ATRT-02. Neuropsychological function in infant atypical teratoid/rhabdoid tumor versus low-grade glioma survivors reflects tumor malignancy and multimodal treatment [Abstract]

BACKGROUND: Therapy of infants with brain tumors predisposes these patients to increased risks for cognitive sequelae, especially following radiotherapy. Neuropsychological outcome gains importance for those 40-60% of patients with an atypical teratoid/rhabdoid tumor (ATRT) who survive beyond 2 years. Still, reports on cognitive late-effects in children with ATRT are scarce compared to other pediatric brain tumor groups. We analyzed neuropsychological outcome for long-term ATRT-survivors registered in EU-RHAB and infant low-grade glioma (LGG) survivors from the SIOP-LGG 2004-study and LGG-registry. PATIENTS+METHODS: Age at diagnosis of both cohorts was 0-36 months. ATRT-patients (n=13) treated with up to 54Gy radiotherapy (median age 22 months (±7.1)) were evaluated with the “ATRT-Neuropsychology” tool based on SIOPE-BTG QoS-Group recommendations at median 6.8 years (±2.8) after diagnosis. LGG-patients (n=15) treated without radiotherapy (4/15 with chemotherapy) were analyzed with the German “Neuropsychological-Basic-Diagnostic” tool 5.2 years (±0.6) post-diagnosis. RESULTS: The ATRT- vs. LGG-cohorts were comparable for median age at diagnosis, sex-ratio and tumor-localization, though they differed slightly in median age at assessment (9.5/7.2 years (±2.5/1.1)). Results of age-appropriate tests showed increased impairments for ATRT-patients in fluid intelligence (FI) (p=.006, d=1.214) and in visual-spatial processing (VSP) (p<.001, d=2.233) compared to LGG-patients. The median for neuropsychological test results of ATRT-patients spanned from considerably below the normal to the lower normal range (median=65-90), while results of LGG-patients were mostly in the lower normal range (median=83-103). Results for psychomotor speed abilities (PMS) were distinctly below the norm for both patient groups (p=.002-.007). CONCLUSION: Infant ATRT- and LGG-patients develop significant impairments in PMS abilities following multimodal treatment. Long-term survivors of ATRT suffer from additional FI and VSP deficits. Our data suggest that high malignancy requiring multimodal treatment determines the inferior cognitive outcome for the ATRT-cohort. Long-term neuropsychological monitoring (and treatment options) should be implemented as standard of care in ATRT- and LGG-trials

QOL-31. Neuropsychological functioning and quality of life in infant AT/RT survivors: focus on fluid intelligence and visual processing [Abstract]

BACKGROUND Understanding the long-term cognitive sequelae in infant brain tumor survivors remains incomplete, particularly regarding the impact of tumor type, multimodal treatment, and other patient-related factors. This retrospective analysis explores neuropsychological and quality of survival (QoS) outcomes in survivors of atypical teratoid/rhabdoid tumors (AT/RT) and extracranial malignant rhabdoid tumors of soft tissues (eMRT) and kidneys (RTK), all treated within the same framework. Neuropsychological data from children with AT/RT were compared to data from children with non-irradiated low-grade glioma (LGG). METHODS Patients (0 - 36 months at diagnosis) underwent various treatments, including radio-chemotherapy for AT/RT (n = 13) and eMRT/RTK (n = 7), chemotherapy only for LGG (n = 4) and eMRT/RTK (n = 1), or observation for LGG (n = 11). Neuropsychological evaluations were conducted at a median of 6.8 years (AT/RT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post-diagnosis. RESULTS Impairments were observed for all tumour types. Patients with AT/RT exhibited impairments in fluid intelligence (p =.041; d = 1.11) and visual processing (p =.001; d = 2.09) when compared to LGG-patients. Both groups demonstrated deficits in psychomotor speed and attention abilities (p <.001–.019; d = 0.79–1.90). Diagnosis significantly predicted cognitive outcomes, whereas gender and age-related variables did not. QoS outcomes for all rhabdoid patients indicated lower scores in psychosocial functioning (p =.023; d = 0.78) and quality of life (p =.006; d = 0.79) compared to healthy controls. CONCLUSIONS Infant rhabdoid tumor survivors experience cognitive and quality-of-life sequelae. Patients with AT/RT are especially vulnerable to impairments in fluid intelligence and visual processing, while infant LGG-patients without radiotherapy demonstrated comparable deficits in psychomotor and attention abilities. Close monitoring of neuropsychological and quality of life outcomes is crucial for early onset and multimodal treatment

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies

Background The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). Patients and methods Following surgery, patients (0–36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. Results We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001–.019; d = 0.79–1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. Conclusion Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae

Comparison of fitness scores of genes important during phosphorus-limited growth and phosphate starvation and seventeen other previously tested stresses or growth conditions.

<p>Genes with the potential to inform about responses specific to phosphate-limited conditions are listed along the y-axis on the right. Experimental conditions are labeled on top, along the x-axis. The color bar in the top right corner shows colors assigned to the numerical values of fitness scores: negative scores representing fitness defects are blue, positive scores representing fitness benefits are yellow, and fitness-neutral scores are black. The first seven columns starting from the left show scores measured and reported in the current study, the adjacent seventeen columns show scores measured by previous studies and stored in the <a href="http://microbesonline.org" target="_blank">microbesonline.org</a> database. The names of genes with predicted direct roles in phosphorus homeostasis are labeled by light blue-colored boxes. The names of genes with predicted or confirmed direct roles in the biosynthesis of the cell envelope are labeled by rose-colored boxes. The names of genes with predicted roles in transport are labeled by yellow-colored boxes, those encoding the Hmc complex are labeled by green-colored boxes.</p

Neurocognitive Outcomes in Pediatric Patients Following Brain Irradiation

Advanced radiation techniques can reduce the severity of neurocognitive sequelae in young brain tumor patients. In the present analysis, we sought to compare neurocognitive outcomes after proton irradiation with patients who underwent photon radiotherapy (RT) and surgery. Neurocognitive outcomes were evaluated in 103 pediatric brain tumor patients (proton RT n = 26, photon RT n = 30, surgery n = 47) before and after treatment. Comparison of neurocognitive outcomes following different treatment modalities were analyzed over four years after treatment completion. Longitudinal analyses included 42 months of follow-up after proton RT and 55 months after photon RT and surgery. Neurocognitive assessment included standardized tests examining seven domains. A comparison of neurocognitive outcomes after RT (proton and photon with >90% additional surgery) and surgery showed no significant differences in any neurocognitive domain. Neurocognitive functioning tests after proton RT failed to identify alterations compared to baseline testing. Long-term follow up over four years after photon RT showed a decrease in non-verbal intelligence (−9.6%; p = 0.01) and visuospatial construction (−14.9%; p = 0.02). After surgery, there was a decline in non-verbal intelligence (−10.7%; p = 0.01) and processing speed (14.9%; p = 0.002). Differences in neurocognitive outcomes between RT and surgical cohorts in direct intermodal comparison at long-term follow-up were not identified in our study, suggesting that modern radiation therapy does not affect cognition as much as in the past. There were no alterations in long-term neurocognitive abilities after proton RT, whereas decline of processing speed, non-verbal intelligence, and visuospatial abilities were observed after both photon RT and surgery. Domains dependent on intact white matter structures appear particularly vulnerable to brain tumor treatment irrespective of treatment approach.Advanced radiation techniques can reduce the severity of neurocognitive sequelae in young brain tumor patients. In the present analysis, we sought to compare neurocognitive outcomes after proton irradiation with patients who underwent photon radiotherapy (RT) and surgery. Neurocognitive outcomes were evaluated in 103 pediatric brain tumor patients (proton RT n = 26, photon RT n = 30, surgery n = 47) before and after treatment. Comparison of neurocognitive outcomes following different treatment modalities were analyzed over four years after treatment completion. Longitudinal analyses included 42 months of follow-up after proton RT and 55 months after photon RT and surgery. Neurocognitive assessment included standardized tests examining seven domains. A comparison of neurocognitive outcomes after RT (proton and photon with >90% additional surgery) and surgery showed no significant differences in any neurocognitive domain. Neurocognitive functioning tests after proton RT failed to identify alterations compared to baseline testing. Long-term follow up over four years after photon RT showed a decrease in non-verbal intelligence (−9.6%; p = 0.01) and visuospatial construction (−14.9%; p = 0.02). After surgery, there was a decline in non-verbal intelligence (−10.7%; p = 0.01) and processing speed (14.9%; p = 0.002). Differences in neurocognitive outcomes between RT and surgical cohorts in direct intermodal comparison at long-term follow-up were not identified in our study, suggesting that modern radiation therapy does not affect cognition as much as in the past. There were no alterations in long-term neurocognitive abilities after proton RT, whereas decline of processing speed, non-verbal intelligence, and visuospatial abilities were observed after both photon RT and surgery. Domains dependent on intact white matter structures appear particularly vulnerable to brain tumor treatment irrespective of treatment approach.Dietmar Hopp Stiftun