Author: Huiming Dong, Jonathan Pham, X. Sharon Qi, Ann Raldow 👨🔬
Affiliation: Department of Radiation Oncology, University of California, Los Angeles 🌍
Purpose: The study aimed to investigate longitudinal apparent diffusion coefficient (ADC) as an early biomarker of treatment response in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT) with MR-guided short-course radiotherapy (SCRT).
Methods: Ten LARC patients, enrolled in a prospective clinical trial, treated with 0.35T MR-guided short-course radiotherapy (25Gy/5Fx) followed by 16 weeks of mFOLFOX were included. Diffusion-weighted single-shot echo-planar (DW-ssEPI) MRIs (b-values of 0,300,500s/mm2) were acquired at simulation, 3rd fraction, and 5th fraction of radiotherapy treatment on the 0.35T MR-LINAC (ViewRay MRIdian) or 1.5T MR Simulator (Siemens Magnetom Sola). DW-ssEPI ADC quantification was validated for both MRI scanners using a Diffusion Phantom (CaliberMRI), comprising of 0-50% polyvinylpyrrolidone vials. ADC maps were estimated using mono-exponential fitting, and the ADC of gross tumor volume was evaluated at each of the three timepoint for every patient. Patient response (clinical complete or incomplete) was assessed 8-12 weeks after completion of neoadjuvant therapy using digital rectal examination endoscopy and MRI. Mean tumor ADC at each timepoint as well as ADC change among these timepoints were calculated from the optimal operating point of receiver operating characteristic (ROC) curve for treatment response prediction.
Results: Four out of ten (40%) LARC patients achieved cCR. DW-ssEPI Diffusion Phantom mean ADC bias/within-subject Coefficient of Variation were 1.61±4.59%/1.11±0.63% and 0.80±1.26%/0.21±0.19% for 0.35 MR-LINAC and 1.5T MR simulator, respectively. ADC increase throughout treatment was associated with cCR. Mean ADC of 1.32×10-3 mm2/s at the 5th fraction was the most predictive of treatment response and demonstrated an AUC, sensitivity, and specificity of 0.83,0.75, and 0.83.
Conclusion: Longitudinal ADC analysis using high- and low-field MRI shows potential as a non-invasive biomarker for early treatment response prediction in LARC patients. This approach may support non-operative management recommendations for SCRT responders, reducing the need for radical surgery and its associated morbidities.