Lessons learnt from the medical and psychosocial evaluation of childhood acute lymphoblastic leukemia (ALL) survivors enrolled in EORTC Children Leukemia Group Trials between 1971 and 1998 and future perspectives for long-term outcome research

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. With dramatic improvements in survival observed since the 70's, it progressively became evident that the long-term survivors faced late morbidity, late mortality and psychosocial troubles. In 2010, the EORTC developed the retrospective 58LAE study in order to evaluate the long-term outcome of the 2621 eligible childhood ALL survivors enrolled between 1971 and 1998. The first sub-project project showed that ETV6-RUNX1 positive patients had better long-term outcome and had specific sensitivities to treatments. The second sub-project showed that omission of cranial radiotherapy did not increase the risk of relapse and was associated with a higher incidence of second neoplasms and late toxicities in medium and high-risk patients, without central nervous system (CNS) involvement. The third subproject identified hematopoietic stem cell transplantation, cranial radiotherapy and having a relapse as risk factors for worse socio-economic outcome. Finally, the fertility status of the survivors was also evaluated. The 58LAE project has raised several challenges when translated into the "real-life" setting, which include the difficulties of following childhood cancer survivors throughout their transition to adult life; the statistical analysis of a cohort of patients treated in multiple clinical trials and along different years; the need for combining different approaches to gather sufficient quality patient data; and the challenge of overcoming the healthcare administrative and regulatory obstacles. New ways of addressing survivorship studies are needed to address these challenges

Long-term outcome evaluation of medium/high risk acute lymphoblastic leukaemia children treated with or without cranial radiotherapy in the EORTC 58832 randomized study.

We investigated the long-term outcome, the incidence of second neoplasms (SN) and the rate of late adverse effects (LAE) in children with central nervous system (CNS) negative medium/high-risk de novo acute lymphoblastic leukaemia (ALL), in first complete remission (CR1) at end of late intensification, randomized to receive no cranial radiotherapy (No CRT, n = 92) versus CRT (standard arm, n = 84) in the non-inferiority EORTC 58832 study (1983-1989). Median follow-up was 20 years (range 4-32 years). The 25-year disease-free survival rate (+/-SE) was 67.4 +/- 4.9% without CRT and 70.2 +/- 5.0% with CRT. The 25-year incidence of isolated (6.5 +/- 2.6% vs. 4.8 +/- 2.3%) and any CNS relapse {8.7 +/- 2.9% vs. 11.9 +/- 3.5%; hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.28-1.79]; test of non-inferiority: P = 0.01} was not increased without CRT. The 25-year SN incidence in CR1 was 7.9 +/- 4.6% vs. 11.0 +/- 4.2%. The 25-year event-free and overall survival rates were quite similar in both arms [59.5 +/- 6.3% vs. 60.5 +/- 5.9%, HR 0.94 (95% CI 0.57-1.52), and 78.1 +/- 4.3% vs. 78.5 +/- 4.5%, HR 1.00 (95% CI 0.53-1.88)]. Omission of CRT was associated with dramatic decrease in CNS and endocrine LAE rates. In conclusion, our data suggest that, with proper systemic and intrathecal CNS prophylaxis, CRT could totally be omitted in CR1 without jeopardizing survival, while decreasing LAE in childhood ALL

Long-term outcome evaluation of medium/high risk acute lymphoblastic leukaemia children treated with or without cranial radiotherapy in the EORTC 58832 randomized study

We investigated the long-term outcome, the incidence of second neoplasms (SN) and the rate of late adverse effects (LAE) in children with central nervous system (CNS) negative medium/high-risk de novo acute lymphoblastic leukaemia (ALL), in first complete remission (CR1) at end of late intensification, randomized to receive no cranial radiotherapy (No CRT, n = 92) versus CRT (standard arm, n = 84) in the non-inferiority EORTC 58832 study (1983-1989). Median follow-up was 20 years (range 4-32 years). The 25-year disease-free survival rate (±SE) was 67·4 ± 4·9% without CRT and 70·2 ± 5·0% with CRT. The 25-year incidence of isolated (6·5 ± 2·6% vs. 4·8 ± 2·3%) and any CNS relapse {8·7 ± 2·9% vs. 11·9 ± 3·5%; hazard ratio (HR) 0·71 [95% confidence interval (CI) 0·28-1·79]; test of non-inferiority: P = 0·01} was not increased without CRT. The 25-year SN incidence in CR1 was 7·9 ± 4·6% vs. 11·0 ± 4·2%. The 25-year event-free and overall survival rates were quite similar in both arms [59·5 ± 6·3% vs. 60·5 ± 5·9%, HR 0·94 (95% CI 0·57-1·52), and 78·1 ± 4·3% vs. 78·5 ± 4·5%, HR 1·00 (95% CI 0·53-1·88)]. Omission of CRT was associated with dramatic decrease in CNS and endocrine LAE rates. In conclusion, our data suggest that, with proper systemic and intrathecal CNS prophylaxis, CRT could totally be omitted in CR1 without jeopardizing survival, while decreasing LAE in childhood ALL.status: publishe