Abstract 5544
Background
Several studies have suggested that combining radiotherapy (RT) to immunotherapy (IO) may be synergistic but many questions are still pending regarding the radiation modalities to optimize this combination, such as the choice of the lesion to irradiate. Radiomics consists in the analysis of quantitative data extracted from standard medical imaging to generate imaging biomarkers. A previous study published in The Lancet Oncology has shown that a radiomic signature could predict the CD8 cells infiltration, which is associated with the activity of anti-PD-1/PD-L1. We aimed to assess whether this biomarker could help to guide IO-RT combinations.
Methods
Patients from three clinical studies of IO-RT combinations with advanced solid tumors in two institutions were screened. Patients with available baseline (E0) and first evaluation (E1) CTs were included. Immunotherapy consisted in 4 different drugs. Hypofractionated conformal RT or stereotactic RT of one tumor lesion was delivered after the start of IO for most of the patients. The irradiated lesion and a sample of non-irradiated lesions were delineated from E0 and E1 CTs. Radiomics features were extracted and the published radiomic signature was applied to estimate the CD8 cells.
Results
84 patients were included. 244 tumor lesions were delineated on the E0 CT, including the 84 lesions which were selected for irradiation. Median time between IO and RT start was 21 days (IQR: 9-24), and 2.4 mo between E0 and E1 (IQR: 1.3 - 3). 80 irradiated lesions and 152 non irradiated lesions remained at E1. At baseline, the volume and the radiomic score of TIL (RS) were not different between the two groups (irradiation or no) (p = 0.94 and 0.50). While the mean volume of the analyzed lesions was not different from E1 to E0 (p = 0.15), irradiated lesions were significantly smaller at E1 (p = 0.03). A high RS in the irradiated lesion at E1 (compared to the median value) was associated with PFS (HR = 0.57, IC95%: 0.345-0.95, p = 0.031) irrespective of the volume in multivariate analysis but was not significantly associated with OS.
Conclusions
Radiomic score of the irradiated lesion was associated with PFS. Such biomarker may help to guide the selection of the lesion to irradiate in IO-RT combinations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gustave Roussy Cancer Campus.
Funding
Fondation pour la Recherche Médicale, SIRIC-SOCRATE 2.0, Fondation ARC, Amazon.
Disclosure
R. Sun: Travel / Accommodation / Expenses: AstraZeneca. N.L. Sundahl: Travel / Accommodation / Expenses: Merck Sharpe & Dohme; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb. P. Ost: Research grant / Funding (institution): Merck Sharpe & Dohme; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Travel / Accommodation / Expenses: Ferring Pharmaceuticals; Honoraria (self): Bayer. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Jansen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Orion. E. Deutsch: Advisory / Consultancy, Research grant / Funding (institution): Roche Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD. All other authors have declared no conflicts of interest.
Resources from the same session
3664 - Longitudinal changes in cell-free DNA (cfDNA) methylation levels identify early non-responders to treatment in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3212 - Multigene panel testing results for hereditary breast cancer in 1325 individuals: implications for gene selection and considerations for guidelines.
Presenter: Georgios Tsaousis
Session: Poster Display session 3
Resources:
Abstract
2591 - PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Presenter: Julia Quintanilha
Session: Poster Display session 3
Resources:
Abstract
4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.
Presenter: Nuria Chic
Session: Poster Display session 3
Resources:
Abstract
3439 - Early on-treatment vs pre-treatment tumor transcriptomes as predictors of response to neoadjuvant therapy for HER2-positive inflammatory breast cancer
Presenter: Sonia Pernas
Session: Poster Display session 3
Resources:
Abstract
2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)
Presenter: Claudia Cardone
Session: Poster Display session 3
Resources:
Abstract
4061 - Prevalence of EGFR mutations and its correlation with Egyptian patients’ human kinetics (PEEK Study)
Presenter: Adel Ibrahim
Session: Poster Display session 3
Resources:
Abstract
2547 - Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)
Presenter: Sergio Rutella
Session: Poster Display session 3
Resources:
Abstract
4671 - Clinicopathological and molecular criteria assessment for the screening of hypermutated proficient mismatch repair (pMMR) colorectal cancers (CRC) with exonucleasic domain POLE (edPOLE) mutations (mt).
Presenter: Benoit Rousseau
Session: Poster Display session 3
Resources:
Abstract
3862 - Tumor mutation burden and microsatellite instability in colorectal cancer
Presenter: Francesca Fenizia
Session: Poster Display session 3
Resources:
Abstract