TY - JOUR
T1 - Outcome of SIOP patients with low- or intermediate-risk Wilms tumour relapsing after initial vincristine and actinomycin-D therapy only - the SIOP 93-01 and 2001 protocols
AU - Groenendijk, Alissa
AU - van Tinteren, Harm
AU - Jiang, Yilin
AU - de Krijger, Ronald R
AU - Vujanic, Gordan M
AU - Godzinski, Jan
AU - Rübe, Christian
AU - Schenk, Jens-Peter
AU - Morosi, Carlo
AU - Pritchard-Jones, Kathy
AU - Al-Saadi, Reem
AU - Vaidya, Sucheta J
AU - Verschuur, Arnauld C
AU - Ramírez-Villar, Gema L
AU - Graf, Norbert
AU - de Camargo, Beatriz
AU - Drost, Jarno
AU - Perotti, Daniela
AU - van den Heuvel-Eibrink, Marry M
AU - Brok, Jesper
AU - Spreafico, Filippo
AU - Mavinkurve-Groothuis, Annelies M C
N1 - Funding Information:
The SIOP 93–01 was funded by the ‘Deutsche Krebshilfe’ project number: 70-1899 for Gesellschaft für pädiatrische Onkologie und Hämatologie (GPOH). The Nederlandse Stichting Kindergeneeskundig Kankeronderzoek number 86–04 funded the study in the other countries, as well as the statistical analysis. The Barncancerfonden in Sweden supported the reference pathology. In addition, the SIOP 2001 was funded by Cancer Research UK (grant C1188/A8687 ), the UK National Cancer Research Network and Children's Cancer and Leukaemia Group (CCLGsupporting the study in the UK), Société Française des Cancers de l'Enfant and Association Leon Berard Enfant Cancéreux and Enfant et Santé (supporting the study in France), Gesellschaft für Pädiatrische Onkologie und Hämatologie and Deutsche Krebshilfe (grant 50-2709-Gr2 , supporting the GPOH), Grupo Cooperativo Brasileiro para o Tratamento do Tumor de Wilms and Sociedade Brasileira de Oncologia Pediátrica (supporting the study in Brazil), the Spanish Society of Pediatric Hematology and Oncology and the Spanish Association Against Cancer (supporting the study in Spain) and SIOP-NL. K.P.-J. was partly supported by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre.
Funding Information:
The SIOP 93–01 was funded by the ‘Deutsche Krebshilfe’ project number: 70-1899 for Gesellschaft für pädiatrische Onkologie und Hämatologie (GPOH). The Nederlandse Stichting Kindergeneeskundig Kankeronderzoek number 86–04 funded the study in the other countries, as well as the statistical analysis. The Barncancerfonden in Sweden supported the reference pathology. In addition, the SIOP 2001 was funded by Cancer Research UK (grant C1188/A8687), the UK National Cancer Research Network and Children's Cancer and Leukaemia Group (CCLGsupporting the study in the UK), Société Française des Cancers de l'Enfant and Association Leon Berard Enfant Cancéreux and Enfant et Santé (supporting the study in France), Gesellschaft für Pädiatrische Onkologie und Hämatologie and Deutsche Krebshilfe (grant 50-2709-Gr2, supporting the GPOH), Grupo Cooperativo Brasileiro para o Tratamento do Tumor de Wilms and Sociedade Brasileira de Oncologia Pediátrica (supporting the study in Brazil), the Spanish Society of Pediatric Hematology and Oncology and the Spanish Association Against Cancer (supporting the study in Spain) and SIOP-NL. K.P.-J. was partly supported by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre.
Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - PURPOSE: Society 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.PATIENTS AND METHODS: 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]).RESULTS: 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]).CONCLUSION: 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.
AB - PURPOSE: Society 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.PATIENTS AND METHODS: 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]).RESULTS: 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]).CONCLUSION: 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.
KW - Recurrence
KW - SIOP protocol
KW - Treatment outcome
KW - Wilms tumour
UR - http://www.scopus.com/inward/record.url?scp=85122800039&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.12.014
DO - 10.1016/j.ejca.2021.12.014
M3 - Article
C2 - 35042071
SN - 0959-8049
VL - 163
SP - 88
EP - 97
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -