Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC)

Abstract

irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.

The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

“…Complete tumor resection or biopsy (confirming tumor progression) would be performed approximately 29-43 days after the first dose. Primary tumors were assessed for the percentage of residual viable tumor in the resected lung tissue, and MPR defined as tumors with no more than 10% viable tumor cells [18].…”

“…The formula was as follows take ΔSUL max % for example, ΔSUL max % = (SUL max of scan-1 − SUL max of scan-2)/ SUL max of scan-1 × 100%. Response to the neoadjuvant therapy was classified as (1) complete metabolic response (CMR), defined as a complete resolution of 18 F-FDG uptake within the measurable target lesions and other lesions (less than mean liver activity and at the level of surrounding background blood-pool activity) without the advent of new suggestive 18 F-FDG avid lesions; (2) partial metabolic response (PMR), defined as a reduction of 30% or more in the target tumor SUL peak (and an absolute drop of at least 0.8 SUL); (3) progressive metabolic disease (PMD), defined as 30% or more increase in SUL peak and 0.8 unit increase in SUL peak or the advent of new 18 F-FDG avid lesions typical of cancer; (4) stable metabolic disease (SMD), defined as disease other than CMR, PMR, or PMD [20].…”

“…Furthermore, the tumor response patterns of immunotherapy may differ compared with conventional chemotherapeutic agents or targeted therapies, and the accuracy of response assessment is radiologically challenging [6][7][8]. 18 F-FDG PET-CT is the most useful tool for evaluating changes of lesion on molecular level. The mechanism of FDG uptake within tumor cells is concerned with the presence of glucose metabolism, hypoxia, and angiogenesis [9][10][11].…”

“…In a recent study, FDG PET was considered to provide more useful information on assessing response of advanced NSCLC to immunotherapy than that of computed tomography (CT) [15]. On the basis of these findings, 18 F-FDG PET-CT in predicting immunotherapy response to NSCLC seems to be a valuable and important research area in clinical application. Sintilimab is a recombinant humanized anti-PD-1 monoclonal antibody injection that blocks interactions between PD-1 and its ligands and has been tested regarding the safety and activity in patients with advanced stage solid tumor and was approved for lymphoma by Chinese Center for Drug Evaluation in China in 2018 [16].…”

“…Phase I/II development of sintilimab for use in solid tumors is underway in the USA, with the US FDA accepting an Investigational New Drug Application for sintilimab in January 2018 [16]. The current study aims to evaluate the relationship between tumor metabolic parameters of 18 F-FDG PET-CT and the surgical pathology of the neoadjuvant sintilimab in resectable NSCLC patients, and to investigate if PET-CT has the potential to predict the major pathologic response (MPR), which predict improved long-term patient outcome [17,18].…”