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. 2017 Nov 21;117(11):1723-1731.
doi: 10.1038/bjc.2017.347. Epub 2017 Oct 24.

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up

Clare Frobisher  1 , Adam Glaser  2 , Gill A Levitt  3 , David J Cutter  4 , David L Winter  1 , Emma R Lancashire  1 , Kevin C Oeffinger  5 , Joyeeta Guha  6 , Julie Kelly  1 , Raoul C Reulen  1 , Michael M Hawkins  1
Affiliations

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up

Clare Frobisher et al. Br J Cancer. .

Abstract

Background: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors.

Methods: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level.

Results: Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs-5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death-2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition-14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively.

Conclusions: Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form and declare: Dr Frobisher, Dr Lancashire, Dr Reulen, Professor Hawkins, Mr Winter and Ms Kelly reports grants from Department of Health, England, grants from Cancer Research UK, grants from Kay Kendall Leukaemia Fund, grants from PanCareSurFup, European 7th Framework Programme; Dr Glaser reports he was Clinical Director of the National Cancer Survivor Initiative at the Department of Health, England between 2010 and 2013; the remaining authors have no conflict of interest.

Figures

Figure 1
Figure 1
NCSI Levels of follow-up care. (A) The NCSI clinical levels of care (NHS Improvement, 2011a). (B) NCSI Levels of clinical follow-up defined in terms of type of childhood cancer and treatment received. Abbreviations: S=surgery; R=Radiotherapy; C=Chemotherapy; HODG=Hodgkin's lymphoma; NHL=Non-Hodgkin's lymphoma; CNS=Central Nervous System; NEURO=Neuroblastoma; RETINO=Retinoblastoma; STS=soft tissue sarcoma. (C) NCSI Levels of clinical follow-up for ALL survivors. Note: There were insufficient survivors of other specific types of leukaemia for meaningful analysis and therefore such survivors are not considered further within this study.
Figure 2
Figure 2
Risks of adverse health events after all childhood cancers except leukaemia. (A) Observed and expected risks of any subsequent primary neoplasm after all childhood cancers except leukaemia. Abbreviations: incl=including; NGCNS=Non-glioma central nervous system tumours; NMSC=non-melanoma skin cancer; obs=observed. The cross bars are 95% CI. Log-rank test for equality of observed risks yields P<0.0001. (B) Observed and expected risks of any fatal non-neoplastic event after all childhood cancers except leukaemia. Log-rank test for equality of observed risks yields P<0.00005. (C) Observed risks of any non-fatal non-neoplastic condition after all childhood cancers except leukaemia. Log-rank test for equality of observed risks yields P<0.00005.
Figure 3
Figure 3
Risks of adverse health events after acute lymphoblastic leukaemia. (A) Observed and expected risks of any subsequent primary neoplasm after acute lymphoblastic leukaemia. incl=including; NGCNS=Non-glioma central nervous system tumours; NMSC=non-melanoma skin cancer; obs=observed. The cross bars are 95% CI. Log-rank test for equality of observed risks comparing Levels 2 and 3 yields P=0.2052. (B) Observed and expected risks of any fatal non-neoplastic event after acute lymphoblastic leukaemia. Log-rank test for equality of observed risks comparing Levels 2 and 3 yields P=0.0018. (C) Observed risks of any non-fatal non-neoplastic condition after acute lymphoblastic leukaemia. Log-rank test for equality of observed risks comparing Levels 2 and 3 yields P=0.0002.
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