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APT histogram parameters for Response Prediction of Neoadjuvant Chemotherapy in Rectal Cancer: A Prospective Study1Department of Radiology, West China Hospital, Sichuan University, Cheng du, China, 2Colorectal Cancer Center，Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China, 3Department of Radiology, West China Hospital, Sichuan University, Chengdu, China, 4Philips Healthcare, China, Beijing, China, 5Philips Healthcare, China, Chengdu, China
Synopsis
Keywords: Cancer, fMRI, rectal cancer
Early imaging prediction of neoadjuvant chemotherapy (NACT) response would enable a personalized treatment approach to improve therapeutic response and avoid treatment morbidity in rectal cancer. Morphological changes base on T2 weighted MRI and free dispersion limitation of water molecules in tumor have limited value in evaluating efficacy after NACT. Amide proton transfer (APT)–weighted MRI, indirectly detecting the concentration of tissue macromolecular proteins, could help to inform us of the proliferation and biological status of tumor cells. The aim of this study is to determine if APT MRI is useful in early assessment of treatment response in persons with rectal cancer.Synopsis
Early imaging prediction of neoadjuvant chemotherapy (NACT) response would enable a personalized treatment approach to improve therapeutic response and avoid treatment morbidity in rectal cancer. Morphological changes base on T2 weighted MRI and free dispersion limitation of water molecules in tumor have limited value in evaluating efficacy after NACT. Amide proton transfer (APT)–weighted MRI, indirectly detecting the concentration of tissue macromolecular proteins, could help to inform us of the proliferation and biological status of tumor cells. The aim of this study is to determine if APT MRI is useful in early assessment of treatment response in persons with rectal cancer.Summary of Main Findings
We found that APTkurtosis may be an effective biomarker to predict NACT response, and the APTkurtosis obtained after 1 cycle is expected to first provide accurate efficacy information.Introduction
Neoadjuvant chemotherapy (NACT) is recommended for low to moderate-risk rectal cancer (RC) before the total mesorectal excision [1,2], while only limited patients would achieve pathologic complete response (pCR) [3]. The indicators used to evaluate the NACT efficacy are mainly based on T2 morphological information, including the long diameter, thickness, and volume of the tumor [4,5], with a certain delay. In addition, diffusion weighted magnetic resonance imaging (DW-MRI), the only imaging technology for non-invasive detection of the restriction of free diffusion of water molecules in human body, is still limited in distinguishing between tumors and fibrosis after treatment [6]. Amide proton transfer (APT) imaging generates APT contrast via the amide protons located on the backbone of mobile proteins and peptides. APT MRI signal intensity increased in tumor cells which have an increased concentration of cytosolic mobile proteins owing to increased metabolic activities and cellular density [7]. Therefore, evaluating the protein content of tumor cells through APT imaging could help to inform us of the proliferation and biological status of tumor cells. Furthermore, histogram analysis may provide more information than the average alone [8]. However, whether APT can effectively distinguish the patients who are effective or not after neoadjuvant chemotherapy and when to promptly predict efficacy remains unclear. In this study, we prospectively and continuously investigated the APT values before, during and after NACT, aiming to determine the earliest time point and the most effective indicators for evaluation of NACT response in RC.Image Acquisition
MR protocol consisted of oblique axial T2-weighted sequence and APT sequence. MR images were collected at 5 time points (TPs), including TP1 (before treatment), TP2 (after 7 days), TP3 (after 1 cycle), TP4 (after 2 cycles) and TP5 (before operation), in all patients respectively. Regions of interest (ROI) of T2 images were manually placed on the tumor region, avoiding the necrotic, cystic and hemorrhagic regions in the whole tumor and were registered to APT maps to construct the APT histogram, including the mean, skewness and kurtosis [8].Statistics Analysis
APT histogram parameters between two groups were compared. For parameters with significant differences between groups, the changes at different time points for visualization of APT parameters and receiver operating characteristic (ROC) curve performed. Multiple comparative analyses were carried out to compare the difference of parameters between time points. Comparison of the areas under the curve (AUC) was performed.Results
Between June 2021 and October 2022, 29 consecutive patients with biopsy-proven RC were recruited. The APTkurtosis of TP3 and TP5 were lower in pCR group (0.56±0.32 and 0,54±0.47, respectively) than in non-pCR group (0.89±0.57 and 1.32±1.58, respectively) (P values = 0.023 and 0.005, respectively; Fig 1). However, there were no diferences in other APT parameters among the 5 TPs between the two groups. The cutoff values, sensitivity, specificity and area under curve (AUC) of the APTkurtosis at TP3 and TP5 were -1.035, 100%, 80% and 0.825 (P =0.024), and -1.030, 100%, 80% and 0.887 (P =0.007) (P =0.467 for AUC of TP3 vs TP5; Fig. 2).Discussion
Our study demonstrated that APTkurtosis may contribute to predicting response in RC after 1 cycle of NACT and before operation with similar AUC values, and 1 cycle after NACT may be the earliest time for predicting pCR. Few studies evaluated the efficacy of neoadjuvant therapy by using APT values only before treatment or surgery [9,10,11] or evaluated the histopathological factors related to prognosis in RC without any neoadjuvant therapy before surgery [12,13,14,15]. Due to the limited sample size, our study was unable to evaluate the value of APT in evaluating the rectal fibrosis after treatment like Martens et al. [9]. Additionally, we found no difference between the pCR and non-PCR groups in the mean, kurtosis and skewness of APT values before treatment, which was different from the study of Chen al. [11]. More studies are needed to explore and verify the value of APT in efficacy prediction of NACT in RC. Our limitations lie in the relatively small sample size and some patients had small lesions. In addition, we didn't compare APT parameters with ADC or other parameters, which needs further exploration in future research.Conclusion
APT imaging is a promising noninvasive technique for monitoring and predicting therapeutic response in rectal cancer patients undergoing NACT and APTkurtosis after one cycle may be recommended to early predict the NACT efficacy in the future.Acknowledgements
No acknowledgement found.References
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Figures
Figure 1 The changes of APTkurtosis at different time points between groups
* P <0.05
