The importance of radioresistance in cervical cancer treatment failure indicates that certain biomarkers may be useful for cervical cancer treatment individualization. However, to date, no study has analyzed the role of the gene expression signature of the three RNA species (ANXA2-NDRG1-STAT1) to predict radiosensitivity/resistance in cervical cancer patients undergoing exclusive CTRT. The previously validated three-gene signature may enable stratification in LACC patients treated with the current standard of care, represented by exclusive CTRT.

The importance of radioresistance in cervical cancer treatment failure indicates that certain biomarkers may be useful for cervical cancer treatment individualization. Several biomarkers of cervical cancer radioresistance have been previously studied and proposed; however, none of these has been the subject to further clinical studies and implemented into clinical practice. Recently, a panel of three protein coding genes (ANXA2-NDRG1-STAT1) differently expressed in radiosensitive LACC patients compared with the radioresistant ones, has been proposed by our institution. The population of LACC patients included in a previous study was treated with neo-adjuvant CTRT followed by radical surgery. However, to date, no study has analyzed the role of the gene expression signature of the three RNA species (ANXA2-NDRG1-STAT1) to predict radiosensitivity/resistance in cervical cancer patients undergoing exclusive CTRT. The previously validated three-gene signature may enable stratification in LACC patients treated with the current standard of care, represented by exclusive CTRT.

Inclusion Criteria:

• Age > 18 years
• Histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
• FIGO 2018 stage IIB and IIIC1[38]
• Treatment with exclusive chemoradiation including brachytherapy
• Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer
• Has radiographically evaluable disease, measurable per RECIST 1.1
• Negative pregnancy test
• Adequate hematologic, renal, and hepatic functions, with following blood tests:

Neutrophils > 1500/μL Platelets > 100.000/ μL Hemoglobin > 9 g/dL Serum creatinine < 1.8 mg/dL Total bilirubin < 3 mg/ dL LDH < 3x normal value GOT < 3x normal value GPT < 3x normal value ALP < 3 x normal value

Exclusion Criteria:

• Rare cervical cancer histologies (neuroendocrine, glassy cells, serous, endometrioid etc)
• Neo-adjuvant treatment
• Patients included in other clinical trials
• Patients refusing to sign informed consent
• Contraindications to radiotherapy
• Contraindications to pelvic radiotherapy: ulcerative colitis, diverticulitis, chronic pelvic inflammatory disease, previous pelvic radiotherapy

Patients with histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix FIGO stage IIB and IIIC1.