Evidence map›Paper›PMID 38423050›Full record

SynthesisThe Lancet. Oncology2024

Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis.

Laila A Gharzai, Emily Morris, Krithika Suresh, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Paul M Harari, Adam S Garden, Shlomo Koyfman, Jimmy J Caudell and 13 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
4.6field-weighted citation impact, top 5% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Trial
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 15 institutions in 2 countries.

Laila A GharzaiDepartment of Radiation Oncology, Northwestern University, Chicago, IL, USA.
Emily MorrisDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Krithika SureshDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Phuc Felix Nguyen-TânDepartment of Radiation Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.
David I RosenthalDepartment of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Maura L GillisonDepartment of Thoracic and Head/Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Paul M HarariDepartment of Radiation Oncology, University of Wisconsin, Madison, WI, USA.
Adam S GardenDepartment of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shlomo KoyfmanDepartment of Radiation Oncology, University of Cleveland Medical Center, Cleveland, OH, USA.
Jimmy J CaudellDepartment of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Christopher U JonesDepartment of Radiation Oncology, Sutter Cancer Research Consortium, Novato, CA, USA.
Darrion L MitchellDepartment of Radiation Oncology, Ohio State University, Columbus, OH, USA.
Greg KremplDepartment of Otolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
John A RidgeDepartment of Otolaryngology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Michael F GensheimerDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
James A BonnerDepartment of Radiation Oncology, University of Alabama at Birmingham Medical Center, Birmingham, AL, USA.
Edith FilionDepartment of Radiation Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.
Neal E DunlapDepartment of Radiation Oncology, The James Graham Brown Cancer Center at University of Louisville, Louisville, KY, USA.
William A StokesDepartment of Radiation Oncology, Emory University, Atlanta, GA, USA.
Quynh-Thu LeDepartment of Radiation Oncology, Stanford University, Stanford, CA, USA.
Pedro Torres-SaavedraNRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.
Michelle MierzwaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Matthew J SchipperDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address: mjschipp@med.umich.edu.
The University of Texas MD Anderson Cancer Center · USCentre Hospitalier de l’Université de Montréal · CAStanford University · USUniversity of Michigan–Ann Arbor · USEmory University · USFox Chase Cancer Center · USJames Graham Brown Foundation · USMoffitt Cancer Center · USNorthwestern University · USNRG Oncology · USThe Ohio State University · USUniversity Hospitals of Cleveland · USUniversity of Alabama at Birmingham · USUniversity of Oklahoma Health Sciences Center · USUniversity of Wisconsin–Madison · US

Funding

NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Statistics CoreU10CA180822 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Elaina Harper · 2014 to 2026
$146.4M
National Clinical Trials Network Research at the University of WisconsinUG1CA233277 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Lisa M Barroilhet, Andrew M. Baschnagel · 2019 to 2026
$4.9M
Overcoming Hypoxic Resistance in Non-Small Cell Lung Cancer By Targeting Mitochondrial MetabolismR01CA262388 · NCI · OHIO STATE UNIVERSITY · PI DENKO, NICHOLAS C., LI, ZIHAI · 2021 to 2025
$3.6M
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA262388NCI NIH HHS U10 CA180822NCI NIH HHS U10 CA180868NCI NIH HHS UG1 CA233277
6 · The paper itself

Abstract

backgroundThe increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy.

methodsWe did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r

findingsWe analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r

interpretationWe identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints.

fundingNRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

Indexed as

Carcinoma, Squamous CellOropharyngeal NeoplasmsAdolescentAdultBiomarkersFemaleHumansMaleMiddle AgedMotivationBiomarkers

Identifiers

PMID38423050
PMCPMC10962533
OpenAlexW4392180709

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.