Figure 1.
Clinicopathological features and prognostic impact of pretreatment ctDNA burden in trial patients with high-risk demographics. (A) Sample collection and radiological imaging according to the study protocol. (B) Swimmers plot of the individual patients and their follow-up in the study. Median follow-up time was 61 months. (C) Kaplan-Meier survival estimates for OS (red) and FFS (blue) for the study cohort of 101 patients. (D) Waterfall plot of the pretreatment ctDNA burden (concentration) measured in 100 patients. Color fills of the plot represent end-of-therapy responses according to PET-CT. Below, the cut-point for high ctDNA burden identified by random sampling of the cohort. (E,G) Box plots of pretreatment ctDNA burden according to (E) different countries of study enrollment and (G) age-adjusted international prognostic index (aaIPI). Note the similar levels between study countries in (E) suggesting similar preanalytical factors affecting the measurements. Below the plots, median ctDNA burden and numbers of patients per group are reported. (F) Dot plot showing the correlation between radiologically measured metabolic tumor volume (x-axis, MTV, mL) and pretreatment ctDNA burden (y-axis, hGE/mL). Logarithmic scales on both axes. Spearman correlation. Dot colors represent countries of enrollment. (H) Kaplan-Meier survival estimate for OS according to high pretreatment ctDNA burden threshold identified by bootstrapping the cohort. Log-rank test. (I-K) Forest plots of Cox-proportional hazard model hazard ratios, 95% coincidence intervals, and P values. Asterisk denotes Cox proportional hazards assumption violation. (I) Univariate model of pretreatment ctDNA burden for different clinical endpoints. (J) Univariate models for OS according to pretreatment ctDNA burden (log hGE/mL) stratified according to different clinical high-risk subgroups. (K) Multivariable model for OS according to pretreatment ctDNA burden, aaIPI, and MTV. (L) Kaplan-Meier survival estimate for FFS according to different pretreatment ctDNA burden quartiles. Four-way log-rank test. ND, not detected; OS, overall survival; PFS, progression-free survival; RFS, recurrence-free survival; FFS, failure-free survival (defined as a time period between the date of trial entry and the last date of follow-up or the date of progression, lack of response, death for any reason, or discontinuation/change of therapy because of toxicity); DEN, Denmark; FIN, Finland; NOR, Norway; SWE, Sweden.

Clinicopathological features and prognostic impact of pretreatment ctDNA burden in trial patients with high-risk demographics. (A) Sample collection and radiological imaging according to the study protocol. (B) Swimmers plot of the individual patients and their follow-up in the study. Median follow-up time was 61 months. (C) Kaplan-Meier survival estimates for OS (red) and FFS (blue) for the study cohort of 101 patients. (D) Waterfall plot of the pretreatment ctDNA burden (concentration) measured in 100 patients. Color fills of the plot represent end-of-therapy responses according to PET-CT. Below, the cut-point for high ctDNA burden identified by random sampling of the cohort. (E,G) Box plots of pretreatment ctDNA burden according to (E) different countries of study enrollment and (G) age-adjusted international prognostic index (aaIPI). Note the similar levels between study countries in (E) suggesting similar preanalytical factors affecting the measurements. Below the plots, median ctDNA burden and numbers of patients per group are reported. (F) Dot plot showing the correlation between radiologically measured metabolic tumor volume (x-axis, MTV, mL) and pretreatment ctDNA burden (y-axis, hGE/mL). Logarithmic scales on both axes. Spearman correlation. Dot colors represent countries of enrollment. (H) Kaplan-Meier survival estimate for OS according to high pretreatment ctDNA burden threshold identified by bootstrapping the cohort. Log-rank test. (I-K) Forest plots of Cox-proportional hazard model hazard ratios, 95% coincidence intervals, and P values. Asterisk denotes Cox proportional hazards assumption violation. (I) Univariate model of pretreatment ctDNA burden for different clinical endpoints. (J) Univariate models for OS according to pretreatment ctDNA burden (log hGE/mL) stratified according to different clinical high-risk subgroups. (K) Multivariable model for OS according to pretreatment ctDNA burden, aaIPI, and MTV. (L) Kaplan-Meier survival estimate for FFS according to different pretreatment ctDNA burden quartiles. Four-way log-rank test. ND, not detected; OS, overall survival; PFS, progression-free survival; RFS, recurrence-free survival; FFS, failure-free survival (defined as a time period between the date of trial entry and the last date of follow-up or the date of progression, lack of response, death for any reason, or discontinuation/change of therapy because of toxicity); DEN, Denmark; FIN, Finland; NOR, Norway; SWE, Sweden.

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