Objective To investigate the predictive value of tumor iodine concentration obtained with dual-energy CT (DECT) for treatment response in patients treated with immune checkpoint inhibitors (ICI). Materials and methods Retrospective single-center study of consecutive metastatic melanoma and renal cell carcinoma (RCC) patients undergoing first-line ICI treatment. The iodine concentration measurement time points include prior to initiation of therapy (baseline [BL]), after initiation (follow-up [FU1]), and either time point nearest to 12 months or at time of progression (final follow-up [FFU]). Target lesion DECT-based whole-volume tumor normalized iodine concentration average (NICave) and size measurements were obtained. Reference standard was individual lesion FFU status categorized as responders or nonresponders per RECIST 1.1. Logistic regression model assessed NICave change and FU1 lesion response as predictors of FFU lesion outcome. Model’s performance was summarized with AUC. Intraclass correlation coefficient (ICC) summarized inter-rater agreement of NICave. Results Forty-six patients were included (mean age 61 ± 11 years, 12 women; 16 melanoma). Sixty-four of 175 target lesions were confirmed nonresponders at FFU. In a multivariable model, lesion status at FU1 (odds ratio [OR]: 27.4, p < 0.001) and changes in NICave from BL to FU1 (OR: 2.42 per 1-SD increase, p = 0.019) were significant predictors of lesion status at FFU. The model’s AUC was 0.86 (95% CI: 0.76–0.93). Inter-rater reliability of NICave was 0.98 (95% CI: 0.97–0.99). Conclusions Changes in iodine concentration from baseline to first follow-up improve identification of delayed responding metastatic melanoma and RCC lesions treated with immune checkpoint inhibitor, initially classified as nonresponders by size change. Key Points <Emphasis Type="BoldItalic">Question</Emphasis> How can pseudoprogression/delayed treatment response in metastatic renal cell carcinoma (RCC) and melanoma patients on first-line immune checkpoint inhibitors be accurately identified? <Emphasis Type="BoldItalic">Findings</Emphasis> Combining iodine concentration change from Dual-energy CT (baseline to first follow-up) with RECIST-based lesion size change improved prediction of final lesion outcome. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> DECT-based whole-volume tumor iodine concentration for target lesions is useful as a predictive imaging biomarker for distinguishing delayed response from true progression in patients with metastatic RCC and melanoma treated with first-line immune checkpoint inhibitors. Graphical Abstract

Dual-energy CT iodine concentration as a biomarker for immunotherapy treatment response in metastatic melanoma and renal cell carcinoma patients

期刊论文
发表日期：

2025年1月28日

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Natalie Wiley,
Mladen Zecevic,
Vivian Ho,
Matthew J. Stolzberg,
Danielle Cox,
Erik V. Soloff,
Evan Hall,
Carolyn L. Wang

摘要

Objective

To investigate the predictive value of tumor iodine concentration obtained with dual-energy CT (DECT) for treatment response in patients treated with immune checkpoint inhibitors (ICI).

Materials and methods

Retrospective single-center study of consecutive metastatic melanoma and renal cell carcinoma (RCC) patients undergoing first-line ICI treatment. The iodine concentration measurement time points include prior to initiation of therapy (baseline [BL]), after initiation (follow-up [FU1]), and either time point nearest to 12 months or at time of progression (final follow-up [FFU]). Target lesion DECT-based whole-volume tumor normalized iodine concentration average (NICave) and size measurements were obtained. Reference standard was individual lesion FFU status categorized as responders or nonresponders per RECIST 1.1. Logistic regression model assessed NICave change and FU1 lesion response as predictors of FFU lesion outcome. Model’s performance was summarized with AUC. Intraclass correlation coefficient (ICC) summarized inter-rater agreement of NICave.

Results

Forty-six patients were included (mean age 61 ± 11 years, 12 women; 16 melanoma). Sixty-four of 175 target lesions were confirmed nonresponders at FFU. In a multivariable model, lesion status at FU1 (odds ratio [OR]: 27.4, p < 0.001) and changes in NICave from BL to FU1 (OR: 2.42 per 1-SD increase, p = 0.019) were significant predictors of lesion status at FFU. The model’s AUC was 0.86 (95% CI: 0.76–0.93). Inter-rater reliability of NICave was 0.98 (95% CI: 0.97–0.99).

Conclusions

Changes in iodine concentration from baseline to first follow-up improve identification of delayed responding metastatic melanoma and RCC lesions treated with immune checkpoint inhibitor, initially classified as nonresponders by size change.

Key Points

Question How can pseudoprogression/delayed treatment response in metastatic renal cell carcinoma (RCC) and melanoma patients on first-line immune checkpoint inhibitors be accurately identified?

Findings Combining iodine concentration change from Dual-energy CT (baseline to first follow-up) with RECIST-based lesion size change improved prediction of final lesion outcome.

Clinical relevance DECT-based whole-volume tumor iodine concentration for target lesions is useful as a predictive imaging biomarker for distinguishing delayed response from true progression in patients with metastatic RCC and melanoma treated with first-line immune checkpoint inhibitors.

Graphical Abstract