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Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study.

ABSTRACT: Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8⁺ T cells (P = 0.033), CD20⁺ B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1⁺ cells (P = 0.042), and PD-L1⁺CD68⁺ macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20⁺ cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56^bright cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8⁺ cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20⁺ and CD163⁺ macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4⁺ T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8⁺ cells pre-NACT (P = 0.042) were independently associated with improved OS.

SUBMITTER: Cao G

PROVIDER: S-EPMC10040680 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study.

Cao Guangming G Hua Dingchao D Li Jinfeng J Zhang Xuefang X Zhang Zhiqiang Z Zhang Bei B Bei Ting T Cui Lina L Chen Shiqing S Wang Shuzhen S Zhu Lei L

Frontiers in immunology 20230313

Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8<s ...[more]

PMID: 36993949

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Project description:Study objectiveTo evaluate the effect of surgical approach on overall survival (OS) for women with advanced, epithelial ovarian cancer (EOC) after neoadjuvant chemotherapy (NACT) and determine the sociodemographic and clinical factors associated with surgical approach.DesignThe primary exposure was surgical approach to interval cytoreduction, minimally invasive versus open, and was evaluated by intention to treat. Primary outcome was OS. Associations were examined using Chi-squared tests, Wilcoxon rank sum tests, and multivariate logistic regression. Survival analysis was performed with Kaplan-Meier methods and Cox proportional hazards.SettingThe National Cander Database was used to identify eligible patients.PatientsWomen diagnosed with stage IIIC/IV EOC from 2010-2016.InterventionsPatients were included if they were treated with NACT within 90 days of diagnosis before interval cytoreductive surgery (CRS).Measurements and main resultsA total of 8085 women were identified; 6713 (83%) underwent open interval CRS, and 1372 (17%) underwent minimally invasive interval CRS. The proportion undergoing minimally invasive CRS after NACT increased from 2% in 2010 to 11% in 2016, a nearly 6-fold increase. There was no difference in OS between women who underwent minimally invasive and open interval CRS (median OS 36.5 vs 35.2 months, HR 0.94, 95% CI, 0.86-1.04). After adjusting for demographic and clinical variables, including age, race, ethnicity, income, and Charlson/Deyo score, no difference in OS was observed (HR 0.95, 95% CI, 0.86-1.04). Women of older age (OR 1.35, 95% CI, 1.05-1.74) and Hispanic ethnicity (OR 1.46, 95% CI, 1.14-1.88) had increased odds of receiving minimally invasive CRS after NACT, whereas low income (<$38000/year) women had decreased odds (OR 0.76, 95% CI, 0.60-0.97, p = .03). Length of stay differed for patients undergoing minimally invasive versus open interval CRS (3 vs 5 days, p <.01), but there was no difference in need for postoperative readmission.ConclusionsMinimally invasive CRS has similar survival outcomes to open CRS among women with EOC who have undergone NACT.

Project description:BackgroundOvarian cancer is often diagnosed in advanced stages, when survival is poor. Treatment advances have been made, but are inconsistently implemented. Our purpose was to project the maximum life expectancy gains that could be achieved in women with stage IIIC epithelial ovarian cancer if the implementation of available chemotherapy regimens could be optimized.MethodsWe used a microsimulation model to estimate life expectancy benefits associated with "optimized" implementation of four post-operative chemotherapy options: standard intravenous chemotherapy; intraperitoneal + intravenous chemotherapy; bevacizumab + intravenous chemotherapy; and hyperthermic intraperitoneal chemotherapy + intravenous chemotherapy. Optimized implementation was defined as follows. Patients triaged to primary cytoreductive surgery received intraperitoneal + intravenous chemotherapy if optimally or completely cytoreduced, and bevacizumab + intravenous chemotherapy if suboptimally cytoreduced. Patients triaged to neoadjuvant chemotherapy received hyperthermic intraperitoneal chemotherapy at interval cytoreductive surgery if optimally or completely cytoreduced, and standard IV chemotherapy if suboptimally cytoreduced. Life expectancy associated with optimized implementation was compared with that of current utilization practices, estimated using published literature and the National Cancer Database. Effects of model uncertainty were evaluated in sensitivity analyses.ResultsLife expectancy associated with optimized implementation vs. current practice was 76.7 vs. 64.5 months (life expectancy gain = 12.2 months). Providing intraperitoneal + intravenous chemotherapy to all eligible patients was the largest driver of life expectancy gains, due to both the potential benefit conferred by intraperitoneal + intravenous chemotherapy and the proportion of eligible women who do not receive intraperitoneal + intravenous chemotherapy in current practice.ConclusionPopulation-level life expectancy in stage IIIC epithelial ovarian cancer could be substantially improved through greater uptake of available chemotherapy regimens.

Dataset Information

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study.

Publications

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study.

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