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Diffusion kurtosis MRI as a predictive biomarker of response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

ABSTRACT: This study assessed the feasibility of using diffusion kurtosis imaging (DKI) as a measure of tissue heterogeneity and proliferation to predict the response of high grade serous ovarian cancer (HGSOC) to neoadjuvant chemotherapy (NACT). Seventeen patients with HGSOC were imaged at 3?T and had biopsy samples taken prior to any treatment. The patients were divided into two groups: responders and non-responders based on Response Evaluation Criteria In Solid Tumours (RECIST) criteria. The following imaging metrics were calculated: apparent diffusion coefficient (ADC), apparent diffusion (Dapp) and apparent kurtosis (Kapp). Tumour cellularity and proliferation were quantified using histology and Ki-67 immunohistochemistry. Mean Kapp before therapy was higher in responders compared to non-responders: 0.69?±?0.13 versus 0.51?±?0.11 respectively, P?=?0.02. Tumour cellularity correlated positively with Kapp (rho?=?0.50, P?=?0.04) and negatively with both ADC (rho?=?-0.72, P?=?0.001) and Dapp (rho?=?-0.80, P?

SUBMITTER: Deen SS

PROVIDER: S-EPMC6656714 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Diffusion kurtosis MRI as a predictive biomarker of response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

Deen Surrin S SS Priest Andrew N AN McLean Mary A MA Gill Andrew B AB Brodie Cara C Crawford Robin R Latimer John J Baldwin Peter P Earl Helena M HM Parkinson Christine C Smith Sarah S Hodgkin Charlotte C Patterson Ilse I Addley Helen H Freeman Susan S Moyle Penny P Jimenez-Linan Mercedes M Graves Martin J MJ Sala Evis E Brenton James D JD Gallagher Ferdia A FA

Scientific reports 20190724 1

This study assessed the feasibility of using diffusion kurtosis imaging (DKI) as a measure of tissue heterogeneity and proliferation to predict the response of high grade serous ovarian cancer (HGSOC) to neoadjuvant chemotherapy (NACT). Seventeen patients with HGSOC were imaged at 3 T and had biopsy samples taken prior to any treatment. The patients were divided into two groups: responders and non-responders based on Response Evaluation Criteria In Solid Tumours (RECIST) criteria. The following ...[more]

PMID: 31341212

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Project description:Simple Summary Neoadjuvant chemotherapy (NAC) induced a dynamic change in the TIME that increased the level of immune infiltration, leading to a high number of CD8 T cells with enhanced immune activity. However, increased immune infiltration and immune activity did not present any survival benefit, probably due to concomitant immunosuppression associated with an increase in the proportion of Foxp3+ regulatory T cells. Our results could provide therapeutic strategies to improve the survival benefit from immunotherapies in an NAC setting. Abstract The dynamic changes in the tumor immune microenvironment (TIME) triggered by neoadjuvant chemotherapy (NAC) have not been clearly defined in advanced-stage ovarian cancer. We analyzed the immunologic changes induced by NAC to correlate them with clinical outcomes. We compared the changes in the immune infiltration of high-grade serous carcinoma biopsies before and after NAC via immunohistochemistry (147 paired samples) and whole transcriptome sequencing (35 paired samples). Immunohistochemistry showed significantly increased PD-L1 levels and TIL levels after NAC. Whole transcriptome sequencing revealed that the stromal score, immune score, and cytolytic activity score significantly increased after NAC. An increased tumor-infiltrating lymphocyte (TIL) level in response to NAC was associated with shorter progression-free survival compared with decreased TIL level after NAC. In tumors with increased TIL levels after NAC, the relative fraction of CD8 T cells and regulatory T cells significantly increased with immunohistochemistry. Post-NAC tumors were enriched in gene sets associated with immune signaling pathways, such as regulatory T cell and JAK/STAT signaling pathways. NAC induced dynamic changes in the TIME that increased TIL levels, but their high abundance did not impart any survival benefit. Our data may provide therapeutic strategies to improve the survival benefit from immunotherapies in ovarian cancer.

Dataset Information

Diffusion kurtosis MRI as a predictive biomarker of response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

Publications

Diffusion kurtosis MRI as a predictive biomarker of response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

Similar Datasets

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