Groenendijk, Alissavan Tinteren, HarmJiang, Yilinde Krijger, Ronald RVujanic, Gordan MGodzinski, JanRübe, ChristianSchenk, Jens-PeterMorosi, CarloPritchard-Jones, KathyAl-Saadi, ReemVaidya, Sucheta JVerschuur, Arnauld CRamírez-Villar, Gema LGraf, Norbertde Camargo, BeatrizDrost, JarnoPerotti, Danielavan den Heuvel-Eibrink, Marry MBrok, JesperSpreafico, FilippoMavinkurve-Groothuis, Annelies M C2023-05-032023-05-032022-01-15http://hdl.handle.net/10668/22171Society of International Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG) treatment recommendations for relapsed Wilms tumour (WT) are stratified by the intensity of first-line treatment. To explore the evidence for the treatment of patients relapsing after vincristine and actinomycin-D (VA) treatment for primary WT, we retrospectively evaluated rescue treatment and survival of this patient group. We included 109 patients with relapse after VA therapy (no radiotherapy) for stage I-II primary low- or intermediate-risk WT from the SIOP 93-01 and SIOP 2001 studies. Univariate Cox regression analysis was performed to study the effect of relapse treatment intensity on event-free survival (EFS) and overall survival (OS). Relapse treatment intensity was classified into vincristine, actinomycin-D, and either doxorubicin or epirubicin (VAD), and more intensive therapies (ifosfamide/carboplatin/etoposide [ICE]/≥ 4 drugs/high-dose chemotherapy with haematopoietic stem cell transplantation [HD HSCT]). Relapse treatment regimens included either VAD, or cyclophosphamide/carboplatin/etoposide/doxorubicin (CyCED), or ICE backbones. Radiotherapy was administered in 62 patients and HD HSCT in 15 patients. Overall, 5-year EFS and OS after relapse were 72.3% (95% confidence interval [CI]: 64.0-81.6%) and 79.3% (95% CI: 71.5-88.0%), respectively. Patients treated with VAD did not fare worse when compared with patients treated with more intensive therapies (hazard ratio EFS: 0.611 [95% CI: 0.228-1.638] [p-value = 0.327] and hazard ratio OS: 0.438 [95% CI: 0.126-1.700] [p-value = 0.193]). Patients with relapsed WT after initial VA-only treatment showed no inferior EFS and OS when treated with VAD regimens compared with more intensive rescue regimens. A subset of patients relapsing after VA may benefit from less intensive rescue treatment than ICE/CyCED-based regimens and deserve to be pinpointed by identifying additional (molecular) prognostic factors in future studies.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/RecurrenceSIOP protocolTreatment outcomeWilms tumourAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChildDactinomycinDisease-Free SurvivalDoxorubicinEtoposideFemaleHumansIfosfamideKidney NeoplasmsMaleNeoplasm Recurrence, LocalNeoplasm StagingRetrospective StudiesVincristineWilms Tumorresearch article35042071open access10.1016/j.ejca.2021.12.0141879-0852https://doi.org/10.1016/j.ejca.2021.12.014