Abscopal_effect
Abscopal effect
Hypothesis in the treatment of metastatic cancer
The abscopal effect is a hypothesis in the treatment of metastatic cancer whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term “abscopal” (‘ab’ - away from, ‘scopus’ - target) in 1953 to refer to effects of ionizing radiation “at a distance from the irradiated volume but within the same organism.”[1]
Initially associated with single-tumor, localized radiation therapy, the term “abscopal effect” has also come to encompass other types of localized treatments such as electroporation and intra-tumoral injection of therapeutics.[2] However, the term should only be used when truly local treatments result in systemic effects. For instance, chemotherapeutics commonly circulate through the blood stream and therefore exclude the possibility of any abscopal response.
The mediators of the abscopal effect of radiotherapy were unknown for decades. In 2004, it was postulated for the first time that the immune system might be responsible for these “off-target” anti-tumor effects.[3] Various studies in animal models of melanoma,[4][5] mammary,[5][6] and colorectal tumors[5][7] have substantiated this hypothesis. Abscopal effects of Targeted intraoperative radiotherapy have been seen in clinical studies, including in randomized trials where women treated with lumpectomy for breast cancer combined with whole breast radiotherapy showed reduced mortality from non-breast-cancer causes when compared with whole breast radiotherapy.[8][9] Furthermore, immune-mediated abscopal effects were also described in patients with metastatic cancer.[10] Whereas these reports were extremely rare throughout the 20th century, the clinical use of immune checkpoint blocking antibodies such as ipilimumab or pembrolizumab has greatly increased the number of abscopally responding patients in selected groups of patients such as those with metastatic melanoma [11][12] or lymphoma.[13]