Evidence map›Paper›PMID 31747139›Full record

Observational studyCancer medicine2020

A community-based lung cancer rapid tissue donation protocol provides high-quality drug-resistant specimens for proteogenomic analyses.

Theresa A Boyle, Gwendolyn P Quinn, Matthew B Schabath, Teresita Muñoz-Antonia, James J Saller, Luisa F Duarte, Laura S Hair, Jamie K Teer, Derek Y Chiang, Rebecca Leary and 11 more

Open access · goldAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Molecular Pathology of Lung Cancer.Cold Spring Harbor perspectives in medicine · 2022
    Review
  8. Review
  9. Acylglycerol Kinase-Targeted Therapies in Oncology.Frontiers in cell and developmental biology · 2021
    Review
  10. Article
  11. Emerging oncogenic fusions other thanTranslational lung cancer research · 2020
    Review
  12. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 5 institutions in 3 countries.

Theresa A BoyleDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.ORCID 0000-0001-5950-3970
Gwendolyn P QuinnDepartment of Ob-Gyn, New York University School of Medicine, New York, NY, USA.
Matthew B SchabathDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.ORCID 0000-0003-3241-3216
Teresita Muñoz-AntoniaDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
James J SallerAnatomic Pathology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Luisa F DuarteDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Laura S HairDistrict 12 Medical Examiner's Office, Sarasota, FL, USA.
Jamie K TeerDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Derek Y ChiangNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Rebecca LearyNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Connie C WongNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Alexander SavchenkoNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Angad P SinghNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
LaSalette CharetteNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Kate MendellNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Gullu GorgunNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Scott J AntoniaDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Alberto A ChiapporiDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Benjamin C CreelanDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Jhanelle E GrayDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Eric B HauraDepartment of Oncologic Science, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
University of South Florida · USNovartis (United States) · USMoffitt Cancer Center · USNew York University · USOffice of the Chief Medical Examiner · CA

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Ethical Issues in Maintaining a Rapid Tissue Donation ProgramR21CA194932 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SCHABATH, MATTHEW B. · 2015 to 2016
$403k
NCI NIH HHS P30 CA076292NCI NIH HHS R21 CA194932
6 · The paper itself

Abstract

backgroundFor the advancement of cancer research, the collection of tissue specimens from drug-resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post-therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment-resistant lung cancers.

methodsConsent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non-tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin-fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD-L1) clones. Next-generation sequencing was performed on 13 specimens from 5 patients.

resultsPostmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD-L1 IHC revealed heterogeneity within and between tumors. An AGK-BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule-associated protein-like 4 to anaplastic lymphoma kinase (EML4-ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells.

conclusionsPost-therapy specimens demonstrated PD-L1 heterogeneity and an acyl glycerol kinase to B-rapidly accelerated fibrosarcoma (AGK-BRAF) fusion in a patient with an EML4-ALK-positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance.

Indexed as

Adenocarcinoma of LungAgedB7-H1 AntigenBiomarkers, TumorCommunity-Based Participatory ResearchDrug Resistance, NeoplasmEvolution, MolecularFemaleFloridaGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansImmunohistochemistryLungLung NeoplasmsMaleAGK protein, humanB7-H1 AntigenBiomarkers, TumorBRAF protein, humanCD274 protein, humanEML4-ALK fusion protein, humanOncogene Proteins, FusionPhosphotransferases (Alcohol Group Acceptor)Proto-Oncogene Proteins B-rafdonationheterogeneitylung cancerPD-L1rapid autopsyresistance mutationspecimen quality

Identifiers

PMID31747139
PMCPMC6943158
OpenAlexW2991043538

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Registered trials

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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.