COMPARISON OF RADIOLOGICAL CRITERIA FOR HYPERPROGRESSIVE DISEASE IN RESPONSE TO IMMUNOTHERAPY

Immunotherapy(IOT) is yet a cornerstone of cancer therapy but distinct patterns of response challenge patients’ benefit. Hyperprogressive disease(HPD) is a concerning acceleration of tumor growth induced by IOT and impacting patients safety.The lack of standard radiological criteria for HPD makes its study challenging. We performed a retrospective comparison of Champiat, Saâda-Bouzid, Matos and Kas criteria for HPD in our patient series to study the clinical impact, correlation and accuracy among criteria. From 182 advanced cancer patients treated with early phase IOT trials, 71 had progressive disease at first evaluation and were eligible for the study. Pre-baseline, baseline and first assessment CT SCANs were independently evaluated by two research oncologists and a senior radiologist. Patients considered HPD by Champiat, Saâda-Bouzid, Matos, and Kas criteria were studied for tumor growth rate (TGR) to perform a statistical comparison among them. Of 71 evaluable patients, 17(23,9%),17(23.9%),23(32.4%), and 6(8.4%) had HPD by Champiat, Saâda-Bouzid, Matos and Kas definitions, respectively. The KR20 showed low internal consistency among the four criteria associated to Matos’ discrepancy with the others.Concordance measured by Cohen’s Kappa value showed the highest association between Champiat and Saâda-Bouzid criteria, with 12 out of 17 patients agreement (Kappa=0.613), and the lowest between Champiat and Matos’, with just 8 patientsconcordance (Kappa=0.172).The agreement among the four criteria was studied by Jaccard similarity index and varied from 55% (Champiat and Saâda-Bouzid) to 21% (Saâda-Bouzid and Kas). Champiat and Saâda-Bouzid criteria showed a statistically significant difference between pre-baseline and post-baseline TGR in HPD patients (p= .00 and p= .04, respectively), which could not be confirmed with the Matos'(p= 0.701) or Kas criteria (p=.073).Significant differences in progression-free survival were observed between non-hyperprogressors and hyperprogressors by all criteria. Hyperprogression is an Immunotherapy-related acceleration of tumor growth, as reflected by the changes in tumor growth rate dynamics resulting in a negative clinical impact in a meaningful proportion of cancer patients. Pre-baseline CT scans and tumor growth rate evaluations are required to identify Hyperprogression. Our analysis favors the use of the Saâda-Bouzid method, as it fully captures the hyperprogression phenomenon and is more convenient to use.