1. Wiley, Frieda

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Dexamethasone exhibits antileukemic properties in patients who have acute myeloid leukemia and prolongs survival, according to a new study. The corticosteroid's most notable indications in cancer treatment make this finding important. Historically a mainstay in oncology as prophylaxis for nausea and chemotherapy-induced emetogenesis, dexamethasone demonstrated an ability to suppress/decrease tumor growth in cancerous cells of the pancreas, breast, and lung by apparently modulating inflammatory chemoresistant pathways. New data indicate that adjuvant administration of dexamethasone can improve survival in patients underdoing surgery.

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The desire to explore additional potential indications and benefits of dexamethasone happened somewhat serendipitously, and the study's authors use the findings from other research to inform their current work.


"In addition to the in vitro observations, there were previous retrospective studies that reported survival benefits of intraoperative dexamethasone administration in patients undergoing surgery for pancreatic cancer," said Maximilian Schaefer, MD, PhD, Director of the Center for Anesthesia Research Excellence at Beth Israel Deaconess Medical Center in Boston. "These findings encouraged us to look into a broader and diverse patient sample with different cancers."


In a retrospective study, researchers included 74,058 patients who underwent surgery to excise solid malignancies from 2005 and 2020 at Beth Israel Medical Center and from 2007 to 2015 at Massachusetts General Hospital in Boston. Intraoperative exposure to dexamethasone served as the primary exposure, while researchers deemed mortality 90 days post-operation as the primary outcome.


Patients averaged 63+/-13 years of age in the no dexamethasone arm and 56+/-13 in the interventional arm. Nearly half of the patients who did not receive dexamethasone were male (46.4%, n=22,696), while slightly more than a quarter in the dexamethasone arm (25.7%, n=6,465) were male. Both groups had similar body mass indices, 27.78+/-6.39 and 27.63+/-6.37, respectively.


Similarly, both arms had near-equal values for the Charlson Comorbidity Index: 2(2,6) for the no dexamethasone arm and 2(2,3) for the dexamethasone arm. Only 1.3 percent (n=639) in the no dexamethasone arm and 0.7 percent (n=165) in the dexamethasone arm had a history of drug abuse. Nearly 13 percent (12.7%, n=6,199) of patients in the dexamethasone arm and 7.5 percent (1,680) in the dexamethasone arm had a history of smoking. Hypertension proved a greater issue in both arms, with 19,557 patients (40.0%) in the no dexamethasone arm and 6,324 (25.1%) in the dexamethasone arm had hypertension. Less than 2 percent of patients in both arms received preoperative chemotherapy.


Slightly more than one-third (34.0, n=25,178/74,058) of patients subjected to surgery were administered dexamethasone intraoperatively (mean dose [SD] 7.0 [+/-2.4] mg).


Less than 1 percent (0.83% n=209/25,017) of the patients who received dexamethasone intraoperatively died within the 90-day period following surgery. The mortality for patients not administered intraoperative dexamethasone was more than 3-fold that of the patients who received intraoperative dexamethasone (3.2% n=1,543/48,880). The data also indicated that dexamethasone administration intraoperatively reduced the risk of 90-day mortality in patients with acute myeloid leukemia (aOR 0.68; 95% CI: 0.57-0.81; pv0.001).


Both groups had marked intraoperative differences. For example, surgeries in the dexamethasone arm lasted more than 33 percent longer on average (152/99,243) than it did for the no dexamethasone group (95/56,175). Moreover, a greater percentage of people in the interventional arm required anesthesia (n=23,995; 95.3%) than in the nontreatment arm (n=32,323; 66.1%). Patients in the dexamethasone arm also had higher fluid requirements (1,100 mL [800, 1,900] versus 800 mL [500, 1,300]) in the no dexamethasone arm.


In addition, subgroup analyses of the data indicate intraoperative intervention may also improve outcomes in patients who have other cancers. These include breast cancer (aOR: 0.22; 95% CI: 0.11-0.45; p<0/011), and reproductive cancers affecting the ovary, uterus, and cervix (aOR: 0/33; 95% CI: 0.16-0.66; P=0.002).


"Our findings suggest that a cheap, common intervention such as the administration of dexamethasone, which is typically given for prophylaxis of nausea and vomiting after anesthesia, may have an effect on survival after cancer surgery," said Schaefer. "We think that our study encourages anesthesiologists to administer dexamethasone during cancer surgery. We now need studies that look into specific types and subtypes of cancer, such as lung cancer of non-smokers."


The study's authors think the results of their research are promising and lay the foundation for future studies to substantiate their findings.


"Our findings also suggest that dexamethasone may have different effects in different tumors based on the degree the immune system is required for control of cancer growth," noted Schaeffer. "This is why we think that next studies should look more specifically into different types of cancer."


Frieda Wiley is a contributing writer.