The abscopal effect and its implications for radiotherapy-immunotherapy combinations

Abstract

Abscopal effects (from "ab" "scopus" meaning away from target) have grown from being a mere curiosity to providing an insight into more complex and previously unrecognised effects of radiotherapy (RT) that can be exploited alongside synergistic effects of immunotherapy, particularly immune checkpoint inhibitors (ICI), that counteract the actions of tumours to suppress an immune response against them.The report by Aoyama et al. in this issue (1) is one of a long line of case reports of the abscopal effect, although in this instance the first time this has been reported in a solitary extramedullary plasmacytoma of the thyroid. First described by Mole in 1953 (2), the typical occurrence is in a patient with widespread disease where one site of involvement is irradiated, and clinical responses are observed at other sites also. Two systematic reviews have collated well over 50 case reports (3,4). A wide range of RT fractionation was used, though mostly representative of the range of doses and fractionation used for palliative (i.e., non-curative) RT. In both reviews, the median total dose delivered was 31-32 Gy (with a wide range) and the median dose per fraction 3 Gy (range, 0.15-26 Gy). In 2 of 46 cases this was delivered with brachytherapy and in 8 with stereotactic radiotherapy (SRT) (3). In general, abscopal effects were first apparent within weeks of completing RT and the median time to confirmation of an abscopal response was 2-4 months (range, 0.5-24 months) (3,4) with a median time to progression at these sites of 6 months (range, 0.7-14 months) (3). At 5-year, overall survival was 63% and distant progression-free survival 45% (4), suggesting that these responses might result in better outcomes, or perhaps more likely, that cancers open to immune-manipulation might carry a better than average prognosis. However, these systematic reviews do show that abscopal effects are seen more commonly with some cancer types than others. In fact, two-thirds of all reports are in patients with non-small cell lung cancer, renal cancer, melanoma, lymphoma or hepatocellular carcinoma (4). Even allowing for a degree of under-reporting, given the number of patients who have received RT for metastatic disease over the same time-period, abscopal effects are very rare. However, in a series of 28 patients with renal cell cancer receiving SRT to inoperable primary tumours or to metastatic sites, there were four patients (14%) in whom non-irradiated metastases had regressed at least temporarily (5).The main conclusions to be drawn from this collection of case reports are that abscopal effects are more frequently observed with certain cancer types, and that these responses can be quite prolonged. There are no clear markers that might predict for abscopal effects, although a review of possible biomarkers did identify a raised absolute lymphocyte count following initiation of ICI or following RT, a higher pre-treatment neutrophil to lymphocyte ratio, or the presence of tumour infiltrating lymphocytes in biopsy material as having some pre...

Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review

“…Additionally, what is the best radiation procedure? Studies by Rowell et al, 14 Abuodeh et al, 10 and Hatten et al 15 were summarized. According to these reports, palliative radiation therapy was used in most cases, with a median total delivered dose of 31–32 Gy, median dose per fraction of 3 Gy, median time to confirmed response of 2–4 months, and median progression free survival of 6 months.…”

“…Additionally, what is the best radiation procedure? Studies by Rowell et al, 14 Abuodeh et al, 10 and Hatten et al 15 were summarized.…”

Predicting the Abscopal Phenomenon—Letter to the Editor

“…The authors define the abscopal effect as “regression of distant nontreated sites following primary irradiation to a specific site”, the likelihood of which tends to increase in the presence of immunotherapy, particularly immune checkpoint inhibitors (ICIs; ref. 2 ).…”