## 2 Materials and Methods  
### Patients Selection Criteria and Treatment Workflow  
Patients affected by LACC (FIGO IB2-IVA) were enrolled in this study, with the following inclusion criteria: Patients affected by biopsy proven LACC with no evidence of distant metastases at the radiological staging exams; Eastern Cooperative Oncology Group (ECOG) performance status \(\leq\)2, no pregnancy or breastfeeding at the moment of nCRT and at least 18 years old at the time of diagnosis.  
Informed consent for therapy and image analysis purposes was acquired from all patients. Patients presenting clinical contraindications to MRI (e.g., presence of non MRI-compatible implanted devices, claustrophobia or major psychiatric disorders) or denying specific consent to MR guided radiotherapy (MRgRT) were not included.  
The diagnostic workflow consisted in a gynecological exam, a diagnostic 1.5 T MR of the abdominal-pelvic site and a whole-body \({}^{18}\)FDG-positron emission tomography (PET)-CT staging scan.  
All the patients underwent nCRT, combining weekly 40 mg/m\({}^{2}\) of cisplatin with concurrent MRgRT, administered using a simultaneous integrated boost (SIB) technique delivered in 22 fractions and prescribing a dose value of 50.6 Gy (2.3 Gy/fraction) to clinical target volume (CTV)1 and 39.6 Gy (1.8 Gy/fraction) to CTV2 [20].  
All the patients signed a specific informed consent describing in detail the chosen therapeutic approach.  
Radiotherapy was delivered using a 0.35 T MRgRT hybrid unit (ViewRay Inc., Mountain View, CA, USA) and therapy volumes were delineated on the 0.35 T TRUFI MR scan acquired during treatment simulation and using co-registered diagnostic 1.5 T staging MR and \({}^{18}\)FDG PET-CT images as supporting imaging.  
The Gross Tumor Volume (GTV) was identified using the MR and PET-CT supporting images. CTV1 coincided to GTV and CTV2 was delineated as the union of the entire cervix, the uterus, parametria, vagina (entire or upper half, according to presence or absence of disease) and the corresponding drainage nodal.  
If the pelvic nodes resulted positive at staging imaging, the common iliac nodes were included in the CTV2 volume, while the para-aortic nodes were included in case that the common nodes were positive [20]. CTV1 and CTV2 were expanded with 5 mm isotropic margin to generate the corresponding planning target volumes, following the institutional MRgRT guidelines [21].  
An online adaptive procedure was administered in the treatment fractions where the positioning MR image showed that the GTV was not included in the Planning Target Volume (PTV) margins. GTV, PTV, bladder, bowel bag and rectum were re-contoured in case of online adaptive.  
From six to eight weeks after the end of the treatment a restaging was performed, through a gynecological visit and a new MRI and \({}^{18}\)FDG PET-CT acquisition. A Querleu-Morrow radical hysterectomy with pelvic lymphadenectomy was performed for each patient within 8 weeks of the end of nCRT [8].  
Pathological response to treatment was evaluated on surgical specimens, and three categories of treatment response were identified:  
Complete response (pR0), as absence of any residual tumor cells at any site;  
Microscopic response (pR1), as presence of persistent tumor foci not exceeding 3 mm for the maximum dimension;  
Macroscopic response (pR2), as presence of persistent tumor foci exceeding 3 mm for the maximum dimension  
pCR was considered in case of pR0 [25].