Bone and Soft-Tissue Sarcoma Risk in Long-Term Survivors of Hereditary Retinoblastoma Treated With Radiation

Ruth A Kleinerman, Sara J Schonfeld, Byron S Sigel, Jeannette R Wong-Siegel, Ethel S Gilbert, David H Abramson, Johanna M Seddon, Margaret A Tucker, Lindsay M Morton, Ruth A Kleinerman, Sara J Schonfeld, Byron S Sigel, Jeannette R Wong-Siegel, Ethel S Gilbert, David H Abramson, Johanna M Seddon, Margaret A Tucker, Lindsay M Morton

Abstract

Purpose: Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors.

Patients and methods: In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses. We conducted analyses separately for bone and soft-tissue sarcomas occurring in the head and neck (in/near the radiotherapy field) versus body and extremities (out of field).

Results: Of 105 bone and 124 soft-tissue sarcomas, more than one half occurred in the head and neck (bone, 53.3%; soft tissue, 51.6%), one quarter in the body and extremities (bone, 29.5%; soft tissue, 25.0%), and approximately one fifth in unknown/unspecified locations (bone, 17.1%; soft tissue, 23.4%). We noted substantially higher risks compared with the general population for head and neck versus body and extremity tumors for both bone (SIR, 2,213; 95% CI, 1,671 to 2,873 v SIR, 169; 95% CI, 115 to 239) and soft-tissue sarcomas (SIR, 542; 95% CI, 418 to 692 v SIR, 45.7; 95% CI, 31.1 to 64.9). Head and neck bone and soft-tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood, reaching a 60-year cumulative incidence of 6.8% (95% CI, 5.0% to 8.7%) and 9.3% (95% CI, 7.0% to 11.7%), respectively. In contrast, body and extremity bone sarcoma incidence flattened after adolescence (3.5%; 95% CI, 2.3% to 4.8%), whereas body and extremity soft-tissue sarcoma incidence was rare until age 30, when incidence rose steeply (60-year cumulative incidence, 6.6%; 95% CI, 4.1% to 9.2%), particularly for females (9.4%; 95% CI, 5.1% to 13.8%).

Conclusion: Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.

Figures

FIG 1.
FIG 1.
Frequency of histology of subsequent sarcomas after retinoblastoma (Rb) and in the SEER program by age and location. (A) Bone after Rb, (B) soft-tissue after Rb, (C) bone in SEER, and (D) soft-tissue in SEER. The distribution of other soft-tissue sarcomas in Rb and SEER are presented in the Data Supplement. MFH, malignant fibrous histiocytoma.
FIG 2.
FIG 2.
Cumulative incidence of subsequent sarcomas after retinoblastoma by location (head/neck v body/extremities). (A) Bone and (B) soft tissue.
FIG 3.
FIG 3.
Cumulative incidence of subsequent soft-tissue sarcomas after retinoblastoma by location (head/neck v body/extremities) and sex.

References

    1. Kleinerman RA, Schonfeld SJ, Tucker MA. Sarcomas in hereditary retinoblastoma. Clin Sarcoma Res. 2012;2:15.
    1. Marees T, Moll AC, Imhof SM, et al. Risk of second malignancies in survivors of retinoblastoma: More than 40 years of follow-up. J Natl Cancer Inst. 2008;100:1771–1779.
    1. Reulen RC, Frobisher C, Winter DL, et al. Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA. 2011;305:2311–2319.
    1. Temming P, Arendt M, Viehmann A, et al. Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center. Pediatr Blood Cancer. 2017;64:71–80.
    1. Fidler MM, Reulen RC, Winter DL, et al. Risk of subsequent bone cancers among 69 460 five-year survivors of childhood and adolescent cancer in Europe. J Natl Cancer Inst. 2018;110:183–194.
    1. Bright CJ, Hawkins MM, Winter DL, et al. Risk of soft-tissue sarcoma among 69 460 five-year survivors of childhood cancer in Europe. J Natl Cancer Inst. 2018;110:649–660.
    1. Fujiwara T, Fujiwara M, Numoto K, et al. Second primary osteosarcomas in patients with retinoblastoma. Jpn J Clin Oncol. 2015;45:1139–1145.
    1. Fletcher O, Easton D, Anderson K, et al. Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst. 2004;96:357–363.
    1. Acquaviva A, Ciccolallo L, Rondelli R, et al. Mortality from second tumour among long-term survivors of retinoblastoma: A retrospective analysis of the Italian Retinoblastoma Registry. Oncogene. 2006;25:5350–5357.
    1. Kleinerman RA, Tucker MA, Sigel BS, et al. Patterns of cause-specific mortality among 2053 survivors of retinoblastoma, 1914-2016. J Natl Cancer Inst. 2019;111:961–969.
    1. Hawkins MM, Wilson LM, Burton HS, et al. Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst. 1996;88:270–278.
    1. Wong FL, Boice JD, Jr, Abramson DH, et al. Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. JAMA. 1997;278:1262–1267.
    1. Wong JR, Morton LM, Tucker MA, et al. Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy. J Clin Oncol. 2014;32:3284–3290.
    1. Rodjan F, Graaf P, Brisse HJ, et al. Second cranio-facial malignancies in hereditary retinoblastoma survivors previously treated with radiation therapy: Clinic and radiologic characteristics and survival outcomes. Eur J Cancer. 2013;49:1939–1947.
    1. Abramson DH, Ellsworth RM, Kitchin FD. Osteogenic sarcoma of the humerus after cobalt plaque treatment for retinoblastoma. Am J Ophthalmol. 1980;90:374–376.
    1. Steliarova-Foucher E, Stiller C, Lacour B, et al. International Classification of Childhood Cancer, third edition. Cancer. 2005;103:1457–1467.
    1. World Health Organization . International Classification of Diseases for Oncology, First Revision. ed 3. Geneva, Switzerland: World Health Organization; 2013.
    1. Noone A, Howlader N, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute.
    1. Preston DL, Lubin J, Pierce DA, et al. Epicure User Guide. Ottawa, ON, Canada: Risk Sciences International; 2015.
    1. Gooley TA, Leisenring W, Crowley J, et al. Estimation of failure probabilities in the presence of competing risks: New representations of old estimators. Stat Med. 1999;18:695–706.
    1. Friedman DN, Lis E, Sklar CA, et al. Whole-body magnetic resonance imaging (WB-MRI) as surveillance for subsequent malignancies in survivors of hereditary retinoblastoma: A pilot study. Pediatr Blood Cancer. 2014;61:1440–1444.
    1. Villani A, Tabori U, Schiffman J, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: A prospective observational study. Lancet Oncol. 2011;12:559–567.
    1. Ballinger ML, Best A, Mai PL, et al. Baseline surveillance in Li-Fraumeni syndrome using whole-body magnetic resonance imaging: A meta-analysis. JAMA Oncol. 2017;3:1634–1639.
    1. Chauveinc L, Mosseri V, Quintana E, et al. Osteosarcoma following retinoblastoma: Age at onset and latency period. Ophthalmic Genet. 2001;22:77–88.
    1. MacCarthy A, Bayne AM, Brownbill PA, et al. Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004. Br J Cancer. 2013;108:2455–2463.
    1. Francis JH, Kleinerman RA, Seddon JM, et al. Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma. Gynecol Oncol. 2012;124:254–259.
    1. Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma: A possible age effect on radiation-related risk. Ophthalmology. 1998;105:573–579, discussion 579-580.
    1. Moll AC, Imhof SM, Schouten-Van Meeteren AY, et al. Second primary tumors in hereditary retinoblastoma: A register-based study, 1945-1997—Is there an age effect on radiation-related risk? Ophthalmology. 2001;108:1109–1114.
    1. Kleinerman RA, Tucker MA, Abramson DH, et al. Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst. 2007;99:24–31.
    1. Berrington de Gonzalez A, Kutsenko A, Rajaraman P. Sarcoma risk after radiation exposure. Clin Sarcoma Res. 2012;2:18.
    1. Schwartz B, Benadjaoud MA, Cléro E, et al. Risk of second bone sarcoma following childhood cancer: Role of radiation therapy treatment. Radiat Environ Biophys. 2014;53:381–390.
    1. Henderson TO, Rajaraman P, Stovall M, et al. Risk factors associated with secondary sarcomas in childhood cancer survivors: A report from the Childhood Cancer Survivor study. Int J Radiat Oncol Biol Phys. 2012;84:224–230.
    1. Gianferante DM, Mirabello L, Savage SA. Germline and somatic genetics of osteosarcoma: Connecting aetiology, biology and therapy. Nat Rev Endocrinol. 2017;13:480–491.
    1. Cancer Genome Atlas Research Network Comprehensive and integrated genomic characterization of adult soft tissue sarcomas. Cell. 2017;171:950–965.e28.
    1. Dommering CJ, Mol BM, Moll AC, et al. RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma patients. J Med Genet. 2014;51:366–374.
    1. Chaussade A, Millot G, Wells C, et al. Correlation between RB1germline mutations and second primary malignancies in hereditary retinoblastoma patients treated with external beam radiotherapy. Eur J Med Genet. 2019;62:217–223.
    1. Abramson DH, Daniels AB, Marr BP, et al. Intra-arterial chemotherapy (ophthalmic artery chemosurgery) for group D retinoblastoma. PLoS One. 2016;11:e0146582.
    1. Abramson DH, Shields CL, Munier FL, et al. Treatment of retinoblastoma in 2015: Agreement and disagreement. JAMA Ophthalmol. 2015;133:1341–1347.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa