Imaging Assessment of Tumor Response in the Era of Immunotherapy

Abstract

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.

Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

“…Given that most of our patients are not Arizona residents and may have undergone imaging at various locations, in addition to the short treatment duration at Envita renders imaging and tumor markers as unreliable biomarkers for our patient outcome assessment. Tumor response following treatment is commonly assessed using imaging techniques; response evaluation criteria in solid tumors (RECIST) and positron emission tomography (PET) response criteria in solid tumors (PERCIST) have been the established morphologic and metabolic response criteria to predict outcomes and dictate treatment [54]. Immunotherapy often causes the tumor to increase followed by a decrease, a phenomenon known as "pseudoprogression", discrediting the use of computed tomography or magnetic resonance imaging for evaluation [54] [55].…”

“…Tumor response following treatment is commonly assessed using imaging techniques; response evaluation criteria in solid tumors (RECIST) and positron emission tomography (PET) response criteria in solid tumors (PERCIST) have been the established morphologic and metabolic response criteria to predict outcomes and dictate treatment [54]. Immunotherapy often causes the tumor to increase followed by a decrease, a phenomenon known as "pseudoprogression", discrediting the use of computed tomography or magnetic resonance imaging for evaluation [54] [55]. An immune response can also cause 18F-fluorodeoxyglucose (FDG), used as a diagnostic radioactive tracer for PET, uptake in tumors thereby invalidating the use of FGD-PET imaging for follow-up after immunotherapy [54].…”

“…Immunotherapy often causes the tumor to increase followed by a decrease, a phenomenon known as "pseudoprogression", discrediting the use of computed tomography or magnetic resonance imaging for evaluation [54] [55]. An immune response can also cause 18F-fluorodeoxyglucose (FDG), used as a diagnostic radioactive tracer for PET, uptake in tumors thereby invalidating the use of FGD-PET imaging for follow-up after immunotherapy [54].…”

Pseudoprogression in advanced non-small cell lung cancer treated with combination chemoimmunotherapy: a case report

“…However, recent NSCLC clinical trials of combination chemotherapy plus ICI have employed standard RECIST [ 15 , 16 ]. Additionally, these trials perform and act on early radiographic efficacy assessments (typically after 2 cycles, approximately 6 weeks after treatment initiation), in contrast to the later and confirmatory assessments recommended for immunotherapy [ 17 ].…”