Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives

Abstract

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Keywords: EASL; MDA criteria; PERCIST; RANO criteri; RECICL; RECIST; WHO criteria; irRC; mRECIST.

Figure 1

Decision algorithm for choosing response criteria.

Figure 2

Pre- and Post FDG PET in a 47 y/o female with metastatic breast Cancer and multiple osseous metastases. Baseline study shows focal sites of activity in the bone marrow space, without discernible anatomic abnormality. About 6 weeks after starting therapy, there is diffuse marrow activation; however, there is relative loss of normal marrow activity where tumor was previously seen, and there is new sclerotic change at those sites. About 4 months after starting therapy, there is still diffuse marrow activation with loss of normal marrow activity where tumor was, and increased sclerosis on CT images. Unfortunately, about 10 months after starting therapy, she relapsed, with new focal sites of activity, without anatomic abnormality (similar to baseline study), whereas previously tumor sites have become densely sclerotic and remain without activity to suggest active tumor.

Figure 3

Pre- and Post FDG PET in an 82 old female with gastro-intestinal stromal tumor (GIST). Baseline FDG/PET study was performed off tyrosine kinase inhibitor therapy and she was initiated on a therapy. Repeat study was performed two weeks after initiation of Gleevec^® (Imatinib) a specific c-KIT inhibitor. Both anatomic and metabolic response was seen. Although there was still a residual anatomic abnormality, the tumor had complete metabolic response. This illustrates that the power of early functional imaging.

Figure 4

PRE and POST CT and PET/CT in a female in her 40’s with recurrent GIST. She has had multiple prior therapies and had relapsed from several TKI’s. After 2 weeks of novel therapy, she has had a complete metabolic response, but only a partial anatomic response.

Figure 5

Pre and Post FDG PET CT in a 22 y/o male with Hodgkin lymphoma (nodular sclerosis type). He had complete metabolic response after 2 cycles of chemotherapy (ABVD) but only partial anatomic response. He completed 6 cycles of therapy with complete metabolic response but residual anatomic abnormalities. He had consolidation radiation therapy, about 1 month after completing chemotherapy; about 2 months after completing radiation therapy, there was no change. It is not uncommon to have residual masses after therapy for lymphoma, especially Hodgkin lymphoma, which may complicate anatomic response assessment.