Advanced therapeutic strategy for radiation-induced osteosarcoma in the skull base: a case report and review
© Yamada et al.; licensee BioMed Central Ltd. 2012
Received: 28 March 2012
Accepted: 7 July 2012
Published: 10 August 2012
A review of patients with skull base osteosarcoma secondary to radiation (radiation-induced osteosarcoma: RIOS) of the pituitary tumor shows the mean survival of approximately 7 months (2 weeks – 16 months). This warning prognosis seems to stem from two factors, 1) the anatomical complexity of the skull base for total resection of the tumor, and 2) standard adjuvant therapies for the tumor yet to be established. Contrary to the general belief, the authors report an unusually long survival of a 75-year-old woman with a history of osteosarcoma that developed in the same sequence 20 years after pituitary tumor radiation. On her recent admission, she complained of frontal headaches and MRI studies showed a tumor in the sphenoid sinus. Endoscopic trans-nasal tumor removal allowed for histological diagnosis of an osteosarcoma. However, further rapid tumor growth necessitated a radical tumor resection followed by a combined chemotherapy with ifosfamide, cisplatin, and etoposide (ICE). Despite temporary suppression of the tumor growth, the chemotherapy was discontinued due to severe pancytopenia that occurred after three courses of treatment. Shortly after the discontinuation of ICE therapy, the tumor size increased again rapidly, requiring a novel radiation therapy, Cyber-knife treatment. Following this radiation, the tumor growth was arrested, and the patient remains healthy without neurological symptoms over 24 months. The outcome of Cyber-knife in this case suggests that this specific therapy must be considered for the unresectable skull base RIOS.
KeywordsOsteosarcoma Skull base Radiation-induced Surgery Chemotherapy Cyber-knife
The incidence of radiation-induced osteosarcoma (RIOS) is from 0.01% to 0.03% of all irradiated patients[1, 2], and accounts for 5.5% of all osteosarcomas. Histologically, RIOS is characterized by more aggressive features than primary osteosarcoma[3, 4]. Particularly in craniofacial osteosarcomas, the 5-year survival rate is 70% in primary osteosarcomas and 17% in RIOS[5, 6]. This discrepancy in prognosis reflects the difficulty in total resection of the latter, because of its anatomical features. As a contrast, we present a case of skull base RIOS in a patient with much longer survival than any reported cases.
Review of skull base radiation-induced osteosarcoma
Age (year) Sex
Radiation dose (Gy)
Site of OS
Amine & Sugar (1976)
Tanaka et al. (1989)
Salvati et al. (1994)
radiation (50 Gy)
Gnanalingham et al. (2002)
Hansen et al. (2003)
Bembo et al. (2004)
Patel et al. (2011)
surgery chemotherapy cyber-knife
24 months ~
Discussion and conclusions
In 1948, Cahan et al. described the following conditions as a definition of the radiation-induced sarcoma: 1) the initial and secondary neoplasms are of significantly different histological type; 2) the secondary neoplasm must arise within the irradiated area; 3) there must be a long latency period after radiation (>5 years); and 4) all sarcomas must be proven histologically. Our case fulfilled all these four conditions, and the diagnosis of RIOS was established. The most frequent radiation-induced sarcoma is fibrosarcoma, and osteosarcoma is extremely rare[8, 9]. Based on our review of seven reports, the median survival time of skull base RIOS is 7 months (range 2 weeks to 16 months). The main causes of the early death after surgery were bleeding from the tumor or internal carotid artery (ICA), and occlusion of ICA. Fatal ICA damage can be attributed to aggressive tumor removal in the cavernous sinus. Although some reports described the effectiveness of chemotherapy using methotrexate, ifosfamide, doxorubicin, carboplatin, vincristine, or etoposide, their results are variable[10–12], and a definite protocol has not been established. In the presence of uncontrollable rapid regrowth of the intracranial RIOS, which are known to be resistant to any type of treatment, we selected Cyber-knife irradiation as a novel treatment. This radiation method has three advantages over others: 1) it utilizes its ability to be focused on the target, using the multi-angled planes. Therefore, the dose delivery is superior to Linear accelerator (Linac), which provides the radiation energy only in the single plane, 2) the sizes of tumors of irregular shapes can be evaluated by CT or MRI during Cyber-knife treatment, and radiation doses can be adjusted to maximize the radiation effects. Since the tumor of our patient extended into the cavernous sinus, and different air sinuses, three dimensional evaluation can be done during treatment, 3) Cyber-knife does not require cumbersome equipment as proton beam and gamma knife treatment. In the literature, no report on Cyber-knife treatment is found to demonstrate its effectiveness on RIOS. Our patient’s remarkable daily activity speaks itself for the control of RIOS regrowth by Cyber-knife. We present a case of skull base RIOS with an exceptionally long survival by a combination of endoscopic resection and cyber-knife radiation.
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.
Source of funding
The authors have no funding declared.
Ifosfamide, cisplatin, and etoposide
Magnetic resonance imaging.
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