ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 13 Summary of Current Studies of Atypical Responses Limitations of the majority of studies described above are that they: 1) Generally focus on exceptional responders; 2) Usually do not state a definitive intent to share de-identified data on a secure platform (with a few exceptions); and 3) Potentially overemphasize the role of molecular aberrations while rarely investigating other important factors that may play a key part in an atypical response. Other Definitions In their editorial, Subbiah and Subbiah (2015) have defined exceptional responders as patients who obtain “a complete response, showing no radiographic evidence of the cancer where previously widely metastatic cancer was noted” [8]. In another editorial, Chau and Lorch (2015) described exceptional responders as “a minority of patients with cancer who respond to drugs in an unexpected and often dramatic degree” [9]. These definitions are not quantifiable. In a short report, another group defined exceptionally responding breast cancer patients as those with a “highly durable (≥5 years) or ongoing clinical response” [10], a definition that is related only to the chemotherapy drug Xeloda® (capecitabine). Summary of Definitions of Atypical Responses Although multiple attempts have been made to define an atypical response, these definitions vary considerably and focus mainly on exceptional responders. Therefore, a more precise framework for exceptional responders, rapid progressors, and exceptional survivors is needed. To complete this emerging picture of patients with atypical responses, we propose that the scientific community adopt the following framework: • “Exceptionalresponder”:apatientwhohasanunusuallyfavorableresponsetoaspecifictreatment protocol compared to other patients on the same protocol • “Rapid progressor”: a patient who has an unusually poor response, or no response, to a specific treatment protocol compared to other patients on the same protocol • “Exceptional survivor”: an advanced stage patient who has far outlived his or her prognosis for reasons that are not fully understood irrespective of whether the patient exhibited an atypical response to specific therapy(ies). Such a patient may be considered to have an atypical response to the disease itself by considerably outliving his or her prognosis. These proposed categories can be customized for the cancer type or subtype and the clinical