Prospective validation of diffusion-weighted MRI as a biomarker of tumor response and oncologic outcomes in head and neck cancer: Results from an observational biomarker pre-qualification study

Radiother Oncol. 2023 Jun:183:109641. doi: 10.1016/j.radonc.2023.109641. Epub 2023 Mar 27.


Purpose: To determine DWI parameters associated with tumor response and oncologic outcomes in head and neck (HNC) patients treated with radiotherapy (RT).

Methods: HNC patients in a prospective study were included. Patients had MRIs pre-, mid-, and post-RT completion. We used T2-weighted sequences for tumor segmentation which were co-registered to respective DWIs for extraction of apparent diffusion coefficient (ADC) measurements. Treatment response was assessed at mid- and post-RT and was defined as: complete response (CR) vs. non-complete response (non-CR). The Mann-Whitney U test was used to compare ADC between CR and non-CR. Recursive partitioning analysis (RPA) was performed to identify ADC threshold associated with relapse. Cox proportional hazards models were done for clinical vs. clinical and imaging parameters and internal validation was done using bootstrapping technique.

Results: Eighty-one patients were included. Median follow-up was 31 months. For patients with post-RT CR, there was a significant increase in mean ADC at mid-RT compared to baseline ((1.8 ± 0.29) × 10-3 mm2/s vs. (1.37 ± 0.22) × 10-3 mm2/s, p < 0.0001), while patients with non-CR had no significant increase (p > 0.05). RPA identified GTV-P delta (Δ)ADCmean < 7% at mid-RT as the most significant parameter associated with worse LC and RFS (p = 0.01). Uni- and multi-variable analysis showed that GTV-P ΔADCmean at mid-RT ≥ 7% was significantly associated with better LC and RFS. The addition of ΔADCmean significantly improved the c-indices of LC and RFS models compared with standard clinical variables (0.85 vs. 0.77 and 0.74 vs. 0.68 for LC and RFS, respectively, p < 0.0001 for both).

Conclusion: ΔADCmean at mid-RT is a strong predictor of oncologic outcomes in HNC. Patients with no significant increase of primary tumor ADC at mid-RT are at high risk of disease relapse.

Keywords: DWI; Head and neck cancer; Imaging Biomarker; Oncologic outcomes; Radiation Therapy; Tumor response.

Publication types

  • Observational Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Diffusion Magnetic Resonance Imaging / methods
  • Head and Neck Neoplasms* / diagnostic imaging
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Magnetic Resonance Imaging
  • Neoplasm Recurrence, Local* / diagnostic imaging
  • Prospective Studies


  • Biomarkers