In the Journals

Tissue biomarkers linked to shorter vascular leiomyosarcoma-specific survival

Beta-catenin and insulinlike growth factor 1 receptor appeared associated with poor disease-specific survival in patients with vascular leiomyosarcomas, according to retrospective study results published in JAMA Surgery.

Vascular leiomyosarcomas are rare, comprising approximately 5% of all leiomyosarcomas; however, these tumors are aggressive, and adjuvant treatments have not improved outcomes compared with surgery, according to study background.

Thus, Keila E. Torres, MD, PhD, assistant professor in the department of surgical oncology at The University of Texas MD Anderson Cancer Center, and colleagues sought to evaluate outcomes of patients with vascular leiomyosarcoma. Researchers also evaluated the association between vascular leiomyosarcomas and immunohistochemical molecular markers to determine their potential prognostic and therapeutic value.

Torres and colleagues conducted a retrospective medical review of 63 patients (median age at diagnosis, 58 years; range, 22-78) who presented at MD Anderson Cancer Center between January 1993 and April 2012. Treatment modalities included surgery alone (52%); surgery plus chemotherapy (21%); surgery plus radiation (14%); and surgery, chemotherapy and radiation (14%).

Median follow-up was 5.1 years (range, 0.87-13.9).

Sixty-five percent of patients achieved 5-year disease-specific survival (DSS).

Forty-two patients (66%) developed recurrent disease, with a median time to recurrence of 33 months. Local recurrence occurred in six patients after a median of 43 months, and distant recurrence occurred in 16 patients after a median of 25 months.

The 20 patients who presented with synchronous local and distal disease demonstrated a shorter median time to recurrence (15 months; P = .04).

The most frequent sites of distant metastases included the lung (42%), liver (31%), bone (22%), abdomen (17%) and other sites, including the brain and soft tissue (19%).

Univariate analyses of patient, tumor and treatment characteristics did not demonstrate any significant associations with DSS; however, treatment with surgery plus radiation demonstrated a trend toward improved survival (HR = 0.43; 95% CI, 0.19-1.01).

Further, immunohistochemical analyses for biomarkers on a tissue microarray of 26 primary vascular leiomyosarcoma specimens showed poorer DSS appeared associated with higher expression of cytoplasmic beta-catenin (HR = 5.33; 95% CI, 0.97-29.3) and insulinlike growth factor 1 receptor (HR = 2.74; 95% CI, 1.14-6.56).

Study limitations included the small sample size, retrospective design, long interval and variability of treatment modalities received by the patients, according to Torres and colleagues.

“Although we were unable to find significance in many treatment variables, likely owing to the disease’s heterogeneity, we did find correlation between the proteins beta-catenin and insulinlike growth factor 1 receptor and worse outcomes, which suggests further avenues of investigation into the biology of the disease and targeted therapy,” the researchers wrote.

In an accompanying editorial, Eric K. Nakakura, MD, PhD, associate professor of surgery at University of California, San Francisco, wrote that these study findings may have implications for other sarcoma subtypes.

“Leiomyosarcomas arising from various vessels may share key signaling pathways that drive other forms of cancer,” Nakakura wrote. “As new therapies targeting these signaling pathways are developed, there is the hope of improving the outcome of patients with cancer, including those patients with extremely rare types of cancer that share these molecular alterations.” – by Cameron Kelsall

Disclosure: The researchers and Nakakura report no relevant financial disclosures.

Beta-catenin and insulinlike growth factor 1 receptor appeared associated with poor disease-specific survival in patients with vascular leiomyosarcomas, according to retrospective study results published in JAMA Surgery.

Vascular leiomyosarcomas are rare, comprising approximately 5% of all leiomyosarcomas; however, these tumors are aggressive, and adjuvant treatments have not improved outcomes compared with surgery, according to study background.

Thus, Keila E. Torres, MD, PhD, assistant professor in the department of surgical oncology at The University of Texas MD Anderson Cancer Center, and colleagues sought to evaluate outcomes of patients with vascular leiomyosarcoma. Researchers also evaluated the association between vascular leiomyosarcomas and immunohistochemical molecular markers to determine their potential prognostic and therapeutic value.

Torres and colleagues conducted a retrospective medical review of 63 patients (median age at diagnosis, 58 years; range, 22-78) who presented at MD Anderson Cancer Center between January 1993 and April 2012. Treatment modalities included surgery alone (52%); surgery plus chemotherapy (21%); surgery plus radiation (14%); and surgery, chemotherapy and radiation (14%).

Median follow-up was 5.1 years (range, 0.87-13.9).

Sixty-five percent of patients achieved 5-year disease-specific survival (DSS).

Forty-two patients (66%) developed recurrent disease, with a median time to recurrence of 33 months. Local recurrence occurred in six patients after a median of 43 months, and distant recurrence occurred in 16 patients after a median of 25 months.

The 20 patients who presented with synchronous local and distal disease demonstrated a shorter median time to recurrence (15 months; P = .04).

The most frequent sites of distant metastases included the lung (42%), liver (31%), bone (22%), abdomen (17%) and other sites, including the brain and soft tissue (19%).

Univariate analyses of patient, tumor and treatment characteristics did not demonstrate any significant associations with DSS; however, treatment with surgery plus radiation demonstrated a trend toward improved survival (HR = 0.43; 95% CI, 0.19-1.01).

Further, immunohistochemical analyses for biomarkers on a tissue microarray of 26 primary vascular leiomyosarcoma specimens showed poorer DSS appeared associated with higher expression of cytoplasmic beta-catenin (HR = 5.33; 95% CI, 0.97-29.3) and insulinlike growth factor 1 receptor (HR = 2.74; 95% CI, 1.14-6.56).

Study limitations included the small sample size, retrospective design, long interval and variability of treatment modalities received by the patients, according to Torres and colleagues.

“Although we were unable to find significance in many treatment variables, likely owing to the disease’s heterogeneity, we did find correlation between the proteins beta-catenin and insulinlike growth factor 1 receptor and worse outcomes, which suggests further avenues of investigation into the biology of the disease and targeted therapy,” the researchers wrote.

In an accompanying editorial, Eric K. Nakakura, MD, PhD, associate professor of surgery at University of California, San Francisco, wrote that these study findings may have implications for other sarcoma subtypes.

“Leiomyosarcomas arising from various vessels may share key signaling pathways that drive other forms of cancer,” Nakakura wrote. “As new therapies targeting these signaling pathways are developed, there is the hope of improving the outcome of patients with cancer, including those patients with extremely rare types of cancer that share these molecular alterations.” – by Cameron Kelsall

Disclosure: The researchers and Nakakura report no relevant financial disclosures.