Secondary osteosarcoma in patients previously treated for childhood cancer: Three case reports

Shimatani,Akiyoshi; Aono,Masanari; Hoshi,Manabu; Oebisu,Naoto; Iwai,Tadashi; Takada,Naoki; Hara,Junichi; Nitani,Chika; Nakamura,Hiroaki

doi:10.3892/mco.2018.1752

Secondary osteosarcoma in patients previously treated for childhood cancer: Three case reports

Authors:
- Akiyoshi Shimatani
- Masanari Aono
- Manabu Hoshi
- Naoto Oebisu
- Tadashi Iwai
- Naoki Takada
- Junichi Hara
- Chika Nitani
- Hiroaki Nakamura
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Affiliations: Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka 545‑8585, Japan, Department of Orthopedic Surgery, Osaka City General Hospital, Osaka 534‑0021, Japan, Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Osaka 534‑0021, Japan
Published online on: October 26, 2018 https://doi.org/10.3892/mco.2018.1752
Pages: 153-158

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Abstract

The prognosis of childhood cancers has improved markedly, and the proportion of long‑term survivors has increased in recent years. However, with the increase in the number of long‑term survivors, the development of latent treatment‑related adverse effects, such as secondary malignancies, has generated new problems. Secondary cancer is defined as a histologically distinct malignancy that develops at least 2 months after the completion of treatment for primary cancer. Genetic factors and acquired conditions associated with treatment modalities are possible causes of secondary malignancy development. Genetic factors include the presence of Li‑Fraumeni syndrome (LFS) and retinoblastoma. In terms of acquired factors, radiation and chemotherapy have been reported to be the most strongly associated with secondary malignancy development. The use of alkylating agents and topoisomerase II inhibitors for the treatment of childhood cancer increases the subsequent risk of secondary tumors. We herein investigated three cases of secondary osteosarcoma several years after treatment for primary cancer. In the three patients, the familial history did not appear to fit the clinical diagnostic criteria of LFS or retinoblastoma. The patients had not received previous radiation therapy to the anatomical site of the secondary cancer. However, high dosages of alkylating agents and topoisomerase II inhibitors had been administered for the treatment of primary cancer. The exact link between chemotherapy and secondary cancer remains elusive, but the possibility of an association should be considered. Following the development of multidisciplinary therapies, long‑term follow‑up and monitoring of latent adverse effects may be necessary for childhood cancer survivors.

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1	Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML, Conrad E, Ferguson W, Gebhardt M, Goorin AM, et al: Osteosarcoma: A randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin and high-dose methotrexate. J Clin Oncol. 23:2004–2011. 2005. View Article : Google Scholar : PubMed/NCBI
2	Raymond AK, Ayala AG and Nuutila S: Conventional osteosarcomaWorld Health Organization classification of tumors: Pathology and genetics; tumors of soft tissue and bone. Fletcher CDM, Unni KK and Mertens F: International Agency for Research on Cancer; Lyon: pp. 24–70. 2002
3	Uni KK and Inwards CY: OsteosarcomaDahlin's bone tumors. 6th edition. Uni KK and Inwards CY: Wolters Kluwer, Lippincott Williams and Wilkins; Philadelphia: pp. 122–157. 2010
4	Arndt CA and Crist WM: Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 341:342–352. 1999. View Article : Google Scholar : PubMed/NCBI
5	Henderson TO, Whitton J, Stovall M, Mertens AC, Mitby P, Friedman D, Strong LC, Hammond S, Neglia JP, Meadows AT, et al: Secondary sarcomas in childhood cancer survivors: A report from the childhood cancer survivor study. J Natl Cancer Inst. 99:300–308. 2007. View Article : Google Scholar : PubMed/NCBI
6	Smith MA, Seibel NL, Altekruse SF, Ries LA, Melbert DL, O'Leary M, Smith FO and Reaman GH: Outcomes for children and adolescents with cancer: Challenges for the twenty-first century. J Clin Oncol. 28:2625–2634. 2010. View Article : Google Scholar : PubMed/NCBI
7	Cho Y, Jung GH, Chung SH, Kim JY, Choi Y and Kim JD: Long-term survivals of stage IIb osteosarcoma: A 20-year experience in a single institution. Clin Orthop Surg. 3:48–54. 2011. View Article : Google Scholar : PubMed/NCBI
8	Bielack SS, Kempf-Bielack B, Heise U, Schwenzer D and Winkler K: Combined modality treatment for osteosarcoma occurring as a second malignant disease. Cooperative German-Austrian-Swiss Osteosarcoma Study Group. J Clin Oncol. 17:11641999. View Article : Google Scholar : PubMed/NCBI
9	Bielack S, Beck J, Delling G, Gerein V, Grümayer R, Hiddemann W, Jobke A, Jürgens H, Kornhuber G, Kotz R, et al: Neoadjuvant chemotherapy of osteosarcoma. Results of the cooperative studies COSS-80 and COSS-82 after 7 and 5 years. Klin Padiatr. 201:275–284. 1989.(In German). View Article : Google Scholar : PubMed/NCBI
10	Yonemoto T, Hosono A, Iwata S, Kamoda H, Hagiwara Y, Fujiwara T, Kawai A and Ishii T: The prognosis of osteosarcoma occurring as second malignancy of childhood cancers may be favorable: Experience of two cancer centers in Japan. Int J Clin Oncol. 20:613–616. 2015. View Article : Google Scholar : PubMed/NCBI
11	Pizzo PA and Poplack DG: Principles and practice of pediatric oncology. Wolters Kluwer; Sixth edition. 2015
12	Meadows AT, Friedman DL, Neglia JP, Mertens AC, Donaldson SS, Stovall M, Hammond S, Yasui Y and Inskip PD: Second neoplasm in survivors of childhood cancer: Findings from the childhood cancer survivor study cohort. J Clin Oncol. 27:2356–2362. 2009. View Article : Google Scholar : PubMed/NCBI
13	Neglia JP, Friedman DL, Yasui Y, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT and Robison LL: Second malignant neoplasms in five-year survivors of childhood cancer: Childhood cancer survivor study. J Natl Cancer Inst. 93:618–629. 2001. View Article : Google Scholar : PubMed/NCBI
14	Tucker MA, D'Angio GJ, Boice JD Jr, Strong LC, Li FP, Stovall M, Stone BJ, Green DM, Lombardi F, Newton W, et al: Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med. 317:588–593. 1987. View Article : Google Scholar : PubMed/NCBI
15	Hudson MM: Late complications after leukemia therapy. Cambridge University Press; pp. 701–713. 2012
16	Millard NE and De Braganca KC: Medulloblastoma. J Child Neurol. 31:1341–1353. 2016. View Article : Google Scholar : PubMed/NCBI
17	Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, et al: Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): Long-term results from a prospective, multicentral trial. Lancet Oncol. 7:813–820. 2006. View Article : Google Scholar : PubMed/NCBI
18	Chetaille B, Massard G and Falcoz PE: Mediastinal germ cell tumors. Anatomopathology, classification, teratomas and malignant tumors. Rev Pneumol Clin. 66:63–70. 2010.(In French). View Article : Google Scholar : PubMed/NCBI
19	Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, Gerl A, Fossa SD, Beyer J, Pont J, Kanz L, et al: Extragonadal germ cell tumors of the mediastinum and retroperitoneum: Results from an international analysis. J Clin Oncol. 20:1864–1873. 2002. View Article : Google Scholar : PubMed/NCBI
20	Smoll NR and Hamilton B: Incidence and relative survival of anaplastic astrocytomas. Neuro Oncol. 16:1400–1407. 2014. View Article : Google Scholar : PubMed/NCBI
21	Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, et al: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 328:1725–1731. 1993. View Article : Google Scholar : PubMed/NCBI
22	Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA and Miller RW: A cancer family syndrome in twenty-four kindreds. Cancer Res. 48:5358–5362. 1988.PubMed/NCBI
23	Kay RM, Eckardt JJ and Mirra JM: Osteosarcoma and Ewing's sarcoma in a retinoblastoma patient. Clin Orthop Relat Res. 323:284–287. 1996. View Article : Google Scholar
24	Andersson A, Enblad G, Tavelin B, Björkholm M, Linderoth J, Lagerlöf I, Merup M, Sender M and Malmer B: Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma. Br J Cancer. 98:1001–1005. 2008. View Article : Google Scholar : PubMed/NCBI
25	Hisada M, Garber JE, Fung CY, Fraumeni JF Jr and Li FP: Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst. 90:606–611. 1998. View Article : Google Scholar : PubMed/NCBI
26	Bhatia S and Sklar C: Second cancers in survivors of childhood cancer. Nat Rev Cancer. 2:124–132. 2002. View Article : Google Scholar : PubMed/NCBI
27	Longhi A, Ferrari S, Tamburini A, Luksch R, Fagioli F, Bacci G and Ferrari C: Late effects of chemotherapy and radiotherapy in osteosarcoma and Ewing sarcoma patients: The Italian Sarcoma Group Experience (1983–2006). Cancer. 118:5050–5059. 2012. View Article : Google Scholar : PubMed/NCBI
28	Hawkins MM, Wilson LM, Burton HS, Potok MH, Winter DL, Marsden HB and Stovall MA: Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst. 88:270–278. 1996. View Article : Google Scholar : PubMed/NCBI
29	Thirman MJ and Larson RA: Therapy-related myeloid leukemia. Hematol Oncol Clin North Am. 10:293–320. 1996. View Article : Google Scholar : PubMed/NCBI
30	Corbett AH and Osheroff N: When good enzymes go bad: Conversion of topoisomerase II to a cellular toxin by antineoplastic drugs. Chem Res Toxicol. 6:585–597. 1993. View Article : Google Scholar : PubMed/NCBI