Postirradiation Sarcoma in Retinoblastoma: Induction or Predisposition?

Abstract

\s=b\An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods.(Arch Otolaryngol Head Neck Surg 1988;114:640-644) A recent review of patients presenting to the Stanford (Ca¬ lif) University Head and Neck Tumor Board with postirradiation sarcomas revealed that most had been irra¬ diated for retinoblastoma and devel¬ oped osteogenic sarcoma as their sec¬ ond primary sarcoma. Another pa¬ tient was brought to our attention who also developed an osteogenic sar¬ coma following irradiation for retino¬ blastoma, but outside the field of irra¬ diation in her lower extremity. This latter case prompted the question of whether these secondary head and neck sarcomas were radiation induced or if long-term survivors were simply expressing a genetic predisposition to develop second malignant neoplasms. To answer this question, four new patients with postirradiation sarco¬ mas developing after treatment for ford, CA 94305 (Dr Fee). retinoblastoma are described herein, with a review of the literature. We describe a possible genetic predisposi¬ tion for development of osteogenic sarcoma as a second primary sarco¬ ma, and propose a role for radiation induction. METHODS AND MATERIALSHead and Neck Tumor Board records at Stanford University Medical Center were reviewed from 1980 to 1985. Patients selected had a history of retinoblastoma and developed second sarcomas fulfilling the criteria of Cahan et al1 for radiationinduced sarcoma, with the modifications of Arien et al2: (1) microscopic or roentgeno¬ graphic evidence of an initial nonmalignant state, or a malignant state devoid of osteoid production; (2) development of sar¬ coma within the field of radiation; (3) long disease-free latency period between irradi¬ ation and onset of second primary symp¬ toms or tumor (eg, three years); and (4) histologie documentation of the sarcoma.One case was excluded because the sec¬ ondary tumor, although undifferentiated on initial histologie sections, proved to be recurrent retinoblastoma.The literature review was based on a MEDLINE search of the English literature for the 20-year period from 1966 to 1985, referencing postradiation (rad...

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“…The reported risk varies widely, but a cumulative incidence of 1% for each year of life has been suggested as an approximate estimate. Earlier reports indicated that many of these malignancies are radiation or chemotherapy induced [43][44][45][46]. However, more recent studies [46][47][48][49] suggest that the development of second primary neoplasms in patients with hereditary retinoblastoma results partly from a genetic predisposition and partly from the potentiating effect of radiotherapy on tumorigenesis through mutation of the second Rb gene (RB1) allele, the first RB1 allele being mutated in all patients with hereditary retinoblastoma [50].…”

Head and Neck Osteosarcoma—The Ongoing Challenge about Reconstruction and Dental Rehabilitation

“…Guadagnolo and colleagues noted that the vast majority of HN osteosarcomas arise in either the mandible or maxillary bone [8,9] with 85% of cases involving mandible and maxilla (45% mandible and 40% maxilla) [8,10]. A small number of patients present a history of previous radiotherapy (RT), with consequent osteosarcoma, which was likely radiation-induced [3,[11][12][13]. These tumors and the ones arising de novo seem to have similar histopathology, appearance and prognosis.…”

Experimental induction of rhabdomyosarcoma in mice with fractionated doses of β-irradiation

“…In all, 68% of the children treated with therapeutic irradiation for retinoblastoma, a malignant tumor of the retina, develop bone and soft-tissue sarcomas, with 75% occurring within the irradiated ®eld (Meadows et al 1985). Although osteosarcoma is the predominant tumor histology, these individuals often develop rhabdomyosar-comas arising from the orbital or temporal musculature (Meadows et al 1977;Hawkins et al 1987;Schwartz et al 1988;Hasegawa et al 1998). Radiation-induced secondary tumors in retinoblastoma survivors tend to be more aggressive (Meadows et al 1985), and these individuals tend to do poorly as compared to others with sporadic origin of these tumors.…”