Overexpression of inhibitors of apoptosis proteins (IAPs) in patients treated for locally advanced cervical cancer with exclusive radio-chemotherapy may have a prognostic role on the local recurrence rate at 24 months.
Cervical cancer remains one of the most common cancers in women in terms of both incidence and mortality. Human Papilloma Virus carriage is a necessary condition for the development of these cancers but is not the only factor responsible for malignant transformation. Numerous molecular alterations come into play in the development of these tumours, involving the activation of oncogenes or the inactivation of tumour suppressor genes. Treatment of locally-advanced cancer is based on radiotherapy or a combination of radiotherapy and chemotherapy. Responses to anti-neoplastic treatments remain very heterogeneous from one woman to another. Predicting the response to these treatments would make it possible to envisage early therapeutic alternatives for patients identified as not very sensitive to standard treatments. IAPs (inhibitors of apoptosis proteins), which include XIAP, cIAP1 and cIAP2, are proteins involved in many cancers and capable of downregulating tumour cell apoptosis. It seems justified to investigate the role of these IAPs in resisting apoptosis-inducing anti-neoplastic treatments such as chemotherapy or radiotherapy. The aim of our study is to assess the prognostic role of overexpression of IAPs in locally advanced cervical cancer treated exclusively with radio-chemotherapy. This research seems all the more important as IAP-inhibiting molecules are currently being studied in other types of cancer (ear, nose and throat cancers) and appear to have a very encouraging radiosensitising effect. The hypothesis is that overexpression of IAPs in patients treated for locally advanced cervical cancer with exclusive radio-chemotherapy has a prognostic role on the local recurrence rate at 24 months.
Study Type
OBSERVATIONAL
Enrollment
180
Blocks containing formalin-fixed, paraffin-embedded (FFPE) biopsies will be used to analyse the expression of XIAP, cIAP1 and cIAP2 proteins by immunohistochemistry. The antibodies will be selected on the basis of the literature and their validation for this technology (Schnoell et al. 2020). The immunohistochemical techniques will be performed on an automated immunolabelling machine (DakoLink®) after antigen demasking. The specific binding of primary antibodies will be revealed by the application of Flex reagent (Dako Agilent), a dextran polymer coupled on the one hand to anti-mouse and anti-rabbit immunoglobulins, and on the other hand to a large number of horseradish peroxidase (HRP) molecules. 3,3'-Diaminobenzidine (DAB) will be used as a substrate for this enzyme to highlight the specific expression of the biomarker. The use of an automated system will ensure the reproducibility of inter-sample labelling.
CHU de Nîmes
Nîmes, Gard, France
RECRUITINGPrognostic role of overexpression of XIAP on the rate of local recurrence in patients treated for locally advanced cervical cancer.
Overexpression of the Inhibitor of Apoptosis Proteins XIAP will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer. The H-score for XIAP will be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.
Time frame: Baseline
Prognostic role of overexpression of XIAP on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.
Overexpression of the Inhibitor of Apoptosis Proteins XIAP will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer. The H-score for XIAP will be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.
Time frame: 24 months
Prognostic role of overexpression of cIAP1 on the rate of local recurrence in patients treated for locally advanced cervical cancer.
Overexpression of Inhibitors of the Apoptosis Protein cIAP1 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.The H-score for cIAP1 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.
Time frame: Baseline
Prognostic role of overexpression of cIAP1 on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.
Overexpression of the Inhibitor of Apoptosis Protein cIAP1 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.The H-score for cIAP1 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.
Time frame: 24 months
Prognostic role of overexpression of cIAP2 on the rate of local recurrence in patients treated for locally advanced cervical cancer.
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Overexpression of the Inhibitor of Apoptosis Protein cIAP2 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.The H-score for cIAP2 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.
Time frame: Baseline
Prognostic role of overexpression of cIAP2 on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.
Overexpression of the Inhibitor of Apoptosis Protein cIAP2 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer. The H-score for cIAP1 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.
Time frame: 24 months
Local recurrence of cervical cancer
Local recurrence of cervical cancer at 24 months follow-up according to RECIST v1.1 criteria: Yes/No. RECIST 1.1 is a standard way to measure the response of a tumor to treatment in which Complete Response = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. Partial Response = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Overall survival at 24 months follow-up in patients treated for locally advanced cervical cancer.
A. Overall survival in patients treated for locally advanced cervical cancer at baseline.
Death will be recorded as YES/NO
Time frame: Baseline
A. Overall survival at 24 months follow-up in patients treated for locally advanced cervical cancer.
Death will be recorded as YES/NO
Time frame: 24 months
B. Progression-free survival in patients treated for locally advanced cervical cancer.
The time from diagnosis to death from any cause will be recorded in months and days.
Time frame: Baseline
B. Progression-free survival at 24 months follow-up in patients treated for locally advanced cervical cancer.
The time from diagnosis to death from any cause will be recorded in months and days.
Time frame: 24 months
B. Progression-free survival in patients treated for locally advanced cervical cancer: RECIST criteria
The time between diagnosis and progression according to v1.1 of the RECIST criteria or death from any cause will be recorded in days. RECIST 1.1 is a standard way to measure the response of a tumor to treatment in which Complete Response = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. Partial Response = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Baseline
B. Progression-free survival at 24 months follow-up in patients treated for locally advanced cervical cancer: RECIST criteria
The time between diagnosis and progression according to v1.1 of the RECIST criteria or death from any cause will be recorded in days. RECIST 1.1 is a standard way to measure the response of a tumor to treatment in which Complete Response = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. Partial Response = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: 24 months
B. Progression-free survival in patients treated for locally advanced cervical cancer. H-score
The histochemical scoring assessment (H-SCORE) will be recorded on a scale of 0-300
Time frame: Baseline
B. Progression-free survival at 24 months follow-up in patients treated for locally advanced cervical cancer: H-score
The histochemical scoring assessment (H-SCORE) will be recorded on a scale of 0-300
Time frame: 24 months
C. Correlation between the Inhibitor of Apoptosis Protein XIAP expression and Programmed Death - Ligand 1 expression.
The expression level of XIAP and the expression level of PD-L1 in biopsies will be measured by immunohistochemistry.
Time frame: Baseline
C. Correlation between the Inhibitor of Apoptosis Protein cIAP1 expression and Programmed Death - Ligand 1 expression.
The expression level of cIAP1 and the expression level of PD-L1 in biopsies will be measured by immunohistochemistry.
Time frame: Baseline
C. Correlation between the Inhibitor of Apoptosis Protein cIAP2 expression and Programmed Death - Ligand 1 expression.
The expression levels of cIAP2 and expression level of PD-L1 in biopsies will be measured by immunohistochemistry.
Time frame: Baseline
D. Correlation between the Inhibitor of Apoptosis Protein XIAP expression and lymphocytic tumour infiltration (LTI).
The expression level of XIAP and the level of lymphocytic tumour infiltration will be measured as % in biopsies.
Time frame: Baseline
D. Correlation between the Inhibitor of Apoptosis Protein cIAP1 expression and lymphocytic tumour infiltration (LTI).
The expression level of cIAP1 and the level of lymphocytic tumour infiltration will be measured as % in biopsies.
Time frame: Baseline
D. Correlation between the Inhibitor of Apoptosis Protein cIAP2 expression and lymphocytic tumour infiltration (LTI).
The expression level of cIAP2 and the level of lymphocytic tumour infiltration will be measured as % in biopsies.
Time frame: Baseline