**Author details**

**7. Tumor response evaluation of immunotherapy**

been detected.

92 Immunopathology and Immunomodulation

the tumor with or without edema [97].

tion with survival.

**8. Conclusion**

An issue that has been recently recognized is the measurement of antitumor effect of immu‐ notherapy. The cytotoxicity of chemotherapeutic agents often produces a measurable change in the size of the target lesions within weeks of the initial administration. Response for solid tumors is most frequently assessed using WHO or RECIST criteria [90,91]. For cytotoxic agents, these guidelines assume that an early increase in tumor growth and/or appearance of new lesions signal progressive disease (PD) and the term "progression" became synonymous with drug failure. Cessation of the currently used chemotherapy is thus recommended once PD has

On the other hand, immunotherapeutic agents enhance antitumor immune responses [92] and achievement of stable disease (SD) may also be viewed as an indicator of meaningful thera‐ peutic effect. Beyond that, additional novel response patterns, observed with these agents, raise concerns about the interpretation and characterization of WHO or RECIST criteria. In studies with cytokines, cancer vaccines, and monoclonal antibodies, response classified as CR, PR, or SD has been shown to occur after an initial increase in tumor burden characterized as PD by WHO or RECIST criteria [93-96]. Therefore, conventional response criteria may not adequately assess the activity of immunotherapeutic agents because PD (by initial radio‐ graphic evaluation) does not necessarily reflect therapeutic failure. Thus, in order to system‐ atically characterize additional patterns of response in patients treated with immunotherapy, underlying WHO criteria were evolved into immune-related response criteria (irRC) [97]. The core novelty of the irRC is the incorporation of measurable new lesions into "total tumor burden" and comparison of this variable to baseline measurements (before and after WHO PD, but not after confirmed irPD). Clinical activity often appears to be delayed following immunotherapeutic treatment and a period of apparent progression (as defined by the existing response criteria) may occur, followed by response. Four types of distinct response patterns have been described (two conventional and two new, unique to immunotherapy): 1) imme‐ diate response; 2) durable stable disease; 3) response after tumor burden increase; and 4) response in the presence of new lesions. The apparent increase in tumor burden that sometimes precedes response in patients receiving immune therapy may reflect either continued tumor growth until a sufficient immune response develops or transient immune-cell infiltration into

The use of irRC for response evaluation with immunotherapeutic treatment is considered clinically meaningful as they appear to be related to favorable survival. However, they are still in early development and prospective trials need to evaluate their role and potential associa‐

A lot of scientific evidence has been recently accumulated over the role of the immune system in the prevention, development and progression of solid tumors. All this knowledge is

Assia Konsoulova1,2

Address all correspondence to: dr.konsoulova@gmail.com

1 Medical Oncology Clinic, University Hospital Sveta Marina, Varna, Bulgaria

2 University of Medicine, Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria

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## **Chapter 6**
