Evidence map›Paper›PMID 26177983›Full record

ArticleCancer2015

Phase 1 adaptive dose-finding study of neoadjuvant gemcitabine combined with radiation therapy for patients with high-risk extremity and trunk soft tissue sarcoma.

William W Tseng, Shouhao Zhou, Christina A To, Peter F Thall, Alexander J Lazar, Raphael E Pollock, Patrick P Lin, Janice N Cormier, Valerae O Lewis, Barry W Feig and 4 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.Journal of the National Comprehensive Cancer Network : JNCCN · 2022
    Guideline
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
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.

William W TsengSection of Surgical Oncology, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
Shouhao ZhouDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Christina A ToDepartment of Medical Oncology, Keck School of Medicine, University of Southern California, Los Angeles, California.
Peter F ThallDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Alexander J LazarDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Raphael E PollockDivision of Surgical Oncology, James Comprehensive Cancer Center, Ohio State University, Columbus, Ohio.
Patrick P LinDepartment of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Janice N CormierDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Valerae O LewisDepartment of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Barry W FeigDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kelly K HuntDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Matthew T BalloDepartment of Radiation Oncology, University of Tennessee Health Sciences Center, Memphis, Tennessee.
Shreyaskumar PatelDepartment of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Peter W T PistersUniversity Health Network, Toronto, Canada.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Kathrin Milbury · 1985 to 2026
$290.8M
STATISTICAL METHODS FOR COMPLEX CANCER TRIALSR01CA083932 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI THALL, PETER F · 2000 to 2017
$2.3M
NCI NIH HHS R01 CA083932
6 · The paper itself

Abstract

backgroundThis study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed-dose external-beam radiation therapy (EBRT) for patients with resectable, high-risk extremity and trunk soft tissue sarcoma (STS).

methodsGemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity types. The TSWM is a Bayesian procedure that choses each cohort's dose to have a posterior mean total toxicity burden closest to a predetermined clinician-defined target. Clinicopathologic and outcome data were also collected.

resultsThirty-six patients completed the study. According to the TSWM, the gemcitabine MTD was 700 mg/m(2). At this dose level, 4 patients (24%) experienced grade 4 toxicity; no toxicity-related deaths occurred. All tumors were resected with microscopically negative margins. Pathologic responses of >90% tumor necrosis were achieved in 17 patients (47%); 14 (39%) had complete responses. With a median follow-up of 6.2 years, the 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 85%, 80%, and 86%, respectively.

conclusionsThe TSWM combines data from qualitatively different toxicities and can be used to determine the MTD for a drug given as part of a multimodality treatment. Neoadjuvant gemcitabine plus radiation therapy is feasible and safe in patients with high-risk extremity and trunk STS. Major pathologic responses can be achieved, and after complete resection, long-term clinical outcomes are encouraging.

Indexed as

AdultBayes TheoremChemoradiotherapy, AdjuvantDeoxycytidineDose Fractionation, RadiationDrug Administration ScheduleExtremitiesGemcitabineHumansMaximum Tolerated DoseMiddle AgedNeoadjuvant TherapyRadiation-Sensitizing AgentsSarcomaSurvival AnalysisTorsoDeoxycytidineGemcitabineRadiation-Sensitizing Agentsgemcitabineneoadjuvantradiationsarcomatoxicity

Identifiers

PMID26177983
PMCPMC4777348

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.