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Optimizing the radiation therapy dose prescription for pediatric medulloblastoma : Minimizing the life years lost attributable to failure to control the disease and late complication risk

Brodin, N. Patrik ; Vogelius, Ivan R. ; Björk-Eriksson, Thomas ; Munck Af Rosenschöld, Per LU orcid ; Maraldo, Maja V. ; Aznar, Marianne C. ; Specht, Lena and Bentzen, Soren M. (2014) In Acta Oncologica 53(4). p.462-470
Abstract

Background. A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Methods. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton... (More)

Background. A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Methods. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton therapy; 3) risk-adaptive photon treatment lowering the dose to part of the craniospinal (CS) target volume situated close to critical risk organs. Results. Late toxicity is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th thoracic vertebrae (Th1-Th10), and 36 Gy to the remaining CS volume, estimated a LYL reduction of 0.90 years (95% CI -0.18-2.41 years). Proton therapy with 36 Gy to the whole CS volume was associated with significantly fewer LYL compared to the risk-adapted photon strategies, with a mean LYL difference of 0.50 years (95% CI 0.25-2.60 years). Conclusions. Optimization of RT prescription strategies considering both late complications and the risk of recurrence, an all-cause mortality dose painting approach, was demonstrated. The risk-adapted techniques compared favorably to the standard, and although in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk-adapted strategies.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Oncologica
volume
53
issue
4
pages
462 - 470
publisher
Taylor & Francis
external identifiers
  • pmid:24274390
  • scopus:84896915055
ISSN
0284-186X
DOI
10.3109/0284186X.2013.858824
language
English
LU publication?
no
additional info
Funding Information: Work supported by a grant from the Danish Child Cancer Foundation to Patrik Brodin. søren Bentzen acknowledges support from the National Cancer institute grant no. 2P30 Ca 014520-34.
id
05740871-5065-4092-9bfe-17477aeab626
date added to LUP
2023-07-19 09:38:58
date last changed
2024-01-05 03:25:53
@article{05740871-5065-4092-9bfe-17477aeab626,
  abstract     = {{<p>Background. A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Methods. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton therapy; 3) risk-adaptive photon treatment lowering the dose to part of the craniospinal (CS) target volume situated close to critical risk organs. Results. Late toxicity is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th thoracic vertebrae (Th1-Th10), and 36 Gy to the remaining CS volume, estimated a LYL reduction of 0.90 years (95% CI -0.18-2.41 years). Proton therapy with 36 Gy to the whole CS volume was associated with significantly fewer LYL compared to the risk-adapted photon strategies, with a mean LYL difference of 0.50 years (95% CI 0.25-2.60 years). Conclusions. Optimization of RT prescription strategies considering both late complications and the risk of recurrence, an all-cause mortality dose painting approach, was demonstrated. The risk-adapted techniques compared favorably to the standard, and although in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk-adapted strategies.</p>}},
  author       = {{Brodin, N. Patrik and Vogelius, Ivan R. and Björk-Eriksson, Thomas and Munck Af Rosenschöld, Per and Maraldo, Maja V. and Aznar, Marianne C. and Specht, Lena and Bentzen, Soren M.}},
  issn         = {{0284-186X}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{462--470}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oncologica}},
  title        = {{Optimizing the radiation therapy dose prescription for pediatric medulloblastoma : Minimizing the life years lost attributable to failure to control the disease and late complication risk}},
  url          = {{http://dx.doi.org/10.3109/0284186X.2013.858824}},
  doi          = {{10.3109/0284186X.2013.858824}},
  volume       = {{53}},
  year         = {{2014}},
}