J Korean Med Sci.  2016 Aug;31(8):1254-1261. 10.3346/jkms.2016.31.8.1254.

Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey

• Koh KN
• Yoo KH
• Im HJ
• Sung KW
• Koo HH
• Kim HS
• Han JW
• Yoon JH
• Park HJ
• Park BK
• Baek HJ
• Kook H
• Lee JA
• Lee JM
• Lee KC
• Kim SK
• Park M
• Lee YH
• Lyu CJ
• Seo JJ

• KMID: 2373753
• DOI: http://doi.org/10.3346/jkms.2016.31.8.1254

Abstract

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.

Keyword

Childhood; Cancer; Survivors; Second Neoplasm

MeSH Terms

Adolescent
Antineoplastic Agents/therapeutic use
Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy
Child
Child, Preschool
Disease-Free Survival
Hospitals
Humans
Infant
Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy
Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy
Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy
Osteosarcoma/diagnosis/epidemiology
Retrospective Studies
Stem Cell Transplantation
Survival Rate
Transplantation, Autologous
Young Adult
Antineoplastic Agents

Figure

• 

  Fig. 1 The latency period between the diagnosis of primary and second malignant neoplasms. ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CNS, central nervous system; MDS, myelodysplastic syndrome.

• 

  Fig. 2 Survival outcomes of the patients with second malignant neoplasm. (A) The 5-year overall survival rates of patients with second malignant neoplasms. (B) The 5-year overall survival rates of patients with AML, MDS, CNS tumors, osteosarcoma, and thyroid carcinoma. AML, acute myeloid leukemia; CNS, central nervous system; MDS, myelodysplastic syndrome.

Reference

1. Armstrong GT, Liu W, Leisenring W, Yasui Y, Hammond S, Bhatia S, Neglia JP, Stovall M, Srivastava D, Robison LL. Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2011; 29:3056–3064.

2. Jenkinson HC, Hawkins MM, Stiller CA, Winter DL, Marsden HB, Stevens MC. Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain. Br J Cancer. 2004; 91:1905–1910.

3. Neglia JP, Friedman DL, Yasui Y, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst. 2001; 93:618–629.

4. Olsen JH, Garwicz S, Hertz H, Jonmundsson G, Langmark F, Lanning M, Lie SO, Moe PJ, Møller T, Sankila R. Second malignant neoplasms after cancer in childhood or adolescence. Nordic Society of Paediatric Haematology and Oncology Association of the Nordic Cancer Registries. BMJ. 1993; 307:1030–1036.

5. Reulen RC, Frobisher C, Winter DL, Kelly J, Lancashire ER, Stiller CA, Pritchard-Jones K, Jenkinson HC, Hawkins MM; British Childhood Cancer Survivor Study Steering Group. Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA. 2011; 305:2311–2319.

6. Meadows AT, Friedman DL, Neglia JP, Mertens AC, Donaldson SS, Stovall M, Hammond S, Yasui Y, Inskip PD. Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2009; 27:2356–2362.

7. Seo JJ, Yoon SY, You CW, Shin HY, Ahn HS, Lyu CJ, Kim BS, Kim KY, Lee KS, Park JS, et al. A multicenter clinical study on second malignancies after treatment of childhood cancer. Korean J Pediatr Hematol Oncol. 1998; 5:113–121.

8. Garwicz S, Anderson H, Olsen JH, Døllner H, Hertz H, Jonmundsson G, Langmark F, Lanning M, Möller T, Sankila R, et al. Second malignant neoplasms after cancer in childhood and adolescence: a population-based case-control study in the 5 Nordic countries. The Nordic Society for Pediatric Hematology and Oncology. The Association of the Nordic Cancer Registries. Int J Cancer. 2000; 88:672–678.

9. Berger C, Trombert-Paviot B, Casagranda L, Mialou V, Frappaz D, Plantaz D, Collardeau-Frachon S, Freycon F. Second malignant neoplasms following childhood cancer: a study of a recent cohort (1987-2004) from the childhood cancer registry of the Rhône-Alpes region (ARCERRA) in France. Pediatr Hematol Oncol. 2011; 28:364–379.

10. Sun WF, Cheng FW, Lee V, Leung WK, Shing MK, Yuen PM, Li CK. Second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China. Chin Med J (Engl). 2011; 124:3686–3692.

11. Rihani R, Bazzeh F, Faqih N, Sultan I. Secondary hematopoietic malignancies in survivors of childhood cancer: an analysis of 111 cases from the surveillance, epidemiology, and end result-9 registry. Cancer. 2010; 116:4385–4394.

12. Schmiegelow K, Levinsen MF, Attarbaschi A, Baruchel A, Devidas M, Escherich G, Gibson B, Heydrich C, Horibe K, Ishida Y, et al. Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia. J Clin Oncol. 2013; 31:2469–2476.

13. Ishida Y, Maeda M, Urayama KY, Kiyotani C, Aoki Y, Kato Y, Goto S, Sakaguchi S, Sugita K, Tokuyama M, et al. Secondary cancers among children with acute lymphoblastic leukaemia treated by the Tokyo Children's Cancer Study Group protocols: a retrospective cohort study. Br J Haematol. 2014; 164:101–112.

14. Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, Vardiman JW, Rowley JD, Larson RA. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood. 2003; 102:43–52.

15. Huh HJ, Lee SH, Yoo KH, Sung KW, Koo HH, Kim K, Jang JH, Jung C, Kim SH, Kim HJ. Therapy-related myeloid neoplasms in 39 Korean patients: a single institution experience. Ann Lab Med. 2013; 33:97–104.

16. Barnard DR, Woods WG. Treatment-related myelodysplastic syndrome/acute myeloid leukemia in survivors of childhood cancer--an update. Leuk Lymphoma. 2005; 46:651–663.

17. Gow KW, Lensing S, Hill DA, Krasin MJ, McCarville MB, Rai SN, Zacher M, Spunt SL, Strickland DK, Hudson MM. Thyroid carcinoma presenting in childhood or after treatment of childhood malignancies: an institutional experience and review of the literature. J Pediatr Surg. 2003; 38:1574–1580.

18. Tucker MA, Jones PH, Boice JD Jr, Robison LL, Stone BJ, Stovall M, Jenkin RD, Lubin JH, Baum ES, Siegel SE, et al. Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group. Cancer Res. 1991; 51:2885–2888.

19. Chojnacka M, Pędziwiatr K, Skowrońska-Gardas A, Perek-Polnik M, Perek D, Olasek P. Second brain tumors following central nervous system radiotherapy in childhood. Br J Radiol. 2014; 87:20140211.

20. Broniscer A, Ke W, Fuller CE, Wu J, Gajjar A, Kun LE. Second neoplasms in pediatric patients with primary central nervous system tumors: the St. Jude Children's Research Hospital experience. Cancer. 2004; 100:2246–2252.

21. Devarahally SR, Severson RK, Chuba P, Thomas R, Bhambhani K, Hamre MR. Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence. Pediatr Hematol Oncol. 2003; 20:617–625.

22. Kamran SC, Berrington de Gonzalez A, Ng A, Haas-Kogan D, Viswanathan AN. Therapeutic radiation and the potential risk of second malignancies. Cancer. Forthcoming. 2016.

23. Berrington de Gonzalez A, Gilbert E, Curtis R, Inskip P, Kleinerman R, Morton L, Rajaraman P, Little MP. Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose-response relationship. Int J Radiat Oncol Biol Phys. 2013; 86:224–233.