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

Nils P. Brodin, Ivan R. Vogelius, Thomas Björk-Eriksson, Per Munck Af Rosenschöld, Maja V. Maraldo, Marianne C. Aznar, Lena Specht, Soren M. Bentzen

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)462-470
Number of pages9
JournalActa Oncologica
Volume53
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

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Medulloblastoma
Prescriptions
Radiotherapy
Pediatrics
Proton Therapy
Photons
Recurrence
Craniospinal Irradiation
Thoracic Vertebrae
Neoplasms
Paintings
Mortality
Uncertainty
Therapeutics
Radiation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Hematology
  • Medicine(all)

Cite this

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, Nils P.; Vogelius, Ivan R.; Björk-Eriksson, Thomas; Munck Af Rosenschöld, Per; Maraldo, Maja V.; Aznar, Marianne C.; Specht, Lena; Bentzen, Soren M.

In: Acta Oncologica, Vol. 53, No. 4, 2014, p. 462-470.

Research output: Contribution to journalArticle

Brodin, Nils P. ; Vogelius, Ivan R. ; Björk-Eriksson, Thomas ; Munck Af Rosenschöld, Per ; Maraldo, Maja V. ; Aznar, Marianne C. ; Specht, Lena ; Bentzen, Soren M. / 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. In: Acta Oncologica. 2014 ; Vol. 53, No. 4. pp. 462-470.
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T2 - Minimizing the life years lost attributable to failure to control the disease and late complication risk

AU - Brodin, Nils P.

AU - Vogelius, Ivan R.

AU - Björk-Eriksson, Thomas

AU - Munck Af Rosenschöld, Per

AU - Maraldo, Maja V.

AU - Aznar, Marianne C.

AU - Specht, Lena

AU - Bentzen, Soren M.

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N2 - 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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