2900 Predictors of survival in glioblastoma patients treated with fotemustine at first relapse after Stupp regimen: Analysis of GLIOSTRY (GLIOblastoma regiSTRY) of the AINO (Italian Association of Neuro-Oncology)

AbstractSteroids are the cornerstone of the treatment of childhood nephrotic syndrome. The optimal duration for the first episode remains a matter of debate. The aim of this study is to determine whether the 8 weeks International Study of Kidney Disease in Children (ISKDC) regimen is equally effective as the 12 weeks steroid regimen from the German society of pediatric nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie [APN]). An individual patient data (IPD) meta-analysis of randomized controlled trials reporting on prednisolone treatment for a first episode of childhood nephrotic syndrome was conducted. European trials aimed at investigating the ISKDC and/or APN steroid regimen were selected. The lead investigators of the selected trials were requested to provide the IPD of the specific treatment groups. Four trials included European cohorts using dosing schedules according to the regimens studied. IPD of two trials were available. A significant difference was found in time to first relapse after cessation of steroid treatment between the 8 and 12 weeks treatment group with a median time to relapse of 29 and 63 days, respectively. Moreover, relapse rate ratios during total follow-up were 51% higher for the 8 weeks regimen. Finally, younger children have a significantly lower time to first relapse and frequently relapsing nephrotic syndrome.Conclusions: The results of this IPD meta-analysis suggest that the 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen. Moreover, this study highlights the importance of using uniform definitions to enable accurate comparison and interpretation of trial results.Trial registration: Registration number: CRD42020199244, date of registration 16-08-2020 What is Known:• Steroids are the cornerstone of the treatment of childhood nephrotic syndrome, however the optimal duration for the first episode remains a matter of debate.• Currently, the 8 weeks ISKDC protocol and 12 weeks APN protocol are among the most frequently used protocols in Europe. What is New:• The 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen for the treatment of a first episode of nephrotic syndrome.• Younger children have a significantly shorter time to first relapse and time to frequent relapsing nephrotic syndrome.

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ESTRO vision 2030: the young Italian Association of Radiotherapy and Clinical Oncology (yAIRO) commitment statement

La radiologia medica ◽

10.1007/s11547-021-01398-w ◽

2021 ◽

Author(s):

Francesca De Felice ◽

Luca Boldrini ◽

Carlo Greco ◽

Valerio Nardone ◽

Viola Salvestrini ◽

...

Keyword(s):

Clinical Oncology ◽

Action Plan ◽

Italian Association ◽

Radiation Oncologists ◽

Vision 2030 ◽

Gain Access

AbstractThe aim of this document is to share the action plan from the young Italian Association of Radiotherapy and Clinical Oncology (yAIRO). We believe it is important to enhance a constructive dialog between societies. The hope is to offer to young radiation oncologists a wealth of opportunities to refine their skills and gain access to the latest developments, according to a shared European vision.

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Unravelling the Sequential Interplay of Mutational Mechanisms during Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia

Genes ◽

10.3390/genes12020214 ◽

2021 ◽

Vol 12 (2) ◽

pp. 214

Author(s):

Željko Antić ◽

Stefan H. Lelieveld ◽

Cédric G. van der Ham ◽

Edwin Sonneveld ◽

Peter M. Hoogerbrugge ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Clonal Evolution ◽

Leukemic Cells ◽

Proliferative Potential ◽

Disease Evolution ◽

Pediatric Acute Lymphoblastic Leukemia ◽

First Relapse ◽

Mutational Processes

Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is characterized by clonal heterogeneity. Genomic mutations can increase proliferative potential of leukemic cells and cause treatment resistance. However, mechanisms driving mutagenesis and clonal diversification in ALL are not fully understood. In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. Based on mutation allele frequencies at diagnosis and subsequent relapses, we clustered mutations into groups and performed cluster-specific mutational profile analysis and de novo signature extraction. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity. The associated signatures SBS2 and SBS13 were present already at diagnosis, and although emerging mutations were lost in later relapses, the process remained active throughout disease evolution. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling ultraviolet light-driven DNA damage, and thiopurine-associated damage at first relapse. In conclusion, our data shows that investigation of mutational processes in clusters separated in time may aid in understanding the mutational mechanisms and discovery of underlying causes.

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Depatuxizumab Mafodotin (Depatux-M) Plus Temozolomide in Recurrent Glioblastoma Patients: Real-World Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO)

Cancers ◽

10.3390/cancers13112773 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2773

Author(s):

Marta Padovan ◽

Marica Eoli ◽

Alessia Pellerino ◽

Simona Rizzato ◽

Claudia Caserta ◽

...

Keyword(s):

Real World ◽

Recurrent Glioblastoma ◽

Second Line ◽

Ocular Toxicity ◽

Phase 2 ◽

Second Line Therapy ◽

Italian Association ◽

Phase 2 Trial ◽

Line Therapy ◽

Ecog Ps

Background: Depatuxizumab Mafodotin (Depatux-M; ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population. Materials and Methods: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The primary endpoints of the study were overall survival and safety. Results: A total of 36 patients were enrolled. The median age was 57 years, ECOG PS was 0–1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. The median OS was 8.04 months (95% CI, 5.3–10.7), the 12 month-OS was 37%. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. Grade 3 ocular toxicity occurred in 11% of patients; no grade 4 ocular toxicity was reported. No death was considered to be drug-related. Conclusions: The study reported the first “real world” experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Overall, the results are close to those reported in the previous phase 2 trial. Toxicity was moderate and manageable.

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