Radiation recall reactions: An oncologic enigma

Development and resolution of cutaneous RRR (cRRR). cRRR occur on average, 40 days after radiation. The time from exposure to the trigger drug to cRRR is typically 8 days. cRRR are of variable severity and may or may not coincide precisely to previous irradiation fields. cRRR have the pathoclinical features of acute or chronic inflammation, and resolve usually within days to weeks. Inflammation can be severe, sometimes leading to tissue necrosis. [Display omitted] •Radiation recall reactions (RRR) are a rare but well-known phenomenon to oncologists.•Previously irradiated regions develop a reactivated radiation response after the patient is exposed to a drug.•RRR effect pleiotropic tissues, but are most commonly reported for skin, lung and alimentary mucosa.•The molecular pathology of RRR is poorly defined, although RRR may result from chronic oxidative stress or low-level tissue cytokine release.•The severity of RRR is usually relatively mild, but may they may result in tissue necrosis. Radiation recall reactions (RRR) are uncommon but are a well-known phenomenon to oncologists. Tissue damage in a prior irradiation portal is ‘recalled’ after the administration of a drug, historically cytotoxics, or more recently, targeted or immunotherapeutic agents. Even COVID-19 vaccines are a reported cause. RRR are enigmatic in that their cause is unknown, but they generally have the histopathological and clinical features of acute or chronic inflammation. They can occur in a variety of tissues, the commonest being skin, which accounts for two-thirds of reported cases. They are generally relatively mild and self-limiting once the trigger drug is stopped, although severe cases with tissue necrosis have occurred. Rechallenge with drug does not necessarily cause reactivation of the reaction. Symptomatic treatment with steroids and antihistamines are usually effective, but their impact on the clinical course is unclear. Various hypotheses have been proposed as to the mechanism of RRR; a non-immune fixed drug reaction-like condition, dysregulated release of reactive oxygen species, abnormalities of tissue vasculature and impaired DNA repair. All could lead to a characteristic inflammatory microenvironment, resulting in dysfunction of tissue stem cells, keratinocyte necrosis and dermal abnormalities. Alternatively or in addition, low levels of inflammatory tissue cytokines induced by previous irradiation might be further upregulated by drug exposure. Most information in this