From the Journals

VTE risk may be high throughout disease course in uterine serous carcinoma

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Not yet time for prolonged thromboprophylaxis, but vigilance warranted

It has been reported in previous literature that the risk of developing VTE is typically within 48 hours of surgical staging, and guidelines have focused on risk factors to identify patients needing extended thromboprophylaxis after surgery. Therefore, Gressel et al. set forth to identify risk factors and timing of development of VTE in women with uterine serous carcinoma.

The study retrospectively evaluated 413 women with uterine serous cancer from 1999 to 2016. Of these, 70 women (about 17%) were diagnosed with a VTE. There was not a statistically significant association between age, body mass index, race, or surgical approach with risk of VTE. However, stage and/or having two or more medical comorbidities were significant. Compared with stage I patients, stage III and IV patients had a 2.6- and fourfold increase in risk, respectively. Not surprisingly, hypertension and cardiovascular disease (CVD) were independently associated with risk of VTE development; odds ratio 2.97 and 1.87, respectively. Interestingly, in the women diagnosed with VTE, 84% were outside the 6-week postoperative period and 31% occurred during chemotherapy treatment. The median time to develop VTE was 13.2 months and occurred sooner in women with advanced stage.

In this study, the majority of patients developed a VTE outside of the standard 28-day thromboprophylaxis window. This finding suggests that there is a subset of patients who would benefit from longer duration of thromboprophylaxis. Perhaps patients with hypertension, CVD, and/or advanced stage malignancy would benefit from thromboprophylaxis throughout their treatment.

Dr. Antonio Castaneda, a gynecologic oncology fellow at The Ohio State University in Columbus

Dr. Antonio Castaneda


Based on the data presented, at this time, we cannot recommend treating patients with the above risk factors during the entirety of their care. Although further studies and even a nomogram may help determine who is likely to benefit from prolonged prophylaxis, it is unknown if doing so would result in significant decreased morbidity or increased adverse events (e.g. bleeding, thrombocytopenia). However, this should remain a topic for further evaluation and providers should remain vigilant for prevention and diagnosis of VTE in at-risk patients by adhering to validated risk assessment tools and clinical evaluation.

Antonio Castaneda, MD, is a gynecologic oncology fellow at The Ohio State University in Columbus. He said he had no relevant financial disclosures.


 

FROM OBSTETRICS & GYNECOLOGY

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

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