Generic Portal

TY - JOUR

T1 - Adolescents and young adults with rhabdomyosarcoma treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) protocols

T2 - a cohort study

AU - Ferrari, Andrea

AU - Chisholm, Julia C.

AU - Jenney, Meriel

AU - Minard-Colin, Veronique

AU - Orbach, Daniel

AU - Casanova, Michela

AU - Guillen, Gabriela

AU - Glosli, Heidi

AU - van Rijn, Rick R.

AU - Schoot, Reineke A.

AU - Cameron, Alison L.

AU - Rogers, Timothy

AU - Alaggio, Rita

AU - Ben-Arush, Myriam

AU - Mandeville, Henry C.

AU - Devalck, Christine

AU - Defachelles, Anne-Sophie

AU - Coppadoro, Beatrice

AU - Bisogno, Gianni

AU - Merks, Johannes H. M.

N1 - Funding Information: We thank Ilaria Zanetti for her contribution to the statistical analysis. The authors also thank the patients, caregivers, and medical staff involved in this study in the recruiting countries. The overall organisation of this study was supported by the Fondazione Città della Speranza (Padova, Italy). In France the study has been supported by Association Léon Berard Enfant Cancéreux grant 2005. In the UK the study has been supported by Cancer Research UK. During the rhabdomyosarcoma 2005 study (but not related to it) the European paediatric Soft tissue sarcoma Study Group received unrestricted grants from Chugai and Roche. This work represents independent research supported by the National Institute for Health Research Biomedical Research Centre at The Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, London (JCC). JCC is supported by the Giant Pledge through the Royal Marsden Cancer Charity. Funding Information: We thank Ilaria Zanetti for her contribution to the statistical analysis. The authors also thank the patients, caregivers, and medical staff involved in this study in the recruiting countries. The overall organisation of this study was supported by the Fondazione Città della Speranza (Padova, Italy). In France the study has been supported by Association Léon Berard Enfant Cancéreux grant 2005. In the UK the study has been supported by Cancer Research UK. During the rhabdomyosarcoma 2005 study (but not related to it) the European paediatric Soft tissue sarcoma Study Group received unrestricted grants from Chugai and Roche. This work represents independent research supported by the National Institute for Health Research Biomedical Research Centre at The Royal Marsden National Health Service Foundation Trust and the Institute of Cancer Research, London (JCC). JCC is supported by the Giant Pledge through the Royal Marsden Cancer Charity. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Background: Adolescent and young adult patients with rhabdomyosarcoma often have poorer outcomes than do children. We aimed to compare the findings of adolescent and young adult patients with children enrolled in two prospective clinical protocols. Methods: This retrospective observational analysis was based on data from the European paediatric Soft tissue sarcoma Study Group (EpSSG) rhabdomyosarcoma 2005 trial (phase 3 randomised trial for localised rhabdomyosarcoma, open from April, 2006, to December, 2016) and the EpSSG MTS 2008 protocol (prospective, observational, single-arm study for metastatic rhabdomyosarcoma, open from June, 2010, to December, 2016), which involved 108 centres from 14 different countries in total. For this analysis, patients were categorised according to their age into children (age 0–14 years) and adolescents and young adults (age 15–21 years). For the analysis of adherence to treatment and toxicity, only patients with high-risk localised rhabdomyosarcoma included in the randomised part of the rhabdomyosarcoma 2005 study were considered. The primary outcome of event-free survival (assessed in all participants) was defined as the time from diagnosis to the first event (eg, tumour progression, relapse) or to the latest follow-up. Secondary outcomes were overall survival, response to chemotherapy, and toxicity. Findings: Our analysis included 1977 patients, 1720 children (median age 4·7 years; IQR 2·6–8·4) and 257 adolescents and young adults (16·6 years; 15·8–18·0). 1719 patients were from the EpSSG rhabdomyosarcoma 2005 study (1523 aged <15 years and 196 aged 15–21 years) and 258 patients were from the EPSSG MTS 2008 study (197 aged <15 years and 61 aged 15–21 years). Adolescent and young adult patients were more likely than were children to have metastatic tumours (61 [23·7%] of 257 vs 197 [11·5%] of 1720; p<0·0001), unfavourable histological subtypes (119 [46·3%] vs 451 [26·2%]; p<0·0001), tumours larger than 5 cm (177 [68·9%] vs 891 [51·8%]; p<0·0001), and regional lymph node involvement (109 [42·4%] vs 339 [19·7%]; p<0·0001). Adolescent and young adult patients had lower 5-year event-free survival (52·6% [95% CI 46·3–58·6] vs 67·8% [65·5–70·0]; p<0·0001) and lower 5-year overall survival (57·1% [50·4–63·1] vs 77·9% [75·8–79·8]; p<0·0001) than did children. The multivariable analysis confirmed the inferior prognosis of patients aged 15–21 years (hazard ratios 1·48 [95% CI 1·20–1·83; p=0·0002] for poorer event-free survival and 1·73 [1·37–2·19; p<0·0001] for poorer overall survival). Modifications of administered chemotherapy occurred in 13 (15·3%) of 85 adolescents and young adults, and in 161 (21·4%) of 754 children. Grade 3–4 haematological toxicity and infection were observed more frequently in children than in adolescent and young adult patients. Interpretation: This study found better outcomes for adolescent and young adult patients than those reported in epidemiological studies (eg, the EUROCARE-5 study reported 5-year overall survival of 39·6% for patients aged 15–19 years in the 2000–07 study period), suggesting that adolescent and young adult patients, at least up to age 21 years, can be treated with intensive paediatric therapies with no major tolerability issues and should be included in paediatric rhabdomyosarcoma trials. However, the inferior outcomes in adolescent and young adult patients compared with those in children, despite receiving similar therapy, suggest that a tailored and intensive treatment strategy might be warranted for these patients. Funding: Fondazione Città della Speranza.

AB - Background: Adolescent and young adult patients with rhabdomyosarcoma often have poorer outcomes than do children. We aimed to compare the findings of adolescent and young adult patients with children enrolled in two prospective clinical protocols. Methods: This retrospective observational analysis was based on data from the European paediatric Soft tissue sarcoma Study Group (EpSSG) rhabdomyosarcoma 2005 trial (phase 3 randomised trial for localised rhabdomyosarcoma, open from April, 2006, to December, 2016) and the EpSSG MTS 2008 protocol (prospective, observational, single-arm study for metastatic rhabdomyosarcoma, open from June, 2010, to December, 2016), which involved 108 centres from 14 different countries in total. For this analysis, patients were categorised according to their age into children (age 0–14 years) and adolescents and young adults (age 15–21 years). For the analysis of adherence to treatment and toxicity, only patients with high-risk localised rhabdomyosarcoma included in the randomised part of the rhabdomyosarcoma 2005 study were considered. The primary outcome of event-free survival (assessed in all participants) was defined as the time from diagnosis to the first event (eg, tumour progression, relapse) or to the latest follow-up. Secondary outcomes were overall survival, response to chemotherapy, and toxicity. Findings: Our analysis included 1977 patients, 1720 children (median age 4·7 years; IQR 2·6–8·4) and 257 adolescents and young adults (16·6 years; 15·8–18·0). 1719 patients were from the EpSSG rhabdomyosarcoma 2005 study (1523 aged <15 years and 196 aged 15–21 years) and 258 patients were from the EPSSG MTS 2008 study (197 aged <15 years and 61 aged 15–21 years). Adolescent and young adult patients were more likely than were children to have metastatic tumours (61 [23·7%] of 257 vs 197 [11·5%] of 1720; p<0·0001), unfavourable histological subtypes (119 [46·3%] vs 451 [26·2%]; p<0·0001), tumours larger than 5 cm (177 [68·9%] vs 891 [51·8%]; p<0·0001), and regional lymph node involvement (109 [42·4%] vs 339 [19·7%]; p<0·0001). Adolescent and young adult patients had lower 5-year event-free survival (52·6% [95% CI 46·3–58·6] vs 67·8% [65·5–70·0]; p<0·0001) and lower 5-year overall survival (57·1% [50·4–63·1] vs 77·9% [75·8–79·8]; p<0·0001) than did children. The multivariable analysis confirmed the inferior prognosis of patients aged 15–21 years (hazard ratios 1·48 [95% CI 1·20–1·83; p=0·0002] for poorer event-free survival and 1·73 [1·37–2·19; p<0·0001] for poorer overall survival). Modifications of administered chemotherapy occurred in 13 (15·3%) of 85 adolescents and young adults, and in 161 (21·4%) of 754 children. Grade 3–4 haematological toxicity and infection were observed more frequently in children than in adolescent and young adult patients. Interpretation: This study found better outcomes for adolescent and young adult patients than those reported in epidemiological studies (eg, the EUROCARE-5 study reported 5-year overall survival of 39·6% for patients aged 15–19 years in the 2000–07 study period), suggesting that adolescent and young adult patients, at least up to age 21 years, can be treated with intensive paediatric therapies with no major tolerability issues and should be included in paediatric rhabdomyosarcoma trials. However, the inferior outcomes in adolescent and young adult patients compared with those in children, despite receiving similar therapy, suggest that a tailored and intensive treatment strategy might be warranted for these patients. Funding: Fondazione Città della Speranza.

UR - http://www.scopus.com/inward/record.url?scp=85134214110&partnerID=8YFLogxK

U2 - 10.1016/S2352-4642(22)00121-3

DO - 10.1016/S2352-4642(22)00121-3

M3 - Article

C2 - 35690071

VL - 6

SP - 545

EP - 554

JO - The Lancet Child and Adolescent Health

JF - The Lancet Child and Adolescent Health

SN - 2352-4642

IS - 8

ER -