TORONTO, August 31 – Currently, there is no reliable clinical indicator to accurately assess the treatment response of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) patients. Determining whether the nCRT-treated LARC patients should adopt the “Watch & Wait” approach to avoid over-treatment or whether they should receive subsequent intensive treatments to minimize disease recurrence is still a challenge in clinical practices. A recent prospective study published in the journal of PLOS Medicine, led by Fudan University Shanghai Cancer Center, Shanghai Medical College, and Geneseeq Technology Inc., demonstrated that circulating tumor DNA (ctDNA) in combination with magnetic resonance imaging (MRI) could facilitate the prediction of pathological complete response (pCR) before surgery, and the study also showed pioneer works in using ctDNA to estimate recurrence risk and prognosis in LARC patients.

This study recruited 119 LARC patients who were treated with nCRT plus total mesorectal excision (TME) from the year 2016 to 2017, and serial plasma samples at baseline, during nCRT, and after surgery were collected and subjected to deep targeted-panel sequencing of 422 cancer-related genes. As the traditional MRI approach was not sufficient to predict pCR, researchers in this study compared different pCR prediction models that incorporate only ctDNA features, only MRI data, or the combination of ctDNA and MRI data.

Notably, by combining the results of ctDNA and MRI, the prediction model (AUC=0.886) demonstrated a superior capacity to predict pCR and non-pCR patients, compared with the models that only utilized one set of data (AUC=0.818 and 0.729, respectively). As a result, the newly developed combination model could more accurately assess the treatment response of nCRT. This could help patients access personalized subsequent treatment plans and help reach the optimal balance between quality of life and treatment efficacy. Moreover, the researchers discovered certain pathological risk features, as well as the detection of some diver genetic alterations in ctDNA, were highly correlated with disease recurrence, so these ctDNA and pathological features could be potentially used to predict patients’ prognosis for LARC.

“Accurate predictions of response to therapy will direct patients to the most appropriate treatment regimes,” says Dr. Hua Bao, the Director of Research & Development at Geneseeq. Since 2017, Geneseeq continues to work on minimal residual disease (MRD) monitoring through its CALIBRATETM (monitoring post-surgery CAncer recurrence by ctDNA LIquid Biopsy RATing) program for colorectal cancer patients.