Evidence map›Paper›PMID 27993569›Full record

ArticleThe Lancet. Oncology2017

A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study.

Jacob G Scott, Anders Berglund, Michael J Schell, Ivaylo Mihaylov, William J Fulp, Binglin Yue, Eric Welsh, Jimmy J Caudell, Kamran Ahmed, Tobin S Strom and 11 more

Erratum issued Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04738214 (Development of a Genome-based Platform for Personalized Treatment in Locally Advanced Rectal Cancer Patients), which is not on this map. Cited by 258 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
258citing papers in PubMed, 1 pooled it
33.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04738214 unknown statusnot on this mapstarted 2021, after this paper: background citation

Development of a Genome-based Platform for Personalized Treatment in Locally Advanced Rectal Cancer Patients

Typeobservational_patient_registrySponsorYonsei UniversityRan2021 to 2025Enrolled39ConditionsLocally Advanced Rectal CancerArmsNeoadjuvant CCRT+operation +/- adjuvant treatment
3 · Its place in the literature

Who cites it

258 citing papers in PubMed, 1 synthesis or guideline pooled it, 463 citations in OpenAlex.

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198 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 2 institutions in 1 country.

Jacob G ScottDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Anders BerglundDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Michael J SchellDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Ivaylo MihaylovDepartment of Radiation Oncology, University of Miami, Miami, FL, USA.
William J FulpDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Binglin YueDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Eric WelshDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Jimmy J CaudellDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Kamran AhmedDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Tobin S StromDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Eric MellonDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Puja VenkatDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Peter JohnstoneDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
John FoekensDepartment of Medical Oncology and Cancer Genomics, Erasmus Medical Center, Rotterdam, Netherlands.
Jae LeeDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Eduardo MorosDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
William S DaltonDeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Steven A EschrichDepartment of Integrated Bioinformatics and Biostatistics, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Howard McLeodDeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Louis B HarrisonDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Javier F Torres-RocaDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address: javier.torresroca@moffitt.org.
Moffitt Cancer Center · USUniversity of Miami · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Molecular Profiling to Predict Response to ChemotherapyR21CA101355 · NCI · H. LEE MOFFITT CANCER CTR &RES INST · PI YEATMAN, TIMOTHY J · 2003 to 2004
$725k
Validation of a Predictive Model of Clinical Response to Concurrent RadiochemotheR21CA135620 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI TORRES-ROCA, JAVIER F · 2009 to 2010
$712k
NCI NIH HHS P30 CA076292NCI NIH HHS R21 CA101355NCI NIH HHS R21 CA135620
6 · The paper itself

Abstract

backgroundDespite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose.

methodsWe used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical 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 Glioblastoma Patient Cohort (n=98).

findingsWe calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66-172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13-3·94, p=0·018).

interpretationA GARD-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.

fundingNone.

Indexed as

Genome, HumanModels, GeneticAdultAgedAged, 80 and overBiomarkers, TumorFemaleFollow-Up StudiesGlioblastomaHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsPrognosisBiomarkers, Tumor

Identifiers

PMID27993569
PMCPMC7771305
OpenAlexW2566074209

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.