T-lymphocytes and hypoxia predicts survival after brachytherapy in locally advanced cervical cancer
OC-0090
Abstract
T-lymphocytes and hypoxia predicts survival after brachytherapy in locally advanced cervical cancer
Authors: Trine Tramm1, Jan Alsner2, Patricia Switten Nielsen1, Jeanette Bæhr Georgsen1, Jens Overgaard2, Jacob Christian Lindegaard3
1Aarhus University Hospital, Pathology, Aarhus C, Denmark; 2Aarhus University Hospital, Experimental Clinical Oncology, Aarhus C, Denmark; 3Aarhus University Hospital, Oncology, Aarhus C, Denmark
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Purpose or Objective
Presence of CD8 positive (CD8+), cytotoxic T-lymphocytes in treatment naïve tumor has been found to be a predictive factor for benefit of radiotherapy (RT) in breast cancer with improved distant tumor control translating into superior survival (1). Following employment of chemoradiation (CRT) and image guided adaptive brachytherapy (BT), loco-regional control in locally advanced cervical cancer (LACC) has improved considerably and systemic relapse is now the dominant problem. The aim of this study was to investigate, if presence of tumorinfiltrating T-lymphocytes is a prognostic factor in LACC.
Material and Methods
Multiplex chromogen immunohistochemistry was performed on paraffin embedded biopsies containing pre-treatment tumor tissue obtained from 189/190 consecutive patients from a previous study on hypoxia in squamous cell LACC treated 2005-2016 (2). Subsets of T-lymphocytes was visualized using CD4, CD8, FOXP3 and AE1/3 as tumor marker. Area fraction of the various immune cells (area of immune cells/area of tissue) was determined by digital image analysis, and two groups were generated for each marker based on median values. Hypoxia status was reported previously (2).
The FIGO2009 stage distribution among the 189 patients was IB-IIA 10%, IIB 64% and III-IVA 26%. Pathological pelvic nodes (N1) were found in 76 (40%) and para-aortic nodes (N2) in 23 (12%) patients. All patients received pelvic external beam RT of 45-50 Gy/25-30 fx including also the para-aortic region in 38 (20%). Concomitant weekly cisplatin was given to 145 (77%). All patients were treated with BT with mean CTVHR volume of 35 cm3 and a D90 of 92 GyEQD2. Endpoints were extra-pelvic control (EPC), disease free survival (DFS), and overall survival (OS) calculated from start of CRT. EPC was analysed using Aalen-Johansen estimator and cause-specific Cox regression, DFS and OS using Kaplan-Meier estimator and Cox regression.
Results
Median observation times were 5.1 years (EPC) and 7.1 years (OS). EPC was obtained in 140/188 (74%). High levels of CD8+, CD4+, and FOXP3+ cells, and a ‘less’ hypoxic profile were significantly associated with improved OS (Figure 1). Similar trends were observed for EPC and DFS but only the association between hypoxia and DFS was significant. On continuous scales, CD4 and CD8 were correlated (Figure 2A). ‘Less’ hypoxia was significantly associated with high levels of CD4, CD8 (p values < 0.0001) but not with FOXP3 (Figure 2B).
Conclusion
Presence of pre-existing, tumorinfiltrating T-lymphocytes and hypoxic status are prognostic factors for overall survival for LACC with squamous cell histology after BT. High infiltration of CD4+ and CD8+ T-cells was found to correlate with a ‘less’ hypoxic profile. Evaluation of immune cell infiltration and hypoxia may be carried out on pre-treatment biopsies and may assist in selecting high risk patients for adjuvant systemic treatment following CRT and BT.
1 doi: https://doi.org/10.1016/S0167-8140(22)02604-4
2 doi: https://doi.org/10.1080/0284186X.2021.1979249
