Understanding patterns of pathologic response following neoadjuvant immunotherapy for solid tumors

The widespread use of immunotherapeutics in oncology [immune-oncology (IO)] today represents a fundamental shift in the clinical approach to elimination of cancer cells. In contrast to the directly cytotoxic and/or cytostatic effects of conventional chemotherapy, radiotherapy, and targeted therapies, drugs directed at immune checkpoints, including PD-1/PD-L1 and CTLA4, harness the patient's immune system to effect tumor cell killing [1]. IO approaches have shown particular promise in solid tumors with a high burden of immunogenic neoantigens, such as non-small-cell lung cancer (NSCLC) and melanoma, and currently represent standard of care treatment of at least a subset of patients with these tumor types [2]. Radiographic studies of tumors undergoing immunotherapy have identified some distinctive patterns of tumor response, such as pseudoprogression and development of new lesions despite shrinking of the baseline tumor, triggering proposals for revised approaches to radiographic response evaluation in IO-treated patients [3, 4]. These unique radiographic patterns are thought to represent tumor infiltration by immune cells, however, the actual reasons for dynamic changes in radiographic tumor appearance can only be inferred from imaging studies.