# Tumour mutation burden drives survival outcomes in pancreatic ductal adenocarcinoma and enables noninvasive prediction via dual-layer spectral CT

## TL;DR

High tumor mutation burden in pancreatic cancer is linked to better survival, and a new CT scan method can predict this mutation burden noninvasively.

## Contribution

DLCT-derived normalized iodine concentration is shown to be a superior noninvasive predictor of TMB in PDAC compared to conventional imaging metrics.

## Key findings

- High TMB in PDAC is associated with better progression-free survival.
- A TMB cutoff of 5 mut/Mb effectively stratifies patients into distinct prognostic groups.
- Normalized iodine concentration from DLCT outperforms conventional CT metrics in predicting TMB.

## Abstract

To evaluate the prognostic significance of tumour mutation burden (TMB) in pancreatic ductal adenocarcinoma (PDAC) and explore the performance of dual-layer spectral CT (DLCT) for noninvasive TMB evaluation.

This retrospective analysis enroled patients with histopathologically confirmed PDAC who underwent DLCT between June 2019 and December 2023. Clinical, qualitative radiological, and quantitative conventional CT and DLCT parameters were evaluated. Survival analysis evaluated TMB’s association with progression-free survival (PFS) and identified an optimal TMB cutoff. Independent TMB predictors were identified through univariable and LASSO regression. Predictive performance was quantified via receiver operating characteristic and precision-recall curve assessments.

Among 75 patients (mean age 60.4 ± 11.2 years; 41 males, 34 females), median TMB was 2.13 mut/Mb (interquartile range: 1.00–4.26). A 5 mut/Mb cutoff revealed distinct prognostic groups, with high-TMB cases exhibiting better PFS (median PFS: 7 vs 5 months, p = 0.02). Normalised iodine concentration in the pancreatic phase (nICa) was the sole independent TMB predictor (area under the curve [AUC] = 0.901; cutoff = 0.089; accuracy = 89.3% [89.1–89.6%], sensitivity = 81.8% [59.0–100%], specificity = 90.6% [83.5–97.8%]), surpassing conventional CT attenuation metrics (nCTa, AUC = 0.834), peripancreatic tumour infiltration (AUC = 0.679), and their combined model (AUC = 0.864) with significant net reclassification improvement (all p < 0.05). Precision-recall curve validation reinforced nICa’s superior predictive capacity. Patients classified by nICa-predicted high TMB status demonstrated better PFS (median PFS: 7 vs 5 months, p = 0.04).

Elevated TMB is a positive biomarker for PFS in PDAC. DLCT-derived nICa facilitates precise, noninvasive TMB prediction, outperforming conventional imaging parameters and supporting its potential role in therapeutic stratification.

Elevated tumour mutational burden (TMB) in PDAC correlated with prolonged PFS. DLCT provided noninvasive, accurate TMB quantification, enabling meaningful survival stratification.

High TMB in patients with PDAC portends better PFS, particularly those receiving combination immunotherapy.A clinically applicable TMB cutoff of 5 mut/Mb was identified, stratifying patients into biologically distinct low- and high-TMB prognostic groups.DLCT-derived pancreatic phase normalized iodine concentration emerged as a superior noninvasive TMB biomarker compared to conventional imaging parameters.

High TMB in patients with PDAC portends better PFS, particularly those receiving combination immunotherapy.

A clinically applicable TMB cutoff of 5 mut/Mb was identified, stratifying patients into biologically distinct low- and high-TMB prognostic groups.

DLCT-derived pancreatic phase normalized iodine concentration emerged as a superior noninvasive TMB biomarker compared to conventional imaging parameters.