A. Marabelle

Prospective validation of a prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score (GRIm-Score).

INTRODUCTIONnLife expectancy evaluation is crucial when selecting patients who may benefit from phase I studies. The Royal Marsden Hospital (RMH) prognostic score, based on three objective variables (number of metastatic sites, lactate dehydrogenase (LDH) and serum albumin) was validated in patients treated with cytotoxics and targeted therapies. We aimed to determine if those factors were applicable to immune-checkpoint therapies (ICTs) in phase I trials and to evaluate new variables that may preclude a better prognosis in patients receiving ICT.nnnPATIENTS AND METHODSnWe conducted a retrospective analysis of survival risk factors in a discovery cohort of 155 patients enrolled into ICT phase I trials at our institution. We computed univariate analysis and multivariate analysis (MVA) of demographics, clinical and biological data to assess their prognostic value for overall survival (OS). MVA results were used to build a prognostic score for OS. A validation cohort of 113 patients enrolled in phase I ICT trials was used to prospectively validate this score.nnnRESULTSnA total of 155 patients (M/F: 83/72; median age 59) receiving an experimental ICT between March 2012 and January 2016 were included in the discovery cohort. An MVA assessing the RMH score variables showed that low albumin (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.05-2.86) and LDHxa0>xa0upper limit normal (ULN) (HR 1.88, 95% CI 1.12-3.15) were independent negative prognostic factors for OS. Interestingly, neutrophil-to-lymphocyte ratio (NLR)xa0>xa06 (HR 1.75, 95% CI 1.04-2.95) was associated with a decrease in OS. The number of metastases was not associated with a poorer outcome for this ICT cohort (HR 0.83, 95% CI 0.51-1.35). A risk score based on the results of the MVA (NLRxa0>xa06xa0=xa01; LDHxa0>xa0ULNxa0=xa01; albuminxa0<xa035xa0g/lxa0=xa01) showed that patients presenting a high score (>1) had a significantly shorter OS (20.4 weeks; 95% CI 5.7-35.2) compared to those with a low score (0 or 1) (68.9 weeks; 95% CI 50-83.7) (HR 2.9, 95% CI 1.87-4.64). In the validation cohort of 113 patients, again the patients presenting a high score showed an inferior OS (HR 6.3, 95% CI 2.7-14.8).nnnCONCLUSIONnIn ICT phase I trials, traditional prognostic variables included in the RMH score may be suboptimal to determine patients prognosis. In this context, the NLR is a significant prognostic variable. The Gustave Roussy Immune Score, based on albumin, LDH and NLR, allows a better selection of patients for ICT phase I trials.

Immuno-Oncology in Cancer Care is a Fantastic Opportunity for Interventional Oncology: IO4IO (Interventional Oncology for Immuno-Oncology) Initiative

Immuno-oncology is a rapidly expanding weapon in the anti-cancer arsenal of modern oncology. The revolution of immuno-oncology in cancer care is the result of intense research over the past decade in cancer immunology that has provided solid evidence that tumours can be recognised and controlled by the host immune system, a process known as immunosurveillance [1, 2]. Systemic immuno-targeted therapies are now approved treatment options in many cancer types because of their clinical efficacy even in relapsing/refractory patients through different primary cancer locations. These novel immuno drugs allow an enhancement of patients’ anti-cancer immunity, namely by blocking inhibitory pathways and inhibitory cells in the tumour microenvironment. The most common strategy is to use checkpoint inhibitors such as antibodies against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed death-1 (PD-1) or its ligand, programmed death ligand-1 (PDL-1). Other strategies aim to enhance the specificity of anti-tumour immunity using antibodies directed to well-defined tumour antigens with the help of either cancer vaccines, potent adjuvants or various types of immunomodulating agents, such as pattern recognition receptor agonists, recognising pathogen-associated molecular patterns or immunostimulatory monoclonal antibodies. Oncolytic viruses and peptides are used to release tumour antigens in order to stimulate immunity [3, 4]. Furthermore, in vitro expansion of the patient’s own T-cells, which can be genetically modified for specificity towards a specific tumour-associated antigen called chimeric antigen receptor T cell (CAR T-cells), is also now an FDA-approved therapy in blood cancer. Those therapies are currently used systemically, and experience in their local application mainly refers to melanoma, while local application for solid organ tumours is still insufficiently explored. Immuno-oncology carries new opportunities for interventional oncology, and it is vital for interventional radiologists/ oncologist to actively engage in enhancing immuno-oncology. A critical value of interventional oncology is the expertise in target selection, sampling and treatment administration. Image guidance ensures safe access and precise distribution to the tumour or peri-tumoural environment through either direct puncture or intra-arterial routes, even when deeply located or adjacent to vulnerable structures. Interventional oncology treats tumours locally, including percutaneous ablation (radiofrequency, microwave and cryoablation, and irreversible electroporation), but also intra-arterial therapies delivering drugs, embolics or radio isotopes selectively to the tumour-feeding arteries with excellent tolerance, rendering treatment easily repeatable if needed. Even if complete destruction of some targeted tumours can be achieved with interventional oncology treatments, such therapy is often limited due to the tumour size or the number of tumour lesions.