Estimation of Tumor Response With Linac MRI-guided Adaptive Radiotherapy for Locally Advanced Cervical Cancer

The management of locally advanced cervical cancer (Figo \>IB) is based on radiochemotherapy (RCT) followed by brachytherapy. At present there is no personalized treatment, all patients undergoing radiochemotherapy will follow a conventional treatment by external radiotherapy (46 Gy in 23 sessions associated with cisplatin (CDDP) weekly) and brachytherapy to achieve a total equivalent biological dose around 80-90 Gy).The efficacy of this treatment has been proven for most patients, almost 80% being in complete response after RCT. Nevertheless, on an individual scale, there remains a significant variation in the tumor response, with patients who respond from the first week of treatment, "early responders" or, on the contrary, others who present significant tumor residues after external beam radiotherapy.Various macroscopic tumor volume (GTV) response patterns have been identified based on magnetic resonance imaging (MRI) at diagnosis and MRI before brachytherapy, implying very different clinical target volumes for brachytherapy technique. The difference in tumor volume response has been identified as having a major impact on treatment response.

This is the first study attempting to evaluate tumor response in real time during radiochemotherapy treatment. Knowing the tumor response during treatment will make it possible to modify the management of locally advanced cervical cancer, several therapeutic options might then be discussed depending on the early response to treatment: dose de-escalation for early responders, reduction of time total treatment, personalization of brachytherapy management (technique and dose).

This observational study will allow rapid identification of responder and non-responder patients and might be used as a basis for personalized treatment strategies


Eligibility Criteria:
Inclusion Criteria:

- Women aged ≥ 18 and ≤ 70 years old.

* Histologically confirmed cervical cancer: stage IB2-IVA squamous cell carcinoma or adenocarcinoma (FIGO 2018 criteria), regardless of pelvic lymph node status, no positive lomboaortic lymph nodes. Patients should have no metastatic localization of disease.
* Performance index ≤ 1 (WHO).
* Hematological function: polymorphonuclear neutrophils \> 1.5 x 109/L, platelets \> 100 x 109/L, hemoglobin \> 8,5 g/dL.
* Liver function: total bilirubin \< 20 µmol/L or \< 12mg/L
* Renal function: creatinine clearance MDRD (Modification of diet in renal disease) \>40 ml/min creatinine
* Serum pregnancy test within 7 days before the start of study treatment if risk of pregnancy mentioned by the patient
* Patient able to sign an informed consent form

Exclusion Criteria:

* Previous treatment with radiotherapy, chemotherapy, targeted therapy or immunotherapy treatment for cancer of the cervix or for any other cancer within the previous 5 years.
* Live vaccine, such as yellow fever vaccine.
* History of pelvic irradiation or prior surgical treatment for cancer of the cervix (excluding diagnostic conization).
* Contraindication to MRI imaging (pace maker, metal prosthesis, phobia, etc.)
* Contraindication to the use of cisplatin.
* Inability to perform the follow-up required by the study for geographical, social or psychological reasons.
* History of HIV, HBV or HCV infection with positive serology.
* Pregnant or breastfeeding woman