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Genome-Based Model for Adjusting Radiotherapy Dose Shows Promise

Key Points

  • Genomic-adjusted radiation dose values vary widely despite the use of standard radiotherapy doses within different tumor types.
  • Genomic-adjusted radiation dose values were associated with clinical outcome in cohorts with different cancers.

In a retrospective cohort–based study reported in The Lancet Oncology, Scott et al found that individual patient genomic-adjusted radiation dose was associated with outcomes across different cancer types.

Study Details

In the study, gene-expression–based radiation-sensitivity index and a linear quadratic model were used to derive genomic-adjusted radiation dose; high genomic-adjusted radiation dose values predict greater therapeutic effect for radiotherapy and, potentially, improved clinical outcome.

Data from the prospective observational Total Cancer Care (TCC) protocol were used to calculate genomic-adjusted radiation dose for primary tumors (8,271 tissue samples) from 20 disease sites treated with standard radiotherapy doses. Multivariate analysis was used to test for the effect of genomic-adjusted radiation dose on outcome in five clinical cohorts: Erasmus Breast Cancer cohort (n = 263), Karolinska Breast Cancer cohort (n = 77), Moffitt Lung Cancer cohort (n = 60), Moffitt Pancreas Cancer cohort (n = 40), and The Cancer Genome Atlas (TCGA) Glioblastoma cohort (n = 98).

Genomic-adjusted radiation dose values varied widely (range = 1.66–172.4) in the TCC cohort despite the use of uniform radiotherapy doses within each disease type, with values also ranging widely within tumor types. Median values were lowest for gliomas and sarcomas and highest for cervical and oropharyngeal head and neck cancers.

On multivariate analysis, genomic-adjusted radiation dose level was significantly associated with relapse-free survival in the Karolinska Breast Cancer cohort (hazard ratio [HR] = 7.4, P = .014), local control in the Moffitt Lung Cancer cohort (HR = 3.4, P = .016), and overall survival in the TCGA Glioblastoma cohort (HR = 1.9, P = .019) and the Moffitt Pancreas Cancer cohort (HR = 2.6, P = .029). In the Erasmus Breast Cancer cohort, 5-year distant metastasis–free survival was longer in patients with high genomic-adjusted radiation dose values (≥ 75th percentile) vs those with low values (HR = 2.11, P = .018).

The investigators concluded: “A [genomic-adjusted radiation dose]-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology.”

Javier F. Torres-Roca, MD, of Moffitt Cancer Center and Research Institute, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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