Radiation recall is an uncommon and unpredictable acute inflammatory reaction localized to a site of previous radiation therapy. It is usually triggered by administration of a medication or a vaccine.

It is most common with certain chemotherapies including anthracyclines (doxorubicin), taxanes (docetaxel, paclitaxel), antimetabolites (gemcitabine, capecitabine, pemetrexed), and targeted therapies (epidermal growth factor receptor inhibitors [EGRFIs], B-Raf proto-oncogene [BRAF] inhibitors, and immune checkpoint inhibitors). Radiation recall has also been seen after the use of medications such as nonsteroidal antiestrogens, interferon alpha-2b, antituberculosis drugs, antibiotics, simvastatins, and vaccines (ie, COVID-19 vaccines).

The incidence is estimated to be between 6% and 9%. The time interval between completion of radiation therapy and radiation recall has ranged from 2 days to 15 years. The time interval between the first dose of chemotherapy or trigger drug and the development of radiation recall has ranged between 18 hours to 15 years (most commonly ≥ 7 days) following completion of radiation therapy.

The most common tumors in radiation recall patients are breast cancers (53%) and breast / chest wall tumors (47%). The skin is affected in over two-thirds of radiation recall cases, but reactions in other organs have also been reported, including the lungs, esophagus, small intestine, muscles, central nervous system, and skin and mucosa of the head and neck.

Two-thirds of cases involve the skin. Clinical manifestations vary from mild-to-moderate erythema, vesicle formation, and skin peeling to severe reactions involving ulceration and necrosis. As in acute radiation dermatitis, radiation recall is graded and treated according to the severity of the cutaneous reaction. Severity is independent of prior radiation dose and independent of the severity of acute radiation dermatitis during or immediately after radiation therapy.

Mucous membranes may also be involved, giving rise to stomatitis, which may be ulcerative, and pulmonary radiation recall reactions may occur in prior radiation fields, giving rise to pneumonitis. Enterocolitis, vulvovaginitis, and optic neuritis have also been reported.

Radiation recall reactions often resolve within 1-2 weeks to a few months after discontinuation of the culprit drug. In some cases, permanent fibrotic changes can occur.

The exact etiology is unclear and depends on many factors, including radiation therapy doses, type of systemic therapy, time from end of radiation therapy to start of systemic therapy, and systemic therapy doses. An idiosyncratic drug hypersensitivity reaction is considered the best explanation for all the characteristics of radiation recall. Localized hypersensitivity involves direct activation of nonimmune inflammatory pathways combined with the lower inflammatory response threshold induced by radiation. Keratinocyte necrosis resulting in cumulative direct DNA damage and oxidative stress is also thought to play a role.