Single and multiple metachronous osteosarcoma tumors after therapy

Abstract

BACKGROUNDThe objective of the current study was to determine the incidence, clinical and pathologic characteristics, and outcome of patients with conventional osteosarcoma who developed metachronous tumors after treatment for the primary tumor and prevention of pulmonary metastases.METHODSThe medical records of 270 pediatric patients (younger than age 18 years) were reviewed. The prevention and absence of pulmonary metastases was confirmed by chest radiographs and computerized scans of the lungs. Radionuclide bone scans were used to confirm the absence of skeletal metastases.RESULTSEleven patients with metachronous tumors were identified. Index primary tumors involved the femur (n = 8), the tibia (n = 2), and the radius (n = 1). Single metachronous tumors developed in the femur (n = 6), in the humerus (n = 1), and multifocal in multiple bones (n = 4). Two patients later developed second metachronous tumors. The interval between identification of the primary tumor to development of the single metachronous tumors varied from 11 months to 78 months and from 12 months to 42 months for synchronous multifocal tumors. Metachronous tumors were treated with single‐agent cisplatin or ifosfamide. Only 1 patient experienced > 90% tumor necrosis. Pulmonary metastases were not detected in 10 of 11 patients at the time metachronous tumors were discovered. In the 11th patient, synchronous pulmonary metastasis with the metachronous tumor was noted. Three patients had a prior history of bilateral retinoblastoma. The Li–Fraumeni syndrome may have been present in another patient. Six patients died. Five patients have survived for 20+ to 50+ months after the appearance, treatment, and resection of metachronous tumors.CONCLUSIONSWith improvement in the cure rate, metachronous osteosarcoma should be recognized as an important sequela in long‐term survivors. The etiology of this disease is unknown. Speculation rests on a skeletal multicentric origin, which includes an inherited predisposition to develop osteosarcoma in retinoblastoma and in the Li–Fraumeni syndrome. Meticulous follow‐up is required to permit early detection and successful therapeutic intervention. Cancer 2003. © 2003 American Cancer Society.

Bilateral synchronous tibial periosteal osteosarcoma with familial incidence

“…The third and fourth types consist of both early (5- 24 months) and late (>24 months) metachronous lesions, respectively. These classifications may have prognostic implications as the synchronous form has had a uniformly poorer outcome, whereas the late metachronous form may be amenable to treatment with intent to cure [1,[5][6][7][8][9]. However, these data have been described for conventional high-grade OS and not for periosteal OS.…”

“…Of these, 16 had lung metastasis and only one had intramedullary metastasis to the bone in contralateral leg. Jaffe et al [1] described a case of periosteal OS with a metachronous osteoblastic intramedullary lesion in the contralateral femur after 3 years. This patient was suspected to have Li-Fraumeni syndrome and died 12 months later with pulmonary and intracranial metastases.…”

“…These may be synchronous (more than one lesion at presentation) or metachronous (new tumor developing after the initial treatment) [1][2][3][4][5][6]. The incidence of multifocal OS has ranged from 1.5 to 5.4% in large series, with the synchronous type being rarer [1][2][3][7][8][9][10][11].…”

Retinoblastoma

“…In the general population, only 7% of osteosarcomas follow other malignancies, and almost half of these cases occur in retinoblastoma survivors (Hauben et al 2003). Likewise, although multifocal OS accounts for only 4% of all osteosarcomas, 25% of those occur in retinoblastoma survivors (Jaffe et al 2003). Osteosarcoma is the most common malignancy in survivors of retinoblastoma, both in the irradiated and the non-irradiated areas, and account for 25-40% of all second malignancies (Kleinerman et al 2005;Yu et al 2009;Abramson and Frank 1998;Aerts et al 2004;Acquaviva et al 2006;Moll et al 2001).…”

DNA repair systems

“…Pa ents with unilateral tumours usually have be er prognosis than pa ents with bilateral and trilateral tumours. All individuals with re noblastoma are at increased (over 250-fold) cumula ve life me risk for pinealoblastoma and osteosarcoma, as muta ons in the RB1 gene play a role in the pathogenesis of these tumours as well [540].…”