Evidence map›Paper›PMID 29053185›Full record

Trial reportCancer2018

Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704.

Yaacov R Lawrence, Jennifer Moughan, Anthony M Magliocco, Alexander C Klimowicz, William F Regine, Rex B Mowat, Thomas A DiPetrillo, William Small, Jeffry P Simko, Talia Golan and 4 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00003216 (A Phase III Study of Pre and Post Chemoradiation 5-FU vs. Pre and Post Chemoradiation Gemcitabine for Postoperative Adjuvant Treatment of Resected Pancreatic Adenocarcinoma), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-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.

NCT00003216 phase3completednot on this map

A Phase III Study of Pre and Post Chemoradiation 5-FU vs. Pre and Post Chemoradiation Gemcitabine for Postoperative Adjuvant Treatment of Resected Pancreatic Adenocarcinoma

TypeinterventionalSponsorRadiation Therapy Oncology GroupRan1998Enrolled518ConditionsPancreatic CancerArmsfluorouracil, gemcitabine hydrochloride, radiation therapy
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. MLH1 promoter methylation in pancreatic ductal adenocarcinoma: frequent but not prognostic.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  2. Article
  3. Proteomics in pancreatic cancer.Biomarker research · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
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

14 authors at 12 institutions in 2 countries.

Yaacov R LawrenceDepartment of Oncology, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel HaShomer, Israel.
Jennifer MoughanStatistics and Data Management Center, NRG Oncology, Philadelphia, Pennsylvania.
Anthony M MaglioccoDepartment of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida.
Alexander C KlimowiczBoehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut.
William F RegineUniversity of Maryland School of Medicine, Baltimore, Maryland.
Rex B MowatToledo Clinic Cancer Centers, Toledo, Ohio.
Thomas A DiPetrilloDepartment of Radiation Oncology, Rhode Island Hospital/The Warren Alpert Medical School of Brown University, Providence, Rhode, Island.
William SmallDepartment of Radiation Oncology, Loyola University Medical Center, Chicago, Illinois.ORCID 0000-0002-1623-9863
Jeffry P SimkoDepartment of Pathology, University of California-San Francisco Medical Center, San Francisco, California.
Talia GolanDepartment of Oncology, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel HaShomer, Israel.
Kathryn A WinterStatistics and Data Management Center, NRG Oncology, Philadelphia, Pennsylvania.
Chandan GuhaDepartment of Radiation Oncology, Montefiore Medical Center, Bronx, New York.
Christopher H CraneMemorial Sloan Kettering Cancer Center, New York, New York.
Adam P DickerDepartment of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.
NRG Oncology · USThomas Jefferson University · USBoehringer Ingelheim (United States) · USBrown University · USLoyola University Medical Center · USMemorial Sloan Kettering Cancer Center · USMoffitt Cancer Center · USMontefiore Medical Center · USTel Aviv University · ILToledo Clinic Cancer Center · USUniversity of California San Francisco Medical Center · USUniversity of Maryland, Baltimore · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
RTOG Foreign AccrualU10CA021661 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI CURRAN, WALTER J. · 1985 to 2013
$150.3M
Statistics CoreU10CA180822 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mei-Yin C Polley · 2014 to 2026
$146.4M
NRG Oncology NCORP Research Base-BIQSFPUG1CA189867 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI Deborah Watkins Bruner, Lisa A. Kachnic · 2014 to 2026
$140.5M
NRG Oncology Biospecimen BankU24CA196067 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI Tanner J. Freeman, Nilsa Del Carmen Ramirez Milan · 2015 to 2026
$42.6M
RTOG Foreign AccrualsU10CA037422 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI BRUNER, DEBORAH WATKINS · 1985 to 2013
$30.4M
RTOG Tissue BankU24CA114734 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI CURRAN, WALTER J. · 2005 to 2014
$9.0M
NCI NIH HHS P30 CA008748NCI NIH HHS U10 CA021661NCI NIH HHS U10 CA037422NCI NIH HHS U10 CA180822NCI NIH HHS U10 CA180868NCI NIH HHS U24 CA114734NCI NIH HHS U24 CA196067NCI NIH HHS UG1 CA189867
6 · The paper itself

Abstract

backgroundThe majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation.

methodsSamples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value.

resultsImmunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001).

conclusionsIn the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society.

Indexed as

Chemoradiotherapy, AdjuvantAdultAgedAged, 80 and overDNA DamageFemaleHumansMaleMiddle AgedMutL Protein Homolog 1Pancreatic NeoplasmsProportional Hazards ModelsProspective StudiesMLH1 protein, humanMutL Protein Homolog 1adjuvantbiomarkerschemotherapyclinical trial phase 3mutL protein homolog 1 (MLH1)pancreatic neoplasmsradiotherapytumor

Identifiers

PMID29053185
PMCPMC5780226
OpenAlexW2767166587

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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.