## 3 Results  
The clinical characteristics of the patients enrolled in this study at diagnosis and after surgery are reported in Table 1.  
The median age of the patients at the diagnosis was 50.2 years (range 32-84 years), while pCR was achieved in 11/16 patients leading to a pCR rate of 68.7%. Table 2 summarizes the treatment fractions analyzed, with the corresponding physical and biological doses [34]. The median tumor volumes obtained by the two observers with the corresponding ranges and the results of the inter-observer analysis (\(p\)-value of Mann-Whitney test and ICC) are summarized in Table 3, to varying of the BED levels in Table 3.  
High absolute agreement was observed in the GTV delineations performed by the two observers for all the different investigated time points, reporting no statistically significant differences in terms of Mann-Whitney test and high values in terms of ICC. \begin{table}
\begin{tabular}{c c c} \hline  & **Clinical Characteristics** & **Cases (Percentage)** \\ \hline  & **Histology at the diagnosis** & \\ \multirow{2}{*}{} & Squamous cell carcinoma & 15 (94\%) \\  & Clear cell adenosquamous carcinoma & 1 (6\%) \\ \hline  & **FIGO Stage at the diagnosis** & \\ \multirow{2}{*}{} & IIA & 5 (31.3\%) \\  & IIB & 10 (62.5\%) \\  & IIIC1 & 1 (6.2\%) \\ \hline  & **Nodal status** & \\ \multirow{2}{*}{} & cN0 & 5 (31.3\%) \\  & cN1 & 11 (68.7\%) \\ \hline  & **Pathological Response** & \\ \multirow{2}{*}{} & pR0 & 11 (68.7\%) \\  & pR1 & 3 (18.8\%) \\ \multirow{2}{*}{} & pR2 & 2 (12.5\%) \\ \hline \end{tabular}
\end{table} 
Table 1: Clinical information of the patients enrolled in the study. The ERI\({}_{\text{TCP}}\) was calculated at the different BED levels considering the contours of both observers and its ability in predicting treatment outcome was quantified by means of the ROC curves, as reported in Figure 2. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**ERI** & **Fraction** & **Physical Dose** & **BED** \\ \hline ERI\({}_{\text{14\,Gy}}\) & 5 & 11.5 Gy & 14.1 Gy \\ \hline ERI\({}_{\text{28\,Gy}}\) & 10 & 23 Gy & 28.3 Gy \\ \hline ERI\({}_{\text{42\,Gy}}\) & 15 & 34.5 Gy & 42.9 Gy \\ \hline ERI\({}_{\text{54\,Gy}}\) & 19 & 43.7 Gy & 53.8 Gy \\ \hline ERI\({}_{\text{62\,Gy}}\) & 22 & 50.6 Gy & 61.7 Gy \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Analyzed fractions and corresponding physical and biological biologically effective doses (BED) values, considering an \(\alpha/\beta\) equal to 10 Gy for the tumor. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**BED**} & \multicolumn{2}{c}{**Median Tumor Volume (cc)**} & \multirow{2}{*}{\(p\)**-Value (Mann–Whitney)**} & \multirow{2}{*}{**ICC**} \\ \cline{2-3} \cline{5-5}  & **Observer 1** & **Observer 2** & \\ \hline
0 Gy & 50.5 & 45.9 & \\ (Simulation) & (7.4–243.6) & (10.4–259.3) & 0.13 & 0.99 \\ \hline
14 Gy & 33.7 (6.3–173.4) & 33.1 (8.5–155.5) & 0.57 & 0.98 \\ \hline
28 Gy & 25.8 (4.3–122.3) & 21.5 (8.1–108.4) & 0.18 & 0.98 \\ \hline
42 Gy & 22.2 (4.0–84.5) & 20.0 (7.0–72.9) & 0.23 & 0.96 \\ \hline
54 Gy & 14.7 (3.4–60.8) & 33.1 (3.5–59.6.5) & 0.53 & 0.95 \\ \hline
62 Gy & 11.6 (1.5–50.2) & 13.0 (2.6–51.7) & 0.32 & 0.97 \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Results of inter-observer variability to varying of the different BED levels. Figure 2: Receiver operating characteristic (ROC) curves calculated at different BED levels considering the two observers. The ROC curves comparison performed using the DeLong test has reported no significant difference in the predictive performance of ERI\({}_{\text{TCP}}\) to varying of the observer for all the BED levels analyzed. In particular, a p-value of 0.41 was obtained comparing the ROC curves in case of 14 Gy, \(p\) = 0.77 in case of 28 Gy, \(p\) = 0.74 in case of BED = 42 Gy, \(p\) = 0.63 for BED = 54 Gy and \(p\) = 0.42 for BED = 62 Gy.