer upon diagnosis. Inhibition of VCAM-1 expression through chemotherapy has been shown to decrease tumor burden and improve prognosis. Jennifer M. Scalici, MD, from the department of Obstetrics and Gynecology, University of Virginia in Charlottesville, Va., and colleagues evaluated VCAM-1 targeted SPECT/CT as a biomarker for response to standard platinum chemotherapy.
“Although extensive retrospective data support aggressive surgery as important in improving overall survival, some will present with disease that is not resectable (e.g., intraparenchymal liver metastases) or will be too medically ill to undergo surgery safely, without significant morbidity,” wrote Scalici et al. “In these cases, neoadjuvant chemotherapy has been shown to allow optimal cytoreduction without significant morbidity. Unfortunately, as many as 20 percent of women in either scenario (i.e., upfront surgery or neoadjuvant chemotherapy) will not achieve first remission, and some will experience disease progression during primary therapy. Up to 90 percent of women who entered remission will experience recurrence through a process that is poorly understood and succumb to platinum-resistant disease within 2–3 years.”
In order to understand the relationship between VCAM-1 expression and disease progression, researchers combined retrospective immunohistological evaluations from 58 biopsied women with varying stages of metastatic ovarian cancer and prospective therapy response imaging in both preclinical mouse studies and in women with metastatic ovarian cancer. Results from the retrospective review showed a significant correlation between tumor stage and VCAM-1 expression in peritoneal metastases. Immunohistochemistry results were negative for VCAM-1 expression in stage 1 tumors, but 29 percent positive for stage II and 73 percent positive for stage III tumors, which showed promise for better staging and selection for chemotherapy. Additionally, another set of 32 patients underwent SPECT imaging to evaluate VCAM-1 expression and response to therapy. Findings revealed that 15 percent of women exhibited VCAM-1 expression following chemotherapy versus 72 percent of women who had only undergone surgery.
“Together, these observations indicate that in addition to the presence of VCAM-1 at the earliest stages of peritoneal spread (i.e., stage II patients with secondary implants), expression is responsive to treatment,” wrote the authors. “This observation implies that VCAM-1 is regulated directly by platinum agents. Alternatively, because neoadjuvant chemotherapy is provided to reduce tumor burden, its effect on VCAM-1 expression might not be direct but rather a result of the loss of tumor, thus offering the tantalizing hypothesis that VCAM-1 could be used to reflect tumor burden and identify patients responding to platinum-based treatment.”
The mirroring of tumor response to therapy and VCAM-1 expression could lead to improved selection and therapy monitoring and potentially overall survival, but further studies are needed to confirm VCAM-1 expression as a marker of metastatic disease and potential response to platinum chemotherapy.