Pediatric Cancer

PD 04 - Pediatrics 1 - Poster Discussion

1032 - Modeling the Risk of Neurocognitive Effects from Radiation Therapy in Childhood Cancer Survivors: Initial Results From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) CNS Task Force

Sunday, October 21
5:15 PM - 5:21 PM
Location: Room 217 C/D

Modeling the Risk of Neurocognitive Effects from Radiation Therapy in Childhood Cancer Survivors: Initial Results From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) CNS Task Force
M. Avanzo1, P. Stavinoha2, P. Brodin3, P. D. Aridgides4, I. El Naqa5, S. L. McGovern6, C. M. Ronckers7, L. S. Constine8, and A. Mahajan9; 1Division of Medical Physics, Centro di Riferimento Oncologico Aviano IRCCS, Aviano, Italy, 2Division of Pediatrics, MD Anderson Cancer Center, Houston, TX, 3Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 4Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, NY, 5Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 6The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Pediatric Oncology, Emma Children’s Hospital / Academic Medical Center, Amsterdam, Netherlands, 8Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, 9Department of Radiation Oncology, Mayo Clinic, Rochester, MN

Purpose/Objective(s): Brain injury from radiation therapy (RT) includes necrosis and neurocognitive (NC) impairment which can affect childhood cancer survivors’ quality-of-life. PENTEC seeks to quantitate RT dose-dependence of adverse effects and the risk modification by age and other factors. The PENTEC CNS task force reports preliminary results of RT related NC outcomes.

Materials/Methods: A literature search for studies reporting incidence of RT associated NC sequelae (impaired IQ, NC function, or need for special education) was performed. Prescribed doses were converted to equivalent 2 Gy/fraction (EQD2). The Lyman-Kutcher-Burman formalism with generalized equivalent uniform dose (gEUD) was used for modeling normal tissue complication probability (NTCP) of NC effects. For whole brain (WB)/craniospinal or partial brain (PB) RT it was assumed that the prescribed dose uniformly irradiated the entire brain or 1/8 of the brain, respectively. In this analysis, a simple composite variable reflecting various NC endpoints was used. The model was fitted using a weighted least squares method and corrected for the patient number in each study. Best-fit parameter confidence intervals were determined using a bootstrap resampling technique.

Results: The search identified 1173 abstracts; each was evaluated by 2 reviewers. 219 studies with useful information were short-listed. The 62 highest scored articles were abstracted and the 19 studies (21 data sets, 1498 patients) with objective NC testing and RT data were analyzed (Table). Preliminary results show a sigmoidal dose-response for NC impairments: D50 corresponding to 50% risk of complication of 26.6 Gy (68% CI 25.5-27.9 Gy); slope of dose response 0.35 (0.31-0.40) and volume parameter 0.46 (0.40-0.59). The model indicates a 5% NC risk associated with 11.3 Gy WB and 29.8 Gy PB RT.
Study Year

Pts

WB/CS Dose (Gy) Focal Dose(Gy) Neurocognitive Function Decline Incidence of Endpoint %
Fouladi 2003

31

-

52.2

IQ

0

Fouladi Focal 2005

38

-

54

IQ < 70

23.6

Fouladi CSI 2005

14

18-30

51.9

IQ

71.4

Waber 1995

27

18

-

IQ

0

Krull 2013

102

24

-

IQ

52

Vern-Gross 2014

34

-

59.4

IQ

0

Agbahiwe 2017

48

36

56

IQ

54.1

Merchant 2000

8

23.4-32

50.4

IQ

12.5

Merchant 2004

88

-

23.4-32

IQ

0

Merchant 2009

78

-

54

IQ

100

Merchant 2014

77

-

52.13

IQ

0

Merchant 2014

58

23.4-39.6

55.8

NC

100

Edelstein 2011

24

18

-

General

50

Waber 2004

125

18

-

General

0

Christopherson 2014

39

28.8

54

General

49

Krull 18 Gy 2013

167

18

-

General

12.3

Krull 24 Gy 2013

186

24

-

General

27

Jakacki 2004

6

18

54

Status

50

Cheng 2016

22

23.4

40

Process Speed

33.3

Van Dijk 2012

285

21-24.8

49.3-51.3

Disorder

14.4

Yeom 2013

41

18-39.6

54

Special Ed

70

Conclusion: The initial results of this meta-analysis confirm a RT dose and volume relationship to NC injury risk. Further model refinement will include the effect of age, chemotherapy and include a formal evaluation of heterogeneity across studies.

Author Disclosure: M. Avanzo: None. P. Stavinoha: None. P.D. Aridgides: None. I. El Naqa: Research Grant; NIH. Advisory Board; Endectra LLC. S.L. McGovern: Independent Contractor; MD Anderson Physicians Network. Honoraria; American College of Radiology. Travel Expenses; American College of Radiology. C.M. Ronckers: None. L.S. Constine: Chair; American College of Radiology. A. Mahajan: Secretary; PTCOG-NA. Membership; PROS.

Michele Avanzo, PhD

Disclosure:
Employment
Centro di Referimento Ocnologico di Aviano: Medical Physicist: Employee

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Send Email for Michele Avanzo


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1032 - Modeling the Risk of Neurocognitive Effects from Radiation Therapy in Childhood Cancer Survivors: Initial Results From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) CNS Task Force



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