Biomarker expression and impact on clinical outcomes in an international study of chemoradiation and MRI-based image-guided brachytherapy for locally advanced cervical cancer: BIOEMBRACE.

PURPOSE: BIOEMBRACE-I was designed to study the impact of biomarkers in addition to clinic-pathological factors on disease outcomes in patients treated with chemoradiation and MRI-guided brachytherapy (BT) for locally advanced cervical cancer in EMBRACE study. PATIENT AND METHODS: Between 2018-2021, eight EMBRACE-I sites contributed tumour tissue for immunohistochemistry of p16, PD-L1 and L1CAM. These biomarkers and clinicopathological factors (FIGO 2009 stage, nodal status, histology, necrosis on MRI) were analysed to predict poor response at brachytherapy (BT) (high-risk clinical target volume [HR-CTV] ≥40cc) at BT), and 5-year local control, pelvic control and disease-free survival (DFS). Interaction between p16, PD-L1, radiotherapy dose (HR-CTV D90) and disease outcomes was investigated. Univariable and multivariable analysis were performed. RESULTS: Two-hundred sixty-four patients were included. The median HR-CTV D90 was 89 (86-95) Gy. p16 positive (pos), PD-L1>1% and L1CAM ≥ 10% was noted in 86.6%, 20.1% and 17.8% respectively. P16 negative (neg) status (OR 2.0 (1.0-5.7), p=0.04), necrosis on MRI (OR 2.1 (1.1-4.3), p<0.02) independently predicted for HR-CTV≥40cc, as did FIGO stage and tumour width >5cm. PDL1>1% was associated with reduced local (82% vs. 94%, p=0.02) and pelvic control (79% vs. 89%, p=0.02). HR-CTV D90 <85Gy was associated with inferior 5-year local control in p16+ patients especially if PD-L1 was co-expressed. On multivariable analysis, PD-L1>1% was the only independent factor for 5-year local control (HR 3.3, p=0.04) and L1CAM ≥50% for pelvic control (HR 5.5 (1.3-23.3), p =0.02). CONCLUSIONS: P16 neg status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1>1% and L1CAM≥50% have an independent impact on local and pelvic control suggesting impact of biomarker expression on outcomes. Further validation is needed.

Hyperspectral Imaging for Tissue Classification after Advanced Stage Ovarian Cancer Surgery-A Pilot Study.

The most important prognostic factor for the survival of advanced-stage epithelial ovarian cancer (EOC) is the completeness of cytoreductive surgery (CRS). Therefore, an intraoperative technique to detect microscopic tumors would be of great value. The aim of this pilot study is to assess the feasibility of near-infrared hyperspectral imaging (HSI) for EOC detection in ex vivo tissue samples. Images were collected during CRS in 11 patients in the wavelength range of 665−975 nm, and processed by calibration, normalization, and noise filtering. A linear support vector machine (SVM) was employed to classify healthy and tumorous tissue (defined as >50% tumor cells). Classifier performance was evaluated using leave-one-out cross-validation. Images of 26 tissue samples from 10 patients were included, containing 26,446 data points that were matched to histopathology. Tumorous tissue could be classified with an area under the curve of 0.83, a sensitivity of 0.81, a specificity of 0.70, and Matthew's correlation coefficient of 0.41. This study paves the way to in vivo and intraoperative use of HSI during CRS. Hyperspectral imaging can scan a whole tissue surface in a fast and non-contact way. Our pilot study demonstrates that HSI and SVM learning can be used to discriminate EOC from surrounding tissue.