1 / 14

Role of Whole Brain Radiotherapy in Primary CNS Lymphoma: G-PCNSL-SG-1 Trial

Should whole brain radiotherapy be standard for newly diagnosed primary central nervous system lymphoma? This study evaluated omission of WBRT from HDMTX treatment in adult patients with PCNSL. Results showed no OS difference with or without WBRT but PFS benefits in subgroups. Age and KPS were key risk factors, and late neurotoxicity was more common with WBRT.

adolfo
Télécharger la présentation

Role of Whole Brain Radiotherapy in Primary CNS Lymphoma: G-PCNSL-SG-1 Trial

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Should whole brain radiotherapy be considered standard of care in newly diagnosed primary central nervous system lymphoma? The G-PCNSL-SG-1 randomized phase IV trialE.Thiel , A. Korfel, P. Martus, L. Kanz, Griesinger F, P Rauch, L. Fischer, T. Pietsch, M. Bamberg, M. Welleron behalf of G-PCNSL-SG

  2. Background • High-dose methotrexate (HDMTX) is considered standard of care for newly diagnosed PCNSL. • The role of whole brain radiotherapy (WBRT) is controversial. • Delayed neurotoxicity limits the acceptance of HDMTX+WBRT as a standard of care.

  3. G-PCNSL-SG-1 trial design • newly diagnosed PCNSL • immunocompetent adult patients • creatinine clearance >50 ml/min Randomization: A1/B1 versus A2/B2 HDMTX 4g/m2 d1 1999-2007* HDMTX 4g/m2 d1 + Ifo 1.5g/m2 d3-5 2007-2009* CR CR No CR No CR A1: Cons. WBRT B1: Rescue WBRT A2: Watch and wait B2: HD-Ara-C * + 3 x 8 mg Dexamethasone (d1-10), 1st cycle only

  4. Statistical considerations • Hypothesis: omission of WBRT from first-line • treatment does not compromise OS (non-inferiority design). • Omission of WBRT was defined as non-inferior to WBRT if the lower two-sided 95% confidence limit of the • hazard ratio of WBRT versus no WBRT was not below 0.9. • 60% power to prove non-inferiority of omission of WBRT in case of a hazard ratio of 1.2 of WBRT versus no WBRT. • Sample size required: 151 patients per group.

  5. Flow diagram of all patients n=551 entered n=24 early drop-out / recruitment error CR 182 (34.6%) PR 101 (19.2%) SD/PD 24/123 (4.6/23.4%) Unknown 30 (5.7%) Died 66 (12.5%) n=526 fulfilled the eligibility criteria and received HDMTX n=66 died n=49 dropped out n=411 entered the post- HDMTX phase (ITT) n=93 protocol violation (49 WBRT arms, 44 no WBRTarms) n=318 per protocol n=154 WBRT n=164 no WBRT

  6. Patients characteristics (PP population, n=318) • med. age 61 (19-84) • male/female 183/135 • med. Karnofsky 80 (30-100) • diagnostic procedure: stereotactic biopsy 184 (57.8%) partial/total resection 97 (30.6%) open biopsy 32 (10.1%) CSF cytomorphology 3 (0.9%) no data 2 (0.6%) • lymphoma cells in the CSF 26 (8.2%) • ocular involvement on slit lamp 9 (2.8%)

  7. PFS and OS : PP patientsWBRT n=154, no WBRT n=164 PFS 18.3 vs. 12 mo (P=.13) OS 32.4 vs. 37.1 mo (P=.7)

  8. OS and PFS: PP patients with CR after HDMT WBRT n=56, no WBRT n=96 PFS 36.3 vs. 21.5 mo (P=.038) OS 38.8 vs. 39.4 (P=.56)

  9. OS and PFS: PP patients without CR after HDMTXWBRT n=98, no WBRT n=68 PFS 5.6 vs. 3 mo (P=.003) OS 24.3 vs. 18.6 mo (P=.1)

  10. PFS and OS : ITT patientsWBRT = 203, no WBRT = 208 PFS 15.5 vs. 9.9 mo (P=.041) OS 34.4 vs. 32.1 (P=.94)

  11. The influence of age and KPS on OS(n=526) Age (<60 n=189; ≥60 n=337) KPS (≥70 n=275; <70 n=163) 38.4 vs. 14.2 mo. (P<.005) 31.5 vs. 9.8 mo. (P<.005)

  12. Late neurotoxicity(PP pts. with CR) P=.054 P=.04 WBRT WBRT No WBRT No WBRT Clinical evaluation Neuroradiologic evaluation Clinical evaluation n=45 WBRT, n=33 no WBRT Neuroradiologic evaluation n=51 WBRT, n=36 no WBRT

  13. Conclusions • first randomized phase IV study on PCNSL • no significant difference for OS with versus without WBRT • PFS prolongation in subgroup analyses confirms the role WBRT for disease control; lack of OS benefit reflects effectivity of salvage treatments • age and KPS most important risk factors • late neurotoxicity more frequent with WBRT

  14. Thanksto All patients 75 participatingcenters

More Related