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Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report
© Okuma et al; licensee BioMed Central Ltd. 2011
Received: 19 May 2010
Accepted: 19 March 2011
Published: 19 March 2011
The abscopal effect is the effect of radiation therapy at a site distant to the area of irradiation. This is not a common event and has not been clearly defined, resulting in few reported cases in the literature. We discuss this phenomenon in a patient with hepatocellular carcinoma.
A 63-year-old Japanese man underwent extended right hepatic lobectomy for hepatocellular carcinoma. During his follow-up examination, a single lung metastasis and a single mediastinal lymph node metastasis were found. Trans-catheter arterial embolization was initially attempted to treat the mediastinal tumor, however this approach failed to take effect and carried risks of spinal artery embolism. External-beam irradiation, with a dose of 2.25 Gy per fraction, was performed using an antero-posterior parallel-opposed technique (total dose, 60.75 Gy). A computed tomography scan performed one month after starting radiotherapy showed a remarkable reduction of the mediastinal lymph node metastasis. In addition to this, we observed spontaneous shrinking of the lung metastasis, which was located in the right lower lobe and out of the radiation field. No chemotherapy was given during the period. There has been no recurrence of either the lung metastasis or the mediastinal lymph node metastasis during a follow-up 10 years after the radiotherapy.
We observed a rare abscopal effect in a site distant from the area of irradiation. Irradiation of the mediastinum resulted in tumor mass regression in the untreated lung tumor.
An abscopal effect has been defined as a reaction outside an irradiated area but within the same organism , that can result in a tumor in a non-irradiated area being spontaneously reduced. Since the first report of an abscopal effect by Mole in 1953 , several other cases have been reported in malignant lymphoma [3–5], hepatocellular carcinoma (HCC)  and malignant melanoma . In 2007, Takaya et al. described an abscopal effect in a case of toruliform para-aortic lymph node metastasis in a patient with advanced uterine cervical carcinoma. This patient was treated with external whole-pelvis and intra-cavitary irradiation to the primary pelvic lesion, successfully resulting in disappearance of the lesion. Moreover, para-aortic lymph node metastases outside the irradiated field also spontaneously disappeared .
The mechanism of the abscopal effect has not been clearly defined. We report here the case of a patient who showed an abscopal effect on lung metastases of HCC.
During follow-up as an out-patient, our patient was observed to have dyspnea (Hugh-Jones 1-2), slight cough and slight sputum. AFP levels had decreased to 23 ng/mL, and PIVKA-II to 13 mAU/mL.
A CT scan performed four years after the radiation therapy showed a lymph node swelling with a diameter of 3.5 cm in the area of origin of the left gastric artery. At this time, AFP and PIVKA-II were elevated to 1990 ng/mL and 1990 mAU/mL respectively, but with no pathologic evidence of recurrence. Stereotactic body radiotherapy for the lesion was performed, with 30 Gy in three fractions. The recurrent tumor disappeared. Six and a half months after the stereotactic body radiotherapy, no obvious recurrent disease was found.
Many case reports describing spontaneous regression of HCC can be found in the literature. Since 1982, about 60 cases have been reported as abscopal effects or spontaneous regressions. These cases were reviewed by Oquiñena et al. in 2009 . Although many similar reports have been published [3, 4, 6–8, 10], the abscopal effect is still a rare phenomenon, and the mechanism has not been clearly defined. Lin et al. proposed two mechanisms involving ischemia and an immune response . First, mitotic inhibitors (cytokines) induced by local radiation are released into the circulation and mediate a systemic anti-tumor effect. This hypothesis is supported by reports that circulating tumor necrosis factor levels are elevated after radiotherapy, and have coincided with the regression of an HCC situated away from the radiation field [2, 12]. Second, irradiation of a tumor in one site induces the release of circulating tumor antigen or inflammatory factors, which may then mediate an augmented immune response against non-irradiated, malignant lesions expressing similar tumor antigens. It has previously been shown that local radiotherapy increases the activity of natural killer cells [13, 14]. Dewan et al. presented the hypothesis that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody . Although these hypotheses have some merit, at present they remain to be confirmed.
We observed a rare abscopal effect in a site distant from the area of irradiation. Irradiation of a tumor in the mediastinal resulted in tumor mass regression in an untreated lung metastasis of HCC.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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