Purpose: We aim to describe the characteristics of patients with childhood-onset craniopharyngioma and to analyze factors that impair quality of life (QoL) in this population. Methods: multicenter national study including patients treated between 2008-2022, from 2 to 25 years of age diagnosed with craniopharyngioma. QoL was assessed once during patient’s follow-up by age-adapted versions Pediatric Quality of Life Inventory (PedsQL TM) questionnaire. Results: Sixty-six patients were included. Median age at diagnosis was 5 years (IQR 3-8), while median follow-up was 7.4 years (IQR 2.8-9.7). Most craniopharyngioma were suprasellar (93.9%) and 59.7% had hypothalamic involvement (HI). All patients underwent surgery, 44.4% received radiotherapy and 23.6%, intra-cystic therapy. Most frequent long-term complications were visual deficit (72.7%) and endocrine impairment (94.5%). Patients exhibited hypothyroidism requiring hormone replacement (92.4%), hypocortisolism (80.3%), diabetes insipidus (86.4%) and/or growth hormone therapy (50%). When parents evaluated QoL, PedsQL TM median score was 53.8 points out of 100 (IQR 41-71.6). Higher scores were noted when patients assessed their own QoL [median-score 64.8 (IQR 57.3-81.8)], observing statistical-significant differences (p=0.019). QoL was impaired by repeated surgeries (r -0.44; p=0.014), HI [median-score 51.5 (IQR 39-63.8) vs 76.4 (59-84.8); p=0.001], radiotherapy [median-score 51.9 (IQR 38.1-61.3) vs 63.8 (IQR 49-82.5); p=0.02] and longer follow-up (r-0.3; p=0.01). Conclusion: In our study, most patients had significant comorbidities and low overall QoL scores, which was mainly affected by repeated surgery, radiation, and HI. The complex management of these patients requires multidisciplinary teams that can warrant the hypothalamic preservation and prompt intervention to prevent and identify sequelae.

Background T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on pediatric T-LBL are scarce and, therefore, its molecular landscape has not been fully elucidated yet. Procedure To characterize the genetic and molecular heterogeneity of paediatric T-LBL, 33 patients were analyzed using an integrated approach, including targeted next generation sequencing, RNA-sequencing transcriptome analysis and copy-number arrays. Results Copy number and mutational analyses allowed the detection of recurrent homozygous deletions of 9p/CDKN2A (78%), trisomy 20 (19%) and gains of 17q24-q25 (16%), as well as frequent mutations of NOTCH1 (62%), followed by BCL11B (23%), WT1 (19%) and FBXW7, PHF6 and RPL10 genes (15%, respectively). This genetic profile did not differ to that described in T-ALL in terms of mutation incidence and global genomic complexity level but unveiled virtually exclusive 17q25 gains and trisomy 20 in T-LBL. Additionally, we identified novel gene fusions in paediatric T-LBL including NOTCH1-IKZF2, RNGTT-SNAP91 and DDX3X-MLLT10, the latter being the only one previously described in T-ALL. Moreover, clinical correlations highlighted the presence of Notch pathway alterations as a factor related to favorable outcome. Conclusions In summary, the genomic landscape of paediatric T-LBL is similar to that observed in T-ALL and Notch signaling pathway deregulation remains the cornerstone in its pathogenesis, including not only mutations but fusion genes targeting NOTCH1.