Radiation recall reaction causing cardiotoxicity
Radiation recall phenomenon is a tissue reaction that develops within a previously irradiated area, precipitated by the subsequent administration of certain chemotherapeutic agents. It commonly affects the skin, but can also involve internal organs with functional consequences. To our best knowledge, this phenomenon has never been reported as a complication on the heart and should be consider as a potential cause of cardiotoxicity.
Radiation recall reaction (RRR) refers to an inflammatory reaction within a previously treated radiation field. The reaction occurs in response to the combined effect of radiotherapy and a second precipitating agent, mainly with chemotherapeutic drugs. We would like to describe a case of RRR that involved the heart.
We present a 56-year old man with a prior history of adenocarcinoma of the lung with metastasis to cervical lymph nodes and brain diagnosed in 2006. He was initially treated with chemotherapy in 2006. Subsequently, he required stereotactic radiation to the chest and cervical lymph nodes with a total dose of 7000 CGy. Since his initial therapies, he has received multiple chemotherapy treatments including cisplatin, docetaxel, bevacizumab, erlotinib, and gemcitabine. Most recently, he was started on sorafenib.
Five month later, he presented with chest pain. No significant electrocardiographic changes were present and his troponin level was normal. An echocardiogram showed mildly decreased left ventricular systolic function with an ejection fraction of 45%. The anterior wall was hypokinetic and there was a small pericardial effusion.
Interestingly, the abnormal myocardial wall segments demonstrated on FDG-PET/CT, echocardiography and CMR also corresponded to the previously irradiated area. Due to these findings, sorefanib was discontinued. He had no recurrent chest pain.
Radiation recall reaction (RRR) refers to an inflammatory reaction within a previously treated radiation field. The reaction occurs in response to the combined effect of radiotherapy and a second precipitating agent. The second precipitating agent has been observed mainly with chemotherapeutic drugs. It can occur months or even many years after irradiation, suggesting that the mechanism may be different from radiosensitization . Skin is the major site of radiation recall toxicity. But, the phenomenon has also been described in other organs including the lung, digestive tract, muscle, and central nervous system. However, to the best of our knowledge radiation recall toxicity has never been reported in the heart.
We believe our case of a 56 year-old man with new onset chest pain in the setting of remote radiation therapy and ongoing chemotherapy likely represents an instance of radiation recall myocarditis. Features such as acute onset reduced ejection fraction with regional wall motion abnormalities, regional inflammation and edema on FDG-PET/CT and T2 weighted CMR, and regional enhancement on LGE-CMR may result from a variety of causes, including ischemic heart disease. Our patient underwent coronary angiography and had no evidence of obstructive coronary disease. Other possibilities might include infiltrative disease like cardiac sarcoidosis or myocarditis . However, it would be highly improbable for our patient to develop de novo infectious myocarditis or sarcoid in precisely the same anatomic distribution as the previous radiation field.
We propose that the diagnosis of radiation recall reaction myocarditis induced by chemotherapy is established in our case by a history of chemotherapy after thoracic radiotherapy, with CMR and FDG-PET/CT showing evidence of inflammation in the irradiated areas of the myocardium. When radiation therapy is followed by chemotherapy, subclinical damage from irradiation can be unmasked or potentiated and ultimately manifest clinically as RRR.
Radiation recall phenomenon is a tissue reaction that develops within a previously irradiated area, precipitated by the subsequent administration of certain chemotherapeutic agents. It commonly affects the skin, but can also involve internal organs with functional consequences. While undoubtedly rare and previously unreported, radiation recall phenomenon should be considered as a potential cause of cardiotoxicity in the appropriate context.
This case report was approved by the IRB of University of Minnesota Medical Center and the requirement for the individual consent was waived based on retrospective design.
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