Evidence map›Paper›PMID 39631145›Full record

Trial reportEBioMedicine2024

Adjuvant rituximab and elevated intratumoural CD8 expression are associated with sustained disease control after radiotherapy in a randomised trial of systemic therapy in early-stage follicular lymphoma.

Michael P MacManus, John F Seymour, Hennes Tsang, Richard Fisher, Colm Keane, Muhammed B Sabdia, Soi C Law, Jay Gunawardana, Karthik Nath, Stephen H Kazakoff and 30 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

40 authors.

Michael P MacManusPeter MacCallum Cancer Institute, Melbourne, VIC, Australia; University of Melbourne, VIC, Australia. Electronic address: Michael.Macmanus@petermac.org.
John F SeymourPeter MacCallum Cancer Institute, Melbourne, VIC, Australia; University of Melbourne, VIC, Australia.
Hennes TsangMater Research Institute, University of Queensland, Brisbane, QLD, Australia.
Richard FisherPeter MacCallum Cancer Institute, Melbourne, VIC, Australia.
Colm KeaneFrazer Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia.
Muhammed B SabdiaMater Research Institute, University of Queensland, Brisbane, QLD, Australia.
Soi C LawMater Research Institute, University of Queensland, Brisbane, QLD, Australia.
Jay GunawardanaMater Research Institute, University of Queensland, Brisbane, QLD, Australia.
Karthik NathMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Stephen H KazakoffQueensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.
Mario L Marques-PiubelliMD Anderson Cancer Centre, Houston, TX, USA.
Daniela E DuenasMD Anderson Cancer Centre, Houston, TX, USA.
Michael R GreenMD Anderson Cancer Centre, Houston, TX, USA.
Daniel RoosRoyal Adelaide Hospital, Adelaide, SA, Australia.
Peter O'BrienGenesis Cancer Care, Newcastle, NSW, Australia.
Andrew McCannAuckland City Hospital, Auckland, New Zealand.
Richard TsangPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Sidney DavisThe Alfred, Melbourne, VIC, Australia.
David ChristieGenesis Cancer Care, Tugun, QLD, Australia.
Chan CheahSir Charles Gairdner Hospital, Perth, WA, Australia.
Benhur AmanuelPathWest Laboratory Medicine WA, Australia.
Tara CochraneGold Coast University Hospital, Gold Coast, QLD, Australia.
Jason ButlerRoyal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Anna JohnstonRoyal Hobart Hospital, Hobart, TAS, Australia.
Mohamed ShanavasMater Adult Hospital, Brisbane, QLD, Australia.
Li LiOchsner Health, New Orleans, LA, USA.
Claire VajdicUNSW Kirby Institute, Sydney, NSW, Australia.
Robert KridelPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Victoria SheltonPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Samantha HershenfieldPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Tara BaetzQueen's University, Kingston, Ontario, Canada.
David LebrunQueens Cancer Research Institute, Kingston, Ontario, Canada.
Nathalie JohnsonMcGill Centre for Translational Research in Cancer, Quebec, Canada.
Marianne BrodtkorbOslo University Hospital, Norway.
Maja LudvigsenAarhus University Hospital, Aarhus, Denmark.
Francesco d'AmoreAarhus University Hospital, Aarhus, Denmark.
Ella R ThompsonPeter MacCallum Cancer Institute, Melbourne, VIC, Australia.
Piers BlomberyPeter MacCallum Cancer Institute, Melbourne, VIC, Australia; University of Melbourne, VIC, Australia.
Maher K GandhiMater Research Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia. Electronic address: m.gandhi@uq.edu.au.
Joshua W D TobinMater Research Institute, University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Brisbane, QLD, Australia. Electronic address: j.tobin@uq.edu.au.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundWe report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.

methodsPatients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).

findingsBetween 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR] = 0.60, 95% CI = 0.37-0.98, p = 0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR = 0.44, 95% CI = 0.16-1.18, p = 0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p = 0.045). PFS of IFRT + R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT + CVP) was superior (HR = 0.36, 95% CI = 0.13-0.82, p = 0.013). Amongst PET-staged patients, PFS differences between IFRT + R-CVP vs. IFRT were maintained (HR = 0.38, 95% CI = 0.16-0.89, p = 0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR = 0.45, 95% CI = 0.26-0.79, p = 0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p = 0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p = 0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease.

interpretationAdjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL.

fundingCancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

Indexed as

Lymphoma, FollicularNeoplasm StagingRituximabAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCD8-Positive T-LymphocytesFemaleHumansMaleMiddle AgedTreatment OutcomeRituximabCD8Early-stage follicular lymphomaNeoantigen. randomized clinical trialRadiotherapyRituximab

Identifiers

PMID39631145
PMCPMC11663783

What OpenQuestion holds

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LicenceCC BY-NC
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.