The following article features coverage from the Society of Gynecologic Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to results of a prospective study of circulating cell-free DNA sequencing performed on specimens that were collected at diagnosis and following surgery from women with newly diagnosed endometrial cancer, detection of tumor mutations in postsurgical specimens of cell-free DNA may be associated with a poor prognosis. These findings were accepted for presentation at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and released on March 28, 2020.

The aim of this study was to determine whether circulating cell-free DNA sequencing could detect tumor mutations in the setting of newly diagnosed endometrial cancer and, if so, whether the results were associated with tumor burden and/or the histologic subtype of endometrial cancer.

High-throughput DNA sequencing of tumor tissue specimens of primary endometrial cancer was performed using a testing platform of 468 cancer-related genes that was approved by the US Food and Drug Administration (FDA). Ultra-high–depth sequencing was also performed on matched specimens of cell-free DNA using a panel of 129 genes that were a subset of the 468 genes from the sequencing platform performed on tumor tissue. Cell-free DNA specimens were collected at diagnosis and following surgery. Presurgical tumor burden was evaluated using MRI.

Of the 44 patients with endometrial cancer enrolled in the study, sufficient cell-free DNA was collected preoperatively for only 29 patients. Interestingly, 15 of these patients had stage IA disease, and the remaining patients had disease classified as stage IIB (2 patients), stage III (10 patients), and stage IV (2 patients). In addition, there was a wide range of histological subtypes represented in this sample set, including endometrioid grade 1 (7 patients), endometrioid grade 2 to grade 3 (9 patients), serous (6 patients), clear cell (2 patients), undifferentiated (1 patient), carcinosarcoma (3 patients), and adenosarcoma (1 patient).


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Cell-free DNA sequencing of this presurgical subset of samples revealed a median of 10 nonsynonymous somatic mutations (ie, mutations that alter the protein amino acid sequence). One or more of these mutations was also observed in the primary tumor in 20%, 60%, and 100% of endometrial cancers classified as stage IA, stage III, and stage IV, respectively.

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Perhaps unsurprisingly, the likelihood of detection of a mutation in specimens of cell-free DNA was higher for patients with a higher tumor volume. In addition, mutations were less likely to be detected in preoperative cell-free DNA specimens from patients with endometrial cancer characterized by endometrioid compared with other histologies.

Postoperative cell-free DNA sequencing analyses were successfully performed for 25 of the 29 patients in the preoperative data set, although mutations were detected in the postoperative specimens of only 5 of these patients.

Notably, this subgroup of 5 patients had residual disease following surgery or disease recurrence within 1 year of primary therapy. In comparison, only 1 of the 20 patients without detectable mutations in postoperative cell-free DNA specimens experienced disease progression within 2 years.

In summarizing the findings from this study, the study authors stated that “mutation detection in cell-free DNA of endometrial cancer patients varies according to disease burden and tumor type, and may portend a poor outcome for patients if identified postsurgically.”

Read more of Cancer Therapy Advisor‘s coverage of SGO 2020 by visiting the conference page.

Reference

Ashley CW, Brown D, Lakhman Y, et al. Mutation detection in cell-free DNA using ultra-high depth sequencing in prospectively collected newly diagnosed endometrial cancer. Submitted to: Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer. Abstract LBA 2.