Tumour cell density quantified by artificial intelligence is associated with differential benefit from irinotecan-based chemo-radiotherapy in locally advanced rectal cancer: a post-hoc study of the phase 3 ARISTOTLE trial
Abstract
Background: Tumour cells and tumour-associated stroma are key components of the tumour microenvironment, and their interaction impacts disease progression and treatment resistance in rectal cancer. This study introduces a computational approach to quantify tumour cell density (TCD) within epithelial and stromal regions and assess whether treatment response differs according to TCD status in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT).
Methods: The data of 414 ARISTOTLE trial (ISRCTN09351447) participants with available digitised pre-treatment biopsies were analysed in this study. We defined TCD as the proportion of tumour cells within the tumour and stroma tissues and quantified TCD using an AI framework applied to digitised haematoxylin and eosin-stained whole-slide images. The patients were stratified as TCD-high/TCD-low using a cut-off value of 0.5 (50% of tumour cells). The TCD status was combined with treatment arms [CRT (capecitabine + radiotherapy) and IrCRT (experimental capecitabine + irinotecan + radiotherapy)] to stratify the disease-free survival (DFS), overall survival (OS) and pathological complete response (pCR) rates.
Findings: Among the patients analysed, 188 (45%) of 414 patients were classified as TCD-high and 226 (55%) as TCD-low. A significant treatment-TCD interaction was observed for both DFS (χ2 = 6.88, p = 0.009) and OS (χ2 = 10.61, p = 0.001). In the TCD-high subgroup, the use of IrCRT was…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 414 participants or records.
Read the paper
Related studies
- Preliminary Toxicity Analysis of 3DCRT versus IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial
- Adaptive Radiotherapy for Head and Neck Cancer: Initial Clinical Outcomes from a Prospective Trial
- American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology
- Motion Management Strategies and Technical Issues Associated with Stereotactic Body Radiotherapy of Thoracic and Upper Abdominal Tumors: A Review from NRG Oncology
- High-dose-rate interstitial brachytherapy as a monotherapy for localized prostate cancer: treatment description and preliminary results of a phase I/II clinical trial
- Highly efficient training, refinement, and validation of a knowledge-based plan quality control system for radiotherapy clinical trials
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.