Subsequent neoplasms in survivors of childhood central nervous system tumors

Risk after modern multimodal therapy

Karen Tsui, Amar Gajjar, Chenghong Li, Deokumar Srivastava, Alberto Broniscer, Cynthia Wetmore, Larry E. Kun, Thomas E. Merchant, David W. Ellison, Brent A. Orr, Frederick Boop, Paul Klimo, Jordan Ross, Leslie L. Robison, Gregory Armstrong

Research output: Contribution to journalArticle

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Abstract

Background. Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs. Methods. Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT+chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study. Results. Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years, and 6.0% (95%CI: 4.6%-7.7%) at 20 years fromdiagnosis. Riskswere highest for subsequent glioma, all grades (SIR=57.2; 95%CI: 36.2-85.8) and acute myeloid leukemia (SIR=31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT+chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated withmultimodal therapy, cumulative incidence of SNwas 12.0%(95%CI: 6.4%-19.5%) at 20 years, no different than survivors treatedwith RTalone (11.3%, P=.44). Conclusion. The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure tomultimodal therapy compared with RTalone. Continued follow-up of survivors as they age is essential.

Original languageEnglish (US)
Pages (from-to)448-456
Number of pages9
JournalNeuro-Oncology
Volume17
Issue number3
DOIs
StatePublished - Jan 1 2015

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Central Nervous System Neoplasms
Survivors
Neoplasms
Incidence
Radiotherapy
Therapeutics
Drug Therapy
Medulloblastoma
Implosive Therapy
Acute Myeloid Leukemia
Glioma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

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Subsequent neoplasms in survivors of childhood central nervous system tumors : Risk after modern multimodal therapy. / Tsui, Karen; Gajjar, Amar; Li, Chenghong; Srivastava, Deokumar; Broniscer, Alberto; Wetmore, Cynthia; Kun, Larry E.; Merchant, Thomas E.; Ellison, David W.; Orr, Brent A.; Boop, Frederick; Klimo, Paul; Ross, Jordan; Robison, Leslie L.; Armstrong, Gregory.

In: Neuro-Oncology, Vol. 17, No. 3, 01.01.2015, p. 448-456.

Research output: Contribution to journalArticle

Tsui, K, Gajjar, A, Li, C, Srivastava, D, Broniscer, A, Wetmore, C, Kun, LE, Merchant, TE, Ellison, DW, Orr, BA, Boop, F, Klimo, P, Ross, J, Robison, LL & Armstrong, G 2015, 'Subsequent neoplasms in survivors of childhood central nervous system tumors: Risk after modern multimodal therapy', Neuro-Oncology, vol. 17, no. 3, pp. 448-456. https://doi.org/10.1093/neuonc/nou279
Tsui, Karen ; Gajjar, Amar ; Li, Chenghong ; Srivastava, Deokumar ; Broniscer, Alberto ; Wetmore, Cynthia ; Kun, Larry E. ; Merchant, Thomas E. ; Ellison, David W. ; Orr, Brent A. ; Boop, Frederick ; Klimo, Paul ; Ross, Jordan ; Robison, Leslie L. ; Armstrong, Gregory. / Subsequent neoplasms in survivors of childhood central nervous system tumors : Risk after modern multimodal therapy. In: Neuro-Oncology. 2015 ; Vol. 17, No. 3. pp. 448-456.
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abstract = "Background. Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs. Methods. Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT+chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study. Results. Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0{\%} (95{\%} CI: 2.3{\%}-3.9{\%}) at 10 years, and 6.0{\%} (95{\%}CI: 4.6{\%}-7.7{\%}) at 20 years fromdiagnosis. Riskswere highest for subsequent glioma, all grades (SIR=57.2; 95{\%}CI: 36.2-85.8) and acute myeloid leukemia (SIR=31.8; 95{\%} CI: 10.2-74.1). Compared with RT alone, RT+chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95{\%} CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated withmultimodal therapy, cumulative incidence of SNwas 12.0{\%}(95{\%}CI: 6.4{\%}-19.5{\%}) at 20 years, no different than survivors treatedwith RTalone (11.3{\%}, P=.44). Conclusion. The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure tomultimodal therapy compared with RTalone. Continued follow-up of survivors as they age is essential.",
author = "Karen Tsui and Amar Gajjar and Chenghong Li and Deokumar Srivastava and Alberto Broniscer and Cynthia Wetmore and Kun, {Larry E.} and Merchant, {Thomas E.} and Ellison, {David W.} and Orr, {Brent A.} and Frederick Boop and Paul Klimo and Jordan Ross and Robison, {Leslie L.} and Gregory Armstrong",
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T1 - Subsequent neoplasms in survivors of childhood central nervous system tumors

T2 - Risk after modern multimodal therapy

AU - Tsui, Karen

AU - Gajjar, Amar

AU - Li, Chenghong

AU - Srivastava, Deokumar

AU - Broniscer, Alberto

AU - Wetmore, Cynthia

AU - Kun, Larry E.

AU - Merchant, Thomas E.

AU - Ellison, David W.

AU - Orr, Brent A.

AU - Boop, Frederick

AU - Klimo, Paul

AU - Ross, Jordan

AU - Robison, Leslie L.

AU - Armstrong, Gregory

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background. Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs. Methods. Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT+chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study. Results. Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years, and 6.0% (95%CI: 4.6%-7.7%) at 20 years fromdiagnosis. Riskswere highest for subsequent glioma, all grades (SIR=57.2; 95%CI: 36.2-85.8) and acute myeloid leukemia (SIR=31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT+chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated withmultimodal therapy, cumulative incidence of SNwas 12.0%(95%CI: 6.4%-19.5%) at 20 years, no different than survivors treatedwith RTalone (11.3%, P=.44). Conclusion. The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure tomultimodal therapy compared with RTalone. Continued follow-up of survivors as they age is essential.

AB - Background. Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs. Methods. Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT+chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study. Results. Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years, and 6.0% (95%CI: 4.6%-7.7%) at 20 years fromdiagnosis. Riskswere highest for subsequent glioma, all grades (SIR=57.2; 95%CI: 36.2-85.8) and acute myeloid leukemia (SIR=31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT+chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated withmultimodal therapy, cumulative incidence of SNwas 12.0%(95%CI: 6.4%-19.5%) at 20 years, no different than survivors treatedwith RTalone (11.3%, P=.44). Conclusion. The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure tomultimodal therapy compared with RTalone. Continued follow-up of survivors as they age is essential.

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