PMID- 22954771
OWN - NLM
STAT- MEDLINE
DCOM- 20130322
LR  - 20220409
IS  - 1879-355X (Electronic)
IS  - 0360-3016 (Linking)
VI  - 85
IP  - 3
DP  - 2013 Mar 1
TI  - Dose-effect relationships for adverse events after cranial radiation therapy in 
      long-term childhood cancer survivors.
PG  - 768-75
LID - S0360-3016(12)00952-2 [pii]
LID - 10.1016/j.ijrobp.2012.07.008 [doi]
AB  - PURPOSE: To evaluate the prevalence and severity of clinical adverse events (AEs) 
      and treatment-related risk factors in childhood cancer survivors treated with 
      cranial radiation therapy (CRT), with the aim of assessing dose-effect 
      relationships. METHODS AND MATERIALS: The retrospective study cohort consisted of 
      1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT 
      delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), 
      and as total body irradiation (TBI). Individual CRT doses were converted into the 
      equivalent dose in 2-Gy fractions (EQD(2)). Survivors had received their 
      diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A 
      complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 
      AEs was available from our hospital-based late-effect follow-up program. We used 
      multivariable logistic and Cox regression analyses to examine the EQD(2) in 
      relation to the prevalence and severity of AEs, correcting for sex, age at 
      diagnosis, follow-up time, and the treatment-related risk factors surgery and 
      chemotherapy. RESULTS: There was a high prevalence of AEs in the CRT group; over 
      80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both 
      representing significant increases in number of AEs compared with survivors not 
      treated with CRT. Additionally, the proportion of severe, life-threatening, or 
      disabling AEs was significantly higher in the CRT group. The most frequent AEs 
      were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using 
      the EQD(2), we found significant dose-effect relationships for these and other 
      AEs. CONCLUSION: Our results confirm that CRT increases the prevalence and 
      severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect 
      relationships with the cumulative EQD(2) instead of total physical dose connects 
      the knowledge from radiation therapy and radiobiology with the clinical 
      experience.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - van Dijk, Irma W E M
AU  - van Dijk IW
AD  - Department of Radiation Oncology, Academic Medical Center, Amsterdam, The 
      Netherlands. i.w.vandijk@amc.uva.nl
FAU - Cardous-Ubbink, Mathilde C
AU  - Cardous-Ubbink MC
FAU - van der Pal, Helena J H
AU  - van der Pal HJ
FAU - Heinen, Richard C
AU  - Heinen RC
FAU - van Leeuwen, Flora E
AU  - van Leeuwen FE
FAU - Oldenburger, Foppe
AU  - Oldenburger F
FAU - van Os, Rob M
AU  - van Os RM
FAU - Ronckers, Cecile M
AU  - Ronckers CM
FAU - Schouten-van Meeteren, Antoinette Y N
AU  - Schouten-van Meeteren AY
FAU - Caron, Huib N
AU  - Caron HN
FAU - Koning, Caro C E
AU  - Koning CC
FAU - Kremer, Leontien C M
AU  - Kremer LC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120903
PL  - United States
TA  - Int J Radiat Oncol Biol Phys
JT  - International journal of radiation oncology, biology, physics
JID - 7603616
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Cranial Irradiation/*adverse effects
MH  - Dose Fractionation, Radiation
MH  - Dose-Response Relationship, Radiation
MH  - Female
MH  - Head and Neck Neoplasms/epidemiology/etiology
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Neoplasms, Radiation-Induced/epidemiology
MH  - Neoplasms, Second Primary/epidemiology/etiology
MH  - Prevalence
MH  - Radiation Injuries/epidemiology
MH  - Regression Analysis
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - *Survivors
MH  - Whole-Body Irradiation/adverse effects
MH  - Young Adult
EDAT- 2012/09/08 06:00
MHDA- 2013/03/23 06:00
CRDT- 2012/09/08 06:00
PHST- 2012/04/24 00:00 [received]
PHST- 2012/07/12 00:00 [revised]
PHST- 2012/07/13 00:00 [accepted]
PHST- 2012/09/08 06:00 [entrez]
PHST- 2012/09/08 06:00 [pubmed]
PHST- 2013/03/23 06:00 [medline]
AID - S0360-3016(12)00952-2 [pii]
AID - 10.1016/j.ijrobp.2012.07.008 [doi]
PST - ppublish
SO  - Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):768-75. doi: 
      10.1016/j.ijrobp.2012.07.008. Epub 2012 Sep 3.