## 4 Discussion  
This study investigated the use of ERI\({}_{\text{TCP}}\) as pCR predictor in CC patients undergoing nCRT, analyzing MR images acquired using a low field MRgRT unit.  
Being a morphological parameter, ERI\({}_{\text{TCP}}\) can predict the response to nCRT by modelling the tumor volumetric regression during the treatment, simply using the information due to the volumetric variation of the tumor during the therapy: This makes ERI\({}_{\text{TCP}}\) easy to use and generalizable to MR images acquired using different techniques and imaging parameters, as already demonstrated in the framework of rectal cancer [22; 23; 35].  
One of the peculiarities of this study is represented by the possibility to correlate image-based parameters directly to histopathological data, being quite uncommon in the context of CC, as generally  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**BED** & **AUC (95\% CD)** & **Best Cut-Off** & **Sensitivity** & **Specificity** & **Youden Index** \\ \hline
14 Gy & 0.80 (0.51–1) & 149.5 & 90.9 & 80 & 0.71 \\ \hline
28 Gy & 0.84 (0.58–1) & 96.0 & 90.9 & 80 & 0.71 \\ \hline
42 Gy & 0.80 (0.53–1) & 54.0 & 90.9 & 80 & 0.71 \\ \hline
54 Gy & 0.74 (0.47–1) & 31.5 & 90.9 & 60 & 0.50 \\ \hline
62 Gy & 0.78 (0.53–1) & 16.4 & 81.8 & 80 & 0.62 \\ \hline \hline \end{tabular}
\end{table}
Table 4: Indicators of the predictive performance of the early regression index (ERI\({}_{\text{TCP}}\)) index in the case of cervical cancer at different BED levels.  
Figure 3: ERI\({}_{\text{TCP}}\) values calculated at the most significant BED level for both observers (one column the highest predictive performance (BED = 28 Gy), no significant difference was observed using the DeLong’s test (all \(p\)-values were \(>\)0.05).  
the patients affected by this disease are addressed to brachytherapy and not to surgery, not allowing comparisons with histopathological ground truth.  
The limited dimension of the population analyzed in this hypothesis generating study does not allow to draw definitive conclusions regarding the clinical use of this index, although it is interesting to observe that the predictive performance of this parameter is high and persists between independent observers.  
The highest ERI\({}_{\text{TCP}}\) performance in predicting pCR was observed when a BED value of 28 Gy was reached, with an AUC of 0.84, a sensitivity of 0.91 and a specificity of 0.8: The high value of sensitivity reported by this index may allow to successfully identify the patients that will undergo complete response since the second week of nCRT, avoiding unnecessary overtreatments and paving the way towards effective treatment personalization.  
Although the [PERSON]'s test did not report statistically significant differences between the ROC curves calculated at different timings (probably due to the reduced number of cases analyzed), it is interesting to observe that the most significant ERI\({}_{\text{TCP}}\) timing identified for CC is the same observed for rectal cancer, regardless the obvious biological and histological differences that make the shrinkage pace not comparable in the two scenarios: This could be one of the reasons why the threshold value identified as best-cut off (96) is very different from the value of 13 observed in the rectal cancer experience [22; 23].  
A second study including an external cohort of patients is therefore recommended to validate the findings reported in this preliminary experience and confirm the most suitable timing and BED value. Unfortunately, the collection of homogeneous cohorts of patients affected by CC and undergoing nCRT will be particularly challenging, as most of these patients are generally addressed to brachytherapy, according to international guidelines [5].