Dataset Information

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis.

ABSTRACT:

Background

Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC).

Methods

Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node).

Results

Tumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions.

Conclusions

Following NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis.

Clinical trial registration

ClinicalTrials.gov NCT01505829.

SUBMITTER: Winfield JM

PROVIDER: S-EPMC7961011 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis.

Winfield Jessica M JM Wakefield Jennifer C JC Brenton James D JD AbdulJabbar Khalid K Savio Antonella A Freeman Susan S Pace Erika E Lutchman-Singh Kerryn K Vroobel Katherine M KM Yuan Yinyin Y Banerjee Susana S Porta Nuria N Ahmed Raza Shan E SE deSouza Nandita M NM

British journal of cancer 20210104 6

<h4>Background</h4>Diffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC).<h4>Methods</h4>Participants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained fro ...[more]

PMID: 33398064

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Project description:BackgroundMagnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement.MethodsA systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies.ResultsData were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: -4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: -0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson's/Spearman's correlations was wide (0.21-0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common.ConclusionMagnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson's/Spearman's correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted.

Project description:ImportanceRandomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.ObjectiveTo investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.Design, setting, and participantsA retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy.ExposuresExposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group).Main outcomes and measuresTemporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score.ResultsA total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P < .001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P = .007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P = .07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score-weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype-specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n = 1447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas.Conclusions and relevanceDespite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.

Dataset Information

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis.

Background

Methods

Results

Conclusions

Clinical trial registration

Publications

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis.

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