Laura M. Chambers

Gram-positive targeting antibiotics are associated with progression and death in women with platinum-sensitive recurrent high grade epithelial ovarian cancer

Assessment of probiotic and prebiotic use in gynecologic cancer patients: a systematic review

To evaluate evidence on the impact of probiotics and prebiotics on clinical outcomes, treatment efficacy, quality of life, safety, and translational endpoints in patients with gynecologic cancers. A systematic search of PubMed, Embase, and Scopus was conducted in March 2023 and updated through September 2025. Gray literature sources (ClinicalTrials.gov, reference lists) were also reviewed. Eligible studies included randomized controlled trials and prospective interventional studies in women with gynecologic cancers (cervical, endometrial, ovarian, uterine, and vulvar) undergoing treatment. Interventions were probiotic, prebiotic, or dietary fiber supplementation. Eligible outcomes included treatment toxicity, stool consistency, quality of life, postoperative outcomes, oncologic outcomes, safety, and microbiome endpoints. Exclusions were retrospective studies, case reports, reviews, conference abstracts, and studies without cancer-related outcomes. Three independent reviewers screened studies using Covidence, with disagreements resolved by consensus or adjudication. Risk of bias was assessed with the Cochrane Risk of Bias 2.0 tool. Due to heterogeneity in strains, dosing, and outcomes, structured narrative synthesis was conducted rather than meta-analysis. From 2308 screened records, 9 randomized controlled trials involving 663 patients were included. Seven studies evaluated probiotics and 2 assessed prebiotics/fiber. Most focused on radiation-induced toxicity in cervical (n=415) and endometrial cancer (n=170) patients. Probiotics significantly reduced incidence and severity of radiation-induced diarrhea, improved stool consistency, and decreased antidiarrheal use (P<.05). Prebiotics alone showed minimal benefit. One perioperative study found probiotics accelerated bowel recovery and reduced postoperative complications. Three translational studies showed probiotics reduced gut permeability but did not alter microbial composition. No trials examined chemotherapy or immunotherapy outcomes, progression-free survival, or overall survival. Adverse events were infrequent and no major safety concerns were identified. Probiotic supplementation demonstrates consistent benefit in reducing radiation-induced gastrointestinal toxicity in gynecologic cancer patients, while prebiotics alone show limited efficacy. Evidence gaps include effects on chemotherapy, immunotherapy, oncologic outcomes, and survival. Heterogeneity in formulations limits clinical applicability, and standardized strain-specific trials are needed. Future research should evaluate long-term oncologic outcomes, optimize microbiome-directed interventions, and establish safety in immunocompromised populations.

Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research

Abstract Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued preclinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for the evaluation of the tumor–immune interaction in an immunocompetent host, most closely mimicking the tumor–immune interaction in patients with cancer. Unfortunately, significant disparities exist about syngeneic models in gynecologic malignancy, in which queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Published data exist about the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for preclinical models in endometrial and cervical cancers will support physician scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.

Use of prophylactic closed incision negative pressure therapy is associated with reduced surgical site infections in gynecologic oncology patients undergoing laparotomy

Surgical site infection after surgery for gynecologic cancer increases morbidity. Prophylactic closed incision negative pressure therapy has shown promise in reducing infectious wound complications across many surgical disciplines. This study aimed to determine whether closed incision negative pressure therapy is associated with reduced surgical site infections in gynecologic oncology patients undergoing laparotomy compared with standard dressings. This was a retrospective case-control study of patients undergoing laparotomy for known or suspected gynecologic cancer from Jan. 1, 2017, to Feb. 1, 2020. Patients were matched in a 1:3 ratio (closed incision negative pressure therapy to standard dressing) by body mass index, age, diabetes, bowel surgery, smoking, and steroid use. Surgical site infection was defined according to the Centers for Disease Control and Prevention. Multivariable logistic regression using backward selection was performed. Of the 1223 eligible patients undergoing laparotomy, 64 (5.2%) received closed incision negative pressure therapy dressings and were matched to 192 (15.7%) controls. There were no differences in medical comorbidities (P>.05), site or stage of malignancy (P>.05), duration of surgery (P=.82), or surgical procedures (P>.05). Use of closed incision negative pressure therapy was associated with reduction in all adverse wound outcomes (20.3% vs 40.1%; P<.001). In particular, closed incision negative pressure therapy was associated with a significant reduction in both superficial incisional surgical site infections (9.4% vs 29.7%; P<.001) and deep incisional surgical site infections (0.0% vs 6.8%; P=.04). In multivariable analysis, use of closed incision negative pressure therapy was associated with significant reduction in the incidence of superficial incisional infections alone (odds ratio, 0.29; 95% confidence interval, 0.12-0.73; P=.008) and both superficial and deep incisional infections (odds ratio, 0.29; 95% confidence interval, 0.12-0.71; P=.007). Use of prophylactic closed incision negative pressure therapy after laparotomy in gynecologic oncology patients was found to be associated with reduced superficial incisional and deep incisional infections compared with standard dressings. Furthermore, closed incision negative pressure therapy was associated with reduction in all other adverse wound outcomes. Closed incision negative pressure therapy may be considered for surgical site infection prevention in high-risk gynecologic oncology patients undergoing laparotomy.

Disruption of the Gut Microbiota Confers Cisplatin Resistance in Epithelial Ovarian Cancer

Abstract Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death. Despite initial responses to intervention, up to 80% of patient tumors recur and require additional treatment. Retrospective clinical analysis of patients with ovarian cancer indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. Here, we assessed whether antibiotic (ABX) treatment would impact growth of EOC and sensitivity to cisplatin. Immunocompetent or immunocompromised mice were given untreated control or ABX-containing (metronidazole, ampicillin, vancomycin, and neomycin) water prior to intraperitoneal injection with EOC cells, and cisplatin therapy was administered biweekly until endpoint. Tumor-bearing ABX-treated mice exhibited accelerated tumor growth and resistance to cisplatin therapy compared with control treatment. ABX treatment led to reduced apoptosis, increased DNA damage repair, and enhanced angiogenesis in cisplatin-treated tumors, and tumors from ABX-treated mice contained a higher frequency of cisplatin-augmented cancer stem cells than control mice. Stool analysis indicated nonresistant gut microbial species were disrupted by ABX treatment. Cecal transplants of microbiota derived from control-treated mice was sufficient to ameliorate chemoresistance and prolong survival of ABX-treated mice, indicative of a gut-derived tumor suppressor. Metabolomics analyses identified circulating gut-derived metabolites that were altered by ABX treatment and restored by recolonization, providing candidate metabolites that mediate the cross-talk between the gut microbiome and ovarian cancer. Collectively, these findings indicate that an intact microbiome functions as a tumor suppressor in EOC, and perturbation of the gut microbiota with ABX treatment promotes tumor growth and suppresses cisplatin sensitivity. Significance: Restoration of the gut microbiome, which is disrupted following antibiotic treatment, may help overcome platinum resistance in patients with epithelial ovarian cancer. See related commentary by Hawkins and Nephew, p. 4511